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Table of Content

    15 July 2022, Volume 25 Issue 20
    Guide Interpretation
    Interpretation of Consensus on Diagnosis and Management of Cushing's Disease: a Guideline Update of the International Pituitary Society——Diagnosis
    Huiwen TAN, Yu TANG, Yerong YU, Jianwei LI, Jiaqi LI, Zhenmei AN, Chun WANG, Yi WEI
    2022, 25(20):  2435-2442.  DOI: 10.12114/j.issn.1007-9572.2022.0190
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    Cushing disease, the most common cause of endogenous Cushing's syndrome characterized by hypercortisolemia, is a clinical syndrome caused by adrenocorticotropic hormone (ACTH) ——secreting pituitary adenomas. The excessive secretion of ACTH in Cushing's disease stimulates bilateral adrenal hyperplasia and causes hypercortisolemia, which can lead to a series of severe clinical syndromes such as electrolyte imbalance, glucose and lipid metabolism disorders, involving multiple organs and systems in the body. The clinical symptoms of Cushing's disease are complex and diverse, and its diagnosis and treatment are extremely challenging. In December 2021, the International Pituitary Society released the Consensus on Diagnosis and Management of Cushing's Disease: a Guideline Update, which focuses on the complications and comorbidities of Cushing's disease, such as hypercoagulability, cardiovascular disease, metabolic bone disease, growth hormone deficiency and infection, etc.; discusses the application of the latest evidence in clinical practice, with a particular focus on new treatment and screening options, diagnostic algorithms, and best practices for preventing disease recurrence. Based on the latest evidence-based medical evidence, this article focuses on the interpretation of Cushing's disease——related laboratory examinations, imaging examinations, diagnosis and treatment management procedures, and recurrence monitoring discussed in the Consensus on Diagnosis and Management of Cushing's Disease: a Guideline Update, in order to improve the general practitioners and specialists'understanding of this syndrome and improve the prognosis of patients with Cushing's disease.

    Article
    Associations of Predicted Body Fat Mass and Fat Percentage with Insulin Resistance among a Middle-aged and Elderly Non-diabetic Population
    Haiyan RUAN, Liying LI, Yi ZHENG, Xiaoping CHEN, Sen HE
    2022, 25(20):  2443-2449.  DOI: 10.12114/j.issn.1007-9572.2022.0181
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    Background

    Identifying insulin resistance (IR) is of important clinical value as it is a pathological basis of multiple diseases, such as metabolic syndrome, type 2 diabetes, hypertension, and atherosclerosis. Numerous previous studies have suggested that excessive gain of fat is closely associated with IR. Dual-energy X-ray absorptiometry is often clinically used as the golden standard for measuring human body fat, but its health economic cost is high.

    Objective

    To assess the associations of predicted fat mass (pFM) and predicted fat percent (pFP) with IR in a middle-aged and elderly population without diabetes in Chengdu.

    Methods

    In May 2007, a cross-sectional survey was conducted by trained medical workers in Chenghua District, Chengdu, Sichuan. A total of 711 middle-aged and elderly individuals were selected as surveyees by random cluster sampling, and 570 of them were included for analysis after excluding 141 with diabetes. The survey includes filling in a standardized questionnaire, a physical examination, and a laboratory test. The homeostasis model assessment of IR (HOMA-IR) , pFM, and pFP were calculated.

    Results

    Among the 570 subjects, the range of HOMA-IR was from 0.01 to 5.50, with a median value of 1.05 (0.72, 1.53) ; the range of pFM was from 2.34 to 41.41 kg, with a value of mean (SD) of (18.59±6.47) kg; the range of pFP was from 13.95% to 48.46%, with a median value of 28.97 (23.77, 37.39) %. The prevalence of IR was 20.17% (115/570) . The results suggested the HOMA-IR value and IR prevalence increased with the increase of pFM and pFP (P<0.001) . Multivariate Logistic regression analysis indicated that both pFM〔OR=3.22, 95%CI (2.45, 4.33) 〕 and pFP〔OR=3.51, 95%CI (2.61, 4.84) 〕 were associated with IR (P<0.05) . For predicting IR, the area under the receiver operating characteristic curve (AUC) was 0.777〔95%CI (0.733, 0.822) 〕with 38.10 kg as the optimal cut-off value for pFM, and 0.719〔95%CI (0.668, 0.769) 〕with 17.74% as the optimal cut-off value for pFP, respectively. And the AUC for four common traditional anthropometric indicators, namely waist circumference, body mass index, waist-to-height ratio (WHtR) and a body shape index (ABSI) was 0.749〔95%CI (0.700, 0.798) 〕, 0.753〔95%CI (0.706, 0.801) 〕, 0.768〔95%CI (0.722, 0.815) 〕, and 0.618〔95%CI (0.561, 0.675) 〕, respectively. Especially, the AUC of pFM or pFP was greater than that of ABSI (Z=4.452, P<0.001; Z=2.486, P=0.013) .

    Conclusion

    In this middle-aged and elderly non-diabetic population of Chengdu, pFM and pFP were independently associated with IR, and also could well discriminate IR. But pFM and pFP was only superior to ABSI.

    Development and Applicability Assessment of a TCM-based Risk Prediction Model for Major Adverse Cardiovascular and Cerebrovascular Events in Type 2 Diabetics with Stable Angina Pectoris
    Zhongrui WANG, Yu FU, Ruixia ZHAO, Haibin YU, Mingyi SHAO, Shuxun YAN, Jinghui HAN, Huijuan LIU, Rong ZHU, Jiayao YUAN, Leilei LI, Weifeng CUI, Xian WANG
    2022, 25(20):  2450-2456.  DOI: 10.12114/j.issn.1007-9572.2022.0085
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    Background

    Early treatment is crucial to the delay of the progression of type 2 diabetes mellitus with stable angina pectoris (T2DM-SAP) , which has poor prognosis, such as high rates of disability and mortality. As traditional Chinese medicine (TCM) has unique advantages in preventing diseases, developing a model with TCM and western medicine factors associated with major adverse cardiovascular and cerebrovascular events (MACCEs) incorporated may be a reliable tool that could be used to predict the risk of MACCEs in patients with T2DM-SAP.

    Objective

    To develop and assess the applicability of a risk prediction model for MACCEs in T2DM-SAP patients using identified risk factors associated with MACCEs in this group.

