1.Xuefu Zhuyutang Ameliorates Metabolic-associated Fatty Liver Disease via AMPK Signaling Pathway
Ming HAN ; Ying ZHANG ; Lingya KONG ; Jun DAI ; Ting ZHANG ; Zhihong MA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):1-12
ObjectiveTo investigate the therapeutic mechanism of Xuefu Zhuyutang (XFZYT) for metabolic-associated fatty liver disease (MAFLD) through integrated network pharmacology and animal experiments. MethodsNetwork pharmacology was utilized to predict the core components, key therapeutic targets, and signaling pathways of XFZYT in the treatment of MAFLD. For animal experiments, a rat model of MAFLD was established by feeding a high-cholesterol diet for 4 weeks. Intervention was then administered with low-dose (2 g·kg-1) and high-dose (4 g·kg-1) XFZYT for 2 weeks. Biochemical assays were performed to measure the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). In addition, the activities of superoxide dismutase (SOD) and catalase (CAT) and levels of malondialdehyde (MDA) and glutathione (GSH) in the serum were measured. The same way was adopted to measure the levels of TC and TG in the liver tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the serum levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-α). Histopathological evaluations included hematoxylin and eosin (HE) staining for liver tissue morphology, Oil Red O staining for lipid deposition, and dihydroethidium (DHE) probe staining for reactive oxygen species (ROS) levels. Western blot analysis was conducted to assess the protein levels of AMP-activated protein kinase (AMPK), phosphorylated (p)-AMPK, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB), and p-NF-κB in the liver tissue. Untargeted metabolomics analysis of the serum was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). ResultsNetwork pharmacology analysis predicted 155 potential targets of XFZYT for MAFLD treatment, with core targets including signal transducer and activator of transcription 3 (STAT3), protein kinase B1 (Akt1), TNF, and IL-6. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment primarily implicated the AMPK signaling pathway. Animal experiments demonstrated that compared with the normal group, the model group exhibited dyslipidemia, hepatic function impairment, pronounced hepatic lipid deposition, and inflammatory manifestations, with elevated serum levels of AST, ALT, TC, TG, LDL, and MDA (P<0.05), reduced HDL and GSH levels plus decreased SOD and CAT activities (P<0.05), downregulated protein levels of Nrf2, HO-1, and p-AMPK (P<0.05), and upregulated protein level of p-NF-κB (P<0.05) in the liver tissue. Compared with the model group, XFZYT intervention groups showed significant amelioration of dyslipidemia and hepatic function impairment, markedly reduced hepatic lipid deposition and inflammatory cell infiltration, decreased serum levels of AST, ALT, TC, TG, LDL, and MDA (P<0.05), increased HDL and GSH levels plus enhanced SOD and CAT activities (P<0.05), upregulated protein levels of Nrf2, HO-1, and p-AMPK (P<0.05), and downregulated protein level of p-NF-κB (P<0.05). Serum metabolomics revealed 511 differentially expressed metabolites (231 upregulated and 280 downregulated) between normal and model groups, while XFZYT groups versus model group showed 94 differential metabolites (51 upregulated and 43 downregulated). Among them, 11 metabolites displayed the most significant alterations, with enriched pathways including glycerolipid metabolism, cholesterol metabolism, and insulin resistance, multiple of which demonstrated AMPK association. ConclusionXFZYT alleviates MAFLD by regulating the AMPK signaling pathway and associated metabolic networks.
2.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.
