1.Mechanism of action of Gegen QinLian Decoction in improving non-alcoholic fatty liver disease by inhibiting ferroptosis based on the Nrf2/SCLC7A11/GPX4 pathway
Qian LUO ; Tao LUO ; Zhenzhen SONG ; Fang LIANG ; Junsen LI ; Shuhong PENG ; Lan CAO ; Haiping ZHAO ; Changhua ZHANG
Chinese Journal of Comparative Medicine 2025;35(2):72-84
Objective To investigate the mechanism of action of the nuclear factor erythroid 2-related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4)signaling pathway in non-alcoholic fatty liver disease(NAFLD),and to explore the mechanism of Gegen QinLian Decoction for the treatment of NAFLD,using in vivo and in vitro experiments.Methods Rats were fed with high-fat chow for 24 weeks to induce NAFLD,and were then divided randomly into normal(C),model(M),high-,medium-,and low-dose Gegen QinLian Decoction(GGQLT-H,GGQLT-M,GGQLT-L),and metformin(Met)groups.From week 25 onwards,the rats were administered the corresponding drugs by gavage for 2 weeks according to the grouping,until sampling.Levels of the oxidative stress markers malondialdehyde(MDA)and glutathione(GSH)in the liver tissues were measured in each group using biochemical kits and ferrous iron(Fe2+)in rat liver tissues was detected using a Fe2+kit.Nrf2,heme oxygenase-1(HO-1),SLC7A11,glutathione synthetase(GSS),GPX4,and acyl coenzyme A synthetase 4(ACSL4)mRNA levels in rat liver tissues were measured by reverse transcription quantitative polymerase chain reaction.For cellular experiments lipid acc umulation was induced in HepG2 hepatocellular carcinoma cells using 1 mmol/L free fatty acid,to mimic the NAFLD in vitro model.Different concentrations of Gegen QinLian Decoction and metformin-containing serum were added for treatment.Lipid accumulation was detected in the cells in each group by Oil red O staining.The MDA and GSH contents of HepG2 cells in the different groups were determined using appropriate kits,and the ferrous contents were detected using a cell-specific ferrous kit.Expression levels of Nrf2,HO-1,SLC7A11,GSS,GPX4,and ACSL4 mRNA was detected in each group of cells using reverse transcription quantitative polymerase chain reaction.Results In the animal experiments,MDA and Fe2+liver levels were significantly higher in the M group than in the C group,while GSH levels were significantly lower(P<0.01).GGQLT-H,GGQLT-M and Met groups showed significantly reduced MDA and Fe2+and elevated GSH levels compared with the M group(P<0.01,P<0.05).High-and medium-dose Gegen QinLian Decoction and metformin increased Nrf2,HO-1,GSS,and GPX4 mRNA and decreased ACSL4 mRNA expression levels(P<0.01,P<0.05).In cellular experiments,lipid droplets were significantly increased in the HepG2 cell M group compared with those in the C group,and lipid droplets were significantly reduced by Gegen QinLian Decoction and metformin.MDA and Fe2+levels were significantly increased and GSH levels were significantly decreased in the HepG2 M group compared with the levels in the C group(P<0.01),while all doses of Gegen QinLian Decoction and metformin significantly decreased MDA and Fe2+levels(P<0.01)and increased the GSH content(P<0.01,P<0.05).Nrf2,GSS,GPX4,and SLC7A11 mRNA expression levels in the GGQLT-H group,Nrf2,HO-1,and SLC7A11 in the GGQLT-L group,HO-1,SLC7A11,and GSS in the GGQLT-M group,and GSS,Nrf2,and HO-1 in the Met group were all significantly increased compared with the findings in the M group(P<0.01,P<0.05).ACSL4 mRNA expression levels were significantly decreased in the GGQLT-M and GGQLT-L groups and the Met group(P<0.01,P<0.05).Conclusions Gegen QinLian Decoction can improve NAFLD by inhibiting ferroptosis,and its mechanism may he related to regulation of the Nrf2/SLC7A 11/GPX4 signaling pathway.