    Methods

    Participants were 674 inpatients with T2DM-SAP who received diagnostic and treatment services from The First Affiliated Hospital of Henan University of CM from 2012 to 2019. Through the hospital information system, electronic medical records and follow-up data of these patients were collected, including demographics, clinical characteristics, laboratory parameters, TCM symptoms and syndrome differentiation, and outcome (prevalence of MACCEs) . Patients were classified into a MACCEs group (n=190) and a non-MACCEs group (n=484) by prevalence of MACCEs. Independent risk factors for MACCEs in T2DM with SAP were identified using univariate and multivariate Logistic regression, and used to develop a nomogram-based predictive model. Then the model was internally validated using the bootstrap approach, and its predictive value was estimated using ROC analysis, C-index, calibration plot, Hosmer-Lemeshow test and decision curve analysis.

    Results

    Based on the multivariate Logistic regression analysis, the factors associated with MACCEs in T2DM-SAP patients (P<0.05) included age〔OR=1.033, 95%CI (1.014, 1.052) 〕, cerebrovascular disease history〔OR=3.799, 95%CI (2.529, 5.750) 〕, serum creatinine〔OR=1.005, 95%CI (1.002, 1.008) 〕, dark purple tongue〔OR=2.756, 95%CI (1.285, 5.935) 〕, decreased tongue coating〔OR=2.083, 95%CI (1.025, 4.166) 〕, thready pulse〔OR=5.822, 95%CI (1.867, 20.359) 〕, and obstruction of collateral channels caused by wind-phlegm〔OR=2.525, 95%CI (1.466, 4.387) 〕. The predictive model constructed using the above-mentioned factors showed moderate predictive power {C-index=0.769〔95%CI (0.729, 0.809) 〕, sensitivity=69.47%, specificity=75.00%} , indicating a good degree of distinction. The calibration plot showed the average absolute error between the predictive and actual adverse outcome risks was 0.011, with a C-index of 0.761 after fitting bias correction. The Hosmer-Lemeshow test showed a good calibration (χ2=6.004, P=0.647) . The decision curve analysis displayed a threshold probability of >30%, indicating that the model may be clinically beneficial.

    Conclusion

    The risk predictive model for MACCEs in T2DM-SAP patients was developed using the associated factors (including age, cerebrovascular disease history, serum creatinine, dark purple tongue, decreased tongue coating, thready pulse, and obstruction of collateral channels caused by wind-phlegm) identified by us, which has been proven to have good discrimination, calibration, and clinical effectiveness, and could be used as a tool for assessing the risk of MACCEs in patients with T2DM-SAP.

    Relationship between Obesity and Proteinuria in Type 2 Diabetic Patients
    Yilin MA, Jiangfeng KE, Junwei WANG, Lianxi LI
    2022, 25(20):  2457-2461.  DOI: 10.12114/j.issn.1007-9572.2022.0089
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    Background

    Obesity is a risk factor for the development of metabolic syndrome, type 2 diabetes mellitus (T2DM) , atherosclerosis and other diseases, but the correlation between obesity and albuminuria in diabetic patients has been insufficiently explored.

    Objective

    To investigate the correlation between obesity and albuminuria in patients with T2DM.

    Methods

    T2DM inpatients were consecutively recruited from Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital from January 2007 to June 2009. The general clinical data, physical and laboratory examination results were collected. In accordance with prevalence of obesity (defined as BMI≥25 kg/m2) , the patients were divided into obese group and non-obese group (BMI<25 kg/m2) , then the obese cases were further divided into mild (25 kg/m2≤BMI<30 kg/m2) , moderate (30 kg/m2≤ BMI<35 kg/m2) , and severe obesity subgroups (BMI≥35 kg/m2) . Albuminuria was diagnosed as 24-hour urinary albumin excretion≥30 mg/24 h. The relationship between obesity and albuminuria was analyzed by binary Logistic regression.

    Results

    In all, 3 023 T2DM cases were enrolled, including 1 609 non-obese cases, and 1 414 obese cases (1 196 cases of mild obesity, 206 cases of moderate obesity and 12 cases of severe obesity) . Compared with non-obese cases, obese cases had higher prevalence of alcohol consumption, hypertension, and history of anti-hypertensive mediation use (P<0.05) . Additionally, obese cases had higher average levels of systolic blood pressure, diastolic blood pressure, waist-to-hip ratio, fasting plasma glucose, 2-h postprandial blood glucose, serum creatinine, fasting C-peptide, 2-hour postprandial C-peptide, triglyceride, total cholesterol, low-density lipoprotein, alanine aminotransferase, and serum uric acid, and lower average levels of glycosylated hemoglobin and high-density lipoprotein (P<0.05) . Obese cases also had higher average level of 24-h urinary albumin excretion 〔13.7 (7.6, 42.6) mg/24 h〕 than did non-obese cases 〔9.7 (6.0, 22.3) mg/24 h〕 (P<0.05) . The prevalence of albuminuria (30.0%, 424/1 414) in obese cases was significantly higher than that of non-obese cases (20.2%, 325/1 609) (P<0.05) . Binary Logistic regression analysis showed that obesity was closely associated with albuminuria in T2DM〔OR=1.266, 95%CI (1.013, 1.582) , P<0.05〕 after adjusting for confounding variables.

    Conclusion

    Obesity may be an independent risk factor of albuminuria in T2DM. So controlling obesity is very important in decreasing the risk of albuminuria in T2DM patients.

    Effect of Probiotic Intervention on Class Ⅳ andⅤLupus Nephritis
    Meng HUANG, Cunjun HUANG, Qiujuan OU, Hongbo DAI, Jiede HE, Hang LIANG, Zhe CHEN, Qiubi XU
    2022, 25(20):  2462-2467.  DOI: 10.12114/j.issn.1007-9572.2022.02.001
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    Background

    As an adjuvant therapy, probiotics can significantly improve the therapeutic effect in lupus nephritis. But there is a lack of comparative studies of efficacies of drug treatments and effects of probiotics on gut flora.

    Objective

    To observe the therapeutic efficacy, and gut flora changes induced by probiotics as an adjuvant therapy for lupus nephritis.

