1.From Gene Expression to Transcriptome-wide Association Study: Development and Comparison of Methodology
Kun FANG ; Guozhuang LI ; Linting WANG ; Qing LI ; Kexin XU ; Lina ZHAO ; Zhihong WU ; Jianguo ZHANG ; Nan WU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):223-229
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.
2.FGF21 overexpression upregulates SIRT1/GPX4 to inhibit ferroptosis and relieve CCl4 mouse acute liver injury
Xutao LING ; Qianqian HUANG ; Lun ZHANG ; Fang XIE ; Nan BAI ; Yingxia WANG ; Haoran HUA ; Haoze WANG ; Wenjing DAI ; Kexin LI ; Jianqing WANG
Acta Universitatis Medicinalis Anhui 2026;61(6):1053-1060
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.
3.Expression and functional study of FKBP10 in oral squamous cell carcinoma
FANG Zhikai ; JIN Hui ; YANG Shan ; JIANG Nan ; ZHANG Mingyu ; ZHOU Shuang ; LI Chang ; LI Lili
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(7):529-541
Objective:
To investigate the expression and functional role of FK506 binding protein 10 (FKBP10) in oral squamous cell carcinoma (OSCC), and to provide a research basis for the estimated prognosis and targeted therapy of OSCC.
Methods:
A total of 284 OSCC samples and 19 normal samples were selected from the Cancer Genome Atlas (TCGA) database, and diagnostic analysis was performed to determine mRNA expression. Survival analysis for FKBP10 and OSCC was conducted on a gene expression profile interaction analysis website. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression of FKBP10 in four OSCC cell lines and SAS and SCC9 cells transfected with siRNA. The cell proliferation ability of FKBP10-silenced cells was detected using the CCK8 method, and the cell cycle distribution and apoptosis were detected by flow cytometry. Cell migration and invasion ability were detected through wound healing and invasion experiments. The expression changes of total protein and phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT) after FKBP10 silencing were analyzed by proteomics and Western Blot.
Results:
According to the analysis of gene expression levels, the mRNA expression level of FKBP10 in OSCC was significantly higher than that in normal tissues (P < 0.001). In terms of diagnosis, the expression level of FKBP10 has unique diagnostic value for OSCC (P < 0.05). The survival analysis of FKBP10 and OSCC showed that a high expression of FKBP10 led to a decrease in patient survival and poor prognosis (P < 0.05). The expression of FKBP10 mRNA and protein in OSCC cell lines was higher than that in normal oral keratinocytes (P < 0.001). Silencing FKBP10 can reduce the proliferation, invasion, and migration ability of SAS and SCC9 (P < 0.001), and also block their cell cycle in the G0/G1 phase (P < 0.001), with a significant increase in apoptosis (P < 0.05). Protein mass spectrometry and Western blot analysis revealed that FKBP10 silencing significantly downregulated the expression of multiple proteins in the RAP1 signaling pathway, mainly RAP guanine nucleotide exchange factor 1 (RAPGEF1) (P < 0.05) and the phosphorylation of PI3K-AKT proteins (P < 0.05).
Conclusion
FKBP10 is highly expressed in OSCC, leading to poor prognosis for patients. Downregulated FKBP10 expression can inhibit the proliferation, migration, and invasion ability of OSCC cells, hinder cell cycle progression, and promote apoptosis via the RAP1-PI3K-AKT axis. FKBP10 is a potential therapeutic target and prognostic biomarker for OSCC.
4.Lumbar temperature change after acupuncture or moxibustion at Weizhong (BL40) or Chize (LU5) in healthy adults: A randomized controlled trial.
Si-Yi ZHENG ; Xiao-Ying WANG ; Li-Nan LIN ; Shan LIU ; Xiao-Xiao HUANG ; Yi-Yue LIU ; Xiao-Shuai YU ; Wei PAN ; Jian-Qiao FANG ; Yi LIANG
Journal of Integrative Medicine 2025;23(2):145-151
BACKGROUND:
There is a gap in understanding the effects of different acupoints and treatment methods (acupuncture and moxibustion) on microcirculatory changes in the lumbar region.
