Chinese General Practice-Online first Articles

Perceptions of Hierarchical Medical System and Associated Factors in Key Primary Care Practitioners

MA Cong, WANG Wei, YUAN Ying, SUN Yanchun, XU Fang, YAN Fei

Background　The establishment and improvement of hierarchical medical system will help optimize health resource allocation and develop a sound healthcare-seeking pattern. As the key practitioners of hierarchical medical system，primary care workers' perception of the system is vital to the implementation of the system，so studying their perception of the system and associated factors is of great significance. Objective　To analyze primary care professionals' perceptions of hierarchical medical system and associated factors based on the results of 2018 Sixth China National Health Survey，providing a reference for further improvement of the system. Methods　From April to October 2019，one representative urban district and one suburban county were chosen from each of six selected provinces in which hierarchical medical system has been implemented. Then by stratified random sampling，about six community health centers/township health centers were extracted from each district（county）（46 community health centers and 30 township health centers in total），in which primary care professionals who were on duty on the day of survey were invited to attend a questionnaire survey for understanding their demographics，perceptions of the importance and effectiveness of，as well as barriers to the implementation of hierarchical medical system. Results　Altogether，1 308 cases who effectively completed the survey were included for final analysis. According to the analysis，the benefits of implementing hierarchical medical system were：improving the health service system〔approved by 1 231 cases（94.11%）〕，improving the healthcare services for patients and residents〔agreed by 1 219 cases（93.2%）〕；improving the quality of medical services〔1 209（92.43%）〕；improving the efficiency of medical services〔1 189（90.9%）〕；improving doctor-patient relationship〔1 087（83.1%）〕；reducing the medical risk〔786（60.09%）〕；reducing medical expenses〔611（46.71%）〕. As for the outcome of implementing hierarchical medical system，its implementation would not hinder the development of health institutions〔982 cases（75.08%）〕. When it comes to the barriers to the implementation of hierarchical medical system，there were no relevant incentives〔759 cases（58.03%）〕，patients and their families' were unwilling to accept hierarchical medical system due to getting used to free healthcare-seeking pattern〔753 cases（57.57%）〕，there were no unified bi-directional referral criteria and system〔712 cases（45.57%）〕，the implementation of hierarchical medical system may lead to conflict of interests between medical institutions〔451 cases（34.48%）〕，there was no an effective referral route〔403 cases（30.81%）〕，their medical institutions had insufficient capacities to effectively implement hierarchical medical system〔387（29.59%）〕. Univariate analysis revealed that primary care professionals' perceptions of hierarchical medical system differed significantly by province，sex，educational background，professional title，type of their medical institution，and type of post（P<0.05）. Multiple linear regression analysis indicated that province，sex，educational background，professional title，and officially budgeted post were associated with primary care professionals' perceptions of hierarchical medical system（P<0.05）. Conclusion　These primary care professionals had good perceptions of the importance and effectiveness of the implementation of hierarchical medical system，but also showed their concerns about the barriers to its implementation. Professional title and province were associated with their perceptions of the system. To promote the implementation of hierarchical medical system，it is suggested that the government departments increase investment，improve policy details，provide corresponding incentives，and carry out targeted publicity and education.

Polypharmacy Management in Elderly Patients with Multimorbidity

Active implementation of patient-centered polypharmacy management for older adults with multimorbidity can help to identify and correct the medication errors that patients may have，avoid the occurrence of potential medication errors，reduce and control the development of drug-related diseases，improve the clinical treatment effect，and delay the disease progression，thereby facilitating the achievement of targets for disease control，and improvement of quality of life of patients. In the light of problems of polypharmacy in Chinese elderly patients with multimorbidity，we summarized relevant interventions including strengthening top-level design of management，building multidisciplinary teams，innovating medication management technologies，and meeting patients'needs of drug information，providing a reference for medication management of these patients. We found that problems of polypharmacy in Chinese elderly patients are serious，and actively exploring multiple approaches to polypharmacy management based on medication features of these patients may be a key breakthrough for addressing the problems.

Prevalence and Influencing Factors of Sedentary Behavior in Community Stroke Patients

FU Zhongrong, ZHANG Zhenxiang, LIN Beilei, MEI Yongxia, WANG Wenna

Background　As a kind of unhealthy lifestyle，sedentary behavior is closely related to poor prognosis of stroke patients. So it is of great significance to understand sedentary behavior prevalence in stroke patients，and to formulate intervention measures based on its influencing factors. Objective　To investigate sedentary behavior prevalence and associated factors in stroke patients in the community，providing a reference for the development of targeted interventions. Methods　From August to December 2020，by use of convenience sampling，230 eligible community stroke patients from Zhengzhou（including individuals who underwent reexaminations in neurology and neurosurgery clinics of three grade A tertiary hospitals and those who were from three communities） were selected to attend a survey using Demographic Questionnaire，Sedentary Behavior Questionnaire，the Chinese version of Fatigue Severity Scale，the Chinese version of Stroke Self-Efficacy Questionnaire，and Social Support Scale. Binary Logistic regression analysis was used to explore associated factors of sedentary behavior. Results　The survey achieved a response rate of 97.8%. The average daily sedentary time of the respondents was（7.10±2.75）hours，and 179 cases（79.6%） had daily sedentary time ≥5 hours. The daily sedentary time differed significantly by age，living in rural or urban areas，education level，number of complications，number of chronic diseases and fatigue（P<0.05）. Binary Logistic regression analysis showed that age，number of complications，number of chronic diseases and fatigue had significant impacts on sedentary behavior（P<0.05）. Conclusion　The prevalence of sedentary behavior in community-dwelling patients with stroke was high. It is recommended that health managers develop targeted interventions measures based on the above factors associated with sedentary behavior，thereby reducing sedentary behavior prevalence in this group.

Research Status and Thinking of Minimal Clinically Important Difference in Patient-reported Outcome Assessment Tool for Allergic Rhinitis

ZHANG Peng, REN Jiaming, GUAN Jiarui, XIE Yang

As the patient-reported outcome（PRO）assessment tool has been increasingly used in the clinical efficacy evaluation of patients with allergic rhinitis（AR），the judgment and interpretation of changes in measurement results of assessment tools have become increasingly important. For the judgment of clinical research results，not only the statistical differences，but also the minimum clinically important difference（MCID）must be paid attention to.This paper systematically sorts out the MCID of the AR-PRO assessment tool，in order to provide a reference for AR-related clinical diagnosis and treatment decision-making and the objectification of the PRO assessment tool.

Prevalence，Awareness，Treatment and Control Rates of Hypertension in Chinese Adults: Trend and Associated Factors from 1991 to 2015

YAO Xi, PEI Xiaoting, QU Zhe

Background　As a major common chronic noncommunicable in Chinese adults，hypertension is associated with increased risk of a variety of cardiovascular and cerebrovascular diseases such as coronary atherosclerosis and stroke. Hypertension has become a major public health issue in China due to increasing prevalence but low treatment and control rates. Objective　To estimate the spatio-temporal and demographic distribution of hypertension in Chinese adults from 1991 to 2015. Methods　Data were collected from nine waves of the China Health and Nutrition Survey conducted between 1991—2015，involving adults（≥18 years old） with complete information，including age，sex，blood pressure values，demographic characteristics，smoking，drinking status，height，weight，waist circumference，blood pressure value and diseasehistory. The trends of hypertension prevalence，awareness，treatment and control rates and associated factors in adults during the period of 25 years were analyzed. Results　In 1991，the prevalence，awareness，treatment and control ratesof hypertension in adults were 14.77%（1 291/8 743），27.58%（356/1 291），15.80%（204/1 291），and 5.89%（76/1 291），respectively，whilethese four indicators in 2015 were 32.67%（4 520/13 834），48.08%（2 173/4 520），40.51%（1 831/4 520），and 14.65%（662/4 520），respectively. There was an increasing tread for prevalence of hypertension from 1991 to 2015. Increasing trends of awareness，treatment and control rates were found from 2000 to 2015. The prevalence，awareness，treatment and control rates of hypertension were alwaysaffected by age，gender，behavior habits，knowledge level and other factors. Conclusion　The treatment and control rates of hypertension in Chinese adults are increasing，but still relatively lower in comparison to its increasing prevalence. So it is recommended for relevant government departments to take measures to enhance hypertension treatment and control rates in adults，so that the progression of hypertension would be delayed.

Characteristics of Cancer Epidemiology among 0-14 years old Chinese Children，2005—2015

　Background　Cancer has become a leading cause of death for Chinese children，imposing a great economic burden on society and families. Therefore，it is extremely important to understand the epidemicsizes and trends of childhood malignancies. Objective　To analyze the epidemiological characteristics of childhood cancer in China from 2005 to 2015，so as to provide evidence for the formulation of prevention and control strategies and rational allocation of health resources concerning childhood cancer in China. Methods　Data regarding cancer incidence and mortality in Chinese 0-14 years old children during 2008 to 2018 were collected from the Chinese Cancer Registry Annual Report. Age-standardized incidence and mortality rates were computed by dividing the number of child deaths caused by cancer by the fifth national population census （2010） and multiplying by 100 000. Joinpoint Regression Program was used to compute the annual percentage change （APC） to analyze the temporal trends of annual child cancer incidence and mortality rates. Results　（1） During the period of 2005-2015，the median crude incidence rate and median crude mortality rate of cancer in 0-14 years old were 9.35/100 000，and 3.91/100 000，respectively. The median crude incidence and median crude mortality rate of 0-4 years old group were higher than those of 5~9 years old group and 10~14 year group（P<0.05）. （2） The median crude incidence rate （10.21/100 000 vs 8.91/100 000） and median crude mortality rate（4.18/100 000 vs 3.47/100 000） of cancer in male children aged 0-14 years old were higher than those of female children of the same age（P<0.05）. （3） The median crude incidence rate（10.87/100 000 vs 7.20/100 000） and median crude mortalityrate（4.08/100 000 vs 3.54 /100 000） of cancer in urban children aged 0-14 years old were higher than those of rural children of the same age（P<0.05）. （4） The median crude mortality rate of cancer showed an upward trend in 0-14 years old in the period of 2005 to 2015 （APC=1.01%，P<0.05）；amomg them，the median crude mortality rate showed an decreased trend(APC = - 1.19%, P < 0.05); the median crude mortality in the 5-9 years old group showed an increased trend (APC = 2.50%, P < 0.05); The median crude mortality rate in the 10-14 years old group was stable over time （5） The median crude incidence rate and median crude mortality rate of cancer in rural 0-14-year-olds in rural areas presented an upward trend over the period 2005 to 2015（APC=7.73%，2.22%，P<0.05）. （6） The top six cancers among children aged 0-14 years old in this period were: leukemia，brain cancer，lymphoma，bone cancer，kidney cancer and liver cancer. Conclusion　The cancer incidence and mortality rates in Chinese 0-14 years old children showed different features by time，age group or geographical region（rural or urban）. Priorities for containing cancer should be given to rural children，5-9 years old children or children with brain cancer or leukemia.

Ovarian Cancer in China：Trends in Incidence and Mortality，2005—2016

Background　The health impairment caused by ovarian cancer in female population has become a global focus. However，there is a lack of research on ovarian cancer incidence and mortality trends in Chinese female population. Objective　To describe the trends of ovarian cancer incidence and mortality in China from 2005 to 2016 by analyzing the incidence and death data of ovarian cancer collected from Chinese Cancer Registry Annual Report，providing a basis for the scientific prevention and control of ovarian cancer in China. Methods　The incidence and mortality of ovarian cancer in China during 2005 to 2016 were collected and input into Excel spreadsheets，then the annual age-standardized incidence rate，age-standardized mortality rate，age-specific incidence rate and age-specific mortality rate were computed. Joinpoint Regression Program was used to estimate the annual percentage change（APC），and average annual percentage change（AAPC） to analyze the temporal trends of annual ovarian cancer incidence and mortality rates. Results　The incidence rateof ovarian cancer showed a trend of rapid increase over the period of 2005 to 2016（AAPC=7.25%，P<0.05）. The annual age-standardized ovarian cancer incidence rate in urban areas was higher than that in rural areas in each year. The ovarian cancer incidence rate increased obviously with age in women over the age of 35，and peaked in those aged 55 years old. From 2005 to 2016，the overall ovarian cancer mortality rate showed a rapid upward trend（AAPC=6.06%，P<0.05）. The age-standardized ovarian cancer mortality rate in urban areas was higher than that in rural areas. The mortality rate increased rapidly with age in women over 35 years of age，but decreased gradually in those aged over 75 years. Conclusion　Both ovarian cancer incidence and mortality rates during 2005 to 2016 in China increased rapidly，but with age-specific and urban-rural differences. Therefore，targeted interventions should be taken，and strategies for ovarian cancer prevention and treatment should be developed to reduce the risk of ovarian cancer.

The Clinical Value of PET-CT in The Diagnosis of Pre-pulseless Takayasu's ArteritisPresenting as Fever of Unknown Origine

ZENG Keqin, YIN Yufeng, REN Tian, ZHOU Erye, WANG Mingjun, WU Jian

Background　Takayasu's arteritis （TAK） presenting asfever of unknown origin （FUO） is rare in clinic. Diagnosis is difficult in the early stageas the non-specific clinical symptoms and signs，the lack of imaging findings of great artery stenosis and occlusionof patients. With the wide application of positron emission computed tomography/computed tomography （PET-CT） in the diagnosis and differential diagnosis of FUO，it may contribute to the early diagnosis of TAK.Objective　To investigate the application value of PET-CT in the diagnosis and condition assessment of early TAK presenting asFUO. Methods　The clinical presentations，laboratory examinations，PET-CT findings，and treatment outcomes of 7 cases of TAK presenting asFUO thateventually diagnosed by PET-CTfrom January 2013 to January 2021were retrospectively analyzed，andthe medical literaturefrom 1991to2021was reviewed.Results　All the 7 patients were female，the age of onsetranging from 27 to 58 years old，with an average age of（37.9±10.6） years. The course of disease was from 1 to 6 months，with an average of（3.9±2.4）months. FUOwas thefirstsymptomof all patients（100%），which may be accompanied by palpitation （14.3%），dizziness （28.6%），headache （14.3%），fatigue （28.6%） and other non-specific clinical symptoms.Laboratory tests showed elevated levels of leukocytes （71.4%），platelets （57.1%），erythrocyte sedimentation rate （ESR）（100%），C-reactive protein （CRP）（85.7%），tumor necrosis factor-α （TNF-α）（42.9%） and interleukin-6 （IL-6）（85.7%）. Color Doppler ultrasound，computed tomography angiography （CTA） and magnetic resonance angiography （MRA） showed no stenosis and occlusion of large arteries，while PET-CT showed inflammatory changes in arterial walls at multiple locations，including thecending aorta （28.6%），aortic arch （14.3%），common carotid artery （28.6%），subclavian artery （28.6%），thoracic aorta （14.3%），abdominal aorta （14.3%） and renal artery （14.3%）. Conclusion　PET-CT is helpful in the diagnosis and condition assessment of pre-pulseless Takayasu's arteritis presenting as FUO.

Clinicopathological Manifestations of Kidney Injury in Leukemia

WANG Yina, DONG Bao, LI Xin, SHAO Chunying, ZUO Li, WANG Mei, YAN Yu

Background　Kidney is a major extramedullary organ involved in leukemia，but clinicians have insufficient understanding of it due to rare case reports. Objective　To analyze the clinicopathological manifestations of kidney injury in leukemia. Methods　Five patients with kidney injury in leukemia were recruited from Peking University People’s Hospital from June 2010 to June 2020. Their demographics，clinical manifestations，ultrasonic and laboratory examination results，pathological examination results of renal biopsy species，therapeutic regimen and follow-up were retrospectively analyzed. Results　All these patients were male，with an onset age ranging from 19 to 73 years old. Two of them had B-cell acute lymphoblastic leukemia after allogeneic stem cell transplantation，the remaining three had B-cell chronic lymphocytic leukemia. All of them had acute kidney injury with proteinuria，and pathologically manifestation of acute interstitial nephritis. In addition，two of them also had leukemia-related glomerular disease. Renal pathology indicated extramedullary recurrence in the two cases of B-cell acute lymphoblastic leukemia，and progression in the other three cases of B-cell chronic lymphoblastic leukemia. Four patients received regular chemotherapy，and two of them obtained a reduction in serum creatinine levels，but the other two showed no improvement in renal function. Conclusion　Kidney injury in leukemia commonly manifests as acute kidney injury clinically，acute interstitial nephritis pathologically，and may be complicated by secondary glomerulopathy. Prompt renal biopsy，especially immunohistochemical staining for renal interstitial infiltrating cells，may be helpful for accurate diagnosis and appropriate treatment guidance.

Novel Developments in the Relationship of Gut Microbiota and Immune Regulation with Childhood Asthma

CUI Tianyi, LIU Jiarui, LYU Bin, GAO Xiumei, ZHAO Xin

Bronchial asthma，commonly known as asthma，is a frequently seen chronic respiratory disease that seriously threatens human health. More than 300 million people have had asthma worldwide，and most of them are children. Epidemiological investigations have shown that the prevalence of asthma among Chinese children aged 0-14 is 2.32%，and it is increasing year by year. Children are more prone to gut flora imbalance due to underdeveloped immune system，and physiologically successional changing of gut flora，which leads to the destruction of the intestinal mucosal barrier and local immune imbalance，eventually causing the development of asthma. We reviewed the latest advances in the immune regulatory mechanism of childhood asthma，and its association with gut microbiota，as well as interventions targeting gut microbiota，providing new ideas for the treatment of childhood asthma.

Metabolomics in Childhood Asthma

WU Ruijian, HUANG Yuge, LUO Lianxiang

As the most common chronic disease in children，bronchial asthma is highly underdiagnosed with complex pathogenesis. By qualitative and quantitative analyses of changes in low molecular weight molecules or metabolites in biological samples，metabolomics provides a new method to search biomarkers and pathogenesis. We reviewed the application of metabolomics in childhood asthma，which attempts to find the potential biomarkers and pathogenesis of childhood asthma by analyzing the samples of blood，exhaled breath，feces and urine of asthmatic children and healthy children using targeted or untargeted research approaches，providing help for clinical diagnosis and treatment of childhood asthma. Considerable progress has been made in metabolomics in childhood asthma，but due to factors such as individual differences，sample collection，data analysis，and genomic heterogeneity，metabolomics analysis of childhood asthma is still facing challenges.

