Table of Content

15 March 2023, Volume 26 Issue 08

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Editorial

Nanoparticle- and Exosome-based Targeted Drug Delivery Systems Used in the Diagnosis and Treatment of Atherosclerosis: Opportunities and Challenges

LIU Taotao, LI Tianrong, WANG Xue, CHEN Jiameng, SHUAI Zhiqin, LI Lisheng, XU Shangfu

2023, 26(08):  903-910.  DOI: 10.12114/j.issn.1007-9572.2022.0795

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Atherosclerosis is a chronic inflammatory disease in which atheromatous plaque long-termly accumulates and obstructs the intima of medium and large arteries, causing first severe stenosis and blood flow disorders, and then ischemia and hypoxia in tissues and organs. Nanomedicines have received widespread attention for their unique advantages over conventional drugs in the treatment of atherosclerosis. This article detailedly reviews several nanoparticle- and exosome-based targeted drug delivery systems in anti-atherosclerosis research, briefly describes the synthesis of representative nanomaterials, analyses their targeting properties and outlines the benefits and inherent challenges of nanomedicines. Despite the challenges that need to be addressed and refined, nanoparticles and exosomes used as drug delivery vehiclesin treatments for atherosclerosis hold great promise and are expected to have wider clinical applications.

Original Research

Relationship between Ectodysplasin A and Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus

QIAN Fangfang, CAI Zhensheng, GU Tian, LI Haoxiang, ZHAO Li, YANG Ling, DENG Xia, YUAN Guoyue

2023, 26(08):  911-916.  DOI: 10.12114/j.issn.1007-9572.2022.0660

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Background

Hepatokines are a variety of proteins secreted by the liver, a key organ involved in systemic metabolism and endocrine, directly affect the liver glycolipid metabolism, and play an important role in the development of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM). Ectodysplasin A (EDA) is a newly discovered hepatokine, which is considered to be strongly related to diabetes, obesity and insulin resistance.

Objective

To assess the relationship between serum EDA level and the risk of NAFLD in patients with T2DM.

Methods

One hundred and thirty T2DM patients, including 74 males (56.92%) and 56 females (43.08%), with a mean age of (55.6±12.4) years, were recruited from Department of Endocrinology, Affiliated Hospital of Jiangsu University between November 2017 and November 2020. Baseline data, results of glucose tolerance test, insulin response test, C-peptide response to glucagon test, and color Doppler ultrasound of the abdomen were collected. Baseline data were compared between patients with ultrasound-detected NAFLD (n=80) and those without (n=50). Pearson correlation analysis was used to evaluate the correlation between serum EDA and the other clinical and biochemical indices. Multiple linear regression analysis was used to explore the influencing factors of EDA level. Multivariate Logistic regression analysis was used to explore the effect of EDA level on the risk of NAFLD.

Results

Compared with non-NAFLD group, NAFLD group had much younger mean age, shorter mean duration of T2DM, but significantly higher mean levels of BMI, fasting insulin (FIns), 2-hour postprandial insulin responses (2 hIns), fasting C-peptide (FCP), 2-hour postprandial C-peptide (2 hCP), homeostasis model assessment of insulin resistance (HOMA-IR), triacylglycerol (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood uric acid (SUA), urea nitrogen (BUN), and EDA level (P<0.05). Pearson correlation analysis showed that the serum EDA level was positively correlated with age, FIns, 2 hIns, HOMA-IR, and AST (r=0.222, 0.186, 0.233, 0.204, 0.189, P<0.05). Multiple linear regression analysis showed that age〔β=1.957, 95%CI (0.412, 3.502), P=0.013〕, WHR〔β=-328.845, 95%CI (-638.903, -18.788), P=0.038〕, 2 hIns〔β=0.523, 95%CI (0.036, 1.011), P=0.036〕 and AST〔β=2.148, 95%CI (0.520, 3.776), P=0.010〕were independently associated with EDA (P<0.05). Multivariate Logistic regression analysis demonstrated that EDA was still associated with NAFLD after adjusting for multiple confounding factors〔OR=1.006, 95%CI (1.002, 1.010), P=0.007〕.

Conclusion

In T2DM patients with NAFLD, the level of serum EDA was significantly increased, and potentially associated with elevated risk of NAFLD, which suggests that serum EDA level may play a role in the development of NAFLD in T2DM. Our study may provide a theoretical basis for early screening or treatment of NAFLD.

Establishment of a Risk Prediction Model for Thrombotic Events in Chinese Patients with Hypertrophic Cardiomyopathy

RUAN Haiyan, LI Liying, ZHANG Muxin, ZHENG Yi, HE Sen

2023, 26(08):  917-926.  DOI: 10.12114/j.issn.1007-9572.2022.0592

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Background

Thrombotic events are a major complication of hypertrophic cardiomyopathy (HCM). There are only two available risk prediction models for thrombotic events, HCM Risk-CVA score and French HCM score developed by foreign scholars, yet the former one has been found to have limited predictive value in Chinese HCM patients.

Objective

To develop a risk prediction model for thrombotic events in Chinese patients with HCM.

Methods

A retrospective cohort study design was used. Five hundred and thirty-seven HCM patients who admitted to West China Hospital of Sichuan University from 2010 to 2018 were recruited. Post-discharge health status was collected by use of telephone follow-up or checking the treatment status recorded in the electronic medical record system once every 6 to 12 months until a composite thrombotic event (defined as the endpoint event) or death occurred or the determined thrombotic risk assessment day of this study (2019-12-31). Univariate and multvariate Cox regression analyses were applied to build a thrombotic risk prediction model, and its internal validation was tested in a resample using the bootstrapping technique.

