Objective To establish and evaluate a mouse model of acute myocardial infarction(AMI)with coronary heart disease(CHD)that integrates syndrome differentiation with disease diagnosis,based on the"deficiency-stagnation-toxicity"pathogenesis.Methods Forty-eight ICR mice were randomly divided into four groups using a random number table:sham-operated,normal diet,high-choline,and trimethylamine N-oxide(TMAO).From weeks 1 to 8,each group received corresponding dietary and water interventions.From the 9th week,the normal diet,high-choline,and TMAO groups underwent coronary artery ligation(left anterior descending artery,LAD).In contrast,the sham-operated group only had suture placement without ligation,maintaining the same dietary and water interventions.Data on general signs,body weight,food and water intake,urine and feces,auricle and paw conditions,and behavioral patterns were collected and compared macroscopically and microscopically to determine the syndrome type of the high-choline-induced AMI mouse model and observe changes in the"deficiency-stagnation-toxicity"syndrome indicators.After 12 weeks,echocardiography,hematoxylin-eosin(HE)staining,and Masson′s trichrome staining were used to assess cardiac function,myocardial tissue cellular morphology changes,and myocardial fibrosis levels,respectively.The stability and reliability of the model were evaluated by observing the fluorescence intensity of inflammatory cytokines in the myocardial tissues of each group using immunofluorescence.Results Mice in all groups post-AMI surgery exhibited significant weight loss,dull fur,lethargy,and reduced activity.Mice in the high-choline and TMAO groups showed more sluggish responses to stimuli.The high-choline and TMAO groups displayed increased food intake but slow weight gain from weeks 1 to 4,developing into a trend of"increased food and water intake with weight loss"from 5 to 8 weeks,accompanied by yellowish urine and dry stools(P<0.01).Postoperatively(9-12 weeks),body weight significantly decreased,with the most prominent weight loss observed in the high-choline group.The high-choline and TMAO groups exhibited abnormal RGB values in auricles and paws(P<0.01),and behavioral tests showed a significant decline in open-field activity(P<0.01).Cardiac function and pathological examinations revealed that,compared with the sham-operated and normal diet groups,mice in the high-choline and TMAO groups had increased left ventricular end-diastolic and end-systolic volumes(P<0.01),decreased left ventricular ejection fraction and fractional shortening(P<0.01),and elevated heart indices(P<0.05).HE staining of myocardial tissues indicated more pyknotic nuclei and inflammatory cell infiltration in the high-choline and TMAO groups.Masson′s trichrome staining showed extensive blue-stained collagen fiber distribution in the infarct border zones of the high-choline and TMAO groups,with aggravated fibrosis(P<0.05).Immunofluorescence revealed elevated interleukin-1 beta and tumor necrosis factor-alpha levels in the high-choline and TMAO groups compared with the sham-operated and normal diet groups(P<0.01).Conclusion A high-choline diet combined with LAD ligation successfully established an animal model of AMI with CHD that integrates syndrome differentiation with disease diagnosis,based on the"deficiency-stagnation-toxicity"pathogenesis.This model not only embodies the traditional Chinese medicine theory′s understanding of the pathogenic features of"deficiency-stagnation-toxicity",but also serves as a reference for assessing the interventional effects of Chinese herbal compound prescriptions and facilitating research on syndrome patterns in traditional Chinese medicine.