Status of Diagnosis and Expert Advice of Developmental Disorder Related to Childhood Rehabilitation

In order to standardize the diagnosis and nomenclature of dvelopmental disorder in China ，and ensure that clinical professionals can be able to diagnose and treat these diseases early and accurately ，the Rehabilitation Group of Pediatrics Branch of Chinese Medical Association has organized relevant experts to discuss many times and formulated this recommendation based on the current actual situation in China.The paper mainly includesthe diagnosis and naming status， evaluation and expert advice ofhigh-risk infants， developmental delay，global developmental delay，1anguage disorder，mental retardation，autism spectrum disorder， developmental coordination disorder，the objective is to provide reference and guidance for clinical professionals in the diagnosis， evaluation and treatment of developmental disorderin children.

Autoimmune Neutropenia in Children：Clinical Characteristics of 22 Cases

SUN Qing, XIE Yao, WU Penghui, LI Shuo, ZHAO Weihong

Background　Autoimmune neutropenia （AIN） is a common chronic neutropenia in children，but it in children has been rarely reported. Objective　To analyse clinical characteristics，diagnosis，treatment，and follow-up of children with AIN，aiming at providing support for clinicians. Methods　A retrospective design was used. Participants were 22 children with AIN recruited from Department of Pediatrics，Peking University First Hospital from 2012 to 2020. Their clinical and follow-up data were collected and analyzed. Results　Of the 22 cases，15 were male and 7 were female；with 6 months as the median initial diagnosis age. Among the results of 82 routine blood tests performed for all cases，severe，moderate and mild neutropenia accounted for 62.2%（51/82），30.5%（25/82），and 7.3%（6/82），respectively. Two cases（9.1%） were diagnosed with moderate neutropenia and other 20（90.1%） were diagnosed with severe neutropenia by the lowest absolute neutrophil count（ANC）. Six children （27.3%） also had other clinical manifestations besides neutropenia. Twelve cases（54.5%） underwent the examination of bone marrow cell morphologies. Six cases （27.3%） underwent gene test. 95.5% of the cases had infections，and 54.5% of them had severe infections，but no life-threatening infections. The leading pathogen of infections was virus. The upper respiratory tract was the most common infected area. By the end of September 2021，the ANC of 11 cases returned to the normal level，and the median of AIN of them was 25 （range: 7-42） months. Conclusion　Most AIN children had moderate to severe neutropenia，and they were prone to infections mostly caused by virus，and the most usually were upper respiratory tract infections，but rarely life-threatening. The median duration of AIN，a self-limited disease，for our reported cases was 25 months.

The Study of the Value of High Mobility Group Protein B1 Combined with Acute Physiological Score in the Diagnosis and Prognosis of Children with Severe Pneumonia

KANG Ping, LI Yi, TANG Yu

　Background　Severe pneumonia in children is a common respiratory critical illness，and accurate assessment of its prognosis is the key to reasonable clinical decision-making. High mobility group protein B1（HMGB1）and acute physiology score（APS）have high prognostic significance for adult critically ill patients. Objective　To investigate the value of HMGB1 combined with APS in the diagnosis and prognosis of children with severe pneumonia. Methods　The data of 55 children with severe pneumonia（severe pneumonia group）treated in Henan Children's Hospital from May 2020 to February 2021 were collected and the childrenwere divided into the improvement group（n=41）and the poor outcome group（n=14）according to the prognosis. Data of 60 children with common pneumonia（common pneumonia group）and 40 children with healthy physical examination（control group）who were treated in this hospital during the same period. The APS score and HMGB1 level at admission of each groupwere compared. The correlation between APS and HMGB1 was analyzed. The risk factors affecting the prognosis of severe pneumonia were analyzed by Logistic regression. The value of HMGB1，APS and combined variables in the diagnosis and prognosis of children with severe pneumonia was analyzed by ROC curve. Results　The HMGB1 level and APS score of the severe pneumonia group were significantly higher than those of the normal pneumonia group（P<0.05）；The HMGB1 level and APS score of the poor prognosis group were significantly higher than those of the prognosis group（P<0.05）.The results of correlation analysis showed that there was a positive correlation between HMGB1 and APS in severe pneumonia group（r=0.542，P<0.001）. Logistic regression analysis showed that HMGB1 level〔OR=8.411，95%CI（1.411，50.137），P<0.05〕，APS score〔OR=5.724，95%CI（1.108，29.572），P<0.05〕 were the independent risk factors for poor prognosis in children with severe pneumonia. The area under ROC curve for the combined diagnosis of HMGB1 and APS for the diagnostic value was 0.975〔95%CI（0.918，0.996）〕，and the optimal cut-off value was -0.203，and the sensitivity was 98.18%，and the specificity was 96.67%. The area under ROC curve for the combined diagnosis of HMGB1 and APS for the prognosis of pneumonia was 0.923〔95%CI（0.819，0.978）〕，and the optimal cut-off value was -0.030，and the sensitivity was 97.56%，and the specificity was 92.86%. Conclusion　Both HMGB1 level and APS score at admission are independent risk factors for the poor prognosis of severe pneumonia，and the combination of the two can further improve the diagnostic performance and prognosis of pneumonia.

Longitudinal Study of Catch-up Growth Assessed by Anthropometric Parameters in Very Premature Infants within 3 Years Old

QIN Qiaozhi, ZHAO Xueqin

Background　The improvement in perinatal medicine has promoted the increase of survival rate in very premature infants. Since growth and developmental delays will have a long-term impact on them，early catch-up growth is extremely important. However，there are few longitudinal studies on anthropometric parameters for assessing catch-up growth in such infants. Objective　To investigate the increasing trend of body weight，body length and head circumference（HC） of very premature infants within 3 years old，providing evidence for promoting scientific catch-up growth in such infants. Methods　Participants were selected from Northern Jiangsu People's Hospital during August 2017 to September 2018，including 120 ICU-treated very premature infants delivered at 28-32 weeks of gestation，who were divided into two group 〔small for gestational age（SGA）group（n=11） and appropriate for gestational age（AGA）group（n=109）〕，and 121 full-term infants. Body weight and length as well as HC were measured at 40 weeks，3，6，12，24 months of corrected age and 36 months，respectively，and z-scores and growth rates of these three parameters were calculated. Results　The z-scores of body weight，body length and HC differed statistically across SGA，AGA and full-term infants within 12 months of corrected age（P<0.05）. The catch–up growth for weight peaked within 3 months of corrected age in AGA infants and full-term infants，and it peaked within 3 to 6 months of corrected age in SGA infants. The growth for height showed a significant increase trend within 6 months of corrected age in AGA and full-term infants. For SGA infants，the catch–up growth for height peaked within 3 to 6 months of corrected age. The HC of AGA infants had an obvious trend of catch-up growth within 3 months of corrected age，while SGA infants'catch-up growth for HC was obvious after 3 monthsof corrected age，and it gradually slowed down after 12 months of corrected age. The body weight growth rate varied statistically across SGA，AGA and full-term infants during 40 weeks to 12 months of corrected age（P<0.05）. There were statistically differences of growth rates in body length and HC between the three groups during 40 weeks to 24 months of corrected age（P<0.05）. Conclusion　The trends of catch-up growth for body weight，height and HC were significantly different between SGA and AGA infants within 3 years old. Compared with AGA infants，the early catch-up growth rates of these three parameters in SGA infants were slower and imbalanced. Compared to full-term infants，the early catch-up growth rates of the three parameters in very premature infants were significantly slower. And the time point of peak for catch-up growth for each parameter varied significantly between SGA and AGA infants.

Clinical Characteristics and Risk Factors of Pulmonary Atelectasis in Pediatric Tracheobronchial Tuberculosis

　Background　Due to nonspecific clinical and thoratic imaging characteristics，pediatric tracheobronchial tuberculosis（TBTB）is easy to be misdiagnosed or missed. And repeated infections，lung function deterioration and even lobectomy could be induced if pulmonary atelectasis occurs in pediatric TBTB，causing great harm to children's health.Objective　To investigate the clinical characteristics and risk factors of pulmonary atelectasis in pediatric TBTB，providing clinical evidence for interventionally managing pediatric TBTB and for exploring the pathogenesis of this disease. Methods　A retrospective study was conducted. Participants were TBTB children（≤14 years old） who were selected from Public Health Clinical Center of Chengdu from July 2017 to November 2019 . TBTB children were ivided into two groups based on whether accompanied with pulmonary atelectasis，with atelectasis（n=23） and without atelectasis（n=137）.Baseline data，including demographics，clinicalsymptoms，complications，results of etiological test，chest imaging and bronchoscopic examination，were collected. Binary Logistic regression equation was used to analyze the risk factors of pulmonary atelectasis in pediatric TBTB. Results　One hundred and sixty patients were enrolled，with a male-to-female ratio of 1.08∶1，an median age of 12（9，13）years old. The prevalence of pulmonary atelectasis at admission was 14.4%（23/160）. Among the cases with pulmonary atelectasis，the prevalence of pulmonary atelectasis occurring in the right lung，and the right middle lobe was 65.2%（15/23），and 39.1%（9/23），respectively. Compared with those without pulmonary atelectasis，those with pulmonary atelectasis had younger median age of onset〔9（8，12）years old vs 12（10，13）years old〕，and lower rate of tuberculous cavities〔4.3%（1/23）vs 27.0%（37/137）〕（P<0.05）. Moreover，those with pulmonary atelectasis had lower prevalence of bilateral lobes involved（χ2=5.692，P=0.017）. Those with pulmonary atelectasis had higher prevalence of granulation hyperplasia TBTB than those without（χ2=11.915，P=0.001）. Age 〔OR=0.827，95%CI（0.710，0.965）〕and granulation hyperplasia TBTB〔OR=7.382，95%CI（1.979，27.539）〕were independent risk factors associated with pulmonary atelectasis in pediatric TBTB（P<0.05）. Conclusion　In our study，pulmonary atelectasis occurred in 14.4% of the children with TBTB，which was more present in the right lung，especially the right middle lobe. Younger age and granulation hyperplasia TBTB were associated with pulmonary atelectasis in pediatric TBTB.

Efficacy and Safety of Spironolactone in the Treatment of Resistant Hypertension：a Meta-analysis

　Background　As a special type of hypertension，resistant hypertension has complex etiology，is difficult to treat，and more likely to lead to target organ damage. Recent studies have found that common triple combination antihypertensive therapies plus low-dose spironolactone could effectively control blood pressure in patients with resistant hypertension，but the efficacy and safety of such treatments need to be further verified due to small scales of these studies. Objective　To perform a systematical review of the efficacy and safety of spironolactone for resistant hypertension. Methods　Randomized controlled trials（RCTs） on spironolactone for resistant hypertension were identified in databases of PubMed，Web of Science，The Cochrane Library，CNKI，VIP，and WanFang from inception to May 3rd，2021. Two researchers separately screened the RCTs，extracted data and assessed the risk bias of eligible studies. Meta-analysis was conducted using RevMan5.3. Results　Twenty RCTs were included，nine of which did not report randomization methods，one used randomization based on the sequence of numbers including odd and even numbers of admission （pseudo-randomization），seven did not report whether blinding was used，four were open-labeled，three described allocation concealment，and one had no complete results with no safety parameters for post-treatment of the controls. Meta-analysis revealed that compared to placebo and blank control groups，spironolactone-treated group had much lower clinic blood pressure，24-hour ambulatory blood pressure（ABP），daytime blood pressure and nighttime blood pressure（P<0.05）. Compared with patients treated with other antihypertensive drugs，spironolactone-treated patients had notably lower clinic systolic blood pressure（SBP），24-hour ABP，daytime SBP，nighttime SBP and self-measured home SBP（P<0.05）. Compared with those treated with renal nerve denervation，spironolactone-treated patients had significantly reduced daytime blood pressure and nighttime SBP（P<0.05）.In terms of safety，compared with those treated with placebo，spironolactone-treated patients had elevated serum potassium and creatinine（P<0.05）. Compared with patients treated with other antihypertensive drugs，spironolactone-treated patients had elevated serum potassium level（P<0.05）. Compared with those with renal nerve denervation，spironolactone-treated patients had elevated serum creatinine level（P<0.05）.Conclusion　Comparatively speaking，spironolactone is effective and safe for resistant hypertension. Due to limited quantity and quality of included studies，the conclusion still needs to be further verified by more high-quality studies.

Is the Change of Cytokines Related to Renal Damage in Children with IgA Vasculitis

WANG Mengdi, DU Yue

Background　The long-term prognosis of IgA vasculitis（IgAV） depends on thedegreeof renal damage. Studies on the pathogenesis of renal injury in IgAV have found that cytokines play an important role in mediating and driving the process of renal damage. Objective　To investigate the significance and value of cytokine in the process of renal damage in IgAV by exploring the changes of serum cytokine level in children with IgAV renal damage. Methods　194 IgAV children hospitalized in the Department of Pediatric，Shengjing Hospital of China Medical University from January 2018 to June 2020 were selected as research subjects. They were divided into IgAV group（n=97） and IgAV renal damage group （n=97） according to the presence or absence of renal damage，and 60 healthy children who underwent physical examination in the pediatric health department of our hospital during the same period were selected as the control group. The cytokines（IL-2，IL-4，IL-6，IL-10，IL-17，IFN-γ，and TNF-α），absolute lymphocyte count，immunoglobulin A，and immunoglobulin E were collected from the children. Multivariate Logistic regression was used to analyze the factors influencing IgAV renal damage，and the receiver operating curve （ROC） of the diagnostic value of cytokines on the characteristics of IgAV renal damage was drawn. Results 　The IL-2 level in the lgAV group were higher than those in the lgAV renal damage group and the control group，and the IL-2 level in the lgAV renal damage group was higher than that in the control group（P<0.05）；IL-17 level in the lgAV renal damage group were higher than those in the lgAV group and the control group，and IL-17 level in the lgAV group was higher than that in the control group（P<0.05）；IL-6，IL-10，and TNF -α level were higher in the lgAV renal damage group than those in the lgAV renal damage group and the control group（P<0.05）；IFN-γ level were higher in the lgAV renal damage group and the control group than that in the lgAV group（P<0.05）. Multivariate Logistic regression analysis showed that IL-2，IL-17，IFN-γ，and TNF-α were influencing factors in developing IgAV renal damage（P<0.05）. The AUC of IL-12 for predicting IgAV renal damage was 0.589，with a sensitivity of 38.0% and specificity of 47.0%. The AUC of IL-17 for predicting IgAV renal damage was 0.621，with a sensitivity of 47.4% and specificity of 77.3%. The AUC of IFN-γ for predicting IgAV renal damage was 0.688，with a sensitivity of 75.0% and specificity of 55.7%. The AUC of TNF-α for predicting IgAV renal damage was 0.614，with a sensitivity of 42.0% and specificity of 37.0%. The AUC of IL-17 and IFN-γ combined for predicting IgAV renal damage was 0.710，with a sensitivity of 71.1% and specificity of 66%. Conclusion　Serum cytokines IL-17 and IFN-γ are closely associated with the development of renal damage in IgA vasculitisrenal damage，early detection of both levels and dynamic monitoring of their changes can serve as an early warning for early detection of renal involvement and adjustment of treatment plans.

Development，Reliability and Validity of the Health Management Service Skills Training Evaluation Scale for Rural Doctors

Background　Few studies have evaluated the effectiveness of health management services sills trainings for rural doctors，and there is a lack of effective evaluation toolsin China. Objective　To develop the Health Management Service Skills Training Evaluation Scale for Rural Doctors（HMSSTESRD），and test its reliability and validity. Methods　The initial version of HMSSTESRD was developed using the framework of Kirkpatrick model，then was revised using expert consultation and group discussion，and was pretested using a survey with a sample of 100 cases conducted between May to June，2021. The scale was further revised according to the survey，and analyzed using reliability analysis and exploratory factor analysis，then the formal version was determined. In July 2021，the formal scale was retested in a sample（n=306），and was revised according to the test results，and was subjected to confirmatory factor analysis，homogeneous reliability analysis，compositereliability analysis，discriminant validity analysis，and structural validity analysis. Results　The formal scale consists of 15 entries in 4 dimensions：reaction，learning，behavior，and results. The KMO index was 0.847，Bartlett's test of sphericity was significant
（χ2=1 862.826，P<0.05），and the percentage of explained total variance in exploratory factor analysis was 87.575%. The results of the confirmatory factor analysis were χ2/df=3.906，RMSEA=0.098，CFI=0.961，IFI=0.961，and NFI=0.948，indicating that the model fit was basically good. When it comes to the formal scale，the Cronbach's α was 0.967. The Cronbach's α for each dimension（reaction，learning，behavior，and results） was 0.962，0.958，0.971，and 0.919，respectively. And the CR values for these dimensions were 0.963，0.958，0.971，and 0.919，respectively. The arithmetic square root of AVE was greater than the correlation coefficient between the factors. Theinter-dimension correlation coefficients were 0.538 to 0.842，and the dimension-scalecorrelation coefficients were 0.754 to 0.934. Conclusion　The HMSSTESRD developed by us has been proved to have good reliability and validity，which could be used as an effective tool for assessingtheeffectiveness of health management service skills trainingsfor rural doctors.

Review of Complementary and Alternative Medicine Therapies for Irritable Bowel Syndrome

SHI Yunzhou, ZHENG Hui, CHEN Min, LI Zhigang, YU Shuguang

Irritable bowel syndrome（IBS） is a functional gastrointestinal disorder frequently encountered clinically. Many IBS patients use complementary and alternative medicine（CAM） therapies for better treatment results when their conditions could not be improved by first-line drug treatment. However，due to limitations of quality and quantity of studies about CAM therapies，most of these therapies for IBS have not been recommended by relevant consensuses and guidelines. We overviewed common CAM therapies for IBS，detailed three types，namely，natural products，psychosomatic therapies，and Chinese medicine，aiming at increasing clinical workers and patients' understanding and application of these therapies.

