Increased serum exosomal miR-134 expression in the acute ischemic stroke patients.

BACKGROUND: The exosomal miRNAs have been emerged as biomarkers and therapeutic targets for various diseases, however, the function of exosomal miRNAs in stroke remains largely unknown. METHODS: The blood samples from acute ischemic stroke (AIS) patients and normal controls were collected. The exosomes were isolated from the blood samples, which were confirmed by electron microscopy and western blot with the specific exosomes biomarker CD9, CD63 and Tsg101. RESULTS: RT-qPCR analysis showed that exosomal miR-134 was significantly increased in AIS patients within 24 h after stroke onset compared with that of control group. Highly expressed exosomal miR-134 was correlated with the National Institutes of Health Stroke Scale (NIHSS) scores, infarct volume and positively associated with the worse prognosis of the stroke patients. Additionally, the exosomal miR-134 was strong positively correlated with the expression of serum interleukin 6 (IL-6) and plasma high-sensitivity C relative protein (hs-CRP). The receiver operating characteristic (ROC) curve suggested that miR-134 might be a potential factor to discriminate AIS patients from non-stroke controls. CONCLUSIONS: The exosomal miR-134 as a possible novel biomarker for the diagnosis and prognosis of stroke.

LncRNA SNHG12 ameliorates brain microvascular endothelial cell injury by targeting miR-199a.

Long non-coding RNAs regulate brain microvascular endothelial cell death, the inflammatory response and angiogenesis during and after ischemia/reperfusion and oxygen-glucose deprivation/reoxygenation (OGD/R) insults. The long non-coding RNA, SNHG12, is upregulated after ischemia/reperfusion and OGD/R in microvascular endothelial cells of the mouse brain. However, its role in ischemic stroke has not been studied. We hypothesized that SNHG12 positively regulates ischemic stroke, and therefore we investigated its mechanism of action. We established an OGD/R mouse cell model to mimic ischemic stroke by exposing brain microvascular endothelial cells to OGD for 0, 2, 4, 8, 16 or 24 hours and reoxygenation for 4 hours. Quantitative real-time polymerase chain reaction showed that SNHG12 levels in brain microvascular endothelial cells increased with respect to OGD exposure time. Brain microvascular endothelial cells were transfected with pcDNA-control, pcDNA-SNHG12, si-control, or si-SNHG12. After exposure to OGD for 16 hours, these cells were then analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, trypan blue exclusion, western blot, and capillary-like tube formation assays. Overexpression of SNHG12 inhibited brain microvascular endothelial cell death and the inflammatory response but promoted angiogenesis after OGD/R, while SNHG12 knockdown had the opposite effects. miR-199a was identified as a target of SNHG12, and SNHG12 overexpression reversed the effect of miR-199a on brain microvascular endothelial cell death, the inflammatory response, and angiogenesis. These findings suggest that SNHG12 suppresses endothelial cell injury induced by OGD/R by targeting miR-199a.

Associations of TF Gene Polymorphisms with the Risk of Ischemic Stroke.

Ischemic stroke (IS) is the main cause of mortality and disability in China; thus, this study aimed to examine the association between six variants and their haplotypes within the transferrin (TF) gene and the risk of IS in the Southern Chinese Han population. Genotyping was performed using the Sequenom MassARRAY platform for 249 IS patients and 249 age- and sex-matched controls. The association between polymorphisms and IS risk was tested by Chi squared test and haplotype and stratification analysis. Odds ratios (ORs) and confidence intervals (CIs) were estimated by unconditional logistic regression analysis. The results of genetic model analyses indicated that the two SNPs (rs1880669 and rs2692695) were associated with decreased IS risk under the co-dominant, dominant, and additive models. Additionally, rs4525863 was also associated with decreased IS risk both under the dominant and additive models in males. Moreover, the CG haplotype of TF (rs1880669 and rs2692695) was significantly associated with a decreased risk of IS in the total population and males. Our findings suggested that polymorphisms (rs4525863, rs1880669, and rs2692695) of the TF gene might be a protective factor for IS in Southern Chinese Han population. Further large prospective studies are required to confirm these findings.

Association of RTEL1 gene polymorphisms with stroke risk in a Chinese Han population.