Results

Due to data missing, 24 cases were excluded, and the other 513 cases were finally included. During a median follow-up of 4.2 years (IQR: 1.3-6.2 years), thrombotic events occurred in 42 cases (8.18%), with an annual morbidity rate of 2.10%〔95%CI (1.47%, 2.73%) 〕. By multivariate Cox regression analysis, age, prior thrombotic event and left ventricular ejection fraction (LVEF) were identified (P<0.05) and used for constructing the formula of SAAE score (S=prior stroke and other thrombotic events, A=atrial fibrillation, A=age, E=LVEF) for predicting thrombotic events after being weighted based on the regression coefficient. Internal validation suggested that SAAE score could discriminate thrombotic events in the whole population {Harrell's C-index=0.773〔95%CI (0.688, 0.858) 〕}, with a calibration slope of 1.006, and could well discriminate 1-year, 3-year and 5-year thrombotic events (Harrell's C-index=0.790, 0.799, 0.735), with a good calibration ability. In addition, the SAAE score also performed well in distinguishing thrombotic events in patients with or without atrial fibrillation {Harrell's C-index=0.669〔95%CI (0.548, 0.791) 〕, 0.647〔95%CI (0.498, 0.795) 〕}, with good calibration ability. Besides that, SAAE score could partially discriminate 1-year, 3-year and 5-year thrombotic events in these two groups, with certain calibration ability. For three groups (whole study population, patients with/without atrial fibrillation), SAAE score could discriminate the risk of thrombotic events (either low, moderate or high) excellently. For the whole study population, SAAE score was better than HCM Risk-CVA score in distinguishing thrombotic events (P=0.013). Decision curve analysis showed the net benefit of SAAE score was better than HCM Risk-CVA score at different prediction time points (1, 3 and 5 years) .

Conclusion

This thrombotic events risk prediction model developed by us for Chinese HCM patients, namely SAAE score, could well stratify the risk of thrombotic events.

Correlation between Adiponectin and Free Testosterone Index and Insulin Resistance in Patients with Polycystic Ovary Syndrome

TANG Zixuan, LI Jing, HUANG Qi, ZHANG Ying, ZHANG Han, WANG Qian, ZHANG Lin, CHENG Yao, LIAO Xin

2023, 26(08):  927-932.  DOI: 10.12114/j.issn.1007-9572.2022.0611

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Background

Polycystic ovary syndrome (PCOS) is closely related to insulin resistance and free testosterone index (FAI), but a large number of studies are still needed to provide a reference for its diagnosis and treatment.

Objective

To explore the correlation of adiponectin (ADPN) with FAI and insulin resistance at different testosterone concentrations in PCOS patients, and to further investigate the clinical value of adiponectin in PCOS.

Methods

From October 2017 to April 2020, 116 patients with PCOS and 45 healthy women of normal reproductive age (control group) who were treated in outpatient or inpatient hospital of Zunyi Medical University Affiliated Hospital were selected as the research objects. The general data of the research subjects were collected, and laboratory index examinations were conducted: on the 3rd to 5th day of the menstrual cycle of regular menstruation or when there was no dominant follicle in the B-ultrasound examination of irregular menstruation, and the patient's cubital venous blood was collected on an empty stomach after fasting for 12 hours to detect fasting blood glucose (FPG), fasting insulin (FINS), Glycated hemoglobin (HbA_1c), triacylglycerol (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone, testosterone (TEST), sex hormone binding globulin (SHGB), dehydroepiandrosterone sulfate (DHEA-S), ADPN. The homeostasis model-assessed insulin resistance index (HOMA-IR) and FAI were calculated. PCOS patients were divided into PCOS with hyperandrogenemia group (HA group, n=65) and PCOS without hyperandrogenemia group (non-HA group, n=51) according to whether they had hyperandrogenism (TEST≥2.44 nmol/L). The HA and non-HA groups were further divided into 4 subgroups according to the quartile values of TEST levels. The correlation between ADPN and other indicators and the influencing factors of FAI and ADPN were analyzed.

Results

Compared with the control group, the body mass, BMI, waist circumference, hip circumference, WHR, FPG, FINS, HOMA-IR, HbA_1c, TG, LDL, FSH, TEST, FAI were increased, and HDL was decreased in the non-HA and HA group of PCOS patients (P<0.05). Compared with the non-HA group, the TG, HOMA-IR, TEST and FAI of the HA group were increased, while the HDL, FSH, progesterone, SHBG and ADPN of the HA group were decreased (P<0.05). There were significant differences in ADPN between HA group and non-HA group with different TEST level subgroups (P<0.05). After adjustment for BMI, ADPN in PCOS patients was negatively correlated with HOMA-IR, FAI, and TEST (P<0.001). In the HA group, ADPN was negatively correlated with HOMA-IR, FAI, and TEST (P<0.05) ; in the non-HA group, ADPN in the group was negatively correlated with HOMA-IR, FAI (P<0.05), and had no correlation with TEST (P=0.061). In the non-HA group, ADPN and BMI were the influencing factors of FAI, and HOMA-IR, FAI and BMI were the influencing factors of ADPN (P<0.05). In the HA group, ADPN was the influencing factor of FAI and HOMA-IR, and FAI were the influencing factors of ADPN (P<0.05) .

Conclusion

ADPN is negatively correlated with and mutually affects free testosterone index, and this relationship is not affected by TEST concentrations, and by measuring serum ADPN levels can simultaneously reflect the high androgen levels and the degree of insulin resistance in PCOS patients, ADPN is expected to be an important reference index for the diagnosis and condition evaluation.

Developmental Delay/Mental Retardation of Unknown Origin in Children: Genetic Analysis of 93 Cases

WANG Jing, LIU Yun, HUANG Haoyu, WU Jinting, LIU Chunming, ZHANG Yangping, WANG Wenjuan

2023, 26(08):  933-938.  DOI: 10.12114/j.issn.1007-9572.2022.0595

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Background

It is hard to make an early and accurate diagnosis of developmental delay (DD) /mental retardation (MR) in children due to complex etiology, diverse and heterogeneous clinical manifestations of the disease. There are few large-sample analyses of the clinical and genetic test data of these children in China.