    Methods

    Ninety-eight patients with class Ⅳ andⅤlupus nephritis were selected from Department of Nephrology, Affiliated Hospital of Xiangnan University from 2019 to 2020, and randomized into a routine group (routine treatment) and an intervention group (routine treatment plus probiotics) under allocation concealment. Intergroup comparison of clinical efficacies was conducted after 24-week treatment in terms of levels of 24-hour urine protein, blood urea nitrogen, serum creatinine, serum IgE, IgG, and serum inflammatory markers, as well as fecal flora changes and fecal short-chain fatty acid concentrations.

    Results

    A total of 93 cases (46 in routine group, and 47 in intervention group) who completed the therapeutic follow-up were included for final analysis. Both groups had no statistically significant differences in sex ratio, mean age, BMI, baseline levels of systolic blood pressure, diastolic blood pressure, hemoglobin, serum albumin, serum creatinine, complement C3 and complement C4 (P>0.05) . At the end of treatment, the intervention group demonstrated lower mean Systemic Lupus Erythematosus Disease Activity Indexof Renal (P<0.05) . The 24-hour urinary protein, blood urea nitrogen and serum creatinine decreased notably in both groups at the end of 4, 12 and 24 weeks of treatment (P<0.05) , and the 24-hour urinary protein and blood urea nitrogen in intervention group at the end of 24-week treatment were even more lower (P<0.05) . When the 24-week treatment ended, serum IgE and IgG levels decreased notably in both groups (P<0.05) , and they deceased even more significantly in intervention group (P<0.05) . Moreover, serum C-reactive protein, IL-6 and TNF-α decreased significantly in both groups (P<0.05) , and they deceased even more significantly in the intervention group (P<0.05) . Linear discriminant analysis effect size analysis indicated that at baseline, harmful gut flora such as Helicobacter pylori, Clostridium, and Enterococcus, significantly increased while Verrucomicrobia and other beneficial gut flora significantly decreased in all participants. After the 24-week treatment, the above-mentioned harmful gut flora decreased and beneficial gut flora increased in all participants, and such changes were more significant in the intervention group. Fecal acetic acid, propionic acid, and butyric acid increased significantly in all participants compared to the baseline levels, and they increased even more significantly in the intervention group (P<0.05) .

    Conclusion

    Adjuvant treatment of lupus nephritis with probiotics could promote the recovery of renal function, by elevating the abundance of Akkermansiaceae, contents of fecal acetic acid, propionic acid, and butyric acid, and lowering serum immunoglobulin.

    Effect of CPET-based Precisely Prescribed Aerobic Exercise on Cardiopulmonary Fitness and Sleep Quality in Stroke Patients
    Zhen QIAN, Tongbo LU, Jun HE, Qiuxiang RUAN, Chaolan WANG, Xin WANG
    2022, 25(20):  2468-2474.  DOI: 10.12114/j.issn.1007-9572.2022.0030
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    Background

    Cardiopulmonary problems will increase the risk of health harms yet they are often neglected in clinical rehabilitation treatment for stroke patients. In addition, sleep problems also often affect the rehabilitation effect in these patients, while routine drug treatment could not achieve satisfactory effect.

    Objective

    To assess the effect of precisely prescribed exercise on cardiopulmonary fitness and sleep quality in stroke patients.

    Methods

    Sixty-four stroke inpatients were recruited from Rehabilitation Department, Changzhou Dean Hospital from April 2020 to August 2021, and equally randomized into a control group and an experimental group. At baseline, cardiopulmonary fitness was assessed using cardiopulmonary exercise testing (CPET) , and sleep quality was assessed using Pittsburgh Sleep Quality Index (PSQI) for both groups. Then control group received 12-week routine rehabilitation training, while experimental group received 12-week routine rehabilitation training plus aerobic exercise precisely prescribed based on baseline CPET parameters. Intra- and inter-group comparisons were made between pre- and post-training major CPET parameters, dyspnea and leg fatigue measured by the Borg Scale and sleep quality.

    Results

    At the end of training, the experimental group demonstrated higher peak oxygen uptake (VO2peak) , percentage of predicted peak oxygen uptake (VO2peak%pred) , peak metabolic equivalent (METpeak) , peak heart rate (HRpeak) , peak load, and anaerobic threshold (AT) , and lower intensity of perceived dyspnea and leg fatigue than the control group (P<0.05) . The above-mentioned eight parameters improved significantly after training in the experimental group (P<0.05) . The experimental group had lower post-training scores of six domains (subjective sleep quality, sleep latency, sleep duration, sleep disturbances, use of sleep medication, daytime dysfunction) and lower post-training total score of PSQI than the control group (P<0.05) . The total score of PSQI and the scores of its seven domains were all lowered significantly when the training was finished (P<0.05) .

    Conclusion

    The precisely prescribed aerobic exercise by the results of CPET could effectively improve the cardiopulmonary fitness, exercise intensity, exercise endurance, and sleep quality as well as the sense of exercise fatigue in stroke patients.

    Adverse Pregnancy Outcomes and Associated Factors in Adolescent Primiparous Women
    Wenming ZHUANG, Li ZHANG, Jing ZHANG, Rongmin HU
    2022, 25(20):  2474-2481.  DOI: 10.12114/j.issn.1007-9572.2022.0278
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    Background

    Stubbornly high pregnancy prevalence in adolescent females worldwide, results in numerous adverse pregnancy outcomes, causing wide public concern. Thereby, it is pressing to study the pregnancy characteristics, adverse pregnancy outcomes and associated factors in adolescent primiparous females.

    Objective

    To examine adverse pregnancy outcomes and related factors in adolescent primiparous females via comparing pregnancy outcomes of them with those of emerging and early adult females.

    Methods

    Primiparous females (n=12 222, <35 year old) with ≥28 weeks of gestation were recruited from Ningbo Women and Children's Hospital during 2019—2020, including 210 aged 13-19 (adolescent group) , 1 729 aged 20-24 (adult group 1) , and 10 283 aged 25-34 (adult group 2) . Data were collected for maternal demographics, pregnancy complications, comorbidities, delivery course and adverse fetal outcomes. The associations of age, marital status, education background, rural or urban living, income, body mass index (BMI) with adverse maternal and fetal outcomes were analyzed.

