Abstract:Aim To determine the effects of aerobic exercise training on aging-associated selective changes of the function of the spontaneous transient outward currents and the large-conductance Ca²⁺-activated K⁺ channels in cerebral arteries. Methods Male Wistar rats aged 19～21 months were randomly assigned to sedentary （O-SED） and exercise-trained groups （O-EX）.Two-month-old rats were used as Young control.After 12 weeks,the segment of cerebral arteries was carefully dissected free,and separated into smooth muscle cells by two steps digestion. Results Whole-cell patch clamp showed that aging decreased the density of whole-cell K⁺ current and iberiotoxin-sensitive whole-cell K⁺ current； The amplitude of spontaneous transient outward currents was decreased by aging， while there was no significant difference in the frequency； Inside-out patch clamp recording on cerebral arteries myocytes showed that aging decreased the open probability and Ca²⁺/voltage sensitivity of single large-conductance Ca²⁺-activated K⁺ channel； The opening time was decreased by aging,whereas the close time was increased.However,exercise training inhibited all of these changes. Conclusion These data suggest that regular aerobic exercise can attenuate the functional downregulation of spontaneous transient outward currents/large-conductance Ca²⁺-activated K⁺ channels in aging cerebral arteries myocytes,which may be one of the important mechanisms underlying the beneficial effects of aerobic exercise on aging arteries.

Abstract:Aim To explore the effect of trimetazidine on cardiomyocyte apoptosis after coronary microembolization （CME） in swine. Methods Fifteen swine were randomly and equally assigned into sham-operated （control） group,CME group and trimetazidine group.CME was induced by injection of microspheres selectively into left anterior descending artery for control group,the same dose of normal saline was substituted for microspheres and those in trimetazidine group were pretreated with trimetazidine 30 min before microspheres injection.Cardiac function was assessed by echocardiography,cardiomyocyte apoptosis was detected by TUNEL staining,and the expression levels of caspase-8 and caspase-3 were measured by Western blot 9 h after operation. Results Compared with sham-operated group,cardiac function was significantly decreased in CME group （P<0.05） However,cardiac function was significantly improved in trimetazidine group compared with CME group （P<0.05）.Compared with control group,myocardial apoptosis rate and the levels of activated caspase-8 and -3 increased significantly in CME group （P<0.05）.Again,these effects were ameliorated by trimetazidine （P<0.05）. Conclusion Trimetazidine pretreatment suppressed post-CME myocardial apoptosis and improved cardiac function probably by inhibiting myocardial death receptor-mediated apoptotic pathway.

Abstract:Aim To investigate the effect of metformin on angiotensin Ⅱ （AngⅡ） -induced proliferation of adult rat cardiac fibroblasts （CF） and its underlying mechanism. Methods The adult rat CF was isolated by a combination of trypsin and collagenase Ⅱ digestion.The cell proliferation was induced by AngⅡ （100 nmol/L） stimulation,and the CF was treated with metformin in different concentrations （10,50,and 200 μmol/L）.The proliferation of CF was evaluated by MTT assay,and the DNA synthesis was detected by EdU incorporation.The expression of endothelial nitric oxide synthase （eNOS） and phosphorylated endothelial nitric oxide synthase （p-eNOS） were detected by Western blot.The level of NO in CF culture supernatant fluids was measured by nitrate reductase method. Results Stimulation with AngⅡ for 48 h induced the proliferation of adult rat CF,and this effect was inhibited by pretreatment of CF with metformin in a concentration-dependent manner.Metformin significantly increased the phosphorylation level of eNOS in CF as well as the level of NO in cell culture supernatant fluids in a concentration-dependent manner.In addition,pretreatment of CF with eNOS inhibitor L-NAME markedly attenuated the inhibitory effect of metformin on AngⅡ-induced cell proliferation. Conclusion Metformin inhibits AngⅡ-induced proliferation of adult rat CF,and this effect may be associated with the activation of the eNOS/NO pathway.

