Objective To investigate the effects of CYP2C9 and VKORC1 gene polymorphism on warfarin stable dose and myocardial injury in patients after heart valve replacement in Qiandongnan region.Methods Clinical data of 110 patients in Qi-andongnan who underwent heart valve surgery at Guizhou Medical University's Second Affiliated Hospital's Cardiothoracic De-partment(form November 2019 to October 2024)were collected.According to CYP2C9*3 genotype,patients were divided into wild type(AA type)and mutant type(AC type and CC type),and VKORC1-1639G>A genotype was divided into wild type(GG type)and mutant type(GA type and AA type).Levene variance homogeneity test was performed first to compare warfarin dose between different genotypes and INRcompliance timebetween groups.The factors affecting the stable dose of warfarin werean-alyzed by hierarchical regression.BP neural network model is used for risk prediction.Generalized linear mixed effects model(GLMMs)was used to analyze the relationship between CYP2C9 and VKORC1 gene status and postoperative myocardial inju-ry.Results The distribution of all genes was consistent with Hardy-Weinberg genetic balance(both P>0.05).CYP2C9*3 and VKORC1-1639G>A gene status were significantly different from atrial fibrillation,myocardial injury,thrombosis and hemor-rhage,and combined drugs(amiodarone,rifampicin,phenobarbital,voriconazole)(all P<0.05).The compliance rate(TTR)and warfarin stable dose of warfarin anticoagulation therapy for CYP2C9*3 genotype AA were significantly higher than that of genotype AC(both P<0.01),and the INR compliance time was significantly lower than that of genotype AC(both P<0.01).The warfarin stable dose and INR reach time of VKORC1-1639G>A genotype GG+GA were significantly higher than geno-type AA(both P<0.01),and TTR was significantly lower than genotype AA(both P<0.01).Stratified regression analysis showed that CYP2C9,VKORC1,age,amiodarone,BSA,BMI and gender had significant effects on warfarin stable dose(all P<0.05).BP neural network model construction showed that CYP2C9 and VKORC1 had the highest contribution to model classifi-cation,followed by amiodarone,BSA,BMI,gender and age.The model verification results showed that the accuracy was 93.54％,the sensitivity and specificity were 85.62％and 95.89％,respectively.The positive predictive value was 94.23％,the negative predictivevaluewas 93.15％,and the ROC AUC fitting of thepredictionmodelwas 0.958.The levels of cTnI,CK-MB and hs-CRP in CYP2C9*3 and VKORC1-1639G>A mutant patients were significantly higher than those in wild-type patients(P<0.05).GLMMs model analysis showed that CYP2C9 and VKORC1 gene mutations were still statistically associated with the risk of postoperative myocardial injury regardless of adjustment factors(P<0.01).Conclusion The CYP2C9 * 3 and VKORC1-1639G>A gene polymorphisms in patients who underwent heart valve replacement surgery in Qiandongnan area sig-nificantly affect the stable dose of warfarin and the rate of achieving anticoagulation targets.Moreover,the mutant genes are closely related to the increase in postoperative myocardial injury indicators and the increased risk.

Objective:To analyze the awareness of HCV infection status and willingness for HCV-RNA testing among hepatitis C cases in four provinces in China and to provide a reference for adjusting HCV prevention and control strategies.Methods:From September 2021 to September 2022, a cross-sectional survey was conducted using stratified random cluster sampling in four provinces (Jiangsu, Henan, Hubei, and Yunnan) in China, with an estimated sample size of 6 468 participants. The questionnaire included sociodemographic information, HCV infection awareness, willingness for HCV-RNA testing, and history of high-risk behaviors from the survey participants. Logistic regression models were used to analyze the factors associated with HCV infection awareness and willingness for HCV-RNA testing among hepatitis C cases. Statistical analysis was performed using R 4.1.3 software.Results:A total of 10 563 hepatitis C cases were surveyed. The awareness rate of HCV infection was 86.74% (9 162/10 563), and the willingness rate for HCV-RNA testing was 85.21% (9 001/10 563). Multivariate logistic regression models analysis showed that the awareness rate of HCV infection was lower among individuals aged ≥60 years, urban residents (with New Rural Cooperative Medical Insurance ), those without a history of blood transfusion, those without a history of paid blood donation, those without a history of injection drug use, and those without a family member with hepatitis C case.The awareness rate was higher among individuals with high or technical secondary school education, college education or above, and those married with a spouse (all P<0.05). In terms of willingness for HCV-RNA testing, it was lower among females, individuals aged ≥60 years, and those without a history of blood transfusion, paid blood donation, or injection drug use. The willingness was higher among farmers or migrant workers, employees of enterprises or institutions, and those in other occupations (all P<0.05). Conclusions:There was room for improvement in the awareness proportion of HCV infection and willingness for HCV-RNA testing among hepatitis C cases in the four provinces of China. More convenient policies and measures should be provided to increase the awareness rate of HCV infection and the willingness to undergo HCV-RNA testing in this population.

