Dynamic selection of high-affinity aptamers using a magnetically activated continuous deflection microfluidic chip.

To accelerate the discovery of high-affinity aptamers, a magnetically activated continuous deflection (MACD) chip was designed. The MACD chip could achieve dynamic selection in a continuous flow, which meant that the binding and separation were carried out consecutively. Dynamic selection could make selection efficient. Low-affinity sequences could be eluted in time and high-affinity sequences could be enriched via dynamic selection. The stringency of the conditions could be further increased by lowering the target concentration in the dynamic selection. Finally, a C.al3 aptamer with high-affinity and high-specificity for Candida albicans (C. albicans) was obtained through six rounds of selection. Its dissociation constant (Kd) was 7.9 nM. This demonstrated that dynamic selection using a MACD chip was an effective method for high-affinity aptamer selection.

Genetic polymorphism of the Dab2 gene and its association with Type 2 Diabetes Mellitus in the Chinese Uyghur population.

Objective: The human Disabled-2 (Dab2) protein is an endocytic adaptor protein, which plays an essential role in endocytosis of transmembrane cargo, including low-density lipoprotein cholesterol (LDL-C). As a candidate gene for dyslipidemia, Dab2 is also involved in the development of type 2 diabetes mellitus(T2DM). The aim of this study was to investigate the effects of genetic variants of the Dab2 gene on the related risk of T2DM in the Uygur and Han populations of Xinjiang, China. Methods: A total of 2,157 age- and sex-matched individuals (528 T2DM patients and 1,629 controls) were included in this case-control study. Four high frequency SNPs (rs1050903, rs2255280, rs2855512 and rs11959928) of the Dab2 gene were genotyped using an improved multiplex ligation detection reaction (iMLDR) genotyping assay, and the forecast value of the SNP for T2DM was assessed by statistical analysis of clinical data profiles and gene frequencies. Results: We found that in the Uygur population studied, for both rs2255280 and rs2855512, there were significant differences in the distribution of genotypes (AA/CA/CC), and the recessive model (CC vs. CA + AA) between T2DM patients and the controls (P < 0.05). After adjusting for confounders, the recessive model (CC vs. CA + AA) of both rs2255280 and rs2855512 remained significantly associated with T2DM in this population (rs2255280: OR = 5.303, 95% CI [1.236 to -22.755], P = 0.025; rs2855512: OR = 4.892, 95% CI [1.136 to -21.013], P = 0.033). The genotypes (AA/CA/CC) and recessive models (CC vs. CA + AA) of rs2855512 and rs2255280 were also associated with the plasma glucose and HbA1c levels (all P < 0.05) in this population. There were no significant differences in genotypes, all genetic models, or allele frequencies between the T2DM and control group in the Han population group (all P > 0.05). Conclusions: The present study suggests that the variation of the Dab2 gene loci rs2255280 and rs2855512 is related to the incidence of T2DM in the Uygur population, but not in the Han population. In this study, these variations in Dab2 were an independent predictor for T2DM in the Uygur population of Xinjiang, China.

Genetic analysis of DNA methylation in dyslipidemia: a case-control study.

Background: Coronary heart disease has become the leading cause of death in developed countries, and dyslipidemia is closely associated with the risk of cardiovascular disease. Dyslipidemia is caused by the abnormal regulation of several genes and signaling pathways, and dyslipidemia is influenced mainly by genetic variation. AMFR, FBXW7, INSIG1, INSIG2, and MBTPS1 genes are associated with lipid metabolism. In a recent GWAS study, the GRINA gene has been reported to be associated with dyslipidemia, but its molecular mechanism has not been thoroughly investigated. The correlation between the DNA methylation of these genes and lipid metabolism has not been studied. This study aimed to examine the relationship between the DNA methylation of these genes and the risk of dyslipidemia by comparing the methylation levels of dyslipidemia and control samples. Methods: A case-control research method was used in this study. The patient's blood samples were collected at the Heart Center of the First Affiliated Hospital of Xinjiang Medical University. In the Xinjiang Han population, 100 cases of hyperlipidemia and 80 cases of the control group were selected. The two groups were age and gender-matched. Quantitative methylation analysis of CpG sites in the gene promoter regions of six genes was performed by Solexa high-throughput sequencing. Results: The DNA methylation levels of 23 CpG sites in six genes were shown to be associated with hyperlipidemia, and a total of 20 DNA methylation haplotypes showed statistically significant differences between the two groups. When compared with the control group, the dyslipidemia group had significantly higher levels of methylation in the GRINA gene (2.68 vs 2.36, P = 0.04). Additionally, we also discovered a significant methylation haplotype of GRINA (P = 0.017). Conclusion: The findings of this study reveal that the DNA methylation of GRINA increases the risk for dyslipidemia in humans.

