Objective To study the role of endothelial cells on the inflammatory cytokine release in septic shock through the septic shock serum stimulating human primary endothelial cells (HPAEC) and peripheral blood mononuclear cells(PBMC).Methods PBMC isolated from healthy people by density gradient centrifugation.HPAEC cell surface markers CD144 and von Willebrand factor(vWF) molecule expression by RT-PCR and Western blot.Serum levels of IL-6,TNF-α,MCP-1 from septic shock patients and healthy human detected by ELISA.HPAEC and PBMC were stimulated with the isolated serums and LPS,respectively.ELISA was used to detect the supernatant IL-6,TNF-α,MCP-1 levels.HPAEC membrane molecules ICAM-1 expression was detected by flow cytometry with serum shock and LPS stimulation.Supernatant levels of IL-6,TNF-α,MCP-1 of HPAEC with S1P1 receptor agonist CYM-5442 pretreatment was detected by ELISA after shock serum stimulation.Results Endothelial cell markers CD144 and vWF molecules could be detected in the HPAEC.Levels of inflammatory cytokines IL-6,TNF-α,MCP-1 in patients with septic shock serum were significantly higher than healthy people (P＜0.01).PBMC and HPAEC with LPS or shock serum treatment respectively,compared with normal group,levels of inflammatory cytokines in the culture supernatant were significantly higher(P＜0.01).For PBMC,the level of inflammatory cytokines between shock group and LPS group were not significantly different (P＞0.05).But for HPAEC,levels of inflammatory cytokines in the supernatant of the shock group compared to the LPS group was significantly higher (P＜0.01).Similarly,when two cells after LPS stimulation,IL-6,TNF-α levels of HPAEC's supernatant were significantly lower than PBMC' s (P＜0.01),MCP-1 levels was no difference (P＞ 0.05).But when the stimulation of shock serum,HPAEC of IL-6,TNF-α levels and PBMC no significant difference (P ＞0.05).MCP-1 was significantly increased (P＜0.01).Shock patients serum stimulation S1P1 receptorspecific agonist CYM-5442 pretreatment of HPAEC with pretreatment of S1P1 receptor specific agonist CYM-5442,the culture supernatant of inflammatory cytokines IL-6,TNF-α,MCP-1 levels were significantly lower (P＜0.01).Conclusion Endothelial cells may play a central role on the release of inflammatory cytokine during septic shock.

Objective To investigate the influence of extracellular high mobility group box 1 (HMGB1) on viral replication in HTLV-1 infected T cells.Methods HMGB1 in culture supernatants of adult T-cell leukemia virus 1 (HTLV-1) virus-negative cell:Jurkat,MOLT4 cells and HTLV-1 virus-positive cells:MT2,MT4,was detected by ELISA;The HTLV-1 long terminal repeat reporter gene (pHTLV-1-LTR-luc) was transfected into MT2 cells by Tfx-50-mediated transfection,and 0.25,0.50,0.75 μg/ml of HMGB1 polyclonal antibody(HMGB1 PcAb) and its isotype control rabbit IgG antibodies,0.03,0.1,0.3 μg/ml rhHMGB1 and its control PBS,were added into culture supernatant respectively,then luciferase activity was detected after 48 h;Similarly,0.25 μg/ml HMGB1 PcAb and the isotype control antibody,0.3 μg/ml rhH-MGB1 and the control PBS were added to the culture supernatant of MT2 cell,the viral gene,pol1,pol2,gag,env,etc,were performed by real-time PCR.Results Culture supernatant HMGB1 levels has no significant difference between HTLV-1 positive cells MT2 and MT4 and the other two virus-negative T cell lines;Compared with isotype control antibody group,the culture supernatant,to which is added 0.25 μg/ml HMGB1 PcAb,can significantly inhibit the HTLV-1-LTR transcriptional activity and suppress the expressions of the viral gene pol1,pol2,gag,env.Compared with the control PBS,0.3 μg/ml rhHMGB1 significantly promotes the transcriptional activity of the HTLV-1-LTR and the expressions of the viral gene pol1,pol2,gag,env.Conclusion The extracellular HMGB1 can promote viral replication of HTLV-1 infected T cells.

Objective To investigate the relationship of the 5-lipoxygenase-activating (ALOX5AP) gene polymorphisms with ischemic stroke in Uygur Xinjiang.Methods One hundred and ninety-seven Uygur patients with ischemic stroke and 200 Uygur healthy controls in Xinjiang were collected in our study from October 2011 to October 2012.The SG13S32 locus polymorphisms of A LOX5A P gene were determined by using PCR-restriction fragment length polymorphism technique.The case-control analysis was used to analyze the genotypes distributions and allele frequencies.Results There were statistical differences in the distributions of AC genotypes of SG13S32 locus in ALOX5AP gene between patient group and control group (P＜0.05) and AC genotypes of SG13S32 locus in ALOX5AP gene significantly increased the risk of ischemic stroke (OR=5.27,95％CI:2.75-11.73).The distributions of all genotypes showed no statistical differences between male and female in the patient group (P＞0.05).The distributions of all genotypes showed no statistical differences between patients of different TOAST ratio (P＞0.05).Conclusion The ALOX5A P gene SG13S32 locus polymorphisms are associated with risk of ischemic stroke in Xinjiang Uygur population; risk of ischemic stroke does not associate with gender and TOAST ratio.

