1.Characteristics of mitochondrial translational initiation factor 2 gene methylation and its association with the development of hepatocellular carcinoma
Huajie XIE ; Kai CHANG ; Yanyan WANG ; Wanlin NA ; Huan CAI ; Xia LIU ; Zhongyong JIANG ; Zonghai HU ; Yuan LIU
Journal of Clinical Hepatology 2025;41(2):284-291
ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 (MTIF2) gene methylation and its association with the development and progression of hepatocellular carcinoma (HCC). MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples, including survival curve analysis, methylation signature analysis, the association of tumor signaling pathways, and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level, and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races, ethnicities, BMI levels, and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation (hazard ratio [HR]=0.492, P<0.001), while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels (P>0.05). The methylation profile of the MTIF2 gene based on different ages, sexes, BMI levels, races, ethnicities, and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age, and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population (P<0.05); the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ (P<0.05). Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population (P<0.05). ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.
2.Construction and empirical study of selection system for drug directory of county-level medical community based on multi-criteria decision analysis
Yinan GUO ; Xiuheng YU ; Yuqing XIE ; Shixin XIANG ; Huan LIN ; Youqi LONG ; Yu ZHAO
China Pharmacy 2025;36(8):914-919
OBJECTIVE To explore the construction of selection system for drug directory of the county-level medical community based on multi-criteria decision analysis, and provide decision-making basis for the selection of drug directory of medical community. METHODS Taking county-level medical community in Chongqing as an example,Delphi method and analytic hierarchy process were employed to construct the selection system for drug directory of the county-level medical community. Selected drugs were quantitatively scored based on the constructed index system, and the drug directory was selected according to the drug’s comprehensive score. The implementation effect of the directory was then evaluated through questionnaire surveys one year after the implementation of the directory. RESULTS The expert authority coefficients of the two rounds of consultation were> 0.8, with Kendall’s W values of 0.213 and 0.196, respectively (P<0.001). Finally, the selection system for drug directory of the medical community was determined to include five evaluation dimensions: safety, effectiveness, economy, accessibility, and innovation, along with eight evaluation indicators. In the drug directory selected according to the above method, the proportions of centrally procured drugs, medical insurance drugs, and essential drugs had all increased compared to before the selection; the comprehensive scores of chemical drugs ranged from 50.25 to 96.31 scores, and the proportion of drugs scoring between 70 and 100 scores had increased from 78.06% before selection to 85.82%. Among them, antiparasitic drugs had the highest comprehensive scores, while drugs for the digestive tract and metabolism were the most numerous. The evaluation scores of each indicator and the comprehensive scores of drugs in the drug directory after the selection process increased significantly than before selection (P< 0.05). CONCLUSIONS The selection system for drug directory of the county-level medical community constructed in this study is scientific, objective and operable. This process facilitates the promotion of standardized and unified management of drugs in the medical community.
