1.Analysis of Chronic Gouty Arthritis Animal Models Based on Clinical Characteristics of Traditional Chinese and Western Medicine
Yan XIAO ; Siyuan LIN ; Fan YANG ; Qianglong CHEN ; Xiaohua CHEN ; Meiling WANG ; Zhen ZHANG ; Jiali LUO ; Youxin SU ; Jiemei GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):84-92
ObjectiveBased on the clinical characteristics of chronic gouty arthritis (CGA) in both traditional Chinese and western medicine, this study aims to systematically evaluate the clinical concordance of existing CGA animal models, providing recommendations for establishing animal models that align with the pathological characteristics of CGA and the manifestations of traditional Chinese medicine syndromes. MethodsBy comprehensively retrieving Chinese and international databases such as China National Knowledge Infrastructure, Wanfang, VIP Chinese Science and Technology Periodical Database (VIP), and PubMed, all relevant literature on CGA animal models was collected. Based on the guidelines, the diagnostic criteria of both traditional Chinese and western medicine were summarized and organized. The evaluation indicators for the CGA model were constructed with reference to existing evaluation modes, and the CGA animal models were analyzed to systematically evaluate the clinical concordance of existing models. ResultsThe current methods used to construct CGA animal models mainly include monosodium urate crystal induction, high-protein diet induction (poultry lack urate oxidase), and high-fat diet combined with urate oxidase inhibitors and joint injection. Based on 11 pieces of included literature, the traditional Chinese and western medicine scoring data of each model were extracted, and the average scoring values of all models were ultimately calculated. The results show that the average clinical concordances of existing CGA animal models in both traditional Chinese and western medicine are 43.33% and 64.44%, respectively. Among them, the model with the highest clinical concordance rate is the one with a high-fat diet combined with potassium oxonate to induce hyperuricemia plus joint injection, achieving 83.33% clinical concordance in western medicine and 60% in traditional Chinese medicine. This model aligns well with the pathogenic characteristics and pathological changes of clinical CGA. ConclusionAlthough current CGA animal models can simulate some pathological characteristics of CGA, they struggle to comprehensively reflect the complex pathological processes of CGA and the characteristics of traditional Chinese medicine syndromes. Therefore, in the future, it is necessary to establish the CGA animal models that incorporate the clinical disease and syndrome characteristics of traditional Chinese and western medicine and formulate the uniform model evaluation criteria, providing more precise tools for CGA mechanism research and the development of traditional Chinese medicine.
2.Mechanism of Wumeiwan on Inhibiting Fatty Acid Metabolism Reprogramming in Prevention and Treatment of Colorectal Cancer Based on Multi-omics Analysis
Gang XIAO ; Shusen YANG ; Mingming SI ; Yanyan YANG ; Hailiang WEI ; Shuguang YAN ; Hui LUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):21-30
ObjectiveTo investigate the mechanism by which Wumeiwan suppresses the development and progression of colorectal cancer(CRC) through the regulation of fatty acid metabolic reprogramming, thereby providing new experimental evidence for the prevention and treatment of CRC. MethodsA total of 120 C57BL/6 mice were randomly divided into the blank group, model group, Wumeiwan high-, medium-, and low-dose groups(54, 27, 13.5 g·kg-1), and the mesalazine group(0.01 g·kg-1), with 20 mice in each group. Except for the blank group, all mice were subjected to azoxymethane(AOM)/dextran sulfate sodium(DSS) treatment to establish an inflammation-associated CRC model. One week after AOM injection, mice in the treatment groups received intragastric administration of the designated drugs, while the blank and model groups received an equal volume of purified water, continuing until 20 d after the intervention endpoint. Hematoxylin-eosin(HE) staining was used to observe colonic histopathological alterations, and immunohistochemistry for vascular