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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 ( K d ) was 7.9 nM. This demonstrated that dynamic selection using a MACD chip was an effective method for high-affinity aptamer selection.

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., Competing Interests: The authors declare there are no competing interests., (©2023 Li et al.)

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., Competing Interests: The authors declare that they have no competing interests., (© 2022 Liu et al.)

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.

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.

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., (© 2020 The Author(s).)

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.

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 ( δ D and δ 18 O) of Luo River water were -56‰ and -7.9‰, and -55‰ and -8.1‰ in the flood season and normal season, respectively. Mean δ D and δ 18 O 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 HCO 3 -SO 4 -Ca-Mg in the main stream of the YRB, and the ratios of Ca 2+ and HCO 3 - molar equivalent concentrations in the flood season were lower than those in the normal season, while the ratios of SO 4 2- 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.

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.

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-1β,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&lt;0. 01,P&lt;0. 05),and downregulate the expressions of PTGS2 and JUN( P&lt;0. 01). However,there was no significant effect on MAPK8,IL-1β and ICAM1. Ginseng&apos;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.

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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2019 The Author(s).)

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.

Objective: To investigate CT and MRI characteristics of primary spinal large B cell lymphoma., Methods: CT and MRI data of 23 patients with primary spinal large B cell lymphoma confirmed by histopathology were retrospectively analyzed from March 2011 to August 2015. Among them, including 14 males and 9 females aged from 28 to 70 years old with an average of 53.4 years old. The clinical manifestation mainly focus on pain around spinal and minority peripheral nerve symptom. The courses of disease ranged from 2 weeks to 3 months with an average of 9 weeks. Nine patients underwent CT plain scan, 8 patients underwent plain and enhanced CT; 21 patients underwent MRI plain scan and enhanced; 15 patients underwent CT and MRI examination. The location, bone changes, shape, density, signal intensity and enhancement characteristics of lesions were observed and compared with pathology., Results: Location and size of lesion showed cervical vertebrae in 1 case, thoracic vertebrae in 16 cases, lumbar vertebrae in 2 cases, and sacral vertebrae in 4 cases. Mass was larger, the largest cross-sectional size of group was up to 73 mm× 125 mm. CT examination showed that 11 cases with "cloud and mist" shape change, 6 cases with compression fractures, and with "floating ice" shape change, 9 cases with "oversleeve" shape change, 11 cases with spinal stenosis; enhancement scan showed obvious reinforcement. MRI showed slightly low signal on T1WI and T2WI were slightly high signal, and signal was uneven, and enhancement scan showed obvious reinforcement, 13 of 16 cases with spinal canal stenosis changed like "oversleeve", intervertebral space showed no significant stenosis. Comparison of CT and MRI showed the manifestation of bone destruction by CT was superior than that of MRI, but the range of lesion, and related surrounding structures were not better than MRI. MRI displayed the range of lesion usually bigger than CT. Pathology results showed that 23 patients were all primary spinal large B cell lymphoma., Conclusions: Primary spinal large B cell lymphoma has certain features in age, location and imaging findings. The "cloud and mist", "floating ice" and "oversleeve" shape bony destruction by CT and MRI has certain significance to diagnosis of primary spinal large B cell lymphoma., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

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., (Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: CONFLICTS OF INTEREST All authors do not have a commercial or other association that might pose a conflicts of interest.

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.

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., Competing Interests: CONFLICTS OF INTEREST The authors declare that there are no competing financial interests.

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.