3.Clinical features of recompensation in autoimmune hepatitis-related decompensated cirrhosis and related predictive factors
Xiaolong LU ; Lin HAN ; Huan XIE ; Lilong YAN ; Xuemei MA ; Dongyan LIU ; Xun LI ; Qingsheng LIANG ; Zhengsheng ZOU ; Caizhe GU ; Ying SUN
Journal of Clinical Hepatology 2025;41(9):1808-1817
ObjectiveTo investigate the clinical features and outcomes of recompensation in patients with autoimmune hepatitis (AIH)-related decompensated cirrhosis, to identify independent predictive factors, and to construct a nomogram prediction model for the probability of recompensation. MethodsA retrospective cohort study was conducted among the adult patients with AIH-related decompensated cirrhosis who were admitted to The Fifth Medical Center of PLA General Hospital from January 2015 to August 2023 (n=211). The primary endpoint was achievement of recompensation, and the secondary endpoint was liver-related death or liver transplantation. According to the outcome of the patients at the end of the follow-up, the patients were divided into the recompensation group (n=16) and the persistent decompensation group(n=150).The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data with heterogeneity of variance; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups; the Kaplan-Meier method was used for survival analysis; the Cox proportional-hazards regression model was used to identify independent predictive factors, and a nomogram model was constructed and validated. ResultsA total of 211 patients were enrolled, with a median age of 55.0 years and a median follow-up time of 44.0 months, and female patients accounted for 87.2%. Among the 211 patients, 61 (with a cumulative proportion of 35.5%) achieved recompensation. Compared with the persistent decompensation group, the recompensation group had significantly higher white blood cell count, platelet count (PLT), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid, prothrombin time, international normalized ratio (INR), SMA positive rate, Model for End-Stage Liver Disease (MELD) score, Child-Pugh score, and rate of use of glucocorticoids (all P0.05), as well as significantly lower age at baseline, number of complications, and death/liver transplantation rate (all P0.05). At 3 and 12 months after treatment, the recompensation group had continuous improvements in AST, TBil, INR, IgG, MELD score, and Child-Pugh score, which were significantly lower than the values in the persistent decompensation group (all P0.05), alongside with continuous increases in PLT and albumin, which were significantly higher than the values in the persistent decompensation group (P0.05). The multivariate Cox regression analysis showed that baseline ALT (hazard ratio [HR]=1.067, 95% confidence interval [CI]: 1.010 — 1.127, P=0.021), IgG (HR=0.463,95%CI:0.258 — 0.833, P=0.010), SMA positivity (HR=3.122,95%CI:1.768 — 5.515, P0.001), and glucocorticoid therapy (HR=20.651,95%CI:8.744 — 48.770, P0.001) were independent predictive factors for recompensation, and the nomogram model based on these predictive factors showed excellent predictive performance (C-index=0.87,95%CI:0.84 — 0.90). ConclusionAchieving recompensation significantly improves clinical outcomes in patients with AIH-related decompensated cirrhosis. Baseline SMA positivity, a high level of ALT, a low level of IgG, and corticosteroid therapy are independent predictive factors for recompensation. The predictive model constructed based on these factors can provide a basis for decision-making in individualized clinical management.
4.Pathogenetic investigation of an outbreak of upper respiratory tract infection in a kindergarten in Baiyin City, Gansu Province
Shu LIANG ; Hui ZHANG ; Zhibo XIE ; Genxia GAO ; Biao WANG ; Miao WANG ; Huan WEI ; Xiaoshu ZHANG
Chinese Journal of Preventive Medicine 2024;58(10):1593-1597
This study focuses on the cases(mainly characterized by respiratory symptoms such as cough, runny nose, fever, sore throat, and nasal congestion)of an outbreak of upper respiratory tract infections in a kindergarten in Jingyuan County, Baiyin City, Gansu Province, in May 2023. The epidemiological data were collected, and pharyngeal swab specimens were also obtained from the patients. The specimens of the research participants were subjected to respiratory multi-pathogen testing, and the positive specimens were further analyzed by sequencing the second hypervariable region (HRV2) of the G gene of respiratory syncytial virus (RSV) and constructing a phylogenetic tree. A total of 90 patients were collected, with an incidence rate of 22.84% (90/394), and the highest incidence was observed in the junior class group at 29.55%. Among the 17 pharyngeal swab specimens collected, 16 specimens were identified with the A subtype of respiratory syncytial virus. Sequencing analysis confirmed that it was the A subtype ON1 genotype. Based on the aforementioned testing results, it can be concluded that the current epidemic was primarily caused by infection with the A subtype of respiratory syncytial virus. Following the implementation of intervention measures, the epidemic has been effectively controlled.