    Results

    Adolescent primiparas had higher proportions of individuals with unmarried status, junior high school or lower education level, rural living, and an unstable income, as well as less mean prenatal care visits than the other two groups (P<0.05) . Moreover, adolescent primiparas also had higher rates of placental abruption, maternal anemia, vaginal delivery, perineal laceration, premature labor, (very) low-birth-weight infant, and stillbirth (P<0.05) . Multivariate Logistic regression analysis demonstrated that in adolescent primiparas, 13-24 years, unmarried and BMI<18.5 kg/m2 were associated with lower risk of gestational diabetes (P<0.05) ; gravida≥3 and BMI≥28 kg/m2 were risk factors for gestational diabetes (P<0.05) ; 13-24 years, unmarried, unstable income and BMI≥28 kg/m2 were risk factors for vaginitis (P<0.05) ; 13-19 year-old, unmarried, junior high school or lower education level and unstable income were risk factors for placental abruption (P<0.05) ; gravida≥3 was the risk factor for placenta previa (P<0.05) ; 13-24 years, unmarried, junior high school or lower education level, rural living and unstable income were risk factors for maternal anemia (P<0.05) ; BMI≥28.0 kg/m2 was associated with lower risk of maternal anemia (P<0.05) . Further analysis showed that 13-24 years, unmarried, junior high school or lower education level, rural living and BMI<18.5 kg/m2, were associated with higher possibility of having vaginal delivery (P<0.05) , whereas gravida≥3 was associated with higher possibility of having cesarean section (P<0.05) . Aged 13-19 years, unmarried, junior high school or lower education level, unstable income, gravida≥3, and BMI<18.5 kg/m2 or ≥28.0 kg/m2 were risk factors for premature labor (P<0.05) . Aged 13-19 year-old, unmarried, junior high school or lower education level, rural living, unstable income, gravida≥3, and BMI<18.5 kg/m2 were risk factors for (very) low-birth-weight infants (P<0.05) . 20-24 year-old was associated with lower risk of fetal distress (P<0.05) . 13-19 year-old and unmarried were risk factors for stillbirth (P<0.05) . 13-24 years, junior high school or lower education level, rural living, unstable income, and gravida≥3 were risk factors for neonatal asphyxia (P<0.05) .

    Conclusion

    Adolescent primiparous females were featured by high rates of having unmarried status, rural living, an unstable income, low education level, fewer prenatal care visits, and adverse pregnancy outcomes. Younger age, unmarried, poor socioeconomic status, higher number of pregnancies, and excessive low or high BMI were risk factors for adverse pregnancy outcomes in this group. Healthcare specialists should schedule prenatal examinations for these people based on the high risk factors accordingly. And government at all levels and affiliated adolescent institutions should offer appropriate social and economic support for teenage mothers to reduce adverse pregnancy outcomes.

    Prenatal Diagnosis and Pregnancy Outcome Analysis of High-risk Fetuses Suggested by Noninvasive Prenatal Screening
    Yan LUO, Bingyi ZHAO, Yanmei SUN, Haishen TIAN, Yali LI, Yanshang ZHANG, Jian GAO, Zhiqiang CUI
    2022, 25(20):  2482-2488.  DOI: 10.12114/j.issn.1007-9572.2022.0019
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    Background

    Noninvasive prenatal screening is more effective in screening for fetal aneuploidy than does traditional serological screening. We attempted to analyze the real-world data about the positive predictive value (PPV) for chromosome aneuploidy, and chromosome copy number variation (CNV) obtained by noninvasive prenatal testing (NIPT) , and to explore the pregnancy outcome for fetuses with sex chromosome aneuploidies and chromosome microdeletion or microduplication determined by pregnant women.

    Objective

    To assess the clinical value of karyotype analysis and chromosomal microarray analysis (CMA) of the testing results of NIPT.

    Methods

    Five-hundred and twenty-eight pregnant women who were found with a fetus at high risk of chromosome aneuploidy, and CNV by NIPT were selected from Department of Reproductive and Genetic Medicine, Hebei General Hospital, from January 1, 2014 to December 31, 2018. Amniocentesis or umbilical vein puncture was performed in them to obtain fetal cells for a definite prenatal diagnosis using karyotype analysis and CMA. All delivered cases were followed up by telephone within one year after childbirth to understand the pregnancy outcome.

    Results

    Prenatal diagnosis analysis revealed that 447 fetuses were at high risk of chromosome aneuploidy. And PPVs for the risk of trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, and other chromosome aneuploidy were 82.86% (174/210) , 51.52% (34/66) , 12.50% (4/32) , 50.82% (62/122) , and 5.88% (1/17) , respectively. Another 81 fetuses were at high risk of CNVs. CMA suggested that copy number variations were found in 28 cases (PPV 34.57%) , and the proportion with a clear pathogenic significance reached 24.69% (20/81) . Among the subjects under 35 years and 35 years or older, the proportions of abnormal results confirmed by prenatal diagnosis were 48.51% (147/303) and 70.22% (158/225) , respectively, showing statistically significant difference (χ2=24.938, P<0.05) . Out of the 62 pregnant women diagnosed with fetal sex chromosome abnormality, 13 (20.97%) continued with the pregnancy. Eight cases were reported no clear significance in CMA, among them one case was lost to follow-up, other seven cases chose to continue pregnancy. Among the seven infants, five were born healthy and developed normally, one girl had six fingers in both hands and the remaining one's situation was unknown.

    Conclusion

    The real-world data regarding PPVs for chromosomal aneuploidies and CNVs by NIPT, and follow-up of pregnancy outcome obtained by us, provide a reliable basis for clinical genetic counseling and treatment. It is recommended to perform karyotype analysis and CMA for a pregnant woman with a fetus with suspected chromosomal abnormality (extra or missing chromosomes, chromosome microdeletion, or microduplication) suggested by NIPT, to identify chromosome inversion, balanced translocation, low proportion chimerism and some morphological abnormalities, so as to improve the detection rate of fetal chromosome abnormalities.

    Study on the Relationship between Intestinal Microflora Differences and the Incidence of Preeclampsia in Pregnant Women in the Early and Middle Stages of Pregnancy
    Lei MO, Ping ZHONG
    2022, 25(20):  2489-2492.  DOI: 10.12114/j.issn.1007-9572.2022.0188
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    Background

    Severe preeclampsia can progress to eclampsia and threaten the life safety of mothers and infants, while intestinal flora composition changes may be involved in the occurrence and development of preeclampsia, but there is no clear evidence.