OBJECTIVE:
This study aimed to assess the thermal effects of acupuncture at Weizhong (BL40), with acupuncture at Chize (LU5) and moxibustion at both acupoints as control interventions.
DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS:
In this randomized controlled trial, 140 healthy participants were equally divided into four groups: acupuncture at BL40 (Acu-BL40), acupuncture at LU5 (Acu-LU5), moxibustion at BL40 (Mox-BL40) and moxibustion at LU5 (Mox-LU5). Participants underwent a 30-minute session of their assigned treatment. Infrared thermal imaging was used to collect temperature data on the areas of interest for analysis.
MAIN OUTCOME MEASURES:
The primary measure was the change in average temperature of the observed area after the intervention. The secondary measures included periodic temperature changes every 5 min and the temperature changes of the Governor Vessel and Bladder Meridian in the observed area after the intervention.
RESULTS:
Significant interactions were observed between treatments and acupoints affecting temperature (P < 0.001). The Acu-BL40 group showed a notably higher increase in mean temperature after 30 min compared to the Acu-LU5 and Mox-BL40 groups, with increases of 0.29 (95% confidence interval [CI] = 0.17 to 0.41) and 0.24 (95% CI = 0.08 to 0.41) °C, respectively.
CONCLUSION:
Acupuncture at BL40 acupoint can significantly increase the mean temperature in the observed area, highlighting the specific thermal effect of acupuncture compared to moxibustion in the lumbar area. This suggests a potential therapeutic benefit of acupuncture at BL40 for managing lumbar conditions.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT05665426). Please cite this article as: Zheng SY, Wang XY, Lin LN, Liu S, Huang XX, Liu YY, Yu XS, Pan W, Fang JQ, Liang Y. Lumbar temperature change after acupuncture or moxibustion at Weizhong (BL40) or Chize (LU5) in healthy adults: A randomized controlled trial. J Integr Med. 2025; 23(2): 145-151.
Adult
;
Female
;
Humans
;
Male
;
Young Adult
;
Acupuncture Points
;
Acupuncture Therapy
;
Body Temperature
;
Healthy Volunteers
;
Lumbosacral Region/physiology*
;
Moxibustion
;
Adolescent
6.Molecular Characterization of New Recombinant Human Adenoviruses Detected in Children with Acute Respiratory Tract Infections in Beijing, China, 2022-2023.
Yi Nan GUO ; Ri DE ; Fang Ming WANG ; Zhen Zhi HAN ; Li Ying LIU ; Yu SUN ; Yao YAO ; Xiao Lin MA ; Shuang LIU ; Chunmei ZHU ; Dong QU ; Lin Qing ZHAO
Biomedical and Environmental Sciences 2025;38(9):1071-1081
OBJECTIVE:
Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control.
METHODS:
Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes.
RESULTS:
Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16.
CONCLUSION
A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans
;
Adenoviruses, Human/isolation & purification*
;
Respiratory Tract Infections/epidemiology*
;
Child, Preschool
;
Child
;
Recombination, Genetic
;
Male
;
Beijing/epidemiology*
;
Infant
;
Female
;
Phylogeny
;
Adenovirus Infections, Human/epidemiology*
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Acute Disease
;
Genome, Viral
7.Association of Body Mass Index with All-Cause Mortality and Cause-Specific Mortality in Rural China: 10-Year Follow-up of a Population-Based Multicenter Prospective Study.