3.Secular trends in energy and macronutrient intake across different occupational groups in nine provinces of China, 1989–2018
Yu WU ; Jiguo ZHANG ; Liusen WANG ; Lixin HAO ; Chang QU ; Yumeng SONG ; Zhihong WANG ; Huijun WANG ; Bing ZHANG ; Hongru JIANG ; Gangqiang DING
Journal of Environmental and Occupational Medicine 2026;43(2):145-152
Background With China's socio-economic development, the dietary structure of Chinese residents has gradually shifted from a traditional Eastern pattern characterized by high carbohydrate intake to a relatively high-fat Western dietary model, alongside a growing burden of chronic diseases. However, dietary changes may vary across different occupational groups. Objective To analyze the long-term trends in dietary energy and three major macronutrient intake among various occupational groups aged 18-59 years in nine provinces of China from 1989 to 2018, providing a scientific basis for developing occupation-specific dietary intervention strategies. Methods Based on 11 waves of data (1989–2018) from the China Health and Nutrition Survey (CHNS),
4.Cardiometabolic risk factor trends across different occupational groups in nine provinces of China, 2009–2018
Yu WU ; Hongru JIANG ; Lixin HAO ; Liusen WANG ; Weiyi LI ; Shaoshunzi WANG ; Zijian WANG ; Zhihong WANG ; Huijun WANG ; Bing ZHANG ; Lili CHEN ; Gangqiang DING
Journal of Environmental and Occupational Medicine 2026;43(2):153-159
Background With China's socioeconomic development, significant lifestyle changes have occurred among occupational groups, leading to alterations in cardiovascular metabolic risk factors. However, few studies have examined the secular trends of these risk factors in China's working population. Objective To analyze the trends in cardiovascular metabolic risk factors among the occupational population in nine provinces of China from 2009 to 2018, and to explore the associations between different occupational types and these risk factors, along with their clustering patterns, thereby providing evidence for targeted interventions. Methods This study utilized data from the China Health and Nutrition Survey (CHNS) in 2009, 2015, and 2018. The dataset covered
5.Change trend of compound obesity among different occupational groups in nine provinces of China from 1993 to 2018
Lixin HAO ; Yu WU ; Liusen WANG ; Lili CHEN ; Boya ZHAO ; Zhongting LU ; Zhihong WANG ; Bing ZHANG ; Hongru JIANG ; Huijun WANG
Journal of Environmental and Occupational Medicine 2026;43(2):160-167
Background The global prevalence of obesity is on the rise and is closely associated with various chronic non-communicable diseases such as cardiovascular diseases and diabetes. There is a relative lack of long-term dynamic studies on compound obesity among occupational populations. Objective To explore the changing trends of compound obesity among different occupational groups aged 18–59 years in nine provinces (autonomous regions, municipalities) of China from 1993 to 2018, and to provide a scientific basis for formulating targeted weight management strategies for occupational populations. Methods A total of
6.Association between changes in body mass index and hypertension among different occupational groups
Zhongting LU ; Lili CHEN ; Hongru JIANG ; Lixin HAO ; Liusen WANG ; Weiyi LI ; Yu WU ; Huijun WANG ; Bing ZHANG ; Jiguo ZHANG ; Zhihong WANG
Journal of Environmental and Occupational Medicine 2026;43(2):168-173
Background With rising obesity rates and earlier hypertension onset among occupational populations, there is an urgent need to elucidate the long-term cardiovascular impacts of dynamic body weight patterns. Current evidence lacks trajectory modeling studies examining occupation-specific prevention strategies. Objective To investigate the association between long-term body mass index (BMI) trajectories and incident hypertension risk in Chinese working adults, and to examine occupation-specific heterogeneity in this relationship. Methods A dynamic sub-cohort of 4 413 occupational participants was constructed from ten survey waves (1991–2018) of the China Health and Nutrition Survey (CHNS). Eligible individuals had valid key BMI records at three or more independent follow-ups before the outcome event; the individual baseline was set as the year of their first participation in the survey. Group-based trajectory modeling (GBTM) was used to identify BMI change patterns. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence interval (CI) for hypertension incidence across trajectory groups, with stratified analysis by occupational categories. Results Among
7.Influencing factors for postoperative malignant glaucoma in patients with primary angle-closure glaucoma
Jing LYU ; Jingfei BAN ; Zhihong ZHANG ; Yanan LI
International Eye Science 2026;26(4):711-717