Abstract:Aim To evaluate the protective effects and possible mechanisms of probucol on atherosclerosis in hyperlipidemic type 2 diabetic mice. Methods The hyperlipidemic type 2 diabetic （db/db-LDLR^－/－） mice were generated by the cross between leptin receptor deficient （db/db） mice and low density lipoprotein receptor knockout （LDLR^－/－） mice.8-week-old db/db-LDLR^－/－ mice were fed with high fat diet （HFD） mixed with 0.5% probucol,diabetic （db/db-LDLR^－/－） and non-diabetic （LDLR^－/－） control mice were fed with the same HFD without probucol addition.At 2 and 4 months after HFD,plasma lipids and glucose levels were measured.At 4 months after HFD,glucose tolerance and “en face” total aortic atherosclerotic plaque sizes were measured. Results Compared with type 2 diabetic HFD control group,probucol had strong protective effects on reducing plasma total cholesterol （TC）,triglyceride （TG）,glucose levels,improving glucose tolerance,and decreasing atherosclerotic lesions.Meanwhile,high density lipoprotein cholesterol （HDLC）/TC levels were unchanged. Conclusions Probucol had striking antiatherogenic effects under type 2 diabetic condition with hyperlipidemia.It might be an effective therapy in type 2 diabetic macrovascular disease.

Abstract:Aim To detect the role and mechanism of excessive activation of （pro）renin receptor （（P）RR） in hyperglycemia induced endothelial dysfunction. Methods Endothelial cells were cultured in vivo and intervened with glucose of different concentrations （15,30 mmol/L） and different courses （24 h,48 h）.The mRNA and protein levels of （P）RR and markers reflecting vascular function were measured.（P）RR expression was then inhibited by siRNA to observe the corresponding changes mentioned before. Results Both protein and mRNA expression of endothelial cells was significantly increased by hyperglycemia.Hyperglycemia upregulated the expression of endothelin-1 （ET-1） and inhibited the synthesis of nitric oxide （NO）.（P）RR-siRNA couldn’t inhibit the expression of ET-1 protein,although it could inhibit its mRNA elevation in hyperglycemia.（P）RR-siRNA could significantly inhibit NO reduction in hyperglycemia.Hyperglycemia inhibited the expression of endothelial nitric oxide synthase （eNOS） and provoked the synthesis of asymmetric dimethylarginine （ADMA）,which could be significantly inhibited by （P）RR-siRNA. Conclusions Hyperglycemia activated （P）RR expression in endothelial cells.Hyperglycemia induced vascular endothelial dysfunction might be mediated by （P）RR via ADMA/eNOS pathway.

Abstract:Aim To investigate the effects of tetramethylpyrazine on expressions of insulin-like growth factor-1 receptor （IGF-1R） and apoptosis-related proteins in cerebral cortex of neonatal streptozotocin （STZ）-induced diabetic rats.

Abstract:Aim To explore the correlation of elasticity change between carotid artery and femoral artery in patients with high-normal blood pressure. Methods Intima-media thickness （IMT） in the bilateral carotid artery and femoral artery was measured by two-dimensional ultrasound in 76 patients （including male 42 cases and female 34 cases,mean age 47.56±10.54 years old） with high-normal blood pressure and 50 cases of normal control group （including male 26 cases and female 24 cases,mean age 48.16±11.17 years old）,carotid artery and femoral artery elastic parameters of β,Ep,arterial compliance （AC） and pulse wave velocity （PWV） were detected by echo tracking technology,and correlation of carotid artery and femoral artery was analyzed. Results Compared with normal control group,β,Ep,PWV of carotid artery and femoral artery were increased conspicuously in high-normal blood pressure group （P<0.001）,AC was lower significantly in high-normal blood pressure group （P<0.001）.There was no difference in IMT of carotid artery and femoral artery between the two groups respectively （P>0.05）.The correlation coefficients of β,Ep,PWV in carotid artery and femoral artery in patients with high-normal blood pressure were 0.354,0.304 and 0.360 （P<0.001）,which was a significant positive correlation.There were no significant correlation of IMT and AC between carotid and femoral artery （r＝0.108,P＝0.184 r＝0.114,P＝0.163）. Conclusion The carotid and femoral artery elasticity decreased and involved simultaneously before the artery IMT had ultrasonic morphological change.

