皮质下缺血性血管病患者注意执行功能损害特征的研究

目的探讨皮质下缺血性血管病(SIVD)患者注意-执行功能损害的特征。方法收集SIVD患者95例,并按照认知功能分为无认知障碍组(NCI)29例、血管性认知障碍非痴呆组(VCI-ND组)40例、血管性痴呆组(VaD组)26例。对所有患者进行全面神经心理测查并分析。结果 95例SIVD患者中,有VCI患者66例,占69.5%,其中VCI-ND患者40例,占VCI总数的60.6%。3组患者执行功能各项测验(DS-F除外)均以VaD组损害最严重,NCI组最轻,3组比较差异有统计学意义(P<0.01)。VCI-ND组和VaID组注意-执行标准分数在各项认知域评分中最低。结论 SIVD患者认知损害的突出领域是注意执行功能,再认和即刻记忆相对保留是其记忆损害的特点。抑郁和其他精神行为异常多见于认知障碍患者。     

皮质下缺血性脑血管病执行功能损害与脑白质结构的相关性研究

目的 探讨皮质下缺血性脑血管病(SIVD)执行功能损害、MRI脑白质病变和DTI脑白质的微结构变化及其临床相关因素.方法 应用Stroop色词测验(CWT)、连线测验(TMT) 和积木测试(BDT)评价24例SIVD患者和14例认知正常老年人的执行功能,其中SIVD患者分为痴呆(VD)组12例,认知障碍无痴呆(VCIND)组12例;依据年龄相关白质改变的评分方法(ARWMCrs) 测量常规MRI上白质病变程度,同时应用DTI分别测定额、颞、顶、枕叶及胼胝体压部白质正常区的各向异性分数(FA)和平均扩散率(MD)值,分析各影像学测量指标与执行功能的相关性.结果 (1)与健康对照组比较,VD组执行功能三项测验均显著减退,VCIND组BDJ评分降低,TMT时间延长,差异有统计学意义(P<0.05);(2)与对照组相比较,VD、VCIND组白质病变评分增高,分别为12.820±3.573、10.500±2.953(P＜0.05);胼胝体压部MD值均升高,具有统计学差异(P＜0.05);VD患者双额叶、右颞叶、右枕叶、双顶叶及胼胝体压部FA值下降(P＜0.05);VCIND组左额叶、双顶叶白质FA值下降(P＜0.05);(3)与SIVD患者执行功能相关的影像学指标有:左额叶、双颞叶、右顶叶白质正常区FA值、胼胝体压部MD值(P＜0.05).结论 (1)SIVD患者存在执行功能障碍,与其脑白质病变程度可能有关;(2)DTI可以显示SIVD患者常规MRI无法显示的脑白质选择性微结构损害;(3)SIVD患者的多个脑白质区FA及MD与CWT、TMT和BDT存在相关性,提示白质微结构的损害可能反映执行功能的下降.     

皮质下缺血性血管性疾病患者的步态障碍

皮质下缺血性血管性疾病(subcortical ischemic vascular disease,SIVD)是一组由脑部小血管疾病导致的以皮质下多发性腔隙性脑梗死和脑白质病变为主要病理损害的缺血性脑血管病.SIVD是导致血管性认知障碍的最主要原因,SIVD还可出现步态障碍,如帕金森样步态、额叶步态、走路不稳或无明显诱因的频繁跌倒等.有研究表明,老年人步态异常可能是血管性痴呆的早期标志.文章对SIVD导致步态障碍的病理学机制、临床特点、临床意义、分析与评价、治疗等方面做了综述.     

皮质下缺血性血管性疾病患者的步态障碍

皮质下缺血性血管性疾病(subcortical ischemic vascular disease,SIVD)是一组由脑部小血管疾病导致的以皮质下多发性腔隙性脑梗死和脑白质病变为主要病理损害的缺血性脑血管病.SIVD是导致血管性认知障碍的最主要原因,SIVD还可出现步态障碍,如帕金森样步态、额叶步态、走路不稳或无明显诱因的频繁跌倒等.有研究表明,老年人步态异常可能是血管性痴呆的早期标志.文章对SIVD导致步态障碍的病理学机制、临床特点、临床意义、分析与评价、治疗等方面做了综述.     