Ablation of Plasma Prekallikrein Decreases Low-Density Lipoprotein Cholesterol by Stabilizing Low-Density Lipoprotein Receptor and Protects Against Atherosclerosis.

BACKGROUND: High blood cholesterol accelerates the progression of atherosclerosis, which is an asymptomatic process lasting for decades. Rupture of atherosclerotic plaques induces thrombosis, which results in myocardial infarction or stroke. Lowering cholesterol levels is beneficial for preventing atherosclerotic cardiovascular disease. METHODS: Low-density lipoprotein (LDL) receptor (LDLR) was used as bait to identify its binding proteins in the plasma, and the coagulation factor prekallikrein (PK; encoded by the KLKB1 gene) was revealed. The correlation between serum PK protein content and lipid levels in young Chinese Han people was then analyzed. To investigate the effects of PK ablation on LDLR and lipid levels in vivo, we genetically deleted Klkb1 in hamsters and heterozygous Ldlr knockout mice and knocked down Klkb1 using adeno-associated virus-mediated shRNA in rats. The additive effect of PK and proprotein convertase subtilisin/kexin 9 inhibition also was evaluated. In addition, we applied the anti-PK neutralizing antibody that blocked the PK and LDLR interaction in mice. Mice lacking both PK and apolipoprotein e (Klkb1-/-Apoe-/-) were generated to assess the role of PK in atherosclerosis. RESULTS: PK directly bound LDLR and induced its lysosomal degradation. The serum PK concentrations positively correlated with LDL cholesterol levels in 198 young Chinese Han adults. Genetic depletion of Klkb1 increased hepatic LDLR and decreased circulating cholesterol in multiple rodent models. Inhibition of proprotein convertase subtilisin/kexin 9 with evolocumab further decreased plasma LDL cholesterol levels in Klkb1-deficient hamsters. The anti-PK neutralizing antibody could similarly lower plasma lipids through upregulating hepatic LDLR. Ablation of Klkb1 slowed the progression of atherosclerosis in mice on Apoe-deficient background. CONCLUSIONS: PK regulates circulating cholesterol levels through binding to LDLR and inducing its lysosomal degradation. Ablation of PK stabilizes LDLR, decreases LDL cholesterol, and prevents atherosclerotic plaque development. This study suggests that PK is a promising therapeutic target to treat atherosclerotic cardiovascular disease.

Genetic variation of RNF145 gene and blood lipid levels in Xinjiang population, China.

