Cryptotanshinone inhibits cytotoxin-associated gene A-associated development of gastric cancer and mucosal erosions

BACKGROUND Approximately 90%of new cases of noncardiac gastric cancer(GC)are related to Helicobacter pylori(H.pylori),and cytotoxin-associated gene A(CagA)is one of the main pathogenic factors.Recent studies have shown that the pharmacological effects of cryptotanshinone(CTS)can be used to treat a variety of tumors.However,the effects of CTS on H.pylori,especially CagA+strain-induced gastric mucosal lesions,on the development of GC is unknown.AIM To assess the role of CTS in CagA-induced proliferation and metastasis of GC cells,and determine if CagA+H.pylori strains causes pathological changes in the gastric mucosa of mice.METHODS The effects of CTS on the proliferation of GC cells were assessed using the Cell Counting Kit-8(CCK-8)assay,and the abnormal growth,migration and invasion caused by CagA were detected by CCK-8 and transwell assays.After transfection with pSR-HA-CagA and treatment with CTS,proliferation and metastasis were evaluated by CCK-8 and transwell assays,respectively,and the expression of Src homology 2(SH2)domain–containing phosphatase 2(SHP2)and phosphorylated SHP2(p-SHP2)was detected using western blotting in AGS cells.The enzymelinked immunosorbent assay was used to determine the immunoglobulin G(IgG)level against CagA in patient serum.Mice were divided into four groups and administered H.pylori strains(CagA+or CagA-)and CTS(or PBS)intragastrically,and establishment of the chronic infection model was verified using polymerase chain reaction and sequencing of isolated strains.Hematoxylin and eosin staining was used to assess mucosal erosion in the stomach and toxicity to the liver and kidney.RESULTS CTS inhibited the growth of GC cells in dose-and time-dependent manners.Overexpression of CagA promoted the growth,migration,and invasion of GC cells.Importantly,we demonstrated that CTS significantly inhibited the CagAinduced abnormal proliferation,migration,and invasion of GC cells.Moreover,the expression of p-SHP2 protein in tumor tissue was related to the expression of IgG against CagA in the serum of GC patients.Additionally,CTS suppressed the protein expression levels of both SHP2 and p-SHP2 in GC cells.CTS suppressed CagA+H.pylori strain-induced mucosal erosion in the stomach of mice but had no obvious effects on the CagA-H.pylori strain group.CONCLUSION CTS inhibited CagA-induced proliferation and the epithelial-mesenchymal transition of GC cells in vitro,and CagA+H.pylori strains caused mucosal erosions of the stomach in vivo by decreasing the protein expression of SHP2.

Isolation and Characterization of the Cytoplasmic Male Sterility Associated Gene of Cotton(Gossypium harknessii)

Cytoplasmic male sterility(CMS) is a maternally inherited trait that results in the failure to produce functional pollen.It was identified in many plants,and it is widely used to exploit heterosis.

Pathogenesis of chronic enteropathy associated with the SLCO2A1 gene:Hypotheses and conundrums

Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.

Genome-wide association with transcriptomics reveals a shade-tolerance gene network in soybean

Shade tolerance is essential for soybeans in inter/relay cropping systems.A genome-wide association study(GWAS)integrated with transcriptome sequencing was performed to identify genes and construct a genetic network governing the trait in a set of recombinant inbred lines derived from two soybean parents with contrasting shade tolerance.An improved GWAS procedure,restricted two-stage multi-locus genome-wide association study based on gene/allele sequence markers(GASM-RTM-GWAS),identified 140 genes and their alleles associated with shade-tolerance index(STI),146 with relative pith cell length(RCL),and nine with both.Annotation of these genes by biological categories allowed the construction of a protein–protein interaction network by 187 genes,of which half were differentially expressed under shading and non-shading conditions as well as at different growth stages.From the identified genes,three ones jointly identified for both traits by both GWAS and transcriptome and two genes with maximum links were chosen as beginners for entrance into the network.Altogether,both STI and RCL gene systems worked for shade-tolerance with genes interacted each other,this confirmed that shadetolerance is regulated by more than single group of interacted genes,involving multiple biological functions as a gene network.