Objective To construct an animal model of dilated cardiomyopathy(DCM)with heart failure toxin syndrome that conforms to the characteristics of traditional Chinese medicine(TCM)syndrome and identify potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.Methods Fifteen male SD rats were divided into a blank control,doxorubicin,or DCM with heart failure toxin syndrome group using a random number table method,with five rats per group.The doxorubicin group received intraperitoneal injection of doxorubicin at a dose of 1.25 mg/kg,administered on the first and fourth days of each week,along with a standard diet.The DCM with heart failure toxin syndrome group,in addition to the doxorubicin treatment,was given 42％white liquor(10 mL/kg)via gavage every other day,along with a 45％high-fat feed and 10％fructose water.The blank control group received intraperitoneal injection of an equivalent volume of phosphate-buffered saline at the same time points as the doxorubicin group,along with a standard diet.The model was established for 10 weeks.At the fourth and tenth weeks of modeling,echocardiography was performed to measure left ventricular ejection fraction(LVEF),fractional shortening(FS),systolic left ventricular posterior wall thickness(LVPWs),diastolic left ventricular posterior wall thickness,systolic left ventricular internal diameter(LVIDs),and diastolic left ventricular internal diameter(LVIDd);macroscopic changes in fur color of the rats were assessed using the red-green-blue colorimetric method.After modeling,the open field test was conducted to evaluate the exercise tolerance of the rats,and the grip strength test was performed to assess changes in forelimb grip strength.Hematoxylin-eosin,Masson,and wheat germ agglutinin staining were used to evaluate pathological changes in cardiac tissue.Bulk RNA sequencing analysis was performed to identify differentially expressed genes(DEGs)in the hearts of rats between the blank control and the DCM with heart failure toxin syndrome groups.Using DCM,the Blue value of rat fur color,and forelimb grip strength as phenotypic traits,weighted gene co-expression network analysis(WGCNA)was performed to screen for characteristic module gene sets(MEs)associated with DCM with heart failure toxin syndrome.Overlapping analysis was performed on DEGs,immune-related gene sets,and MEs,and the intersecting genes were identified as potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.The sensitivity and specificity of these targets were evaluated using receiver operating characteristic(ROC)curve analysis.Results Compared with the blank control group,at the tenth week of modeling,the LVEF,FS,and LVPWs of rats in the doxorubicin group and the DCM with heart failure toxin syndrome group decreased,whereas LVIDs and LVIDd increased,and the movement distance of the open field test and forelimb grip strength were reduced(P＜0.05).At the 10th week of modeling,the Blue value of fur color in the DCM with heart failure toxin syndrome group was significantly lower than that of the blank control and doxorubicin groups(P＜0.05).Compared with the blank control group,rats in the doxorubicin and DCM with heart failure toxin syndrome groups exhibited significant cardiac dilation and increased immune cell infiltration in cardiac tissue,accompanied by collagen deposition and cardiomyocyte hypertrophy.Bulk RNA sequencing identified 2,003 DEGs,including 1,082 downregulated genes and 921 upregulated genes.WGCNA results revealed that the MEturquoise module had the strongest positive correlation with DCM and the strongest negative correlation with the Blue value and forelimb grip strength.The overlapping analysis identified four intersecting genes:bone morphogenetic protein 6(Bmp6),serine-threonine-protein kinase 1(Pak1),proto-oncogene JunD(JunD),and S100 calcium-binding protein A3(S100A3).ROC curve analysis demonstrated that these four genes exhibited high sensitivity and specificity for DCM with heart failure toxin syndrome.Conclusion The rat model constructed by intraperitoneal injection of doxorubicin combined with a high-fat feed,fructose water,and white liquor gavage closely aligns with the characteristics of the DCM with heart failure toxin syndrome.Bmp6,JunD,Pak1,and S100A3 are potential biomarkers or therapeutic targets for DCM heart failure toxin syndrome.

