Role of cyclophilin A in aggravation of myocardial ischemia reperfusion injury via regulation of apoptosis mediated by thioredoxin-interacting protein.

BACKGROUND: The progression and persistence of myocardial ischemia/reperfusion injury (MI/RI) are strongly linked to local inflammatory responses and oxidative stress. Cyclophilin A (CypA), a pro-inflammatory factor, is involved in various cardiovascular diseases. However, the role and mechanism of action of CypA in MI/RI are still not fully understood. METHODS: We used the Gene Expression Omnibus (GEO) database for bioinformatic analysis. We collected blood samples from patients and controls for detecting the levels of serum CypA using enzyme-linked immunosorbent assay (ELISA) kits. We then developed a myocardial ischemia/reperfusion (I/R) injury model in wild-type (WT) mice and Ppia-/- mice. We utilized echocardiography, hemodynamic measurements, hematoxylin and eosin (H&E) staining, immunohistochemistry, enzyme-linked immunosorbent assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining to determine the role of CypA in myocardial I/R injury. Finally, we conducted an in vitrostudy, cell transfection, flow cytometry, RNA interference, and a co-immunoprecipitation assay to clarify the mechanism of CypA in aggravating cardiomyocyte apoptosis. RESULTS: We found that CypA inhibited TXNIP degradation to enhance oxidative stress-induced cardiomyocyte apoptosis during MI/RI. By comparing and analyzing CypA expression in patients with coronary atherosclerotic heart disease and in healthy controls, we found that CypA was upregulated in patients with Coronary Atmospheric Heart Disease, and its expression was positively correlated with Gensini scores. In addition, CypA deficiency decreased cytokine expression, oxidative stress, and cardiomyocyte apoptosis in I/R-treated mice, eventually alleviating cardiac dysfunction. CypA knockdown also reduced H2O2-induced apoptosis in H9c2 cells. Mechanistically, we found that CypA inhibited K48-linked ubiquitination mediated by atrophin-interacting protein 4 (AIP4) and proteasomal degradation of TXNIP, a thioredoxin-binding protein that mediates oxidative stress and induces apoptosis. CONCLUSION: These findings highlight the critical role CypA plays in myocardial injury caused by oxidative stress-induced apoptosis, indicating that CypA can be a viable biomarker and a therapeutic target candidate for MI/RI.

Increased Cyclic Guanosine Monophosphate and Interleukin-1Beta Is Activated by Mitochondrial Dysfunction and Associated With Heart Failure in Atrial Fibrillation Patients.

Background: This study aimed to identify the association of cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator interferon genes (cGAS-STING) pathway with heart failure (HF) in atrial fibrillation (AF) patients. Methods: We prospectively enrolled 106 AF patients without evidence of HF. The serum levels of 2'3'-cyclic GMP-AMP (2'3'-cGAMP) and interleukin (IL)-1ß were measured by enzyme-linked immunoassay (ELISA). To determine the underlying mechanism, we supplemented the complex I inhibitor rotenone and the specific cGAS inhibitor RU.521 in neonatal rat ventricular cardiomyocytes. Results: During 18-month follow-up, serum concentrations of 2'3'-cGAMP (baseline 51.82 ± 11.34 pg/mL vs. follow-up 124.50 ± 75.83 pg/mL, Ppaired t < 0.01) and IL-1ß (baseline 436.07 ± 165.82 vs. follow-up 632.48 ± 119.25 ng/mL, Ppaired t < 0.01) were substantially upregulated in AF patients with HF as compared with those without HF. Furthermore, serum 2'3'-cGAMP and IL-1ß levels at 18-month follow-up were independently associated with the occurrence of HF in AF patients. Inhibition of cGAS by RU.521 effectively reversed the upregulation of 2'3'-cGAMP and STING phosphorylation induced by mitochondrial dysfunction, accompanied with inhibition of nod-like receptor protein 3 (NLRP3) inflammasome, IL-1ß and IL-18 secretion. Conclusions: Induction of mitochondrial dysfunction causes an upregulation of 2'3'-cGAMP and activation of NLRP3 inflammasome through cGAS-STING pathway in cardiomyocytes.

Atrial natriuretic peptide T2238C gene polymorphism and the risk of cardiovascular diseases: A meta­analysis.