5.circNHSL1 inhibits proliferation and promotes apoptosis of human breast cancer cell line through regulating miR-125b-5p/HMGB3 axis
Basic & Clinical Medicine 2024;44(12):1678-1684
Objective To investigate the regulation of miR-125b-5p/HMGB3 axis by circNHSL1 on the biological behavior of breast cancer cells.Methods The breast cancer cells T47D were divided into si-NC group,si-circNH-SL1 group,miR-NC group,and miR-125b-5p mimic group and si-circNHSL1+miR-125b-5p inhibitor group.The expression of circNHSL1 and miR-125b-5p in breast cancer tissues and adjacent tissues was determined using RT-qPCR.Western blot was conducted to detect the protein expression of high mobility group protein 3(HMGB3).Dual luciferase reporter gene assay was used to confirm the interaction between circNHSL1 and miR-125b-5p,miR-125b-5p and HMGB3.The proliferation rate was measured by CCK-8 method;the colony formation assay was applied to detect the colony formation numbers;flow cytometry was used to measure cell apoptosis rate;Transwell assay was used to detect the numbers of migratory and invasive cells.Results Compared with adjacent tissues,cir-cNHSL1 and HMGB3 expression in breast cancer tissues was significantly increased(P<0.05),while the expres-sion of miR-125b-5p was significantly decreased(P<0.05).miR-125b-5p directly bound to circNHSL1 and HMGB3,respectively.The circNHSL1 knockdown down regulated circNHSL1 and HMGB3 expression and upregu-lated miR-125b-5p expression in T47D cells(P<0.05).After transfection with miR-125b-5p mimic,miR-125b-5p expression was up-regulated and HMGB3 expression was down-regulated(P<0.05).Moreover,transfection of miR-125b-5p inhibitor reversed the effect of circNHSL1 silencing on the expression of miR-125b-5p and HMGB3.Low expression of circNHSL1 or high expression of miR-125b-5p increased the cell inhibition rate,colony formation and apoptosis rate of T47D and decreased the number of migratory and invasive cells(P<0.05).Moreover,trans-fection of miR-125b-5p inhibitor saved the effect of circNHSL1 silencing on cell phenotypes(P<0.05).Conclusions Interfering with circNHSL1 might promote cell apoptosis and inhibit cell proliferation,migration and invasion in breast cancer cell by up-regulating the miR-125b-5p/HMGB3 axis.
6.Effects of Chaihuang Yishen Granule on renal fibrosis in unilateral ureteral obstruction mice and its mechanisms
Ke-Huan XIE ; Hao-Jun ZHANG ; Rui-Zhi TAN ; Hong-Wei SU ; Peng LIU ; Ping LI ; Li WANG
Medical Journal of Chinese People's Liberation Army 2024;49(7):804-813
Objective To investigate the effects of Chaihuang Yishen Granules on renal fibrosis in unilateral ureteral obstruction(UUO)mice and its underlying mechanisms.Methods Twenty-four 8-week-old male C57BL/6 mice were randomly divided into control group,model group,and low and high dose groups of Chaihuang Yishen Granules(6 in each group).In control group,only right kidney ureter was exposed and dissected.In model group,the UUO animal model was established by UUO.In low and high dose groups,mice were administered intragastrically at doses of 3.8 and 7.6 g/kg of Chaihuang Yishen Granules respectively,following the model group's method to establish the UUO model.After 7 days,the mice were euthanized and renal samples were collected.HE and Masson staining were used to observe pathological changes and fibrosis degree of the kidneys in each group,Sirius red staining was used to observe collagen deposition.The expression levels of α-smooth muscle actin(α-SMA),fibronectin(FN),type Ⅰ collagen(Col-Ⅰ),glycogen synthase kinase 3β(GSK-3β),and β-catenin related proteins were detected using Western blotting.Changes in A33 and GSK-3β,β-catenin mRNA levels were measured by RT-PCR.Additionally,a normal transformed C3H mouse kidney-1(TCMK1)was used as control(normal group);an in vitro fibrosis model was established using TCMK1 stimulated with Transforming Growth Factor-β(TGF-β);and an in vitro drug model was established using TCMK1 treated with serum containing Chaihuang Yishen Granules.A33 was overexpressed in TCMK1 cells using a transfection with an A33 overexpression plasmid,and changes in fibrosis-related indicators and the expression of A33 and GSK-3β,β-catenin mRNA were observed.Results RT-PCR results showed that,compared with control group,A33 level was significantly increased