银杏叶提取液对不同类型脑小血管病患者认知功能改善的观察

目的对比分析银杏叶提取液对不同类型脑小血管病(CSVD)患者认知功能的改善情况。方法收集2016年3月至2018年4月西安交通大学第二附属医院老年神经内科收治的123例CSVD患者,根据类型分成三组:脑白质病变组(WML,n=43),腔隙性脑梗死组(LI,n=36)及WML+LI组(n=44);同时选取同时间段门诊就诊的44例无影像学病变的头痛患者作为对照组。收集患者的临床资料,检测血清转化生长因子β(TGF-β)、肿瘤坏死因子α(TNF-α)及Aβ肽1-40(Aβ1-40)短肽水平;分别采用蒙特利尔认知量表(MoCA)、简易智力状态评估量表(MMSE)及痴呆评定量表(CDR)评估患者的认知能力、智力状态及痴呆程度。结果四组患者在年龄、性别、吸烟史、高血压、糖尿病、高血脂及家族史中差异无统计学意义(P> 0.05)。TGF-β、TNF-α及Aβ1-40短肽表达结果显示,与治疗前比较,差异具有统计学意义(F=17.064、30.336、28.808,均P <0.01)。给予银杏叶提取液治疗后,WML组和LI组TNF-α和Aβ1-40短肽水平比较有统计学意义(t=2.459、2.713、-4.777、-5.942,P <0.05),但TGF-β水平差异无统计学意义(P> 0.05)。WML+LI组TGF-β、TNF-α及Aβ1-40短肽水平与治疗前相比均有统计学意义(t=-2.572、4.653、-11.039,P <0.05)。MoCA和MMSE总评分比较结果显示,治疗前WML、LI及WML+LI组的MoCA和MMSE评分结果均较对照组低(F=20.285、3.799、46.285、23.644,P <0.05),给与银杏叶提取液治疗后均显著增加,差异有统计学意义(t=-2.316、-2.911、-4.626、-4.162、-4.373、-11.157,P<0.05)。在WML+LI组中MMSE评分的提升具有统计学意义(t=-5.324,P <0.05)。CDR评分比较结果显示,对照组患者主要集中在无痴呆和可疑痴呆,WML、LI及WML+LI组患者主要分布在无痴呆、可疑痴呆、轻度痴呆及中度痴呆,均无重度痴呆患者。四组患者在无痴呆、可疑痴呆、轻度痴呆及中度痴呆人数分布上的差异均具有统计学意义(χ2=65.942、10.318、18.667、9.034,P <0.05),但在WML、LI及WML+LI组中差异无统计学意义(P> 0.05)。结论银杏叶提取液能够有效降低不同类型CSVD患者血清中TGF-β、TNF-α及Aβ1-40短肽水平,改善患者的认知功能和临床预后,在WML+LI组患者中的疗效更甚。     

血管性认知损害的筛查工具与早期诊断

血管性认知损害(vascular cognitive impairment,VCI)是由脑血管病危险因素(如高血压、心脏病、糖尿病和高血脂等)、明显(如脑梗死和脑出血等)或不明显的脑血管病(如白质疏松和慢性脑缺血等)引起的从轻度认知障碍到痴呆的综合征[1,2].目前较为统一的意见是VCI包括3个内容[3～6]:非痴呆型血管性认知损害 (vascular cognitive impairment,no dementia,VCIND)、血管性痴呆(vascular dementia,VD )、AD伴血管病变(即混合性痴呆,mixed AD/VD).与血管性痴呆相比,其内涵有了扩展,认知障碍不强调记忆力损害,只要有某些认知领域的功能下降,即使没有记忆力减退,仍然可定性为认知障碍;同时,"血管性"不特指脑出血或梗死,还包括各种可能影响脑功能的心脑血管病变.     