Expression and significance of fat mass and obesity associated gene and forkhead transcription factor O1 in non-alcoholic fatty liver disease

Background Non-alcoholic fatty liver disease （NAFLD） is a complex disorder and has been closely linked to obesity.The fat mass and obesity-associated （FTO） gene is a newly discovered gene related to obesity,which enhances oxidative stress and tipogenesis in NAFLD.The forkhead transcription factor O1 （FoxO1） is another important gene involved in NAFLD,which causes lipid disorders when insulin resistance appears in the liver.However,the interactions between FTO and FoxO1 during the pathogenesis of NAFLD have not been fully elucidated.This study was designed to identify the relationship between these two factors that are involved in the development of NAFLD.Methods This study includes two parts referred to as animal and cell experiments.Twelve female SPF C57BL/6 mice were fed a high-fat diet to serve as an NAFLD animal model.Aspartate aminotransferase （AST）,alanine aminotransferase （ALT）,total triglyceride （TG）,total cholesterol （TC）,alkaline phosphatase （ALP）,high-density lipoprotein （HDL）,and low-density lipoprotein （LDL） were measured.Immunohistochemical analysis was used to detect the expression and histological localization of FTO,FoxO1,and adenosine monophosphate （AMP）-activated protein kinase （AMPK）.The L02 cells were exposed to high fat for 24,48,or 72 hours.Oil red O staining was used to detect intracellular lipid droplets.Reverse transcription-polymerase chain reaction was used for analyzing the levels of FTO and FoxO1 mRNA.Results At the end of 10 weeks,ALP,ALT,AST,and LDL were significantly increased （P ＜0.01）,while TC and TG were also significantly higher （P ＜0.05）.In addition,HDL was significantly decreased （P ＜0.05）.The FTO and FoxO1 proteins were weakly expressed in the control group,but both FTO and FoxO1 were expressed significantly higher （P ＜0.01） in the experimental group,and the expression of the two factors was significantly correlated.AMPK in the high-fat group showed a low level of correlation with FTO,but not with FoxO1.Oil Red O staining results showed that the cells cultured in 50％ fetal bovine serum for 24,48,or 72 hours exhibited steatosis.FTO and FoxO1 mRNA were increased in the high-fat group compared with the normal group （P ＜0.01）.The expression levels of FTO and FoxO1 mRNA were the highest at 48 hours （P ＜0.05）.Conclusions A high-fat diet leads to higher expression of FTO,phosphorylation of FoxO1,and decreased phosphorylation of AMPK.These results suggest that the interactions between FTO and FoxO1 are closely related to the pathogenesis of NAFLD.

Identification of Differentially Expressed Genes Associated with Cotton Fiber Development in a Chromosomal Substitution Line(CS-B22sh)

One of the impediments in the genetic improvement of cotton fiber is the paucity of information about genes associated with fiber development.Availability of chromosome arm substitution line CS-

Genetic Variants in the ELOVL5 but not ELOVL2 Gene Associated with Polyunsaturated Fatty Acids in Han Chinese Breast Milk

The present study was designed to examine the contributions of the fatty acid elongase （ELOVL） gene polymorphisms to the levels of polyunsaturated fatty acids （PUFAs） in breast milk. Two hundred and nine healthy Han Chinese mothers were included in the study. Carriers of minor alleles of SNPs （rs2397142 and rs9357760） in ELOVL5 were associated with higher levels of linoleic acid （LA）, dihomo-γ-linolenic acid （DGLA）, arachidonic acid （AA）, docosatetraenoic acid （DTA）, docosahexenoic acid （DHA）, while in rs209512 of ELOVL5 the carriers of minor alleles had lower levels of DTA compared to major homozygote alleles （P ranged from 0.004-0.046）, and genetically explained variability ranged from 3.2% for eicosapentaenoic acid （EPA） to 6.0% for LA. Our findings demonstrated that common variation in ELOVL5 gene encoding rate-limiting enzymes in the metabolism of PUFAs contribute to the PUFAs in breast milk.

