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.

Animal experiments are essential tools in biomedical research, serving as a bridge between basic research and clinical trials. Systematic reviews and meta-analyses (SRs/MAs) of animal experiments are crucial methods for integrating evidence from animal experiment, which can facilitate the translation of findings into clinical research, reduce translational risks, and promote resource integration in basic research. With the continuous development of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, its application in SRs/MAs of animal experiments has gained increasing attention. This article first outlines the principles and specific applications of the GRADE methodology in SRs/MAs of animal experiments, including qualitative descriptive systematic reviews, meta-analyses, and network meta-analyses. It then deeply analyzes the misuse of the GRADE methodology in practice, including incorrect evidence grading, improper classification of evidence, misapplication in qualitative systematic reviews, inconsistencies between the documentation of the upgrading and downgrading process and results, and inappropriate use for making recommendations. Furthermore, this article comprehensively discusses the factors influencing the grading of evidence certainty in SRs/MAs of animal experiments, including the impact of bias risk, indirectness, inconsistency, imprecision, and publication bias on evidence downgrading, as well as the role of large effect sizes and cross-species consistency in evidence upgrading. Finally, in response to the issues discussed, improvement strategies are proposed, including further research and optimization of the GRADE methodology for SRs/MAs of animal experiments, the development of reporting guidelines tailored to the characteristics of SRs/MAs in animal experiment research, and enhanced professional training for researchers in the GRADE methodology. This article aims to improve the quality of evidence in SRs/MAs of animal experiments, strengthen their reliability in clinical decision-making, and promote the more efficient translation of findings from animal experiment research into clinical practice.

Purpose To investigate interhemispheric homotopic functional connectivity in patients with neuropsychological systemic lupus erythematosus(NPSLE)during resting state and its relationship with clinical indicators and neuropsychological scales.Materials and Methods This prospective study enrolled 35 patients with NPSLE and 31 healthy controls(control group)from Taizhou People's Hospital Affiliated to Nanjing Medical University(June 2020 to March 2023).All participants underwent resting state functional MRI and completed neuropsychological assessments including mini-mental state examination,Montreal cognitive assessment,hospital anxiety and depression scale,fatigue scale for motor and cognitive functions,along with laboratory tests(C3,C4,IgA,IgM,IgG).Image preprocessing and voxel-mirrored homotopic connectivity(VMHC)calculations were performed using DPABI V7.0 on Matlab R2013b.Between-group differences in VMHC values were compared,and correlations between VMHC values in significant regions and neuropsychological/clinical data were analyzed.Results The NPSLE group demonstrated significantly lower mini-mental state examination and Montreal cognitive assessment scores compared with those in control group(t=-6.297,-7.001,both P=0.001).Patients with NPSLE exhibited significantly decreased VMHC values in bilateral parahippocampal gyri,precentral gyri,middle frontal gyri,and medial/paracingulate gyri compared with those in control group(family-wise error corrected,voxel-level P<0.001,cluster-level P<0.05).In the NPSLE group,VMHC values in precentral gyri showed positive correlation with IgA levels(r=0.351,P=0.039),while VMHC values in medial/paracingulate gyri positively correlated with IgA(r=0.345,P=0.043)and negatively with C4(r=-0.368,P=0.030).Conclusion Patients with NPSLE demonstrate abnormal interhemispheric homotopic functional connectivity,and the correlation between imaging metrics and clinical data in differential brain regions may facilitate early diagnosis of NPSLE while providing novel insights into the neuropathological mechanisms of cerebral injury.

Deep brain stimulation(DBS)has witnessed rapid advancement as a neurosurgical intervention over the past four decades,addressing movement disorders and a spectrum of neuropsychiatric conditions.Notably,subthalamic nucleus deep brain stimulation(STN-DBS)is widely implemented in the management of Parkinson's disease(PD)patients experiencing refractory motor fluctuations and complications,and has shown promise in ameliorating non-motor symptoms(NMS).However,the long-term efficacy of STN-DBS on NMS remains a subject of scholarly discourse.This review endeavors to synthesize current knowledge regarding the long-term impacts,underlying mechanisms,and future research directions of STN-DBS in the context of NMS in Parkinson's disease.

[Purpose]To analyze the trend of incidence rates of gallbladder cancer in Qidong City of Jiangsu Province from 1972 to 2021.[Methods]The incidence data of gallbladder cancer from 1972 to 2021 were collected from the Qidong Tumour Registry database,the crude incidence rate(CR),age-standardized rate by Chinese standard population(ASRC),age-standardized rate by world standard population(ASRW)of gallbladder cancer were calculated.Trend analysis was per-formed using Joinpoint 4.9.1.0 software to calculate the average annual percentage change(AAPC)of gallbladder cancer incidence rates,and time trend analysis was performed on the overall inci-dence rate by sex and age.[Results]A total of 1 369 cases of gallbladder cancer occurred in Qi-dong City from 1972 to 2021,accounting for 0.93％of all malignant tumors.The overall CR of gallbladder cancer was 2.44/105 in 50 years,ASRC was 0.88/105 and ASRW was 1.45/105.The truncated rate of 35～64 years old was 1.98/105,the cumulative incidence of gallbladder cancer at 0～74 years old was 0.16％,and the risk of cumulative incidence of gallbladder cancer was 0.16％.CR was slightly higher in women than that in men,but after standardization it was slightly higher in men than that in women.The sex ratio of CR,ASRC and ASRW was 0.89,1.07 and 1.06,respectively.With the increase of age,the incidence of gallbladder cancer was also increased.The age of onset was slightly increased in last 50 years.In last 50 years,there was an upward trend in the overall incidence of gallbladder cancer,the incidence both for men and women,and the inci-dence of each age group.[Conclusion]The incidence of gallbladder cancer in Qidong City has increased considerably during the past 50 years,and continuing attention should be paid to the prevention and treatment of gallbladder cancer especially for the key populations.