Mechanism of Huangqi Jianzhong Decoction in Treating Diarrhea Predominant Irritable Bowel Syndrome Based on Network Pharmacology and Molecular Docking Technology

YE Kun, LEI Min, XIE Xin, ZHENG Hui, CHEN Min, YU Shuguang

Background　Clinical treatment often achieves unsatisfactory effect for irritable bowel syndrome（IBS），a common complex functional gastrointestinal disease. Huangqi Jianzhong Decoction is widely used for diarrhea IBS（IBS-D），and its efficacy has been recognized，but the mechanism is unclear and relevant studies are rare. Objective　To explore the potential mechanism of Huangqi Jianzhong Decoction in the treatment of IBS-D based on network pharmacology and molecular docking. Methods　TCMSP database was adopted to acquire the active ingredients and corresponding targets of all herbals in Huangqi Jianzhong Decoction. And targets related to IBS-D were identified using GeneCards，OMIM，TTD，Drug Bank and PharmGKB databases. Then the intersection of herbal targets and IBS-D-related targets were selected to obtain the potential therapeutic targets of Huangqi Jianzhong Decoction for IBS-D. Cytoscape，String and Metascape were used to construct an “herbals-active ingredients-target” network map，draw the protein-protein interaction network（PPI），and conduct genetic ontology（GO） enrichment and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway analyses. AutoDock Vina and PyMOL were used for the visualization of molecular docking results. Results　Finally，we obtained 123 active ingredients and 247 potential targets of Huangqi Jianzhong Decoction，3 486 IBS-D related targets，and 180 intersected herbals targets and IBS-D-related targets. A total of 2 376 items of biological process，194 items of molecular function and 115 items of cellular component were identified through GO enrichment analysis. Enrichment analysis of KEGG signaling pathway revealed MAPK，NF-κB，cAMP，estrogen and other related signal pathways. The molecular docking results showed that the main active ingredients of Huangqi Jianzhong Decoction in the treatment of IBS-D are quercetin，kaempferol，β-sitosterol，isorhamnetin，formononetin，stigmasterol，calycosin，7-O-methylisomucronulatol，and they showed good binding to core proteins AKT1，TP53，TNF，IL-6，CASP3，IL-1B，EGFR and CTNNB1. Conclusion　Therefore，we speculated that Huangqi Jianzhong Decoction may plays a role in the treatment of IBS-D by enhancing intestinal barrier function，reducing visceral hypersensitivity，reducing inflammatory response and regulating intestinal flora.

Factors Associated with Compliance and Association between Compliance and Recurrence in Patients with Acute Pancreatitis

YAN Liyanran, WANG Yaqian, WU Rina, CHEN Tianran, ZHANG Xueli

Background　Acute pancreatitis is one high-incidence acute abdominal condition，which is closely related to dietary habits and lifestyle. Patients' compliance with medical advice also directly affects treatment effect and prognosis. There are some studies on compliance in patients with acute pancreatitis，but little attention has been paid to its association with recurrence. Objective　To investigate the factors associated with compliance with medical advice and the association between compliance and recurrence in patients with acute pancreatitis. Methods　By use of convenience sampling，four grade A tertiary hospitals in Shijiazhuang City（The First Hospital of Hebei Medical University，the Second Hospital of Hebei Medical University，the Third Hospital of Hebei Medical University，and the Fourth Hospital of Hebei Medical University） were selected as survey settings，in which patients with acute pancreatitis treated from 2019 to 2021 were selected as the subjects. Then the patients were surveyed using a self-designed questionnaire for investigating their demographics，awareness level of acute pancreatitis，and health belief during the three days prior to discharge，and were followed up by telephone at 3，6，and 12 months after the questionnaire survey for acquiring the recurrence. They also attended another survey using a self-designed questionnaire at the last telephone follow-up for understanding their compliance. Results　In all，100 cases attended the survey，97 of them（97.0%） who effectively responded to the survey were included for final analysis. Among the 97 respondents，62（63.9%） were fully compliant，27（27.8%） partially compliant，and 8（8.3%） non-compliant. Multivariate Logistic regression analysis showed that gender〔OR=9.393，95%CI（1.909，46.223）〕，age〔OR=1.048，95%CI（1.000，1.099）〕，education level〔OR=0.572，95%CI（0.333，0.985）〕，and awareness level of acute pancreatitis〔OR=0.902，95%CI（0.834，0.976）〕 were associated with compliance in patients with acute pancreatitis（P<0.05）. During the 12 months of follow-up，41 patients（42.3%） relapsed and 56（57.7%） did not. There was a statistically significant difference in compliance of patients with and without recurrence（χ2=7.082，P=0.029）. Multivariate Logistic regression analysis showed that male〔OR=10.798，95%CI（1.034，112.781）〕，alcohol consumption〔OR=16.546，95%CI（1.310，209.049）〕，cholelithiasis〔OR=8.502，95%CI（1.694，42.673）〕，hyperlipidemia〔OR=5.287，95%CI（1.098，25.450）〕，partial compliance〔OR=0.115，95%CI（0.014，0.947）〕，and noncompliance〔OR=0.036，95%CI（0.003，0.513）〕 were risk factors for the recurrence of acute pancreatitis（P<0.05）.Conclusion　The factors affecting the compliance of patients with acute pancreatitis include gender，age，educational level，and awareness of acute pancreatitis，and compliance may be a key associated factor of the recurrence rate. Therefore，to reduce the development and recurrence of acute pancreatitis，it is suggested to take actions in accordance with the associated factors of compliance to promote relevant health education to improve patients' compliance with medical advice and ability of self-management. In addition，actions should be taken to reduce the influence of risk factors of recurrence of acute pancreatitis，such as improving unhealthy eating habits，quitting drinking，actively treating hyperlipidemia and other underlying diseases，and curing cholelithiasis and other predisposing factors as soon as possible.

Advances in Diagnosis and Management of Acute Kidney Injury Induced by Crush Syndrome

WANG Jinxiang, DONG Yuxin, ZHAO Yibo, MENG Xianglong, CHAI Yanfen, JIN Heng

Crush syndrome（CS） often occurs in victims of natural disasters，trauma and traffic accidents，which mainly manifests as hypovolemic shock，acute kidney injury（AKI），hyperkalemia，and acidosis，among which AKI is a major cause of the continuing high mortality of CS. Current treatments for AKI induced by CS include early rehydration，symptomatic treatment and renal replacement therapy，but the effects are not satisfactory. There are no standard treatment options for CS-related AKI，so identifying the pathogenesis of this disease and formulating an effective treatment regimen may be problems need to be solved urgently. This article reviews the latest advances in pathogenesis and treatment strategies of CS-related AKI.

Reducing the Risk of Adverse Events in Patients with Type 2 Diabetes Who are Poorly Treated with Metformin Combined with Acarbose：Dipeptidyl Peptidase-4 Inhibitor is Better Than Insulin

Background　Clinically，when metformin （Met） combined with acarbose （Aca） cannot achieve the ideal hypoglycemic effect，a third drug will be usually added，such as insulin （Ins） or dipeptidyl peptidase-4 inhibitor （DPP-4i）etc.，but there are few reports on the effect of triple therapy on complications related to type 2 diabetes （T2DM）. Objective　To explore the risk of adverse events of DPP-4i combined with Met and Aca，Ins combined with Met and Aca in the treatment of T2DM patients，in order to provide help for the choice of drugs for clinical T2DM treatment. Methods　In the retrospective cohort study，patients diagnosed with T2DM and treated with Met+Aca+ DPP-4i or Met+Aca+Ins in Shijiazhuang Second Hospital from November 1，2017 to August 1，2020were selected as the study subject. Telephone follow-up was conducted from November 20，2017 to August 4，2020，the follow-up wasn't terminated until a preset outcome occurred，then that was recorded. The four prespecified outcome events were non-fatal cardiovascular disease，death from all causes，severe hypoglycemic events，and composite events （including all-cause death，composite non-fatal cardiovascular events，and severe hypoglycemic events）. Propensity score matching （1∶1 ratio for data matching，caliper value set to 0.02） was used，and multivariate Cox proportional hazards regression model was used to analyze the risk of composite events in T2DM patients after drug treatment. Stratified analysis was performed on the effect of each covariate on the risk of composite events in patients treated with different drugs. Results　Finally，1 570 patients with T2DM were enrolled，including 1 089 patients who received Met+Aca+Ins treatment （Met+Aca+Ins group） and 481 patients who received Met+Aca+DPP-4i treatment （Met+Aca+DPP-4i group）. There were 434 cases in both groups after propensity score matching. Compared with the Met+Aca+Ins group，the incidences of comprehensive events （6.53/100 person-per year），non-fatal cardiovascular disease （5.03/100 person-years），all-cause death （0.73/100 person-per year），and severe hypoglycemic （0.73/100 person-er year） were lower in the Met+Aca+ DPP-4i group. The multivariate Cox proportional hazards regression model analysis showed that the risk of composite events in the Met+Aca+DPP-4i group was 67% lower than the Met+Aca+Ins group 〔HR=0.34，95%CI（0.23，0.50），P<0.001〕，the risk of composite non-fatal cardiovascular disease decreased by 52% compared with the Met+Aca+Ins group 〔HR=0.48，95%CI （0.30，0.77），P=0.002〕，and the risk of all-cause mortality was higher than the Met+Aca group. The Met+Aca+Ins group group decreased by 81% 〔HR=0.19，95%CI（0.07，0.56），P=0.003〕，and the risk of severe hypoglycemia decreased by 80% compared with the Met+Aca+Ins group 〔HR=0.20，95%CI（ 0.07，0.59），P=0.003〕. The survival curve was drawn with the composite event as the outcome event. The results of Log-rank test showed that the survival rate of Met+Aca+DPP-4i group was higher than the Met+Aca+Ins group （χ2=32.849，P<0.001）. The results of covariate interaction analysis showed that in patients with adequate sleep （>7 h/d），non-smoking，and no family history of cardiovascular disease，Met+Aca+DPP-4i treatment reduced the incidence of composite events in T2DM patients compared with Met+Aca+Ins treatment（P values were 0.008，0.031，and 0.042，respectively）. Conclusion　After failure treatment of Met and Aca in T2DM patients，the supplementation of DPP-4i was associated with a lower risk of comprehensive events，cardiovascular disease，all-cause mortality，and severe hypoglycemia compared with the Ins addition，particularly in patients with adequate sleep，no smoking，and without family history of cardiovascular disease.

Associated Factors of Osteoporosis in Elderly Patients with Stable Chronic Conditions

DAI Jingrong, LI Jie, HE Xu, LI Yang, LI Yan

Background　China is seeing increasingly osteoporosis prevalence as ageing marches on. However，the specific etiology and pathogenesis of osteoporosis are still unclear，and there are still limitations in its prevention and treatment. Objective　To investigate osteoporosis prevalence and associated factors in older Chinese patients with stable chronic conditions. Methods　Three hundred and two elderly inpatients with stable chronic conditions who underwent a reexamination in Department of Geriatrics，the First People's Hospital of Yunnan Province from November 2020 to September 2021 were recruited. Dual-energy X-ray absorptiometry（DXA） was used to measure lumbar spine and hip bone mineral density（BMD）. T value ≤-2.5 was defined as osteoporosis. Demographic data were collected. Comprehensive geriatric assessment was conducted via a self-developed online platform named Comprehensive Geriatric Assessment. Fasting venous blood samples were collected and measured for serum biomarkers. Results　Among the patients，126（41.7%） were found with osteoporosis，and other 176（58.3%） without. Binary Logistic regression analysis indicated that insomnia〔OR=2.096，95%CI （1.040，4.228）〕，multiple chronic conditions〔OR=1.223，95%CI（1.101，1.358）〕，elevated homocysteine〔OR=1.045，95%CI （1.002，1.089）〕 were associated with increased risk of osteoporosis（P<0.05），while elevated serum uric acid level〔OR=0.996，95%CI（0.994，0.999）〕 was associated with decreased risk of osteoporosis（P<0.05）.Conclusion　The prevalence of osteoporosis in these older patients with stable chronic conditions was 41.7%. The probability of osteoporosis may be decreased with elevated serum uric acid level，and increased with elevated homocysteine，insomnia and multiple chronic conditions.

Research Agenda for General Practice / Family Medicine and PrimaryHealth Care in Europe. European General Practice Research Network，Maastricht 2009.

Bioinformatic Analysis of Potential Key Genes in Castration-resistant Prostate Cancer Development

Background　Castration-resistant prostate cancer（CRPC） is one of the most prevalent cancers in males with a high fatality rate. Its molecular mechanism is still unclear，and there is no effective treatment. Objective　To explore the key genes involved in CRPC development using bioinformatic analysis，offering new ideas for the diagnosis and treatment of CRPC. Methods　The data set GSE32269 which contains human primary prostate cancer and CRPC was downloaded from the Gene Expression Omnibus database for further bioinformatic analysis. R language was used to identify differentially expressed genes（DEGs） in CRPC. Gene Ontology（GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway analysis of DEGs were further performed by using DAVID. A protein-protein interaction（PPI） network of DEGs was constructed by using STRING database for screening potential key genes. And the identified potential key genes were further analyzed by survival analysis and receiver operating characteristic（ROC） curve analysis. Results　279 DEGs were identified in microarray dataset GSE32269. GO enrichment analysis and KEGG pathway analysis revealed that cell division，mitosis and cell cycle signaling pathways may play an important role in the development of CRPC. PPI network screening revealed that there were 15 potential key genes，among which CDC20，MAD2L1 and NUSAP1 expressed differentially in CRPC patients：those with highly expressed CDC20，MAD2L1 and NUSAP1 had statistically lower overall survival rate and disease-free survival rate than did those with low expressed CDC20，MAD2L1 and NUSAP1（P<0.05）. The area under the ROC curve of CDC20，MAD2L1 and NUSAP1 to predict the occurrence of CRPC were 0.933，0.762，and 0.950，respectively，indicating that each of them may have a high diagnostic value for CRPC. Conclusion　CDC20，MAD2L1 and NUSAP1 may be key candidate genes associated with the development of CRPC.

Association and Predictive Value of Maternal Serum Clq/ Tumor Necrosis Factor-related Protein-3 Ratio with Gestational Diabetes Mellitus in Early Pregnancy：a Prospective Study

ZHANG Liqian, GUO Yanwei, XU Qian, YANG Ting, MAO Shufang

Background　Gestational diabetes mellitus （GDM） is characterized by increased insulin resistance. As serum complement Clq/ tumor necrosis factor-related protein 3 （CTRP3） ratio is closely related to insulin resistance，which may be involved in the development of GDM. However，the association and predictive value of serum CTRP3 ratio with GDM in early pregnancy have been rarely reported. Objective　To explore the association and predictive value of serum CTRP3 ratio with GDM in early pregnancy，providing new ideas for the prevention and treatment of GDM. Methods　Women in early pregnancy who underwent regular obstetric examinations in Obstetric Clinic，Affiliated Hospital of Chengde Medical University，were prospectively and consecutively enrolled from June 2018 to March 2019. Demographics，fasting plasma glucose（FPG），fasting insulin （FINS），glycosylated hemoglobin （HbA1c），triglyceride （TG），total cholesterol （TC），high-density lipoprotein cholesterol （HDL-C），low-density lipoprotein cholesterol （LDL-C） and serum CTRP3 ratio measured at 6-14 weeks of gestation were collected. The 75 g oral glucose tolerance test（OGTT） was performed to screen GDM at 24-28 weeks of gestation. Results　Finally，368 of the 393 cases were enrolled for analysis，including 81（22.01%） who were detected with GDM by the 75 g OGTT. Compare with those with normal glucose tolerance（NGT） diagnosed by the 75 g OGTT，GDM cases had much greater average age，pre-pregnancy BMI，FPG，HbA1c，FINS，and TG（P<0.05），but showed no significantly different composition of ethnic groups，average baseline gestational age，HDL-C，LDL-C and TC （P> 0.05）. Serum CTRP3 ratio in GDM group was lower than that in NGT group 〔0.528 0 （0.461 3，0.634 0） μg/L vs 0.604 8 （0.510 8，0.666 0） μg/L，P=0.01〕. Multivariate logistic regression analysis showed that serum CTRP3 ratio was an independently associated with GDM in early pregnancy 〔aOR=0.101 （0.010，0.997），P<0.05〕. The AUC of serum CTRP3 ratio in predicting GDM in early pregnancy was 0.622〔95%CI（0.571，0.672）〕with 49.38% sensitivity，and 72.13% specificity when≤0.524 2 μg/L was chosen as the optimal cutoff value. The AUC of a combined prediction model（serum CTRP3 ratio in combination with age，pre-pregnancy BMI，FPG and HbA1c） in predicting GDM in early pregnancy was 0.841〔95%CI（0.799，0.877）〕，with 69.14% sensitivity and 89.30% specificity when >0.135 0 was chosen as the optimal cutoff value. The AUC of the combined prediction model was greater than that of serum CTRP3 ratio（Z=5.634，P<0.001）. Conclusion　Increased serum CTRP3 ratio may be associated with lowered risk of GDM，so it could be used as an independent predictor for GDM in early pregnancy. Furthermore，its combined use with maternal demographic and metabolic indicators may produce a better predictive value for GDM in early pregnancy.