Interleukin-8 gene polymorphism is associated with acute coronary syndrome in a Han Chinese population

Background Acute coronary syndrome(ACS) is one of the most common forms of heart diseases.Recent studies have revealed that interleukin(IL)-8 plays a kev role in the development of atherosclerosis plaque and its complications, but the relationship of its common variants with ACS has not been extensively studied.Methods We tested the hypothesis that variants in IL-8-251 A/T was associated with susceptibility to ACS and its recurrence in a Chinese case-control study comprising 675 patients with ACS and 636 control subjects and replicated the investigation in an independent study comprising 360 cases and 360 control subjects. The plasma concentration of IL-8 was measured by enzyme-linked immunosorbent assay.Results IL-8 -251A】T poly-morphism was associated with increased susceptibility to ACS (P=0.004;OR=1.30 CI:1.12-1.53).Replication in the second study yielded similar results.IL-8 -251 A/T may affect the expression of IL-8 by the evidence that augmented IL-8 production revealed in serum of the AMI patients by ELISA. Conclusions IL-8 -251 A/T polymorphism is associated with ACS risk in Chinese Han population and An allele of IL-8- 251A/T may be an independent predictive factor.

p53 Gene Mutations in Asbestos Associated Cancers

The accumulation of mutant p53 protein in cancer cells was observed by immunohistochemistry analysis. DNA was extracted from paraffin-embedded tissue. Exons 5, 7 and 8 were amplified and studied by PCR-SSCP and sequencing analysis. Ten cases of asbestos associated cancer tissue were studied, of which five cases had adenocarcinoma, and the other five had mesothelioma, squamous carcinoma, small cell lung cancerl adenosquamous carcinoma and malignant lymphoma respectively. Employing monoclonal antibody PAb1801, five cases were found to be mutant p53 protein mpitive. Seven cases were found to have mutations by PCRSSCP. A total of 7 cases (8 mutations) were found to be positive and 4 cases were found to be opitive by both of these analyses. Of the 8 mutations found by SSCP analysis, 4(50%, 4/8)were clustered in exon 8. A high mutation frequency was noticed in adenocarcinoma (80%,4/5). ffequencing analysis on two specimens revealed two hotspot mutations. In codon 234,TAC for tyrooin was mutated to AAC fOr aspar8gine by a T to A transversion of the first letter. In codon 273, CGT for arginine was mutated to AGT for serine by a C to A transversion of the first letter. ln conclusion, the mutation of p53 gene is common in asbestos associated cancers. However, the mutational spectrum of asbestos associated cancers might be different from that of non-asbestos associated cancers.

Implication of proliferation gene biomarkers in pulmonary hypertension

Objective/Background:Proliferation is a widely recognized trigger for pulmonary hypertension(PH),a life-threatening,progressive disorder of pulmonary blood vessels.This study was aimed to identify some proliferation associated genes/targets for better comprehension of PH pathogenesis.Methods:Human pulmonary arterial smooth muscle cells(hPASMCs)were cultured in the presence or absence of human recombinant platelet derived growth factor(rhPDGF)-BB.Cells were collected for metabolomics or transcriptomics study.Gene profiling of lungs of PH rats after hypoxia exposure or of PH patients were retrieved from GEO database.Results:90 metabolites(VIP score>1,fold change>2 or<0.5 and p<.05)and 2701 unique metabolism associated genes(MAGs)were identified in rhPDGF-BB treated hPASMCs compared to control cells.In addition,1151 differentially expressed genes(313 upregulated and 838 downregulated)were identified in rhPDGF-BB treated hPASMCs compared to control cells(fold change>2 or<0.5 and p<.05).152 differentially expressed MAGs were then determined,out of which 9 hub genes(IL6,CXCL8,CCL2,CXCR4,CCND1,PLAUR,PLAU,HBEGF and F3)were defined as core proliferation associated hub genes in protein proten interaction analysis.In addition,the hub gene-based LASSO model can predict the occurrence of PH(AUC=0.88).The expression of CXCR4,as one of the hub genes,was positively correlated to immune cell infiltrates.Conclusion:Our findings revealed some key proliferation associated genes in PH,which provide the crucial information concerning complex metabolic reprogramming and inflammatory modulation in response to proliferation signals and might offer therapeutic gains for PH.