Dyslipidemia is one of the main risk factors for coronary heart disease (CHD). The E3 ubiquitin ligase which is encoded by the ring finger protein 145 (RNF145) gene is very important in the mediation of cholesterol synthesis and effectively treats hypercholesterolemia. Thus, the purpose of the present research is to investigate the connection between the polymorphism of the RNF145 gene and cholesterol levels in the populations in Xinjiang, China. A total of 1396 participants (Male: 628, Female: 768) were included in this study for genetic analysis of RNF145 gene, and we used the modified multiple connection detection response (iMLDR) technology to label two SNPs (rs17056583, rs12188266) of RNF145 genotyping. The relationship between the genotypes and the lipid profiles was analyzed with general linear model analysis after adjusting confounding variables. Through the analysis of the two SNPs in RNF145 gene, we discovered that both rs17056583 and rs12188266 were related to total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations (All P < 0.001). In addition, the association of rs17056583 and rs12188266 with lipid profiles concentrations is still statistically significant after multivariate adjustment of sex, age, smoking, obesity, drinking, diabetes, hypertension and lipid profiles. Meanwhile, we also found that rs17056583 was associated with high triglycerides concentrations before and after adjustment (All P < 0.001). Our study shows that both rs17056583 and rs12188266 SNPs of RNP145 gene are related to TC and LDL-C concentrations in Xinjiang population.

TBL2 methylation is associated with hyper-low-density lipoprotein cholesterolemia: a case-control study.

BACKGROUND: HMGCR, SCAP, SREBF1, SREBF2 and TBL2 are well-known genes that are involved in the process of lipid metabolism. However, it is not known whether epigenetic changes of these genes are associated with lipid metabolism. In this study, the methylation levels of the HMGCR, SCAP, SREBF1, SREBF2 and TBL2 genes were analyzed between samples from a hyper-low-density lipoprotein cholesterolemia (hyper-LDL) group and a control group to examine the association between the methylation levels of these genes and the risk of hyper-LDL. METHODS: In this study, a case-control approach was used to explore the association between DNA methylation and hyper-LDL. The DNA methylation levels of HMGCR, SCAP, SREBF1, SREBF2 and TBL2 genes and 231 CpG sites in the promoter regions of these genes were measured in 98 hyper-LDL participants and 89 participants without hypo-LDL. RESULTS: Compared with participants without hyper-LDL, patients with hyper-LDL TBL2 gene had lower methylation levels (11.93 vs. 12.02, P = 0.004). The methylation haplotypes with significant abundance in the TBL2 gene are tcttttttttt (P = 0.034), ctttttttcct (P = 0.025), ctctttctttt (P = 0.040), ccttttttttt (P = 0.028), and tctttttttttttttt. CONCLUSION: The study demonstrates that participants with hyper-LDL have lower methylation of TBL2. The results suggest that DNA methylation of TBL2 can decrease the risk for hyper-LDL in humans.

APLP2 gene polymorphisms are associated with high TC and LDL-C levels in Chinese population in Xinjiang, China.

Hyperlipidemia is one of the main risk factors for coronary artery disease (CAD). In the present study, we aimed to explore whether the single-nucleotide polymorphisms (SNPs) in amyloid precursor-like protein (APLP) 2 (APLP2) gene were associated with high lipid levels in Chinese population in Xinjiang, China. We recruited 1738 subjects (1187 men, 551 women) from the First Affiliated Hospital of Xinjiang Medical University, and genotyped three SNPs (rs2054247, rs3740881 and rs747180) of APLP2 gene in all subjects by using the improved multiplex ligation detection reaction (iMLDR) method. Our study revealed that the rs2054247 SNP was associated with serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) levels, and high-density lipoprotein cholesterol (HDL-C) in additive model (all P<0.05). The rs747180 SNP was associated with serum TC and LDL-C levels in additive model (all P<0.05). Our study revealed that both rs2054247 and rs747180 SNPs of the APLP2 gene were associated with high TC and LDL-C levels in Chinese subjects in Xinjiang.

[Water Sources and Factors Controlling Hydro-chemical Compositions in the Yiluo River Basin].