The present study aimed to investigate the association between atrial natriuretic peptide (ANP) T2238C (rs5065) gene polymorphism and the risk of cardiovascular disease. Relevant literature was obtained by searching databases. The odds ratios (ORs) of the ANP T2238C locus genotype distribution in the case group of cardiovascular diseases and the control group of a non-cardiovascular population were pooled using R software. Sensitivity analysis was used to verify the stability of the results. Egger's linear regression test was used to assess the publication bias of the included literature. Studies were classified according to quality assessment score of the Newcastle-Ottawa scale, year, region, sample size and underlying disease for subgroup analysis, and meta-regression analysis was performed. A total of 12 studies comprising 45,619 patients were included. ANP rs5065 mutant gene C allele was a significant risk factor for myocardial infarction relative to T allele (OR=2.55, 95% CI=1.47-4.43, P=0.0008), CC+CT genotype was a significant risk factor for cerebrovascular events relative to TT (OR=1.14, 95% CI=1.04-1.26, P=0.0048) and the mutant CC genotype was a potential risk factor for the composite cardio-cerebral vascular events (CVE) relative to CT+TT (OR=1.40, 95% CI=0.96-2.04, P=0.081). In studies fulfilling the Hardy-Weinberg equilibrium, the CC genotype was a significant risk factor for the composite CVE relative to TT (OR=2.39, 95% CI=1.40-4.10, P=0.0018) and the CC genotype was a significant risk factor for composite CVE relative to CT+TT (OR=2.41, 95% CI=1.41-4.13, P=0.0015). The P-value of the Egger's test for publication bias was 0.436, which was not statistically significant. The results of the sensitivity analysis were relatively stable. Subgroup analysis indicated that the publication year was a potential source of heterogeneity. Regression analysis was performed for the recessive model in the composite CVE and the results showed that the study region (Europe) was one of the sources of heterogeneity (P=0.016). In conclusion, ANP 2238T/C mutation may increase the risk of myocardial infarction, cerebrovascular events and composite CVE.

A single-center clinical study of acute kidney injury associated with acute myocardial infarction.

OBJECTIVE: To investigate the risk factors of acute kidney injury (AKI) patients with acute myocardial infarction (AMI) and establish potential microRNA (miRNA) biomarkers in the peripheral blood of AMI-AKI patients. METHODS: Patients hospitalized from 2016 to 2020 and diagnosed with AMI (with AKI or without AKI groups) were recruited. The data of the two groups were compared and the risk factors of AMI-AKI were analyzed by logistic regression. The receiver operator characteristics (ROC) curve was drawn and the predictive value of risk factors in AMI-AKI was evaluated. Six AMI-AKI patients were selected and six healthy subjects were enrolled as the control. The peripheral blood samples of the two groups were collected for miRNA high-throughput sequencing. RESULTS: A total of 300 AMI patients were collected, including 190 patients with AKI and 110 patients without AKI. Multivariate logistic regression analysis indicated that diastolic pressure (68-80 mmHg), urea nitrogen, creatinine, serum uric acid (SUA), aspartate aminotransferase (AST), and left ventricular ejection fraction were the dependent risk factors of AMI-AKI patients (P < 0.05). ROC curve showed that the incidence of AMI-AKI patients was most correlated with urea nitrogen, creatinine, and SUA. In addition, 60 differentially expressed miRNAs were identified between AMI-AKI and controls. Then, hsa-miR-2278, hsa-miR-1827, and hsa-miR-149-5p were more corrected with predictors. Twelve of them targeted 71 genes involved in phagosome, oxytocin signaling pathway, and microRNAs in cancer pathways. CONCLUSION: Urea nitrogen, creatinine, and SUA were the dependent risk factors and important predictors for AMI-AKI patients. Three miRNAs may be considered as biomarkers for AMI-AKI.

Therapeutic efficacy of liraglutide versus metformin in modulating the gut microbiota for treating type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease.