高同型半胱氨酸血症与皮质下缺血性血管病患者认知功能障碍的关系

目的探讨高同型半胱氨酸血症(Hhcy)及叶酸、维生素B12缺乏与皮质下缺血性血管病(SIVD)不同程度认知功能障碍的相关性。方法将119例SIVD患者按照简易精神状态量表(MMSE)认知功能程度的不同分为痴呆组与非痴呆组。其中痴呆组54例,非痴呆组65例。对所有受试者检测其同型半胱氨酸(Hcy)及血清叶酸、维生素B12水平。结果痴呆组血浆Hcy水平为(43±9)μmol/L,显著高于非痴呆组的(20±6)μmol/L(P<0.01);血清叶酸和维生素B12水平分别为(8±4)nmol/L、(290±154)pmol/L,显著低于非痴呆组的(13±3)nmol/L、(504±141)pmol/L(均P<0.01)。采用Spearm an相关方法分析,显示不同性别的Hcy水平与MMSE分数均呈负相关(男:r=-0.685,女:r=-0.689,二者均P<0.01),与年龄均呈正相关(男:r=-0.592,女:r=0.576,二者均P<0.01);Hcy水平与糖尿病、血脂、高血压、吸烟、饮酒等其他危险因素无明显相关性(P>0.05)。结论伴随血浆Hcy水平增高SIVD认知功能障碍程度加重,Hhcy可能是SIVD认知功能障碍的独立危险因素,叶酸、维生素B12缺乏是间接引起Hhcy,而导致SIVD重要的营养因素。     

皮质下缺血性脑血管病患者睡眠质量及其与认知功能、抑郁的相关性研究

目的分析皮质下缺血性脑血管病(SIVD)患者睡眠质量,并探讨其与认知功能、抑郁的相关性。方法选取2016年9月—2017年12月合肥市第二人民医院神经内科收治的SIVD患者62例作为病例组,根据颅脑磁共振成像(MRI)检查结果分为白质病变(WML)组20例和腔隙性梗死(LI)组42例;另选取同期体检健康者43例作为对照组。比较对照组与病例组受试者一般资料、匹兹堡睡眠质量指数量表(PSQI)评分、Epworth嗜睡量表(ESS)评分、蒙特利尔认知评估量表(MoCA)评分和Beck抑郁量表(BDI)评分,比较WML组与LI组患者PSQI评分和ESS评分,睡眠质量指标与SIVD患者认知功能、抑郁程度指标的相关性分析采用Pearson相关分析。结果 (1)对照组与病例组受试者性别、年龄及糖尿病发生率比较,差异无统计学意义(P0.05);病例组患者受教育年限短于对照组,高血压发生率高于对照组(P0.05)。(2)对照组与病例组受试者睡眠潜伏期、睡眠持续性、睡眠效率、睡眠紊乱及使用睡眠药物评分比较,差异无统计学意义(P0.05);病例组患者PSQI总分、主观睡眠质量评分、日间功能紊乱评分及ESS评分高于对照组(P0.05)。(3)对照组与病例组受试者命名、注意、语言、抽象、定向评分比较,差异无统计学意义(P0.05);病例组患者MoCA总分及视空间与执行功能、延迟回忆评分低于对照组,BDI评分高于对照组(P0.05)。(4)WML组与LI组患者PSQI总分及睡眠潜伏期、睡眠持续性、睡眠效率、睡眠紊乱、使用睡眠药物评分比较,差异无统计学意义(P0.05);WML组患者主观睡眠质量、日间功能紊乱、ESS评分高于LI组(P0.05)。(5)Pearson相关分析结果显示,主观睡眠质量评分与SIVD患者视空间与执行功能评分呈负相关,与BDI评分呈正相关(P0.05);日间功能紊乱评分与SIVD患者MoCA总分、视空间与执行功能评分、延迟回忆评分呈负相关,与BDI评分呈正相关(P0.05);ESS评分与SIVD患者延迟回忆评分呈负相关,与BDI评分呈正相关(P0.05)。结论 SIVD患者睡眠质量较差,主要表现为主观睡眠质量下降、日间功能紊乱及嗜睡,其中WML患者较LI患者更为严重,且主观睡眠质量下降、日间功能紊乱及嗜睡与认知功能下降和抑郁有一定关系。     