Objective

To perform an analysis of genetic test results of children with DD/MR, providing evidence for genetic diagnosis, treatment plan formulation and prognosis assessment in such children.

Methods

Ninety-three children with DD/MR of unknown origin were selected from Department of Rehabilitation, Kunming Children's Hospital from September 2017 to September 2021. Whole-exome sequencing (WES) was performed to explore pathogenic gene mutations associated with clinical manifestations. Copy number variation (CNV) detection was conducted to examine the characteristics of pathogenic CNVs. The detection of gene mutations was analyzed.

Results

The DD/MR in the children was mainly manifested by motor or global DD, or MR, and with a developmental level falling behind normal developmental milestones. Seventy-four cases (79.6%) were detected with genetic variants, and the detection rate was 79.6%, among whom 40 (43.0%) with pathogenic gene mutations, 13 (14.0%) with gene CNVs, and 21 (22.6%) with mutations of uncertain significance. The genetic test results involved more than 50 pathogenic genes in total. The most prevalent disease caused by gene mutation was spinal muscular atrophy caused by mutations in the SMN1 gene (10.0%, 4/40), followed by Bethlem myopathy-1 caused by mutations in the COL6A2 gene (7.5%, 3/40) and Joubert syndrome-21 caused by mutations in CSPP1 (5.0%, 2/40) .

Conclusion

Pathative gene mutations and gene copy number variants may be main causes of DD/MR. SMN1, COL6A2, and CSPP1 are common mutated genes in DD/MR patients. WES combined with CNV detection may greatly contribute to the exploration of the etiology of DD/MR, especially for DD/MR manifested by atypical phenotypes and clinical manifestations.

Bioinformatics Analysis of the Role of Epicardial Adipose Tissue in Coronary Artery Disease

CHAI Yan, ZHAO Yuqing, GUO Xunan, WANG Dongying, BIAN Yunfei

2023, 26(08):  939-950.  DOI: 10.12114/j.issn.1007-9572.2022.0487

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Background

Cardiovascular disease (CVD) is a common and frequently occurring disease, and the prevalence and mortality of which are increasing rapidly. Atherosclerosis (AS) is the pathological basis of ischemic CVD. Studies have shown that epicardial adipose tissue (EAT) promotes the progression of AS by secreting exosomes and bioactive substances, but the mechanism of action still needs to be further studied.

Objective

To perform a bioinformatics analysis of role of EAT in coronary artery disease (CAD) at cellular and molecular levels by identifying the differentially expressed genes (DEGs) in EAT to explore the status of immune cell infiltration, and to assess and verify whether EAT is derived from DEGs in exosomes in CAD patients.

Methods

We downloaded GSE64554 and GSE120774 datasets about EAT from the GEO database and performed a bioinformatics analysis using R language and related packages. We first used R language to screen the DEGs in EAT and CAD patients, then used GO/KEGG enrichment analysis to establish a protein interaction network to explore biological functions of the screened genes and transcription factors potentially involved in their regulation process. After that, we conducted a weighted gene co-expression network analysis (WGCNA) of EAT in GSE64554 dataset to obtain a gene module related to CAD phenotype, then crossed the hub genes in this module and DEGs in EAT to obtain the key common genes. We used Cibersort to characterize the immune cell infiltration in EAT. Then we obtained DEGs from blood exosomes of CAD patients and healthy controls included in the exoRbase database, crossed DEGs in EAT and blood exosomes to identify the common genes to be used as diagnostic and therapeutic markers for CAD, and their values were tested by qRT-PCR measurement of clinical samples. The selected genes were analyzed by GO/KEGG and Metascape enrichment analyses.

Results

A total of 1 511 DEGs in EAT of CAD patients were identified, including 956 with up-regulated expression and 555 with down-regulated expression. By crossing the DEGs in EAT and hub genes in modules associated with CAD closely, we identified DDX47, FEM1C, NOL11, SRP54, ABI1, PATL1, BNIP2, C1orf159, and CHCHD4 as key genes in the development of CAD. Immune cell infiltration analysis showed that the abundance of immature CD₄⁺ T cells increased while expression abundance of resting dendritic cells decreased in EAT of CAD patients (P<0.05). A total of 1 658 DEGs in exosomes of CAD patients, including 278 with up-regulated expression and 1 380 with down-regulated expression. One hundred and twenty-nine common DEGs were obtained by cross-tabbing DEGs in EAT and exosomes of CAD patients, among which BPI, BIRC5, CXCL12, RNASE1 and F2R with higher expression abundance were selected as potential diagnostic and therapeutic markers for CAD. By qRT-PCR detection, CAD patients were found with increased mRNA expression levels of BPI, BIRC5, CXCL12, RNASE1 (P>0.05), and decreased F2RmRNA expression level (P<0.05) than controls. GO/KEGG enrichment analysis showed that DEGs in EAT were mainly involved in the cytosol, MHC protein complex, RNA degradation, antigen processing and presentation. A PPI network was built, in which RPS27A gene was identified as a gene with the highest degree of connectivity by use of Cytoscape plugin CytoHubba with MCC algorithm. Metascape enrich analysis indicated that DEGs enriched mainly in cellular response to DNA damage, RNA metabolism, regulation of cell stress responses, and adaptive immune system. By an analysis of TRRUST datasets, we predicted that transcription factor CIITA may play a role in the regulation of DEGs in EAT influencing CAD.

Conclusion

EAT may be involved in the development of CAD through proinflammatory and immune pathways, in which DDX47, FEM1C, NOL11, SRP54, ABI1, PATL1, BNIP2, C1orf159, CHCHD4 and RPS27A may play a vital role as the key genes. The abundance of naive CD₄⁺ T cells significantly increased while that of resting dendritic cells decreased obviously in EAT from CAD patients. BPI, BIRC5, CXCL12, RNASE1 and F2R may be excreted by EAT and have the potential as markers in CAD diagnosis and treatment.