endothelial growth factor(VEGF) was performed to evaluate neovascularization and tumor invasion. Metabolomics combined with Kyoto Encyclopedia of Genes and Genomes(KEGG) and metabolite set enrichment analysis(MSEA) was applied to identify key CRC-related metabolic pathways, which were further validated by transcriptomic Gene Ontology(GO) enrichment and gene heatmap analysis. Subsequently, Western blot was performed to determine the expression levels of core proteins in these pathways, and immunofluorescence was used to analyze their localization and co-expression patterns in tissues, thereby elucidating the mechanism of Wumeiwan from multiple biological dimensions. ResultsCompared with the blank group, mice in the model group exhibited a significant decrease in body weight and a significant increase in the disease activity index(DAI) score(P<0.05), with pronounced colonic mucosal damage accompanied by aggravated tumor invasion. Compared with the model group, Wumeiwan intervention markedly improved body weight loss and reduced DAI score, attenuated mucosal injury, and significantly decreased VEGF expression level(P<0.05). Multi-omics analysis revealed that differential metabolites and genes across groups were commonly enriched in fatty acid metabolism, fatty acid biosynthesis, and other lipid-related pathways. Relative to the blank group, the model group showed significant upregulation levels of fatty acid synthesis-related genes, including sterol regulatory element-binding protein 1(SREBP1), fatty acid synthase(FASN), stearoyl-CoA desaturase 1(SCD1), as well as saturated fatty acids(P<0.05). Compared with the model group, treatment with Wumeiwan significantly reduced the expression of key genes involved in fatty acid metabolic pathways, including SREBP1, FASN, and SCD1(P<0.05). Western blot results further confirmed that proteins in this pathway were significantly elevated in the model group, whereas they were markedly downregulated following Wumeiwan treatment(P<0.05). Immunofluorescence analysis demonstrated enhanced co-localization of SREBP1 with the cancer-associated fibroblast(CAF) marker α-smooth muscle actin(SMA) in the model group, whereas this co-localization signal was attenuated after Wumeiwan intervention(P<0.05). ConclusionWumeiwan can improve survival outcomes and alleviate colonic pathological damage in CRC mice, its therapeutic mechanism may be closely associated with the regulation of fatty acid metabolic reprogramming mediated by the SREBP1/FASN/SCD1 signaling pathway.
3.Comparative analysis of the characteristics of imported malaria cases in Nanning City in 2024 and the same period of the previous year
Shu-lin WEI ; Zhi-qiang QU ; Yuan-yuan LUO ; Yan-cui HUANG ; Shu-qin DIAO ; Xue LI ; Sheng-long YANG ; Xiao-yu HUANG ; Mi-fang LUO
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):81-84
Objective To investigate the epidemiological characteristics of malaria and provide a basis for developing improved prevention and control measures. Methods Data were obtained from the Chinese Disease Prevention and Control Information System. Malaria surveillance data for Nanning City from January 1,2023, to December 31,2024, were exported from the Infectious Disease Reporting Information Management Subsystem. The characteristics of the two groups of malaria cases were compared. Results A total of 103 imported malaria cases were reported in Nanning City in 2024, representing a 38.32% decrease compared with the same period of the previous year. No statistically significant difference were observed between cases reported in 2023 and 2024 in terms of average age, gender ratio, proportion of parasite species, and monthly reporting distribution;however, statistically significant differences were found in the proportion of reporting areas and current residence areas(χ2= 13.572 and 10.355, respectively; P = 0.001 and 0.035, respectively). The proportion of cases reported in Shanglin County and the proportion of cases residing in Shanglin County were both lower than those during the same period of the previous year. Conclusions The high aggregation of imported malaria cases in Nanning City has decreased. Medical institutions in areas other than Shanglin County should strengthen their vigilance against malaria.
