Objective: Schizophrenia is a complex and devastating psychiatric disorder with a strong genetic background. However, much uncertainty still exists about the role of genetic susceptibility in the pathophysiology of schizophrenia. TEA domain transcription factor 1 (TEAD1) is a transcription factor associated with neurodevelopment and has modulating effects on various nervous system diseases. In the current study, we performed a case–control association study in a Northeast Chinese Han population to explore the characteristics of pathogenic TEAD1 polymorphisms and potential association with schizophrenia. Methods: We recruited a total of 721 schizophrenia patients and 1,195 healthy controls in this study. The 9 single nucleotide polymorphisms (SNPs) in the gene region of TEAD1 were selected and genotyped. Results: The genetic association analyses showed that five SNPs (rs12289262, rs6485989, rs4415740, rs7113256, and rs1866709) were significantly different between schizophrenia patients and healthy controls in allele or/and genotype frequencies. After Bonferroni correction, the association of three SNPs (rs4415740, rs7113256, and rs1866709) with schizophrenia were still evident. Haplotype analysis revealed that two strong linkage disequilibrium blocks (rs6485989-rs4415740-rs7113256 and rs16911710-rs12364619-rs1866709) were globally associated with schizophrenia. Four haplotypes (C-C-C and T-T-T, rs6485989-rs4415740-rs7113256; G-T-A and G-T-G, rs16911710-rs12364619-rs1866709) were significantly different between schizophrenia patients and healthy controls. Conclusion The current findings indicated that the human TEAD1 gene has a genetic association with schizophrenia in the Chinese Han population and may act as a susceptibility gene for schizophrenia.

Variations in the dynein axonemal heavy chain gene, dynein axonemal heavy chain 6 (DNAH6), lead to multiple morphological abnormalities of the flagella. Recent studies have reported that these deficiencies may result in sperm head deformation. However, whether DNAH6 is also involved in human acrosome biogenesis remains unknown. The purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and flagella. Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University (Hefei, China). Hematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure. Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants. We identified three novel deleterious variants in DNAH6 among three unrelated families. The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants. Additionally, deficiencies in the acrosome, abnormal chromatin compaction, and vacuole-containing sperm heads were observed in these patients with DNAH6 variants. The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot. After intracytoplasmic sperm injection (ICSI) treatment, the partner of one patient with a DNAH6 variant achieved successful pregnancy. Overall, novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified, and the findings indicated ICSI as an effective clinical treatment for such patients.

OBJECTIVE: To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines. METHODS: Randomized controlled trials (RCTs) were identified by searching China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), PubMed, Cochrane Library, and Embase Databases from the inceptions until December 2020. The Cochrane Handbook was used to evaluate the risk of bias in the included studies. Data analysis was conducted using RevMan 5.3 software. RESULTS: Totally 19 RCTs with 2,331 participants were included in this review. Results showed that in improving arrhythmia (13 RCTs, n=1,877, RR=0.37, 95%CI 0.25 to 0.52, P<0.00001), the treatment group was superior to the control group. In terms of reducing left ventricular end-diastolic diameter (LVEDD, 2 RCTs, n=128, MD=-0.79, 95%CI -0.93 to -0.65, P<0.00001) and left ventricular end systolic diameter (LVESD, 2 RCTs, n=128, MD=-0.58, 95%CI -0.82 to -0.35, P<0.00001), the treatment group was also better than the control group. In reducing myocardial enzymes such as creatine kinase (CK) [(3 RCTs, n=256, SMD=-0.80, 95%CI -1.16 to -0.44, P<0.0001), (2 RCTs, n=126, SMD=-0.62, 95%CI -0.98 to -0.26, P=0.0007)], the treatment group was superior to the control group. CONCLUSION Shengmai San has a positive effect on the treatment of cardiotoxicity from anthracyclines. However, in the future, it is still necessary to conduct high-quality RCTs to verify its efficacy.
Anthracyclines/adverse effects* ; Cardiotoxicity/etiology* ; Drug Combinations ; Drugs, Chinese Herbal/adverse effects* ; Humans

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.
Antiviral Agents/therapeutic use* ; Glucocorticoids/therapeutic use* ; Hematopoietic Stem Cell Transplantation/methods* ; Humans ; Pneumonia/etiology* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