Protective Effect of Far Infrared Therapy Using HITH-4 Type Apparatus and External Use of Hirudoid for Autogenous Arteriovenous Fistula in Diabetic Dialysis Patients

HU Chunyan, LI Yajing, GENG Tonghui, ZHANG Dongxue

2023, 26(08):  951-954.  DOI: 10.12114/j.issn.1007-9572.2022.0550

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Background

The maintenance of autogenous arteriovenous fistula (AVF) is crucial to diabetics with hemodialysis. Far infrared therapy (FIR) can significantly improve the condition of AVF in these patients. But the protective effectiveness of FIR using HITH-4 type apparatus combined with external use of Hirudoid for AVF in diabetic patients is less reported.

Objective

To explore the protective effect of FIR using HITH-4 type apparatus and external use of Hirudoid for AVF in diabetic hemodialysis patients.

Methods

Sixty diabetic patients with hemodialysis were selected from 2020-01-01 to 2020-06-01 in the Department of Nephrology, the Fourth Hospital of Hebei Medical University using an AVF, and equally, randomly divided into a control group and an intervention group. The control group received local application of Hirudoid Cream, and the intervention group received FIR using HITH-4 type apparatus for irradiating the limb of the arteriovenous fistula side and local application of Hirudoid Cream. The puncture point healing time, disappearance time of the puncture site scab, dialysis blood flow, arterial pressure, brachial artery blood flow and complications of AVF were compared between the two groups after a six-month intervention.

Results

Two groups had no significant differences in demographics (P>0.05). Compared with the control group, the puncture point healing time and disappearance time of the puncture site scab in the intervention group were significantly shorter (P<0.05). The dialysis blood flow and arterial pressure in the intervention group were significantly higher (P<0.05). The brachial artery blood flow in the intervention group was also much higher (P<0.05). The incidence of internal fistula complications in the intervention group was much lower (P<0.05) .

Conclusion

FIR using HITH-4 type apparatus and external use of Hirudoid could effectively protect and maintain the AVF, and reduce the risk of vascular stenosis and vascular complications in diabetics with hemodialysis.

Clinical Effect of Mussel Adhesive Protein with Tongyangxiao Lotion in Grades 1 and 2 Mixed Hemorrhoids

TIAN Maosheng, GAO Jihua, XU Jiancheng, QI Wenyue, WANG Linyue, GAO Ce

2023, 26(08):  955-962.  DOI: 10.12114/j.issn.1007-9572.2022.0545

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Background

Hemorrhoids are a highly prevalent disease, which have been a health challenge to people for a long time, seriously affecting the life, work, study, and the quality of life. The development of hemorrhoids is closely related to the imbalance of the mucosal barrier function of the anal cushion and the destruction of the mucus barrier and the mucosal barrier. How to treat hemorrhoids simply and efficiently has become a concern of clinicians.

Objective

To comprehensively assess the clinical efficacy of mussel adhesive protein (MAP) with fumigation and sitz bath with Tongyangxiao Lotion (a traditional Chinese medicine) in the treatment of grades 1 and 2 mixed hemorrhoids.

Methods

A prospective, randomized, single-blind, controlled study design was used. 298 anorectal outpatients with grades 1 and 2 hemorrhoids were selected from Hebei University of Chinese Medicine in 2021, and equally randomized into an experimental group and a control group. All patients were given general treatment such as diet and life guidance, and a 10-day fumigation and sitz bath with Tongyangxiao Lotion. The experimental group additionally received a 10-day treatment with topical use of MAP concurrently. The primary efficacy indicators include the response level (cure, marked response, response, non-response) and recurrence rate. The secondary efficacy indicators include the visual analogue scale (VAS) score, clinical symptom score, quality of life score, and safety index.

Results

276 patients actually completed this study, including 140 in the experimental group and 136 in the control group; 135 males and 141 females, with a median age of 38 (29, 48) years. There were no significant differences between two groups in gender ratio, mean age, distribution of course, and grade of mixed hemorrhoids, VAS score, clinical symptom score, anal mean canal resting pressure, hemorrhoid disease and the Crohn's Anal Fistula Quality of Life (CAF-QoL) score and past history (P>0.05). The VAS score, clinical symptom score, hematochezia score, rectal tenesmus score, hemorrhoid mucosa score, hemorrhoid nucleus size score of the two groups differed between two groups on the 4th, 7th or 10th day of follow-up (P<0.05). On the 10th day of follow-up, the VAS score, clinical symptom score, hematochezia score and hemorrhoid size score of the experimental group were lower than those in the control group (Z=-4.681, -3.784, -1.994, -3.411, P<0.05). The VAS score, clinical symptom score, anal canal resting pressure and CAF-QoL score decreased in both groups after treatment (P<0.05). The post-treatment VAS score (Z=-4.681), clinical symptom score (Z=-3.784), anal canal resting pressure (t=2.566), and CAF-QoL score (t=6.827) in the experimental group were lower than those in the control group (P<0.05). The experimental group had higher overall response rate (96.43% vs 91.18%) than the control group (χ²=8.557, P=0.036). The experimental group also had higher cure rate (84.28% vs 69.85%) (χ²=8.157, P=0.004). No complications and adverse reactions were found in both groups during the treatment period. There was no significant difference in the recurrence rate between the experimental group and control group (3.23% vs 5.33%) (P>0.05) .

Conclusion

MAP combined with sitz bath with Tongyangxiao Lotion acted rapidly, which had better performance in repairing the barrier function of the anal cushion, improving the clinical symptoms, reducing the tension of the internal anal sphincter, and improving the quality of life in patients with grades 1 and 2 mixed hemorrhoids.

Application of Unilateral Biportal Endoscopy Technique in the Treatment of Lumbar Brucellosis Spondylitis

WANG Xiangbin, LONG Yubin, WANG Chong, LI Yong, MAIWULAN· Mansuerjiang, TIAN Zheng, AIKEBAIER· Younusi

2023, 26(08):  963-971.  DOI: 10.12114/j.issn.1007-9572.2022.0714

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Background

The unilateral biportal endoscopy (UBE) technique is a new minimally invasive spinal surgical technique, which has been used to treat various degenerative spinal diseases in recent years. However, there is no literature reporting this technique for the treatment of lumbar brucellosis spondylitis (LBS) .