Novel Association of Killer Cell Immunoglobulin-like Receptor Genes with EBV-infectious Diseases in Children

Killer cell immunoglobulin-like receptors （KIRs） which are mainly expressed on natural killer （NK） cells are implicated in many virus infections. However, it is unclear whether or not KIRs are associated with susceptibility to Epstein-Barr virus （EBV） infection related diseases. Therefore, the purpose of our study was to investigate possible correlation between polymorphisms of KIR genes and infectious mononucleosis （IM）/EBV-associated hemophagocytic Iymphohistiocytosis （EBV-HLH）. The polymorphisms of KIR genes were detected by polymerase chain reaction with sequence-specific primers （PCR-SSP）. The results would contribute to clarify the association of KIRs with EBV induced diseases, and provide new insights into the role of NK cells and innate immune response against viral infections and/or subsequent progression.

Association between essential hypertension and polymorphisms of beta 1 adrenergic receptor gene G1165C (Gly389Arg) in Chinese Mongolian population

BACKGROUND： The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is helpful to develop researches on the genetics of various diseases including hypertension in Mongolian population. OBJECTIVE： To analyze the association between the polymorphism of beta1 adrenergic receptor （β1-AR） gene G1165C （Arg389Gly）, an important candidate gene for various diseases of cardiovascular system, and essential hypertension in Mongolian population. DESIGN ： A cross-sectional study SETTINGS： Department of Neurology, the First Affiliated Hospital of Inner Mongolia Medical College; Wulate Houqi Red Cross Society. PARTICIPANTS： The survey was carried out from February 2003 to March 2005. Totally 239 Mongolian residents, whose blood relations of 3 generations were all Mongolians, were selected from Wulate Houqi, Inner Mongolia, and they were all informed with the survey and detected items. Based on the diagnostic standard of hypertension set by WHO in 1999, the subjects were divided into two groups according to the level blood pressure： ① Normal blood pressure group （n=117）： systolic blood pressure （SBP） 〈 140 mm Hg （1 mm Hg =0.133 kPa）, diastolic blood pressure （DBP） 〈 90 mm Hg, and those having histories of cerebrovascular disease, heart disease, diseases of liver, kidney and tiroides, and diabetes mellitus were excluded. ② Essential hypertension group （n=122）： including 51 patients with simple high SBP. All the enrolled subjects had no blood relationship with each other, and had no history of miscegenation. METHODS ： The body height, body mass, waist circumference and blood lipids were measured routinely, and their habits of smoking and drinking were also investigated. Penpheral venous blood （5 mL） was drawn, the genome DNA was extracted, and the polymorphisms of the β1-AR Gl165C （Gly389Arg） genotype were detected with the Sequenom system. Polymerase chain reaction （PCR） experiment and SNP detection were performed in Huada Gene Laboratory of Bejing, then the univariate analysis of variance was applied in the sample comparison among groups, and the chi-square test was used to compare the genotypes and allele frequencies. The odd ratio （OR） and 95% confidence interval （CO were calculated. MAIN OUTCOME MEASURES： The distributions of β1-AR Gl165C （Gly389Arg） genotypes and alleles were observed. RESULTS： A11 the 239 subjects were involved in the analysis of results, and no one missed, ①Comparison of β1-AR G1165C （Gly389Arg） genotypes and allele distnbutions： In Mongolian population, the frequencies of CC and GG＋GC genotypes at β1-AR G1165C （Gly389Arg） site in the essential hypertension group （72%, 28%） were not significantly different from those in the normal blood pressure group （67%, 33%） （xz=0.841, P=-0.359; OR 0.773, 95%Cl： 0.445-1.342）; The frequencies of C and G alleles also had no significant differences between the essential hypertension group （85%, 15%） and the normal blood pressure group （82%, 18%） （x^2=1.136, P=-0.287; OR： 0.769, 95%Cl： 0.747-1.248）. ②The frequencies of CC and GG＋GC genotypes at β1-AR G1165C （Gly389Arg） site had no significant differences between the patients with simple high SBP （71%, 29%） and the normal blood pressure group （x^2=0.250, P=-0.617; OR： 0.833, 95%C/： 0.408-1.703）; The frequencies of C and G alleles were not significantly different between the patients with simple high SBP （86%, 14%） and the normal blood pressure group （x^2=0.670, P=-0.413; OR 0.766, 95%Cl： 0.404-1.453）. CONCLUSION： In Mongolian population, the distributions of the genotypes and alleles of β1-AR Gl165C （Gly389Arg） have no obvious differences between the subjects with normal blood pressure and the patients with essential hypertension （including simple SBP increase）, which suggests that G1165C （Glu389Asp） site of β1-AR gene may be not a genetic mark of essential hypertension and simple high SBP in Mongolian population.