Metformin and liraglutide are used in the treatment of type 2 diabetes mellitus (T2DM) complicated with nonalcoholic fatty liver disease (NAFLD). Although these drugs can alter the intestinal microbiome, clinical data are required to explore their mechanisms of action. Using 16S sequencing technology, we analyzed and compared the intestinal bacterial community structure and function between patients before and after treatment (12 weeks) with the two drugs (metformin or liraglutide, n = 15) and healthy controls (n = 15). Moreover, combined with 19 clinical indices, the potential therapeutic mechanisms of the two drugs were compared. The studied clinical indices included those associated with islet ß-cell function (FPG, FINS, HbA1c, and HOMA-IR), inflammation (TNF-α, IL-6, and APN), lipid metabolism (TC, TG, and LDL-C), and liver function (ALT, AST, and GGT); the values of all indices changed significantly after treatment (p < 0.01). In addition, the effect of the two drugs on the intestinal bacterial community varied. Liraglutide treatment significantly increased the diversity and richness of the intestinal bacterial community (p < 0.05); it significantly increased the relative abundances of Bacteroidetes, Proteobacteria, and Bacilli, whereas metformin treatment significantly increased the relative abundance of Fusobacteria and Actinobacteria (p < 0.05). Metformin treatment increased the complexity and stability of the intestinal bacterial network. However, liraglutide treatment had a weaker effect on the intestinal bacterial network, and the network after treatment was similar to that in healthy controls. Correlation matrix analysis between dominant genera and clinical indicators showed that the correlation between the bacterial community and islet ß-cell function was stronger after liraglutide treatment, whereas the correlation between the bacterial community and inflammation-related factors was stronger after metformin treatment. Functional prediction showed that liraglutide could significantly affect the abundance of functional genes related to T2DM and NAFLD (p < 0.05), but the effect of metformin was not significant. This study is the first to report the changes in the intestinal bacterial community in patients treated with metformin or liraglutide and the differences between the mechanisms of action of metformin and liraglutide. Metformin or liraglutide has a therapeutic value in T2DM complicated with NAFLD, with liraglutide having a weaker effect on the intestinal bacterial community but a better therapeutic efficacy.

Analysis of risk factors for different subtypes of acute coronary syndrome.

AIMS: To investigate the different risk factors among different subtypes of patients with acute coronary syndrome (ACS). METHODS: A total of 296 patients who had ACS were retrospectively enrolled. Blood and echocardiographic indices were assessed within 24 hours after admission. Differences in risk factors and Gensini scores of coronary lesions among three groups were analyzed. RESULTS: Univariate analysis of risk factors for ACS subtypes showed that age, and levels of fasting plasma glucose, amino-terminal pro-brain natriuretic peptide, and creatine kinase isoenzyme were significantly higher in patients with non-ST-segment elevation myocardial infarction (NSTEMI) than in those with unstable angina pectoris (UAP). Logistic multivariate regression analysis showed that amino-terminal pro-brain natriuretic peptide and the left ventricular ejection fraction (LVEF) were related to ACS subtypes. The left ventricular end-diastolic diameter was an independent risk factor for UAP and ST-segment elevation myocardial infarction (STEMI) subtypes. The severity of coronary stenosis was significantly higher in NSTEMI and STEMI than in UAP. Gensini scores in the STEMI group were positively correlated with D-dimer levels (r = 0.429) and negatively correlated with the LVEF (r = -0.602). CONCLUSION: Different subtypes of ACS have different risk factors. Our findings may have important guiding significance for ACS subtype risk assessment and clinical treatment.

Relationship between M235T and T174M polymorphisms in angiotensin gene and atrial fibrillation in Uyghur and Han populations of Xinjiang, China.

OBJECTIVE: To elucidate the association between angiotensin gene (AGT) M235T and T174M genetic polymorphisms in Han and Uyghur patients with atrial fibrillation (AF) in Xinjiang, China. METHODS: 100 cases of patients with AF of Han and 100 cases of patients with AF of Uyghur were selected as the experimental group, and 100 cases of patients with non-AF of Uyghur and non-AF of Han were selected as the control group. We amplified the AGT M235T site and AGT T174M site by PCR in 4 groups of patients, verified the polymorphism of the sites by gene sequencing, and compared their differences in each group. RESULTS: The high risk factors for AF such as sex, left atrial diameter (LAD), right atrial diameter (RAD), and coronary heart disease were significantly different between the Han case group and the control group (P < 0.05). There were significant differences in age, LAD, RAD, coronary heart disease and smoking as contributors to AF between Uyghur case group and control group (P < 0.05). The genotype frequency distribution of AGT M235T and AGT T174M loci in the AF group and control group of Han and Uyghur was in accordance with Hardy-Weinberg equilibrium law test. There was a significant difference in genotype frequency and allele frequency of AGT M235T locus between Han group, Uyghur AF group and control group (P < 0.05). CONCLUSION: The AGT M235T and AGT T174M loci were associated with the occurrence of atrial fibrillation in the Han and Uyghur ethnic groups in Xinjiang.

Comparative analysis of clinical characteristics, imaging and laboratory findings of different age groups with COVID-19.