Objective

To investigate the effectiveness and feasibility of the UBE technique in the treatment of LBS.

Methods

This study selected 13 patients with LBS who received the UBE treatment in the Department of Orthopaedics, the First Affiliated Hospital of Xinjiang Medical University from January 2020 to June 2021. The operative duration, the estimated blood loss and complications were recorded. Clinical outcomes of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the visual analog scale (VAS) scores of low back and leg, Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), American Spinal Injury Association (ASIA) neurological classification, and lordotic angle were analyzed. All patients were assessed using the modified Macnab criteria at 1-year follow-up after operation. The intervertebral bone graft fusion was evaluated using Bridwell grading criteria.

Results

The operation time was 145-210 minutes, with an average of (177.31±19.54) minutes. The estimated blood loss was 120-290 ml, with an average of (176.15±43.79) ml. There were 2 complications, with an incidence rate of 2/13. ESR and CRP levels returned to normal at the 3-month follow-up. The VAS scores of low back and leg, JOA score, and ODI were significantly improved compared to those before operation at each postoperative follow-up time point, and the differences were statistically significant (P<0.05). The modified Macnab criteria evaluation at 1-year follow-up showed that the outcomes were excellent in 10 cases, good in 2 cases, fair in 1 case, and no patient showed poor outcomes, with a rate of excellent and good was 12/13. The lordotic angle decreased from preparation (47.18°±6.88°) to predischarge (40.83°±6.71°), and there was no significant loss of angle at 1-year follow-up after operation. Bony fusion was obtained in all patients at 1-year follow-up after operation, of which 12 cases were grade Ⅰ and 1 case was grade Ⅱ, with a fusion rate of 12/13.

Conclusion

UBE technique is an effective, safe and feasible surgical procedure for treating LBS.

Monographic Research·Frailty in Cancer Patients

Perceived Influencing Factors of Preoperative Frailty among Elderly Patients with Gastric Cancer from the Perspective of Health Ecology: a Qualitative Study

DING Lingyu, JIANG Xiaoman, MIAO Xueyi, CHEN Li, ZHU Hanfei, LU Jinling, HU Jieman, XU Xinyi, XU Qin

2023, 26(08):  972-979.  DOI: 10.12114/j.issn.1007-9572.2022.0732

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Background

Preoperative frailty is a severely unhealthy status that reflects the reduction of overall physiological reserve, which is highly prevalent in elderly patients with gastric cancer. Understanding the perceived influencing factors of preoperative frailty can provide an important basis for developing individualized intervention plans.

Objective

To perform a qualitative descriptive study to identity the perceived influencing factors of preoperative frailty among elderly gastric cancer patients using the theory of health ecology.

Methods

A qualitative descriptive study was conducted based on health ecology theory. Purposive sampling method was used to select 29 frail elderly patients who would undergo gastric cancer surgery in the First Affiliated Hospital with Nanjing Medical University from February to June 2021 for semi-structured interview. Directed content analysis was used for data analysis.

Results

Five themes and thirteen sub-themes were extracted: physiological traits, including accumulated aging-related losses, obvious gastrointestinal symptoms, and successive attacks of multiple diseases; behavioral characteristics, including lack of exercise behavior and overexertion; interpersonal networks, including insufficient peer social interaction, lack of parent-child interaction, and lack of communication and self-disclosure between couples; living and working conditions, including heavy individual financial burden, heavy unplanned family care tasks, insufficient information resources for health and disease management; macro factors, including limited medical services and medical insurance support.

Conclusion

This study described the effects of different perceived factors on preoperative frailty among elderly gastric cancer patients from the perspective of health ecology. Medical workers should formulate and implement systematic prehabilitation programs based on the above factors to improve the patients' preoperative anti-stress capacity and postoperative outcomes.

Preoperative Frailty and Postoperative Adverse Outcomes among Elderly Patients with Gastric Cancer

MIAO Xueyi, DING Lingyu, LU Jinling, HU Jieman, ZHU Hanfei, CHEN Li, XU Xinyi, XU Qin

2023, 26(08):  980-988.  DOI: 10.12114/j.issn.1007-9572.2022.0740

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Background

Due to great differences in physiological reserve, psychological status and social functioning, frailty in elderly patients with gastric cancer may present various subtypes. The relationship between preoperative frailty and postoperative adverse outcomes in them still remains to be further explored.

Objective

To explore the relationship between preoperative frailty subtypes and postoperative adverse outcomes〔total complications, prolonged length of stay (PLOS), low quality of life (QOL), and disability〕among elderly patients with gastric cancer.

Methods

From March to October 2021, 404 elderly gastric cancer patients were selected from Department of Gastric Surgery, the First Affiliated Hospital with Nanjing Medical University by convenience sampling. The General Demographic Data Questionnaire and Tilburg Frailty Indicator were used to collect demographics and frailty status before surgery. Total complications and PLOS were collected from the electronic medical records, and the status of disability and QOL were obtained using a telephone follow-up at one month after discharge. Univariate Logistic regression was performed to explore the influencing factors of postoperative adverse outcomes. Multivariate Logistic regression analysis was performed to analyze the association of preoperative frailty subtypes with postoperative adverse outcomes, with potential confounders adjusted.