Objective:To analyze the awareness of HCV infection status and willingness for HCV-RNA testing among hepatitis C cases in four provinces in China and to provide a reference for adjusting HCV prevention and control strategies.Methods:From September 2021 to September 2022, a cross-sectional survey was conducted using stratified random cluster sampling in four provinces (Jiangsu, Henan, Hubei, and Yunnan) in China, with an estimated sample size of 6 468 participants. The questionnaire included sociodemographic information, HCV infection awareness, willingness for HCV-RNA testing, and history of high-risk behaviors from the survey participants. Logistic regression models were used to analyze the factors associated with HCV infection awareness and willingness for HCV-RNA testing among hepatitis C cases. Statistical analysis was performed using R 4.1.3 software.Results:A total of 10 563 hepatitis C cases were surveyed. The awareness rate of HCV infection was 86.74% (9 162/10 563), and the willingness rate for HCV-RNA testing was 85.21% (9 001/10 563). Multivariate logistic regression models analysis showed that the awareness rate of HCV infection was lower among individuals aged ≥60 years, urban residents (with New Rural Cooperative Medical Insurance ), those without a history of blood transfusion, those without a history of paid blood donation, those without a history of injection drug use, and those without a family member with hepatitis C case.The awareness rate was higher among individuals with high or technical secondary school education, college education or above, and those married with a spouse (all P<0.05). In terms of willingness for HCV-RNA testing, it was lower among females, individuals aged ≥60 years, and those without a history of blood transfusion, paid blood donation, or injection drug use. The willingness was higher among farmers or migrant workers, employees of enterprises or institutions, and those in other occupations (all P<0.05). Conclusions:There was room for improvement in the awareness proportion of HCV infection and willingness for HCV-RNA testing among hepatitis C cases in the four provinces of China. More convenient policies and measures should be provided to increase the awareness rate of HCV infection and the willingness to undergo HCV-RNA testing in this population.

Objective To investigate the effects of CYP2C9 and VKORC1 gene polymorphism on warfarin stable dose and myocardial injury in patients after heart valve replacement in Qiandongnan region.Methods Clinical data of 110 patients in Qi-andongnan who underwent heart valve surgery at Guizhou Medical University's Second Affiliated Hospital's Cardiothoracic De-partment(form November 2019 to October 2024)were collected.According to CYP2C9*3 genotype,patients were divided into wild type(AA type)and mutant type(AC type and CC type),and VKORC1-1639G>A genotype was divided into wild type(GG type)and mutant type(GA type and AA type).Levene variance homogeneity test was performed first to compare warfarin dose between different genotypes and INRcompliance timebetween groups.The factors affecting the stable dose of warfarin werean-alyzed by hierarchical regression.BP neural network model is used for risk prediction.Generalized linear mixed effects model(GLMMs)was used to analyze the relationship between CYP2C9 and VKORC1 gene status and postoperative myocardial inju-ry.Results The distribution of all genes was consistent with Hardy-Weinberg genetic balance(both P>0.05).CYP2C9*3 and VKORC1-1639G>A gene status were significantly different from atrial fibrillation,myocardial injury,thrombosis and hemor-rhage,and combined drugs(amiodarone,rifampicin,phenobarbital,voriconazole)(all P<0.05).The compliance rate(TTR)and warfarin stable dose of warfarin anticoagulation therapy for CYP2C9*3 genotype AA were significantly higher than that of genotype AC(both P<0.01),and the INR compliance time was significantly lower than that of genotype AC(both P<0.01).The warfarin stable dose and INR reach time of VKORC1-1639G>A genotype GG+GA were significantly higher than geno-type AA(both P<0.01),and TTR was significantly lower than genotype AA(both P<0.01).Stratified regression analysis showed that CYP2C9,VKORC1,age,amiodarone,BSA,BMI and gender had significant effects on warfarin stable dose(all P<0.05).BP neural network model construction showed that CYP2C9 and VKORC1 had the highest contribution to model classifi-cation,followed by amiodarone,BSA,BMI,gender and age.The model verification results showed that the accuracy was 93.54％,the sensitivity and specificity were 85.62％and 95.89％,respectively.The positive predictive value was 94.23％,the negative predictivevaluewas 93.15％,and the ROC AUC fitting of thepredictionmodelwas 0.958.The levels of cTnI,CK-MB and hs-CRP in CYP2C9*3 and VKORC1-1639G>A mutant patients were significantly higher than those in wild-type patients(P<0.05).GLMMs model analysis showed that CYP2C9 and VKORC1 gene mutations were still statistically associated with the risk of postoperative myocardial injury regardless of adjustment factors(P<0.01).Conclusion The CYP2C9 * 3 and VKORC1-1639G>A gene polymorphisms in patients who underwent heart valve replacement surgery in Qiandongnan area sig-nificantly affect the stable dose of warfarin and the rate of achieving anticoagulation targets.Moreover,the mutant genes are closely related to the increase in postoperative myocardial injury indicators and the increased risk.