静息态功能磁共振在皮质下缺血性血管性认知损害中的应用

皮质下缺血性血管病(subcortical ischemic vascular disease, SIVD)被认为是引起血管性认知损害(vascular cognitive impairment, VCI)的最重要和常见的原因。若能早期发现皮质下缺血性血管性认知损害(subcortical ischemic vascular cognitive impairment, SIVCI)或皮质下血管性认知损害(subcortical vascular cognitive impairment, sVCI)患者,会使血管性痴呆(vascular dementia, VaD)在发生之前得到识别甚至逆转其进程成为可能。最近的研究显示,静息态功能磁共振(resting-state fMRI, rsfMRI)有可能为 SIVCI 的诊断提供客观依据。文章对 rsfMRI 在 SIVCI 诊断中的应用进行了综述。     

脑小血管病与轻度认知功能障碍的关系

目的探讨脑小血管病变（SVD）与轻度认知功能障碍（MCI）的关系。方法收集临床SVD相关的MCI（SVD-MCI）患者66例和认知功能正常的老年人57例作为对照组。根据视觉评分,评估白质病变（WML）和内侧颞叶萎缩（MTA）病变的程度,并记录大脑不同部位腔隙性梗死（LI）的数目,应用多元Logistic回归分析LI、WML和MTA与SVD-MCI之间的相关性。结果①与对照组相比,SVD-MCI组患者患高血压比例和血中TC含量明显升高（P〈0.05）;吸烟、患糖尿病的比例和血中总胆固醇、低密度脂蛋白胆固醇含量有所升高,但差异无统计学意义（P〉0.05）;②与对照组相比,SVD-MCI组患者丘脑、侧脑室周围白质和皮质下白质LI的数目明显增加（P〈0.05）;SVD-MCI组患者侧脑室周围和皮质下WML以及双侧MTA评分分值也显著增加（P〈0.05）;③控制了年龄和多种血管危险因素的影响之后,多元Logistic回归分析显示,丘脑LI、侧脑室旁WML和左侧MTA与SVD-MCI相关。结论丘脑LI、侧脑室旁WML和左侧MTA可能是SVD-MCI的独立危险因素,积极预防和治疗SVD,也许可降低MCI的发生率。     

老年脑梗死患者血清可溶性CD40配体和白细胞介素18的变化及意义

目的探讨老年脑梗死患者血清可溶性CD40配体(sCD40L)、白细胞介素18(IL-18)及高敏C反应蛋白(hs-CRP)水平的变化及意义。方法选择急性脑梗死患者80例(脑梗死组),根据年龄分为老年脑梗死患者42例,非老年脑梗死患者38例;根据梗死面积分为腔隙性脑梗死患者38例,非腔隙性脑梗死患者42例;根据神经功能缺损评分分为重型患者16例,中型患者30例,轻型患者34例。同期健康体检者28例(对照组)。采用ELISA法和胶乳凝集法检测血清sCD40L、IL-18及hs-CRP水平。结果与对照组比较,脑梗死组老年脑梗死和非老年脑梗死患者血清sCD40L、IL-18及hs-CRP水平明显升高,腔隙性脑梗死和非腔隙性脑梗死患者血清sCD40L、IL-18及hs-CRP水平明显升高,神经功能缺损中型和重型患者sCD40L、IL-18及hs-CRP水平明显升高,差异有统计学意义(P<0.05,P<0.01)。血清sCD40L与IL-18呈正相关(r=0.7645,P<0.01)。结论脑梗死患者急性期血清sCD40L、IL-18、hs-CRP水平明显升高,且随年龄、梗死体积和神经功能缺损程度增加而加重,sCD40L可能上调IL-18表达,并参与脑梗死炎性反应过程。     

阿司匹林对2型糖尿病患者血清可溶性CD40配体水平的影响

目的观察2型糖尿病（T2DM）患者血清可溶性CD40配体（sCD40L）水平的变化，以及阿司匹林（ASP）对其水平的影响。方法T2DM患者55例按是否服用阿司匹林（ASP）分为DM不服用ASP（DMwithoutASP）组24例和DM服用ASP组（DMwithASP）31例，设对照组33例。采用ELISA法测定血清sCD40L水平。结果DM-ASP组较对照组的sCD40L水平升高（2．14±0．74VS1．89±1．07，P〉0．05），DM＋ASP组CD40L较DM组下降（1．19±0．76，P〈0．01），较对照组下降（P〈0．01）。结论DM患者血清sCD40L升高；服用ASP可降低DM患者sCD40L水平。     

