急性冠脉综合征患者血小板-单核细胞聚集与相关细胞因子的关系

目的研究血小板单核细胞聚集(PMAs)及其相关细胞因子表达与急性冠脉综合征的关系。方法采用流式细胞术同时测定74例急性冠脉综合征(ACS)患者、58例稳定性心绞痛(SAP)患者和46例冠造阴性患者血浆中IL6、IL8、MCP1、sCD40L、sP选择素水平和全血中血小板单核细胞聚集率(PMAs)。结果ACS患者各细胞因子和PMAs水平均显著高于SAP和冠造阴性患者(P<0.01);而IL8、sCD40L、sP选择素和CRP在SAP患者与冠造阴性患者间差异无显著性(P>0.05)。相关性分析显示,各细胞因子及CRP与PMAs均有良好的正相关性(P<0.01),其中IL6和sP选择素与PMAs相关性最高,相关系数r分别为0.484和0.481(P均小于0.001)。Logistic回归分析显示,IL6和PMAs对于ACS的OR值分别为1.024(95%CI1.010～1.039)和1.326(95%CI1.125～1.564)。结论血小板-单核细胞聚集形成、血小板的活化及其相关细胞因子的表达在急性冠脉综征发生和发展过程中起着重要的作用,检测PMAs和IL6水平可以反映冠心病患者冠脉内斑块的稳定性状态。     

血小板和单核细胞活化与急性冠脉综合征发生的关系

目的 研究血小板和单核细胞活化相关细胞因子表达与急性冠脉综合征(ACS)的关系.方法 用流式细胞术同时测定74例ACS、58例稳定性心绞痛(SAP)和46例冠脉造影阴性患者血浆中IL-6、IL-8、MCP-1、sCD40L、sP-选择素和可溶性血管细胞黏附分子(s-VCAM)水平.结果 ACS患者各细胞因子水平均显著高于SAP和冠脉造影阴性患者(P＜0.01);Logistic回归分析显示,CRP、IL-6和sCD40L对于ACS的相对危险度(OR)值和95%可信限(95%CI)分别为2.211(1.294～3.778)、1.015(1.003～1.027)和1.000(1.000～1.000).结论 ACS的发生与血小板的活化及相关的细胞因子表达上调有关,检测CRP、IL-6和sCD40L水平可以反映冠心病患者的疾病稳定性.     

单核细胞趋化蛋白-1在急性冠脉综合征中变化的研究

目的 探讨急性冠脉综合征（ACS）患者单核细胞趋化蛋白-1的变化及其临床意义。方法 136例患者被分为四组，稳定型心绞痛组24例，不稳定型心绞痛组28例，急性心肌梗死组34例，对照组50例。用酶联免疫吸附双抗体夹心法（ELISA）测定各组血清单核细胞趋化蛋白-1水平。应用Beckman全自动生化仪检测各组血清肌酸磷酸激酶及其亚型MB水平。结果 稳定型心绞痛组与对照组比较，单核细胞趋化蛋白-1、血清高敏C-反应蛋白、肌酸磷酸激酶及其亚型MB均无明显差异（P〉0．05）；不稳定型心绞痛组与对照组、稳定型心绞痛组比较，不稳定型心绞痛组血清单核细胞趋化蛋白-1、高敏C-反应蛋白均显著增高（P〈0．05），血清肌酸磷酸激酶及其亚型MB均无明显差异（P〉0．05）；急性心肌梗死组与对照组、稳定型心绞痛组和不稳定型心绞痛组比较，急性心肌梗死组血清高敏C-反应蛋白、单核细胞趋化蛋白-1、肌酸磷酸激酶及其亚MB均明显增高（P〈0．05）。血清单核细胞趋化蛋白-1、高敏C-反应蛋白水平两者之间呈正相关（r=0．78P〈0．05）。结论 ACS患者血清单核细胞趋化蛋白-1水平明显增高，其增高程度与疾病严重程度（心肌损害）呈正相关，与肌酸磷酸激酶及其亚型MB比较，单核细胞趋化蛋白-1在急性冠脉综合征发病与诊断中有重要意义，可作为ACS发病和预后的预测因子。炎症反应在冠状动脉粥样硬化斑块不稳定性中发挥了重要作用。炎症反应与ACS发病及病情进展关系密切。     

急性冠脉综合征患者血小板和白细胞异常表达组织因子的研究

本研究观察急性冠脉综合征（ACS）患者,稳定性心绞痛（SA）患者及健康对照循环中血小板、血小板白细胞聚集体（PLA）和血小板单核细胞聚集体（PMP）组织因子（TF）的表达情况,并探讨其在ACS发病机制中的作用。收集26例ACS患者,29例SA患者及25名正常人（作为对照组）,外周血标本,分离获得单核细胞及富含血小板血浆,用RT-PCR法分别检测组间单核细胞及血小板TF-mRNA的表达,通过流式细胞仪检测组间血小板、PLA和PMP表达TF的比例。结果表明,ACS组、SA组、正常对照组血小板TF mRNA平均表达水平分别为3.11±0.51、1.88±0.78和0.7±0.10,ACS组单核细胞、血小板TF mRNA表达水平与正常对照组有差异（分别为P=0.03,P=0.05）。ACS组患者血小板表达TF比例明显高于SA组及正常对照组（P=0.02）,3组的TF阳性的PLA百分比（%UR）分别为2.7±0.6、0.8±0.2及0.5±0.1（P=0.001）。ACS组TF阳性的血小板单核细胞百分比（%UR）为2.5±0.6,显著高于SA组的1.2±0.3（P=0.02）及对照组的0.8±0.2（P=0.04）。结论：ACS患者血小板及白细胞高表达TF,促进了血小板的活化、凝血和血栓形成,进一步促进高凝状态。TF促血栓形成和促局部炎症作用,协同血小板和白细胞共同参与ACS的发病,最终与ACS疾病发生发展密切相关。     