An important tributary in the middle stream of the Yellow River, the Yiluo River consists of the Luohe River and Yihe River, which converge at Yanshi City. Mining activities were widely distributed in the upstream of the Yiluo River Basin (YRB), while residential areas concentrated in the downstream were coupled with extensively industrial and agricultural activities. To illustrate the influences of variable anthropogenic activities on the hydro-chemical composition of river water of the YRB, water samples from the main stream and tributaries were collected in the flood season (August) and normal season (December), respectively. The hydrogen and oxygen isotope values coupled with cation and anion content were analyzed. Temporal and spatial variations of hydrogen and oxygen isotopes and ion content were utilized to elucidate the sources and factors controlling the hydro-chemical composition of the river water, and to illustrate the pathways of human effects. The results demonstrated that:① Average hydrogen and oxygen isotope values (δD and δ18O) of Luo River water were -56‰ and -7.9‰, and -55‰ and -8.1‰ in the flood season and normal season, respectively. Mean δD and δ18O values of Yi River water were -49‰ and -6.9‰, and -53‰ and -7.8‰ in the flood season and normal season, respectively. These temporal variations indicated that river water was mainly recharged by local atmospheric precipitation. ② The dominant water hydro-chemical type was HCO3-SO4-Ca-Mg in the main stream of the YRB, and the ratios of Ca2+ and HCO3- molar equivalent concentrations in the flood season were lower than those in the normal season, while the ratios of SO42- molar equivalent concentrations were higher than those in the normal season, indicating more sulfate dissolved in the river water in the flood season. ③ Carbonic acid and sulfuric acid simultaneously reacted with carbonate and silicate rocks, and in the Luo River more carbonate rocks were weathered, while in the Yi River more silicate rocks were weathered. ④ Human effects on river water were mainly concentrated in the upstream where wastewater input was derived from mining activities, while in the downstream pollution of the river was due to industrial wastewater and sewage input. ⑤ Spatial variations of sulfate sulfur isotope values were mostly due to differences between anthropogenic activities in the upstream and downstream of the Yiluo River. Negative sulfur isotope values in the upstream river water confirmed dissolved sulfate from sulfide mineral oxidation, which also indirectly verified the rock chemical weathering by sulfuric acid in this area. Positive sulfur isotope values in downstream river water were connected with industrial wastewater and sewage.

Prevalence of Dyslipidemia in Students from Han, Uygur, and Kazakh Ethnic Groups in a Medical University in Xinjiang, China.

In the present study, we aimed to evaluate the prevalence of dyslipidemia in students from different ethnic groups in Xinjiang. It is an observational, cross-sectional study. The sample of 7096 students aged 21-25 years was randomly selected from the clinic of Xinjiang Medical University. Baseline data, serum concentration of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and fasting plasma glucose (FPG) were reported. The prevalence of changes in lipid profile according to Body mass index (BMI) in three ethnic groups was calculated. Compared with Han and Uygur students, TC, LDL-C, TG and FPG levels were lower in kazakh sutdents, while HDL-C level was lower in Uygur students. The prevalence of high TC change was higher in Uygur students, and high LDL-C change was higher in Han students. The prevalence of low HDL-C change was higher in Uygur students, and high TG change was lower in Kazakh students. The prevalence of high TC, LDL-C, TG and low HDL-C changes was observed in normal weight, overweight and obesity groups according to the nutritional status by BMI among students of each ethnic group. The present study demonstrated the prevalence of dyslipidemia in students from different ethnic groups, and enriched the limited data on the early prevention and treatment of dyslipidemia and cardiovascular diseases in Xinjiang medical students crowd.

SOAT1 methylation is associated with coronary heart disease.

BACKGROUND: This study was designed to investigate whether differential DNA methylationin of cholesterol absorption candidate genes can function as a biomarker for patients with coronary heart disease (CHD). METHODS: DNA methylation levels of the candidate genes FLOT1, FLOT2 and SOAT1 were measured in peripheral blood leukocytes (PBLs) from 99 patients diagnosed with CHD and 89 control subjects without CHD. A total of 110 CPG sites around promoter regions of them were examined. RESULTS: Compared with groups without CHD, patients with CHD had lower methylation levels of SOAT1 (P<0.001). When each candidate genes were divided into different target segments, patients with CHD also had lower methylation levels of SOAT1 than patients without (P = 0.005). After adjustment of other confounders, methylation levels of SOAT1 were still associated with CHD (P = 0.001, OR = 0.290, 95% CI: 0.150-0.561). CONCLUSIONS: SOAT1 methylation may be associated with development of CHD. Patients with lower methylation levels in SOAT1 may have increased risks for CHD. Further studies on the specific mechanisms of this relationship are necessary.