Numerous studies have implicated the Wnt pathway in the development and progression of myocardial infarction (MI); however, there are very few investigations addressing the effects of polymorphisms in the Wnt pathway genes on MI susceptibility. We investigated the possible correlation between genetic variations in Wnt pathway genes and MI risk. Three polymorphisms (rs7832767 C > T in SFRP1 gene, rs2293303 C > T in CTNNB1 gene, rs16893344 C > T in WISP1 gene) were finally selected and genotyped in 465 MI patients and 485 healthy controls, using the PCR-RFLP method. We found that the SFRP1 rs7832767 variant allele (T) was associated with a significantly increased risk of MI [TT vs. CC: adjusted odds ratio (AOR) = 3.13, 95% CI = 1.78-5.51; CT/TT vs. CC: AOR = 1.53, 95% CI = 1.12-2.08; TT vs., Cc/ct: AOR = 2.87, 95% CI = 1.66-4.97)]. The significant association with MI risk was also found for the CTNNB1 rs2293303 (CT vs. CC: AOR = 3.48, 95% CI = 2.28-5.33; TT vs. CC: AOR = 7.37, 95% CI = 2.08-26.16; CT/TT vs. CC: AOR = 3.72, 95% CI = 2.46-5.62; TT vs., Cc/ct: AOR = 5.52, 95% CI = 1.58-19.28), and WISP1 rs16893344 polymorphisms (CT vs. CC: AOR = 2.43, 95% CI = 1.70-3.47; TT vs. CC: AOR = 5.17, 95% CI = 1.85-14.41; CT/TT vs. CC: AOR = 2.58, 95% CI = 1.83-3.66; TT vs., Cc/ct: AOR = 3.88, 95% CI = 1.41-10.64). The associations remain significant in stratified analysis by demographic and clinical characteristics of participants, with few exceptions. Our study provided the first evidence of the association between polymorphisms in the Wnt pathway genes and MI susceptibility in Chinese Han population. Epidemiological studies with larger samples and functional analyses are warranted to further verify our results., Competing Interests: The authors declare no competing financial interests.

Malignant mesothelioma is a rare type of cancer, most commonly associated with exposure to asbestos. Mesothelioma of the peritoneum, the membrane lining the abdominal cavity, is extremely rare. The current study reports the case of a 60-year-old female who presented with intestinal fistula, recurrent incisional hernia and abdominal infection, with no history of asbestos exposure, and was diagnosed with clear cell MPM. Computed tomography scans of the abdomen revealed extensive small bowel adhesions and massive peritoneal effusion. Histological examination of biopsy specimens indicated a diagnosis of malignant peritoneal mesothelioma with clear cell morphology. A laparotomy was performed, with subsequent resection of the bowel with fistula. Follow-up examination performed at 1-year post-surgery revealed that the patient was alive and in generally good health.

To improve the thermostability of xylanase XynZF-2 from Aspergillus niger XZ-3S, a disulfide bridge was introduced in the N-terminal domains by site-directed mutagenesis (V1C and E27C). Simultaneously, the active sites of XynZF-2 were predicted by bioinformatics software and verified by site-directed mutagenesis (E103D and E194D). The mutated active sites xynED- and the mutated disulfide bridge xynDC-encoding genes were constructed and expressed in Escherichia coli BL21 (DE3). Compared to the native xylanase, it was found that the residual activity of the mutated XynED was 0.17%. The optimum temperature of the variant XynDC was increased to 45°C from 40°C of XynZF-2. After treatment at 40°C for 60 min, the variant XynDC retained 66.77% of their original activity, while the XynZF-2 retained about 44.36% residual activity. t1/2(45°C) of the variant XynDC also increased from 7 min to 14 min. The results of the mutated xylanases indicated that the active center of XynZF-2 mainly consisted of two catalytic residues (Glu103 and Glu194), and the introduction of a disulfide bridge in the N-terminal domains can improve the thermostability of XynZF-2.

Three new metal coordination polymers, namely, [Co(DPP)2(H2O)2]·(BS)2·2H2O (1), [Co(DPP)2(H2O)2]·(ABS)2·2H2O (2) and [Co(DPP)2(MBS)2] (3) [DPP = 1,3-di(pyridin-4-yl)propane, BS = phenyl sulfonic acid, ABS = p-aminobenzene sulfonic acid, MBS = p-methylbenzene sulfonic acid] were obtained under hydrothermal conditions. Complexes 1-3 were structurally characterized using X-ray single-crystal diffraction, XRD and IR spectroscopy. Both complexes 1 and 2 display a 1D tape structure. Meanwhile, complex 3 exhibits a 2D layer and further stacks via C-Hπ interactions to generate a three-dimensional supramolecular architecture. These three metal coordination polymers have been applied as catalysts for the green synthesis of a variety of 3,4-dihydropyrimidin-2(1H)-ones under solvent-free conditions through the Biginelli reaction. Interestingly, the catalysis products have been obtained in high yields under eco-friendly synthesis conditions.