Abstract:Aim To analyse characateristic of head and neck CTA by 256-slice CT angiography in patients with cerebral infarction of Oxfordshire Community Stroke Project （OCSP） classification,evaluate the relationship between the degree,location of head and neck artery stenosis and the OCSP classification of responsible side in patients with cerebaral infarction. Methods According to the OCSP classification,300 cases of acute cerebral infarction were divided into total anterior circulation infarct （TACI） （37 cases）,partial anterior circulation infarcts （PACI） （109 cases）,posterior circulation infarct （POCI） （66 cases） and lacunar infarct （LACI） （88 cases）,through retrospective analysis of head and neck CTA by 256-slice CT angiography,responsible vessels characteristic were compared in patients of different types. Results The rate of responsible artery stenosis or occlusion was 86.8%,75.3%,88.5% and 86.3% in patients with acute cerebral infarction of TACI,PACI,POCI and LACI subtype.Statistical significance of responsible artery stenosis or occlusion rate between the subtypes was not found（P>0.05）.The degree of head and neck responsible vessels stenosis was different between the OCSP classification.The most of patients of TACI was severe or occlusion,mild or moderate stenosis was dominated in PACI and LACI,mild stenosis was dominated in POCI.The incidence of stenosis or occlusion in TACI was higher than other subtype （P<0.05）.Tandem stenosis or occlusion of intracranial and extracranial artery were dominated in different subtype of OCSP,especially in PACI and POCI（P<0.05）. Conclusion Head and neck responsible vessels stenosis and the degree of stenosis were related to OCSP classification.256-slice CT angiography of head and neck was helpful to determine the cerebrovascular stenosis,the degree of stenosis and the responsibility vessels.

Abstract:Aim To determine the predictive value of d-dimer （DD） and fibrinogen （FIB） for risk-stratification of patients with transient ischemic attack （TIA）. Methods We designed a prospective study.132 patients with acute TIA in hospitalization were enrolled.These patients were divided into low （0～3 points,46 patients）,medium （4～5 points,70 patients） and high （6～7 points,16 patients） risk groups according to their ABCD² scores.DD and FIB were measured.The primary outcome measure was a composite endpoint event,which was consisted of stroke or death within 90 days,or ≥50% stenosis in a artery association with clinical symptoms,or cardioembolic source warranting anticoagulation. Results According to the results of the composite endpoint,all patients were divided into positive group （34 patients） and negative group （98 patients）.FIB were higher in positive group compared to negative group （P<0.05）.There was no relationship between DD and composite endpoint （P>0.05）.FIB were elevated in patients with ≥50% stenosis （P<0.05）.ABCD² score ≥4 （moderate risk: RR＝2.18,95%CI 1.26～3.61,P＝0.008 high risk group: RR＝3.43,95%CI 1.91～6.39,P＝0.001） and FIB ≥3.5 g/L （RR＝2.81,95%CI 1.05～6.32,P＝0.044） were significantly associated with the composite endpoint. Conclusion FIB is an independent risk factor for TIA,and the combination of FIB and the ABCD² score can improve the ability to predict stroke and death within 90 days after TIA.

Abstract:Aim To investigate the association between plasma omentin-1 level and left ventricular hypertrophy （LVH） in patients with essential hypertension （EH）. Methods We randomly enrolled 55 essential hypertensive patients with or without left ventricular hypertrophy （LVH）,and 32 participants with normal blood pressure.We measured plasma omentin-1 and nitric oxide （NO） levels.Left ventricular hypertrophy was assessed by left ventricular mass index （LVMI）. Results Plasma omentin-1 and nitric oxide levels were significantly decreased in essential hypertensive patients compared to normal control group （P<0.05）,and were further reduced in essential hypertensive patients with left ventricular hypertrophy compared to those without left ventricular hypertrophy （P<0.05）.Pearson correlation analysis showed that plasma omentin-1 was significantly positively related with NO （r＝0.565,P<0.01）,and significantly negatively related with systolic blood pressure,diastolic blood pressure,mean arterial blood pressure,pulse pressure,LVMI （r＝－0.713,－0.699,－0.788,－0.311,－0.675,P<0.05 or P<0.01）.Multiple linear regression analysis showed that omentin-1 was independently related with systolic blood pressure and diastolic blood pressure in patients with EH （bomentin-1＝－2.140,P<0.05 bomentin-1＝－1.382,P<0.05）.Omentin-1 and hypertension course were independently related with LVMI in patients with EH （bomentin-1＝－5.980,P<0.05 bhypertension course＝0.103,P<0.05）. Conclusions Plasma omentin-1 level decreases in hypertensive patients.Omentin-1 is positively related with nitric oxide,and is negatively related with LVMI in essential hypertensive patients.Omentin-1 may be an independent indicator for LVH in essential hypertensive patients.