    Objective

    To investigate the relationship between intestinal flora differences and the incidence of preeclampsia in pregnant women in the early and middle stages of pregnancy.

    Methods

    A total of 455 pregnant women recruited from the Department of Obstetrics, the Second Affiliated Hospital of Guilin Medical University from January 2019 to January 2021 who met the requirements were selected. Pregnant women diagnosed with preeclampsia after 20 weeks of gestation were classified as preeclampsia group (n=32) , and pregnant women without preeclampsia were classified as non-preeclampsia group (n=423) . The clinical data of pregnant women were collected, and fecal samples were collected in the early (≤12+6 weeks) and middle stages of pregnancy (13~27+6 weeks) for bioinformatics analysis of intestinal flora, and the relationship between bioinformatics and the incidence of preeclampsia was analyzed.

    Results

    There were statistically significant differences in age, Shannon index and Simpson index in early pregnancy between preeclampsia group and non-preeclampsia group (P<0.05) . Logistic regression analysis showed that age≥35 years old〔OR=1.894, 95%CI (1.432, 2.369) 〕, low Shannon index in early pregnancy〔OR=0.709, 95%CI (0.465, 0.921) 〕 and low Simpson index in early pregnancy〔OR=0.612, 95%CI (0.354, 0.893) 〕 were independent risk factors for preeclampsia (P<0.05) . ROC curve showed that the optimal cut-off value and AUC of Shannon index for predicting the incidence of preeclampsia in pregnant women in early pregnancy were 6.255 and 0.745〔95%CI (0.652, 0.838) 〕, with the corresponding sensitivity and specificity of 76.58% and 60.00%, respectively. The Simpson index in early pregnancy predicted the onset of preeclampsia with the best truncation value of 0.945 and AUC of 0.724〔95%CI (0.623, 0.826) 〕, and the corresponding sensitivity and specificity were 62.90% and 60.61%, respectively.

    Conclusion

    Decreased Shannon index and Simpson index of fecal intestinal flora in early pregnancy in early pregnancy are independent risk factors for the occurrence of preeclampsia in pregnant women, and have early predictive value for the onset of preeclampsia.

    Dynamic Changes and Associated Clinical Value of Serum Soluble α-Klotho Protein for Patients with Severe Craniocerebral Injury
    Bin REN, Leifang YANG, Xinmin DING, Jifang LIANG
    2022, 25(20):  2493-2497.  DOI: 10.12114/j.issn.1007-9572.2022.0180
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    Background

    The serum soluble α-Klotho protein level may be associated with a lower risk and progression of multiple nervous system diseases. However, there are few reports concerning its dynamic changes and prognostic value in patients with craniocerebral injury.

    Objective

    To assess the dynamic changes of serum soluble α-Klotho protein level and associated prognostic value in patients with serious craniocerebral injury.

    Methods

    Participants were recruited from Shanxi Bethune Hospital from July 2019 to September 2020, including 103 cases of severe craniocerebral injury with surgical treatment and postoperative monitoring from the ICU (case group, including 74 survived and 29 decreased as of the 28th day posterior to admission) , and 50 physical examinees (healthy controls) . Clinical data of case group were collected. ELISA was used to measure the serum soluble α-Klotho protein level for all participants on the 1st, 3rd, 5th, and 7th days posterior to study enrollment.

    Results

    The mean levels of serum soluble α-Klotho protein measured at the four time points in case group were all higher than those of control group (P<0.05) . In case group, the 1st measured mean level of serum soluble α-Klotho protein was lower than the 2nd and 3rd measured levels, the 2nd measured level was higher than the 3rd and 4th measured levels, and the 3rd measured level was higher than the 4th measured level (P<0.05) .The 1st and 4th measured level of serum soluble α-Klotho protein in survival subgroup was higher than that in death subgroup (P<0.05) . In estimating the 28-day in-hospital survival, there was no statistical difference (Z=0.265, P=0.791) in the AUC of serum soluble α-Klotho level measured on postoperative days 1 and 7 {0.686〔95%CI (0.587, 0.774) 〕vs 0.710〔95%CI (0.612, 0.796) 〕} .

    Conclusion

    Elevated serum soluble α-Klotho protein was found in severe craniocerebral injury patients, which reached the peak on the 3rd day after injury. So dynamic monitoring of serum soluble α-Klotho protein may contribute to the assessment of patient clinical condition and prognosis.

    Development and Improvement of Nomograms Predicting the Prognosis in Patients with Severe Multiple Trauma
    Fei YIN, Yun LIU, Xie SHEN
    2022, 25(20):  2498-2506.  DOI: 10.12114/j.issn.1007-9572.2022.0113
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    Background

    Severe multiple trauma prevalence has been increasing recently, which has become the leading cause of labor force loss. Early and rapid assessment of patients' conditions will greatly affect their prognosis, which could be significantly supported by a concise and effective visual scoring system.

    Objective

    To identify and Screen the prognostic factors of severe multiple trauma, and use them to develop two nomograms, then improve them, and verify their clinical application values.

    Methods

    Patients with severe multiple trauma were recruited from the general ICU and EICU, Suzhou Ninth People's Hospital, including 321 treated during December 2015 to December 2020 (model group) , and 136 treated during January to August 2021 (validation group) . General data at admission and clinical data within 24 hours of admission were retrospectively collected. Prognosis (successful or unsuccessful treatment result) was assessed at discharge. Prognostic factors of severe multiple trauma were Screened using univariate and LASSO regression, and used to develop models using multivariate Logistic regression with restricted cubic splines, then based on this, two nomograms were developed, and their calibration accuracies were estimated using the bootstrap approach and decision curve analysis (DCA) . The receiver operating characteristic (ROC) analysis with associated AUC values was used to estimate the prognostic value of two nomograms in severe multiple trauma. External verification of the nomograms was carried out in the validation group to evaluate their clinical application values.