AIM:To analyze the influencing factors of postoperative malignant glaucoma(MG)in patients with primary angle-closure glaucoma(PACG)using logistic regression and decision tree models.METHODS:A retrospective study was conducted on PACG patients who underwent surgery at Eye Hospital of Handan City from March 2020 to March 2025. Patients were divided into two groups: the MG group, who developed MG within 6 mo postoperatively, and the non-MG group. Data were collected from the electronic medical record system. Univariate analysis was performed, followed by multivariate logistic regression to identify independent risk factors. A classification and regression tree model was constructed to visualize the hierarchical relationships among predictors. The predictive performance of the two models was evaluated and compared using receiver operating characteristic(ROC)curve analysis.RESULTS:Totally 182 cases(182 eyes)with PACG were enrolled in this study, including 91 cases(91 eyes)in the MG group and 91 cases(91 eyes)in the non-MG group. In the MG group, there were 53 males and 38 females; 69 cases were aged ≥60 y and 22 cases were aged <60 y. In the non-MG group, there were 47 males and 44 females; 33 cases were aged ≥60 y and 58 cases were aged <60 y. The non-MG group comprised 91 patients, including 47 males and 44 females. Among them, 33 cases were aged ≥60 y, and 58 cases were aged<60 y. The MG group had significantly higher proportions of patients aged ≥60 y, diabetes, moderate-stage PACG, persistent high intraocular pressure(IOP), complete anterior chamber angle closure, lens thickness <4.5 mm, axial length <22 mm, and severe postoperative inflammation compared to the non-MG group(all P<0.01). Multivariate Logistic regression identified the following as independent influencing factors for postoperative MG: age [OR (95%CI)=2.136(1.401-3.255)], PACG stage [OR (95%CI)=2.996(2.044-4.391)], IOP [OR (95%CI)=3.527(1.604-7.755)],anterior chamber angle [OR (95%CI)=4.826(2.498-9.324)], axial length [OR (95%CI)=5.125(1.265-20.771)], and severe postoperative inflammation [OR (95%CI)=2.338(1.478-3.699)](all P<0.05). The decision tree model selected six explanatory variables: age, PACG stage, IOP, anterior chamber angle status, axial length, and severe postoperative inflammation. Axial length was the primary splitting factor at the root node. The areas under the ROC curve(AUC)for the logistic regression and decision tree models were 0.913(0.863-0.950)and 0.921(0.872-0.956), respectively, with no significant difference between them(Z=0.561, P=0.575).CONCLUSION:Both the logistic regression and decision tree models effectively identify key influencing factors for postoperative MG in PACG patients, including age, PACG stage, IOP, anterior chamber angle status, axial length, and severe postoperative inflammation. The decision tree model offers an intuitive, visual representation of risk stratification, facilitating clinical decision-making. Both models are applicable for clinical risk assessment.
8.Serum HCV-RNA detection rate and logistic regression analysis in patients with positive hepatitis C virus IgG antibody
Youli HE ; Yuxin FAN ; Zhihong ZHANG ; Yanhong GU
Journal of Public Health and Preventive Medicine 2026;37(3):118-122
Objective To investigate serum HCV-RNA detection rate in patients with positive hepatitis C virus (HCV) immunoglobulin G (IgG) antibody, and to analyze the related factors of HCV-RNA detection in patients with positive HCV IgG antibody by logistic regression analysis. Methods A retrospective study was conducted on 500 patients with positive HCV IgG antibody. The positive rate of HCV-RNA was counted. Logistic regression analysis was adopted to analyze the related factors of HCV-RNA detection in HCV IgG antibody positive population. Results A total of 317 patients with positive HCV-RNA detection were included in serum HCV-RNA positive group (n=317), and 183 patients with negative HCV-RNA detection were enrolled as serum HCV-RNA negative group (n=183). The diagnosis rate of HCV infection was 63.40% (317/500). Logistic regression analysis showed that abnormal levels of serum ALT, AST, GGT, TBIL, HCV IgG antibody, prothrombin time, and the presence of clinical symptoms were independently correlated with the detection of HCV-RNA in HCV IgG antibody positive individuals (P<0.05). Established 7-factor prediction models and created a nomogram. The chi-square value was 0.586, and P = 0.89 > 0.05. The ROC curve was plotted using pROC, and the area under the ROC curve was 0.912. Conclusion Among the population positive for HCV IgG antibody, the detection rate of serum HCV-RNA is high. Abnormal levels of ALT, AST, GGT, TBIL, IgG antibody, prothrombin time and clinical symptoms are the related factors for the detection of HCV-RNA. These indicators provide a reference for the clinical judgment of the real infection risk of HCV IgG positive individuals.