2.Mechanism of action of Gegen QinLian Decoction in improving non-alcoholic fatty liver disease by inhibiting ferroptosis based on the Nrf2/SCLC7A11/GPX4 pathway
Qian LUO ; Tao LUO ; Zhenzhen SONG ; Fang LIANG ; Junsen LI ; Shuhong PENG ; Lan CAO ; Haiping ZHAO ; Changhua ZHANG
Chinese Journal of Comparative Medicine 2025;35(2):72-84
Objective To investigate the mechanism of action of the nuclear factor erythroid 2-related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4)signaling pathway in non-alcoholic fatty liver disease(NAFLD),and to explore the mechanism of Gegen QinLian Decoction for the treatment of NAFLD,using in vivo and in vitro experiments.Methods Rats were fed with high-fat chow for 24 weeks to induce NAFLD,and were then divided randomly into normal(C),model(M),high-,medium-,and low-dose Gegen QinLian Decoction(GGQLT-H,GGQLT-M,GGQLT-L),and metformin(Met)groups.From week 25 onwards,the rats were administered the corresponding drugs by gavage for 2 weeks according to the grouping,until sampling.Levels of the oxidative stress markers malondialdehyde(MDA)and glutathione(GSH)in the liver tissues were measured in each group using biochemical kits and ferrous iron(Fe2+)in rat liver tissues was detected using a Fe2+kit.Nrf2,heme oxygenase-1(HO-1),SLC7A11,glutathione synthetase(GSS),GPX4,and acyl coenzyme A synthetase 4(ACSL4)mRNA levels in rat liver tissues were measured by reverse transcription quantitative polymerase chain reaction.For cellular experiments lipid acc umulation was induced in HepG2 hepatocellular carcinoma cells using 1 mmol/L free fatty acid,to mimic the NAFLD in vitro model.Different concentrations of Gegen QinLian Decoction and metformin-containing serum were added for treatment.Lipid accumulation was detected in the cells in each group by Oil red O staining.The MDA and GSH contents of HepG2 cells in the different groups were determined using appropriate kits,and the ferrous contents were detected using a cell-specific ferrous kit.Expression levels of Nrf2,HO-1,SLC7A11,GSS,GPX4,and ACSL4 mRNA was detected in each group of cells using reverse transcription quantitative polymerase chain reaction.Results In the animal experiments,MDA and Fe2+liver levels were significantly higher in the M group than in the C group,while GSH levels were significantly lower(P<0.01).GGQLT-H,GGQLT-M and Met groups showed significantly reduced MDA and Fe2+and elevated GSH levels compared with the M group(P<0.01,P<0.05).High-and medium-dose Gegen QinLian Decoction and metformin increased Nrf2,HO-1,GSS,and GPX4 mRNA and decreased ACSL4 mRNA expression levels(P<0.01,P<0.05).In cellular experiments,lipid droplets were significantly increased in the HepG2 cell M group compared with those in the C group,and lipid droplets were significantly reduced by Gegen QinLian Decoction and metformin.MDA and Fe2+levels were significantly increased and GSH levels were significantly decreased in the HepG2 M group compared with the levels in the C group(P<0.01),while all doses of Gegen QinLian Decoction and metformin significantly decreased MDA and Fe2+levels(P<0.01)and increased the GSH content(P<0.01,P<0.05).Nrf2,GSS,GPX4,and SLC7A11 mRNA expression levels in the GGQLT-H group,Nrf2,HO-1,and SLC7A11 in the GGQLT-L group,HO-1,SLC7A11,and GSS in the GGQLT-M group,and GSS,Nrf2,and HO-1 in the Met group were all significantly increased compared with the findings in the M group(P<0.01,P<0.05).ACSL4 mRNA expression levels were significantly decreased in the GGQLT-M and GGQLT-L groups and the Met group(P<0.01,P<0.05).Conclusions Gegen QinLian Decoction can improve NAFLD by inhibiting ferroptosis,and its mechanism may he related to regulation of the Nrf2/SLC7A 11/GPX4 signaling pathway.