4.Diagnostic value of novel inflammatory markers related to routine blood tests in elderly patients with chronic cardiovascular disease complicated with frailty
Xing-Man FAN ; Yan-Yan LI ; Qiong-Yi HE ; Wei-Na LUO ; Xiao-Hua LAN ; Kai-Jie ZHANG ; Meng WANG ; Xiang-Ren KONG ; Hai-Tao ZHANG
Medical Journal of Chinese People's Liberation Army 2025;50(3):301-308
Objective To investigate the diagnostic value of 4 novel inflammatory markers related to routine blood tests,namely neutrophil-to-lymphocyte ratio(NLR),red blood cell distribution width(RDW),hemoglobin-to-RDW ratio(HRR)and systemic immune-inflammation index(SII),in elderly patients with chronic cardiovascular disease(CVD)complicated with frailty.Methods Retrospectively analyze 110 patients with chronic stable CVD who were hospitalized in the cadre ward of cardiovascular medicine at the Air Force Characteristic Medical Center from January 2022 to June 2023.According to the assessment results of the Fried scale,they were divided into three groups:non-frailty group(Fried score=0,n=30),the pre-frailty group(Fried score 1 or 2,n=40)and frailty group(Fried score≥3,n=40).The differences in general information,the impairment rate of daily living activities,miniature nutritional assessment-short form(MNA-SF)scores,mini-mental state examination(MMSE)scores,and the indicators such as NLR,RDW,HRR,and SII among the three groups were compared.Spearman rank correlation was used to analyze the correlation between NLR,RDW,HRR,SII and frailty scores as well as each frailty indicator.Multivariate logistic regression analysis was performed to identify the independent risk factors for frailty in elderly patients with chronic CVD,and the receiver operating characteristic(ROC)curve was used to assess the clinical diagnostic value of NLR and HRR in elderly patients with chronic CVD complicated with frailty.Results Compared with non-frailty group and pre-frailty group,patients in frailty group were older,with higher impaired rates of daily living activities,NLR,RDW,and SII,and lower MNA-SF scores,MMSE scores,and HRR,and differences were statistically significant(P<0.05).Spearman rank correlation analysis showed that the frailty score was positively correlated with NLR(rs=0.354,P<0.001),and RDW(rs=0.448,P<0.001),negatively correlated with HRR(rs=-0.232,P=0.024),and had no significant correlation with SII(rs=0.144,P=0.167).Further analysis of the correlation between the above novel inflammatory markers and the 5 components of frailty showed that NLR was positively correlated with fatigue(rs=0.228,P=0.017),slowed walking speed(rs=0.299,P<0.001),and low physical function(rs=0.319,P<0.001);RDW was positively correlated with decreased grip strength(rs=0.321,P<0.001),slowed walking speed(rs=0.422,P<0.001),and low physical function(rs=0.246,P=0.001);and HRR was negatively correlated with slowed walking speed(rs=-0.230,P=0.025),and low physical function(rs=-0.299,P=0.003).Multivariate logistic regression analysis showed that MNA-SF score(OR=0.577,95%CI 0.342-0.973)was an independent protective factor for pre-frailty in elderly patients with chronic CVD(P<0.05);NLR(OR=7.866,95%CI 1.101-56.185)was an independent risk factor for frailty,while HRR(OR=0.344,95%CI 0.120-0.983)and MNA-SF score(OR=0.292,95%CI 0.146-0.580)were independent protective factors for frailty in elderly CVD patients(P<0.05).The area under the ROC curve of NLR and HRR for diagnosing frailty in elderly patients with chronic CVD were 0.778 and 0.749,respectively.Conclusion NLR and HRR have high clinical diagnostic value for frailty in elderly patients with chronic CVD,and are expected to become effective inflammatory markers for screening elderly patients with chronic CVD complicated with frailty.
5.Effect of Zuogui Pill combined with western medicine in treatment of gestational diabetes mellitus with qi and yin deficiency syndrome
Ling ZENG ; Yan XIAO ; Tao YANG ; Shi LUO
Journal of Clinical Medicine in Practice 2025;29(4):38-43
