Objective To investigate the effects of recombinant adeno-associated virus-mediated myostatin propeptide (MPRO) on uptake and oxidation of glucose,and glycogen synthesis in C2C12 myotubes,as well as the associated molecular mechanism.Methods Mature C2C12 myotubes were assigned to the following 6 groups:control,insulin,green fluorescent protein (GFP),insulin + GFP,MPRO,and insulin + MPRO groups.Glucose uptake,glucose oxidation,and glycogen synthesis were detected by counting radioactivity of 14CO2 or 14C labeled glycogen derived from 2-deoxy-[1-14 C] glucose.The activity of insulin signal pathway was evaluated by Western blot.Results Compared with control group,glucose uptake and glycogen synthesis were significantly increased in insulin and insulin+GFP groups,and further increased in insulin+MPRO group as compared with insulin alone(all P＜ O.05).However,MPRO and insulin had no effect on glucose oxidation.The phosphorylations of insulin receptor (IR) β,insulin receptor substrate 1 (IRS-1),protein kinase B (Akt),glycogen synthase kinase-3 β (GSK-3β),and the expressions of phosphatidylinositol 3-kinase (PI3K) and glucose transporter 4 (Glut4) in membrane were significantly increased in insulin and insulin+GFP groups compared with control group(all P＜0.05),and were further increased after MPRO transfection (all P ＜ 0.05).Conclusion MPRO may increase insulin-stimulated glucose uptake and glycogen synthesis in C2C12 cells by activating the IRS/PI3K/Akt signal pathway.

Background: and Purpose Despite administration of evidence-based therapies, residual risk of stroke recurrence persists. This study aimed to evaluate the residual risk of recurrent stroke in acute ischemic stroke or transient ischemic attack (TIA) with adherence to guideline-based secondary stroke prevention and identify the risk factors of the residual risk. Methods: Patients with acute ischemic stroke or TIA within 7 hours were enrolled from 169 hospitals in Third China National Stroke Registry (CNSR-III) in China. Adherence to guideline-based secondary stroke prevention was defined as persistently receiving all of the five secondary prevention medications (antithrombotic, antidiabetic and antihypertensive agents, statin and anticoagulants) during hospitalization, at discharge, at 3, 6, and 12 months if eligible. The primary outcome was a new stroke at 12 months. Results: Among 9,022 included patients (median age 63.0 years and 31.7% female), 3,146 (34.9%) were identified as adherence to guideline-based secondary prevention. Of all, 864 (9.6%) patients had recurrent stroke at 12 months, and the residual risk in patients with adherence to guidelinebased secondary prevention was 8.3%. Compared with those without adherence, patients with adherence to guideline-based secondary prevention had lower rate of recurrent stroke (hazard ratio, 0.85; 95% confidence interval, 0.74 to 0.99; P=0.04) at 12 months. Female, history of stroke, interleukin-6 ≥5.63 ng/L, and relevant intracranial artery stenosis were independent risk factors of the residual risk. Conclusions There was still a substantial residual risk of 12-month recurrent stroke even in patients with persistent adherence to guideline-based secondary stroke prevention. Future research should focus on efforts to reduce the residual risk.

Objective Abnormalities of lipid profile were considered as risk factors of hemorrhage after ischemic stroke. We aimed to determine the relationship between lipid levels and bleeding in minor stroke or transient ischemic attack (TIA) patients receiving antiplatelet therapy. Methods Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride were tested in a subgroup of 3044 consecutive patients from Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. Patients were randomized to clopidogrel plus aspirin group or single aspirin group. The primary endpoint was any bleeding within 90 days. The secondary endpoint was severe bleeding according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) definition. Cox proportional hazards models were used to assess the associations of lipid levels and outcomes. Results A total of 59 (1.9％) bleeding events occurred at 90 days. High-density lipoprotein cholesterol (adjusted HR=2.16; 95％CI 1.17-4.00, P=0.014) and age (adjusted HR=1.04;95％CI 1.01-1.06, P=0.006) were significantly associated with any bleeding. High-density lipoprotein cholesterol was also associated with severe bleeding (adjusted HR=3.05;95％CI 1.39-6.68, per 1 mmol/L increase). No correlations between outcomes and levels of total cholesterol, low-density lipoprotein cholesterol and triglyceride were found. There was no interaction of any lipid component level with randomized antiplatelet therapy. Conclusions Elevated high-density lipoprotein cholesterol is independently associated with any bleeding and severe bleeding in the patients with acute minor stroke or high-risk TIA on antiplatelet therapy.