Objective: Proprotein convertase subtilisin-like kexin type 9 (PCSK9) gene E670G Polymorphism has been reported to be associated with coronary artery disease (CAD) and risk factors. However, the results remain controversial. We sought to perform a meta-analysis to investigate the relationships between genetic polymorphisms of E670G in PCSK9 gene and the risk of CAD., Methods: Literature searches were performed to identify all published relevant case-control studies without any language restrictions. Meta-analysis was conducted using the Review Manager software (version 5.2). Heterogeneity was investigated and measured using Cochran's Q-statistic and the inconsistency index (I(2)) test; Crude odds ratios (OR) with their corresponding 95% confidence interval (CI) were calculated., Results: A total of 5 case-control studies among 871 patients with CAD and 1144 control subjects were included in the meta-analysis. we found a correlation between PCSK9 genetic polymorphisms and increased risk for CAD under all of the genetic model (allele model: OR: 1.56, 95% CI: 1.21-2.01, P < 0.001; dominant model: OR: 1.46, 95% CI: 1.14-1.88, P = 0.003; recessive model: OR: 3.46, 95% CI: 1.19-10.10, P = 0.02; homozygous model: OR: 3.89, 95% CI: 1.35-11.20, P = 0.01; Heterozygous model: OR: 1.43, 95% CI: 1.08-1.92, P = 0.01; respectively)., Conclusion: The results of the meta-analysis indicated that genetic polymorphism of E670G in PCSK9 gene might be involved in pathogenesis of CAD; the 670G carriers may be closely related to the risk of CAD.

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.

A heterometallic cluster [Ag6Au6(ethisterone)12] of an unprecedented topology was synthesized and characterized. A sensitive and specific probe for estrogen receptor α (ERα) has been developed for the first time based on the enhancement of the Ag6Au6 luminescence., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two windmill-like Ag3Cu5 alkynyl clusters were synthesized and characterized. They display novel PL and ECL properties, which could be modified by changing the substituent on the alkynyl ligands. According to the study of electrochemical behaviours, ECL behaviours and ECL emission spectra of the Ag3Cu5 clusters, a possible ECL mechanism was proposed.

Background: Aberrant expression of Nicotinamide N-methyltransferase (NNMT) has been reported in pancreatic cancer. However, the role of NNMT in pancreatic cancer development remains elusive. Therefore, the present study was to investigate the impact of NNMT on pancreatic cancer cell proliferation, metastatic potential and survival under metabolic stress., Methods: Pancreatic cancer cell line PANC-1 was transfected with NNMT expression plasmid or small interfering RNA of NNMT to overexpress or knockdown intracellular NNMT expression, respectively. Rate of cell proliferation was monitored. Transwell migration and matrigel invasion assays were conducted to assess cell migration and invasion capacity. Resistance to glucose deprivation, sensitivity to glycolytic inhibition, mitochondrial inhibtion and resistance to rapamycin were examined to evaluate cell survival under metabolic stress., Results: NNMT silencing markedly reduced cell proliferation, whereas NNMT overexpression promoted cell growth moderately. Knocking down NNMT also significantly suppressed the migration and invasion capacities of PANC-1 cells. Conversely, NNMT upregulation enhanced cell migration and invasion capacities. In addition, NNMT knockdown cells were much less resistant to glucose deprivation and rapamycin as well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-expressing cells showed opposite effects although the effects were not so striking., Conclusions: These data sugguest that NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress., (© 2015 S. Karger AG, Basel.)