9.Clinical observation and anti-drug antibody monitoring of enzyme replacement therapy in children with Fabry disease
Zhihong LU ; Xinyi SHOU ; Qian LIN ; Lingxia ZHANG ; Haidong FU ; Jianhua MAO
Chinese Journal of Pediatrics 2025;63(1):75-79
Objective:To analyze the efficacy of enzyme replacement therapy and anti-drug antibody production in children with Fabry disease.Methods:The clinical data of 7 children with Fabry disease treated with enzyme replacement therapy for more than 1 year at Children′s Hospital of Zhejiang University School of Medicine from July 2021 to June 2024 were retrospectively analyzed. The basic information and the changes of related clinical indicators before and after treatment were collected. Paired sample t test was used to compare renal function, left heart mass index, pain score and other related indexes before and after treatment. The anti-drug antibodies were detected by enzyme-linked immunosorbent assay. Results:A total of 6 boys and 1 girl were included. The age of diagnosis was (12.2±1.8) years. After 1 year of enzyme replacement therapy, the abnormal substrate globotriaosylsphingosine and brief pain inventory scores of all children were significantly lower than those before treatment ((16±11) vs. (63±42) μg/L, 22±19 vs. 45±29, t=3.88, 3.43, both P<0.05). There were no significant differences in glomerular filtration rate, urinary microalbumin to creatinine and left heart mass index before and after treatment ((124±35) vs. (136±26) ml/(min·1.73 m 2), (9.3±8.3) vs. (3.8±2.5) mg/g, (38±9) vs. (33±6) g/m 2.7, t=1.33, 1.74, 1.19, all P>0.05). Patients 4, 5 and 6 developed anti-drug antibodies at 1 month, 4 months and 1 month after medication, respectively. Patient 4 had persistently high anti-drug antibody titers (absorbance 3.65-3.73) accompanied by urticaria, elevated globotriaosylsphingosine and worsening clinical symptoms. Conclusions:The enzyme replacement therapy can effectively improve the clinical symptoms and reduce the level of globotriaosylsphingosine in children with Fabry disease. The anti-drug antibody is common in patients after long-term enzyme replacement therapy and may diminish the efficacy, which needs dynamic monitoring.