Abstract:Aim To explore the clinical efficacy and safety of edaravone in the treatment of hypertensive cerebral hemorrhage. Methods From January,2011 to June,2014 in our hospital according to the experimental conditions,190 cases of hypertension cerebral hemorrhage were chosen and randomly divided into two groups: edaravone group （95 cases） and control group （95 cases）,the two groups had the base treatment,the neural function defect scale （NIHSS score）,daily life activities ability score （ADL score） and hematoma volume size were recorded and serum C- reactive protein （CRP） concentration was measured,at the same time the adverse reaction was observed in 14 days,21 days before and after treatment.

Abstract:Aim To explore the correlation between P-wave dispersion （PWD） & maximum P-wave duration （Pmax） and left ventricular diastolic function. Methods the paper measures PWD & Pmax of 100 coronary artery disease patients with 12-lead ECG synchronization,who are grouped into greater than 40ms and less than 40ms according to PWD,and grouped into greater than 110ms and less than 110ms according to Pmax.Indices such as severity of coronary stenosis,E/A ratio,DT,LAD,LVEDD,LVEF,paroxysmal atrial fibrillation etc.are compared among groups as well.

Abstract:Aim To investigate the relation between obstructive sleep apnea hypopnea syndrome （OSAHS） and progressive cerebral infarction. Methods 160 patients with acute cerebral infarction,according to the polysomnography （PSG） monitoring results,were divided into pure cerebral infarction group （n＝72） and cerebral infarction with OSAHS group （n＝88）.The related laboratory indexes and the percentage of progressive cerebral infarction were compared between the two groups.According to the sleep apnea hypopnea index （AHI）,the OSAHS group was divided into 3 subgroups: cerebral infarction with mild OSAHS group （28 cases）,cerebral infarction with moderate OSAHS group （29 cases）,cerebral infarction with severe OSAHS group （31 cases）.National Institute of Health Stroke Scale （NIHSS） score were compared among the 3 groups at seventh day after onset. Results The related laboratory indexes and the percentage of progressive cerebral infarction of the cerebral infarction with OSAHS group were higher than those of the pure cerebral infarction group,and the differences were statistically significant （P<0.01）.Cerebral infarction with severe OSAHS group had higher NIHSS score than cerebral infarction with moderate OSAHS group,cerebral infarction with moderate OSAHS group had higher NIHSS score than cerebral infarction with mild OSAHS group,and the differences were statistically significant （P<0.01）. Conclusion OSAHS can easily lead to exacerbation in patients with cerebral infarction,and the severity of OSAHS was positively correlated with the severity of cerebral infarction.