Association of platelet-to-lymphocyte count ratio with myocardial reperfusion and major adverse events in patients with acute myocardial infarction: a two-centre retrospective cohort study.

OBJECTIVE: Insufficient myocardial reperfusion for patients with acute myocardial infarction (AMI) during primary percutaneous coronary intervention (PPCI) has a great influence on prognosis. The aim of this study was to investigate the association of the platelet-to-lymphocyte ratio (PLR) with myocardial reperfusion and in-hospital major adverse cardiac events (MACEs) in patients with AMI undergoing PPCI. DESIGN: Retrospective cohort study. SETTING: Patients and researchers from two tertiary hospitals. PARTICIPANTS: A total of 445 consecutive AMI patients who underwent PPCI between January 2015 and December 2017 were enrolled. Patients were divided into two groups based on the PLR value: patients with PLR values in the third tertile were defined as the high-PLR group (n=150), and those in the lower two tertiles were defined as the low-PLR group (n=295). Explicit criteria for inclusion and exclusion were applied. INTERVENTIONS: No interventions. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures were defined as cardiovascular death, reinfarction or target vessel revascularisation. Secondary outcome measures were defined as stroke, non-lethal myocardial infarction, ventricular tachycardia/ventricular fibrillation and in-hospital mortality. RESULTS: The high-PLR group had insufficient myocardial perfusion (23% vs 13%, p=0.003), greater postprocedural thrombolysis in myocardial infarction flow grade (0-2) (17% vs 10%, p=0.037), greater myocardial blush grade (0-1) (11% vs 4%, p=0.007) and higher B-type natriuretic peptide (BNP) (614±600 vs 316±429, p<0.001) compared with the low-PLR group. Multivariate logistic regression analysis indicated that the independent risk factors for impaired myocardial perfusion were high PLR (OR 1.256, 95% CI 1.003 to 1.579, p=0.056) and high BNP (OR 1.328, 95% CI 1.056 to 1.670, p=0.015). The high-PLR group had significantly more MACEs (43% vs 32%, p=0.029). CONCLUSIONS: This study suggested that high PLR and BNP were independent risk factors for insufficient myocardial reperfusion in patients with AMI. Higher PLR was related to advanced heart failure and in-hospital MACEs in patients with AMI undergoing PPCI.

Acyl-CoA: cholesterol acyltransferases-2 gene polymorphism is associated with increased susceptibility to coronary artery disease in Uygur population in Xinjiang, China.

BACKGROUND: Acyl-CoA: cholesterol acyltransferases (ACAT) is the only enzyme that catalyzes the synthesis of cholesterol esters (CE) from free cholesterol and long-chain fatty acyl-CoA and plays a critical role in cellular cholesterol homeostasis. In the present study, our primary objective was to explore whether the single-nucleotide polymorphisms (SNPs) in ACAT-2 gene were associated with coronary artery disease (CAD) in Uygur subjects, in Xinjiang, China. METHODS: We designed a case-control study including 516 CAD patients and 318 age- and sex-matched control subjects. Using the improved multiplex ligation detection reaction (iMLDR) method, we genotyped two SNPs (rs28765985 and rs7308390) of ACAT-2 gene in all subjects. RESULTS: We found that the genotypes, the dominant model (CC + CT vs TT) and over-dominant model (CT vs CC + TT) of rs28765985 were significantly different between CAD patients and the controls (P=0.027, P=0.012 and P=0.035, respectively). The rs28765985 C allele was associated with a significantly elevated CAD risk [CC/CT vs TT: odds ratio (OR) = 1.48, 95% confidence interval (CI) = 1.02-2.16, P=0.04] after adjustment for confounders. The TC and LDL-C levels were significantly higher in rs28765985 CC/CT genotypes than that in TT genotypes (P<0.05). CONCLUSIONS: Rs28765985 of ACAT-2 gene are associated with CAD in Uygur subjects. Subjects with CC/CT genotype or C allele of rs28765985 were associated with an increased risk of CAD.

