Clopidogrel is an antiplatelet drug widely used in clinical practice now.It has been used as the secondary prevention medication for myocardial infarction,ischemic stroke,and peripheral vascular disease.However,the anti-platelet aggregation effect of clopidogrel has significant individual differences.A large part of patients have clopidogrel resistance phenomenon.The mechanism of clopidogrel resistance is not fully understood.The genetic polymorphism is an important cause of clopidogrel resistance,including ABCB1,CYP2C19,CYP3A4,CYP3A5,P2Y12,and ITGB3.

Objective To investigate the dynamic change of serum high sensitive C-reactive protein (hsCRP) after carotid artery stenting (CAS) and its correlation with in-stent restenosis.Methods The serum hsCRP levels were determined before procedure,at 12 hours,7 days,3 and 6 months after procedure in patients who underwent CAS in the Department of Neurology,Jinling Hospital,Nanjing Their cerebral angiography was reexamined and whether there was in-stent restenosis after 6 months was observed.Results Eighty-four patients treated with CAS were included in the study.Fifteen (24％) had in-stent restenosis after CAS.The stenosis in 3 of them was ＞ 50％,and the stenosis m 12 of them was 30％ to 50％.The serum hs-CRP levels in all patients after procedure were significantly higher than those before treatment (all P ＜ 0.01 ),and they were significantly lower at 6 months after procedure than before treatment (all P ＜0.01).Univariate analysis showed that the proportion of diabetes in the restenosis group was significantly higher than that in the non-restenosis group (P＜0.01).At 7 days (8.83 ± 1.94 mg/L vs.6.77 ± 1.63 mg/L,t =14.398,P=0.044),3 months after procedure (8.26 ± 1.32 mg/L vs.4.58 ± 1.45 mg/L,t =17.569,P =0.008) and 6 months after procedure (7.04 ± i.07 mg/L vs.3.12 ± 1.28 mg/L,t =21.867,P =0.003),the serum hs-CRP levels in the restenosis group were significantly higher than those in the non-restenosis group,and the difference of the serum hs-CRP level (△ hs-CRP) before procedure and at 6 month after procedure was significantly lower than that in the nonrestenosis group (0.85 ± 0.13 mg/L vs.4.89 ± 0.94 mg/L,t =16.987,P =0.000).Multivariate logistic regression analysis showed that /hs-CRP (odds ratio [ OR] 2.392,95％ confidence interval [ CI] 1.538 -3.513; P =0.009) and diabetes (OR 1.840,95％ CI 1.372 -2.241; P =0.023) were the risk factors for instent restenosis.Conclusions The serum hs-CRP level increased significantly at 12 hours after CAS procedure,and then decreased continuously.At 6 months after procedure,the more decrease of the serum hs-CRP level,the lower risk of occurring in-stent restenosis was.

Stroke is a class of complex diseases,and it is the result of the combined action of environmental and genetic factors.With the development of molecular biology techniques,a large number of candidate genes associated with stroke and susceptibility loci have been identified.This article reviews the recent progress in research on the genetics of different subtypes of ischemic stroke.

MicroRNAs (miRNAs) are endogenous non-coding RNAs composed of 18-25 nucleotides,and they may play a role in gene regulation through completely or partially binding to target gene mRNA complementary sequences and make it degrade or prevent its translation.miRNAs play important roles in the onset and pathophysiological processes of ischemic stroke.This article reviews the roles of miRNAs in the etiology of ischemic stroke and pathophysiological mechanisms after stroke,and the potential application of miRNAs is prospected.

Objective To assess true vocal fold (TVF) length and cricothyroid distance(CTD) with ultrasonography in male-to-female (MtF)transsexual voice surgery.Methods Five MtF transsexuals were divided into two groups according to their voice change surgery methods.High-frequency ultrasonography was used to measure the length of true vocal folds and cricothyroid distance.Measurements were compared pre-and post-surgery, and correlations with fundamental frequency (F0) were analyzed.Results The ultrasonography measurements clearly showed the laryngeal structure and TVF measurement marks.After vocal fold shortening and retrodisplacement of anterior commissure(VFSRAC) surgery, the ultrasonographic measurements showed that the shortening length of TVF were 0.37 cm(21%),0.69 cm(37%) and 0.40 cm(25%), respectively.The CTD in ultrasonographicimages were 1.0 cm pre-surgery of cricothyroid approximation (CTA) and-0.33 post-surgery of CTA.The displacement of cricoid cartilage was 1.33 cm, which was consistent with the laryngeal CT image.Conclusion Both TVF length and CTD can be shown by high-frequency ultrasonography, which can be used to quantitatively assessment and follow-up MtF transsexual voice surgery.