Impact of Average Daily Temperature on Stroke Mortality in Pudong New Area：a Time-Series Analysis

Background　With the increasing frequency of extreme weather events due to global climate change，the impact of air temperature on stroke deaths is gaining increasing attention. Objective　This study aimed to evaluate the impact of average daily temperature on stroke mortality in Pudong New Area. Methods　Data were collected from Pudong New Area from January 1，2005 to December 31，2019，including deaths due to stroke （hemorrhagic stroke and ischemic stroke），meteorological information（air temperature，relative humidity，atmospheric pressure），atmospheric pollutants 〔particulate matter 10（PM10），sulfur dioxide （SO2） and nitrogen dioxide （NO2）〕. We used a distributed lag non-linear model （DLNM） to evaluate the impact of average daily air temperature on stroke mortality，and assess the lagged and cumulative effects. Age- and education attainment-specific analyses were performed to identify the susceptible groups. Results　During the period，a total number of 30 337 deaths from stroke were reported in Pudong New Area of Shanghai，and the deaths due to hemorrhagic stroke and ischemic stroke numbered 11 221（36.99%） and 15 308（50.46%），respectively. The average daily deaths from stroke，hemorrhagic stroke and ischemic stroke were 5.54，2.05 and 2.79，respectively. The average daily temperature，relative humidity and air pressure in Pudong New Area were 17.25 ℃，73.75%，and 1 015 hPa，respectively. The average daily concentrations of PM10，SO2 and NO2 were 68.87 μg/m3，28.82 μg/m3，and 44.68 μg/m3，respectively. Using the average median daily temperature（P50=18.2 ℃） as a reference，the strongest cumulative effects of low temperature（P5=3.0 ℃） were observed within 0-14 days lagged （Lag 0-14） for stroke mortality〔RR=1.34，95%CI（1.15，1.56）〕 and hemorrhagic stroke mortality. The impact of low temperature on stroke mortality and hemorrhagic stroke mortality was significantly lagged and cumulated，but its impact on ischemic stroke mortality was not significant. The strongest cumulative effects of high temperature （P95=30.1 ℃） on stroke mortality 〔RR=1.26，95%CI（1.12，1.41）〕 and ischemic stroke 〔RR=1.64，95%CI（1.39，1.93）〕were observed within 0-1 day lagged （Lag 0-1）. High temperature imposed an acute effect on stroke mortality and ischemic stroke mortality，but produced insignificant effect on hemorrhagic stroke mortality. No significant impact of low temperature was observed on stroke mortality in population < 75 years old，but the impact on stroke mortality in population ≥ 75 years old was strongest within Lag 0-14 d. The strongest impacts of low temperature on stroke mortality in population with primary education or below，and in population with secondary education or above were observed within Lag 0-21 d and Lag 0-14 d，respectively. No significant impact of high temperature was observed on stroke mortality in population < 75 years old and population with secondary education and above，but the impact was the strongest on stroke mortality in population ≥ 75 years old and the population with primary education or below within Lag 0-1 d. The impact of high temperature on stroke mortality in population with primary education or below was significantly higher than that in population with secondary education and above within Lag 0-3 d （P<0.05）. Conclusion　Both low and high temperatures were associated with the stroke mortality risk in Pudong New Area. Low temperature increased the risk of death from hemorrhagic stroke，while high temperature increased the risk of death from ischemic stroke. People with primary education or below were more likely to die from strokes in hot environments.

Value of 3D Ultrasonography with Malignancy Risk Model for Screening for Endometrial Cancer with Postmenopausal Bleeding

LU Panping, LIAO Yumei, ZHANG Zhelin

Background　With the increasing incidence and mortality of endometrial cancer （EC），early and effective screening for EC has become a hot research topic. Objective　To investigate the value of three-dimensional （3D） ultrasonography with a malignancy risk model for screening for EC with postmenopausal bleeding （PMB）. Methods　A total of 168 patients who visited the Second Affiliated Hospital of Zhengzhou University for PMB between January 2019 and December 2020 were selected，and 136 of them were found with benign endometrial lesion，other 32 with EC by histopathological examination. All of them underwent 3D transperineal ultrasonography，and parameters such as endometrial volume，vascularization index （VI），flow index （FI），and vascularization-flow index （VFI） were calculated using VOCAL software. Clinical data were retrospectively collected，in which endometrial thickness，recurrent vaginal bleeding，age，body mass index （BMI），and history of diabetes mellitus were included in a malignancy risk model and scored for predicting EC with PMB. The ROC curve was plotted and the area under which （AUC） was calculated to measure the performance of 3D transperineal ultrasonography，malignancy risk model，and the combination of them in predicting EC with PMB. Results　Compared with those with benign endometrial lesion，EC patients had greater average BMI，and higher rate of recurrent vaginal bleeding （P<0.05）. Moreover，they also had thicker average endometrial thickness，greater average endometrial volume as well as higher average VI，FI，and VFI （P<0.05）. In predicting EC with PMB，3D transperineal ultrasonography （the combination of EV，VI，FI and VFI parameters） combined with the malignancy risk model had a greater AUC than did 3D transperineal ultrasonography { 0.949 〔95%CI（0.908，0.989）〕vs 0.883〔95%CI（0.817，0.949）〕}（Z=4.762，P=0.032），and the malignancy risk model { 0.949〔95%CI（0.908，0.989）〕 vs 0.723〔95%CI（0.629，0.817）〕}（ Z=2.613，P=0.018）. The sensitivity，specificity，and Youden index of the combined use of 3D transperineal ultrasonography and malignancy risk model for predicting EC with PMB were 84.4%，96.3%，and 0.807，respectively. Conclusion　The combined use of 3D transperineal ultrasonography and malignancy risk model for predicting EC with PMB has high accuracy，which could be used to initially triage patients.

Chronic Disease Patients Involved in Shared-decision Making in General Outpatient Care in the Community: Current Status and Associated Factors

MA Wenhan, BAI Xuefei, CHEN Zhaojuan, ZHAO Yali

Background　Thegeneral practice clinic in community health centers is facing increasingly complex challenges to meet the medical needs of patients with chronic diseases. To improve chronic disease patients'health outcome and healthcare satisfaction，it will be of great significance to use shared decision-making（SDM） in the diagnostic and therapeutic process in the community，since SDM is a model based on doctor-patient mutual respect and cooperation and shows great promise as a possible major medical decision-making model. Objective　To understand the status and associated factors of chronic disease patients involved in SDM in general outpatient care in the community，aiming to provide evidence for promoting the implementation of SDM in primary care. Methods　We used cluster sampling to select seven general practitioners（GPs）in the clinic of Shuangyushu Community Health Center，Beijing，and 149 chronic disease patients seen by them between October 2019 and January 2020 as the participants. Through non-participant observation at the clinic，we used the Chinese version of the Observer OPTION 5（OPTION-5）as an assessment tool to evaluate the extent to which GPs facilitated patient participating in SDM during the consultation. We used a self-developed general demographic questionnaire to collect patients'demographics，status of illness and treatment，as well as GPs'demographics. We compared the OPTION-5 score of the patients by demographic factors，and used stepwise multiple linear regression to explore the factors affecting patients' participation in SDM. Results　The mean visit length，and OPTION-5 score for the 149 patients were（4.1±2.7）minutes，and〔6.0（4.0 to 7.0）〕，respectively. The OPTION-5 score varied significantly across patients by age group and visit length（P<0.05）. Multiple linear regression analysis showed that patient visit length，prevalence of interruption of counseling due to other people，and prevalence of family member accompaniment to medical visits were associated with patients'participation in SDM（P<0.05）. Conclusion　The participation of these patients in SDM was relatively low. Prolonging GP-patient communication time，improving the ability of GPs to use patient information，ensuring that the diagnosis and treatment process is not interrupted，and giving patients a private space during diagnosis and treatment process may be feasible interventions to improve the participation of chronic disease patients in SDM in primary care.

Analysis of Gut Flora in a Mouse Model of Esophageal Squamous Cell Carcinoma in Situ

ZHANG Yushuang, YU Fuyang, WU Zhongbing, WANG Yiran, LI Jing

Background　With the application and development of high-throughput sequencing-based approaches for gut flora analysis，increasing studies have confirmed that gut flora is closely related to the development of various cancers. The relationship of gut floras with esophageal squamous cell carcinoma （ESCC），a common cancer threatening the health of Chinese people，has attracted extensive attention. Objective　To analyze the diversity of gut floras between a rat model of ESCC in situ and normal mice，to identify the carcinoma-specific bacterial genus in ESCC. Methods　 From August 2020 to May 2021，20 female SPF C57BL/6 mice were randomly and equally divided into control group and model group. Rice in control group were routinely fed and given ordinary drinking water for 32 weeks，and those in model group were routinely fed and received water containing 0.1mg/ml cancer inducer 4-nitroquinoline-1-oxide for 16 weeks，and then only fed with ordinary drinking water for another 16 weeks. Stool samples of both groups were collected，and DNA in faeces was extracted and amplified by PCR，followed by high-throughput sequencing. The obtained sequencing data were divided into operational taxonomic units （OTU） based on the similarity between sequences. The α-diversity，β-diversity and species abundance were further analyzed according to species annotation. Results　No death occurred in the experiment，and the modeling of ESCC was successfully established in model group. Compared with control group，the proportion of Bacteroidota and Firmicutes increased，while the proportion of Verrucomicrobiota and Proteobacteria decreased in model group. Analysis showed that the α-diversity measured by Shannon Diversity Index in model group was lower than that of control group （P<0.05）. As for β-diversity analysis，PCoA diagram showed that the gut floras of control and model groups clustered in different quadrants，suggesting a significant discrepancy between the groups（t=22.444，P=0.004）. At the phylum level，the abundances of unidentified bacteria，Cyanobacteria，Elusimicrobia and Campilobacterota were higher in model group than those in control group （P<0.05）. At the genus level，the abundances of Prevotellaceae_UCG-003，Bacteroides and Lachnospiraceae_NK4A136_group，Ruminococcus，Prevotellaceae_UCG-001，Prevotella，Colidextribacter，Lachnospiraceae_UCG-006 were higher while those of Romboutsia and Turicibacter were lower in model group than those in control group （P<0.05）. LEfSe analysis showed that，at the genus level，the abundances of Prevotellaceae_UCG-003，Escherichia-Shigella，Bacteroides，Lachnospiraceae_NK4A136_group were increased significantly in model group，but the abundance of Romboutsia was increased significantly in control group DZ（P<0.05）. Conclusion　 By comparing the composition of gut flora，we identified the rat model of ESCC may have less diversity of species and specially differentiated bacteria，and Prevotellaceae_UCG-003，Bacteroides，Lachnospiraceae_NK4A 136_group，and Romboutsia could be used as biomarkers for ESCC.

Predictive Value of Hemodynamic Indicators for Bronchopulmonary Dysplasia in Preterm Infants

JIA Nan, HE Yujuan, ZHAO Xiaoxiao, ZHANG Weixing

Background　In China，the growing prevalence of bronchopulmonary dysplasia（BPD）in increased number of survived very preterm and extremely preterm infants，seriously endangers the life and impairs quality of life in this population. However，there are relatively few studies about the correlation between the occurrence of BPD and hemodynamic indicators in preterm infant. Objective　To examine predictive value of the hemodynamic indexes for BPD in premature infants.Methods　One hundred and sixty-one premature infants（gestational age <32 weeks）were selected from Xinxiang Central Hospital from September 2018 to December 2020. The general data（gestational age，birth weight，sex，and mode of delivery）were collected；The basic diseases and other complications of preterm infants were collected，compared between two groups of infants divided by the prevalence of BPD. PI values（measured at 1，12，48，72 and 96 hours after delivery，and on the 5th，6th，and 7th days after delivery，respectively），and serum lactic acid levels（measured at 1，12，and 24 hours after admission，respectively）were collected. Mean arterial pressure（MAP）levels measured by arterial pressure monitoring at 1，12 and 24 hours after admission for 33 infants（16 in BPD group and 17 in the control group）with critical or extremely critical conditions suggested by neonatal critical illness score were also collected.Comparethe results between two groups，the receiver operating characteristic（ROC）curve was plotted to evaluate the predictive value of PI，serum lactic acid and MAP for BPDin preterm infants. Results　Sixty-five out of the 161 cases 〔40.3%（65/161）〕were diagnosed with BPD. Preterm infants with and without BPD had no statistically significant differences in gestational age，birth weight，gender，and mode of delivery（P>0.05）. Preterm infants with BPD had higher incidence of neonatal asphyxia，neonatal respiratory distress syndrome，neonatal pneumonia，and retinopathy of prematurity than those without（P< 0.05）. Preterm infants with and without BPD had no statistically significant differences in sepsis，pulmonary hemorrhage，PDA，IVH，purulent meningitis and anemia（P>0.05）. PI values at 1，12 and 24 hours after birth differed significantly between the two groups（P<0.05）. Serum lactic acid at 1 hour after admission differed significant between the two groups（P<0.05）. MAP levels at different time periods showed no significant differences between critical and extremely critical preterm infants with and without BPD（P>0.05）. In predicting BPD，the PI at 1 hour，12 hour，and 24 hour was 0.847〔95%CI（0.788，0.906），P<0.001〕，0.776〔95%CI（0.705，0.846），P<0.001〕，0.695〔95%CI（0.613，0.778），P<0.001〕，respectively；the optimal cutoff value was chosen as 0.545，1.15，1.45，with the sensitivity of 76.9%，86.2%，81.5% and the specificity of 75.0%，60.4%，51.0%；serum lactic acid at 1 hour after birthhad an AUC of 0.762〔95%CI（0.686，0.837），P<0.001〕，the optimal cutoff value was chosen as 6.55，with the sensitivity of 81.5%，and the specificity of 68.7% . Conclusion　In preterm infants with a gestational age <32 weeks，the change of hemodynamic indicatou PI and lactic acid value maybe correlated with the occurrence of BPD. PI value within 24 hours after birth may be an earlypredictor for BPD，but further research is still needed.　

Ethnic-specific Clinical Features in Children with Non-M3 Acute Myeloid Leukaemia from Yunnan Province

Background　Childhood acute myeloid leukaemia （AML） is a higly heterogenous disorder. But its clinical characteristics according to ethic groups have been rarely studied. Objective　To explore ethnic-specific clinical characteristics and prognosis of paediatric patients with non-M3 AML from Yunnan province. Methods　Paediatric patients with newly diagnosed non-M3 AML were rectuited from Kunming Children's Hospital between January 1，2015 and March 1，2020 . Basic baseline clinical data，including demographic characteristics （ethnic group，gender，age），general information （white blood cell count，haemoglobin，platelet count，lactate dehydrogenase，bone marrow blast cell，FAB classification），karyotype，and genetic information were collected. All patients were followed up from enrolment to 2020-05-31，and treatment protocols，risk stratifications，and prognoses were collected. Results　Seventy-two cases〔51 cases of Han，21 cases of minorities（5 Yi，4 Hui，3 Hani，2 Bai，2 Miao，1 Zhuang，1 Wa，1 Buyi，1 Mongolian and 1 Dai）〕 were enrolled，with a follow-up of 2-60 months. Children of ethnic minorities had higher mean white blood cell count did those of Han（P<0.05）. Follow-up analysis showed that compared with children of Han，children of ethnic minorities had higher risk and moratlity（P<0.05），but domonstrated simailar complete remission rate，recurrence rate and bone marrow transplantation rate after the first course of induction therapy（P>0.05）. Event-free survival rate and overall survival rate of children of Han were higher than those of children of ethnic minorities （χ2=8.098，P=0.004；χ2=12.547，P<0.001）. Conclusion　Non-M3 AML children of Han had lower risk and better prognosis than those of ethnic minorities in Yunnan，but the reason has not been identified.

Research Status and Thoughts on the Comparative Effect of Traditional Chinese Medicine in the Treatment of IBS-D

Diarrhea irritable bowel syndrome（IBS-D） is a common clinical disease with high prevalence and recurrent episodes. Patients with IBS-D often suffer from anxiety and depression，which bring a huge medical burden to the society. There are many clinical treatment options for IBS-D，especially in the field of traditional Chinese medicine（TCM）. Which one is better among traditional Chinese medicine treatment methods has become a common concern of clinicians，patients and medical decision-makers. As the real world research has gradually attracted the keen attention of scholars，the technical methods of comparative effect research（CER） have developed by leaps and bounds in the past five years. By reviewing the CER application of clinical effect assessment in the treatment of IBS-D with TCM，combined with the methodological innovations of comparative effect research in the past five years，this article discusses the current status of CER in the treatment of IBS-D with TCM，and then considers how to design， implement and evaluate the comparative effect of TCM in real-world clinical research.

Clinical Study of Venetoclax with Chemotherapy for Relapsed/Refractory Acute Myeloid Leukemia

CHEN Xiaofeng, WANG Meng, LI Zhongyu, LI Jiajia

Background　 Adults with relapsed/refractory acute myeloid leukemia（AML） have poor prognosis，very low long-term survival rate and cure rate，and limited chemotherapy regimens. Objective　To investigate the safety and efficacy of venetoclax（VEN） with HAAG ［homoharringtonine （HHT），Cytarabine（Ara-C），aclacinomycin（Acla），granulocyte stimulating factor（G-CSF）］ in relapsed/refractory AML. Methods　The clinical data of 10 adult patients with relapsed/refractory AML treated in the First Affiliated Hospital of Bengbu Medical College were analyzed retrospectively，including：clinical characteristics （sex，age，diagnosis，chromosome，gene mutation，prognosis），peripheral blood and bone marrow cytology，and the effect of Ven+Aza+HAAG regimen. Results　Among the 10 patients，there were 7 men and 3 women，with an average age of （47.9±11.3）years；4 cases of M2 and 6 cases of M5 by FAB classification；3 cases of good prognosis，2 cases of fair and 5 cases of poor. The median levels of WBC count，hemoglobin content，and platelet count，as well as median percentage of bone marrow blast cells before chemotherapy of the patients were 4.10×109/L，87.5 g/L，66.00×109/L，and 63.5%，respectively，and after chemotherapy，the values of these four indicators were 3.28×109/L，107.0 g/L，78.00×109/L and 5.5%，respectively. Before VEN+Aza+HAAG regimen combined chemotherapy，the median number of chemotherapy used by the patients was 5. And after the combined therapy，there were 1 case of complete remission（CR）and 4 cases of CR with incomplete count recovery（CRi），3 cases of partial remission（PR），and 2 cases of non-remission （NR）. The objective response rate of 10 patients was 80%，and median survival time was 〔6.5+ （3，8.5）〕months. The toxic and side effects were mainly bone marrow suppression and infection. No patients died of treatment-related complications and other toxic and side effects. Conclusion　Compared with traditional chemotherapy regimen，the use of Ven + Aza + HAAG with chemotherapy could significantly improve the objective response rate and remission degree，and prolong the survival in patients with relapsed/refractory AML，which is worthy of further study and has a prospect of clinical application.