Objective To establish and evaluate a mouse model of acute myocardial infarction(AMI)with coronary heart disease(CHD)that integrates syndrome differentiation with disease diagnosis,based on the"deficiency-stagnation-toxicity"pathogenesis.Methods Forty-eight ICR mice were randomly divided into four groups using a random number table:sham-operated,normal diet,high-choline,and trimethylamine N-oxide(TMAO).From weeks 1 to 8,each group received corresponding dietary and water interventions.From the 9th week,the normal diet,high-choline,and TMAO groups underwent coronary artery ligation(left anterior descending artery,LAD).In contrast,the sham-operated group only had suture placement without ligation,maintaining the same dietary and water interventions.Data on general signs,body weight,food and water intake,urine and feces,auricle and paw conditions,and behavioral patterns were collected and compared macroscopically and microscopically to determine the syndrome type of the high-choline-induced AMI mouse model and observe changes in the"deficiency-stagnation-toxicity"syndrome indicators.After 12 weeks,echocardiography,hematoxylin-eosin(HE)staining,and Masson′s trichrome staining were used to assess cardiac function,myocardial tissue cellular morphology changes,and myocardial fibrosis levels,respectively.The stability and reliability of the model were evaluated by observing the fluorescence intensity of inflammatory cytokines in the myocardial tissues of each group using immunofluorescence.Results Mice in all groups post-AMI surgery exhibited significant weight loss,dull fur,lethargy,and reduced activity.Mice in the high-choline and TMAO groups showed more sluggish responses to stimuli.The high-choline and TMAO groups displayed increased food intake but slow weight gain from weeks 1 to 4,developing into a trend of"increased food and water intake with weight loss"from 5 to 8 weeks,accompanied by yellowish urine and dry stools(P<0.01).Postoperatively(9-12 weeks),body weight significantly decreased,with the most prominent weight loss observed in the high-choline group.The high-choline and TMAO groups exhibited abnormal RGB values in auricles and paws(P<0.01),and behavioral tests showed a significant decline in open-field activity(P<0.01).Cardiac function and pathological examinations revealed that,compared with the sham-operated and normal diet groups,mice in the high-choline and TMAO groups had increased left ventricular end-diastolic and end-systolic volumes(P<0.01),decreased left ventricular ejection fraction and fractional shortening(P<0.01),and elevated heart indices(P<0.05).HE staining of myocardial tissues indicated more pyknotic nuclei and inflammatory cell infiltration in the high-choline and TMAO groups.Masson′s trichrome staining showed extensive blue-stained collagen fiber distribution in the infarct border zones of the high-choline and TMAO groups,with aggravated fibrosis(P<0.05).Immunofluorescence revealed elevated interleukin-1 beta and tumor necrosis factor-alpha levels in the high-choline and TMAO groups compared with the sham-operated and normal diet groups(P<0.01).Conclusion A high-choline diet combined with LAD ligation successfully established an animal model of AMI with CHD that integrates syndrome differentiation with disease diagnosis,based on the"deficiency-stagnation-toxicity"pathogenesis.This model not only embodies the traditional Chinese medicine theory′s understanding of the pathogenic features of"deficiency-stagnation-toxicity",but also serves as a reference for assessing the interventional effects of Chinese herbal compound prescriptions and facilitating research on syndrome patterns in traditional Chinese medicine.

Objective To construct an animal model of dilated cardiomyopathy(DCM)with heart failure toxin syndrome that conforms to the characteristics of traditional Chinese medicine(TCM)syndrome and identify potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.Methods Fifteen male SD rats were divided into a blank control,doxorubicin,or DCM with heart failure toxin syndrome group using a random number table method,with five rats per group.The doxorubicin group received intraperitoneal injection of doxorubicin at a dose of 1.25 mg/kg,administered on the first and fourth days of each week,along with a standard diet.The DCM with heart failure toxin syndrome group,in addition to the doxorubicin treatment,was given 42％white liquor(10 mL/kg)via gavage every other day,along with a 45％high-fat feed and 10％fructose water.The blank control group received intraperitoneal injection of an equivalent volume of phosphate-buffered saline at the same time points as the doxorubicin group,along with a standard diet.The model was established for 10 weeks.At the fourth and tenth weeks of modeling,echocardiography was performed to measure left ventricular ejection fraction(LVEF),fractional shortening(FS),systolic left ventricular posterior wall thickness(LVPWs),diastolic left ventricular posterior wall thickness,systolic left ventricular internal diameter(LVIDs),and diastolic left ventricular internal diameter(LVIDd);macroscopic changes in fur color of the rats were assessed using the red-green-blue colorimetric method.After modeling,the open field test was conducted to evaluate the exercise tolerance of the rats,and the grip strength test was performed to assess changes in forelimb grip strength.Hematoxylin-eosin,Masson,and wheat germ agglutinin staining were used to evaluate pathological changes in cardiac tissue.Bulk RNA sequencing analysis was performed to identify differentially expressed genes(DEGs)in the