    Results

    (1) In the model group, successful and unsuccessful treatment results occurred in 244 and 77 cases, respectively. LASSO regression with multivariate Logistic regression analyses showed that age (OR=1.028) , Glasgow Coma Score (GCS) (OR=0.616) , arterial lactate (OR=1.202) , platelet count (OR=3.888) and Injury Severity Score (ISS) (OR=1.104) were associated with the prognosis of severe multiple trauma (P<0.05) . Hosmer-Lemeshow test indicated that this model fitted the data well (χ2=2.717, P=0.951) , and was appropriate for developing a static and network-based dynamic nomogram (nomogram 1) . LASSO plus multivariate regression analyses with restricted cubic splines revealed that age and GCS had nonlinear correlation with treatment results (P=0.027, 0.001) , and the fit of this model was satisfactory assessed using Hosmer-Lemeshow test (χ2=2.468, P=0.932) , and was appropriate for developing a static and network-based dynamic nomogram (nomogram 2) . Calibration charts showed that the standard curve fitted well with the probability calibration curves of nomograms 1 and 2 (absolute error=0.010, and 0.019) , indicating that the calibration accuracies of both models were good. The AUC of nomogram 1 in predicting the prognosis of severe multiple trauma was 0.963〔95%CI (0.936, 0.981) 〕with 0.414 was the optimal cut-off value, and that of nomogram 2 was 0.974〔95%CI (0.949, 0.988) 〕 with 0.261 as the optimal cut-off value. Nomogram 2 had a larger AUC value than nomogram 1 (Z=-2.400, P=0.016) . The DCA results showed that under any threshold probability (0-100%) , the net benefit rate of nomogram 2 was higher than that of nomogram 1. (2) In the validation group, successful and unsuccessful treatment results occurred in 104 and 32 cases, respectively. The AUC of nomogram 2 predicting the prognosis of severe multiple trauma was 0.949〔95%CI (0.898, 0.979) 〕. And the model fitted well (χ2=5.813, P=0.668) revealed by Hosmer-Lemeshow test. The AUC of nomogram 2 in predicting the prognosis of severe multiple trauma in model and validation groups had insignificant changes (Z=1.124, P=0.263) .

    Conclusion

    Age, GCS, arterial lactate, platelet count and ISS were prognostic factors of severe multiple trauma, and the two nomograms in this study based on these five factors had good prognosis predictive value. In particular, the optimized nomogram 2 had higher accuracy (the network-based dynamic version is available at https://yinfxyz.shinyapps.io/dynnomapp2/) , which was rapid, and easy-to-use, and it can help clinicians to identify patients early and improve the prognosis of patients.

    Cancer Mortality and Trend among Community-living Residents in Central Pudong New Area, Shanghai, 2007—2020
    Jie XU, Wei WANG, Xiaoqiong ZHANG, Juanping LI, Yimin CHEN, Li WANG, Guifen MA
    2022, 25(20):  2507-2512.  DOI: 10.12114/j.issn.1007-9572.2022.0270
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    Background

    The percentage of older population of the total population is increasing in developed areas of developing countries, and the impact and contribution of population composition factors towards cancer mortality are still unclear.

    Objective

    To analyze the epidemiological characteristics and trend of cancer mortality among community-living residents in central Pudong New Area of Shanghai from 2007 to 2020.

    Methods

    From January to December 2021, we retrospectively collected the death data during 2007 to 2020 of registered permanent residents living in Dongming Road Community of Pudong New Area from the all-cause death monitoring database, and population composition data from Pudong New Area Public Security Bureau. We used the crude mortality rate (CMR) , standardized mortality rate (SMR, with reference to the SMR of the general Chinese population in 2010) , and average annual percent change (AAPC) to analyze the status and trends of cancer mortality, and used the decomposition method to estimate the contribution rates of demographic and non-demographic factors to the change of cancer mortality.

    Results

    From 2007 to 2020, a total of 2 446 cancer-induced deaths were reported by the Dongming Road Community, accounting for 28.48% of the total reported deaths (8 589 cases) . The CMR of cancers was 268.56/105, in which the CMR due to lung cancer, colorectal cancer, and gastric cancer was 69.61/105, 33.05/105 and 31.84/105, respectively. The SMR of cancers was 71.46/105 , in which the SMR due to lung cancer, colorectal cancer, and gastric cancer was 33.12/105, 15.46/105, and 15.29/105, respectively. During this period, the CMR for cancers among men, women and the whole population remained stable (Z=1.82, -0.54, 0.87, P>0.05) . The CMR and SMR in men were higher than those in women (u=6.69, P<0.001; Z=-13.22, P<0.001) . The SMR in men showed a downward trend (AAPC=-1.80%, Z=-2.19, P<0.05) , while in women, it remained stable (Z=-1.63, P>0.05) . As in the whole population, it showed a downward trend year by year (AAPC=-1.73%, Z=-3.09, P=0.010) . Furthermore, the CMR for cancers in those aged 65-79 showed a downward trend gradually (AAPC=-4.17%, Z=-1.80, P<0.01) . The difference between the CMR of cancers during 2007—2013 and that during 2014—2020 was 3.80/105. The added value of demographic factors to mortality was 28.97/105, with a contribution rate of 53.51%. And the added value of non-demographic factors to mortality -25.17/105, with a contribution rate of 46.49%.

    Conclusion

    In Dongming Road Community from 2007 to 2020, both SMRs for cancers in the whole population and male residents demonstrated a downward trend, and the CMR for cancers in those aged 65-79 demonstrated a year-by-year downward trend. Older age may be the major demographic factor contributing to the stability of CMR of cancers.

    Methodology Research of TCM
    Strategy and Development of the TCM Syndrome-based Treatment Effectiveness Assessment Scale Using the Mode of Combination of Disease and Syndrome
    Jiansheng LI, Zhenzhen FENG, Yang XIE, Jiajia WANG
    2022, 25(20):  2513-2519.  DOI: 10.12114/j.issn.1007-9572.2022.0059
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    The TCM-based syndrome treatment effectiveness assessment scale could provide a basis for objectively evaluating the effectiveness of syndrome-based treatment and enrich the evaluation system of TCM treatment results. There are no unified and standardized methods for developing this kind of scale. In accordance with the international standards for developing a scale and ideas for developing a scale for assessing TCM treatment results as well as features of the TCM syndrome, and the experience of developing Syndrome Therapeutic Evaluation Scale of Chronic Obstructive Pulmonary Disease, we proposed the general process 〔including seven main parts (forming a research group, pre-designing the basic characteristics of the scale, constructing a framework and item pool, screening the items, forming a draft form of the scale, determining the weight of the items, and test of the scale) , and three key techniques (data mining technology based on association rules and latent structure analysis, item screening based on classical test theory and item response theory, and item weighting based on random forest, factor analysis, and percent weight) 〕 for developing a TCM-based syndrome treatment effectiveness assessment scale, hoping to offer guidance for other relevant studies.