in model group,while it was significantly reduced in both low and high dose groups of Chaihuang Yishen Granules(P<0.05).Western blotting showed that the expression levels of fibrosis-related factors such as α-SMA,FN,Col-Ⅰ in model group were significantly higher than those in control group(P<0.05);while compared with model group,the expression levels of α-SMA,FN,Col-Ⅰ in low and high dose groups of Chaihuang Yishen Granules were significantly lower(P<0.05).HE,Masson,immunohistochemical staining results showed that model group had severe kidney structural damage,significant increase in collagen deposition,and significantly higher expression levels of GSK-3β and β-catenin proteins compared with those in control group(P<0.01).In contrast,low and high dose groups of Chaihuang Yishen Granules had good kidney structure,significant improvement in kidney damage and fibrosis,and significantly lower expression levels of GSK-3β and β-catenin proteins compared with those in model group(P<0.05).In vitro experiment results confirmed that,compared with normal group,A33 overexpression promoted the upregulation of fibrosis-related factors in TCMK1 cells,significantly increase the expression of downstream target genes GSK-3β and β-catenin mRNA in the Wnt/β-catenin signaling pathway(P<0.05),and A33 overexpression reversed the cellular fibrosis changes downregulated by the serum containing Chaihuang Yishen Granules(P<0.01).Conclusion Chaihuang Yishen Granules significantly improve renal fibrosis in UUO mice by downregulating the A33/Wnt/β-catenin signaling pathway,suggesting that A33 may be a potential therapeutic target for renal fibrosis.
7.Pharmacovigilance for Radiopharmaceuticals
Yue SUN ; Yuxuan ZHENG ; Zhenjiang ZHANG ; Yuxian ZHANG ; Ran ZHANG ; Chang LU ; Li ZHANG ; Ding LI ; Jiachen TU ; Jing XIE ; Huan ZHOU ; Jian GONG
Herald of Medicine 2024;43(10):1615-1619
Radiopharmaceuticals play an important role in the medical field,but they also carry certion risks and potential safety concerns.Medical institutions implement pharmacovigilance to ensure the safety of patients'drug use,including the safety of Radiopharmaceuticals.The operation and management of the pharmacovigilance system in the United States and the European Union are relatively mature.China can learn from their advanced concepts and establish our own radiopharmaciligence system.
8.Correlation between individualized coronary volumetric perivascular characterization index and coronary heart disease
Yanchun ZHANG ; Li CHENG ; Yue DAI ; Lixiang XIE ; Hao WANG ; Huan LIU ; Guangyi CHEN
Journal of Practical Radiology 2024;40(9):1444-1448
Objective To explore the correlation between coronary fat attenuation index of perivascular adipose tissue(FAIPVAT),as well as volumetric perivascular characterization index(VPCI),and coronary heart disease(CHD).Methods A total of 112 patients who underwent coronary computed tomography angiography(CCTA)and coronary angiography(CAG)examinations within 2 weeks were selected.The patients were divided into CHD group and control group according to the degree of coronary artery stenosis,and were divided into calcified plaque group,non-calcified plaque group and mixed plaque group according to the nature of plaque.The correlation between FAIPVAT,VPCI and CHD were evaluated.Results Of the 112 patients,71 patients in the CHD group and 41 patients in the control group.There were significant differences in gender,age,FAIPVAT and VPCI between the two groups.FAIPVAT and VPCI were positively correlated with CHD(r=0.445,P<0.01;r=0.669,P<0.01).FAIPVAT and VPCI were analyzed by receiver operating characteristic(ROC)curve,the area under the curve(AUC)of FAIPVAT was 0.770,the cut-off value was-81.659 HU,the sensitiv-ity was 0.592,and the specificity was 0.878,while the AUC of VPCI was 0.892,the cut-off value was 8.056,the sensitivity was 0.887,and the specificity was 0.805.There were significant differences in FAIPVAT and VPCI between non-calcified plaque group and calci-fied plaque group.FAIPVAT and VPCI of mixed plaque group and calcified plaque group were significantly different.Conclusion FAIPVAT and VPCI have some certain correlation with CHD.FAIPVAT and VPCI can accurately evaluate the risk level of CHD and coronary artery inflammation,and the value of individualized VPCI is higher.
