Over the past two decades, genome-wide association study(GWAS) has identified numerous genetic variants and loci associated with heritable diseases. With the gradual maturation and saturation of GWAS methodologies, transcriptome-wide association study(TWAS) offers a novel perspective by linkinggenetic phenotypes to gene expression levels. By integrating TWAS with other multi-omics analyses, researchers can gain a deeper understanding of heritable diseases. This article provides an overview of recent groundbreaking and representative TWAS methods and tools, analyzes their strengths and limitations, and discusses future trends in TWAS development.

ObjectiveTo investigate the protective effect of liver-targeted fibroblast growth factor 21 （FGF21） overexpression against CCl₄-induced acute liver injury （ALI） and its association with silent information regulator 1/glutathione peroxidase 4 （SIRT1/GPX4） expression and ferroptosis-related markers. MethodsFemale ICR mice （8 weeks old） were randomly divided into Control， CCl₄， adeno-associated virus （AAV）-FGF21， and AAV-FGF21 + CCl₄ groups. Liver-targeted FGF21 overexpression was achieved via tail vein injection of AAV8-FGF21 virus with green fluorescent protein （GFP） labeling. ALI was induced by intraperitoneal injection of CCl₄ （0.3 mL/kg）， with sample collection at 12 hours. Body weight and liver weight were recorded to calculate the liver weight/body weight. Alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using a biochemical analyzer. FGF21 expression in liver tissues was detected by immunofluorescence. Hepatic histopathology was evaluated by HE staining. RT-qPCR was performed to assess mRNA expression of ferroptosis and iron metabolism-related genes （ACSL4， PTGS2， HJV， FPN， GPX4）， FGF21， and SIRT1. Protein expression of FGF21， SIRT1， and GPX4 were determined by Western blot. Iron content， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD） activity in liver homogenate were quantified using assay kits. ResultsCompared with the Control group， the FGF21 mRNA and protein expression elevated in CCl₄ group； serum ALT/AST levels and liver weight/body weigh increased. The HE staining results showed that the liver cell membranes were ruptured. The mRNA levels of ACSL4 and PTGS2， the iron content and MDA levels all increased （P<0.01）. The mRNA levels of SIRT1， GPX4， HJV， and FPN， the GSH level and SOD activity all decreased （P<0.05）， and the protein levels of SIRT1 and GPX4 both decreased （P<0.05）. Compared with the CCl₄ group， the serum levels of ALT and AST in the AAV-FGF21 + CCl4 group were decreased （P<0.01）， and the liver/body ratio of mice decreased （P<0.01）. The results of HE staining showed that the degree of liver injury was alleviated. The mRNA levels of ACSL4 and PTGS2， iron content and MDA level all decreased （P<0.01）， while the mRNA levels of SIRT1， GPX4， HJV， FPN， GSH level and SOD activity all increased （P<0.05）. The protein levels of SIRT1 and GPX4 both increased （P<0.05）. ConclusionFGF21 overexpression is associated with enhanced SIRT1/GPX4 expression and suppression of ferroptosis features， thereby contributing to the alleviation of CCl₄-induced ALI.

Objective: To investigate the characteristics of psychological symptoms and the associated factors among students with close contact to tuberculosis in school settings,so as to provide evidence for school tuberculosis control and mental health interventions. Methods: A cross sectional study was conducted in April 2023 from 4 schools in Hangzhou using a multistage cluster random sampling method. Students identified as close contacts of tuberculosis cases ( n =406) were assigned to the exposure group, while non close contact students ( n =426) were matched at a 1∶1 ratio within the same schools as the non exposure group. A questionnaire survey was employed to collect data on general demographic and family sociological information. Psychological symptoms were assessed using the Symptom Check List-90 (SCL-90). A global severity index (GSI) score ≥2.0 was defined as moderate to severe psychological symptoms (MSPS). Logistic regression analysis was performed to identify associated factors. Results: The overall MSPS detection rate was 15.38%. The detection rate in the exposure group (20.69%) was significantly higher than the non exposure group (10.33%)( χ 2=17.14, P <0.05). Multivariate Logistic regression analysis showed that middle or lower family economic status ( OR =1.90, 95% CI =1.10-3.28) and poor interaction with others ( OR =2.95, 95% CI =1.79-4.88) were independent factors associated with MSPS among the exposure group (both P <0.05). Conclusions Students who are close contacts of school tuberculosis cases have a relatively high MSPS detection rate. Poor family economic status and poor interaction with social personnel are the main factors influencing MSPS. Schools should simultaneously strengthen psychological health support targeting factors in tuberculosis prevention and control.