[Purpose]To analyze the survival rate of breast cancer in Qidong City of Jiangsu Province from 1972 to 2019 and to predict the trend in the next 10 years.[Methods]The data of breast cancer collected from Qidong Cancer Registry from 1972 to 2019 were extracted.Observed survival rate(OSR),relative survival rate(RSR),age-adjusted relative survival(ARS)and average annual percentage change(AAPC)of breast cancer were calculated.ARIMA model was used to predict the trend of breast cancer survival rate.[Results]The 5-year RSR increased from 57.30％during 1972-1977 to 89.01％during 2014-2019,and the uptrend of RSR in the 8 periods was statistically significant(P＜0.001).The 5-year ARS increased from 48.12％during 1972-1977 to 85.64％during 2014-2019 with an AAPC of 1.85％(t=10.113,P＜0.001).The 5-year RSR during 1972-2019 for males was 85.22％,and for females was 74.51％.For females,the 5-year RSR in-creased from 56.44％during 1972-1977 to 88.93％during 2014-2019 with an AAPC of 1.29％(t=13.087,P＜0.001),and the 5-year ARS increased from 46.14％during 1972-1977 to 85.23％during 2014-2019 with an AAPC of 1.90％(t=10.369,P＜0.001).The 5-year RSR in the age groups of 25～34,35～44,45～54,55～64,65～74,and over 75 years old were 66.91％,74.69％,76.97％,75.52％,73.44％and 66.40％,respectively;the corresponding AAPCs of 5-RSR in above age groups were 1.02％(t=3.816,P=0.009),1.03％(t=4.936,P=0.003),1.23％(t=5.826,P=0.001),1.86％(t=5.997,P=0.001),2.13％(t=10.245,P＜0.001),and 1.44％(t=6.405,P=0.001),respectively.ARIMA modeling of survival trend prediction showed that 5-RSR and 5-ARS for breast cancer will be ascended to 98.76％and 98.33％by 2028,respectively.[Conclusion]The overall survival rate of registered breast cancer cases in Qidong City has been greatly improved and will be further improved in the future,more attention should be paid to the prevention and treatment of breast cancer.

Objective:To explore the mechanism through which the Ginkgo biloba extract(EGb)ameliorates depres-sion-like behaviors in chronic copper-exposed mice.Methods:A mouse model with depression was induced by chronic oral administration of copper sulfate solution(200 mg/L),followed by oral administration of the EGb(120 mg/L)for one month.Elevated plus-maze test,forced swimming test,and sucrose preference test were employed to detect the de-pression-like behaviors of mice.TUNEL staining was utilized to examine apoptosis in the hippocampal region of mice.Immunohistochemistry was adopted to detect the in situ expression of pro-brain-derived neurotrophic factor(proBDNF)and brain-derived neurotrophic factor(BDNF)in the hippocampal region.RT-qPCR was used to measure the expression of the BDNF mRNA.Western blot was utilized to determine the expressions of proteins such as proBDNF,mature BDNF(mBDNF),cAMP response element binding protein(CREB),phospho-CREB(p-CREB),tyrosine kinase receptor B(TrkB),p75 neurotrophin Receptor(p75NTR),furin,proprotein convertase subtilisin/kexin type 1(PCSK1),and matrix metalloproteinase-9(MMP9).Results:Chronic copper exposure led to depression-like behaviors in mice,in-creased neuronal apoptosis in the hippocampal region,enhanced proBDNF expression and reduced mBDNF expression(P＜0.05),decreased the expression of the downstream receptor protein TrkB and increased the expression of p75NTR(P＜0.05),and decreased the level of CREB and p-CREB(P＜0.05).Meanwhile,the expressions of intracellular proteases furin and PCSK1 in the hippocampal region of mice with depression-like behaviors decreased(P＜0.05),while the expression of extracellular protease MMP9 increased(P＜0.05).EGb was capable of alleviating depression-like behaviors and neuronal apoptosis in mice and partially reversing the abnormal expressions of BDNF,proBDNF,TrkB,p75NTR,CREB,p-CREB,furin,and PCSK1 proteins caused by copper exposure.Conclusion:Chronic copper exposure can lead to depression-like behaviors and apoptosis in mice.EGb can reverse these manifestations and corre-late with the balance of proBDNF/BDNF in the hippocampal region,which may offer novel insights for the treatment of depression.