Juan Juan HUANG ; Yuan Zhi DI ; Ling Yu SHEN ; Jian Guo LIANG ; Jiang DU ; Xue Fang CAO ; Wei Tao DUAN ; Ai Wei HE ; Jun LIANG ; Li Mei ZHU ; Zi Sen LIU ; Fang LIU ; Shu Min YANG ; Zu Hui XU ; Cheng CHEN ; Bin ZHANG ; Jiao Xia YAN ; Yan Chun LIANG ; Rong LIU ; Tao ZHU ; Hong Zhi LI ; Fei SHEN ; Bo Xuan FENG ; Yi Jun HE ; Zi Han LI ; Ya Qi ZHAO ; Tong Lei GUO ; Li Qiong BAI ; Wei LU ; Qi JIN ; Lei GAO ; He Nan XIN
Biomedical and Environmental Sciences 2025;38(10):1179-1193
OBJECTIVE:
This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study.
METHODS:
A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants.
RESULTS:
Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m 2) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m 2) and obesity (≥ 28.0 kg/m 2) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m 2 ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses.
CONCLUSION
This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans
;
Body Mass Index
;
China/epidemiology*
;
Male
;
Female
;
Middle Aged
;
Prospective Studies
;
Rural Population/statistics & numerical data*
;
Aged
;
Follow-Up Studies
;
Adult
;
Mortality
;
Cause of Death
;
Obesity/mortality*
;
Overweight/mortality*
8.Ionizing Radiation Alters Circadian Gene Per1 Expression Profiles and Intracellular Distribution in HT22 and BV2 Cells.
Zhi Ang SHAO ; Yuan WANG ; Pei QU ; Zhou Hang ZHENG ; Yi Xuan LI ; Wei WANG ; Qing Feng WU ; Dan XU ; Ju Fang WANG ; Nan DING
Biomedical and Environmental Sciences 2025;38(11):1451-1457
9.Application of information technology in drug safety in China by bibliometric analysis
Guizhu LIU ; Hang LI ; Nan WANG ; Fang WANG ; Xu HU ; Jiajie TANG
Journal of Pharmaceutical Practice and Service 2025;43(12):625-630
Objective To sort out the current situation and research hotspots of the application of information technology in drug safety in China,reveal the latest research frontier, and provide a basis for the follow-up research. Methods The literature about the application of information technology in the field of drug safety were searched from 2012 to 2022 in three major databases of CNKI, WanFang and VIP databases, and visual analysis was conducted with the help of Citespace software. Results A total of 848 valid papers were included, and the number of annual publications showed a phased growth trend, and the cooperation between authors and publishers was not close enough. The application of information technology in drug safety was mainly reflected in pharmaceutical service, intravenous drug dispensing center and antibacterial drugs. The main technical means of information construction in the field of drug safety were prescription pre-audit system, knowledge base and automation. The research frontiers were mainly intelligence, knowledge base, prescription audit, and proprietary Chinese medicines. Conclusion The application of information technology in drug safety in China is in a period of vigorous development, and cooperation among different regions, institutions, and authors should be strengthened to promote information sharing. In the future, the related research of information technology in the field of Chinese patent medicine should be focused, and the research content of information technology application in drug safety could be further improved.
10.Recommendations for the clinical use of anti-amyloid-β monoclonal antibody for Alzheimer's disease(2025)
Nan ZHI ; Jinwen XIAO ; Rujing REN ; Binyin LI ; Jintao WANG ; Jieli GENG ; Wenwei CAO ; Yaying SONG ; Hualong WANG ; Shuguang CHU ; Guoping PENG ; Jun LIU ; Xiaoyun LIU ; Fang YUAN ; Wen WANG ; Ronghua DOU ; Xia LI ; Ling YUE ; Wenshi WEI ; Xiaoling PAN ; Xiangyang ZHU ; Dian HE ; Weinü FAN ; Jingping SHI ; Nan ZHANG ; Hui ZHAO ; Qin CHEN ; Cuibai WEI ; Xiaochun CHEN ; Gang WANG
Journal of Chongqing Medical University 2025;50(9):1133-1140
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.


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