Objective To observe the clinical effect of Zuogui Pill combined with western medi-cine in treatment of gestational diabetes mellitus(GDM)with qi and yin deficiency syndrome.Meth-ods A total of 92 GDM patients with qi and yin deficiency syndrome from the Second Affiliated Hos-pital of Guizhou University of Traditional Chinese Medicine between January 2022 and October 2023 were enrolled and randomly divided into study group and control group,with 46 patients in each group.The control group received western medicine treatment,while the study group received Zuogui Pill combined with western medicine treatment.Both groups were treated for 4 weeks.The treatment effects,as well as the levels of glycolipid indicators[total cholesterol(TC),triglyceride(TG),fast-ing plasma glucose(FPG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and glycated hemoglobin(HbA1c)],insulin resistance indicators[fasting in-sulin(FINS),homeostasis model assessment of β-cell function(HOMA-β),and homeostasis model assessment of insulin resistance(HOMA-IR)],inflammatory and stress factors[serum amyloid A(SAA),interleukin-6(IL-6),malondialdehyde(MDA),and reactive oxygen species(ROS)],serum microRNA(miR)-21 and miR-149 levels,and occurrence of adverse pregnancy outcomes were compared be-tween the two groups before and after treatment.Results After 4 weeks of treatment,the total ef-fective rate was higher in the study group than that in the control group(P<0.05).After treat-ment,the levels of FPG,HbA1c,TC,LDL-C,and TG were lower,and the levels of HDL-C were higher in both groups than before treatment,and the levels of FPG,HbA1c,TC,LDL-C in the study group were lower than those in the control group,and the level of HDL-C was higher in the study group than that in the control group(P<0.05).After treatment,the levels of FINS and HOMA-IR were lower in both groups than before treatment,and their levels in the study group were lower than those in the control group;the levels of HOMA-β were higher in both groups than before treatment,and its level in the study group was higher than that in the control group(P<0.05).After treat-ment,the levels of SAA,IL-6,MDA,and ROS were lower in both groups than before treatment,and their levels in the study group were lower than those in the control group(P<0.05).Before treatment,there were no statistically significant differences in the levels of serum miR-21 and miR-149 between the two groups(P>0.05);after treatment,the levels of serum miR-21 and miR-149 were lower in both groups than before treatment,and their levels in the study group were lower than those in the control group(P<0.05).Before treatment,the traditional Chinese medicine syndrome score was(8.12±1.31)in the study group and(7.86±1.28)in the control group,with no statisti-cally significant difference between the two groups(P>0.05);after treatment,the traditional Chi-nese medicine syndrome score was(3.31±0.46)in the study group,which was lower than(4.57±0.59)in the control group(t=11.423,P<0.05).Compared with the control group,the incidence of adverse pregnancy outcomes was lower in the study group(P<0.05).Conclusion Zuogui Pill combined with western medicine can effectively improve glycolipid metabolism and insulin resistance in GDM patients and reduce the incidence of adverse pregnancy outcomes.
6.Ursodeoxycholic acid inhibits the uptake of cystine through SLC7A11 and impairs de novo synthesis of glutathione
Fu'an XIE ; Yujia NIU ; Xiaobing CHEN ; Xu KONG ; Guangting YAN ; Aobo ZHUANG ; Xi LI ; Lanlan LIAN ; Dongmei QIN ; Quan ZHANG ; Ruyi ZHANG ; Kunrong YANG ; Xiaogang XIA ; Kun CHEN ; Mengmeng XIAO ; Chunkang YANG ; Ting WU ; Ye SHEN ; Chundong YU ; Chenghua LUO ; Shu-Hai LIN ; Wengang LI
Journal of Pharmaceutical Analysis 2025;15(1):189-207
Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.
7.Quality evaluation of"Sangdi"based on HPLC fingerprints combined with chemometrics
Ping LIU ; Shi-ying LUO ; Meng-jia LI ; Xiao-yan TAN ; Jian-bin SUN ; Wei-zao LUO ; Ce TANG ; Yi ZHANG
Chinese Traditional Patent Medicine 2025;47(1):14-21
AIM To evaluate the quality of Tibetan medicine"Sangdi"based on HPLC fingerprints combined with chemometrics.METHODS The analysis was performed on a 30 ℃ thermostatic Welch Ultimate AQ-C18 column(250 mm × 4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2%phosphoric acid flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 245 nm,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were performed,the contents of gentiopicroside,sweroside,mangiferin,isoorientin,8-hydroxy-1,3,5-trimethoxyxanthone(R2)and 1,8-dihydroxy-3,7-dimethoxyxanthone(R3)were determined.RESULTS There were 18 common peaks in the fingerprints for 15 batches of samples with the similarities of more than 0.90.Six constituents showed good linear relationships within their own ranges(R 2 ≥ 0.999 2),whose average recoveries were 96.93%-103.58%with the RSDs of 0.82%-2.9%.Various batches of samples were clustered into 2 categories,4 principal components demonstrated the accumulative variance contribution rate of 86.404%,mangiferin,gentiopicroside and isoorientin were taken as quality difference markers.CONCLUSION This stable,reliable and reproducibe method can provide a reference for the comprehensive quality evaluation of"Sangdi".