hearts of rats between the blank control and the DCM with heart failure toxin syndrome groups.Using DCM,the Blue value of rat fur color,and forelimb grip strength as phenotypic traits,weighted gene co-expression network analysis(WGCNA)was performed to screen for characteristic module gene sets(MEs)associated with DCM with heart failure toxin syndrome.Overlapping analysis was performed on DEGs,immune-related gene sets,and MEs,and the intersecting genes were identified as potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.The sensitivity and specificity of these targets were evaluated using receiver operating characteristic(ROC)curve analysis.Results Compared with the blank control group,at the tenth week of modeling,the LVEF,FS,and LVPWs of rats in the doxorubicin group and the DCM with heart failure toxin syndrome group decreased,whereas LVIDs and LVIDd increased,and the movement distance of the open field test and forelimb grip strength were reduced(P＜0.05).At the 10th week of modeling,the Blue value of fur color in the DCM with heart failure toxin syndrome group was significantly lower than that of the blank control and doxorubicin groups(P＜0.05).Compared with the blank control group,rats in the doxorubicin and DCM with heart failure toxin syndrome groups exhibited significant cardiac dilation and increased immune cell infiltration in cardiac tissue,accompanied by collagen deposition and cardiomyocyte hypertrophy.Bulk RNA sequencing identified 2,003 DEGs,including 1,082 downregulated genes and 921 upregulated genes.WGCNA results revealed that the MEturquoise module had the strongest positive correlation with DCM and the strongest negative correlation with the Blue value and forelimb grip strength.The overlapping analysis identified four intersecting genes:bone morphogenetic protein 6(Bmp6),serine-threonine-protein kinase 1(Pak1),proto-oncogene JunD(JunD),and S100 calcium-binding protein A3(S100A3).ROC curve analysis demonstrated that these four genes exhibited high sensitivity and specificity for DCM with heart failure toxin syndrome.Conclusion The rat model constructed by intraperitoneal injection of doxorubicin combined with a high-fat feed,fructose water,and white liquor gavage closely aligns with the characteristics of the DCM with heart failure toxin syndrome.Bmp6,JunD,Pak1,and S100A3 are potential biomarkers or therapeutic targets for DCM heart failure toxin syndrome.

Objective: To examine the associations of sleep with overweight/obesity and central obesity in adults, so as to provide insights into improving sleep quality and preventing obesity in adults. Methods: Demographics, height, body weight, waist circumstance and sleep status were collected from the Hubei Provincial Surveillance Program for Adult Chronic Diseases and Their Risk Factors in 2020. Subjects' sleep condiction, overweight/obesity and central obesity were descriptively analyzed. The associations of sleep with overweight/obesity and central obesity were examined using a multivariable logistic regression model. Results: A total of 17 789 participants were recruited, with an average age of (56.21±13.05) years, 61.50% women, and mean duration of (7.18±1.56) h/d. There were 7 019 participants with snoring/asphyxia/suffocation (39.46%), 6 108 participants with sleep difficulty (34.34%), 8 064 participants with night waking at least twice (45.33%), 268 participants taking hypnotics (1.51%), and 6 267 participants with early morning awakening and difficulty in sleep again (35.23%), and there were 8 960 participants with overweight/obesity (50.37%) and 6 148 participants with central obesity (34.56%). Multivariable logistic regression analysis showed that sleep duration of <7 h/d (OR=1.081, 95%CI: 1.007-1.159), snoring/asphyxia/suffocation (OR=2.367, 95%CI: 2.222-2.521), and night waking at least twice (OR=1.106, 95%CI: 1.028-1.191) significantly correlated with overweight/obesity, and sleep duration of >8 h/d (OR=0.834, 95%CI: 0.761-0.913), snoring/asphyxia/suffocation (OR=2.153, 95%CI: 2.019-2.297), and night waking at least twice (OR=1.193, 95%CI: 1.105-1.288) were statistically associated with central obesity. Conclusion Sleep duration, snoring/asphyxia/suffocation and night waking are associated with overweight/obesity and central obesity.

Intestinal injury is a common adverse reaction of clinical chemotherapy drugs, which limits the further application of chemotherapy drugs and causes serious physical and mental burden to patients. At present, the mechanism of chemotherapy-induced intestinal injury is complex, and traditional Chinese medicine has an excellent preventive effect. This article reviews the related mechanisms of intestinal flora imbalance, oxidative stress, inflammatory response, cell apoptosis, and immune damage caused by chemotherapy, and summarizes the role of traditional Chinese medicine in prevention and treatment of oxidative stress, inflammatory response, cell apoptosis, and immune damage.