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Primary aldosteronism(PA)is an important cause of secondary hypertension,and adrenal vein sampling(AVS),as the gold standard for identifying the dominant side in PA,plays a critical role in guiding subsequent therapeutic strategies.AVS is an invasive procedure that is not yet widely available in China.To promote the popularization and standardization of AVS,the Chinese Society of Hypertension(Chinese Research Hospital Association)and the Group of Interventional Diagnosis and Treatment of Hypertension(China International Exchange and Promotive Association for Medical and Health Care)have summarized domestic and foreign evidence and the operational experience of many experts.This consensus has summarized and updated the significance,indications,pre-procedural preparation,procedural steps and key points,prevention and management of complications,and result interpretation of AVS.This consensus provides comprehensive and clinically relevant guidance for the clinical practice and development of AVS,effectively promoting its popularization and standardization.

AIM To investigate effects of petroleum ether fraction from Derris eriocarpa How on glucose and lipid metabolism in a mouse model of metabolic syndrome(MS).METHODS KM mice were fed a high-fat diet and administered streptozotocin intraperitoneally to establish MS models.The MS mice were then randomly assigned to the model group,the metformin hydrochloride group,the lovastatin group,the ursolic acid group,and the high-,medium-and low-dose D.eriocarpa petroleum ether fraction groups,with 10 mice in each group.Ten additional mice maitained on a normal diet served as the normal control group.After 4 weeks of intragastric administration,glucose and lipid metabolism indicators were measured.Hepatic pathological changes were assessed using HE staining and oil red O staining.Liver tissue mRNA expressions of ATF3,PEPCK,FXR,CYP7A1,HNF4ɑ,CYP8B1 and SRB1 were quantified by RT-qPCR.Hepatic protein expressions of ATF3,HNF4ɑ,PEPCK,FXR and CYP7A1 was analyzed by Western blot in MS mice.RESULTS Compared to the model group,the high-dose D.eriocarpa petroleum ether fraction group exhibited significant glucose tolerance improvement(reduced OGTT-AUC,P＜0.01);favorable serum lipid modulation in terms of increased HDL-C levels(P＜0.01)and decreased TG,TC,LDL-C(P＜0.01);reduced renal biomarkers(BUN,SCR)and hepatotoxic indicators of TBA,AST and ALT activities(P＜0.01);alleviated hepatic lipid accumulation and histopathological damage;downregulated mRNA and protein expressions of ATF3,HNF4ɑ and PEPCK,as well as CYP8B1 mRNA expression(P＜0.01);and upregulated mRNA and protein expressions of FXR and CYP7A1,along with SRB1 mRNA expression(P＜0.01).CONCLUSION D.eriocarpa petroleum ether fraction ameliorates glucose and lipid metabolism dysregulation in MS mice by modulating the ATF3/HNF4ɑ/CYP7A1 signaling pathway,consequently eliciting hypoglycemic,hypolipidemic,hepatoprotective and nephroprotective effects.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective:To construct an esophageal language rehabilitation program for patients after total laryngectomy (TL) based on the behavioral change wheel theory and exploring its application effects.Methods:The multidisciplinary team constructed the first draft of the esophageal language rehabilitation program for patients after TL based on the behavioral change wheel theory, combined with a literature review, and used an expert meeting to revise the rehabilitation program to form the final draft of the program. Adopting experimental research, 35 patients after TL who attended the nursing outpatient clinic of Beijing Tongren Hospital, Capital Medical University from February 2023 to May 2023 were selected as the control group by convenience sampling method, and 35 patients after TL who attended the nursing outpatient clinic from June 2023 to September 2023 were selected as the experimental group. The experimental group applied the TL postoperative patients′ esophageal language rehabilitation program based on the behavioral change wheel theory on the basis of conventional nursing measures, and the control group received conventional nursing care. The status of language rehabilitation training, quality of life, social behavioral status, and anxiety and depression status before intervention, 1, 3, 6 months after intervention were compared between the two groups.Results:Both groups of patients completed the study. There were 29 males and 6 females in the control group, with an age of (54.63 ± 10.44) years old. There were 34 males and 1 female in the experimental group, with an age of (55.17 ± 10.67) years old. There was no statistically significant difference in the language rehabilitation training status, quality of life, social behavior status, and anxiety and depression status between the two groups before intervention (all P>0.05). The total scores of speech rehabilitation training in the experimental group at 1, 3, and 6 months after intervention were (32.80 ± 2.49), (39.80 ± 2.75), (51.91 ± 4.20) points, respectively, which were higher than those in the control group (23.40 ± 3.42), (24.40 ± 3.42), (25.80 ± 3.42) points, and the differences were statistically significant ( t=14.53, 23.44, 32.70, all P<0.05). The total scores of quality of life in the experimental group at 1, 3, and 6 months after intervention were (98.91 ± 8.49), (134.66 ± 11.31), (157.97 ± 13.97) points, respectively, which were higher than those in the control group (67.06 ± 7.64), (72.16 ± 7.64), (99.46 ± 8.09) points, and the differences were statistically significant ( t=17.53, 30.16, 21.45, all P<0.05). The scores for social occasion diet and language comprehension in the experimental group at 1, 3, and 6 months after intervention were (40.41 ± 13.94), (40.43 ± 24.08), (40.60 ± 18.56), and (43.71 ± 12.26), (47.40 ± 17.09), (52.50 ± 13.82), respectively, which were higher than those in the control group (30.59 ± 15.98), (30.57 ± 18.28), (27.21 ± 15.27), and (27.29 ± 15.13), (23.60 ± 14.78), (19.50 ± 12.78), and the differences were statistically significant ( t values were -6.88-2.16, all P<0.05). The total scores of anxiety and depression in the experimental group at 1, 3, and 6 months after intervention were (23.74 ± 2.73), (14.89 ± 3.89), (12.11 ± 3.14) points, respectively, which were lower than those in the control group (32.63 ± 1.85), (30.63 ± 1.85), (24.80 ± 2.75) points, and the differences were statistically significant (t=-19.55, -27.10, -17.97, all P<0.05). Conclusions:The esophageal language rehabilitation program for patients after TL based on the behavioral change wheel theory in this study is scientific, feasible, and can improve the patients′ esophageal language expression, quality of life, anxiety and depression, and social behavioral status, which can provide a reference for clinical care.