3.Improvement effect of down-regulation of miR-208a on 5-FU resistance in colorectal cancer cells through targeting SFRP1 for mediating Wnt signaling pathway
Bingbing HU ; Kangning LUO ; Su PENG ; Yuzhong ZHOU ; Maoliang CHEN ; Changhua LIU
Journal of Jilin University(Medicine Edition) 2024;50(4):947-955
Objective:To discuss the effect of downregulating microRNA-208a(miR-208a)on the resistance of the colorectal cancer cells to 5-fluorouracil(5-FU),and to clarify its related molecular mechanism.Methods:Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of miR-208a and secreted frizzled-related protein 1(SFRP1)mRNA in the 5-FU-resistant colorectal cancer cell line HT-29/5-FU and its parent HT-29 cells.The HT-29/5-FU cells were transfected with miR-208a inhibitor plasmid and its negative control plasmid(inhibitor-NC),and SFRP1 small interfering RNA(si-SFRP1)and its negative control plasmid(si-NC),either separately or in combination,followed by treatment with 5-FU.The cells were divided into inhibitor-NC group,miR-208a inhibitor group,miR-208a inhibitor+si-NC group,and miR-208a inhibitor+si-SFRP1 group.MTT assay was used to detect the proliferation activities of the cells and the resistance indexes were calculated;Annexin V-FITC/PI double staining and flow cytometry were used to detect the apoptotic rates of the cells after treated with different concentrations of 5-FU;Western blotting method was used to detect the expression levels of SFRP1,β-catenin,P-glycoprotein(P-gp),and ATP-binding cassette subfamily B member 1(ABCB1)proteins in the cells in various groups;dual-luciferase reporter gene assay was used to validate the targeting relationship between miR-208a and SFRP1.Results:Compared with HT-29 cells,the expression level of miR-208a in the HT-29/5-FU cells was increased(P<0.05),and the expression level of SFRP1 mRNA was decreased(P<0.05).Compared with inhibitor-NC group,the proliferation activity of the cells in miR-208a inhibitor group was decreased(P<0.05),the resistance index was decreased,the apoptotic rate was increased(P<0.05),and the expression levels of β-catenin,P-gp,and ABCB1 proteins in the cells were decreased(P<0.05).The dual-luciferase reporter gene assay results showed that SFRP1 was a target gene of miR-208a and miR-208a could negatively regulate the expression of SFRP1.Compared with miR-208a inhibitor+si-NC group,the proliferation activity of the cells in miR-208a inhibitor+si-SFRP1 group was increased(P<0.05),the resistance index was increased,the apoptotic rate was decreased(P<0.05),and the expression levels of β-catenin,P-gp,and ABCB1 proteins in the cells were increased(P<0.05).Conclusion:Downregulation of miR-208a can improve the resistance of the HT-29/5-FU cells to 5-FU by targeting and upregulating the SFRP1 expression,thereby inhibiting the transmission of the Wnt signaling pathway.
4.Effect of hepatic arterial infusion chemotherapy combined with sintilimab and bevacizumab for treatment of advanced hepatocellular carcinoma with lenvatinib failure
Shuheng YANG ; Changhua JIANG ; Wanjun JIAN ; Qiaomu LUO
Chongqing Medicine 2024;53(21):3257-3263
Objective To explore the applicability,safety and effectiveness of hepatic arterial infusion chemotherapy(HAIC)combined with sintilimab and bevacizumab in the patients with intermediate and ad-vanced hepatocellular carcinoma(HCC)failed by lenvatinib treatment.Methods A total of 62 patients with intermediate and advanced liver cancer failed by lenvatinib treatment in this hospital from February 2023 to February 2024 were selected as the study subjects and divided into the HAIC group(n=13),HAIC+targeted therapy group(n=18)and HAIC+combined therapy group(n=31)according to different treatment regi-mens.The HAIC group only received the HAIC treatment,the HAIC+targeted therapy group adopted the HAIC+lenvatinib combined treatment and the HAIC+combined treatment group received the HAIC+sintil-imab and bevacizumab combined treatment.The objective remission rate(ORR),disease control rate(DCR),median progression-free survival time(mPFS),median overall survival time(mOS),carcinoembryonic antigen(CEA),vascular endothelial growth factor(VEGF),carbohydrate antigen 125(CA125)levels after treatment were observed in 3 groups,and the treatment related adverse