    Thoughts on Key Factors of Clinical Trial Protocol Design for Chronic Atrophic Gastritis Treated with Traditional Chinese Drugs
    Tianyuan WANG, Bo LI, Guozhen ZHAO, Jing HU, Hong WANG, Shuo FENG, Huina ZHANG
    2022, 25(20):  2519-2524.  DOI: 10.12114/j.issn.1007-9572.2022.0065
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    Traditional Chinese Drugs has proven to have unique merits in treating chronic atrophic gastritis (CAG) , but needs to be verified further by high-quality large-sample clinical studies. We detailed the technique essentials of clinical trial protocol design and assessment for CAG treated with Traditional Chinese Drugs, which may be used as a methodological reference for clinical trial protocol design for CAG treated using Traditional Chinese Drugs, promoting the quality improvement of relevant studies. Then we discussed the essentials of relevant clinical trial protocol design, especially the selection of outcome indicators, in accordance with the attributes of Traditional Chinese Drugs, and features and actual needs of such trials, providing ideas for comprehensive evaluation of efficacy of Traditional Chinese Drugs in treating CAG.

    Choice of Outcomes Used in Randomized Controlled Trials Measuring the Efficacy and Safety of Massage Therapy for Cervical Spondylotic Radiculopathy
    Tianxiao FENG, Kangjian LI, Dawei YU, Wanyu SUN, Bifeng FU, Minshan FENG, Ping WANG
    2022, 25(20):  2525-2533.  DOI: 10.12114/j.issn.1007-9572.2022.0001
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    Background

    Massage is an important treatment for cervical spondylotic radiculopathy (CSR) . As massage-related research advances, numerous randomized controlled trials (RCT) concerning massage therapy in CSR have been published, but high-quality evidence is still limited due to some problems in the choice of outcomes.

    Objective

    To evaluate the outcomes used in RCTs in recent 10 years regarding CSR treated using massage, providing a basis for the choice of core outcomes used in studies about massage in CSR.

    Methods

    RCTs regarding CSR treated using massage were searched in databases of CNKI, Wanfang Data, CQVIP, SinoMed, PubMed, EMBase and Cochrane Library from January 2011 to May 2021. Literature screening, data extraction, and risk of bias assessment were performed by two researchers separately. A qualitative analysis was conducted to analyze the outcomes used in the RCTs.

    Results

    In all, 66 RCTs were included, in which the outcomes were categorized into 7 categories based on functional attributes: quality of life (95 times, 41.48%) , symptoms and signs (64 times, 27.95%) , physical and chemical examinations (39 times, 17.03%) , safety events (12 times, 5.24%) , economic assessment (12 times, 5.24%) , long-term prognosis (5 times, 2.18%) , and TCM symptoms/syndromes (2 times, 0.87%) . The most frequently used five outcomes were overall response rate, Visual Analogue Scale (VAS) score, Neck Disability Index score, adverse reactions and adverse events, symptom and sign score, and the measurement time points for which were 17 in total in a period from one day after treatment to the sixth month of follow-up. The above-mentioned outcome indexes are mainly measured at 14 days (27.08%) , 14 days (26.67%) , 14 days (29.17%) , 28 days (28.57%) and 14 days (33.33%) after treatment. The number of RCTs using one, two, three, and at least four outcomes was 5, 20, 14, and 27, respectively. Forty-eight RCTs reported the overall response rate.

    Conclusion

    We found many problems existing in the choice of outcomes used in RCTs assessing massage for CSR. The problems are as follows: primary and secondary outcomes were not defined; alternative outcomes received more attention while endpoint outcomes were neglected; the blinding method was ignored in RCTs using subjective outcomes; there was tremendous heterogeneity between RCTs in the number or combination of outcomes used, composite outcomes were mostly used; there was non-uniformity in measurement times of outcomes. We suggest that further relevant studies should pay attention to sufficient top-level design and preliminary research, and actively take actions to establish a set of core outcomes.

    Definition and Differences of Determination Criteria of the Rate of Chronic Low Back Pain Response to Integrated Traditional Chinese and Western Medicine Treatment in Clinical Studies: a Scoping Review
    Xia LI, Duoduo LI, Luyao CHENG, Ying WAN, Changhe YU
    2022, 25(20):  2534-2540.  DOI: 10.12114/j.issn.1007-9572.2022.0062
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    Background

    The integrated traditional Chinese and Western medicine has proved to be significantly effective in low back pain. But the response rate, a key composite outcome index for assessing the efficacy, has not been unified and standardized in clinical research.

    Objective

    To perform a scoping review of the definition and contents of rate of chronic low back pain response to integrated traditional Chinese and Western medicine in clinical studies with response rate as a composite outcome indicator, offering a reference for appropriately selecting composite outcome indicators of this disease.

    Methods

    Databases including Web of Science, PubMed, EMBase, Cochrane Library, CNKI, CQVIP, Wanfang Data and SinoMed were searched for clinical studies of chronic low back pain treated by integrated traditional Chinese and Western medicine published from January 2015 to December 2019. Two researchers independently enrolled studies according to inclusion and exclusion criteria, extracted data according to the BPICOS principles, and reviewed and summarized the criteria for defining the response rate as a composite outcome indicator.

    Results

    Among 830 included studies, lumbar muscle degeneration had been studied the most 〔178 (21.4%) 〕, followed by the third lumbar transverse process syndrome〔103 (12.4%) 〕, lumbar disc herniation〔91 (11 .0%) 〕, low back pain〔89 (10.7%) 〕, lumbodorsal myofasciitis〔72 (8.7%) 〕, lumbar spinal stenosis〔69 (8.3%) 〕, and lumbar spondylolisthesis〔61 (7.3%) 〕. 808 studies (97.3%) described the reference for the definition of response rate or explained the definition of response rate developed by the author. Specifically, different versions of Criteria for the Diagnosis, Syndrome Differentiation, and Response Assessment of Diseases by Chinese Medicine was referred the most〔271 (32.7%) 〕. Clinical symptoms, level of daily life activities, pain, signs and work & living ability, these five indictors were used most frequently as composite outcome indicators, and 2-5 of them were often randomly used in combination as the third or fourth level of response criteria. In addition, common low back pain measurement tools were also used.