Objective: This study aims to provide scientific basis for rapid screening and early diagnosis of the coronavirus disease 2019 (COVID-19) through analysing the clinical characteristics and early imaging/laboratory findings of the inpatients. Methods: Three hundred and three patients with laboratory-confirmed COVID-19 from the East Hospital of People's Hospital of Wuhan University (Wuhan, China) were selected and divided into four groups: youth (20-40 years, n = 64), middle-aged (41-60 years, n = 89), older (61-80 years, n = 118) and elderly (81-100 years, n = 32). The clinical characteristics and imaging/laboratory findings including chest computed tomography (CT), initial blood count, C-reactive protein [CRP]), procalcitonin (PCT) and serum total IgE were captured and analysed. Results: (1) The first symptoms of all age groups were primarily fever (76%), followed by cough (12%) and dyspnoea (5%). Beside fever, the most common initial symptom of elderly patients was fatigue (13%). (2) Fever was the most common clinical manifestation (80%), with moderate fever being the most common (40%), followed by low fever in patients above 40 years old and high fever in those under 40 years (35%). Cough was the second most common clinical manifestation and was most common (80%) in the middle-aged. Diarrhoea was more common in the middle-aged (21%) and the older (19%). Muscle ache was more common in the middle-aged (15%). Chest pain was more common in the youth (13%), and 13% of the youth had no symptoms. (3) The proportion of patients with comorbidities increased with age. (4) Seventy-one per cent of the patients had positive reverse transcription-polymerase chain reaction results and 29% had positive chest CT scans before admission to the hospital. (5) Lesions in all lobes of the lung were observed as the main chest CT findings (76%). (6) Decrease in lymphocytes and increase in monocytes were common in the patients over 40 years old but rare in the youth. Eosinophils (50%), red blood cells (39%) and haemoglobin (40%) decreased in all age groups. (7) The proportion of patients with CRP and PCT elevation increased with age. (8) Thirty-nine per cent of the patients had elevated IgE, with the highest proportion in the old (49%). Conclusion: The clinical characteristics and imaging/laboratory findings of COVID-19 patients vary in different age groups. Personalised criteria should be formulated according to different age groups in the early screening and diagnosis stage.

Correlation between P-selectin rs1800807 and rs1800808 Gene polymorphisms and plasma soluble P-selectin concentrations in patients with atrial fibrillation complicated with thromboembolism in Xinjiang, China.

This study is to investigate the relationship of P-selectin (Ps) gene rs1800807 and rs1800808 polymorphisms with plasma soluble P-selectin (sPs) in Han, Uygur, and Kazakh people with atrial fibrillation (AF) and thromboembolism (TE) in Xinjiang, China.A total of 778 Han patients (including 131 patients with AF and TE, 229 patients with AF and 418 healthy individuals), 660 Uygur patients (including 118 patients with AF and TE, 232 patients with AF and 310 healthy individuals), and 505 Kazakh patients (including 42 patients with AF and TE, 156 patients with AF and 307 healthy individuals) were enrolled in this study. Polymerase chain reaction-restriction fragment length polymorphism and direct DNA sequence analysis were used to analyze the polymorphisms of rs1800807 and rs1800808 of Ps gene. ELISA was used to determine the plasma sPs level. The association between plasma sPs levels and Ps gene polymorphisms was further analyzed.The sPs concentrations of GG genotype at rs1800807 locus in the Han, Uygur and Kazakh ethnic groups in Xinjiang, China were significantly higher than those of the CC genotype and CG genotype (P < .05). In the rs1800808 locus, plasma sPs concentrations of the heterozygous mutant CT genotypes in Han and Uygur populations were significantly higher than those in the CC and TT genotypes, whereas the plasma sPs concentrations in Kazakh TT genotypes were significantly higher than those in the CC and CT genotypes (P < .05). Among different ethnic groups, there were significant differences in sPs levels of rs1800807 and rs1800808 genotypes (P < .05).Plasma sPs concentrations are associated with Ps genotypes and sPs concentration of the same genotype shows racial differences.

Case-Control Study on the Interaction Effects of rs10757278 Polymorphisms at 9p21 Locus and Traditional Risk Factors on Coronary Heart Disease in Xinjiang, China.