Objective:To investigate the clinical features and associated influencing factors of cognitive impairment in middle-aged and elderly Chinese adult patients undergoing maintenance hemodialysis (HD).Methods:A cross-sectional study was conducted among HD patients from 11 centers in Beijing city from April 2017 to June 2017. A neuropsychological battery covering domains of attention/processing speed, executive function, memory, language, and visuospatial function was applied in cognitive function assessment. Patients were classified as normal cognitive function group and cognitive impairment group according to the fifth version of the diagnostic and statistical manual of mental disorders criteria (DSM-V). Multivariate binary logistic regression was used to analyze the independent influencing factors of cognitive impairment. Results:A total of 613 HD patients were included in the study, and the prevalence of cognitive impairment was 80.91% (496/613). Attention impairment (81.05%) and memory impairment (63.51%) were the most common impaired domains, and 79.23% was concomitant impairment across two or more cognitive domains among those with cognitive impairment. Compared with the patients in the normal cognitive function group, the patients in the cognitive impairment group had senior age, longer dialysis vintage, higher proportion of diabetes, hypertension, and stroke, higher level of serum intact parathyroid hormone (iPTH), lower education level, and lower urea clearance index (Kt/V) (all P<0.05). Factors were independently associated with cognitive impairment including increasing age ( OR=1.110, 95% CI 1.072-1.150, P<0.001), education time>12 years (with education time<6 years as reference, OR=0.323, 95% CI 0.115-0.909, P=0.032), history of diabetes ( OR=2.151, 95% CI 1.272-3.636, P=0.004), history of stroke ( OR=2.546, 95% CI 1.244-5.210, P=0.011), increased dialysis vintage ( OR=1.016, 95% CI 1.010-1.022, P<0.001), reduced Kt/V( OR=0.008, 95% CI 0.002-0.035, P<0.001), and increased iPTH level ( OR=1.002, 95% CI 1.002-1.003, P=0.012). Conclusions:The prevalence of cognitive impairment in middle-aged and elderly adult Chinese patients undergoing HD is high. Memory and attention are the most commonly impaired domains. Increasing age, low education level, history of diabetes and stroke, increased dialysis vintage, reduced Kt/V and increased serum iPTH are the independent influencing factors associated with cognitive impairment.

Objective:To investigate the association between cognitive impairment and all-cause mortality in middle and elderly adult patients undergoing maintenance hemodialysis (HD).Methods:A prospective cohort study was conducted. Patients from 11 HD centers in Beijing between April and June 2017 were enrolled. Baseline data were collected, and a series of neuropsychological batteries covered 5 domains of cognitive function were applied for the assessment of cognitive function. The patients were then classified as normal and cognitive impairment groups according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria (DSM-V) and followed-up until June 2018. The clinical characteristics of the two groups of patients were compared. Kaplan-Meier survival analysis was used to compare the difference in the cumulative survival rate between the two groups. Multivariate Cox regression model was used to analyze the independent influencing factors of all-cause mortality, to determine the relationship between cognitive impairment and different cognitive domain impairments and all-cause death.Results:A total of 613 patients were enrolled, of which 496(80.91%) patients had cognitive impairment. Compared with the normal cognitive function group, the patients in the cognitive impairment group tended to be older, longer dialysis vintage, a higher proportion of diabetes, hypertension, and stroke, increased serum iPTH level, and lower education level and urea clearance index (Kt/V) (all P<0.05). After (49.53±8.42) weeks of follow-up, Kaplan-Meier survival analysis showed that the cumulative survival rate of cognitive impairment group was significantly lower than that of cognitive normal group (Log-rank χ2=8.610, P=0.003). Multivariate Cox regression analysis showed that history of diabetes ( HR=2.742, 95% CI 1.598-4.723, P<0.001), coronary heart disease ( HR=1.906, 95% CI 1.169-3.108, P=0.010), dialysis vintage (every increase of 1 month, HR=1.007, 95% CI 1.003-1.011, P=0.001), serum level of albumin (every increase of 1 g/L, HR=0.859, 95% CI 0.809-0.912, P<0.001), cognitive impairment ( HR=2.719, 95% CI 1.088-6.194, P=0.032) were independently associated with all-cause mortality. Multivariate Cox regression analysis on different cognitive domains also indicated that memory impairment ( HR=2.571, 95% CI 1.442-4.584, P<0.001), executive function impairment ( HR=3.311, 95% CI 1.843-5.949, P=0.001) and three, four, five domains combined impairment ( HR=5.746, 95% CI 1.880-17.565, P=0.002; HR=12.420, 95% CI 3.690-41.802, P<0.001; HR=13.478, 95% CI 3.381-53.728, P<0.001) were independently related to all-cause mortality. Conclusions:Cognitive impairment is an independent risk factor of all-cause mortality in middle and elderly adult patients undergoing maintenance hemodialysis, and the risk is significantly increased in patients with the impairment of the domains of memory, executive function, or in the combination of three to five cognitive domains.