[Analysis of anti-fatigue mechanism and potential targets of ginseng].

Ginseng has effects in reinforcing vital energy,invigorating health effectively and relieving fatigue symptoms,and ginsenoside( GS) is the main component of its anti-fatigue effect. Totally 17 active components and 92 drug targets of ginseng compounds were screened from Traditional Chinese Medicine Systems Pharmacology; and 78 intersecting genes of diseases and drug targets were obtained based on R Language Technology. The protein-protein interaction( PPI) network was constructed by STRING 11. 0 software,and Matthews Correlation Coefficient( MCC) algorithm was used to screen core target genes. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyze the major genes and their roles in regulatory networks. The results indicated that ginseng could regulate the core target genes,including AKT serine/threonine kinase( AKT1),interleukin-1ß,Toll-like receptor binding molecule 1( ICAM1),mitogen-activated protein kinase 8( MAPK8),AP-1 transcription factor subunit( JUN),transducer and activator of transcription 1( STAT1) and prostaglandin peroxidase synthase 2( PTGS2). It could participate in the functions of cytokine receptor binding,cell adhesion molecule binding and tumor necrosis factor receptor superfamily binding,and also regulate the signal pathways of tumor necrosis factor,interleukin 17 and c-type lectin receptor,so as to exert an anti-fatigue effect. Based on the results of network analysis,32 four-week-old male SPFACR mice were randomly divided into control group,low-dose ginsenoside group,middle-dose ginsenoside group and high-dose ginsenoside group. The corresponding drugs were administrated for 3 weeks. The results showed that GS could significantly up-regulate the expressions of STAT1 and AKT1( P<0. 01,P<0. 05),and downregulate the expressions of PTGS2 and JUN( P<0. 01). However,there was no significant effect on MAPK8,IL-1ß and ICAM1. Ginseng's anti-fatigue regulation network was constructed through network pharmacology,and the results were verified by experiments,in order to reveal the anti-fatigue mechanism of ginseng and provide scientific basis for its clinical application.

Association between apolipoprotein B genetic polymorphism and the risk of calcific aortic stenosis in Chinese subjects, in Xinjiang, China.

BACKGROUND: Limited information is available when it comes to the impact of genetic on Calcific Aortic Stenosis (CAS). Apolipoprotein B (apoB) is a key component in lipid metabolism and plays an important role in the dynamic equilibrium of cholesterol. We performed a case-control study to explore the association of apoB genetic polymorphisms with CAS in Chinese subjects, in Xinjiang, China. METHODS: We designed a case-control study including 314 CAS patients and 652 age- and sex-matched control subjects. Using the polymerase chain reaction-restriction fragment length (PCR-RFLP) method, we genotyped two SNPs (rs6725189 and rs693) of apoB gene in all subjects. RESULTS: We found that the rs693 T allele was associated with a significantly elevated CAS risk [TT/CT vs. CC: adjusted odds ratio (AOR) = 1.58, 95% confidence interval (CI) = 1.82-2.10, P = 0.002] and the rs6725189 T allele was also associated with a significantly elevated CAS risk (GT vs. GG: AOR = 1.82, 95% CI = 1.14-2.92, P = 0.013). Furthermore, we also found that the TC levels were significantly higher in rs693 TT/CT genotypes than that in CC genotypes (P < 0.05). CONCLUSIONS: Both rs693 and rs6725189 of the apoB gene are associated with CAS in Chinese subjects, in Xinjiang, China.

Association of genetic variations in the lipid regulatory pathway genes FBXW7 and SREBPs with coronary artery disease among Han Chinese and Uygur Chinese populations in Xinjiang, China.