Ethnopharmacological Relevance: Huang-Lian-Jie-Du-Decotion (HLJDD), an important traditional Chinese medicine formula, has been used for various diseases in clinical practice, and thus has high potential to induce cytochrome P450 (CYP) isoenzymes/P-glycoprotein (P-gp) mediated herb-drug interactions (HDIs) with other co-administered drugs. The purpose of this study was to investigate the in vitro effects of multiple extracts including aqueous extracts, total flavonoids, iridoids, alkaloids from HLJDD on the activities of CYPs in rats (CYP1A2, CYP2C6, CYP2D2, CYP2E1 and CYP3A1) and P-gp, and then to predict potential interactions with co-administered drugs., Materials and Methods: The effects of the four extracts from HLJDD on the CYPs activity were evaluated in rat liver microsomes incubation system, and then determined by LC-MS/MS-based CYPs probe substrate assay. Caco-2 cell monolayer was used to investigate the effect of the four extracts on the efflux of Rhodamine 123 to evaluate their influences on P-gp activity., Results: The results show that total flavonoids and alkaloids exibited strong inhibition on rat CYP isoenzymes activities. Total flavonoids exhibited different inhibitory effects on CYPs activities with an order of CYP3A1>CYP2C6>CYP2E1>CYP1A2>CYP2D2, and the values of IC₅₀ were 4.24, 8.16, 17.56, 19.03, 29.51 μg/mL, respectively. Total alkaloids possessed similar inhibition on CYPs and could strongly inhibit the activity of CYP2D2 (IC₅₀=2.38 μg/mL), CYP3A1 (IC₅₀=2.61 μg/mL), CYP2E1 (IC₅₀=22.35 μg/mL), CYP1A2 (IC₅₀=23.2 μg/mL) and CYP2C6 (IC₅₀=43.09 μg/mL). Moderate degree of inhibition on CYPs activities was observed in aqueous and total iridoids extracts. Results from transport assay revealed that total flavonoids and alkaloids exhibited significant inhibitory effect on P-gp activity as evidenced by strong inhibition on the efflux of Rhodamine-123 with IC₅₀ of 104.6 and 82.6 μg/mL. But aqueous extract showed weak and iridoids had negligible effect on P-gp activity., Conclusions: This study clearly demonstrated that total flavonoids and alkaloids from HLJDD can significantly inhibit the activities of CYPs and P-gp, which should be taken into consideration to predict any potential HDIs when HLJDD and its bioactive components are co-administered with other therapeutic drugs metabolized by CYPs or transported by P-gp., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: The optimal cutoff of the waist-to-hip ratio (WHR) among Han adults in Xinjiang, which is located in the center of Asia, is unknown. We aimed to examine the relationship between different WHRs and cardiovascular risk factors among Han adults in Xinjiang, and determine the optimal cutoff of the WHR., Methods: The Cardiovascular Risk Survey was conducted from October 2007 to March 2010. A total of 14618 representative participants were selected using a four-stage stratified sampling method. A total of 5757 Han participants were included in the study. The present statistical analysis was restricted to the 5595 Han subjects who had complete anthropometric data. The sensitivity, specificity, and distance on the receiver operating characteristic (ROC) curve in each WHR level were calculated. The shortest distance in the ROC curves was used to determine the optimal cutoff of the WHR for detecting cardiovascular risk factors., Results: In women, the WHR was positively associated with systolic blood pressure, diastolic blood pressure, and serum concentrations of serum total cholesterol. The prevalence of hypertension and hypertriglyceridemia increased as the WHR increased. The same results were not observed among men. The optimal WHR cutoffs for predicting hypertension, diabetes, dyslipidemia and ≥ two of these risk factors for Han adults in Xinjiang were 0.92, 0.92, 0.91, 0.92 in men and 0.88, 0.89, 0.88, 0.89 in women, respectively., Conclusions: Higher cutoffs for the WHR are required in the identification of Han adults aged ≥ 35 years with a high risk of cardiovascular diseases in Xinjiang.

The anti-oxidative stress effect of heme oxygenase-1 (HO-1) expression is being increasingly studied. However, few studies regarding HO-1 have been conducted in patients with gestational diabetes mellitus (GDM). In the present study, HO-1 expression was compared in peripheral blood mononuclear cells at 24-28 weeks of pregnancy in patients with GDM and healthy females, to investigate the correlation between HO-1 and oxidative stress by calculation of MDA content in the peripheral blood serum (thiobarbituric acid method), tested ROS (flow cytometry method), HO-1mRNA (RT-PCR method), and HO-1 protein (western blotting method) of Mononuclear cells. The results show that the levels of serum malonaldehyde (MDA), reactive oxygen species (ROS), HO-1 mRNA and HO-1 protein expression in peripheral blood mononuclear cells were higher in the GDM group than in the control group. Correlation analysis showed that the expression levels of HO-1 protein were positively correlated with the HO-1 mRNA expression levels (r=0.680; P=0.000), and the levels of ROS (r=0.572; P=0.000) and MDA (r=0.614; P=0.000). HO-1 mRNA expression levels were found to positively correlate with the levels of MDA (r=0.451; P=0.010) and fasting plasma glucose (FPG; r=0.337; P=0.039). Partial correlation analysis demonstrated that, after removing the effects of body mass index, FPG and 2-h plasma glucose, HO-1 protein expression levels were positively correlated with the levels of HO-1 mRNA expression (r=0.611; P=0.005), ROS (r=0.526; P=0.021) and MDA (r=0.519; P=0.015). These findings indicate that pregnant females with GDM may be protected against oxidative injury due to the induction of adaptive and compensatory expression of HO-1 to guard against oxidative stress induced by high glucose levels.