Burnout and Associated Factors among Family Doctor Team Members in Different Types of Primary Healthcare Institutions：a Comparative Study

Background　Burnout has become a prominent issue as the increase of workload in family doctor team members in primary healthcare institutions during the promotion of contracted family doctor services. There is still a lack of research comparing the differences in burnout among family doctor team members in different types of primary healthcare institutions. Objective　To compare burnout prevalence and associated factors between family doctors in community/township health centers，and those in community health stations/village clinics，providing a basis for improving the mental health status and team stability of family doctors，as well as the quality of services provided by them. Methods　From August 1 to 21，2020，a multistage cluster random sampling method was used to select 760 family doctor team members〔201（26.4%） working at community/township health centers，and 559（73.6%） working at community health stations/village clinics〕 as the participants from primary healthcare institutions in 6 counties/county-level cities /districts of Taian City，Shandong Province. They were invited to attend a survey to complete Demographic Questionnaire and the Chinese version of Maslach Burnout Inventory-General Survey（MBI-GS）. Results　Overall，the prevalence of burnout among the participants was 68.9%（524/760）. The prevalence of burnout of family doctor team members in community health stations/village clinics was higher than that of those in community/township health centers，with a statistically significant difference〔70.8%（396/559）vs 63.7%（128/201）〕（P<0.05）. Family doctor team members in community health stations/village clinics had higher total score of MBI-GS and higher subscale score of professional efficacy than did those in community /township health centers，with a statistically significant difference（P<0.05）. Multivariate Logistic regression analysis showed that：for family doctor team members in community/township health centers，the risk of burnout of those aged 41-50 years is higher than that aged ≤30 years〔OR（95%CI）=7.119（1.770，28.638）〕，the risk of burnout of those with monthly income >4 000 yuan is lower than that with monthly income ≤2 000 yuan〔OR（95%CI）=0.194（0.040，0.941）〕，the risk of burnout of those with high/very high self-rated work pressure is higher than that of those without/little self-rated work pressure〔OR（95%CI）=3.629（1.475，8.929）〕，the risk of job burnout of those who evaluated the incentive mechanism as relative effective/very effective and ordinary was lower than that evaluated the incentive mechanism as very ineffective/less effective〔OR（95%CI） were 0.196（0.052，0.739） and 0.235（0.066，0.834）〕. For the family doctor team members in community health stations/village clinics，the risk of burnout in women is lower than that in men〔OR（95%CI）=0.603（0.396，0.920）〕，the risk of job burnout of those with general and relatively high/very high self-assessment residents' recognition is lower than that with very low/relatively low self-assessment residents' recognition〔OR（95%CI） were 0.258（0.113，0.590） and 0.428（0.199，0.918）〕，the risk of burnout of those with high/very high self-rated job stress is higher than that without/little self-rated job stress〔OR（95%CI）=2.320（1.368，3.935）〕. Conclusion　Family doctor team members in community health stations/village clinics demonstrated higher burnout prevalence，and lower professional efficacy. To reduce the burnout prevalence and improve professional efficacy in family doctor team members，it is suggested to strengthen trainings，increase salary and further improve incentive mechanism for those in community/township health centers，and to increase the number of officially budgeted posts，and promotion opportunities as well as the propaganda of contracted family doctor services for those in community health stations/village clinics. Moreover，the workflow of contracting family doctor services should be simplified in all these institutions.

The Availability of Essential Medicines and Diagnostic Devices for Chronic Obstructive Pulmonary Disease in Primary Care

PENG Bo, ZHANG Xiaojuan, JIANG Xiaotong, ZHENG Jianli, LI Yazi

Background　China has seen a significantly increased prevalence of chronic obstructive pulmonary disease（COPD） recently. But primary care institutions，the main "battlefield" for containing COPD，have shown relatively weak capabilities for the diagnosis and treatment of disease. As there are relatively few large-scale investigations and studies on medicines and diagnostic devices for COPD in primary care，we conducted this study to further understand the weaknesses of current COPD containment in primary care，by which the gap in related research may be made up. Objective　To understand the allocation and availability rate of essential medicines for COPD，and availability rate of spirometer as well as the implementation of pulmonary function tests in primary care. Methods　From February to March 2021，a multi-stage cluster sampling was adopted to select 8 176 community（township） health centers from 31 provinces of China to attend a survey. The rates of availability and allocation of each of the 16 essential medicines for COPD in the 2018 National Essential Medicines List were calculated to estimate the categories and number of these medicines in primary care institutions. The rate of availability of spirometer in these institutions was estimated. And the rate of implementation of pulmonary function tests in these institutions was estimated. Results　Altogether，7 458（91.22%） institutions who gave effective responses to the survey were included for analysis，including
5 901（79.12%） township health centers，and 1 557（20.88%） community health centers. Among the 16 essential medicines for COPD，less than 8 were available in 6 538（87.66%） institutions，at least 1 inhaled antiasthmatic medicines were available in 4 992（66.00%） institutions，and long-acting inhaled antiasthmatic medicines were available in 814（10.91%） institutions. The average availability rate of 16 essential medicines for COPD was 33.30%. The highest ranked three medicines in terms of availability rate were ambroxol〔85.28%（6 360/7 458）〕，aminophylline〔81.17%（6 054/7 458）〕 and compound licorice〔74.48%（5 555/7 458）〕. And the relatively low-ranked three were fluticasone propionate 〔4.89%（365
/7 458）〕，tiotropium bromide〔6.25%（466/7 458）〕，budesonide forterol〔8.61%（642/7 458）〕. The average availability rate of 6 inhaled antiasthmatic medicines in community health centers was 28.31%，and that in township health centers was 4.81%. The average availability rate of 2 long-acting inhaled antiasthmatic medicines in community health centers was 16.18%，and that in township health centers was 5.12%. The average availability rate of spirometers in primary care institutions was 8.94%
（667/7 458）. The average availability rate of spirometers in community health centers was higher than that of township health centers〔18.56%（289/1 557）vs 6.41%（378/5 901），P<0.05〕. Pulmonary function tests were implemented in 10.82%
（807/7 458） of the institutions. The rate of community health centers was higher than that of township health centers in terms of offering pulmonary function testing services〔13.81%（215/1 557） vs 10.03%（592/5 901），P<0.05〕. Conclusion　The available essential medicines for COPD in these primary care institutions were insufficient with unbalanced distribution. Most of available medicines were oral preparations，and inhaled antiasthmatic medicines，especially long-acting inhaled antiasthmatic medicines，were poorly available. Moreover，the availability rate of spirometers and the implementation rate of pulmonary function tests were both relatively low. All these factors negatively influence early screening for and management of COPD in primary care. In view of this，it is recommended that increasing the availability levels of inhaled antiasthmatic medicines and portable spirometers，and the application of pulmonary function tests in primary care，as well as primary care physicians asompetencies and initiatives for the prevention，diagnosis，treatment and rehabilitation of COPD with the delivery of the national essential publish health services for COPD as the starting point of enhancement trainings.

A Comparative Study on the Accuracy of Prognosis of the End-of-life Assessment Form and Common Survival Prediction Scales in Advanced Cancer Patients

YU Wenkai, CHEN Jianlin, LEI Rui, LUO Wei, HU Min, LIU Deng, ZHU Yu, CHEN Qi

Background　Accurately predicting the survival period of patients with advanced cancer can not only lay the foundation for palliative care centers to regulate the admission of patients and provide standardized services，but also help reduce "meaningless" over-treatment in the process of palliative care.However，there is still a lack of comparative study on the common survival prediction scales in China. Objective　To compare the accuracy of the End-of-life Assessment Form and common survival prediction scale〔Palliative Prognostic Index（PPI）、Palliative Performance Scale（PPS）、Karnofsky Score（KPS）〕in predicting the survival of patients with advanced malignant tumors，in order to provide a basis for the selection of survival prediction tools for advanced cancer patients.Methods　Patients with advanced malignant tumors admitted to the hospice ward of Linfen Road Community Health Service Center of Jing'an Distirct of Shanghai from April 1，2018 to February 1，2020 were retrospectively selected as researchsubjects. At the time of admission，the general information questionnaire，End-of-life Assessment Form，PPI，PPS，KPS were used to evaluate the patient，and the survival time of the patient was observed and recorded（from admission to the date of death）. The survival time of all patients was analyzed by Kaplan-Meier method，and the survival curve was drawn. The Kaplan-Meier method was used to calculate the median survival of patients in different groups of each scale，the log-rank test was used to compare the differences in survival among patients in different groups of each scale，and the survival curves were drawn. Finally，by comparing the predicted survival time and the actual survival time of patients with different score segments of each scale，the accuracy rate of the End-of-life Assessment Form，PPI，PPS and KPS in predicting the survival time of patients with advanced malignant tumors were calculated. Results　A total of 315 patients with advanced malignant tumors were included in this study，of which 266（84.4%）patients died during hospitalization and 49（15.6%）patients were censored（right censored，type Ⅲ censored）. The median survival time of 315 patients was 10.00〔95%CI（8.10，11.90）〕d. The median survival time of patients in groups of 20.0~35.0 points，35.5~45.0 points，45.5~50.0 points，50.5~60.0 points and 60.0~100.0 points of the End-of-life Assessment Form were 1.00〔95%CI（0.79，1.22）〕d，5.00〔95%CI（3.92，6.08）〕d，10.00〔95%CI（7.83，12.17）〕d，22.00〔95%CI（18.42，25.58〕d and 45〔95%CI（26.23，63.77〕d（χ2=360.561，P<0.001），respectively；The median survival time of patients in groups of 10~20 points，30~40 points and 50~100 points of KPS were 1.00〔95%CI（0.66，1.34）〕d、7.00〔95%CI（5.23，8.77）〕d and 30.00〔95%CI（20.87，39.13）〕d（χ2=137.280，P<0.001），respectively；The median survival time of patients in groups of 60%~100%，30%~50% and 10%~20% of PPS were 2.00〔95%CI（0.85，3.15）〕d、12.00〔95%CI（9.66，14.34）〕d and 35.00〔95%CI（25.90，44.10）〕d（χ2=139.311，P<0.001），respectively；The median survival time of patients in groups of 0~3.5 points，4.0~5.5 points，6.0~7.5 points，8.0~10.0 points and 10.5~15.0 points of PPI were 33.00〔95%CI（25.39，40.61）〕d、12.00〔95%CI（8.15，15.85）〕d、6.00〔95%CI（4.72，7.28）〕d、3.00〔95%CI（1.76，4.24）〕d and 1.00〔95%CI（0.89，1.11）〕d（χ2=289.831，P<0.001），respectively. The accuracy rate of the End-of-life Assessment Form，KPS，PPS and PPI to predict the survival time were 81.27%（256/315）、57.78%（182/315）、57.46%（181/315）、73.65%（232/315），respectively. Conclusion　The End-of-life Assessment Form，PPI，KPS and PPS can be used to predict the survival time of advanced malignant tumors，but the End-of-life Assessment Form is superior to PPI，KPS and PPS in predicting the survival time of advanced malignant tumors.

A Comparative Analysis of Cervical Cancer Screening Results in 2019 and 2020 in Shihezi Urban Areas，Xinjiang

LIU Yu, WEI Yan, YANG Ping

Background　The results of cervical cancer containment have demonstrated regional differences in China，which may be due to various socioeconomic and cultural developments across regions. Understanding cervical cancer screening results in various regions is of a great significance for developing effective cervical cancer prevention strategies. Objective　To perform a comparative analysis of the results of two yearly cervical cancer screening（2019 and 2020） in urban areas of Shihezi，Xinjiang，to estimate the changes in high-risk human papillomavirus （hrHPV） infection and cervical lesion detection rate in women. Methods　A retrospective design was used. Participants were 46 994 women from Shihezi urban areas who underwent initial cervical cancer screening with an HPV test〔underwent once either between December 2018 and December 2019（the 2019 yearly screening） or between January and June 2020（the 2020 yearly screening）〕 in Shihezi Maternal and Child Health Hospital，Shihezi People's Hospital，and First Affiliated Hospital，School of Medicine，Shihezi University during December 2018 to June 2020. Data of the screening results，including HPV infection rate and subtypes，Thinprep cytologic test results，and pathological diagnosis of cervical biopsy samples taken during a colposcopy were collected，and those of the 2019 yearly screening were compared with those of 2020 yearly screening. Results　There were 18 378，and 28 616 attendees for 2019，and 2020 yearly screenings，respectively，and 44 754 of them finally completed the screening. The completion rate of cervical cancer screening in 2020 was higher than that in 2019 〔97.07% （27 778/28 616） vs （16 976/18 378）〕（P<0.05）. A total of 5 992 cases （12.75%） were detected with HPV infection，among them，the prevalence of HPV 16 and HPV 18 was 18.55%（1 112/5 992），and that of other HPV subtypes was 81.45%（4 880/5 992）. The prevalence of HPV infections in participants of 2020 yearly screening〔11.09%（3 176/28 616）〕was lower than that in participants of 2019 yearly screening〔15.32%（2 816/18 378）〕（P<0.05）. The prevalence of single-type HPV infections in participants of 2019 yearly screening was higher than that in participants of 2020 yearly screening 〔11.38%（2 092/18 378） vs 7.45%（2 674/28 616）〕. The prevalence of multi-type HPV infections in participants of 2019 yearly screening was higher than that in participants of 2020 yearly screening〔3.94%（724/18 378） vs 1.75%（502/28 616）〕. The prevalence of HPV was 10.37%（909/8 767），12.22%（1 916/15 677），13.71%（2 500/18 234） and 15.45%（667/4 316），respectively，in four age groups of participants（30-39，40-49，50-59，and 60-65）in these two yearly screenings totally，showing an increase with age（P<0.05）. The prevalence of HPV showed a decrease in 30-39-year-old participants，so did it in 40-49-year-old，50-59-year-old，and 60-65-year-old participants of 2020 yearly screening （P<0.05）. The top 5 prevalent single HPV subtypes found in 2019 yearly screening were HPV 52（20.84%），HPV 16（14.48%），HPV 53（8.56%），HPV 51（7.93%），and HPV 39/68（7.60%），while those found in 2020 yearly screening were HPV 52（15.07%），HPV 16（12.64%），HPV 58（12.30%），HPV 53（10.25%） and HPV 66（4.75%）. HPV 18 ranked as the 11th most prevalent single HPV subtype in both two screenings. The 30-39-year-old participants of the 2020 yearly screening had lower prevalence of inflammation/condyloma detected by colposcopy than did those of the 2019 yearly screening （47.83% vs 74.36%）. The 50-59-year-old participants of the 2020 yearly screening had lower prevalence of inflammation / condyloma detected by colposcopy than did those of the 2019 yearly screening （65.50% vs 77.22%）. The 30-39-year-old participants of 2020 yearly screening had higher prevalence of colposcopy-detected low-grade squamous intraepithelial lesion（LSIL） than did those of 2019 yearly screening（31.30% vs 5.13%）（P<0.05）. The 40-49-year-old participants of 2020 yearly screening had higher prevalence of colposcopy-detected LSIL than did those of 2019 yearly screening（27.06% vs 16.07%）（P<0.05）. The 50-59-year-old participants of 2020 yearly screening had higher prevalence of colposcopy-detected LSIL than did those of 2019 yearly screening（23.64% vs 8.89%）（P<0.05）. Conclusion　The completion rate of cervical cancer screening in 2020 was obviously better than that in 2019，but it still needs to be further improved. Compared with 2019，HPV infection rate decreased，the major prevalent HPV subtypes changed，and LISL prevalence increased in 30-39 and 50-59 age groups in 2020. Follow-up management is suggested to be strengthened in 30-39 and 50-59 age groups.

Recent Developments in the Prevention and Treatment of Irritable Bowel Syndrome

GAO Lian, HUANG Xiaoming, WU Qingming

Irritable bowel syndrome（IBS） is a chronic functional gastrointestinal disease. The clinical symptoms of IBS mainly include abdominal pain and abnormal bowel movements. Clinically，IBS is divided into four types，which are caused by environmental and host factors，but the exact pathogenesis is unclear. Clinical diagnosis，treatment，and prevention of IBS are rather tricky. In contrast to functional diarrhea and constipation，the most notable symptom for diagnosing IBS is abdominal pain. The treatments for IBS include non-drug treatment and/or drug treatment. In general，the non-drug treatment is delivered in accordance with the patient's physiology and psychology，including professional guidance，dietary intervention，and psychological counseling. And drug treatment is implemented depending on the specific condition of the patient. Recent studies have shown that the intestinal flora is also involved in the incidence and progression of IBS，and the use of probiotics and intestinal microbiota transplantation may be effective treatments for IBS. This article reviews the latest developments in pathogenesis，treatments，prevention strategies，and possible future research directions regarding IBS.

Associated Risk Factors in Group B Streptococcus Infection During Pregnancy

HUANG Yan, WANG Mingying, FENG Junyan, ZHANG Jie

　Background　Group B streptococcus（GBS） infection can give rise to intrauterine infection during pregnancy and postpartum endometritis，and increase the risk of premature birth or stillbirth. So it is essential to improve the detection rate of GBS and to identify risk factors of GBS infection. Objective　To explore the risk factors of GBS infection during pregnancy. Methods　Participants were pregnant women in late pregnancy（n=11 248） who were selected from Department of Obstetrics and Gynecology，Peking University International Hospital from January 2017 to August 2021. All of them underwent screening for GBS infection，4 479 of them used vaginal swab test（single-swab culture group），1 239 used vaginal and rectal swabs tests（double-swab culture group），and other 5 530 used PCR test of vaginal and rectal swabs（double-swab & PCR group），and GBS detection rates in the groups were compared. Then，from the double-swab & PCR group，305 cases who were detected with GBS infection and 2 650 without were selected and compared in terms of information possibly related to GBS infection collected from the medical records，by which potential intrapartum risk factors for GBS infection were identified exploratively. Furthermore，294 of the above-mentioned 305 cases who also underwent vaginal microbiome test were selected，and compared with a random sample of 367 of the above-mentioned 2 650 cases who also underwent vaginal microbiome test，to analyze the association of vaginal microbiota status with GBS infection. Results　The GBS detection rates in single-swab culture group，double-swab culture group，and double-swab & PCR group were 5.96%（266/4 479），8.07（100/1 239），and 10.31%（570/5 530），respectively. The GBS detection rate was lower in single-swab culture group than that of other two groups（P<0.017）. And double-swab & PCR group had a higher GBS detection rate than did double-swab culture group（P<0.017）. Multiple Logistic regression analysis showed that grade Ⅲ or Ⅳ vaginal cleanliness was closely associated with the prevalence of GBS infection in pregnancy〔OR=3.005，95%CI（1.220，7.403），P=0.017〕. Conclusion　PCR test of both vaginal and rectal swabs could increase the GBS detection rate. Vaginitis is a major high-risk factor associated with GBS infection during pregnancy，which needs to be addressed in the process of diagnosis and treatment.

