Association between single nucleotide polymorphisms in Wnk1 gene and ischemic stroke in Chinese Han population / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the association between single nucleotide polymorphisms (SNPs) in Wnk1 gene and ischemic stroke in Chinese Han population.</p><p><b>METHODS</b>A hospital-based case-control study was carried out. The ischemic stroke group included 294 Chinese Han subjects, who were admitted with non-fatal ischemic stroke in departments of neurology of 5 hospitals in Xinjiang during January 2008 through December 2009. Control group included 314 age and sex-matched Han subjects without an inquired history of stroke, hospitalized in departments of surgery of these 5 hospitals. Ten tagging SNPs (tSNPs) of the Wnk1 gene were genotyped, and the association between these tSNPs and ischemic stroke were evaluated. The tSNPs (rs3858703, rs11611246, rs7305065, rs1990021, rs34408667, rs12309274, rs1012729, rs956868, rs12828016 and rs953361) were determined by the Multiplex SNaPshot platform. The data were analyzed by using t-test, Ξ2-test and logistic regression. Linkage disequilibrium and haplotype were analyzed by Haploview software.</p><p><b>RESULTS</b>The rates of alcohol drinking, hypertension ,diabetes and hyperlipidemia in ischemic stroke group were higher than those in control group (37.1% vs 21.0%, 62.9% vs 36.6%, 18.0% vs 6.1% and 36.4% vs 17.5%, respectively, all P<0.01). No significant difference in smoking rate was found between two groups. The genotyping loss rates of all sites were less than 1%. All the tSNPs were examined by Hardy-Weinberg equilibrium test except rs34408667. tSNP rs11611246 in the 4th intron of the Wnk1 gene was significantly associated with ischemic stroke. The distribution frequency of T allele in cases was significantly lower than that in male controls (30.3% vs 35.7%, P =0.046). When the samples were further stratified according to gender, rs11611246 was found to be associated with a reduced risk of ischemic stroke in male cases than in controls. GT and TT genotype frequencies were 43.3% and 7.2% in male cases, 43.1% and 15.2% in male controls, respectively (P=0.038). The T allele was associated with a reduced risk of ischemic stroke, with a per-allele OR of 0.702(95%CI:0.517-0.953, P=0.023) in male cases than in male controls. The significance remained after adjusting the covariates of age (P=0.022), or the covariates of age, BMI, cigarette smoking, alcohol drinking, hypertension, diabetes and hyperlipidemia (P=0.008). No association between other 9 tSNPs and ischemic stroke was noted in Chinese Han subjects.</p><p><b>CONCLUSION</b>The polymorphism of rs11611246 on the 4th intron of Wnk1 gene is associated with a reduced risk of ischemic stroke in Chinese Han population and the T allele might be a protective factor for ischemic stroke in male Chinese Hans.</p>

Proapoptotic and pronecrosis effect of different truncated hepatitis C virus core proteins / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>To study the roles of different truncated hepatitis C virus (HCV) core proteins (CORE) in the pathogenesis of HCV persistent infection and hepatocellular carcinoma (HCC) and to assess intracellular localization in transiently transfected cells.</p><p><b>METHODS</b>Seven truncated GFP (green fluorescent protein)-CORE fusion protein expression plasmids were constructed, which contained HCV CORE sequences derived from tumor tissues (BT) and non-tumor tissues (BNT) from one patient infected with HCV. Amino acid (aa) lengths were BT: 1-172 aa, 1-126 aa, 1-58 aa, 59-126 aa, 127-172 aa; BNT: 1-172 aa and C191: 1-172 aa respectively. Subcellular localization of CORE-GFP was analyzed by con-focal laser scanning microscope. Apoptosis and necrosis were quantified by flow cytometry.</p><p><b>RESULTS</b>Different truncated CORE-GFP localized mainly in the cytoplasm, but nuclear staining was also observed. HCV CORE could induce apoptosis and necrosis, and different truncated COREs could induce cell apoptosis and necrosis at different levels. Among the same length 1-172 aa of BT, BNT and C191, the cell apoptosis and necrosis percentage of BT is highest, and C191 is the lowest (BT>BNT>C191). To the different fragment COREs of BT, N-terminal of CORE induced apoptosis and necrosis higher, compared with that of C-terminal (1-172 aa>1-126 aa>1-58 aa>127-172 aa>59-126 aa).</p><p><b>CONCLUSION</b>These results suggest HCV CORE could induce apoptosis and necrosis of cells, which might play an important role in the pathogenesis of HCV persistent infection and HCC and the different CORE domains of different HCV quasi-species might have some difference in their pathogenesis.</p>

Role of erythrocyte on brain edema development after traumatic intracerebral hemorrhage in rats / 中华创伤杂志

Objective To study the effects of erythrecyte on brain edema after traumatic intrace- rebral hemorrhage(TICH)and explore the mechanisms of erythrocyte in brain edema development follow- ing TICH.Methods Firstly,the brain injury model of SD rat was established by applying a free-fall- ing device,then whole blood(WB),lysed RBC(LRBC)or parked RBC(PRBC)were infused with ste- reotactic guidance into injured cortex to produce the model of TICH.All rats were killed at 1,3,and 5 days after injury.The brain water content was measured,immunohistochomistry(SABC)was applied to test HO-1 and TNF-?expressions.Results 1.In WB group,PRBC group and TBI group,the brain water content was the highest on the third day.The brain water content of LRBC group was markedly higher on the first day than on the third and fifth days.Comparison among the four groups showed the wa- ter content was the highest on the 1st day in LRBC group,and on the 3rd day in WB and PRBC groups; there was no significant difference among the four groups on 5th day.2.The positive expression of HO-1 and TNF-?coincided with the change of the water content in groups of WB,PRBC and LRBC.Conclu- sions In rat model of TICH,RBC plays an important role in delayed brain edema formation(3 days after injury),but has no influence at early stage(1 day after injury).The mechanisms of delayed brain edema involves RBC breakdown and inflammation reaction.