OBJECTIVE: To study the interaction effects of rs10757278 polymorphisms at 9p21 locus and traditional risk factors on coronary heart disease (CHD) in Xinjiang, China. METHODS: This case-control study consecutively enrolled 310 unrelated consecutive CHD patients aged 18-70 years old. All study participants were recruited between January and December 2017 from The Heart Center of The First Affiliated Hospital of Xinjiang Medical University. CHD patients were confirmed by coronary angiography (≥50% diameter stenosis in at least one of the major coronary arteries) according to the American Heart Association criteria for the confirmation of CHD. Healthy subjects were randomly selected from the occupational population, who received physical examination in our hospital and matched to cases on the basis of age (±3 years) and sex, those without medical history of cardiovascular diseases, and 536 subjects were selected as the control group after medical history inquiry, physical examination, cardiac ultrasound, electrocardiogram, and other blood biochemical examinations in the hospital. The occupational stress was evaluated by an effort-reward imbalance questionnaire. An epidemiological survey was conducted to collect clinical data. Chi-squared test, analysis of variance, and binary logistic regression analysis were adopted. RESULTS: Both the case and the control groups showed significant difference in smoking, drinking, physical activity, hypertension, diabetes mellitus, family history of CHD, and body mass index (BMI) (all P < 0.05); prevalence of CHD was not related to occupational stress. There was no significant difference in occupational stress level between the 2 groups (P > 0.05); Differences in rs10757278 genotype between the case group and the control groups were statistically significant; binary logistic regression analysis was used to evaluate the risk factors of CHD. After adjustment for age and sex, significant increased risk effects for CHD were found to be associated with smoking [odds ratio (OR) = 2.311; 95% confidence interval (CI): 1.04-2.499; P < 0.001], physical exercise (OR = 1.365; 95% CI: 1.137-1.639; P < 0.001), hypertension (OR = 4.627; 95% CI: 2.165-10.764; P < 0.001), family history of CHD (OR = 4.103; 95% CI: 3.169-6.892; P < 0.001), BMI (OR = 2.484; 95% CI: 2.036-3.03; P < 0.001), and GG genotype at rs10757278 (OR = 1.978; 95% CI: 1.413-2.769; P < 0.001); We noted that a significant interaction association between GG genotype at rs10757278 and CHD differs across categories of smoking, hypertension, family history of CHD, and BMI. CONCLUSION: GG genotype at rs10757278 may be a risk factor for CHD. And there are interaction effects between GG genotype of rs10757278 in region 9p21 gene and traditional risk factors.

Edoxaban improves atrial fibrillation and thromboembolism through regulation of the Wnt-ß-induced PI3K/ATK-activated protein C system.

Thromboembolism is a commonly observed condition in geriatrics that is caused by vascular endothelial injury, platelet activation, physiological coagulation processes, reduction of anticoagulant activity, decreased fibrinolytic activity and abnormal flow in the heart chamber, artery or vein. The protein C anticoagulant system serves a crucial role in anticoagulant therapy for the treatment of thromboembolism. Previous findings have suggested that edoxaban is an efficient oral anticoagulant in the acute treatment of venous thromboembolism. In the present study, the efficacy of edoxaban on thromboembolism induced by atrial fibrillation was investigated in a mouse model. Inflammatory factors interleukin (IL)-1, -4, -8 and tumor necrosis factor (TNF)-α were analyzed in the sera of mice with fibrillation induced by thromboembolism. Expression and activity of thymic stromal lymphopoietin (TSLP) and activated protein C resistance were investigated in platelets and vascular endothelial cells (VECs). TSLP-induced platelet viability, Wnt-ß phosphorylation and integrin expression were analyzed in platelets. Furthermore, Wnt-ß expression and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in VECs were analyzed. Results demonstrated that the expression levels of IL-1, -4, -8 and TNF-α were significantly downregulated in the sera of mice with fibrillation and thromboembolism following treatment with edoxaban (P<0.01). Furthermore, the expression levels of prostacyclin (PGI2), prostaglandin (PG)E2, PGD2 and PGF2α were significantly increased in the sera of experimental mice that received edoxaban therapy (P<0.01). Results also indicated that edoxaban significantly stimulated the protein expression of TSLP and activated Wnt-ß phosphorylation and integrin expression in platelets (P<0.01). In addition, edoxaban therapy significantly upregulated the expression levels of PI3K and AKT, and subsequently increased the activity of protein C and S in VECs (P<0.01). Notably, edoxaban treatment improved atrial fibrillation and thromboembolism, as determined by pathological analysis. In conclusion, these results suggested that edoxaban elicited beneficial effects for mice with atrial fibrillation induced by thromboembolism through the regulation of the Wnt-ß-induced PI3K/ATK-activated protein C system.

Coreopsis Tinctoria Modulates Lipid Metabolism by Decreasing Low-Density Lipoprotein and Improving Gut Microbiota.