A new xylanase gene (xyn43A) from Aspergillus niger XZ-3S was cloned and expressed in Escherichia coli BL21-CodonPlus (DE3)-RIL. The coding region of the gene was separated by only one intron 86 bp in length. It encoded 318 amino acid residues of a protein with a calculated molecular weight (MW) of 33.47 kDa plus a signal peptide of 19 amino acids. The amino acid sequence of the xyn43A gene showed 77.56% amino acid identity to A. nidulans xylanase, and the phylogenetic tree analysis revealed that xyn43A had close relationships with those of family 43 of glycosyl hydrolases reported from other microorganisms. Three-dimensional structure modeling showed that Xyn43A had a typical five-blade β-propeller fold. The mature peptide encoding cDNA was subcloned into pET-28a (+) expression vector. The resultant recombinant plasmid pET-28a-xyn43A was transformed into Escherichia coli BL21-CodonPlus (DE3)-RIL, and xylanase activity was measured. A maximum activity of 61.43 U/mg was obtained from the cellular extract of E. coli BL21-CodonPlus (DE3)-RIL harboring pET-28a-xyn43A. The recombinant xylanase had optimal activity at pH5.0 and 45°C. Fe(3+), Cu(2+) and EDTA had an obvious active effect on the enzyme.

Objective: To survey the clinical epidemiology and correlations between pathology and clinical features of major groups of kidney diseases in a rural area of China., Methods: From January 1996 to December 2010, histologic diagnosis of renal disease was made on samples collected from 919 patients from a single center in the midland rural area of China. Demographic data were obtained from all patients, and clinical profiles were analyzed in 917 patients., Results: The mean age of the whole group was 33.13 (14.13) years (range 16-72 years). Men accounted for 55.28% (n = 508) and women made up 45.72% (n = 408). Patients aged 16 to 50 years comprised 83.75% of the sample (n = 770). Lupus nephritis was the predominant diagnosis in women; renal diseases were predominant in men. In patients with nephrotic syndrome, mesangial proliferative glomerulonephritis was the most frequent pathologic pattern (39.46%), followed by IgA nephropathy (18.39%), whereas in patients with nephritic syndrome, IgA nephropathy (39.64%) was the most frequent pathologic pattern, followed by mesangial proliferative glomerulonephritis (32.38%). The most common pathologic pattern in patients with secondary glomerulonephritis was Henoch-Schoˇnlein purpura nephritis, followed by lupus nephritis., Conclusions: Mesangial proliferative glomerulonephritis was the most common renal pathologic pattern. Male adolescents were predominant in this group of patients. The most common clinical syndrome was nephrotic syndrome.

This study is purposed to investigate the effects of praeruptorin A (PA) and praeruptorin C (PC) on UGT1A1 in HepG2 cells through hCAR pathway. PA and PC were incubated with HepG2 cells for 24 h and 48 h, mRNA and protein expressions of UGT1A1 were determined by real-time PCR and Western blotting assays. Additionally, effects of PA and PC on UGT1A1 mRNA and protein expressions were also measured after transient transfection of a specific CAR siRNA for 72 h in HepG2 cells. UGT1A1 mRNA and protein expression levels were significantly increased by PA and PC after incubation for 48 h. Moreover, the mRNA and protein up-regulations of UGT1A1 were attenuated by transient transfection of a specific CAR siRNA, suggesting the induction was mediated by CAR. The results suggest that PA and PC can significantly up-regulate UGT1A1 expression partially via the CAR-mediated pathway.