Abstract:Aim To investigate the influential factors on stability of carotid plaques in patients with ischemic stroke （IS）. Methods 171 cases of ischemic stroke patients,were confirmed by color ultrasound diagnostic instrument check to make sure carotid artery plaques.According to the characteristics of magnetic resonance imaging （MRI）,the patients were divided into stable plaque group and unstable plaque group.Logistic regression model was used to estimate the risk factors influencing stability of carotid plaques. Results Of 171 patients,119 （69.59%） patients had unstable plaques and 152 （30.41%） patients had stable plaques.The levels of low density lipoproteins （LDL）,apolipoprotein A1 （ApoA1）,fasting blood glucose （FBG）,glycosylated hemoglobin （GHb）,uric acid （UA） and high-sensitive C-reactive protein （hs-CRP） in the unstable plaque group were higher than those in the stable plaque group.ApoA1 （OR＝3.92,95%CI 2.11～7.25,P＝0.000）,FBG （OR＝1.34,95%CI 1.06～1.69,P＝0.014）,UA （OR＝1.01,95%CI 1.00～1.01,P＝0.001） and hs-CRP （OR＝1.33,95%CI 1.09～1.62,P＝0.005）were independent risk factors of unstable plaques. Conclusions Ischemic stroke incidence rate is high in patients with unstable plaque.Unstability of carotid plaques is closely correlated with ApoA1,FBG,UA and hs-CRP.

Abstract:Aim To investigate the prevalence of primary aldosteronism（PA）in patients with hypertension and analyse the clinical features of confirmed PA. Methods A total of 640 consecutive outpatients with hypertension were enrolled for screening of PA.Plasma aldosterone （ALD） and plasma renin activity （PRA）were determined at 9∶30～10∶00 in the morning after the patients have been up for at least 2h and seated for 5～15 min.The radio of ALD to PRA （ARR） was calculated.Subjects with ARR ≥30 and ALD≥15 ng/dL received confirmatory Catopirl challenge test.Patients with positive results （plasma aldosterone suppressed≤30%） were dignonsed as PA.An enhancement scan was carried out in all the patients dignosed as PA for further clssification of PA subtype. Results Among 640 patients,112（17.5%）had an elevated ARR（≥30）,and 87（13.59%）had both elevated ARR（≥30）and ALD（≥15 ng/dL）.32（5%）definitely diagnosed as PA by Catopirl challenge test with the levers of ALD were suppressed less than 30% with Catopirl.20（3.125%）patients with APA underwent unilateral laparcoscopic adrenalectory,12（1.875%）patients with IHA were treated with spironolactone. Conclusion The prevalence of PA is higher in the hypertentive population,we should pay attention to hypertensive patients with PA screening.Patients with PA have typical clinical features: hypertension,hypokalemia,high urinary potassium,high aldosterone and low renin,high ARR.

Abstract:Aim To investigate the association of apolipoprotein C3 （ApoC3） SstⅠ polymorphism with coronary heart disease （CHD） and plasma triglyceride levels by Meta-analysis. Methods The articles investigating the association between the ApoC3 SstⅠ polymorphism and CHD were searched from the Chinese and English electronic databases.

Abstract:MicroRNA （miRNA） is a kind of non-coding small RNA newly discovered in recent years,which function is as regulators by affecting the stability of target genes mRNA or blocking translation.miR-1 is the most abundant miR expressed in the human heart,and is closely associated with arrhythmia.Large numbers of research report show that regulating miR-1 expression levels can control arrhythmia by up-regulation or down-regulation of numerous ion channels and proteins related to cardiac electrical activity.This paper summarizes the mechanism of the regulation function of miR-1 for arrhythmia.

Abstract:Toll-like receptor 7 （TLR7）,a type Ⅰ transmembrane protein receptor expressed in mammalian cells,has the same structure characters and similar functions as other members of TLR family.In addition to regulating some immune responses induced by virus through the MyD88-dependent signaling pathway,TLR7 can adjust the autophagy of macrophages to mediate the progress of atherosclerosis.Furthermore,it is probably to not only induce the type Ⅰ interferon expression,but also act as autoantigens to activate cellular and humoral immune response mediated by T cells and B cells by all kinds of ligand and endogenous molecules,thus participate in regulating the development of atherosclerosis.Therefore,it is critical that more attention is given to the function and mechanism research of TLR7 in atherosclerosis,which will be a new starting point for the prevention and control of atherosclerosis.

Abstract:This article reviews and summarizes the research data about vertebrobasilar dolichoectasia in recent years.The data about vertebrobasilar dolichoectasia are sorted out and analyzed from the aspects of epidemiology,nosogenesis,imaging diagnosis,clinical manifestations,as well as treatment progress.