We investigated the associations between single nucleotide polymorphisms (SNPs) in the regulator of telomere elongation helicase 1 (RTEL1) gene and stroke in the Chinese population. A total of 400 stroke patients and 395 healthy participants were included in this study. Five SNPs in RTEL1 were genotyped and the association with stroke risk was analyzed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analysis. Multivariate logistic regression analysis was used to identify SNPs that correlated with stroke. Rs2297441 was associated with an increased risk of stroke in an allele model (odds ratio [OR] = 1.24, 95% confidence interval [95% CI] = 1.01-1.52, p = 0.043). Rs6089953 was associated with an increased risk of stroke under the genotype model ([OR] = 1.862, [CI] = 1.123-3.085, p = 0.016). Rs2297441 was associated with an increased risk of stroke in an additive model (OR = 1.234, 95% CI = 1.005, p = 0.045, Rs6089953, Rs6010620 and Rs6010621 were associated with an increased risk of stroke in the recessive model (Rs6089953:OR = 1.825, 95% CI = 1.121-2.969, p =0.01546; Rs6010620: OR = 1.64, 95% CI = 1.008-2.669, p =0.04656;Rs6010621:OR = 1.661, 95% CI = 1.014-2.722, p =0.04389). Our findings reveal a possible association between SNPs in the RTEL1 gene and stroke risk in Chinese population.

Evaluation on the compliance with secondary prevention and influence factors of ischemic stroke in Hainan province, China.

Survivors of ischemic stroke are still at a significant risk for recurrence. Numerous effective strategies for the secondary prevention of ischemic stroke have now been established; however, these guidelines are not widely known. In this retrospective, a multicenter study was conducted from January 2011 to February 2012 in 10 general hospitals, which included 1300 elderly patients who had previously been diagnosed with ischemic stroke and re-admitted to hospitals. Logistic regression models were fitted to determine the relationship between compliance with secondary prevention therapy and each variable of interest. The treatment rates of antihypertensive, antiplatelet and lipid-lowering therapy were only 56.3%, 48.9% and 19.6%, respectively. Multivariate analysis presented that cardiovascular risk factors would motivate patients with hypertension and hyperlipidemia to receive corresponding treatments. However, it is worth noting that they did not influence the use of antiplatelet therapy. In addition, high education, health education and insurance promote the use of secondary prevention in patients. In conclusion, the importance of antiplatelet therapy should not be ignored any more. Besides, health education will raise patients' attention to ischemic stroke.

[Role of acute kidney injury staging by KDIGO criteria in choosing the opportune time of continuous blood purification].

OBJECTIVE: To investigate the role of acute kidney injury staging in multiple organ dysfunction syndrome (MODS) patients with acute kidney injury (AKI) for deciding the opportune time of continuous blood purification (CBP). METHODS: A retrospective study was conducted. One hundred and twenty-six MODS patients with AKI in general intensive care unit (ICU) and emergency intensive care unit (EICU) requiring continuous venous-venous hemofiltration treatment were enrolled. According to the criteria of "Kidney Disease: Improving Global Outcomes Organization (KDIGO standard)" and acute physiology and chronic health evaluation II (APACHEII) score, the patients were stratified into KDIGO 1, 2, 3 groups and APACHEII score of <15, 15-25, >25 groups. ICU survival rate and renal function outcome, CBP treatment total ultrafiltration, average ICU day and the average medical costs of survivals were compared among groups. RESULTS: Compared with APACHEII ≤ 25, KDIGO 1, 2 hospitalized patients had significantly higher survival rate [94.1% (32/34) vs. 76.8% (43/56), P<0.05]. Renal function improvement rate in survivors of KDIGO 1, 2 patients was significantly higher than that in APACHEII ≤ 25 [90.6% (29/32) vs. 62.8 (27/43), P<0.01], and number of patients requiring CBP treatment, mean ICU day, and medical expenses were significantly reduced (CBP treatment of total ultrafiltration: 199.0±44.7 L vs. 239.0 ± 73.3 L, the mean length of stay in ICU: 12.9±3.4 days vs. 15.1±4.8 days, medical expenses: 2.6±0.4 million vs. 3.0±1.0 million, all P<0.05). There was no significant difference in above indexes between survivors in KDIGO 3 and APACHEII>25, and the indexes in KDIGO 3 and APACHEII >25 were worse than those in KDIGD 1, 2 and APACHEII>25. CONCLUSIONS: In patients of MODS accompanied by AKI, compared using as APACHEIIscore≤25 as opportune time to start CBP, to commence the treatment in the period of KDIGO standard 1, 2 cannot only improve patient survival with recovery of renal function, but also can reduce the ICU stay and medical expenses.

