BackgroundStroke is the second most common cause of mortality in China. Although most subtypes of ischemic stroke share similar risk factors, they have different etiologies. Our study aimed to evaluate the different risk factor profiles between the stroke subtypes, lacunar infarcts (LI) and large-artery atherosclerosis (LAA), and clarify the characteristics of current acute ischemic stroke in China.MethodsIn this cross-sectional study, we analyzed the clinical characteristics of 1982 patients with acute ischemic stroke who were admitted to the neurology department at the Peking University First Hospital between 2007 and 2014. Ischemic stroke was further classified into LAA, LI, cardioembolism (CE) and undetermined causes of infarction (UDI) according to TOAST classification. Demographic characteristics, risk factors, as well as the findings of laboratory and imaging tests of 1773 patients with LAA and LI, were analyzed by univariate and multivariate logistic analysis.ResultsOf the 1982 ischemic stroke patients included in this study, 1207 were diagnosed with LAA, 566 with LI, 173 with cardioembolism (CE) and 36 with undetermined causes of infarction (UDI). By comparing the risk factors in multivariate logistic regression analysis, hypertension [odds ratio (OR) = 1.832] and white matter leukoaraiosis (WML) (OR = 1.865) were found to be more strongly correlated with LI than LAA. Low density lipoprotein- cholesterol (LDL-c) (OR = 0.774) were more strongly related to LAA than LI.ConclusionsThis study found that hypertension and WML were more strongly correlated with LI than LAA. LDL-c was more strongly related to LAA than LI.

These results suggest that IgG anti-GM1 antibodies are associated with AMAN, but not with AIDP, and that IgM antibodies against GM1, GM2, and GM3 are associated with facial nerve palsy. Muscle Nerve 55: 470-475, 2017.

This study is applied to the investigation of the long noncoding RNA myocardial infarction associated transcript's (MIAT's) role in regulating the expression of highmobility group box 1 (HMGB1) in cerebral microvascular endothelial cell (CMEC) injury after cerebral ischemia by serving as a competitive endogenous RNA (ceRNA) to sponge microRNA-204-5p (miR-204-5p). The cerebral ischemia model of middle cerebral artery occlusion (MCAO) in rats was established by the suture method, in which rats were injected with empty plasmids and MIAT siRNA plasmids. The cerebral ischemia injury model in vitro was established through oxygen glucose deprivation (OGD) in primary cultured CMECs in rats. The cells were transfected with empty plasmids and MIAT siRNA plasmids. The MIAT/miR-204-5p/HMGB1 axis' function in damage and angiogenesis of CMECs were explored. The binding site between MIAT and miR-204-5p along with that between miR-204-5p and HMGB1 was determined. MIAT was overexpressed in MCAO rats' brain tissue and inhibited MIAT attenuated the injury of brain tissue in MCAO rats. Inhibition of MIAT promoted angiogenesis, promoted miR-204-5p expression and inhibited HMGB1 expression in brain tissue of MCAO rats. Inhibition of MIAT reduced CMEC damage, induced angiogenesis of CMECs, increased the number of surviving neurons, promoted miR-204-5p expression and inhibited HMGB1 expression in CMECs treated with OGD. MIAT promoted HMGB1 expression by competitive binding to miR-204-5p to regulate the injury of CMECs after cerebral ischemia. Our study showed that MIAT promoted HMGB1 expression by competitively binding to miR-204-5p to regulate the injury of CMECs after cerebral ischemia. K E Y W O R D S cerebral ischemia, cerebral microvascular endothelial cells injury, HMGB1, long noncoding MIAT, microRNA-204-5p

Phloretin, a flavonoid present in various plants, has been reported to exert anticarcinogenic effects. However, the mechanism of its chemo-preventive effect on human glioblastoma cells is not fully understood. This study aimed to investigate the molecular mechanism of phloretin and its associated chemo-preventive effect in human glioblastoma cells. The results indicate that phloretin inhibited cell proliferation by inducing cell cycle arrest at the G0-G1 phase and induced apoptosis of human glioblastoma cells. Phloretin-induced cell cycle arrest was associated with increased expression of p27 and decreased expression of cdk2, cdk4, cdk6, cyclinD and cyclinE. Moreover, the PI3K/AKT/mTOR signaling cascades were suppressed by phloretin in a dose-dependent manner. In addition, phloretin triggered the mitochondrial apoptosis pathway and generated reactive oxygen species (ROS). This was accompanied by the up-regulation of Bax, Bak and c-PARP and the down-regulation of Bcl-2. The antioxidant agents N-acetyl-L-cysteine and glutathione weakened the effect of phloretin on glioblastoma cells. In conclusion, these results demonstrate that phloretin exerts potent chemo-preventive activity in human glioblastoma cells through the generation of ROS.