Lack of association between cellular repressor of E1A-stimulated genes(GREG)polymorphisms and coronary artery disease in the Han population of North China

Objectives Phenotypic switching of smooth muscle cells(SMCs) plays a critical role in the pathogenesis of atherosclerotic lesions such as coronary artery disease (CAD).Accumulating evidence demonstrates(hat a cellular repressor of E1A-stimulated genes(CREG) plays a role in the maintenance of the mature phenotype of vascular SMCs. The purpose of the present study was to assess the possible association between CREG and CAD in the Han population of North China.Methods The promoter region of CREG by direct sequencing was conducted in 48 subjects.Then SNP rs2995073 and another 4 tagSNPs(rs4657669,rs3767443, rsl6859185,rs3753921) were selected for the association study.All five selected SNPs were determined in 1161 patients with angiographically proven CAD and 960 controls with normal coronary angiograms to investigate the possible involvement of CREG in CAD.Results Genotype frequencies of the five examined polymorphisms were similarly distributed between CAD group and controls(P】0.05).Further haplotype analysis also found no significant differences in the distributions between CAD group and controls(P】0.05). Conclusions This study did not show an association between common variants of CREG and CAD in the northern Chinese Han population.

TaNRT2.1-6B is a dual-affinity nitrate transporter contributing to nitrogen uptake in bread wheat under both nitrogen deficiency and sufficiency

Multiple nitrate transporter(NRT)genes exist in the genome of bread wheat,and it is of great importance to identify the elite NRT genes for N-efficient wheat cultivar breeding.A candidate gene association study(CGAS)of six N use efficiency(NUE)related traits(grain N concentration(GNC),straw N concentration(SNC),grain yield(GY),grain N accumulation(GNA),shoot total N accumulation(STN)and N harvest index(NHI))was performed based on SNPs in 46 NRT2 genes using a panel composed of 286 wheat cultivars.CGAS identified TaNRT2.1-6B as an elite NRT gene that is significantly associated with four(NHI,SNC,GNA and GY)of the six NUE-related traits simultaneously.TaNRT2.1-6B is located on the plasma membrane and acts as a dual-affinity NRT.The overexpression of TaNRT2.1-6B increased the N influx and root growth of wheat,whereas gene silence lines resulted in the opposite effects.The overexpression of TaNRT2.1-6B also improved GY and N accumulation of wheat under either limited or sufficient N conditions.The data provide the TaNRT2.1-6B gene and the two associated SNP markers as promising powerful tools for breeding wheat cultivars with high N uptake ability and NUE.