BACKGROUND: Hyperlipidemia is a major risk factor for coronary artery disease (CAD). The current study was designed to explore the possible correlation between single nucleotide polymorphisms (SNPs) in the lipid homeostasis regulatory genes F-box and WD repeat domain-containing 7 (FBXW7) and sterol regulatory element-binding proteins (SREBPs) with CAD among Han Chinese and Uygur Chinese populations in Xinjiang, China. RESULTS: In the Uygur Chinese population, rs9902941 in SREBP-1 and rs10033601 in FBXW7 were found to be associated with CAD in a recessive model (TT vs. CT + CC, P = 0.032; GG vs. AG + AA, P = 0.010, respectively), and rs7288536 in SREBP-2 was found to be associated with CAD in an additive model (CT vs. CC + TT, P = 0.045). The difference was statistically significant in the Uygur Chinese population after multivariate adjustments [Odds ratio (OR) = 1.803, 95% confidence interval (CI): 1.036~3.137, P = 0.037; OR = 1.628, 95% CI: 1.080~2.454, P = 0.020; OR = 1.368; and 95% CI: 1.018~1.837, P = 0.037, respectively]. There were also significant interactions between the above-mentioned models in the Uygur Chinese population. However, these relationships were not observed before or after multivariate adjustment in the Han Chinese population. MATERIALS AND METHODS: A total of 1,312 Han Chinese (650 CAD patients and 662 controls) and 834 Uygur Chinese (414 CAD patients and 420 controls) were enrolled in this case-control study. Three SNPs (rs9902941 in SREBP-1, rs7288536 in SREBP-2 and rs10033601 in FBXW7) were selected and genotyped using the improved multiplex ligase detection reaction (iMLDR) method. CONCLUSIONS: The results of this study indicate that variations in the lipid regulatory pathway genes FBXW7 and SREBPs (rs9902941 in SREBP-1, rs7288536 in SREBP-2 and rs10033601 in FBXW7) are associated with CAD in the Uygur Chinese population in Xinjiang, China.

ACAT-1 gene polymorphism is associated with increased susceptibility to coronary artery disease in Chinese Han population: a case-control study.

Several studies suggest an important role of Acyl-CoA: cholesterol acyltransferase-1(ACAT-1) in the development of atherosclerosis. The aim of present study was to investigate whether there exists a possible correlation between genetic variations in ACAT-1 genes and coronary artery disease (CAD) risk. Four polymorphisms (rs1044925, rs11545566, rs12121758 and rs10913733) were finally selected and genotyped in 750 CAD patients and 580 health controls, using the improved multiplex ligation detection reaction (iMLDR) method. We found that the rs11545566 G allele was associated with a significantly elevated CAD risk [GG vs. AA: adjusted odds ratio (AOR) = 1.62, 95% confidence interval (CI) = 1.13-2.32, P = 0.008; GA/GG vs. AA: AOR = 1.67, 95% CI = 1.22-2.29, P = 0.001]. The rs10913733 G allele was also associated with a significantly elevated CAD risk (GG vs. TT: AOR = 1.57, 95% CI = 1.08-2.28, P = 0.018; GT/GG vs. TT: AOR = 1.39, 95% CI = 1.07-1.79, P = 0.013). Multivariate linear regression analysis showed that the rs11545566 polymorphism was independently associated with the Gensini scores (P = 0.005). The Gensini score of subjects in the variant GG genotype group and the GG/GA genotype group were higher than the score of subjects in the AA genotype group (32.49 ± 26.60 and 31.26 ± 26.96 vs. 23.45 ± 21.64; P = 0.001 and 0.002, respectively). Our results demonstrate that ACAT-1 rs1154556 and rs10913733 polymorphism are novel genetic factors in the development of CAD. Rs11545566 was also associated with the severity of CAD.

The burden and correlates of hypertension among Chinese rural population in Han, Uygur, and Kazak: a cross-sectional study.