Objective:To explore sex and rural-urban differences in the associations of different blood pressure levels with the risk of prediabetes.Methods:We used a multi-stage stratified cluster random sampling method to investigate 21 637 residents aged ≥18 years from 10 survey areas in Hubei province in 2020. The data on questionnaire, physical measurements, and laboratory indicators of the participants were collected. The associations of different blood pressure levels with risk of prediabetes by sex and regions were analyzed using multivariate logistic regressions after complex weighting.Results:A total of 16 111 subjects were included. The prevalence (95% CI) of prediabetes, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and IFG complicated with IGT were 25.1% (14.4%-35.9%), 12.7% (3.2%-22.1%), 8.1% (6.3%-9.8%), and 4.4% (2.3%-6.5%), respectively. After multivariate adjustment, the risk of prediabetes, IFG, IGT, and IFG complicated with IGT increased with the increment of blood pressure (both P for trend <0.05). The positive dose-response relationships between blood pressure levels and risk of prediabetes were also significant among male, urban, and rural residents (both P for trend <0.05), and the interactions between sex and blood pressure showed significant associations for risk of prediabetes and IGT (both P for interaction <0.05). Conclusions:Higher blood pressure levels were associated with an increased risk of prediabetes. The association with prediabetes was stronger in males, but no significant difference was found between urban and rural residents. More distinctive and effective prevention and control strategies should be developed for different populations.

Objective: To study the chemical constituents from traditional Chinese (Mongolian) medicine, Lomatogonium carinthiacum and Halenia corniculate. Methods: The chemical constituents were isolated and purified by silicagel column, Sephadex LH-20, ODS and high performance liquid chromategramphy. The structures were identified by NMR and MS analysis technics. Results: Twelve compounds were isolated and identified as isovitexin (1), Luteolin-5-O-β-D-glucoside (2), Isosaponarin (3), Luteolin-7-O-β-D-glucoside (4,7), 1,4,8-Trimethoxy-xanthone-6-O-β-D-glucoronyl-(1 → 6)O-β-Dglucoside (5), friginosideD (6), 1-hydroxy-2,3,5-trimethoxyxanthone (8), 1-hydroxy-2,3,4,5-tetramethoxyxanthone (9), 1-hydroxy-2,3,4,7-tetramethoxyxanthone(10), 1-hydroxy-2,3,4,5,7-pentamethoxyxanthone (11) and usnic acid (12). Conclusion: Compounds 6 and 12 are obtained from L. carinthiacum and H. corniculate for the first time.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

OBJECTIVE：To investigate the effects of rabepr azole on the pharmacokinetic characteristics of clopidogrel and its active metabolite in healthy volunteers with different CYP2C19 genotypes. METHODS ：Healthy volunteers were selected as subjects，and then randomly divided into extensive metabolizer （EM）group，intermediate metabolizer （IM）group，and poor metabolizer（PM）group with 8 subjects in each group ，according to their CYP2C19 genotypes by random number table. In single-dose，randomized，open，two-cycle-crossover design ，each group was given Clopidogrel bisulfate tablets 300 mg or Clopidogrel bisulfate tablets 300 mg+Rabeprazole sodium enteric-coated tablets 20 mg. UPLC-MS/MS method was adopted to detect the concentration of clopidogrel and its active metabolite derivative （MP-H4）. The pharmacokinetic parameters were calculated and compared by DAS 2.0 software. RESULTS ：There was no statistical significance in clinical data as age ，height， body weight ，liver enzymes and serum creatinine among 3 kinds of metabolism subjects （P＞0.05）. Compared with subjects receiving clopidogrel alone ，cmax and AUC 0－t of clopidogrel of subjects combined with rabeprazole in EM group were increased by 36％ and 27％，while those of MP-H 4 were decreased by 34％ and 28％（P＜0.01）；cmax and AUC 0－t of clopidogrel of subjects combined with rabeprazole in IM group were increased by 19％ and 18％，while those of MP-H 4 were decreased by 19％ and 16％ （P＜0.05 or P＜0.01）；there was no statistical significance in cmax and AUC 0－t of clopidogrel and MP-H 4 in PM group after receiving rabeprazole additionally as well as tmax of clopidogrel and MP-H 4 in all metablism subjects ，compared with clopidogrel alone（P＞0.05）. CONCLUSIONS ：Among CYP2C19 EM and IM subjects ，combined use of rabeprazole can significantly increase the exposure of clopidogrel and decrease the exposure of its active metabolite MP-H 4，but has no significant impact on clopidogrel and its active metabolite in CYP2C19 PM subjects.