In vivo electroporation of morpholinos (MOs) into the retina of adult zebrafish is an efficient method to study gene function related to retinal disease and regeneration. However, the currently reported methods are complicated with low MO transfer efficiency and high probability to cause collateral damage. The present study was aimed to optimize the existing MO electroporation methods. Two major changes were made to MO electroporation procedure in zebrafish retina. One was to coat the inner side of the electrode with ultrasonic gel. The other was to replace the commonly used round electrode with novel rectangular one. The results showed that the use of ultrasonic gel reduced collateral damage caused by retinal electroporation and simplified the experimental procedure. The rectangular electrode significantly increased transfection efficiency of MO electroporation. In particular, knocking down the expression of Ascl1a in the retina by using our method significantly inhibited the generation of retinal progenitor cells. These results suggest our method is the optimization of the current MO electroporation methods and may be a better alternative for relevant researchers.

This study aimed to assess the relationship of OAS2 rs739901 5'-flanking C/A polymorphisms with the susceptibility to Enterovirus-71 (EV71) infection.We investigated 294 hand-foot-mouth disease (HFMD) Chinese children with EV71 infection (165 mild cases and 129 encephalitis cases).The improved multiplex ligation detection reaction (iMLDR) technique was used to test the genotypes.In EV71-infected patients,the CA genotype distribution (P=0.007),A allele frequency (OR 1.32,95％ CI 1.0-1.7,P=0.034)and CA+AA carriage frequency (P=0.003) of OAS2 rs739901 5'-flanking were obviously elevated as compared with controls,but there were no statistically significant differences between mild cases and encephalitis cases.In EV71-infected patients,the counts of white blood cells (P=0.034) and blood glucose concentrations (P=0.042) were raised in A carriers (CA+AA).Among different genotypes of encephalitis cases,the contents of cerebrospinal fluid (CSF) showed no significant differences.IFN-γ levels in EV71-infected patients were higher than those in controls (mild group vs.control group,P＜0.01;encephalitis group vs.control group,P＜0.001).In encephalitis cases,IFN-γ levels were reduced (P＜0.05) in A carriers compared to CC genotype,however,there were no significant differences between genotypes CA and AA (P=0.226).These findings suggest that OAS2 rs739901 5'-flanking C/A genetic polymorphisms involve the susceptibility to EV71 infection,and A allele might be a risk factor of the susceptibility to EV-71 infection.

Objectives: This study aimed to observe the change of arachidonic acid-induced platelet aggregation rate (AA-Ag) and short-term adverse reactions after taking 50 or 100 mg/d aspirin(enteric-coated sustained-release formulation) or 100 mg/d aspirin (enteric-coated aspirin tablet)in the elderly Chinese population (aged 60 years or older). Methods: A total of 1 194 participants aged 60 or older, who should be recommended to take aspirin therapy due to medical reasons, were recruited and randomly assigned into three groups to receive enteric-coated sustained-release aspirin tablet (50 mg, once daily, group A), or 100 mg, once daily (group B) or enteric-coated aspirin tablet 100 mg once daily (group C), respectively. AA-Ag was measured after (14±3)days of aspirin treatment. Adverse events and bleeding events were recorded during the (28±3)days of follow-up. Results: The AA-Ag in group A (n=347), B (n=338) and C (n=332) post 14-day aspirin therapy were 6.65 (4.03,10.84)%, 5.89(3.22,10.03) % and 6.00(3.68,10.09) %, respectively (P>0.05). During the 28 days follow-up, the adverse events rate of group A (n=388), B (n=387) and C (n=385) was 3.87%,3.36%, and 7.95%, and the mild bleeding events rate was 3.09%, 2.33%, and 6.23%, respectively. Adverse events rate and mild bleeding events rate were significantly higher in group C than in group A and B (P<0.05). Conclusions: Compared with 100 mg-dose aspirin, 50 mg-dose aspirin achieves similar anti-platelet aggregation effect in this elderly Chinese population. The short-term adverse events and mild bleeding risk of aspirin with enteric-coated sustained-release formulation were fewer than that of enteric-coated formulation.

The paper analyzes the current problems of medical students'humanistic quality and the causes,points out the necessity of strengthening the humanistic quality of medical students,and puts forward the countermeasures to be taken by libraries of medical colleges in the humanistic quality education for college students,including strengthening the construction of medical humanistic resources,doing well of medical humanistic reading guide and entrance education for new students,and strengthening reading promotion activities,etc.