In recent years,stem cell transplantation for the treatment of ischemic stroke has become a hot topic.However,since embryonic stem cells (ESCs) transplantation is limited by the ethics and law,stem cell research was once in trouble.Induced pluripotent stem cells (iPSCs) are a class of cells by introducing the specific transcription factors into somatic cells,which have the similar characteristics with ESCs,and also avoid the ethical issues and immunological rejection,making them become the most ideal replacer of ESCs.Although the current research on iPSCs has made some progress,their induction efficiency and safety issues remain to be resolved.This article reviews the status quo,mechanisms,and problems faced in clinical practice for iPSCs transplantation in the treatment of ischemic stroke.

Objective To investigate the value of hyperintense vessel signs (HVS) on fluidattenuated inversion recovery (FLAIR) sequence for assessing the patterns of collateral blood flow in adult moyamoya disease (MMD).Methods Forty-one adult patients with non-hemorrhagic MMD retrieved from Nanjing Stroke Registry Program between August 2008 and January 2011 were identified by digital cerebral angiography and performed the examination of FLAIR sequence in Jinling hospital.According to the different sites of HVS located in the territory of the middle cerebral artery,the patterns of HVS were classified into grades 0-3: Grade 0,absence of HVS ; Grade 1,HVS limited in the cerebral sulci of temporal lobe and Sylvian fissure ; Grade 2,HVS in the cerebral sulci of frontal and parietal lobe regions and Sylvian fissure;and Grade 3,HVS in the combined territories of Grade 1 and Grade 2.According to the intracerebral collateral blood flow,steno-occlusions of the arteries were classified into three types: Type 1,residual antegrade flow across steno-occlusive lesions; Type 2,retrograde flow via leptomeningeal vessels; Type 3,the combined collateral blood flow of Type 1 and Type 2.The relationship between the patterns of intracerebral collateral blood flow and the location of HVS was analyzed.Results Of 41 adult patients with non-hemorrhagic MMD,there were 3 patients presented with unilateral vascular lesions and 38 with bilateral vascular lesions,so the total number of vascular lesions of the cerebral hemispheres was 79.Because three patients showed the absence of HVS in bilateral hemispheres,the total number of the presence of HVS of the cerebral hemispheres was 73.Therefore,the percentage of the presence of HVS was 92.4％ (73/79) in vascular lesions of the cerebral hemispheres.Importantly,the patterns of slow collateral blood flow corresponding to Grade 1 HVS were all antegrade (7/7) ; the collateral patterns corresponding to Grade 2 HVS were mainly retrograde leptomeningeal flow (95.0％,19/20) ; and the patterns corresponding to Grade 3 HVS were mainly slow combined collateral blood flow(84.8％,39/46).Furthermore,with the changing sites of HVS from the cerebral sulci of temporal lobe to the cerebral sulci of frontal and parietal lobe regions,the directions of collateral flow changed with a shift from antegrade to retrograde,which was statistically significant.Conclusion The different locations of HVS can reflect the different patterns of collateral blood flow,and the locations of HVS may predict the directions of intracerebral collateral blood flow in adult MMD patients.

Objective To evaluate the prognostic value of hyperintense vessel (HV) in patients with acute middle cerebral artery (MCA) occlusion.Methods Seventy-four consecutive patients with first ever stroke(48 male and 26 female,the mean age was (60.7 ± 15.3) years) in the territory of MCA,retrieved from Nanjing Stroke Registry Program between May 2009 and February 2011,were enrolled assubjects.All subjects completed brain MRI,and MRA or DSA indicated proximal MCA occlusion.According to the location and extent of HV,all subjects were classified into 3 groups:without HV,proximal HV and distal HV.Clinical data were obtained and compared among patients with different grades of HV.Logistic regression analysis was employed to confirm the relevant factors of prognosis 90 days after index stroke.Results HV was observed in 49 (66.2％ ) of the 74 enrolled patients.Among patients with HV,7 (9.4％ ) were classified as proximal HV and 42 ( 56.8％ ) as distal HV.Initial NIHSS score ( 11 ( 1 -22) ),10-day NIHSS score ( 13.5(4-25) ),infarction size ( ＞2/3:5 cases(6.8％ ) ),and 90-day mRSscore (3-6 scores:12 cases( 16.2％ )) were significantly lower in patients with distal HV than those without (15(6-25),Z=-3.544;7(0-22),Z=-4.461;20 cases(27.0％),x2 =20.916;27 cases (36.5％),x2 =22.689;all P＜0.01).The NIHSS score decreased from baseline to that on 10 days and the mRS score decreased from 10 days to that on 90 days in patients with distal HV was more than that in patients without distal HV. Multivariate analysis revealed that patients with older age ( OR =1.111,95％ CI 1.036-1.191,P=0.003),high infarction size (OR=3.679,95％ CI 1.35-10.025,P=0.011) worsened outcome,whereas distal HV (P =0.012,OR =0.131,95％ CI 0.027-0.638)improved outcome.Conclusion Distal HV on FLAIR may predict a favorable outcome in patients with acute middle cerebral artery occlusion.