Influence of Physical Exercise Interventions during Pregnancy on Natural Childbirth：a Meta-analysis

JI Moufang, LI Ruobing, WEI Kejing, ZENG Fanhua

Background　Natural childbirth is a normal physiological approach of human reproduction，while in China，the cesarean section rate has exceeded the upper limit recommended by the WHO by more than two times. As a nonpharmaceutical intervention facilitating natural childbirth，physical exercise should be valued by relevant departments. Objective　To perform a meta-analysis of studies regarding effects of physical exercise interventions on promoting natural childbirth probability，and to attempt to recommend a better exercise scheme. Methods　Randomized controlled trials（RCTs） about the effect of intrapregancy physical exercise versus routine care（health duration or irregular physical exercise） improving the probability of natural childbirth published between 1990 and 2021 were searched in databases of CNKI，SinoMed，CQVIP，PubMed，EMBase，Web of Science，and the Cochrane Library. Meanwhile，the references of systematic reviews on relevant RCTs were also searched and reviewed. Data extraction and methodological quality assessment were conducted for the included studies. RevMan 5.2 was used for meta-analysis. GRADE was used to rate the quality of evidence concerning an outcome. Results　A total of 30 studies with 3 910 subjects were included. Meta-analysis found that physical exercise interventions were superior to routine care in improving the natural childbirth rate〔RR=1.34，95%CI（1.28，1.40），P<0.000 01〕. Subgroup analyses revealed that natural childbirth rate was improved the most by physical exercise intervention started later than 24 weeks of gestation，followed by that started at 13-24 weeks of gestation，and earlier than 12 weeks of gestation. With respect to the type of physical exercise，the natural childbirth rate was improved the most by general sports lessons，pelvic floor muscle training，aerobic exercise，gymnastics，birthing ball movement，and yoga. As for the frequency of physical exercise，the natural childbirth rate was improved the most by at least 12 times per week，followed by 3-5 times per week，6-8 times per week，and 9-11 times per week. In terms of the intensity of physical exercise，the natural childbirth rate was improved the most by moderate intensity of physical exercise. With regard to the duration of physical exercise，the natural childbirth rate was improved the most by physical exercise lasting for 30-50 minutes per time，followed by less than 30 minutes per time，and at least 50 minutes per time. In respect to the number of weeks of conducting physical exercise，the natural childbirth rate was improved the most by physical exercise lasting for 8 or less than 8 consecutive weeks，followed by l7-24 weeks，9-16 weeks，and 25-34 weeks. Funnel plot assessing publication bias of the studies was basically symmetrical in shape，indicating that the publication bias was generally weak. The overall quality of evidence concerning improvements in natural childbirth rate by physical exercise interventions in the studies was rated moderate. Conclusion　The results show that proper physical exercise during pregnancy favorably affects the probability of natural childbirth. The natural childbirth probability could be positively influenced by some types of moderate-intensity physical exercise interventions，such as general sports lessons，pelvic floor muscle training，aerobic exercise，gymnastics，birthing ball movement，and yoga，if they are performed at least 12 times per week（30 to 50 minutes each time） within 8 consecutive weeks after 24 weeks of gestation.

Single Nucleotide Polymorphisms in the Mitochondrial Displacement Loop and Age at Onset of Gastric Cancer

Background　It is very difficult to contain persistently high incidence and mortality rates of gastric cancer. Moreover，the age at onset of gastric cancer is becoming earlier. However，there are few studies on the prediction of the age at gastric cancer onset. Objective　To investigate the relationship between single nucleotide polymorphisms （SNPs） in mitochondrial displacement loop （D-Loop） and age at gastric cancer onset. Methods　A total of 150 patients with confirmed gastric cancer by pathologically examination of biopsy samples taken during gastroscopy were recruited from Department of Gastroenterology，the Fourth Hospital of Hebei Medical University between July 1，2007 and December 31，2008. PCR was used to amplify the targeted fragment of peripheral blood mitochondrial DNA，and the mitochondrial D-Loop region was sequenced. Survival curves for patients with different ages of onset of gastric cancer were plotted by the Kaplan-Meier method，and compared by the Log-rank test. Cox regression analysis was used to identify factors associated with age of onset of gastric cancer. Results　The age of onset of patients with different degrees of differentiation was statistically significant （P<0.05）. Log-rank test revealed that patients with 153G genotype had earlier age of onset of gastric cancer than did those with 153 genotype〔（48.0±5.3）vs（60.1±0.8）〕（χ2=7.757，P=0.005）. Multivariate Cox regression analysis indicated that the 153A/G polymorphism in mitochondrial D-Loop was a predictor of age at onset of gastric cancer〔HR=0.323，95%CI（0.140，0.745），P=0.008〕. Conclusion　The 153A/G polymorphism in mitochondrial D-Loop may be used as a novel predictor of the age at onset of gastric cancer. Analyzing the SNPs in mitochondrial D-Loop may contribute to early identification of gastric cancer.

Quality Assessment of Guidelines forVascular Cognitive Impairment Using the AGREEⅡ

MA Huaping, HAN Zhenyun, CHANG Ze, WANG Yuchun, HU Yuli, ZHANG Dingding

Background　As the second primary type of cognitive impairment worldwide，vascular cognitive impairment （VCI） is closely associated with cerebrovascular risks，which imposes a heavy burden on the society and families. Early diagnosis and treatment are important for intervening and reversing VCI. And formulating high-quality clinical guidelines is an effective way to improve diagnosis and treatment levels of VCI. Objective　To assess the quality of guidelines for VCI，aiming at offering support for making clinical decisions for VCI. Methods　From August to November 2021，we searched literature databases and websites in China and abroad to identify guidelines for VCI，and assessed them using the Appraisal of Guidelines for Research & Evaluation（AGREE）Ⅱ. Results　A total of 18 guidelines were enrolled，12 of which are Chinese guidelines and 6 are foreign guidelines；9 of which are evidence-based guidelines，and the other 9 are not. The intraclass correlation coefficient was 0.935，indicating a high degree of agreement between raters. The overall quality of these guidelines was relatively low，since in the six domains，only the average score of Clarity of Presentation was greater than 60%（64.04%），and the average scores of Scope and Purpose （52.31%）and Editorial Independence （42.01%） were between 30% and 60%，and those for other three domains，Stakeholder Involvement（27.24%），Rigor of Development（20.05%）and Applicability（13.83%），were all less than 30%. The grade of recommendation for 6 guidelines was B，and that for other 12 guidelines was C. Conclusion　The overall quality of the included guidelines was rated relatively low，especially their average score for each of the three domains，Stakeholder Involvement，Rigor of Development，and Applicability，was below the average level. It is suggested to enhance the quality of VCI guidelines via improving the details of guidelines strictly under the evidence-based principle.

Correlation between Neutrophil to Lymphocyte Ratio，Platelet to Lymphocyte Ratio and Severity of Biliary Acute Pancreatitis and Concurrent Liver Injury

Background　Neutrophil to lymphocyte ratio（NLR） and platelet to lymphocyte ratio（PLR） have proved to have a certain significance in predicting the severity of pancreatitis，however，at present，there are few relevant studies on the diagnostic and predictive value of NLR and PLR for liver injury in biliary acute pancreatitis（BAP）. Objective　To explore the correlation between NLR and PLR in the severity of BAP and the concurrent acute liver injury（ALI）. Methods　A total of 142 patients with BAP admitted to Emergency Department of the Second Affiliated Hospital of Nanchang University from March 2019 to March 2021 were selected and divided into mild（MAP）/moderately（MSAP） group（n=98） and severe（SAP） group（n=44） according to Atlanta classification. According to whether the liver function is damaged or not，they were divided into ALI group（n=92） and non-ALI group（n=50）. The ALI group was further divided into hepatocyte type liver injury subgroup（n=1），bile duct type liver injury subgroup（n=16） and mixed type liver injury subgroup（n=75）. The general condition and clinical data of patients were collected，and the predictive value of NLR and PLR on the severity of BAP and concurrent ALI was explored by the ROC curve and binary Logistic regression analysis. Results　The NLR and PLR in MAP/MSAP group were lower than those in SAP group（P<0.05）. The NLR and PLR in ALI group were higher than those in non-ALI group（P<0.05）. There was no significant difference in NLR and PLR between bile duct type liver injury subgroup and mixed type liver injury subgroup （P>0.05）. The area under the ROC curve of NLR，PLR and their joint prediction of SAP was 0.809，0.667，0.809，respectively. The area under the ROC curve of NLR，PLR and their joint prediction of ALI in BAP was 0.774，0.767，0.806，respectively. The area under the ROC curve of NLR，PLR and their joint prediction of the occurrence of cholangiocytic liver injury in BAP was 0.813，0.742，0.861，respectively. The area under ROC curve of NLR，PLR and their joint prediction of mixed liver injury in BAP was 0.763，0.770 and 0.794 respectively. The results of binary Logistic regression analysis showed that elevated NLR was a risk factor for SAP〔OR=1.184，95%CI（1.102，1.271），P<0.001〕. Elevated NLR and PLR were the risk factors for ALI in BAP〔OR=1.140，95%CI（1.050，1.238），P=0.002；OR=1.007，95%CI（1.001，1.013），P=0.023〕；elevated NLR was a risk factor for bile duct cell liver injury in BAP〔OR=1.184，95%CI（1.054，1.331），P=0.004〕. Elevated NLR and PLR were risk factors for mixed liver injury in BAP〔OR=1.120，95%CI（1.120，1.221），P=0.011；OR=1.007，95%CI（1.001，1.013），P=0.034〕. Conclusion　NLR and PLR have certain diagnostic and predictive value for the severity of BAP and concurrent liver injury，but NLR is better than PLR，and the combined detection effect is better.

Predictive Value of C-reactive Protein to Albumin Ratio for Microvascular Invasion in Single Small Hepatocellular Carcinoma

YAO Gang, CAO Xinling, LI Tao

Background　The microvascular invasion pathologically diagnosed in hepatocellular carcinoma（HCC） has not been valued enough in previous studies. And there are no unified pathological diagnostic criteria for microvascular invasion in HCC. Besides that，microvascular invasion is not included as a routine pathological indicator for HCC. C-reactive protein to albumin ratio（CAR） is a new systemic inflammatory factor that is closely related to the proliferation，invasion，metastasis and other malignant biological behaviors of HCC. Objective　To investigate the value of CAR in predicting microvascular invasion in single small HCC. Methods　Participants（n=346） who were pathologically diagnosed with HCC following the resection of single liver tumor（diameter≤5 cm） were selected from the First Affiliated Hospital of Xinjiang Medical University from June 2017 to June 2021. Demographic data and calculated CAR were collected. ROC analysis was performed to estimate the predictive value and optimal cut-off value of CAR for microvascular invasion in single small HCC. All patients were divided into two groups according to the optimal cut-off value of CAR（≥0.03 or <0.03），and those with similar propensity scores estimated by Logistic model were matched by 1:1 nearest neighbor matching，yielding two comparison groups with highly similar clinical characteristics，and the microvascular invasion rate between them was compared. Logistic regression was used in the sensitivity analysis of the predictive value of CAR for microvascular invasion in single small HCC before and after the aforementioned matching. Results　One hundred and thirty-one（37.9%） cases were found with microvascular invasion and other 125 without（62.1%）. ROC analysis revealed that the AUC of CAR in predicting microvascular invasion in single small HCC was 0.787〔95%CI（0.697，0.877）〕，with 82.9% sensitivity and specificity 76.4% when the optimal cut-off point was determined as 0.03. Ninety-two of 145 cases with CAR<0.03 and 92 of 201 cases with CAR≥0.03 were successful matched，and the prevalence of microvascular invasion was found to be lower in the former group〔13.0%（12/92）vs 43.5%（40/92）〕（χ2=6.314，P=0.013）. Three Logistic models showed that CAR was an independent predictor of microvascular invasion in single small HCC，regardless of whether the participants were matched or not（P<0.05）. Conclusion　CAR could be used as a predictor for microvascular invasion in single small HCC. CAR≥0.03 may indicate a very high probability of microvascular invasion.

Correlations of BMI and Blood Lipids with Diabetes in an Elderly Health Check-up Population of Luzhou：a Longitudinal Study

ZHANG Wenxin, FAN Song, LIU Xia, LI Xinping, LEI Zhi, LI Ailing

Background　A number of studies have shown that obesity，overweight and dyslipidemia have various strength of correlation with diabetes，but there is a lack of longitudinal studies to verify this issue.Objective　To perform a longitudinal study of diabetes prevalence，and the strength of correlationof body mass index（BMI） and blood lipid with diabetes in an older health check-up population of Luzhou during 2016 to 2019，providing a scientific basis for the formulation of diabetes prevention and treatment strategies for the elderly.Methods　A longitude study design was used. Health check-up data of Luzhou older adults（≥64 years old） in four consecutive years（from 2016 to 2019） were retrospectively collected，including gender，age，BMI，smoking and alcohol consumption，total cholesterol （TC），triglyceride （TG），low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C）. Generalized estimating equation was used to analyze the strength of correlation of BMI，TC，TG，LDL-C and HDL-C with diabetes. Results　The prevalence of diabetes in the participants during 2016-2019 was 10.5%（15 893/151 132），11.5% （17 375/151 132），11.9%（18 019/151 132） and 13.5% （20 394/151 132），respectively.After controlling for gender，age，smoking and alcohol consumption，the analysis using generalized estimating equation revealed that obesity〔OR=2.610，95%CI （2.523，2.700）〕，overweight〔OR=1.749，95%CI （1.710，1.790）〕，increased TC〔OR=1.073，95%CI（1.040，1.106）〕，elevated TG〔OR=2.091，95%CI （2.042，2.140）〕，marginally increased TG〔OR=1.151，95%CI （1.126，1.177）〕，increased LDL-C〔OR=1.264，95%CI （1.219，1.310）〕，marginally increased LDL-C〔OR=1.208，95%CI （1.178，1.240）〕，and decreased HDL-C〔OR=1.552，95%CI （1.506，1.599）〕 were correlated with increased risk of diabetes （P<0.01）. Slightly underweight〔OR=0.763，95%CI （0.73，0.798）〕 and marginally elevated TC 〔OR=0.868，95%CI （0.850，0.886）〕were correlated with decreased risk of diabetes （P<0.01）.Conclusion　The prevalence of diabetes was relatively high in the elderlyhealth check-up population of Sichuan’s Luzhou，which may be closely correlated with overweight / obesity and dyslipidemia. In view of this，it is suggested to lose weight and lower blood lipids to reduce diabetes prevalence and to prevent diabetes in this group.

Associated Factors of Osteoporosis and Physical Fitness in Elderly Chinese Men

Background　As life expectancy increases，the number of elderly patients with osteoporosis rises as well. Many factors affect the development of osteoporosis，and good physical fitness may contribute to having better social adaptability in older people. So it is very important to pay attention to osteoporosis and ensure physical fitness in this group. Objective　To explore the factors associated with osteoporosis，and analyze physical fitness in elderly men，providing a theoretical basis for preventing osteoporosis，improving physical fitness and developing health management programs for this group. Methods　This study was conducted from January 2018 to December 2020. A total of 250 elderly men who underwent bone mineral density（BMD） examination were selected from Health Management Center，Inner Mongolia People's Hospital，and divided into normal BMD，osteopenia and osteoporosis groups by BMD examination results. Data were collected，including baseline information，laboratory results，physical fitness test results〔 including muscular strength （number of elbow bending within 30 seconds，30-second sit-to-stand test results），flexibility （shoulder and arm stretches），balance （stand on one foot with eyes closed），aerobic capacity （2-minute step test），agility/mobility （timed up go test with a minimal space of 2.5 meters）〕. Results　Of the 250 subjects，76 （30.4%） had normal BMD，123 （49.2%） had osteopenia，and 51（20.4%） had osteoporosis. Multivariate Logistic regression analysis demonstrated that abdomen circumference〔OR=0.710，95%CI（0.566，0.891）〕，body mass index 〔OR=0.685，95%CI（0.474，0.990）〕，high-density lipoprotein cholesterol〔OR=74.182，95%CI（3.738，1 472.125）〕，25（OH）D3〔OR=0.745，95%CI（0.619，0.897）〕，and estradiol〔OR=0.784，95%CI（0.665，0.924）〕were associated with osteoporosis in elderly men（P<0.05）. All the subjects successfully completed physical fitness tests，without adverse events. The number of repetitions of sit-to-stands within 30 seconds，results of shoulder and arm stretches，sitting flexion test，and 2-minute step test，duration for stand on one foot with eyes closed，as well as time used for timed up go test with a minimal space of 2.5 meters differed significantly across normal BMD，osteopenia and osteoporosis groups（P<0.05）. The number of elbow bending within 30 seconds showed no significant differences across the three groups（P>0.05）. Conclusion　In elderly men，abdomen circumference，body mass index，high-density lipoprotein cholesterol，25（OH）D3，and estradiol may independently associated with osteoporosis. Physical fitness indices varied significantly by BMD，especially flexibility，balance，aerobic capacity and agility/mobility.