血清可溶性CD40配体水平与缺血性卒中发病风险、严重程度和梗死体积的相关性

目的探讨血清可溶性CD40配体(soluble CD40 ligand,sCD40L)水平与缺血性卒中发病风险、严重程度和梗死体积的相关性.方法纳入连续住院的急性缺血性卒中患者作为病例组,健康体检者作为对照组.收集病例组和对照组人口统计学、血管危险因素和临床资料.采用酶联免疫吸附法测定血清sCD40L水平.缺血性卒中患者根据基线美国国立卫生研究院卒中量表(National Institutes of Health Stroke scale,NIHSS)评分分为轻度卒中组(＜8分)和中重度卒中组(≥8分),根据梗死体积中位数分为大梗死组和小梗死组.结果 共纳入106例急性缺血性卒中患者,其中男性59例(55.7％),女性47例(44.3％),平均年龄(71.31±11.27)岁;对照组86例,其中男性45例(52.3％),女性41例(47.7％),平均年龄(73.56 ±9.32)岁;大梗死组(≥1.8 cm3)41例(38.7％),小梗死组(＜1.8 cm3)65例(61.3％);轻度卒中69例(65.1％),中重度卒中37例(34.9％).缺血性卒中组基线血清sCD40L水平显著高于对照组[(5.61±1.68) mg/L对(3.56±1.32)mg/L;扣9.236,P＜0.01],缺血性卒中组入院14 d时血清sCD40L水平[(4.19±1.45)mg/L]较基线水平显著降低(P＜0.01),但仍然显著高于对照组(P＜0.01).多变量logistic回归分析显示,低密度脂蛋白胆固醇[优势比(odds ratio,OR)3.358,95％可信区间(confidence interval,CI)2.681 ～4.056;P ＜0.001]和血清sCD40L(OR5.103,95％ CI2.317 ～8.903;P ＜0.001)水平较高是缺血性卒中的独立危险因素;血清sCD40L水平较高(第4四分位数对第1四分位数,OR4.017,95％ CI1.608 ～ 10.037;P=0.003)、大动脉粥样硬化性卒中(OR2.321,95％ CI1.014 ～ 5.314;P=0.046)、皮质-皮质下梗死(OR 2.679,95％ CI1.111 ～6.460;P=0.028)和梗死灶体积较大(OR 3.216,95％ CI1.398～7.395;P=0.006)为中重度卒中的独立危险因素;血清sCD40L水平较高(第4四分位数对第1四分位数,OR 3.142,95％ CI1.274 ～7.745;P =0.013)、大动脉粥样硬化性卒中(OR 2.965,95％CI1.299 ～6.767;P=0.010)、皮质-皮质下梗死(OR4.750,95％ CI 1.909～11.818;P＜0.001)和基线NIHSS评分≥8分(OR 8.509,95％ CI3.432 ～21.094;P ＜0.001)为大梗死的独立危险因素.结论血清sCD40L 水平与缺血性卒中发病、梗死体积和严重程度密切相关.     

2型糖尿病正常糖耐量一级亲属血清可溶性CD40配体水平及其相关因素分析

目的本文旨在观察2型糖尿病（T2DM）患者正常糖耐量一级亲属（FDR）血清可溶性CD40配体（sCD40L）水平的变化,并分析相关影响因素。方法在41个T2DM家系中收集糖耐量正常的FDR26名,同时设T2DM患者24例（T2DM组）,健康者21名作为对照（Con组）。采用ELISA法测定血清sCD40L水平。结果NGT-FDR组的sCD40L水平较对照组升高（1．88±0．47vs1．63±0．58,P=0．182）,T2DM组sCD40L水平显著升高（2．14±0．75,P=0．043vsCon组）。sCD40L水平与空腹血糖呈正相关（r=0．325,P=0．006）。结论T2DM患者血清sCD40L明显高于糖耐量正常者;T2DM患者正常糖耐量一级亲属血清sCD40L水平已呈升高趋势;sCD40L水平与空腹血糖水平呈正相关。我们推测sCD40L升高在T2DM自然病程中可能发挥一定作用。     