Tacrolimus (TAC) is an immunosuppressant that has been widely used alone or in combination with prednisone (PRED) to prevent acute rejection after organ transplantation. Wuzhi tablet (WZ, Schisandra sphenanthera extract) is often prescribed with TAC to prevent drug-induced hepatitis. We recently reported that WZ could significantly increase TAC blood exposure by inhibiting P-gp-mediated efflux and CYP3A-mediated metabolism of TAC. PRED is also a substrate of P-gp and is a weak inducer of CYP3A, and drug-drug interactions within this combination therapy might occur. Therefore, the purpose of this study was to investigate the effect of long-term treatment of WZ and PRED on the pharmacokinetics of TAC in rats. After 14 days of co-administration of WZ and PRED, the AUC(0-24h) of oral TAC was increased (from 59.6±37.3 to 95.3±39.4 ng h/ml, p=0.18) and the clearance was decreased (from 38.4±28.4 to 17.7±6.4 l/h/kg, p=0.15). When only co-administered with WZ, AUC(0-24h) of TAC was demonstrated a significantly increase (from 59.6±37.3 to 135.9±34.8 ng h/ml, p<0.05). The concomitant administration of PRED resulted in a reduction in the systemic exposure of TAC and an increase in its clearance, though neither was statistically significant. Thus, our study suggested that the presence of WZ and PRED still could increase the systemic exposure of TAC in rats. The drug-drug interactions among this combination therapy should still be taken into consideration in clinical practice., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Background: Renal biopsy is necessary for diagnosing the pathological changes of primary nephrotic syndrome (NS). However, it is invasive, time-consuming and can not be performed frequent on the same patient. Thus, development of a non-invasive and rapid diagnostic method may improve clinical patient management., Methods: Proteomic tool magnetic bead-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MB-based MALDI TOF MS) was applied to serum to determine peptidome patterns that are characteristic of different pathological changes., Results: Serum specimen from 114 patients with NS (62 were minimal change disease (MCD), 30 were membranous nephropathy (MN), and 22 were focal segmental glomerulosclerosis (FSGS)) and 60 normal individuals were analyzed using MB-based MALDI TOF MS. The peptidome pattern was generated by genetic algorithms using a training set of 31 MCD, 15 MN, 11 FSGS and 30 normal individuals and was validated by an independent testing set of the remaining samples. The serum peptidome pattern, based on a panel of 14 peaks, accurately recognized samples from MCD, MN, FSGS and healthy control with sensitivities of 93.5%, 86.7%, 63.6% and 90.0%, and specificities of 98.2%, 94.4%, 100% and 89.5%, respectively. Moreover, one peptide from peptidome pattern was identified by liquid chromatography tandem mass spectrometry (LC MS/MS) as fibrinogen A., Conclusion: Detection of the serum peptidome pattern is a rapid, non-invasive, high-throughout, and reproducible method for identifying the pathological patterns of patients with nephrotic syndrome.

The secondary structure of the mushroom polyphenoloxidase treated by the high hydrostatic pressure (HHP) was analyzed by the synchrotron radiation circular dichroism (SRCD) and Fourier transform infrared spectroscopy (FTIR). The alpha-helix content of mushroom PPO was decreased after HHP treatment, which indicated that the secondary structure of PPO was changed. There was a discrepancy of the result of the secondary structure content between untreated or HHP-treated mushroom PPO analyzed by SRCD and FTIR spectra, and this discrepancy may be due to the different determination temperature, the concentration of the PPO solution and the spectra analysis method etc. The fluorescence spectra showed that the fluorescence intensity of the mushroom PPO was decreased after HHP treatment, and a red shift was observed after HHP treatment, which indicated that the tertiary structure of the enzyme molecule has been modified.