OBJECTIVE: To investigate the clinical features and prognosis of central nervous system (CNS) invasion in peripheral T-cell lymphoma (PTCL) and construct a risk prediction model for CNS invasion. METHODS: Clinical data of 395 patients with PTCL diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from 1st January 2013 to 31st December 2022 were analyzed retrospectively. RESULTS: The median follow-up time of 395 PTCL patients was 24(1-143) months. There were 13 patients diagnosed CNS invasion, and the incidence was 3.3%. The risk of CNS invasion varied according to pathological subtype. The incidence of CNS invasion in patients with anaplastic large cell lymphoma (ALCL) was significantly higher than in patients with angioimmunoblastic T-cell lymphoma (AITL) (P <0.05). The median overall survival was significantly shorter in patients with CNS invasion than in those without CNS involvement, with a median survival time of 2.4(0.6-127) months after diagnosis of CNS invasion. The results of univariate and multivariate analysis showed that more than 1 extranodal involvement (HR=4.486, 95%CI : 1.166-17.264, P =0.029), ALCL subtype (HR=9.022, 95%CI : 2.289-35.557, P =0.002) and ECOG PS >1 (HR=15.890, 95%CI : 4.409-57.262, P <0.001) were independent risk factors for CNS invasion in PTCL patients. Each of these risk factors was assigned a value of 1 point and a new prediction model was constructed. It could stratify the patients into three distinct groups: low-risk group (0-1 point), intermediate-risk group (2 points) and high-risk group (3 points). The 1-year cumulative incidence of CNS invasion in the high-risk group was as high as 50.0%. Further evaluation of the model showed good discrimination and accuracy, and the consistency index was 0.913 (95%CI : 0.843-0.984). CONCLUSION The new model shows a precise risk assessment for CNS invasion prediction, while its specificity and sensitivity need further data validation.
Humans ; Lymphoma, T-Cell, Peripheral/pathology* ; Prognosis ; Retrospective Studies ; Central Nervous System Neoplasms/pathology* ; Neoplasm Invasiveness ; Male ; Female ; Central Nervous System/pathology* ; Middle Aged ; Adult