BACKGROUND/AIMS: The prevalence of hyperlipidemia is increasing rapidly. The role of Coreopsis tinctoria (CT) in amending lipid metabolism in hyperlipidemia patients has not been reported. This study aims to evaluate the role of CT in altering lipid metabolism in hyperlipidemia patients and to explore the possible mechanisms mediated by gut microbiota in hyperlipidemia mice models. METHODS: A retrospective analysis in 40 hyperlipidemia patients was conducted, in which 20 patients took fenofibrate and another 20 patients normatively drank water with CT. Hyperlipidemia mice models were also established. Blood biochemical tests were performed using an automatic biochemical analyzer. Liver histopathology was observed by hematoxylin and eosin staining. Ileocecal samples were collected from mice, and bacterial DNA was extracted and sequenced by MiSeq sequencing. Bacterial composition and differences were analyzed. RESULTS: In hyperlipidemia patients, CT was associated with decreased triglyceride and low-density lipoprotein (LDL) levels without liver injury. The experimental hyperlipidemia model also verified a similar result. Gut microbial richness and diversity were significantly decreased in hyperlipidemic mice, but increased after CT treatment. Bacterial communities were significantly differentiated between normal controls and hyperlipidemic mice. CT administration improved gut microbiota composition to an approximately normal status. Meanwhile, CT administration attenuated bacterial alterations at the class, order, family, and genus levels in hyperlipidemic mice. Importantly, the genera Barnesiella, Lactobacillus, and Helicobacter achieved high discriminatory power in hyperlipidemic mice relative to normal controls. CONCLUSIONS: CT can modulate blood lipid metabolism with improvement of liver function by decreasing LDL and improving gut microbiota compositions. These findings may provide novel therapeutic strategies for patients with hyperlipidemia.

Relationship between fasting plasma glucose and severity of coronary artery disease in non-diabetic Kazakh population in Xinjiang / 中国介入心脏病学杂志

Objective To investigate the relationship between the fasting blood glucose level and the severity of coronary artery disease among the Kazakh population in Xinjiang. Methods A total of 411 Kazakh patients with no known history of diabetes mellitus were enrolled in this study for highly suspected of coronary artery disease(CAD) and subesquently underwent coronary artery angiography. Coronary artery disease was diagnosed in 280 patients after coronary artery argiography. The severity of the disease was expressed in terms of Gensini score. All subjects were classified into 4 groups according to the level of fasting plasma glucose (FPG)< 5.6 mmol / L, 5.6-6.1 mmol / L, 6.1-7.0 mmol / L and ≥7.0 mmol / L. All the biochemical parameters, clinical data and coronary artery angiographic data were compared, and the possible risk factors related to the severity of coronary artery disease were studied. Results Multivariate logistic regression analysis showed that FPG was significantly associated with coronary artery disease(OR 1.53, 95% CI 1.25-1.87,P<0.001).The results showed that the prevalence of angiographic CAD and the Gensini score increased with the increasing FPG levels among the four groups.The FPG level was significantly correlated with the Gensini score (P<0.001). Conclusions FPG is significantly associated with coronary artery disease and its severity in the Kazakh population in Xinjiang.

Prognostic value of glucose metabolism for non-ST-segment elevation infarction patients with diabetes mellitus and single concomitant chronic total occlusion following primary percutaneous coronary intervention.

Glucose metabolism status may play a predictive role in the severity of the complications among patients with type 2 diabetes mellitus (DM). However, few studies have focused on the prognostic value of glycosylated hemoglobin (HbA1c) and Homeostatic Model Assessment 2 for Insulin Resistance (HOMA2-IR) in patients with DM, non-ST-segment elevation infarction (NSTEMI), and single concomitant chronic total occlusion (CTO) following primary percutaneous coronary intervention (PCI). Short- and long-term prognostic value of HbA1c and HOMA2-IR in patients with DM with NSTEMI and single CTO who received primary percutaneous transluminal coronary intervention (pPCI).Data from 202 patients with NSTEMI and single CTO in nonculprit vessels were included. The incidence of revascularization, cardiogenic shock, ischemic stroke, major bleeding (ie, cerebral hemorrhage or massive hemorrhage of gastrointestinal tract), and cardiac death were combined as composite end points (CEPs). HbA1c was measured on admission and at 12 and 24 weeks after discharge. HOMA2-IR was measured on admission and at 6 and 12 weeks after discharge. The mean value of HbA1c and HOMA2-IR was calculated to determine the impact on 2.5-year CEPs. All patients were assessed during hospitalization and followed for up to 2.5 years after discharge.Mean age was 62.4 ±â€Š11.8 years and 76% were male. Previous MI, lower left ventricular ejection fraction, and higher HbA1c (hazard ratio [HR] = 1.216; 95% confidence interval [CI] = 1.023-1.445; P = .023) were independently associated with a poor prognosis at 2.5 years. Higher HbA1c and HOMA2-IR on admission was associated with CEPs during hospitalization. Mean HOMA2-IR prior to pPCI was associated with revascularization (HR = 1.129; 95% CI = 1.008-1.265; P = .036) and ischemic stroke (HR = 1.276; 95% CI = 1.044-1.560; P = .017) during the 2.5 years follow-up period.Glucose metabolism status reflected by HbA1c and HOMA2-IR may provide prognostic value to patients with NSTEMI, type 2 DM, and single concomitant CTO following PCI. Therefore, patients with NSTEMI, CTO, and poor glycemic control should be carefully evaluated prior to PCI.