Genome-Wide Association Study for Certain Carcass Traits and Organ Weights in a Large White×Minzhu Intercross Porcine Population

Porcine carcass traits and organ weights have important economic roles in the swine industry. A total of 576 animals from a Large White×Minzhu intercross population were genotyped using the Illumina PorcineSNP60K Beadchip and were phenotyped for 10 traits, speciifcally, backfat thickness （6-7 libs）, carcass length, carcass weight, foot weight, head weight, heart weight, leaf fat weight, liver weight, lung weight and slaughter body weight. The genome-wide association study （GWAS） was assessed by Genome Wide Rapid Association using the mixed model and regression-genomic control approach. A total of 31 single nucleotide polymorphisms （SNPs） （with the most signiifcant SNP being MARC0033464, P value=6.80×10-13） were located in a 9.76-Mb （31.24-41.00 Mb） region on SSC7 and were found to be signiifcantly associated with one or more carcass traits and organ weights. High percentage of phenotypic variance explanation was observed for each trait ranging from 31.21 to 67.42%. Linkage analysis revealed one haplotype block of 495 kb, in which the most signiifcant SNP being MARC0033464 was contained, on SSC7 at complete linkage disequilibrium. Annotation of the pig reference genome suggested 6 genes （GRM4, HMGA1, NUDT3, RPS10, SPDEF and PACSIN1） in this candidate linkage disequilibrium （LD） interval. Functional analysis indicated that the HMGA1 gene presents the prime biological candidate for carcass traits and organ weights in pig, with potential application in breeding programs.

Quantitative trait loci for the number of vertebrae on Sus scrofa chromosomes 1 and 7 independently influence the numbers of thoracic and lumbar vertebrae in pigs

Although quantitative trait loci（QTLs） for number of thoracic-lumbar vertebrae have been identified on Sus scrofa chromosomes（SSCs） 1 and 7, the influence of these QTLs on the thoracic and lumbar vertebrae is not clear. The aim of this study was to identify single nucleotide polymorphisms（SNPs） associated with total number of thoracic-lumbar vertebrae and for each trait（number of thoracic and lumbar vertebrae） separately. A total of 581 individuals from an F2 Large White×Minzhu population were genotyped using an SNP60 K chip. Performing a genome-wide association study（GWAS） for total number of thoracic-lumbar vertebrae, 38 significant SNPs were identified in two QTL regions located on SSC1 and SSC7. Performing a GWAS for number of thoracic vertebrae only, 72 significant SNPs were located on SSC7. While performing a GWAS for number of lumbar vertebrae only, 17 significant SNPs were identified on SSC1. Gene mining suggested that the gene encoding orphan nuclear receptor, germ cell nuclear factor（NR6A1） on SSC1 was a strong candidate affecting the number of lumbar vertebrae in pigs. Additionally, genes encoding vertnin（VRTN）, prospero homeobox 2（PROX2）, Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog（FOS）, and transforming growth factor beta 3（TGFB3） may be important candidates affecting the number of thoracic vertebrae in pigs. QTLs on SSC1 and SSC7 independently influenced the numbers of thoracic and lumbar vertebrae. These results shed light on the complex genetic background of vertebrae development in pigs.

Apolipoprotein E gene polymorphisms associated with processing speed and executive functions in healthy Han Chinese

Dear Editor,A few studies have focused on exploring APOE gene- related effects on cognitive functions and brain activities in healthy populations. Bondi et aL found that ε4 carriers perform significantly worse on the California Verbal Learning Test than non-carriers in non-demented old subjects （mean age, 72 years）ε11. But the results are not entirely consistent. For example, Scarmeas et aL found no effect of the E4 allele on neuropsychological performance[2] in young adults, and Jochemsen et al. found that the ε4 allele is associated with age-related cognitive decline[3]. Furthermore, protective and negative effects of the E2 allele on cognition are inconsistent[4＇ s]. APOE E2 is thought to be a protective allele for AD in the elderly population due to its role in the superior cognitive performance of ε2 carriers compared to E3 or E4 carriers[5]. However, the ε2 allele has also been found to have a negative effect on AD pathology[4].