The present study was conducted to investigate the prevalence, awareness, treatment, control, and associated risk factors of hypertension among rural population in Xinjiang Province in Northwest China. The Cardiovascular Risk Survey study was conducted on a representative sample of the Northwest China adult population. A four-stage stratified cluster random sampling scheme was adopted to recruit representative samples. The data were collected by trained staff. Multivariable logistic regression models were used to identify the associated risk factors. Overall, 8295 study participants aged 35-101 years were enrolled. The overall hypertension prevalence was 35.01%. The prevalence of hypertension in Han, Uygur, and Kazak population was 36.84%, 33.32%, and 52.57%, respectively. The hypertension awareness, treatment, control, and control among treated participants were 56.1%, 44.7%, 10.9%, and 24.3%, respectively. Multivariate logistic regression showed that age, body mass index, central obesity, ethnic, and drinking status were identified as risk factors for hypertension. Hypertension was found to be highly prevalent in rural adults in Xinjiang, China, especially in Kazak population. Although the levels of awareness, treatment, and control have improved, it was still lower than developed countries. Effective measures should be adopted to promote the prevention and control of hypertension.

TNF-α mRNA is negatively regulated by microRNA-181a-5p in maturation of dendritic cells induced by high mobility group box-1 protein.

Dendritic cell (DC) can be stimulated by both exogenous pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS) and endogenous damage-associated molecular patterns (DAMPs) such as high mobility group box-1 protein (HMGB1). MicroRNAs (miRNAs) act as post-transcriptional fine tuners of mRNA. Studies have focused mostly on the potential role of miRNAs in DCs maturation triggered by PAMPs, especially LPS, however, little is known about the regulatory mechanism underlying the effects of miRNAs in DC maturation mediated by DAMPs, including HMGB1. Here, we first profiled a miRNA microarray of DCs stimulated by HMGB1 and determined that the up-regulated miRNA miR-181a-5p may act as a regulatory miRNA in these cells. Computational algorithms predicted TNF-α 3'UTR to be targeted by miR-181a-5p, which was confirmed by the experiments involving luciferase reporters. In addition, we found that TNF-α mRNA was down-regulated by miR-181a-5p mimic, and significantly up-regulated by miR-181a-5p inhibitor. Taken together, we identified miR-181a-5p a negative regulator in HMGB1-induced immune responses by targeting TNF-α mRNA in DCs. Moreover, we suggested that miR-181a-5p may play a role in regulating DC responses to HMGB1 and serve as evidence indicating that novel therapies targeting miRNAs may be useful for treating immune dysfunction in the setting of sepsis.

Prevalence of valvular heart diseases and associated risk factors in Han, Uygur and Kazak population in Xinjiang, China.

BACKGROUND: Valvular heart diseases (VHD) is very common in clinical practice and has became the subject of growing attention in the field of cardiovascular medicine. Our aim was to assess the prevalence and correlates of VHD in the general population in Xinjiang, China. METHODS: Using a 4-stage stratified cluster random sampling method, a total of 14618 participants were recruited in the Cardiovascular Risk Survey (CRS) study. The participants' personal information, medical history were assessed by questionnaire. VHD was diagnosed by transthoracic echocardiography. We carried out the statistical analysis utilizing SPSS Statistics version 19.0. RESULTS: In the total study group, VHD was observed in 1397 (9.65%) individuals. The prevalence rates of VHD in Han, Uygur and Kazak group are 13.51%, 2.71% and 12.29% respectively. The prevalence rates of VHD increased strikingly with age (all P < 0.001). The results of multinomial regression analysis indicated that VHD were related to age in Han group, to age smoking and hypertension in Uygur group, to age and hypertension in Kazak group. CONCLUSION: Our research provides a unique prevalence rate of VHD in Xinjiang natural population. The result suggests that VHD are notably common in this population (9.65%) and increase with age. There exists significant difference of prevalence rate between ethnics. The main risk factors of VHD are age, hypertension and smoking. Valvular heart diseases should be regarded as a serious and growing public-health problem.