Association between -44G/A and +71A/G polymorphisms in the connexin 40 gene and atrial fibrillation in Uyghur and Han populations in Xinjiang, China.

We aimed to elucidate the association between connexin 40 (Cx40) genetic polymorphisms and atrial fibrillation (AF) in a Chinese population in Xinjiang comprising Uyghur and Han individuals. We enrolled 275 Uyghur and 305 age- and gender-matched Han subjects, and used polymerase chain reaction to detect single nucleotide polymorphisms (SNPs; -44G/A and +71A/G) in the gene encoding Cx40. A mutation screening was performed by direct sequencing and calculation of genotype and allele frequencies among AF patients and control subjects to determine the relationship between these variants and this condition in Uyghur and Han populations. The two SNPs examined were significantly associated with AF in both ethnic groups. Further analysis showed the SNPs to be in perfect linkage disequilibrium in both AF and control groups among Uyghur and Han individuals. In both populations -44AA genotype and A allele frequencies among AF patients were significantly higher than those in the control group. In addition, under the dominant model (GG vs GA+AA), a significant difference in the distribution of Cx40 -44G/A genotypes was detected between patients and controls. Logistic regression analysis revealed that Cx40 genetic polymorphisms increase AF risk in Uyghur and Han residents of Xinjiang. In conclusion, both the -44G/A and +71A/G variants of the gene encoding this protein are associated with AF in Uyghur and Han populations in northern China.

[Epidemic features of dyslipidemia among Uygur, Kazakh and Han ethnic groups in Urumqi].

Objective: To analyze the epidemic features of dyslipidemia among 39 980 Uygur, Kazak and Han ethnic groups in Urumqi, and to explore the methods of prevention and treatment on dyslipidemia. Methods: The differences of blood total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) of health examination population with different ethnics, genders, and ages were compared, from 2012 to 2014 in the First Affiliated Hospital of Xinjiang Medical University. Results: Among the Uygur, Kazak and Han ethnic groups, the positive rate was respectively 35.0%, 37.0%, 30.3% in TC; 34.5%, 30.1% and 32.0% in TG; 24.9%, 18.3%, and 18.2% in HDL-C; 30.1%, 31.6% and 23.3% in LDL-C. In the same ethnic group, the abnormality rate of blood lipid in the female was lower than that of the male (P<0.001). The blood lipid abnormality rate increased significantly in those with 30-39 years, and reached the highest value in the 50-59 years group, then it decreased in those aged over 60 years (P<0.001). Conclusion: The lipid abnormality rate of the Uygur and Kazak residents was higher than that of the Han nationality, and the abnormal levels of TC and LDL-C were particularly evident in Urumqi.

Prevalence of and risk factors for non-alcoholic fatty liver disease in a Chinese population: An 8-year follow-up study.

AIM: To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease (NAFLD) in a Chinese population. METHODS: A total of 1948 adults from China was followed for 8 years. A cross-sectional study was performed to investigate the prevalence of NAFLD at baseline, and then the participants were followed for 8 years to investigate risk factors for the development of NAFLD. RESULTS: A total of 1948 participants were enrolled at baseline, of whom 691 were diagnosed with NAFLD. During the 8-year follow-up, 337 baseline NAFLD-free participants developed NAFLD. They had a greater increase in body mass index (BMI), serum uric acid, fasting plasma glucose, very low-density lipoprotein cholesterol and a considerable decrease in high-density lipoprotein cholesterol. 123 participants who had NAFLD at baseline lost NAFLD during the 8-year follow-up period. They had a greater decrease in BMI, fasting plasma glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase. CONCLUSION: NAFLD is prevalent in Chinese population with a rapidly increasing tendency. It can be reversed when patients lose their weight, control their hyperlipidemia and hyperglycemia, and reduce the liver enzyme levels.

IL-10 genetic polymorphisms were associated with valvular calcification in Han, Uygur and Kazak populations in Xinjiang, China.