    Conclusion

    Due to the lack of unified standard, composite outcome indicators used for response assessment in clinical studies about chronic low back pain treated by traditional Chinese and Western medicine might have many problems, such as various definitions, division criteria, and assessment items. In view of this, it is suggested to standardize the composite outcome indicators for response assessment in accordance with the CORE Outcome Measurement and Evaluation Tool, and to improve their validity to be used in clinical studies regarding integrated traditional Chinese and Western medicine as unified indicators, thereby improving the quality and value of such studies.

    Socio-Psychological Behaviors
    Mediating Effect of Marital Satisfaction Level on the Relationship between Partner Phubbing and Depression in Late Pregnancy
    Yun TIAN, Yuhong LI, Jingjing ZHAO, Yudong ZHANG, Liu ZHANG
    2022, 25(20):  2541-2546.  DOI: 10.12114/j.issn.1007-9572.2022.0072
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    Background

    The prevention and treatment of depression is a priority among mental health issues in China, and pregnant women are a key target group. Prenatal depression is easily ignored although it is highly prevalent and harmful. To reduce its prevalence, it is crucial to identifying the interaction mechanism between psychosocial factors (such as marital satisfaction and partner support) associated with prenatal depression, and controlling the modifiable risk factors.

    Objective

    To explore the relationship between marital satisfaction, partner phubing and depression in late-pregnancy women, and to assess the level of mediating effect of marital satisfaction on the relationship between the latter two, providing maternal and child healthcare professionals with evidence on interventions for prenatal depression.

    Methods

    Convenience sampling method was used to select women in late pregnancy who underwent routine prenatal check-ups in the Obstetrics Clinic, the First Affiliated Hospital of Anhui Medical University from October 2020 to May 2021. A self-designed general information questionnaire was used to collect sociodemographic and obstetric data. The Partner Phubbing Scale (PPS) was used to assess partner phubbing prevalence. The Quality of Marriage Index (QMI) was used to measure the level of marital satisfaction. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess the prenatal depression prevalence. Mplus 8.3 was used to establish a structural equation model for mediation analysis.

    Results

    Altogether, 300 cases were recruited. All of them were included for analysis except nine cases who returned unresponsive questionnaires, obtaining a survey response rate of 97.00%. The prenatal depression prevalence in the respondents was 40.89% (119/291) . The mean scores of PPS, QMI, and EPDS for them were (25.6±6.3) , (37.9±6.0) , and (8.0±3.5) , respectively. Correlation analysis showed that partner phubbing was negatively associated with marital satisfaction (r=-0.292, P<0.01) , and positively associated with prenatal depression (r=0.350, P<0.01) . Marital satisfaction level was negatively correlated with prenatal depression (r=-0.338, P<0.01) . Mediation analysis revealed that the size of direct effect of partner phubbing on prenatal depression was 0.214, accounting for 82.63% of the total effect. Marital satisfaction partially mediated the relationship between partner phubbing and prenatal depression, with a size of mediation effect of 0.045, accounting for 17.37% of the total effect.

    Conclusion

    Partner phubbing could positively predict depression in late pregnancy, and their relationship may be partially mediated by marital satisfaction. To reduce the prevalence of depression in late pregnancy, maternal and child healthcare professionals could improve the marriage of pregnant woman via providing them with interventions to decrease the prevalence of partner phubbing.

    Advances in Screening for Postpartum Hypomanic Symptoms and Their Relationship with Postpartum Depression and Bipolar Disorder
    Qianqian ZHAO, Yanli ZHOU, Chaoqun XIAO, Wenting LIU, Zhongyi FAN, Yu CHEN
    2022, 25(20):  2547-2550.  DOI: 10.12114/j.issn.1007-9572.2021.02.073
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    Hypomanic symptoms in postpartum women are common but often ignored due to under diagnosis, which may lead to more serious psychological problems, such as postpartum depression and bipolar disorder. We reviewed recent advances in diagnostic criteria and assessment tools regarding postpartum hypomanic symptoms as well as their relationship with postpartum depression and bipolar disorder, aiming to provide physicians and nurses with a scientific basis for more effectively identifying postpartum hypomania.

    Review
    New Research Progress of the Novel Target Drugs for the Treatment of Type 2 Diabetes Mellitus
    Pengxiang ZHANG, Lin ZENG, Lu MENG, Qian HUANG, Gaoxiang WANG, Deliang LIU
    2022, 25(20):  2551-2557.  DOI: 10.12114/j.issn.1007-9572.2022.0115
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    At present, there are many types of drugs for clinical treatment of type 2 diabetes mellitus (T2DM) , there are differences in the hypoglycemic mechanisms and safety of traditional hypoglycemic drugs such as thiazolidinediones, sulfonylureas, biguanides, and insulin. In recent years, an assortment of new target drugs has emerged in an endless stream.New target drugs such as glucokinase activators, multi-site receptor agonists for GLP-1, GIP and glucagon, glucagon receptor inhibitors have gradually assembled the necessities of personalized clinical treatment through different mechanisms. This article reviews the current research progress of new target drugs for T2DM, and analyzes the advantages and disadvantages of clinical research of various new target drugs, in order to provide basic guidance for the clinical treatment of T2DM.

    Novel Developments in Hypomimia in Parkinson's Disease
    Gen HUANG, Huimin CAO, Gang YU
    2022, 25(20):  2558-2562.  DOI: 10.12114/j.issn.1007-9572.2022.0245
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    Hypomimia is one prominent clinical symptom of Parkinson's disease (PD) , which is mainly characterized by a loss or reduction of voluntary, emotional and other facial expressions, and usually appears bilaterally and symmetrically. Factors associated with hypomimia in PD have been extensively studied recently, including basal ganglia dysfunction, facial emotion recognition deficit, and cognitive impairment, but the specific pathophysiological mechanism is still unclear. Hypomimia strongly correlates with the progression of PD, so scientific quantification and evaluation of hypomimia will be of great significance to the diagnosis and treatment of PD. Besides that, there is still controversy over its treatment plan. We reviewed the latest developments in clinical presentations, pathogenesis and treatment of hypomimia in PD.