reactions were recorded.The Kaplan-Meier method was used for conducting the survival analysis.Results According to RECIST1.1 criteria,ORR of the HAIC+combined treatment group was higher than that of the HAIC group and HAIC+targeted therapy group(35.5%vs.23.1%vs.22.2%),DCR was lower than that of the other two groups(83.8%vs.92.3%vs.88.9%),but the differences were not statistically significant and the differences were not statistically sig-nificant(P>0.05).mOS of the HAIC+combined treatment group was longer than that of the HAIC group and HAIC+targeted therapy group[18.1(95%CI:13.3-22.9)months vs.12.6(95%CI:9.0-16.2)months vs.15.9(95%CI:11.5-20.3)months].mPFS in the HAIC+combined treatment group was longer than that in the the HAIC group and HAIC+targeted therapy group[12.0(95%CI:9.4-14.6)months vs.9.7(95%CI:2.2-17.2)months vs.10.1(95%CI:8.3-11.9)months],and the differences were not statistically sig-nificant(P>0.05).The levels of CEA,VEGF and CA125 after treatment in 3 groups were decreased com-pared with before treatment,moreover the levels in the HAIC+combined treatment group was the lowest(P<0.05).There was no statistically significant difference in the incidence rate of adverse reactions among the three groups(P>0.05).Conclusion The HAIC combined with immunotherapy regimen is effective in the pa-tients with intermediate and advanced HCC failed by lenvatinib treatment,moreover which has high safety.
5.Expert consensus on the biosafety recommendation for arthropods of medical importance in field and laboratory
HE Changhua ; LUO Huanle ; YIN Feifei ; HAN Qian ; LIANG Lei ; SHI Yongxia ; YU Xuedong ; SUN Yi ; LIU Qiyong ; WANG Huanyu ; WANG Rong ; SHAN Chao ; DENG Fei ; YUAN Zhiming ; XIA Han
China Tropical Medicine 2024;24(2):119-
The emerging and re-emerging arthropod-borne infectious diseases pose a serious threat to global public health security. Field and laboratory studies of arthropods of medical importance are essential and critical for the prevention and control of arthropod-borne infectious diseases. Various institutions or universities in China have been conducting research in the field or laboratory study of arthropods of medical importance, but up to 2023, it is still lacking detailed biosafety guidelines or recommendations that can guide the related work for arthropods of medical importance. In order to proactively address potential biosafety issues in the field or laboratory activities related to arthropods of medical importance, improve the standardization of arthropod biosafety classification, operations, and protection, and ensure the safety of practitioners, an expert consensus on the biosafety recommendation of arthropods of medical importance in field and laboratory has been developed, aiming to guide the future work of arthropods and ensure the national biosafety and biosecurity of China.
6.Effect of Gegen Qinliantang-medicated Serum on Nonalcoholic Steatohepatitis Based on Nrf2/TXNIP Signaling Pathway
Yue WEI ; Junqing SHENG ; Ziwen CHENG ; Xiaoquan LUO ; Zhenzhen SONG ; Ailan WU ; Lan CAO ; Changhua ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(20):8-16
ObjectiveTo investigate the effect of Gegen Qinliantang (GGQLT)-medicated serum on free fatty acid (FFA)-induced nonalcoholic steatohepatitis (NASH) in vitro model of human hepatoma cells HepG2. MethodNASH model of HepG2 cells was established in vitro, and the cells were intervened with different volume fractions of GGQLT-medicated serum and resveratrol. Intracellular lipid deposition in each group was detected by oil red O staining, the level of reactive oxygen species (ROS) in each group were detected by flow cytometry, the levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), triglyceride (TG) and malondialdehyde (MDA) in each group were detected by kits. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to measure the mRNA expression levels of nuclear transcription factor (NF)E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), quinone oxidoreductase 1 (NQO1), Kelch-like epichlorohydrin-associated protein-1 (Keap1), NF-κB, thioredoxin interacting protein (TXNIP), interleukin-1β (IL-1β) in HepG2 cells of each group. The protein expression of Nrf2, TXNIP in cells of each group was detected by Western blot. ResultFFA induced large accumulation of intracellular lipids. Compared with the normal group, the activities of GSH-Px and SOD were significantly decreased (P<0.01) and the contents of TG, ROS and MDA were significantly increased (P<0.05, P<0.01) in the model group. Compared with the model group, all GGQLT groups and resveratrol group could elevate intracellular SOD activity to different degrees (P<0.05, P<0.01) and significantly reduce the levels of intracellular ROS and MDA (P<0.05, P<0.01), GGQLD high- and medium-dose groups and resveratrol group significantly elevated GSH-Px activity (P<0.01), GGQLD medium- and low-dose groups and resveratrol group significantly decreased TG content (P<0.05, P<0.01). Compared with the model group, GGQLT high- and medium-dose groups and resveratrol group could significantly upregulate the mRNA expression levels of Nrf2, HO-1 and NQO1 (P<0.01), all GGQLT groups and resveratrol group could significantly downregulate the TXNIP protein expression level, as well as significantly downregulate the mRNA expression levels of Keap1, NF-κB (P<0.05, P<0.01). Nrf2-siRNA transfection of cells revealed that Nrf2 expression was significantly downregulated (P<0.01) in the Nrf2-siRNA group of cells by comparing with NC-siRNA group at the corresponding dose of drugs, and the inhibitory effects of GGQLT and resveratrol on TXNIP, IL-1β were attenuated. ConclusionFFA induces the production of ROS and inflammatory factors in HepG2 cells, and GGQLT can improve the anti-inflammatory and antioxidant capacities of cells, and its mechanism may be related to the regulation of Nrf2/TXNIP signaling pathway, so as to improve NASH.
7.Layer-specific strain assessment of left ventricular systolic function in patients with bicuspid aortic valve
Xijun ZHANG ; Haohui ZHU ; Zhenhua WANG ; Changhua WEI ; Shuaiwei LUO ; Limin ZHU ; Jianjun YUAN
Chinese Journal of Ultrasonography 2019;28(1):21-26
Objective To quantitatively evaluate left ventricular ( LV ) systolic function in bicuspid aortic valve (BAV) using layer-specific strain ( LSS) . Methods Thirty BAV patients were divided into normal function (NF) group (10 cases) and non-normal function (N-NF) group (20 cases) based on aortic valvular lesion types ,and 20 healthy volunteers were taken as control group . Longitudinal strain( LS) and circumferential strain (CS) of three-layer myocardium and full thickness myocardium were assessed using layer-specific speckletracking imaging ,available by GE Vivid E9 and EchoPac workstation . Results There was no significant difference in left ventricular ejection fraction( LVEF) among the N-NF group ,NF group and control group ( P > 0 .05) ,all of them within the normal range[(63 .3 ± 7 .1)% ,(64 .6 ± 6 .2)% , ( 65 .3 ± 3 .9)% ] . It showed a gradient decrease from the endocardium to the epicardium in both control and BAV group . LS of endocardium ( LSendo) and LS of epicardium ( LSepi) in N-NF group and NF group were significantly reduced compared with those in control group ( P <0 .05) [ LSendo :( -21 .19 ± 3 .12)%vs ( -23 .06 ± 2 .07 )% vs ( -25 .53 ± 2 .51 )% ;LSepi:( -16 .08 ± 2 .68 )% vs ( -18 .85 ± 2 .12 )% vs ( -20 .72 ± 2 .28)% ] . Compared with control group ,there was no significant difference in NF group in CS of the three-layer myocardial and full-thickness myocardium as well as the LS of the whole medial myocardial layers and full-thickness ( P > 0 .05 ) . Compared with NF group [ CS :( -19 .57 ± 2 .9 )% vs ( -13 .43 ± 2 .19)% vs ( -20 .03 ± 3 .04)% ;LS :( -21 .38 ± 2 .05)% vs ( -18 .85 ± 2 .12)% vs ( -21 .09 ± 2 .03)% ] and control group[CS :( -21 .63 ± 3 .01)% vs ( -14 .34 ± 2 .55)% vs ( -21 .48 ± 2 .16)% ;LS :( -22 .18 ± 2 .30 )% vs ( -20 .72 ± 2 .28 )% vs ( -22 .89 ± 2 .30 )% ] , CS [ ( -16 .78 ± 3 .65 )% vs ( -11 .40 ± 3 .78 )% vs ( -15 .83 ± 2 .61 )% ] and LS [ ( -18 .34 ± 2 .85 )% vs ( -16 .08 ± 2 .68 )% vs ( -18 .51 ± 2 .86)% ] of middle myocardium ,epicardial myocardium and full-thickness myocardium in N-NF group were decreased significantly ( P < 0 .05) . Conclusions It is essential to maintain normal valvular function to prevent the progress of myocardial deterioration . LSendo and LSepi can be used to sensitively identify early left ventricular systolic dysfunction in BAV patients with normal LVEF .