Silent brain infarction and platelet activation in obstructive sleep apnea

RATIONALE: Silent brain infarction (SBI) and increased levels of soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-selectin) are associated with an increased risk of cerebrovascular disease. OBJECTIVES: The aim of this study was to evaluate whether SBI and serum levels of sCD40L and sP-selectin are increased in patients with obstructive sleep apnea (OSA). METHODS: SBI was studied by brain magnetic resonance images in 50 male patients with OSA and 15 obese male control subjects who were free of comorbidities. In addition, the effects of 3 months of treatment with nasal continuous positive airway pressure (nCPAP) on serum parameters were studied in 24 patients with moderate to severe OSA. MEASUREMENTS AND MAIN RESULTS: The percentage of SBI in patients with moderate to severe OSA (25.0%) was higher than that of obese control subjects (6.7%) or patients with mild OSA (7.7%). Serum levels of sCD40L and sP-selectin were significantly higher in patients with moderate to severe OSA than in obese control subjects (p < 0.05) or patients with mild OSA (p < 0.05). In addition, nCPAP significantly decreased serum levels of sCD40L (p < 0.03) and sP-selectin (p < 0.01) in patients with moderate to severe OSA. CONCLUSIONS: These results suggest that serum levels of sCD40L and sP-selectin are elevated and SBI is more common in patients with moderate to severe OSA, leading to elevated cerebrovascular morbidity. Moreover, nCPAP may be useful for decreasing risk in patients with moderate to severe OSA.     

Association of soluble CD40 ligand with carotid atherosclerosis in Japanese type 1 diabetic patients

Aims/hypothesis It has recently been shown that the soluble form of CD40 ligand (sCD40L) interacts with CD40 on vascular cells, leading to a variety of proinflammatory responses, and that serum sCD40L levels can be a predictive marker of cardiovascular events. The aim of this study was to estimate sCD40L levels in type 1 diabetic patients to examine a possible association with carotid atherosclerosis.Subjects and methods Human sCD40L levels in serum and intima–media thickness (IMT) of carotid artery were examined in 80 Japanese type 1 diabetic patients (27 men and 53 women, age 22.8±3.4 years (mean±SD), duration of diabetes 13.2±6.1 years) and 20 healthy age-matched non-diabetic individuals.Results Serum sCD40L levels were significantly (p=0.0185) higher in subjects with type 1 diabetes (2.10±1.33 ng/ml) compared with non-diabetic subjects (1.35±0.88 ng/ml). The greatest IMT (Max-IMT) and averaged IMT (Mean-IMT) were also significantly greater in patients with type 1 diabetes than in control subjects (0.73±0.14 vs 0.64±0.07 mm, p=0.0041, 0.63±0.09 vs 0.57±0.06 mm, p=0.0066, respectively). Levels of sCD40L were statistically significantly associated with Max-IMT (r=0.383, p<0.001) and Mean-IMT (r=0.275, p=0.0058). Furthermore, stepwise multivariate regression analyses demonstrated that sCD40L is a determinant of both Max- and Mean-IMT, independently of conventional risk factors.Conclusions/interpretation It is suggested that increased levels of serum sCD40L are associated with accelerated atherosclerotic change observed in young patients with type 1 diabetes.     

Association between circulating level of CD40 ligand and angiographic morphologic features indicating high-burden thrombus formation in patients with acute myocardial infarction undergoing primary coronary intervention.

BACKGROUND: This study tested the hypothesis that in the acute phase of myocardial infarction (MI), the circulating level of soluble CD40 ligand (sCD40L), an index of platelet activation, is predictive of angiographic morphologic features that indicate high-burden thrombus formation (HBTF) in the infarct-related artery (IRA). METHODS AND RESULTS: This prospective study included 162 consecutive patients: 64 with HBTF and 98 with low-burden thrombus formation (LBTF). All patients had a Killip's classification相似文献   