OBJECTIVE: To study the mechanism of Qushi Huayu Decoction (QHD), a compound of traditional Chinese herbal medicine, in prevention and treatment of non-alcoholic steatohepatitis (NASH). METHODS: Thirty-five Wistar male rats were randomly divided into normal group, untreated group, QHD group and Ganle (diisopropylamine dichloroacetate) group. The rats except those in normal group were subcutaneously injected with carbon tetrachloride (CCl(4)) for 4 weeks (twice per week) and simultaneously fed with high-fat and low-protein diet for 2 weeks to induce NASH. Then, the rats were administrated with QHD, Ganle, or distilled water for 2 weeks, respectively. After harvest, alanine aminotransferase (ALT) activity and tumor necrosis factor-alpha (TNF-alpha) content in serum as well as triglyceride (TG) and free fatty acid (FFA) in liver tissue were evaluated, and relativity analysis among these parameters was performed. Cathepsin B (Ctsb), phospho-inhibitor kappa B (P-IkappaB), TNF-alpha protein expressions in liver tissue were assayed with western-blot. The expression and distribution of ctsb in liver tissue were observed with immunohistochemical method. RESULTS: The contents of TG, FFA and activity of ALT were significantly decreased in QHD group. While in the Ganle group, only the activity of ALT in serum was decreased significantly. Expressions of Ctsb, P-IkappaB and TNF-alpha proteins in liver tissues and serum TNF-alpha level were all enhanced in untreated group which, however, were significantly inhibited in the QHD group. And as expected, there were significant relativities among contents of TG in liver tissues and the content of FFA in liver tissue and activity of ALT in serum, content of TNF-alpha in serum and content of FFA in liver tissue and activity of ALT in serum. CONCLUSION: The inhibiting effects of QHD on fat deposition and inflammation in liver are related with its inhibition on the "FFA-Ctsb-TNF-alpha" pathway of lipo-toxicity.