Results

Two hundred and eighty-five cases were found with preoperative frailty, and the frailty subtypes in them were classified into eight classes: exclusive physical frailty〔77 (19.1%) 〕, exclusive psychological frailty〔78 (19.3%) 〕, exclusive social frailty〔23 (5.7%) 〕, physical and psychological frailty〔63 (15.6%) 〕, physical and social frailty〔13 (3.2%) 〕, psychological and social frailty〔16 (4.0%) 〕, multidimensional frailty (physical, psychological, and social frailty) 〔15 (3.7%) 〕. The other 119 (29.5%) cases had no preoperative frailty. In the univariate Logistic regression, age was the factor influencing total complications〔OR=1.063, 95%CI (1.021, 1.106), P=0.003〕. History of pharmacological treatment〔OR=1.549, 95%CI (1.016, 2.362), P=0.042〕and surgical approach〔OR=2.103, 95%CI (1.191, 3.712), P=0.010〕were the factors influencing PLOS. Marital status〔OR=4.611, 95%CI (1.079, 19.706), P=0.039〕, living in an urban area〔OR=1.614, 95%CI (1.009, 2.582), P=0.046〕, having at least two comorbidities〔OR=1.694, 95%CI (1.038, 2.766), P=0.035〕were the factors influencing postoperative low QOL. Living in an urban area〔OR=0.601, 95%CI (0.390, 0.926), P=0.021〕, history of pharmacological treatment〔OR=1.663, 95%CI (1.082, 2.558), P=0.020〕, and advanced TNM stages〔OR=1.659, 95%CI (1.017, 2.706), P=0.043〕were the factors influencing postoperative disability. In the multivariate Logistic regression, the preoperative multidimensional frailty was independently associated with total complications, with age adjusted〔OR=5.344, 95%CI (1.715, 16.656), P=0.004〕. The preoperative physical frailty〔OR=2.048, 95%CI (1.078, 3.891), P=0.029〕, preoperative psychological frailty〔OR=2.077, 95%CI (1.103, 3.913), P=0.024〕and preoperative multidimensional frailty〔OR=8.321, 95%CI (2.400, 28.848), P<0.001〕were independently associated with PLOS, with history of pharmacological treatment and surgical approach adjusted. Preoperative psychological frailty〔OR=2.620, 95%CI (1.267, 5.418), P=0.009〕, preoperative psychological and social frailty〔OR=11.122, 95%CI (3.253, 38.028), P<0.001〕and preoperative multidimensional frailty〔OR=11.579, 95%CI (2.835, 47.302), P<0.001〕were independently associated with postoperative low QOL, with marital status, living in an urban area, and having at least two comorbidities adjusted.

Conclusion

Medical professionals should pay attention to preoperative frailty prevalence in elderly gastric cancer patients, and assess preoperative frailty in these patients using tools with the multidimensional frailty scale included, and attach great importance to those with exclusive physical frailty, exclusive psychological frailty, psychological and social frailty, and multidimensional frailty before surgery. A targeted prerehabilitation intervention program can be delivered to those with preoperative frailty according to their subtypes of frailty to improve postoperative adverse outcomes and QOL.

Associated Factors of Frailty in Cancer Patients: a Meta-analysis

GUO Yinning, MIAO Xueyi, JIANG Xiaoman, XU Ting, XU Qin

2023, 26(08):  989-996.  DOI: 10.12114/j.issn.1007-9572.2022.0773

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Background

Frailty is common in cancer patients, which seriously affects their prognosis. However, the factors associated with frailty in cancer patients are not clear at present.

Objective

To identify the factors associated with frailty in cancer patients by a meta-analysis, to provide a scientific basis for the development and implementation of related interventions.

Methods

The databases of China National Knowledge Infrastructure (CNKI), CQVIP, WanFang Data, PubMed, Web of Science, Cochrane Library, CINAHL and Embase were comprehensively and systematically searched from inception to August 2022 for included cross-sectional studies, cohort studies or case-control studies reporting associated factors of frailty in cancer patients. Two researchers screened the literature and performed quality evaluation and data extraction. Stata 17.0 and RevMan 5.4 were used for meta-analysis.

Results

Eleven studies were included, among which nine were cross-sectional studies and the other two were cohort studies. Altogether, 2 898 cancer patients were studied, among whom 1 025 were frail, and 12 associated factors of frailty were reported. Meta-analysis showed that the prevalence of frailty in all cancer patients, lung cancer patients, digestive cancer patients, and other cancer patients was 34%〔95%CI (23%, 45%) 〕, 31%〔95%CI (25%, 36%) 〕, 42%〔95%CI (26%, 59%) 〕, and 12%〔95%CI (9%, 16%) 〕, respectively. The risk of frailty in cancer rose with advanced age〔OR=1.16, 95%CI (1.05, 1.27) 〕, combined with other diseases〔OR=1.46, 95%CI (1.28, 1.67) 〕, high BMI〔OR=1.13, 95%CI (1.05, 1.21) 〕, poor nutritional status〔OR=2.77, 95%CI (1.27, 6.06) 〕, high syndrome group scores〔OR=1.07, 95%CI (1.04, 1.09) 〕and depression〔OR=1.27, 95%CI (1.12, 1.44) 〕, but decreased with high education level〔OR=0.78, 95%CI (0.68, 0.90) 〕, albumin level≥35 g/L〔OR=0.33, 95%CI (0.12, 0.90) 〕and high level of instrumental activities of daily living (IADL) 〔OR=0.50, 95%CI (0.42, 0.59) 〕. Egger's test assessing the potential publication bias in 11 studies via funnel plot asymmetry showed that there was a certain publication bias (t=-4.12, P=0.003) .

Conclusion

This meta-analysis revealed that age, education level, comorbidity, BMI, albumin, nutritional status, syndrome group, depression and IADL were the associated factors of frailty in cancer patients. It is necessary for health professionals to pay more attention to cancer patients with advanced age, low education level, combined with other diseases, high BMI, albumin level <35 g/L, poor nutritional status, with syndrome group, depression or low-level activities of daily living, so as to prevent the occurrence of frailty.