急性冠状动脉综合征患者血清sCD40L升高的临床价值

目的观察冠心病不同类型患者中可溶性CD40L(sCD40L)水平的变化及其与白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)之间的关系,进一步探讨急性冠状动脉综合征(ACS)临床识别和预测的炎症指标。方法采用酶联免疫吸附法测定血清可溶性CD40L浓度,采用放免方法测定IL-6和IL-1β浓度。结果急性心肌梗死(AMI)患者sCD40L水平[(4.923±3.41)ng/ml]和不稳定型心绞痛(UAP)患者sCD40L水平[(5.387±3.04)ng/ml]显著高于稳定型心绞痛(SAP)[(2.856±2.34)ng/ml,P<0.05]和对照组患者[(2.221±2.42)ng/ml,P<0.01]。ACS患者sCD40水平与IL-6呈正相关(r=0.49,P=0.008),与IL-1β无相关性(r=0.258,P=0.183),而SAP和对照组患者sCD40L与IL-6、IL-1β无相关性。同时ACS患者sCD40L水平与低密度脂蛋白有显著相关性(r=0.471,P=0.011)。结论ACS患者血清sCD40L与IL-6、IL-1β水平升高,提示其可能与ACS发生有关,是动脉粥样硬化和斑块不稳定的标志。     

Relationship between the serum sCD40L level and aspirin-resistant platelet aggregation in patients with stable coronary artery disease

BACKGROUND: Current evidence supports the central role of inflammation in all phases of the atherosclerotic process, including its thrombotic complications. Increased serum sCD40L may trigger platelet activation, so the aim of the present study was to determine the relation between sCD40L levels and aspirin-resistant platelet aggregation in patients with coronary atherosclerosis. METHODS AND RESULTS: A total of 167 consecutive patients (39-85 years old, 35.9% women) with stable coronary artery disease was enrolled in the study. Platelet function was evaluated by a Platelet Function Analyzer 100 device (PFA-100) with collagen and epinephrine (Col/Epi) and collagen and adenosine diphosphate (ADP) (Col/ADP) cartridges. Aspirin resistance was defined as a closure time (CT) <186 s with Col/Epi cartridges, despite regular aspirin therapy. Serum sCD40L level was determined quantitatively with an ELISA method. Fifty-seven (34.1%) patients had aspirin resistance according to the PFA-100. Mean CT measured with the Col/ADP cartridges was 83+/-18 s (65-101 s). Mean serum sCD40L was 157 pg/ml (6-700 pg/ml) in the entire cohort. Patients with aspirin resistance had a mean serum sCD40L level of 166 pg/ml and patients with aspirin-sensitive platelet aggregation had an sCD40L level of 152 pg/ml (p=0.582). CONCLUSION: The sCD40L level is similar in patients with aspirin-resistant and aspirin-sensitive platelet aggregation according to the PFA-100. There is still need for further studies to elucidate the relationship between aspirin-resistant platelet aggregation and sCD40L, which is now known to be prothrombotic, proinflammatory and to be a risk factor for cardiovascular events.     

Elevated circulating CD40L concentrations in patients with systemic sclerosis

OBJECTIVE: B cell activation, fibrosis, and expression of adhesion molecules on endothelial cells are regulated by soluble CD40L (sCD40L)/CD40 interactions. Since these effects are characteristic in patients with systemic sclerosis (SSc), serum concentrations of sCD40L were determined in patients with SSc. METHODS: Fifty-two Japanese patients with SSc were examined. They were grouped into 24 patients with limited cutaneous SSc (lSSc) and 28 with diffuse cutaneous SSc (dSSc). Serum sCD40L levels were examined by ELISA. As a disease control, serum samples from 20 patients with systemic lupus erythematosus (SLE) were also examined. In addition, a retrospective longitudinal study was performed in 71 serum samples from 18 patients with SSc. RESULTS: Serum sCD40L levels were elevated in SSc patients compared with healthy controls (p < 0.001). Levels of sCD40L in patients with SSc were higher than in patients with SLE (p < 0.001) that had elevated sCD40L levels compared with healthy controls. Among SSc subsets, there were no differences in sCD40L levels between lSSc and dSSc. sCD40L levels correlated positively with C-reactive protein levels in SSc patients (p < 0.0001, r = 0.449). In a cross-sectional study and a longitudinal study, serum sCD40L levels in dSSc patients were persistently elevated, although those in lSSc patients were temporarily elevated at the early phase of the disease process. CONCLUSION: Patients with SSc exhibited elevated sCD40L levels that may correlate with disease activity. These results suggest that CD40/CD40L interactions may be potential therapeutic targets in SSc.