Development，Validity and Reliability of High-risk People's Intention to Use Stroke Screening Scale

Background　The program of screening for stroke in high-risk populations is being carried out vigorously in Chinese communities，the implementation effectiveness of which is closely associated with residents' intention to use the program. However，there is no reliable scale for measuring high-risk residents' intention to use stroke screening. Objective　To develop a scale for measuring high-risk people's intention to use stroke screening，and to assess its reliability and validity，providing a reliable tool for assessing high-risk residents' intention to use stroke screening.Methods　The Theory of Planned Behavior，literature review，field survey and brainstorming were used to develop the item pool of the scale.Then the items were used to form an initial version of High-risk People's Intention to Use Stroke Screening Scale（three domains covering 28 items） after being revised in accordance with the assessment results of two rounds of expert survey with five experts（four stroke researchers and one with a good command of developing a scale） from July to August 2021. After that，the reliability and validity of the initial version of the scale was tested in August to September 2021 with a convenience sample of community residents from Hubei's Xiangyang and Wuhan，and Guangdong's Guangzhou and Huizhou.Results　Altogether，535 residents attended the survey for testing the reliability and validity of the initial version of the scale，and 524 of them（98%） returned responsive questionnaires. The final revised version consists of four domains（positive attitude，negative attitude，subjective norms，perceived behavioral control） with 25 items. The Cronbach's α of the scale was 0.904. And its ICC for test-retest reliability was 0.810. The content validity index of each item （I-CVI） ranged from 0.80 to 1.00. The scale-level CVI/universal agreement （S-CVI/UA） and average scale-level CVI （S-CVI/Ave） were 0.93 and 0.99，respectively. By exploratory factor analysis，four common factors were extracted，and they explained 61.945% of the total variance. The loading for each factor was 0.482-0.828.Confirmatory factor analysis showed that the scale's fit indices were: χ2=361.040，df=267，χ2/df=1.352，RMSEA=0.038，GFI=0.897，CFI=0.958，AGFI=0.875，IFI=0.959，TLI=0.953，NFI=0.859. Conclusion　The scale has proven to be highly reliable and valid，which could be used as a tool for measuring high-risk community-dwelling residents' intention to use stroke screening.

Effect and Mechanism of Action of Acupoint Injection of Puerarin on Myocardial Mitochondria Energy Metabolism in Bupivacaine-poisoned Rats

YU Yan, WANG Chunai, QIN Xiaoyu, LI Yulan, LIANG Xi, WEN Xiaohui, LIU Min

Background　There is no safe and effective antidote for cardiotoxicity induced by bupivacaine，an extensively used anaesthetic. Our previous research shows that acupoint treatment may partially improve bupivacaine-induced cardiotoxicity，but the mechanism of action needs to be further studied. Objective　To observe the effect of acupoint injection of puerarin on mitochondrial energy metabolism in myocardia in bupivacaine-poisoned rats，and to explore its mechanism of action. Methods　This experiment was conducted from January to December 2019. Forty 6-month-old male SPF Wistar rats were selected and equally randomized into a blank group （group C），a model group （group B），a treatment group （group T），and a prevention group （group P）. Interventions were given to the groups as follows：Group P received：0.1 ml puerarin injection injected into bilateral Neiguan acupoints. Then 5 minutes later，bupivacaine-poisoned model was established for three groups（except for group C） using intravenous infusion of 0.5% bupivacaine（10 mg/kg） via femoral vein within 2 minutes. Group C received 0.1 ml of 0.9% sodium chloride solution injected into bilateral Neiguan acpoints. ：Immediately after successful modeling，0.1 ml of 0.9% sodium chloride solution was injected into bilateral Neiguan acupoints for group B，and：0.1 ml puerarin injection was injected into bilateral Neiguan points for C. The rats in group C were sacrificed at the 8th minute of intravenous infusion of 0.9% sodium chloride solution，and those in groups B，T，and P were sacrificed at the 8th minute of intravenous infusion of bupivacaine，then the left ventricular myocardium of all rats were taken out and cardiomyocyte mitochondria were isolated，the structure of which was observed under the transmission electron microscope. The semi-quantitative analysis of mitochondrial structure was evaluated by Flameng classification system. The activity of mitochondrial adenosine triphosphate synthase （ATPase） was measured by ELISA. The content of adenosine triphosphate （ATP） was measured by colorimetric assay. The mitochondrial membrane potential （MMP） was detected by JC-1 fluorescence staining and colorimetry. The protein levels of myocardial mitochondrial peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α），nuclear respiratory factor 1（NRF1），and mitochondrial transcription factor A （mtTFA） were measured by Western blotting. Results　Group C had lower Flameng score than did other three groups（P<0.05）. The Flameng score in group P was lower than that of groups B and T（P<0.05）. Group C had lower activity of ATPase than did groups B and T（P<0.05）. The activity of ATPase in group P was higher than that in groups B and T（P<0.05）. Group C had higher ATP content and MMP，and protein levels of PGC-1α，NRF1 and mtTFA than did other three groups（P<0.05）. Group B had lower ATP content，MMP，and PGC-1α protein level than did groups T and P（P<0.05）. Group B had lower protein level of mtTFA than did groups T and P（P<0.05）. The protein level of mtTFA in group P was higher than that in group T（P<0.05）. Conclusion　Acupoint injection of puerarin could reduce the damage of myocardial mitochondria caused by bupivacaine，and its mechanism of action may be related to puerarin's protection of mitochondrial energy metabolism by regulating the content of ATP synthesis-related proteins PGC-1α，NRF1 and mtTFA in mitochondria.

Correlation of Glycemic Variability and Time in Range with Early Neurological Deterioration in Patients with Acute Ischemic Stroke and Diabetes

WANG Ming, XI Zhi, MENG Qizhe, YANG Xiaopeng

Background　Early neurological deterioration（END） in acute ischemic stroke is associated with permanent neurological deficits and dysfunction，and considered to be an unstable condition requiring comprehensive medical treatment. Moreover，the relationship between END and glycemic variability（GV） remains unclear. Objective　To explore the relationship of GV，time in range（TIR） with END in patients with acute ischemic stroke and diabetes，and based on this，to develop a predictive model. Methods　One hundred and twenty patients with acute ischemic stroke and diabetes（34 with END and 86 without） were selected from the Second Affiliated Hospital of Zhengzhou University from July 2019 to May 2021. Clinical data，GV indices 〔coefficient of variation（CV），standard deviation（SD），mean amplitude of glycemic excursion（MAGE），mean of daily differences（MODD）〕 and TIR measured by the 72-hour ambulatory continuous glucose monitoring were collected. Factors associated with END were explored by multivariate Logistic regression，and used to develop a nomogram for the prediction of END. ROC analysis was conducted to assess the predictive value of nomogram for END. Results　Patients with END had higher mean glycosylated hemoglobin（HbA1c），admission NIH Stroke Scale score，CV，SD，MAGE，and MODD，and lower mean TIR than did those without（P<0.05）. Multivariate Logistic regression analysis indicated that increased CV〔OR=1.194，95%CI（1.027，1.388），P=0.021〕，SD〔OR=11.040，95%CI（1.189，102.473），P=0.035〕，MAGE〔OR=3.063，95%CI（1.062，8.837），P=0.038〕，and MODD〔OR=20.990，95%CI（1.420，201.206），P=0.027〕 were associated with elevated risk of END，and prolonged TIR〔OR=0.877，95%CI（0.789，0.974），P=0.014〕 was associated with decreased risk of END. Internal validation of the predictive value of nomogram incorporating CV，SD，MAGE，MODD and TIR for END using bootstrapping showed that its predicted value was basically consistent with the actual value，demonstrating good predictive ability. For estimating END in acute ischemic stroke combined with diabetes，the AUC of CV，SD，MAGE，MODD and TIR was 0.847〔95%CI（0.765，0.929），P<0.01〕，0.812〔95%CI（0.723，0.901），P<0.01〕，0.850〔95%CI（0.772，0.928），P<0.01〕，0.803〔95%CI（0.710，0.896），P<0.01〕，and 0.825〔95%CI（0.747，0.903），P<0.01〕，respectively. Conclusion　CV，SD，MAGE，MODD and TIR may be influential factors for END in acute ischemic stroke with diabetes，which could partially predict END. It is of clinical significance to take measures to reduce GV and prolong TIR to prevent END.

Participation in Advance Care Planning and Associated Factors among Surrogate Decision Makers of Patients with Hematologic Malignancies

WANG Tianhang, WANG Wen, SHEN Wenting, SHI Baoxin

Background　Advance care planning（ACP）helps patients to obtain medical care meeting their values、goals and preferencesunder the circumstances of loss of decision-making ability. The surrogate decision maker（SDM）plays a key role as the main participantinvolved in the process of ACP. But there are no studies on the participation and role of SDMs in ACP process in China. Objective　To investigate the participation in ACP of SDMs of patients with hematologic malignancies and its associated factors，providing a reference for the development of localized strategies for ACP implementation，and for the promotion of ACP in China. MethodsConvenient sampling was used to select the SDMs of 235 patients with hematologic malignancies recruited from Blood Diseases Hospital，Chinese Academy of Medical Sciences during October 2020 to March 2021. They were invited to compete a survey using self-developed the Chinese version of the 17-item Advance Care Planning Engagement Survey for Surrogate Decision Makers（C-ACP-SDM-17），Chinese version of Mishel Uncertainty in Illness Scale-Family Member form（C-MUIS-FM），Simplified Coping Style Questionnaire（SCSQ），and Social Support Rating Scale（SSRS）. The C-ACP-SDM-17 scores were compared by demographic factors of the SDMs.Pearson correlation analysis was used to explore the correlation of C-ACP-SDM-17 score with C-MUIS-FM，SCSQ，and SSRS scores of SDMs. Multiple linear regression was used to analyze the factors associated with the participation in ACP of SDMs. Results　The average total scores of the C-ACP-SDM-17，C-MUIS-FM，and SSRS of the SDMs were（52.23±13.57），（66.43±12.54）and（40.33±6.78），respectively. And the average scores of two subscales of SCSQ of the SDMs，active coping and passive coping，were（24.34±6.94），and（9.87±4.25），respectively. Male，having experience of involvement in end-of-life medical decision making，awareness of life-sustaining treatment，and knowing of ACP were associated with statistically higher C-ACP-SDM-17 score of SDMs（P<0.05）. The total C-ACP-SDM-17 score of SDMs was negatively correlated with the total score of C-MUIS-FM，and scores of its two subscales，uncertainty and ambiguity，but was positively correlated with the score of active coping. Gender，involvement in end-of-life medical decision making，awareness of life-sustaining treatment，hearing about ACP，level of disease uncertainty，and level of active coping were factors associated with the involvement of SDMs in ACP（P<0.05）. Conclusion　The ACP participation in SDMs of hematologic malignancies patients was above average. To increase their participation level，it is suggested for medical workers to encourage hematologic malignancies patients' male family members or family members with experience of involvement in end-of-life medical decision making to be SDMs，and give them ACP education，explanation of hematologic malignancies，as well as guide them to actively cope with the pressure of decision making.

Development of anIncentive Model for General Practitioners in Fengxian District of Shanghai Based on Herzberg's Motivation-hygieneTheory

Background　In view of the shortage of general practitioners（GPs） and limited community healthcare resources，it is urgently necessary for community health institutions to find accurate and scientific incentive methods to retain GPs and help them to realize their full potential，as well as promote the development of both community health institutions and GPs，thereby benefiting the health promotion of community residents.Objective　To develop an incentive model for GPs to test the performance and effectiveness of current incentives for GPs，so as to put forward suggestions to improve the mechanisms of employing and retaining GPs.Methods　In August 2019，we recruited 204 GPs from 11 community health centers（CHCs） in Shanghai's Fengxian District using stratified random sampling to attend an online survey using a questionnaire named General Practitioners' Perception and Evaluation of Incentive Measures developed based on our previous research results and Herzberg's motivation-hygiene theory. Then from August to September 2019，we invited directors responsible for medical care or public health issues，and medical quality control department heads from the above-mentioned 11 CHCs to attend an online survey using a questionnaire named Workload for General Practitioners in Community Health Centers of Fengxian District developed by usbased on a literature review. Then under the guidance of Herzberg's motivation-hygiene theory，we constructed a structural equation to develop an incentive model for GPs within Fengxian District with representative incentive policies，systems and initiatives related to GPs selected from the survey results as latent independent variables to measure GPs'（responders'） perception and assessment of incentives，and with willingness to work，service radius，and workload of GPs as dependent variables.Results　The average scores for the implementation of incentive measures，and its associated influence on GPs' work status assessed by the 204 GPs were （0.77±0.14），and （0.73±0.19），respectively. The assessment score for implementation of incentive measures for GPs differed significantly by personal health condition and administrative position in the respondents（P<0.05）. The assessment score for the influence of implementing incentive measures on GPs' work status differed significantly by personal health condition in the respondents（P<0.05）.Pearson correlation analysis showed that GPs'work status was associated with the implementation of 25 incentive measures（one incentive measure at the subdistrict level was not included for analysis）（P<0.05）. The top three most highly correlated incentive measures were performance distribution（r=0.652），performance-based salary calculation（r=0.621），and wages and benefits（r=0.614）. Partial correlation analysis indicated that，after controlling for variables such as regional policy environment，local township government，and GPs' work unit，the assessment score for implementation of either regional，or subdistrict or institutional incentive measures for GPs，was positively correlated with the assessment score for the influence of implementation of incentive measures for GPs on GPs' work status（r=0.381，0.387，0.528，P<0.001）. Theaverage assessment score for willingness to work by the respondents was （0.76±0.18） points. Theassessment scores of willingness to work by the respondents differed significantly by work unit（P<0.05）.Structural equation modeling revealed that the implementation of policy incentive measures influenced GPs' workload via GPs' willingness to work. Specifically，the implementation of policy incentive measures increased GPs' willingness to work（w1=0.43），while GPs' willingness to work decreased with the increase of weighted workload（w2=-0.156）.Conclusion　The GPs in Fengxian Districtshowed higher level of willingness to work，namely，relatively high job stability，but they had not been incentivized by policy incentives to be competitive in obtaining improved performance，indicatingthat although policy incentives have produced partial effects on incentivizing GPs，the effects are still unsatisfactory. In the long run，it is necessary to consider whether there will be changes in GPs'retention status due to the lack of work initiative. For GPs，besides a guarantee of stable income，incentives to get more by doing more are also needed，which may be achieved by increasing the incentive authority and proportion of community health institutions when the total amount of incentives is limited.

Research Progress of the Prevention and Treatment of Metabolic Diseases Based on Short Chain Fatty Acids

ZENG Lin, ZHANG Pengxiang, HUANG Qian, WANG Gaoxiang, LI Huilin

Short chain fatty acids（SCFAs） are a class of saturated fatty acids containing 1-6 carbon atoms，which are mainly produced by specific flora in the intestine through the fermentation of dietary fiber，and play an important role in maintaining the homeostasis of the intestinal environment. Recent studies have shown that SCFAs can regulate glucose and lipid metabolism，regulate energy balance，maintain the intestinal barrier and reduce inflammatory responses，eventually participating in the occurrence and development of metabolic diseases such as type 2 diabetes mellitus，obesity，lipid metabolic disorders and nonalcoholic fat liver disease through the above multiple pathways. This article summarizes the mechanism of SCFAs regulating metabolism and the research progress in the prevention and treatment of metabolic diseases，in order to provide more reference materials for the prevention and treatment of metabolic diseases.

Relationships of Skin AGEs and Serum CN-1 with Microvascular Complications in Type 2 Diabetes Mellitus

Background　Hyperglycemia plays a significant role in the development and progression of diabetic complications. While carnosine is a putative scavenger of advanced glycation end products （AGEs），its availability in tissue is limited by the activity of serum carnosinase-1 （CN-1）. So far，the correlations of skin AGEs and serum CN-1 concentration with type 2 diabetes mellitus （T2DM），and microvascular complications in T2DM are still unclear. Objective　To investigate the relationships of skin AGEs，and serum CN-1 with microvascular complications in T2DM to evaluate the predictive values of skin AGEs and serum CN-1 for diabetic complications. Methods　A total of 134 inpatients with T2DM were recruited from the Department of Endocrinology，the First Affiliated Hospital of Anhui Medical University between January and March 2021.Their clinical data were collected. Pearson correlation analysis and Spearman rank correlation analysis were used to examine the correlation between skin AGEs and serum CN-1，and the correlations of skin AGEs and serum CN-1 with demographic and serological data，diabetic microvascular complications and other diseases. The influencing factors of skin AGEs and serum CN-1 were investigated by multiple linear regression analysis. Results　Out of all subjects，there were 13 （9.7%） cases of diabetic retinopathy （DR），38 （28.4%） cases of diabetic nephropathy （DN），56 （41.8%） cases of diabetic peripheral neuropathy （DPN），and 79 （59.0%） cases of diabetic peripheral vascular disease. The skin AGEs level was （80.2 ±10.6） and serum CN-1 concentration was （6.9±3.4） μg/L on average. Correlation analyses demonstrated that gender，age，and DR were positively correlated with skin AGEs （P<0.05），but estimated glomerular filtration rate （eGFR） and CN-1 were negatively correlated with skin AGEs （P<0.05）. Multiple linear regression analysis revealed that gender（B=7.630），age（B=0.408）and DR（B=7.183）were associated with skin AGEs（P<0.05）. Correlation analyses showed that serum CN-1 was increased with age or with the increase in diastolic blood pressure （DBP）（P<0.05），while it decreased with the decline of skin AGEs（P<0.05）. Conclusion　Both skin AGEs and serum CN-1 may have no obvious correlation with most diabetic microvascular complications，such as DN，DPN and diabetic peripheral vascular disease. But different from serum CN-1，skin AGEs may significantly correlated with DR.