Evidence-based Medicine

Effect of Different Modalities of Repetitive Transcranial Magnetic Stimulation on Post-stroke Upper Limb Motor Dysfunction: a Network Meta-analysis

XIONG Dan, XIE Haihua, LI Hao, ZHANG Hong, TAN Jie, ZHAO Ning

2023, 26(08):  997-1007.  DOI: 10.12114/j.issn.1007-9572.2022.0535

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Background

Upper limb motor dysfunction is a common complication after stroke that seriously affects daily living skills of patients. As a common neuroelectrohysiological technique, repetitive transcranial magnetic stimulation (rTMS) has a good effect on post-stroke upper limb motor dysfunction. However, there is still no practice-based evidence on the selection of modalities of rTMS.

Objective

To evaluate the clinical efficacy of four rTMS modalities in post-stroke upper limb motor dysfunction by a network meta-analysis.

Methods

Randomized controlled trials (RCTs) about rTMS for treating upper limb motor dysfunction after stroke were searched with subject words combined with free words as searching terms in PubMed, Embase, Cochrane Library, Web of Science, CBM, CNKI, Wanfang Data, and VIP from inception to February 2022, supplemented by references from retrospective meta-analysis. Two researchers performed literature screening, data extraction, and quality evaluation separately. RevMan 5.0 and Stata 16.0 were used for statistical analysis.

Results

A total of 17 RCTs with 790 cases were included. Six interventions were involved: high frequency-rTMS (HF-rTMS), low frequency-rTMS (LF-rTMS), intermittent theta burst stimulation (iTBS), continuous theta burst stimulation (cTBS), sham stimulation and conventional therapy. Network meta-analysis results showed that HF-rTMS and LF-rTMS had better effects on increasing the FMA-UE score than sham stimulation and conventional therapy (P<0.05). cTBS increased the FMA-UE score more significantly than conventional therapy (P<0.05). LF-rTMS increased the MBI and BI scores more notably than sham stimulation and conventional therapy (P<0.05). HF-rTMS and LF-rTMS reduced the MEP latency more significantly than sham stimulation (P<0.05). The SUCRA ranking of the six interventions in terms of increasing the FMA-UE score showed the following: LF-rTMS (79.9%) >cTBS (75.3%) >HF-rTMS (71.1%) >iTBS (45.8%) >sham stimulation (20.2%) >conventional therapy (7.7%). The SUCRA ranking of decreasing the MAS score revealed the following: iTBS (77.0%) >LF-rTMS (64.1%) >cTBS (61.0%) >HF-rTMS (38.0%) >sham stimulation (30.6%) >conventional therapy (29.2%). The SUCRA ranking of increasing the MBI and BI scores showed the following: LF-rTMS (96.4%) >iTBS (74.9%) >HF-rTMS (38.6%) >sham stimulation (30.7%) >conventional therapy (9.4%). The SUCRA ranking of reducing the MEP latency showed the following: HF-rTMS (80.0%) >LF-rTMS (78.9%) >conventional therapy (58.8%) >iTBS (24.9%) >sham stimulation (7.5%) .

Conclusion

The available evidence indicates that, among four modalities producing better effects than sham stimulation and conventional therapy, namely LF-rTMS, HF-rTMS, iTBS, and cTBS, LF-rTMS was superior to the other three in improving upper limb motor function and daily living skills of stroke patients, iTBS performed best in decreasing upper limb muscle tension, and HF-rTMS did best in intervening the corticospinal excitability.

Non-invasive Brain Stimulation Techniques Can Effectively Relieve Post-stroke Fatigue: a Meta-analysis

GUAN Ningxiao, YAO Zhuoya, LI Ye, LIU Ziwei, LIU Fangli

2023, 26(08):  1008-1014.  DOI: 10.12114/j.issn.1007-9572.2022.0588

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Background

Fatigue is one common symptom in stroke patients, which has been validated by studies to be negatively associated with the recovery of these patients. Non-invasive brain stimulation techniques can effectively promote or inhibit the excitability of cerebral cortex and accelerate neuroplasticity, but the efficacy and safety of the treatment for post-stroke fatigue are not clear.

Objective

To systematically evaluate the effects of non-invasive brain stimulation on post-stroke fatigue.

Methods

We searched randomized controlled trials (RCTs) of the efficacy of non-invasive brain stimulation techniques 〔transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS) 〕 (experimental group) compared with that of regular rehabilitation training (control group) in post-stroke fatigue in PubMed, Web of Science, Embase and the Cochrane Library, CBM, CNKI, VIP, Wanfang Data and other databases from database inception to April 2022. The reported outcomes were assessed using the Fatigue Severity Scale (FSS) and Fugl-Meyer Assessment (FMA) scale. Two researchers conducted literature screening, data extraction and quality evaluation. RevMan 5.3 was used for meta-analysis. GRADE was used to evaluate the quality of the evidence for reported outcomes.

Results

A total of five RCTs with 331 subjects were included, among which three studied the efficacy of rTMS, and the other two studied the efficacy of tDCS. The methodological quality of all RCTs was categorized as grade B. Meta-analysis showed that the experimental group had lower mean FSS scores than the control group〔SMD=-2.13, 95%CI (-3.63, -0.63), P=0.005〕, and had higher FMA scores than the control group〔SMD=6.60, 95%CI (4.33, 8.87), P<0.000 01〕. Sensitivity analysis showed that the results were robust. Egger's test suggested that there was little potential publication bias in this meta-analysis (t=-0.88, P=0.445). The quality of reported evidence regarding three primary outcomes, namely, FSS scores after a 4-week and 8-week non-invasive brain stimulation, and FMA score after non-invasive brain stimulation, was rated as "low" by the GRADE system.

Conclusion

Non-invasive brain stimulation techniques have been proven by included RCTs to be effective in relieving fatigue symptoms, and promoting the recovery of motor functions in patients with post-stroke fatigue. However, due to small sample size and low quality of the evidence about reported outcomes after treatment, the conclusion needs to be further verified by high-quality, large-sample and multicenter RCTs.