8.Inhibitory effects of Shuyu Pills combined with everolimus on TGF-β1-induced epithelial-mesenchymal transition in triple-negative breast cancer cells
Xiao-shan LUO ; Su XIE ; Dou-dou FENG ; Yan-yun MENG ; Jing-zhe ZHAO ; Qing XIE ; Xiang-li LING
Chinese Traditional Patent Medicine 2025;47(7):2190-2197
AIM To investigate the effects of Shuyu Pills combined with evolimus on the epithelial mesenchymal transformation of triple negative breast cancer cells 4T1 and MDA-MB-231 induced by TGF-β1.METHODS The 4T1 and MDA-MB-231 cells were divided into the blank group and the induction group to induce the epithelial mesenchymal transformation with TGF-β1 cytokine treatment,followed by the assignment into the model group,the Shuyu Pills group,the everolimus group and the Shuyu Pills combined with everolimus group.CCK8 method,plate cloning method,cell scratch test and Transewll test were used to detect the proliferation,cloning formation,migration and invasion ability of the cells whose expressions of E-cadherin,N-cadherin,Vimentin,MMP9,MMP2 and pathway proteins PTEN,PI3K,Akt and mTOR were detected by Western blot.RESULTS Compared with the blank group,the induction group displayed a cell morphological change from epithelioid to stromal,decreased expression of E-cadherin protein(P<0.01);and increased protein expressions of N-cadherin and Vimentin(P<0.05).Compared with the model group,each group intervened with the medicine displayed decreased proliferation,clone formation,migration and invasion ability of both kinds of cells(P<0.01);increased protein expressions of PTEN and E-cadherin(P<0.05,P<0.01);and decreased protein expressions of PI3K,Akt,mTOR,N-cadherin,Vimentin,MMP9 and MMP2(P<0.05,P<0.01);and more significantly in the Shuyu Pills combined with evolimus group(P<0.05,P<0.01).CONCLUSION With a more ideal effect than the single uses in inhibiting the TGF-β1-induced epithelial mesenchymal transformation of triple-negative breast cancer cells,the combination use of Shuyu Pills and everolimus may work through the regulation of PI3K/Akt/mTOR signaling pathway.
9.Identifying High-Risk Areas for Type 2 Diabetes Mellitus Mortality in Guangdong, China: Spatiotemporal Clustering and Socioenvironmental Determinants.
Hai Ming LUO ; Wen Biao HU ; Yan Jun XU ; Xue Yan ZHENG ; Qun HE ; Lu LYU ; Rui Lin MENG ; Xiao Jun XU ; Fei ZOU
Biomedical and Environmental Sciences 2025;38(5):585-597
OBJECTIVE:
This study aimed to identify high-risk areas for type 2 diabetes mellitus (T2DM) mortality to provide relevant evidence for interventions in emerging economies.
METHODS:
Empirical Bayesian Kriging and a discrete Poisson space-time scan statistic were applied to identify the spatiotemporal clusters of T2DM mortality. The relationships between economic factors, air pollutants, and the mortality risk of T2DM were assessed using regression analysis and the Poisson Log-linear Model.
RESULTS:
A coastal district in East Guangdong, China, had the highest risk (Relative Risk [RR] = 4.58, P < 0.01), followed by the 10 coastal districts/counties in West Guangdong, China (RR = 2.88, P < 0.01). The coastal county in the Pearl River Delta, China (RR = 2.24, P < 0.01), had the third-highest risk. The remaining risk areas were two coastal counties in East Guangdong, 16 districts/counties in the Pearl River Delta, and two counties in North Guangdong, China. Mortality due to T2DM was associated with gross domestic product per capita (GDP per capita). In pilot assessments, T2DM mortality was significantly associated with carbon monoxide.
CONCLUSION
High mortality from T2DM occurred in the coastal areas of East and West Guangdong, especially where the economy was progressing towards the upper middle-income level.
Diabetes Mellitus, Type 2/epidemiology*
;
China/epidemiology*
;
Humans
;
Risk Factors
;
Spatio-Temporal Analysis
;
Air Pollutants/analysis*
;
Socioeconomic Factors
;
Bayes Theorem
;
Female
;
Male
;
Middle Aged
10.Exploration of New Susceptible Genes associated with Non-Alcoholic Fatty Liver Disease among Children with Obesity Using Whole Exome Sequencing.
Xiong Feng PAN ; Cai Lian WEI ; Jia You LUO ; Jun Xia YAN ; Xiang XIAO ; Jie WANG ; Yan ZHONG ; Mi Yang LUO
Biomedical and Environmental Sciences 2025;38(6):727-739
OBJECTIVE:
This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity.
METHODS:
We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set).
RESULTS:
In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes.
CONCLUSION
In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans
;
Non-alcoholic Fatty Liver Disease/genetics*
;
Child
;
Male
;
Female
;
Genetic Predisposition to Disease
;
Case-Control Studies
;
Exome Sequencing
;
Adolescent
;
Polymorphism, Single Nucleotide
;
Obesity/complications*
;
Pediatric Obesity/complications*
;
China


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