Objective Neuroinflammation following traumatic brain injury (TBI) may give rise to neurodisorder.This study aimed to investigate the effect of intranasal delivery of nerve growth factor ( NGF) on neuroinflammation following TBI and its action mechanism in rats. Methods Thirty-six male adult Sprague-Dawley rats were equally divided into a sham , a TBI, and a TBI+NGF group.The rats in the TBI +NGF group were treated with NGF intranasally at 12 and 24 hours after TBI.The levels of IL-1βand TNF-αin the injured cerebral cortex were detected by ELISA , the DNA-binding activity of NF-κB evaluated by EMSA , and the expres-sion of amyloid-β( Aβ42 ) determined by Western blot . Results NGF attenuated the inflammation following TBI .Compared with the TBI group, the level of IL-1βwas obviously decreased in the TBI +NGF group at 12 hours (70.65 ±3.10 vs 37.51 ±1.92) and 24 hours (68.85 ±8.10 vs 36.23 ±2.99, P<0.05), and so was that of TNF-α(47.12 ±7.38 vs 27.63 ±5.77 and 56.15 ±11.20 vs 29.94 ±8.62, P<0.05).The DNA-binding activity of NF-κB was reduced to 111.62 ±0.49 and 131.52 ±0.88, and the expression of Aβ42 to 0.23 ±0.008 and 0.52 ±0.004 at 12 and 24 hours respectively after treatment with NGF , both with statistically significant differences from the TBI group (P<0.05). Conclusion Intranasal administration of NGF attenuates TBI-induced neuroinflamma-tion in rats, which may be associated with its regulatory effect on the Aβ42/NF-κB signaling pathway .

Objective ToinvestigatetherelationshipbetweenmuscleRASoncogenehomolog (MRAS)genepolymorphismandyoungpatientswithischemicstroke.Methods Atotalof243young patients with ischemic stroke from Nanjing Stroke Registry Program from December 2009 to October 2012 were enrolled retrospectively. At the same time,512 age-and sex-matched healthy controls were selected. The polymorphisms of MRAS genes rs3755751 and rs9289559 loci were analyzed by the modified multiplex PCR-ligase detection reaction assay. The genotype of each locus and the allele frequencies were analyzed and compared. Results (1)The frequencies of AA,AG and GG genotypes for rs3755751 in the stroke group (n=243)were 7. 4%(n=18),37. 0%(n=90),and 55. 6%(n=135),respectively. There were no significant differences compared with those (6. 4%[n=18],36. 9%[n=189]and 56. 6%[n=190]) in the control group (n=512)(P>0. 05). The frequencies of AA,AG and GG genotypes for rs9289559 in stroke group were 7. 0 (n=17)%,42. 0%(n=102),and 51. 0%(n=124),respectively. There were no significant differences compared with 6. 1%,(n=31)37. 9%(n=194),and 56. 1%(n=287)in the control group (P>0. 05). (2)Further construction of an effect model (AA vs. AG+GG and GG vs. AG+AA),there was no significant difference between the stroke group and the control group (P >0. 05 ). Analyzing the effects of different genotypes on plasma lipid levels showed that the high-density lipoprotein cholesterol level of the GG genotype subgroup in the young ischemic stroke group was significantly higher than that rs3755751 of the AG +AA genotype subgroup (OR,6. 80,95%CI 2.18-21.27, P=0. 001 ). Conclusions MRAS gene polymorphism may have no significant correlation with the genetic susceptibility in young patients with ischemic stroke. Polymorphism of rs3755751 may be correlated with the level of serum high-density lipoprotein cholesterol.