Research Methodology

Harvard Alumni Health Study Physical Activity Questionnaire for Chinese College Students: a Cross-validation Study

CHEN Panpan, YU Hongjun, QIU Jun

2023, 26(08):  1015-1021.  DOI: 10.12114/j.issn.1007-9572.2022.0361

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Background

In the field of physical activity and health research, a key issue is to measure and evaluate the physical activity level of different groups by using scientific methods. As a classic scale for measuring physical activity, Harvard Alumni Health Study Physical Activity Questionnaire (HAHS-PAQ) has been verified in many countries and different groups. However, there is still no report of the reliability and validity of this scale in Chinese college students.

Objective

To develop a Chinese version of the HAHS-PAQ (HAHS-PAQ-C) and to test its reliability and validity among Chinese college students.

Methods

The HAHS-PAQ-C was developed using the Brislin's approach. Then from December 2017 to April 2018, freshmen from Tsinghua University were recruited to attend a survey for testing the scale, among whom 116 and 166 cases completed the reliability and validity study, respectively. Spearman rank correlation analysis was used to test the test-retest reliability of the HAHS-PAQ-C and its criterion validity with ActiGraph wGT3X-BT accelerometer as the criterion. The Bland-Altman plot was adopted to evaluate the consistency of two physical activity measurements of HAHS-PAQ-C and ActiGraph wGT3X-BT accelerometer.

Results

The correlation coefficients of total energy consumption, walking, climbing stairs and sports or leisure entertainment measured every other week with 2 repetitions by HAHS-PAQ-C were 0.504, 0.570, 0.711 and 0.429, respectively (P<0.05). Meanwhile, the correlation coefficients of total weekly energy consumption, medium- and high-intensity energy consumption and walking measured by HAHS-PAQ-C and ActiGraph wGT3X-BT accelerometer were 0.441, 0.258 and 0.312, respectively (P<0.05). The result of Bland-Altman plot revealed that the average value of the mean of total energy consumption measured by HAHS-PAQ-C and ActiGraph wGT3X-BT accelerometer was 1 778.78, of which 94.6% (157/166) points were within the 95%CI.

Conclusion

The cross-validation of the HAHS-PAQ-C in Chinese college students has proven it has good reliability and validity, and is feasible to be popularized, which could be used as a physical activity measurement tool for Chinese college students, and will provide assistance to Chinese college students to take exercise and interventions appropriately.

Development of the Chinese Version of TEMPA and Its Reliability and Validity in Stroke Patients

ZHANG Xiaoxue, WANG Ruiyue, FAN Hongyu, WANG Jinzhi, DOU Na

2023, 26(08):  1022-1027.  DOI: 10.12114/j.issn.1007-9572.2022.0391

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Background

Functional assessment is a foundation for rehabilitation treatment, which contributes to the development of the rehabilitation program and the improvement of rehabilitation outcomes. However, there are only few assessment scales with unvaried domains for upper extremity function after stroke.

Objective

To develop the Chinese version of Upper Extremity Performance Test (TEMPA) and to explore its reliability and validity in stroke patients.

Methods

We translated and revised the English version of TEMPA to a Chinese version according to the Brislin's translation procedures of forward-translation, back-translation, review, cultural adaptation and a pre-test. Then from August 2021 to January 2022, the Chinese version of TEMPA, Fugl-Meyer Assessment of Upper Extremity (FMA-UE) and Simple Test for Evaluating Hand Function (STEF) were used to evaluate the upper limb function of 40 patients with stroke recruited from Department of Rehabilitation, Tangshan Workers' Hospital. One week after the first evaluation, the Chinese version of TEMPA (TEMPA-C) was used to evaluate their upper limb function again. The test intra-rater reliability and inter-rater reliability of each dimension of the TEMPA-C were tested by intraclass correlation coefficient (ICC). The internal consistency reliability of TEMPA-C was tested by Cronbach's α. The total score of each dimension and item score of TEMPA-C and the scores of FMA-UE and STEF were analyzed by Pearson correlation analysis to test criterion validity of TEMPA.

Results

The ICC for the intra-rater reliability and the inter-rater reliability of the TEMPA-C functional rating total score was 0.992, and 0.982, respectively. The ICC for the intra-rater reliability and the inter-rater reliability of the TEMPA-C task analysis total score was 0.998 and 0.999, respectively. The Cronbach's α of the TEMPA-C functional rating dimension was 0.858. The score for performing each of the 9 tasks of the TEMPA-C execution speed dimension was negatively correlated with the score of the affected side of STEF, and the correlation coefficient ranged from -0.785 to -0.460. The total score of the TEMPA-C functional rating dimension was positively correlated with the scores of FMA-UE, FMA-UE wrist-hand part and the affected side of STEF, so was the total score of the TEMPA-C task analysis dimension, and the correlation coefficients were all above 0.7.

Conclusion

The TEMPA-C was highly reliable and valid, and could be used in measuring the function of upper extremity in patients with stroke.

Research of Typical Cases

Unilateral Renal Atrophy Due to GREB1L Gene Mutation: a Case Report and Literature Review

SUN Tao, PENG Yingchao, SHI Zhuo, GAO Chunlin, XIA Zhengkun

2023, 26(08):  1028-1030.  DOI: 10.12114/j.issn.1007-9572.2022.0505

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Renal agenesis and hypodysplasia (RAH) are major congenital anomalies of the kidney and urinary tract that often cause chronic kidney disease in children. Genetic factors are closely related to the pathogenesis of RAH. As whole genome sequencing techniques advance, gene mutations have been increasingly reported to be associated with RAH, among which the association of GREB1L gene mutation with renal dysplasia has been confirmed. We reported a cases of unilateral renal atrophy due to GREB1L gene c.4688A>G heterozygous mutation, and reviewed related literature. The gene mutation of the child originated from his mother, which is a rare variation and has incomplete explicit characteristics, and is assessed to be a harmful mutation by a variety of protein hazard prediction softwares. The new mutation site of GREB1L gene found by us, may expand the gene mutation spectrum and clinical spectrum related to RAH.