Brain White Matter Fiber Bundle Alterations and Severity of Depression in Patients with Post-stroke Depression

QI Jie, ZHANG Lei, DENG Lijun, DUAN Xiaodi, DONG Binbin, SUI Rubo

Background　Post-stroke depression（PSD），a common complication in stroke patients，may increase the disability and mortality，however, its pathogenesis is unknown yet. Objective　To observe the white matter fiber bundle alterations by diffusion tensor tractography（DTT），and to explore its correlation with depression in patients with PSD. Methods　Participants were selected from the First Affiliated Hospital of Jinzhou Medical University from September 2019 to September 2020, involving 40 inpatients with first-episode ischemic stroke（20 were found with PSD，and 20 without），and 20 physical examinees as healthy controls. DTT was performed in all participants，fractional anisotropy（FA）and number of fiber bundles in regions of interest（ROIs）were compared across PSD and non-PSD inpatients and healthy controls. Pearson correlation analysis was performed to analyze the correlations of FA and number of fiber bundles on the side of stroke in the ROIs with 24-item Hamilton Rating Scale for Depression（HAMD-24）in PDS inpatients. Results　In PSD inpatients，the FA of inferior fronto-occipital fascicles，corticospinal tract，frontopontine tract，cingulum bundle and uncinate fasciculus on the side of the stroke was significantly lower than those on the contralateral side（P<0.05）. And the number of fiber bundle of inferior fronto-occipital fascicles，corticospinal tract and frontopontine tract on the side of the stroke was significantly less than those on the contralateral side（P<0.05）. Compared to non-PSD inpatients or healthy controls，PSD inpatients demonstrated significantly lower FA of inferior fronto-occipital fascicles，corticospinal tract，frontopontine tract，cingulum bundle and uncinate fasciculus，and notable less number of fiber bundles of inferior fronto-occipital fascicles，corticospinal tract and frontopontine tract on the side of the stroke（P<0.05）. Pearson correlation analysis revealed that，the FA of inferior fronto-occipital fascicles，corticospinal tract，frontopontine tract，cingulum bundle or uncinate fasciculus on the side of the stroke was negatively correlated with HAMD-24 score in PSD inpatients（r=-0.469，-0.769，-0.728，-0.801，-0.839，P<0.05）；the number of fiber bundle of inferior fronto-occipital fascicles，corticospinal tract or frontopontine tract on the side of the stroke was negatively correlated with HAMD-24 score in PSD inpatients（r=-0.858，-0.806，-0.694，P<0.01）.Conclusion　There were impairment changes of structure of inferior fronto-occipital fascicles，corticospinal tract，frontopontine tract，cingulum bundle and uncinate fasciculus in patients with PSD，and these changes may be significantly correlated with the severity of depression，indicating that some white matter fiber bundle alterations may be involved in the onset of PSD.

Association between Subclinical Hypothyroidism and Cardiac Autonomic Neuropathy in Type 2 Diabetes Mellitus

ZHAO Lei, LI Ruqiang, YUAN Mingxia

Background　Cardiac autonomic neuropathy （CAN） is a common and severe chronic diabetic complication，whose association with thyroid function has rarely been reported. Objective　To investigate the association between subclinical hypothyroidism and CAN in type 2 diabetes mellitus（T2DM）. Methods　We performed a retrospective analysis of 564 outpatients and hospitalized patients with T2DM recruited from Beijing Friendship Hospital，Capital Medical University from October 2019 to October 2020. Baseline characteristics，physical and laboratory examination results were collected. Ewing test was performed to identify CAN. The association between subclinical hypothyroidism and CAN was assessed using the Pearson correlation coefficient and Spearman's rank coefficient of correlation. Factors associated with CAN in T2DM were identified using multivariate，stepwise logistic regression. Results　One hundred and twenty-nine subjects （22.9%） were found with CAN，and other 435 without. Subclinical hypothyroidism was detected in 84 cases（14.9%），including 36 with CAN and 48 without. The prevalence of subclinical hypothyroidism in those with CAN〔28.0%（36/129）〕 was higher than that of those without〔11.0%（48/435）〕（χ2=22.346，P<0.001）. For those with CAN，the ratio between maximum and minimum R-R intervals during the Valsalva maneuver demonstrated a negative correlation with the duration of T2DM，glycated hemoglobin，fasting plasma glucose，low-density lipoprotein cholesterol，triacylglycerol，high-sensitivity C-reactive protein，thyroid-stimulating hormone and urine albumin-to-creatinine ratio，while it demonstrated a positive correlation with the diastolic blood pressure （P<0.05）. The multivariate，stepwise logistic regression analysis revealed that subclinical hypothyroidism〔OR=1.717，95%CI（1.246，2.365）〕was independently associated with increased risk of CAN in T2DM（P<0.05）. Conclusion　In type 2 diabetes patients，the level of TSH may be related to CAN，and subclinical hypothyroidism may be an independent associated factor of CAN.

Factors Associated with Community-dwelling Chronic Disease Patients' Experience of Integrated Medical-elderly-nursing Services

ZHU Xuejiao, YANG Min

　Background　The integrated medical-elderly-nursing（IMEN） services are promising to be very effective in addressing healthcare problems in multiple chronic disease patients in an aging society，but the quality of the services has been less focused. Objective　To identify the factors associated with community-dwelling chronic disease patients' experience of IMEN services，so as to provide a reference for improving the experience of this group and the quality of IMEN services. Methods　From June to September 2020，a questionnaire survey was conducted with a convenience sample of 550 community-dwelling chronic disease patients with IMEN services selected from Hanghou，Zhejiang Province，to collect their individual characteristics，understanding of IMEN services，and experience of IMEN services. The Chinese version of SERVQUAL developed based on the GAP Model of Service Quality was used to measure the discrepancy between patients' expectations for IMEN services and their perceptions of the services. With referring to the structure-process-outcome model，a structural equation model was developed，assuming that the features of IMEN services（process factors） were influenced by patients' individual characteristics（structure factors），and both of them affected patients' experience of IMEN services（outcome factors）. Results　The total average score of feeling and expectation of IMEN services for community patients with chronic diseases in Hangzhou is（5.14±0.44），（6.80±0.01），and the total average score of the gap between feeling and expectation is （-1.65±0.44）. Multiple linear regression analysis showed that gender，monthly income，payment method of medical expenses，number of illnesses suffered，prevalence of changing the service team，service items and number of service delivery patterns were associated with the discrepancy between patients' expectations for IMEN services and their perceptions of the services（P<0.05）. The analysis based on the structural equation model revealed that patients' experience of IMEN services was mainly directly affected by the features（duration of contracting the IMEN services，service items，and delivery patterns，smart medical care） of IMEN services（path coefficient=-0.51，P<0.001；direct effect size=-0.51，P=0.002）. Moreover，patients' experience of IMEN services was also directly influenced by individual characteristics（age，education level，self-care ability，number of illnesses）（direct effect size=-0.14，P=0.026），and indirectly influenced by such individual characteristics through features of IMEN services（indirect effect size=0.24，P=0.002）. Conclusion　Community-dwelling chronic disease patients accepted the IMEN services，but their service experience needed to be improved further by interventions such as improving the utilization of IMEN services，enriching the service delivery patterns，making full use of smart medical care and providing more personalized services.

Benefits and Models of Sexual Health Services Providedby General Practitioners

Sexual health is an important component of human health. Ignoring，misunderstanding and having misconceptions of sexual health will greatly impair people's quality of life. Owing to the concept of holistic health in general medicine，influence of biopsychosocial model of health，and family as a vital unit of care，and adherence to protecting patient privacy as a professional responsibility，general practitioners（GPs） have obvious advantages in offering sexual health services. However，more efforts are needed to strengthen the promotion of sexual healthcare knowledge popularization，sexual health screening，and sexual problem diagnosis and treatment in primary care of China. To provide support for Chinese GPs to deliver sexual health services，Department of General Medicine，The University of Hong Kong-Shenzhen Hospital，has pioneered in providing sexual health services and exploring new service delivery models using actions such as constructing a sexual health service team and a genital examination skills workshop，carrying out the consultation about sexual history，and developing a standard diagnostic and therapeutic procedure for sexualproblems.

Ultrasound-based Thyroid Nodule Malignancy Risk Stratification in Differentiating Benign and Malignant Thyroid Nodules：a Comparative Analysis between the C-TIRADS and ATA Guidelines

Background　The 2020 Chinese guidelines for ultrasound malignancy risk stratification of thyroid nodules：the C-TIRADS（C-TIRADS for short）put forward a method for stratifying the malignancy risk of thyroid nodules，but there are few studies about its value in differentiating benign and malignant thyroid nodules. Objective　To compare the value of ultrasound-based thyroid nodule malignancy risk stratification in differentiating malignant and benign thyroid nodule between C-TIRADS and 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer：The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer（ATA guidelines for short）. Methods　A total of 336 inpatients who underwent surgery and ultrasound examination in Bozhou People's Hospital from January 2019 to May 2021 were selected as participants. Four ultrasonologists with a title higher than attending physician were equally randomized into groups A and B for evaluating ultrasonic examination results according to ultrasound-based thyroid nodule malignancy risk stratification in C-TIRADS and ATA guidelines，respectively. The accuracies of ultrasound-based thyroid nodule malignancy stratification in the two guidelines in differentiating malignant and benign thyroid nodules were assessed using intraoperative or postoperative pathological findings (gold standard for diagnosis)，and were further analyzed using ROC analysis. Results　According to intraoperative or postoperative pathological findings，the participants had 367 thyroid nodules in total，including 253 benign nodules and 114 malignant nodules. The nodules were classified as follows according to the TI-RADS in the C-TIRADS by ultrasonologists in group A：（1）253 benign nodules：2 were in TI-RADS 5 category，23，30，and 80 were in categories 4c，4b，and 4a，respectively, 103 were in 3 category, and 15 were in 2 category；（2）114 malignant nodules：24 were in TI-RADS 5 category，59 were in 4c category，22 were in 4b category，6 were in 4a category and 3 were in 3 category. And the classification of nodules according to the ATA guideline by ultrasonologists in group B was：（1）253 benign nodules：13，53，47，118 were high，intermediate，low，and very low suspicion pattern for malignancy，respectively，and 22 were benign pattern；（2）114 malignant nodules：76，24，8，6 were high，intermediate，low，and very low suspicion pattern for malignancy，respectively. ROC analysis showed that，AUCs of ultrasound-based thyroid nodule malignancy risk stratification in differentiating malignant and benign thyroid nodules between C-TIRADS and ATA guidelines were 0.89〔95%（0.815，0.918）〕and 0.78〔95%（0.750，0.876）〕，with significant difference（Z=13.62，P<0.05）. The TI-RADS in the C-TIRADS showed 92.11% sensitivity，78.26% specificity，82.56% accuracy，with Youden index of 0.70 in differentiating 4b category benign and malignant nodules，and demonstrated 97.37% sensitivity，46.64% specificity，62.40% accuracy with Youden index of 0.44 in differentiating 4a category benign and malignant nodules. The ultrasound-based thyroid nodule malignancy risk stratification in ATA guideline showed 87.72% sensitivity，67.98% specificity，74.11% accuracy，with Youden index of 0.56 in differentiating intermediate suspicion pattern for malignancy，and demonstrated 94.74% sensitivity，44.66% specificity，60.22% accuracy with Youden index of 0.39 in differentiating low suspicion pattern for malignancy. Conclusion　The ultrasound-based thyroid nodule malignancy risk stratification in C-TIRADS has higher value in differentiating malignant and benign thyroid nodules than that in ATA guidelines，and the optimal performance of which may be manifested in differentiating malignant and benign thyroid nodules of TI-RADS 4b category.

Clinical Efficacy of Compound Daxueteng Enema plus Dydrogesterone in Post-laparoscopic Adenomyosis Patients with Blood Stasis-heat Syndrome

YING Pian, WANG Jiaxi, YANG Huadi, XU Li, LU Shenyi, WU Yanping

Background　Adenomyosis is a difficult-to-treat gynecological disease with unclear pathogenesis，individualized treatment for which is extensively valued，and the integrated traditional Chinese and western medicine treatment has been proven to have unique benefits merits. Objective　To examine the clinical efficacy of compound Daxueteng enema plus dydrogesterone for post-laparoscopic adenomyosis patients with blood stasis-heat syndrome. Methods　Participants（n=46） were selected from Zhejiang Provincial Hospital of Chinese Medicine during January 2019 to August 2020. All of them received laparoscopic surgery，and were diagnosed with adenomyosis by pathological examination of the surgical specimen，and with blood stasis-heat syndrome by TCM syndrome differentiation. For comparing the effects of two types of postsurgical treatments lasting for three months，they were randomized into a control group （n=22） and a treatment group（n=24），receiving oral dydrogesterone，and oral dydrogesterone plus compound Daxueteng enema，respectively. TCM syndrome score，uterine volume，pain level，menstrual blood loss，ovarian function parameters and serum CA125 were measured at baseline and the end of the three-month treatment. The overall efficacies of two groups were assessed at the end of treatment，and one year after the treatment，respectively. Results　The treatment group had statistically higher overall three-month efficacy than the control group（u=2.140，P=0.032）. Chinese medicine evidence of the treatment group were lower than the control group. After treatment，the VAS score for pain level，Pictorial Blood Loss Assessment Chart score for menstrual blood loss，uterine volume，E2 and CA125 showed a statistical decrease in both groups （P<0.05）. And the VAS score，PBAC score，uterine volume，E2，and CA125 demonstrated better improvements in the treatment group than the control group（P<0.05）. One-year post-treatment follow-up revealed that treatment group and control group had no statistically significant differences in recurrence rate〔20.83%（5/24）vs 45.45%（10/22）〕（χ2=3.166，P>0.05），and pregnancy rate〔8.33%（2/24）vs 9.09%（2/22）〕（χ2=0.008，P>0.05）. Conclusion　Oral dydrogesterone plus compound Daxueteng enema may be superior to oral dydrogesterone alone for post-laparoscopic adenomyosis patients with blood stasis-heat syndrome.

EGFR-TKIs with Anti-angiogenic Drugs as the First-line Treatment for Patients with Advanced EGFR-mutant Non-small Cell Lung Cancer：A Meta-analysis

LI Yong, LONG Yong, ZHAO Chong, ZHANG Guanqing, SU Yanhe

Background　Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKIs） will eventually occur in almost all advanced EGFR-mutant non-small cell lung cancer（EGFR-mutant NSCLC） patients although the therapy has been a standard first-line treatment for such patients. But EGFR-TKIs in combination with anti-angiogenic drugsmay prolong the survival time of these patients. Objective　To explore the efficacy and safety of EGFR-TKIs with anti-angiogenic drugs as the first-line treatment for patients with advanced EGFR-mutant NSCLC. Methods　Databases including CNKI，CQVIP，Wanfang Data Knowledge Service Platform，PubMed，EMBase，and the Cochrane Library were searched from inception to July 2021using subject headings with free-text words，for randomized controlled trials（RCTs） about the first-line treatment of advanced EGFR-mutant NSCLC patients with EGFR-TKIs in combination with anti-angiogenic drugs（combination therapy group）versus EGFR-TKIs alone（monotherapy group）.Two researchers performed literature screening，data extraction（the first author，publication time，the country where the author coming from，study type，sample size，stage of NSCLC，sex，average age，treatment regimen，ECOG PS score，median follow-up time，pathological type，gene mutation type，outcome indicators），separately，and assessed risk of bias in the included RCTs. STATA 15.0 was used formeta-analysis. Results　Nine RCTs were included，involving 1 553 patients. Meta-analysis results showed that the combination therapy was associated with longer progression-free survival（PFS）〔HR=0.61，95%CI（0.54，0.70），P<0.001〕. Further analysis based on PFS revealed that the combination therapy did not significantly prolong the PFS in those aged ≥65 years〔HR=0.80，95%CI（0.59，1.08），P=0.141〕and in those withbrain metastases〔HR=0.65，95%CI（0.39，1.06），P=0.086〕. Moreover，the combination therapy was not superior to monotherapy in terms of prolonging the overall survival〔HR=0.95，95%CI（0.76，1.21），P=0.697〕，and improving the objective response rate〔HR=1.04，95%CI（0.99，1.10），P=0.139〕，and disease control rate〔HR=1.00，95%CI（0.97，1.03），P=0.920〕.However，the rate of adverse eventsabove grade 3〔HR=1.77，95%CI（1.62，1.94），P<0.001〕was significantly increased. Conclusion　By using the combination therapy，advanced EGFR-mutant NSCLC patients may obtain a prolonged PFS，but with increased risk of serious adverse events. In addition，the patients could not obtain a prolonged overall survival，higher objective response rate and disease control rate.

The Glymphatic System：A New Exploration of Pathological Mechanism in Stroke

YI Ting, JIN Shuoguo, YIN Haiyan, GAO Ping, ZHU Tianmin — 2021-12-21 00:00:00.0

The glymphatic system is a system that promotes the exchange and flow of cerebrospinal fluid（CSF）-interstitial fluid（ISF） to maintain the balance of CSF-ISF，and rid the neuropil of toxic proteinaceous metabolites with astroglial water channel aquaporin-4 as the mediator. Increasing evidence has shown that the glymphatic system is strongly related to the pathological changes and outcomes of stroke. Available studies have found that the glymphatic system partially affects post-stroke cerebrospinal fluid circulation and cerebral edema. Different types of strokes include acute ischemic stroke，intracerebral hemorrhage，and subarachnoid hemorrhage also have pathological changes in the glymphatic system. This review summarizes the structure and function of the glymphatic system，and the latest developments in its impact on pathological changes of different types of strokes，providing a new direction for the prevention and treatment of stroke.

Epidemiologic Features and Containment of SARS-CoV-2 Omicron Variant

WU Yu, LIU Jue, LIU Min, LIANG Wannian

Since the first case of the Omicron（B.1.1.529） variant discovered in South Africa was reported to the WHO on November 24，2021，a total of 57 countries（regions） had reported Omicron cases as of December 8，2021. Although Omicron has become the dominant strain in some African countries，its source，infectivity，virulence and vaccine resistance are still unclear，which brings great challenges to pandemic prevention and control in all countries（regions）. We reviewed the latest developments in etiological characteristics，mutation sources，transmission characteristics and possible mechanisms，pandemic status，vaccine protection effect and containment measures regarding Omicron，providing a reference for scientific containment of Omicron mutant.