9.Pathogenetic investigation of an outbreak of upper respiratory tract infection in a kindergarten in Baiyin City, Gansu Province
Shu LIANG ; Hui ZHANG ; Zhibo XIE ; Genxia GAO ; Biao WANG ; Miao WANG ; Huan WEI ; Xiaoshu ZHANG
Chinese Journal of Preventive Medicine 2024;58(10):1593-1597
This study focuses on the cases(mainly characterized by respiratory symptoms such as cough, runny nose, fever, sore throat, and nasal congestion)of an outbreak of upper respiratory tract infections in a kindergarten in Jingyuan County, Baiyin City, Gansu Province, in May 2023. The epidemiological data were collected, and pharyngeal swab specimens were also obtained from the patients. The specimens of the research participants were subjected to respiratory multi-pathogen testing, and the positive specimens were further analyzed by sequencing the second hypervariable region (HRV2) of the G gene of respiratory syncytial virus (RSV) and constructing a phylogenetic tree. A total of 90 patients were collected, with an incidence rate of 22.84% (90/394), and the highest incidence was observed in the junior class group at 29.55%. Among the 17 pharyngeal swab specimens collected, 16 specimens were identified with the A subtype of respiratory syncytial virus. Sequencing analysis confirmed that it was the A subtype ON1 genotype. Based on the aforementioned testing results, it can be concluded that the current epidemic was primarily caused by infection with the A subtype of respiratory syncytial virus. Following the implementation of intervention measures, the epidemic has been effectively controlled.
10.Construction of unplanned offline prediction model for IHD two-stage citrate anticoagulation
Huan WANG ; Pan XIE ; Chao GAO ; Yi WU
Chongqing Medicine 2024;53(5):677-681
Objective To study the risk factors of two-stage citrate anticoagulation in intermittent he-modialysis(IHD)and to establish an unplanned offline prediction model.Methods A retrospective analysis was conducted to include 34 patients and 118 times of treatment with two-stage citrate anticoagulation for IHD in the hospital from January 2019 to February 2023.According to whether the treatment did not reach the treatment time due to the coagulation of the extracorporeal circulation pipeline,118 treatments were divid-ed into the planned units(n=111)and the unplanned units(n=7).Univariate and multivariate logistic re-gression analysis were used to analyze the risk factors of unplanned weaning,and a risk prediction model was established.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of the regression model.Results Univariate analysis showed that there were statistically significant differences in hematocrit(HCT),platelet count(PLT),activated partial thromboplastin time(APTT),and treatment mode between the planned and unplanned units(P<0.05).Multivariate logistic regression analysis showed that HCT and APTT were independent influencing factors for unplanned weaning(P<0.05).The HCT level was represented by A,the APTT level was represented by B,and the prediction model was:Logit(P)=1.304+ 0.206×A-0.378×B.The area under the ROC curve(AUC)of the prediction model was 0.912(95%CI:0.825-0.995,P<0.001),the maximum Youden index was 0.782,the cut off value was 0.113,the sensitivity was 85.7%,and the specificity was 92.5%.Conclusion The prediction model established by multivariate logistic regression analy-sis can make a preliminary judgment on whether coagulation occurs in two-stage IHD treatment.

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