Objective:To explore the effects of combining APR-246 with irradiation for enhancing anti-tumor immune response against 4T1 breast cancer cells, and to develop multiple tumor treatment strategies.Methods:The control group, APR-246 group, irradiation group and irradiation combined APR-246 group were used both in the cell experiment and tumor-bearing mice experiment. The inhibitory effect of APR-246 on the proliferation of 4T1 cells was assessed by using Cell Counting Kit-8. The effect of APR-246 with irradiation on the survival rate of 4T1 cells using clone formation assay was measured. The levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) in tumor cells using a 2’, 7’-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe and a lipid peroxidation sensor, the tumor inhibition rates of different groups of tumor bearing mice were compared, and the proportions of CD4+ and CD8+ T cells and the ratio of M1/M2 macrophages were determined in the tumor microenvironment by flow cytometry.Results:Compared with irradiation group, 2, 4, 6 Gy irradiation combined APR-246 group significantly reduced the survival rates of 4T1 cells ( t = 2.89, 4.15, 2.62, P < 0.05), the 6 Gy irradiation combined APR-246 group significantly increased the levels of ROS ( t = 16.95, P < 0.05) and LPO ( t = 6.09, P < 0.05) in 4T1 cells, and significantly increased the apoptosis rate of 4T1 cells ( t = 10.99, P < 0.05). Meanwhile, from the 16 th day of tumor inoculation, the 10 Gy irradiation combined APR-246 group showed significantly inhibited tumor growth ( t = 2.38-2.91, P < 0.05) and significantly increased proportions of CD4+ and CD8+ T cells ( t = 9.96, 6.28, P < 0.05) and M1/M2 ratio ( t = 15.30, P < 0.05) in tumor tissues. Conclusions:APR-246 combined with irradiation can effectively increase ROS and LPO levels in 4T1 cells, promote tumor cell apoptosis, and induce anti-tumor immune response, thus potentially inhibiting the growth of 4T1 cells.

Intestinal radiosensitivity makes radiation-induced intestinal injury (RIII) as a common complication among individuals exposed to accidental radiation and patients with abdominal or pelvic malignancies receiving radiotherapy. At present, there are no effective measures for the prevention and treatment of RIII. Developing novel prevention and treatment strategies is of great significance for improving the prognosis and quality of life for both individuals exposed to accidental radiation and cancer patients. Lactobacillus, a Gram-positive bacterium, is widely observed in humans and animals. It exhibits notable probiotic functions, including maintaining gut microbiota homeostasis, preserving intestinal barrier, and modulating immune responses. Substantial studies have demonstrated that Lactobacillus has remarkable protective and therapeutic effects against radiation-induced injury, specifically significantly alleviating RIII. These probiotic functions of Lactobacillus make it have high priority to become the chassis of genetically engineered strains. However, multiple factors influence the construction of a genetically engineered strain, limiting the application of Lactobacillus as a chassis. This review focuses on the probiotic functions of Lactobacillus, highlighting advances in research on Lactobacillus and its engineered probiotics in radiation protection and treatment. Furthermore, it summarizes key factors influencing the construction of genetically engineered strains based on the Lactobacillus chassis. It aims to provide insights for developing genetically engineered strains with radioprotective and therapeutic effects using Lactobacillus as the chassis.

Objective To investigate the governance requirements for real world data(RWD)in China's medical standards and specifications,summarize key technical aspects of data governance,and provide refer-ences for RWD governance-related research.Methods Computerized searches were conducted in CNKI,Wan-fang Data,VIP,and SinoMed,as well as the official websites of 29 national medical societies and the National Standard Information Public Service Platform,covering all records from inception to December 12,2023.A data extraction form was developed,and the included standards and specifications were categorized according to the first six RWD governance processes outlined in the Guidelines for Real World Data Used to Generate Real-World Evidence(Trial)issued by the National Medical Products Administration:data security,data extraction,data cleaning,data transformation,data transmission and storage,and quality control.Relevant content on data governance was systematically summarized and comparatively analyzed.Results A total of 32 standards and specifications were included,comprising 15 foundational medical data standards and 17 data gov-ernance technical specifications.Among these,6 addressed data security,6 covered data extraction,5 focused on data cleaning,5 involved data transformation,6 pertained to data transmission and storage,and 4 discussed quality control.Foundational medical data standards included data description elements,terminology,and format standards,broadly covering essential data elements and meeting basic standardization needs.Data gov-ernance technical specifications primarily provided general guidelines for medical data governance,emphasizing requirements and recommendations.While requirements for data security and extraction were relatively well-de-fined,technical guidance on data transformation and quality control remained limited,and implementation pathways for data cleaning,transmission,and storage were insufficiently detailed.Conclusions As real-world evidence plays an increasingly critical role in healthcare decision-making,China's medical standards and speci-fications have established a preliminary governance framework for RWD.However,technical details and practi-cal implementation of RWD governance still require further refinement.