Background: Long-term outcomes for patients with adult idiopathic nephrotic syndrome correlate closely with steroid responsiveness. The aim of this prospective study was to evaluate the difference in serum proteomes between steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) patients and identify potential biomarkers for the prediction of SRNS., Methods: We performed a gel-based proteomic study of serum obtained from SRNS and SSNS patients and healthy controls at the time of presentation (n = 6 for each group). Proteins from the serum samples were separated using 2-D electrophoresis, digested in-gel and subjected to MALDI-TOF-MS/MS analysis. Further validation was performed utilizing Western blot and ELISA. The sensitivities and specificities of the candidate proteins for predicting SRNS were determined using receiver operating characteristic curves., Results: Thirteen differentially expressed proteins were identified as haptoglobin (Hp) with different isoelectric points and molecular weights. Western blot and ELISA analysis of samples from 146 subjects (healthy controls = 52, SSNS = 54, SRNS = 40) showed a markedly increased level of Hp in the serum, but not urine, of SRNS compared to SSNS patients. The optimal serum cutoff level of Hp was set at ≥1,279 µg/ml using the receiver operating characteristic curve. The sensitivity and specificity for predicting SRNS were 85.0 and 96.3%, respectively., Conclusions: This study provides a novel overview of the difference in serum proteomes of SSNS and SRNS patients. Serum Hp may be a useful predictive biomarker for steroid therapy efficacy in the treatment of idiopathic nephrotic syndrome., (Copyright © 2012 S. Karger AG, Basel.)

The title compound, C(34)H(40)N(2)O(4)·2C(3)H(7)NO, was synthesized by the Mannich condensation of ethane-diamine, formaldehyde and p-cresol. In the crystal, the tetra-phenol mol-ecule is arranged around an inversion center. The mol-ecule and the dimethyl-formamide solvate are linked through an O-H⋯O hydrogen bond. An intra-molecular O-H⋯N hydrogen bond occurs in the tetra-phenol mol-ecule, which may influence the mol-ecular confomation. Futhermore, C-H⋯O and π-π stacking inter-actions [centroid-centroid distance = 3.7081 (14) Å] stabilize the crystal packing, building a three-dimensional network.

IN THE CRYSTAL STRUCTURE OF THE TITLE COMPOUND [SYSTEMATIC NAME: 1-(2-hy-droxy-eth-yl)-2-methyl-5-nitro-1H-imidazol-3-ium perchlorate], C(6)H(10)N(3)O(3) (+)·ClO(4) (-), the cations are linked by inter-molecular N-H⋯O hydrogen bonds into zigzag chains along the c axis. The cations and anions are connected by O-H⋯O and C-H⋯O hydrogen bonds. A weak intra-molecular C-H⋯O hydrogen bond is also observed.

In the title compound, C(14)H(17)ClN(2)S, the dihedral angle between the planes of the thia-zole and chloro-phenyl rings is 88.86 (3)°. In the crystal, inversion dimers occur, linked by pairs of N-H⋯N hydrogen bonds.

The crystals of the title salt, C(5)H(12)N(+)·C(11)H(7)O(3) (-), were obtained from a methanol/water solution of 3-hydr-oxy-2-naphthoic acid and piperidine at room temperature. In the crystal structure, the piperidinium cations display a chair conformation and link with hydroxy-naphthoate anions via N-H⋯O and C-H⋯O hydrogen bonds. An intra-molecular O-H⋯O inter-action is also present.

In the title cocrystal, C(10)H(8)O(2)·C(3)H(4)N(2), inter-molecular O-H⋯O and N-H⋯O hydrogen bonds connect the naphthalene-2,3-diol and imidazole mol-ecules into a two-dimensional supra-molecular framework.

In order to obtain the drugs with broader antibacterial spectrum, better antibacterial effect and less side-effect, modifications with lipid solublity group at the position of piperazinyl of ciprofloxacin 13C NMR, ESI-MS and elemental analysis. The lipid solublility of the new compounds was better than that of ciprofloxacin. The results of antibacterial activity in vitro showed that most of the target compounds possessed relatively high inhibiting activity on Escherichia coli and Pseudomonas aeruginosa. The antibacterial activity of the target compound 3d was higher than that of ciprofloxacin against Escherichia coli.

The synthesis and crystal structures of two new NLO-active coordination polymers, [Zn(2-pc)(4-pc)] and [Cd(2-pc)(4-pc)(H(2)O)]xN(2)H(4) (2-pc = 2-pyridine carboxylate, 4-pc = 4-pyridine carboxylate), bridged by in situ generated mixed ligands under solvothermal treatment is described.

Homochiral/heterochiral crystallizations of helical chiral polymer chains bridged by achiral poly-pyridyl ligands dependent on the structures of the bridging ligands and independent on the solvent are described, implying a possible strategy to design achiral crystals of helical chains using chiral bridging ligands.