The urokinase-type plasminogen activator (uPA) loaded hollow nanogels (nUK) were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly (ethylene oxide). The resultant formulation is sensitive to diagnostic ultrasound (US) of 2 MHz. Herein, we evaluated the in vivo sonothrombolysis performance of the nUK on acute ischemic stroke rat model which was established by suture embolization of middle cerebral artery (MCA). Via intravenous (i.v.) administration, the experimental data prove a controlled release of the therapeutic protein around the clots under ultrasound stimulation, leading to enhanced thrombolysis efficiency of the nUK, evidenced from smaller infarct volume and better clinical scores when compared to the i.v. dose of free uPA no matter with or without US intervention. Meanwhile, the preservation ability of the nanogels not only prolonged the circulation duration of the protein, but also resulted in the better blood-brain barrier protection of the nUK formulation, showing no increased risk on the hemorrhagic transformation than the controls. This work suggests that the nUK is a safe sonothrombolytic formulation for the treatment of acute ischemic stroke.

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BackgroundThe present study aimed to investigate the prevalence and risk factors for extracranial carotid artery stenosis (ECAS) and intracranial carotid artery stenosis (ICAS) simultaneously in asymptomatic Chinese pure rural population.MethodsWe analyzed 2589 asymptomatic subjects aged over 30 yr. by ultrasonography and transcranial Doppler simultaneously in 13 isolated villages by door-to-door investigation. Both ECAS and ICAS were defined as more than 50% stenosis. Demographics, medical history documentation, and investigation of biochemical results were performed for each subject. Univariate and multivariate logistic regression analyses were employed to assess the risk factors associated with ECAS and ICAS, respectively.ResultsOne hundred twenty-two (4.7%) residents with ICAS and 56 (2.2%) with ECAS were found in 2589 subjects. Three factors emerged as independent risk factors for ICAS: age (95% confidence interval [CI] = 1.01–1.04, odds ratio [OR] = 1.07), hypertension (95% CI = 1.98–4.37, OR = 2.94), and diabetes mellitus (95% CI = 1.72–4.38, OR = 2.75). As for ECAS, five factors presented as independent risk factors: age (95% CI = 1.09–1.11, OR = 1.10), male sex (95% CI = 1.01–1.02, OR = 1.01), diabetes mellitus (95% CI = 1.10–2.12, OR = 1.53), systolic blood pressure (95% CI = 1.95–2.88, OR = 2.37), and total cholesterol (95% CI = 1.00–1.13, OR = 1.06).ConclusionsICAS and ECAS were relatively common among asymptomatic rural Chinese subjects. Although they shared similar risk factors, differences still existed between them.

MicroRNAs (miRNAs) have already been proposed to be implicated in the development of ischaemic stroke. We aim to investigate the role of miR‐130a in the neurological deficit and angiogenesis in rats with ischaemic stroke by regulating X‐linked inhibitor of apoptosis protein (XIAP). Middle cerebral artery occlusion (MCAO) models were established by suture‐occluded method, and MCAO rats were then treated with miR‐130a mimics/inhibitors or/and altered XIAP for detection of changes of rats’ neurological function, nerve damage and angiogenesis in MCAO rats. The oxygen‐glucose deprivation (OGD) cellular models were established and respectively treated to determine the roles of miR‐130a and XIAP in neuronal viability and apoptosis. The expression levels of miR‐130a and XIAP in brain tissues of MCAO rats and OGD‐treated neurons were detected. The binding site between miR‐130a and XIAP was verified by luciferase activity assay. MiR‐130a was overexpressed while XIAP was down‐regulated in MCAO rats and OGD‐treated neurons. In animal models, suppressed miR‐130a improved neurological function, alleviated nerve damage and increased new vessels in brain tissues of rats with MCAO. In cellular models, miR‐130a inhibition promoted neuronal viability and suppressed apoptosis. Inhibited XIAP reversed the effect of inhibited miR‐130a in both MCAO rats and OGD‐treated neurons. XIAP was identified as a target of miR‐130a. Our study reveals that miR‐130a regulates neurological deficit and angiogenesis in rats with MCAO by targeting XIAP.