10.The role of PKMYT1 in glucocorticoid-induced osteoblast apoptosis
Chengyou YANG ; Hong LUO ; Tao WANG ; Zhihong XIE ; Liang LIANG ; Fanchao LI ; Jianhua WU ; Fei ZHANG ; Wuxun PENG
Chinese Journal of Sports Medicine 2025;44(5):381-393
Objective To investigate the role of membrane-associated tyrosine/threonine-protein ki-nase 1(PKMYT1)in glucocorticoid(GC)-induced osteoblast(OB)apoptosis,providing a theoretical basis and potential therapeutic targets for early-stage steroid-induced avascular necrosis of the femoral head(SANFH).Methods(1)Mouse calvarial osteoblastic cells(MC3T3-E1)were selected for the study.The control group was cultured in standard medium,while the experimental group was subject-ed to osteogenic induction culture,with osteogenic capacity verified by alkaline phosphatase(ALP)and Alizarin Red S(ARS)staining.Then,mouse osteoblasts(mOB)were treated with different con-centrations of GC.After that,apoptosis was detected by using Annexin V-FITC/PI double staining as-say,while cell proliferation was assessed by using Cell Counting Kit-8(CCK8).Moreover,the expres-sions of anti-apoptotic protein B-cell lymphoma/leukemia-2(BCL-2),pro-apoptotic proteins cleaved caspase-3andcleavedcaspase-9(cleavedcaspase 3/9)weredetectedbyusing Westernblotting(WB).Meanwhile,proteomic analysis was employed to identify molecules potentially regulating GC-in-duced apoptosis in mOBs.What's more,quantitative real-time PCR(qPCR)and WB were used to further analyze PKMYT1 expression.(2)mOBs were treated with PKMYT1 inhibitor GSK-1520489A of different concentrations to screen the optimal one,and all subjects were then further divided into a control,a GC,a GSK-1520489A,and a GC+GSK-1520489A group.Later,the expression of PK-MYT1 and apoptosis-related proteins BCL-2 and cleaved caspase 3/9 of all groups were detected us-ing WB,and cell viability and cytotoxicity were evaluated by CCK8 assay,with cell proliferation by using 5-ethynyl-2'-deoxyuridine(EDU)assay and apoptosis by cell live/dead staining and Annexin V-FITC/PI double staining.(3)mOBs were infected with PKMYT1 overexpression lentiviral vectors,and its efficiency was verified by using immunofluorescence,qPCR,and WB.After successful overexpres-sion of PKMYT1,all cells were divided into the control,GC,PKMYT1 overexpression(OE),and OE+GC groups,whose cell proliferation was detected by EDU assay,and apoptosis was assessed by Annexin V-FITC/PI double staining and cell live/dead staining.(4)To verify the changes in PKMYT1 expression in human osteoblasts(hOB),hOBs extracted from human femoral heads of healthy individu-als were chosen into the control group,while those from patients with hormone-induced avascular ne-crosis of the femoral head(hSANFH)were selected into the hSANFH group.Then,PKMYT1 expres-sion in both groups was detected by using qPCR and WB.Results(1)After inducing the differentia-tion of mouse calvarial osteoblastic cells(MC3T3-E1)into mature osteoblasts,under the action of GC,compared with the control group,with the increase of GC concentration,the experimental group showed increased mOB apoptosis(P<0.01)and expression of cleaved caspase 3/9(P<0.01),but de-creased cell viability(P<0.01)and expressionof apoptosis-relatedprotein BCL-2(P<0.01).More-over,according to the proteomic sequencing,significant decrease was observed in the PKMYT1 expres-sion in mature mOBs treated with GC.(2)As to treatment of mOBs with different concentrations of PKMYT1 inhibitor GSK-1520489A,with the increase of concentration,cell viability decreased and cy-totoxicity increased(P<0.001).Moreover,compared with the control group,mOBs proliferation de-creased(P<0.001)and apoptosis increased(P<0.001)in the GSK-1520489A group.Meanwhile,com-pared with the GC group,mOB proliferation decreased(P<0.05)and apoptosis increased significantly(P<0.01)in the GC+GSK-1520489A group.(3)After overexpression of PKMYT1,in comparison with the control group,mOB proliferation increased(P<0.001)but apoptosis did not increase significantly(P>0.05)in the OE group.Moreover,compared with the GC group,mOB proliferation increased(P<0.001)but apoptosis decreased(P<0.001)significantly in the OE+GC group.(4)In hOBs extracted from human femoral head tissues,qPCR and WB results showed that PKMYT1 expression of the hSANFH group was significantly lower than the control group(P<0.001).Conclusion Down regulation of PKMYT1 expression promotes GC-induced apoptosis of mOBs.Conversely,over expression of PK-MYT1 inhibits GC-induced apoptosis of mOBs.Therefore,PKMYT1 may serve as a potential target for the early treatment of SANFH.


Result Analysis
Print
Save
E-mail