OBJECTIVE: Valvular calcification occurs via ongoing endothelial injury associated with inflammation. IL-10 is an anti-inflammatory cytokine and 75% of the variation in IL-10 production is genetically determined. However, the relationship between genetic polymorphisms of IL-10 and valvular calcification has not been studied. The objective of this study was to investigate the association between valvular calcification and IL-10 genetic polymorphisms in the Han, Uygur and Kazak populations in China. PATIENTS AND METHODS: All of the participants were selected from subjects participating in the Cardiovascular Risk Survey (CRS) study. The single nucleotide polymorphisms (SNPs) rs1800871 and rs1800872 of the IL-10 gene were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Three independent case-control studies involving the Han population, the Uygur population and the Kazak population were used in the analysis. RESULTS: For the Han and Kazak populations, rs1800871 was found to be associated with valvular calcification in the recessive model, and the difference remained statistically significant following multivariate adjustment (p<0.001, p=0.031, respectively). For the Han, Uygur and Kazak populations, rs1800872 was found to be associated with valvular calcification in the dominant model, and the difference remained statistically significant following multivariate adjustment (p<0.001, p=0.009, and p=0.023,respectively). CONCLUSION: Both rs1800871 and rs1800872 of the IL-10 gene are associated with valvular calcification in the Han and Kazak populations in China. Rs1800872 is also associated with valvular calcification in the Uygur population.

The Risk Factor Analysis for Type 2 Diabetes Mellitus Patients with Nonalcoholic Fatty Liver Disease and Positive Correlation with Serum Uric Acid.

Recent years, we has witnessed a sharp increase in the complications of Type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD). Here we aimed to determine the risk factors for T2DM patients with NAFLD and the relationship of serum uric acid (SUA) in these complications. We performed retrospective analysis of 300 T2DM patients admitted into our hospital from April 2010 to January 2014. We divided the T2DM patients into two groups based on whether the patients also had NAFLD or not, Group A (without NAFLD, 155 cases) and Group B (with NAFLD, 145 cases). General information of the patients was collected and analyzed statistically. Meanwhile, we detected and compared the blood biochemistry, glucose, and fasting insulin (FINS), and further performed Logistic regression analysis and determined the risk factors in T2DM patients with NAFLD. Significantly higher BMI, waist circumference, hip circumference, WHR, systolic, and diastolic blood pressure were observed in T2DM patients with NAFLD than the patients without NAFLD, which were statistically different (P < 0.05). There were also significant higher levels of TC, TG, ALT, AST, GGT, and SUA in T2DM patients with NAFLD than those in patients without NAFLD, which were statistically different (P < 0.05). Significantly higher levels of FPG, FINS, and HOMA-IR were observed in the T2DM patients with NAFLD than those without, which were statistically significant (P < 0.05). Logistic regression analysis also showed high BMI, WHR, TG, and SUA were independent risk factors in T2DM patients with NAFLD (P < 0.05). Meanwhile, SUA levels were positively correlated with BMI, W, H, WHR, hip circumference, waist circumference, TG, ALT, AST, GGT, FPG, FINS, and HOMA-IR, which were statistically significant (P < 0.05). The risk factors for T2DM patients with NAFLD are mainly BMI, WHR, TG, and SUA. Our findings provide clinical implications for the prevention and early diagnosis of T2DM patients with NAFLD.

Flavonoids furom Coreopsis tinctoria adjust lipid metabolism in hyperlipidemia animals by down-regulating adipose differentiation-related protein.

BACKGROUND: To identify the chemical structure of Coreopsis tinctoria extracts and their effect and mechanism on reducing blood lipid in hyperlipemia mice. METHODS: The flavonoids were extracted from Coreopsis tinctoria. The chemical structure was identified by HPLC. 59 mice were divided randomly into 5 groups. (group 1: normal diet control; group 2: hyperlipemia model; group 3: hyperlipemia mice treated with Coreopsis tinctoria, low dose 100 mg/kg; group 4: hyperlipemia mice treated with Coreopsis tinctoria high dose group 200 mg/kg; group 5 hyperlipemia mice treated with Fenofibrate. After 2 week of hyperlipid diet, the treatment of Coreopsis tinctoria and Fenofibrate were given for another 6 weeks with continuous hyperlipid diet. The TC, TG, HDL, histology, adipose differentiation-related protein (ADRP) expression in different groups were compared. RESULTS: Compared with normal diet group, TC, TG in hyperlipemia model group increased ( P<0.01). After treatment with Coreopsis tinctoria low dose group, high dose group, TC of the hyperlipemia mice decreased (P<0.05) without increasing AST, ALT and ALP. Fenofibrate can also decrease TC and TG but increase AST, ALT and ALP. Expression of hepatic ADRP increased in hyperlipemia mice. Coreopsis tinctoria high dose group 200 mg/kg can inhibit ADRP as Fenofibrate does. CONCLUSION: The flavonoids from Coreopsis tinctoria extracts can reduce blood lipid without liver function damage, showing better anti- hyperlipemia effect than Fenofibrate by down-regulating ADRP.