Effect of HbA1c combined FPG on screening diabetes in health check-up.

OBJECTIVE: To appraise the effectiveness of HbA(1c) and fasting plasma glucose (FPG) on screening diabetes in health check-up. METHODS: A total of 1,337 individuals (male 850, female 487), aged 27 to 91 years with HbA(1c) test were included. Participates with HbA(1c) ≥6.0% or FPG≥6.1 mmol/L underwent oral glucose tolerance test (OGTT). Diabetes mellitus was diagnosed according to the criteria of WHO in 1999, FPG≥7.0 mmol/L and/or OGTT 2 h-postload plasm glucose (2 h-PG)≥11.1 mmol/L. The sensitivity and specificity of HbA(1c) thresholds and FPG or combination test on screening of diabetes were analyzed. RESULTS: A total of 842 subjects had HbA(1c) <6.0%, in which 32 had isolated FPG≥6.1 mmol/L, of 495 had HbA(1c)≥6.0%. Subjects with HbA(1c)≥6.0% had significant increased disorder indexes than those with HbA(1c)<6.0%. 527 subjects who had HbA(1c)≥6.0% or FPG≥6.1 mmol/L underwent OGTT. A total of 234 subjects were newly diagnosed diabetes, including 123 (123/234, 52.56%) with FPG≥7.0 mmol/L, and 111 subjects (111/234, 47.43%) with isolated 2 h-PG≥11.1 mmol/L. Among 234 new diabetes, 91.88% (215 subjects) had HbA(1c)≥6.3%, and 77.40% (181 subjects) had HbA(1c)≥6.5%. HbA(1c)≥6.3% combined FPG ≥7.0 mmol/L increased the positive rate of newly diagnosed diabetes from 91.88% to 96.58%. CONCLUSIONS: HbA(1c) is a practical and convenient tool for screening undiagnosed diabetes in routine health check-up of a large population. Combined use of HbA(1c)≥6.3% and/or FPG≥7.0 mmol/L is efficient for early detection of diabetes.

[Study on dynamic changes in coagulability and von Willebrand factor and its correlation with prognosis of cardiopulmonary resuscitation].

OBJECTIVE: To investigate dynamic changes in coagulability and von Willebrand factor (vWF), and explore their correlation with prognosis of cardiopulmonary resuscitation (CPR). METHODS: Fifty CPR patients were divided into three groups according to the outcome. A group: 25 patients with successful recovery in the initial stage with restoration of spontaneous circulation (ROSC) lasting at least for 72 hours, but died ultimately; B group: 10 patients with successful recovery and finally survived; C group: the control group, 15 patients who died or ROSC<2 hours after CPR. In the course of CPR, dynamic changes in prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fg), platelet count (PLT), D-dimer, antithrombin III (AT III) and vWF were determined at the time of CPR, 24, 48 and 72 hours after ROSC. RESULTS: During CPR, the levels of PT, APTT, TT, D-dimer and vWF were higher, and the levels of Fg, PLT and AT III were lower in group C compared with groups A and B (all P<0.01). There was no significant difference between groups A and B (all P>0.05). In groups A and B, the levels of PT, APTT, TT, D-dimer and vWF increased and the levels of Fg, PLT, AT III decreased 24 hours after ROSC. The changes in all parameters reached peak or valley point at ROSC 48 hours (P<0.05 or P<0.01). At ROSC 72 hours all parameters were improved more obviously in group B (all P<0.01), but not improved in group A (all P>0.05). The levels of PT, APTT, TT, D-dimer and vWF were much higher and the levels of Fg, PLT and AT III were much lower in group A than in group B (P<0.05 or P<0.01). CONCLUSION: Tissue and vascular endothelial injury, endogenous and extrinsic coagulation disorder and fibrinolytic dysfunction are found in the patients undergoing CPR. Their dynamic changes are observed in the course of CPR, and they are valuable in assessing the severity of patients' condition and prognosis.