BACKGROUND: Studies indicated that lipid peroxidation due to increase of free radical is the key factor of ischemia/reperfusion injury.Shinyleaf pricklyash root extracts, rutaceae plant, is bitter in taste, no stimulation, which has the effects of promoting qi, relieving pain, promoting blood circulation by removing blood stasis, dispelling wind and dredging collaterals and antioxidation.OBJECTIVE: To observe the influence of nitidine chloride on myocardial ischemia/reperfusion injury in rats and analyze its mechanism.DESIGN: Randomized controlled study.SETTING: Departmentof Pharmacology and Department of Chemistry,Guangxi Medical University.MATERIALS: A total of 60 healthy Wistar rats were selected, half male and half female, with the body mass of 250-300 g. Nitidine chloride was provided by Department of Chemistry, Guangxi Medical University, batch number 20050609. MS4000U biological signal quantitative record analysis system, 722N evident spectrophotometer, hydrochloric acid verapamil (batch number 020701, 2 mL in each), malondialdehyde (MDA) and superoxide dismutase (SOD) kit were purchased from Guangzhou Longfeida Technology Co., Ltd., Shanghai Precision Scientific Instruments Corporation, Shanghai Harvest Pharmaceutical Co, Ltd. and Nanjing Jiancheng Bioengineering Institute, respectively. Hitachi 7170A full automatic biochemistry analyzer was also applied.METHODS: The experiment was performed at the Department of Pharmacology and Department of Chemistry, Guangxi Medical University between June 2004 and May 2006. ①Totally 60 healthy Wistar rats with normal ECG (half male and half female) were randomly divided into 6 groups:sham operation group, model group, 2, 1, 0.5 mg/kg nitidine chloride groups, positive control group with 10 rats in each group. The rats in the sham operation group received threading without deligation, and 90 minutes later the experiment was accomplished. Other 50 rats received left anterior descending branch of coronary artery deligation, ischemia for 30 minutes reperfusion for 60 minutes. 2 mg/kg verapamil, 2,1,0.5 mg/kg, 5 mL/kgnitidine chloride, saline of the same volume were injected into femoral vein in rats of the positive control group, different doses nitidine chloride groups and model group, respectively 10 minutes before deligating left anterior descending branch of coronary artery. ②Monitoring was conducted successively with standard limb Ⅱ lead ECG when performing reperfusion. Type,incidence rate and duration of cardiac arrhythmia were recorded within 60minutes. Change of ST segment was also recorded after reperfusion for 15minutes and 60 minutes. ③At the end of experiment, serum myocardial enzymology indexes were measured wi th full automatic biochemistry analyzer.MDA content and SOD activity in myocardial tissues were examined with thiobarbituric acid(TBA) method and xanthine oxidase (XOD) method, respectively. ④Measurement data and enumeration data between two groups were compared with t test and x2 test. MAIN OUTCOME MEASURES: Occurrence of cardiac arrhythmia, ECG ST segment elevation, change of serum myocardial enzymology indexes, MDA content and SOD activity of myocardial tissues in rats of each group.RESULTS: A total of 60 rats were involved in the result analysis. ①Degree of cardiac arrhythmia and ECG ST segment elevation of rats: The emergency time of cardiac arrhythmia in 1 and 2 mg/kg nitidine chloride groups was significantly later than that in the model group (P ＜ 0.05,0.01). The duration of cardiac arrhythmia in the 1 and 2 mg/kg nitidine chloride groups and positive control group was obviously shorter than that in the model group (P ＜ 0.05-0.01). The incidence rates of various kinds of cardiac arrhythmia were markedly less than those in the model group (P ＜ 0.01). The degree of ST segment elevation at reperfusion for 15 and 60 minutes was remarkably lower than that in the model group (P ＜ 0.05-0.01). ②Serum myocardial enzyme level: It was significantly higher in the model than the sham operation group after 60-minute myocardial ischemia and reperfusion (P?.01). Activity of myocardial enzyme in the 1 and 2 mg/kg nitidine chloride groups was remarkably lower than that in the model group (P ＜ 0.01,P ＜ 0.05). The level of myocardial enzyme decreased with the increase of nitidine chloride. It was lower significantly in the positive control group than the model group (P ＜ 0.05-0.01 ). ③SOD activity of myocardial tissues: It was markedly lower in the model group than the sham operation group after 60-minute myocardialischemia and reperfusion (P ＜ 0.01); It was dramatically higher than in the 1 and 2 mg/kg nitidine chloride groups than the model group (P ＜ 0.01). The activity also increased with the increase of nitidine chloride. ④MDA content of myocardial tissues: It was distinctly higher in the model group than the sham operation group after myocardial ischemia reperftsion for 60 minutes (P ＜ 0.01). It was remarkably lower in the 1 and 2 mg/kg nitidine chloride groups than the model group (P ＜ 0.01). The content decreased with the increase of nitidine chloride. It was obviously lower in the positive control group than the model group (P ＜ 0.05 ).CONCLUSION: ①1 and 2 mg/kg nitidine chloride can reduce the incidence rate of cardiac arrhythmia in rats with myocardial ischemia and reperfusion, postpone the emergence time of cardiac arrhythmia and shorten its duration, decrease the degree of ST segment elevation after reperfusion for 15 minutes and 60 minutes, which have similar effect with verapamil.② 1 and 2 mg/kg nitidine chloride can reduce the release of myocardial enzyme, relieve the severity of oxygen-derived free radicals injury, and has the effect of protecting myocardial injury during ischemia-reperfusion, in which represents a dose-dependent effect.