BACKGROUND: In the cartilage tissue engineering materials, hyaluronic acid as the representative of polysaccharide materials has good material-cell interface that is beneficial to the growth of chondrocytes, which has become a hot research topic in recent years. OBJECTIVE: To explore the feasibility of injectable hyaluronic acid material loaded with chondrocytes to repair cartilage defects in rats. METHODS: Ninety Sprague-Dawley rats were selected to prepare a cartilage defect model, and they were randomly divided into three groups at the 2nd day after modeling. The experimental group was injected hyaluronic acid hydrogel loaded with chondrocytes into the articular cavity, the control group was injected with hyaluronic acid hydrogel into the articular cavity, and the blank control group received no intervention. At 1, 3 and 6 weeks after injection, the repaired cartilage tissues were taken out for hematoxylin eosin staining, Masson staining, and scanning electron microscope observation, and the expression of heme oxygenase and level of collagen were detected.RESULTS AND CONCLUSION: (1) Hematoxylin eosin staining: at 6 weeks after injection, granulation tissues filled the repair area in the blank control group. The control group was full of yellowish white tissues in the repair area, with distinct boundary with the normal cartilage, the surface was not smooth and the lymphocytes were reduced compared with those at 3 weeks. Repair tissue of the experimental group was semi-transparent and showed a fuzzy boundary with the normal cartilage, and moreover, lymphocyte was significantly reduced compared with those at 3 weeks. (2) Masson staining: at 6 weeks after injection, collagen fiber synthesis in the repair area in the experimental group was the best, successively followed by the control group and the blank control group. (3) Scanning electron microscope observation: at 6 weeks after injection, collagen fiber arrangement in the repair area was irregular and partially broken in the blank control group, and the arrangement became more orderly in the control group but still partially broken. The collagen fibers in the experimental group were arranged orderly, and the boundary with normal cartilage was unclear. (4) Expression of heme oxygenase and level of collagen: at 6 weeks after injection, the expression of heme oxygenase in the experimental group was higher than that in the control group and blank control group (P < 0.05). The levels of collagen in the experimental group at 1, 3 and 6 weeks after injection were higher than those in the control group and the blank control group (P < 0.05). To conclude, hyaluronic acid injectable material loaded with chondrocytes can promote the repair of cartilage defects in rats.

Background and objective Non-small cell lung cancer (NSCLC) has been transformed from the treatment according to histological type to genotype treatment model. The epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genes are the most important drivers in lung cancer. The aim of this study is to explore the clinical characteristics and prognostic factors of patients with advanced NSCLC with different genotypes. Methods We retrospectively reviewed the clinical data of 553 advanced NSCLC patients with EGFR mutations and ALK positive who were hospitalized in the Beijing Chest Hospital from July 2004 to December 2015, and the independent prognostic factors of pa-tients were analyzed by Cox proportional hazards regression model. Results The clinical data of 553 patients (227 with EGFR mutations, 58 with ALK positive, 2 with EGFR and ALK co-mutation and 266 with wild-type) with advanced NSCLC were enrolled in this study. The median survival time of 227 patients with EGFR mutations was 28.7 mo (95%CI: 22.160-35.240), and the performance status (PS) score (0-1) (HR=4.451; 95%CI: 2.112-9.382; P<0.001) and EGFR-tyrosine kinase inhibitors(TKIs) targeted therapy (HR=2.785; 95%CI: 1.871-4.145; P<0.001) were the independent prognostic factors for the survival of patients harboring EGFR mutations. The median survival time of 58 patients with ALK positive was 15.5 mo (95%CI:10.991-20.009), and treatment with crizotinib (P=0.022) was the independent influence factor for the survival of ALK positive patients. The median survival time of 266 patients with wild-type was 12.1 mo (95%CI: 10.660-13.540), and the PS score (0-1) (HR=2.313; 95%CI: 1.380-3.877; P=0.001) and treatment with chemotherapy (HR=1.911; 95%CI: 1.396-2.616; P<0.001) were the independent prognostic factors for the survival of wild-type patients. Conclusion The prognosis of patients with advanced NSCLC is associated with genetic mutation, and targeted therapy has a improvement on survival for patients with EGFR mutations or ALK rearrangement.