8.Herbal Textual Research on Tibetan Medicine "Bangga"
Zhiming LIU ; Songyun QIN ; Jifeng ZHAO ; Xiang LIU ; Changhua WANG ; Zhiwei ZHANG ; Weizao LUO ; Guoyue ZHONG
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(4):636-643
This study was aimed to make clear the origin and clinical applications of the Tibetan medicine "Bangga".Based on the systematical consultation of the Tibetan medical literature documents and the Chinese version,such as The King's Medicine,The Four Medical Tantras,Jing Zhu Materia Medica,the herbal textual research was made on the name,based source,origin and harvesting season,function,indication and etc.of Tibetan medicine "Bangga".The results showed that Tibetan medicine "Bangga" comes from the whole dried plant of Aconitum naviculare Stapf or A.tanguticum (Maxim) Stapf of Ranunculaceae plants.It was concluded that the research on the origin of Tibetan medicine "Bangga" can provide a basis for the application and promotion of quality standards of "Bangga".
9.Case of enuresis after total hysterectomy.
Chinese Acupuncture & Moxibustion 2016;36(5):525-525
Acupuncture Therapy
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Adult
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Female
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Humans
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Hysterectomy
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adverse effects
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Nocturnal Enuresis
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etiology
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therapy
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Ovary
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surgery
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Postoperative Complications
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etiology
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therapy
10.A cross-sectional study of mental disorders in Ximeng Wa Autonomous County of Yunnan Province
Wenxing LU ; Yueqin HUNAG ; Chuanlin LUO ; Hongguang CHEN ; Xinghua XIANG ; Zhaorui LIU ; Jianfen LI ; Ning JI ; Changhua HU ; Ping HUANG ; Huafen YUAN ; Junshan SHA ; Banglei LIAO
Chinese Mental Health Journal 2015;(11):817-825
Objective:To describe the epidemiological characteristics of mental disorders in Ximeng Wa Au-tonomous County and explore psychosocial risk factors of mental disorders. Methods:Two thousand three hundred and eighty one residents aged 1 8 years and over were sampled using multistage sampling in Ximeng Wa Autono-mous County in 2013. All respondents were investigated by face-to-face interview. Mental disorders were screened out by using the General Health Questionnaire (GHQ)and diagnosed according to the International Classification of Diseases Checklist (ICD-10-Checklist)criteria. Results:Life time prevalence of any mental disorder was 19. 86%(419/2110). The lifetime prevalence rates of substance use disorder,anxiety disorder,insomnia,mood disorder, schizophrenia were 12. 99%(274/2110),6. 30%(133/2110),2. 94%(62/2110),2. 32%(49/2110)and 1. 00%(21/2110)respectively. Male (OR=0. 43),older age (35 -49 years,OR=1. 78;50 -64 years,OR=2. 59;≥65 years,OR=3. 5 1 ),unmarried and other marital status (OR=0. 3 1 ),non-Wa and non-Lahu ethnic groups (OR=0. 29)were associated with neurotic,stress-related and somatoform disorders. Male (OR=2. 41),older age (35 -49 years,OR=2. 29;50-64 years,OR=3. 20;≥65 years,OR=4. 58),non-farmer and non-self-employed occupation (OR=0. 41),and non-Wa and non-Lahu ethnic groups (OR=0. 32)were associated with psychoactive substance use disorder. Male (OR =0. 35 ) and order age (≥65 years,OR =3. 05 ) were associated with mood disorders. Conclusion:Lifetime prevalence of any mental disorder,substance use disorders and anxiety disorders are high in Ximeng Wa Autonomous County. Measures should be strengthened against prevalence of mental disorders in ethnic minority areas.

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