The association between common genetic variation in the FTO gene and metabolic syndrome in Han Chinese

Background Genome-wide association studies for type 2 diabetes mellitus （T2DM） identified FTO gene as a locus conferring increased risk for common obesity in many populations with European ancestry. However, the involvement of FTO gene in obesity or T2DM related metabolic traits has not been consistently established in Chinese populations. The objective of this study was to investigate the association of FTO genetic polymorphisms with metabolic syndrome （MetS） in Han Chinese. Methods We tested 41 FTO single nucleotide polymorphisms （SNPs） for association between FTO and MetS-related traits. There were a total of 236 unrelated subjects （108 cases and 128 controls）, grouped according to the International Diabetes Federation （IDF） criteria. Results Of the 41 SNPs examined, only SNP rs8047395 exhibited statistical significance （P=-0.026） under a recessive model, after Bonferroni adjustment for multiple testing （OR 1.64, 95% CI 1.11-2.42; P=-0.014）. The common distributions of this polymorphism among Chineseawith a minor allele frequency （MAF） of 36% in the control group versus 48% in the Met$ group--greatly improved our test power in a relatively small sample size for an association study. Previously identified obesity- （or T2DM-） associated FTO SNPs were less common in Hart Chinese and were not associated with MetS in this study. No significant associations were found between our FTO SNPs and any endophenotypes of MetS. Conclusions A more common risk-conferring variant of FTO for MetS was identified in Han Chinese. Our study substantiated that genetic variations in FTO locus are involved in the pathogenesis of MetS.

Cloning the full-length cDNA of a gene responsible for vascular smooth muscle cell proliferation in atherogenesis and study of function

To clone the full length cDNA of a gene responsible for vascular smooth muscle cell (v SMC) proliferation in atherogenesis, and study its function Methods Oxidized low density lipoprotein (ox LDL) at optimal concentration was used as the stimulant to induce v SMC proliferation in culture medium A cDNA subtractive library of v SMC proliferation specific to ox LDL stimulation was established using subtractive hybridization technique Methods, including blotting, Northern hybridization and gene sequencing, were used to clone new gene fragments By using full length cDNA screening and protein expression techniques, one full length cDNA was cloned and its function was studied Results One full length cDNA was cloned The new gene (Genbank AF 174647) expressed a 44 kDa protein, which might be associated with the activity of ox LDL Conclusion The new gene cloned may be associated with SMC proliferation in atherogenesis

Genetic factors related to the widespread dissemination of ST11 extensively drug-resistant carbapenemase-producing Klebsiella pneumoniae strains within hospital

Background:Carbapenemase-producing Klebsiella pneumoniae(CP-Kp)poses distinct clinical challenges due to extensively drug resistant(XDR)phenotype,and sequence type(ST)11 is the most dominant blaKPC-2-bearing CP-Kp clone in China.The purpose of this current retrospective study was to explore the genetic factors associated with the success of XDR CP-Kp ST11 strains circulated in the intensive care unit(ICU)of a Chinese tertiary hospital.Methods:Six ST11 XDR CP-Kp strains were identified between May and December 2014 and validated by minimum inhibitory concentration examination,polymerase chain reaction,and pyrosequencing.The six ST11 XDR CP-Kp,as well as three multi-drug resistant(MDR)and four susceptible strains,were sequenced using single-molecule real-time method.Comprehensively structural and functional analysis based on comparative genomics was performed to identify genomic characteristics of the XDR ST11 CP-Kp strains.Results:We found that ST11 XDR blaKPC-2-bearing CP-Kp strains isolated from inpatients spread in the ICU of the hospital.Functionally,genes associated with information storage and processing of the ST11 XDR CP-Kp strains were more abundant than those of MDR and susceptible strains,especially genes correlative with mobile genetic elements(MGEs)such as transposons and prophages.Structurally,eleven large-scale genetic regions taken for the unique genome in these ST11 XDR CP-Kp strains were identified as MGEs including transposons,integrons,prophages,genomic islands,and integrative and conjugative elements.Three of them were located on plasmids and eight on chromosomes;five of them were with antimicrobial resistance genes and eight with adaptation associated genes.Notably,a new blaKPC-2-bearingΔΔTn1721-blaKPC-2 transposon,probably transposed and truncated fromΔTn1721-blaKPC-2 by IS903D and ISKpn8,was identified in all six ST11 XDR CP-Kp strains.Conclusion:Our findings suggested that together with clonal spread,MGEs identified uniquely in the ST11 XDR CP-Kp strains might contribute to their formidable adaptability,which facilitated their widespread dissemination in hospital.