单核细胞趋化蛋白-1基因A-2518G多态性与急性冠脉综合征相关性研究

目的 探讨中国苏南地区汉族人群单核细胞趋化蛋白-1(MCP-1)基因启动子区A-2518G单核苷酸多态性与ACS发病的相关性.方法 采用病例-对照研究方法,选择临床确诊的ACS 484例(ACS组),其中急性心肌梗死(AMI) 290例,不稳定性心绞痛(UAP) 194例.经冠脉造影排除冠心病者346例为对照组,包括冠脉硬化症(CAS组)166例和冠脉无狭窄(冠脉正常组)180例.利用聚合酶链式反应-限制性酶切片段长度多态性技术(PCR-RFLP)检测MCP-1基因A-2518G多态性.结果 MCP-1基因A-2518G单核苷酸多态性在ACS组和对照组中均存在AA、AG和GG三种基因型.二组基因型分布符合Hardy- Weinberg平衡(P＞0.05),具有群体代表性.与对照组相比,ACS组中AA (15.32％vs.16.12％)、AG (53.47％ vs.51.86％)和GG(31.21％vs.32.02％)基因型和G(57.95％ vs.57.95％)等位基因频率差异均无统计学意义(P值分别为0.083、0.673、0.821和1.000).对性别、年龄、吸烟、糖尿病、TC和LDL等6个相关因素行Logistic回归分析显示,MCP-1基因A-2518G单核苷酸多态性与ACS的发病无相关性(P＞0.05).对男性ACS、女性ACS、AMI、UAP和早发ACS等5个亚组进行MCP-1基因A-2518G多态性分析,结果显示,男性和女性ACS分别与对照组相比、AMI和UAP分别与冠脉正常组相比以及早发ACS与年龄相匹配的对照组相比,AA、AG和GG基因型和G等位基因频率差异均无统计学意义(均P＞0.05).结论 在中国苏南地区汉族人群中,MCP-1基因存在A-2518G单核苷酸多态性,该多态性与ACS发病无显著相关性.     

血小板平均容积与急性冠脉综合征相关的分析

目的探讨血小板平均容积在急性冠脉综合征中的临床意义。方法测定经冠脉造影及临床资料确诊的256例ACS患者和200例健康体检者的MPV、血小板分布宽度、血小板压积,结合临床资料,比较两组数据的差异。结果ACS组MPV与对照组比较,差异有统计学意义(P<0.01)。UAP组、NSTEMI组及STEMI组MPV与对照组相比较,差异亦有统计学意义(P<0.05)。结论 ACS患者MPV明显增高,其与ACS的发生存在密切关系。临床中可通过检测MPV,及时调整抗血小板的强度,改善患者预后和预防急性心肌梗死的发生、发展。     

C-反应蛋白和急性冠脉综合征

急性冠状动脉综合征 (ACS)危害甚大。冠脉斑块破裂及随之发生的血小板聚集和血栓形成是动脉粥样硬化导致ACS的最重要的机制。如何早期预测斑块破裂是多年来悬而未解的问题 ,病理和临床大量研究显示 ,炎症与ACS密切相关 ,故有人提出冠心病 (尤其ACS)是一种炎症过程。认为炎性因子C -反应蛋白 (CRP) [1] 、白细胞介素 - 6 (IL - 6 )等为ACS的危险因子。1　CRP增高的临床意义CRP在正常情况下以微量形式 (正常值在 10mg/L以下 ,平均值约为 3 5mg/L)存在于健康人血清中 ,当机体有急性炎症、创伤和冠心病时此蛋白会明显升高。CRP浓度…     

关于急性冠脉综合征患者氯吡格雷抵抗的研究

目的评价高负荷剂量氯吡格雷对急性冠状动脉综合征（ACS）患者氯吡格雷抵抗产生的影响。方法所有入选患者随机分为氯吡格雷高负荷剂量（600mg）组和氯吡格雷常规负荷剂量（300mg）组,两组维持剂量均为75mg／d。与服氯吡格雷前、服药后24小时分别测定二磷酸腺苷（ADP）诱导的血小板聚集率,计算血小板聚集抑制率（△A）。△A≤10％（包括负值）时考虑存在氯吡格雷抵抗。结果高剂量组83例,其中△A≤10％（包括负值）者22例（26．5％）。常规剂量组85例ACS,其中△A≤10％（包括负值）者35例（41．2％）,两组相比差异显著（P〈0．05）;对氯吡格雷有效的患者,高负荷剂量组服药后血小板聚集率和血小板抑制率与常规剂量组相比差异显著（P〈0．001）;对氯吡格雷抵抗的患者,高负荷剂量组服药后血小板聚集率和血小板抑制率与常规负荷剂量组相比无显著差异（P〉0．05）。结论高负荷剂量氯吡格雷可以降低ACS患者氯吡格雷抵抗的发生,对氯吡格雷有效的患者可以提高血小板抑制率。     

流式细胞术检测血小板-单核细胞聚集的影响因素

目的探讨流式细胞术检测全血血小板单核细胞聚集(PMAs)的影响因素。方法分别采用枸橼酸钠和K2EDTA作为抗凝剂,多聚甲醛为固定剂,静脉采集9名志愿者全血,室温和4℃条件下放置不同时间。采用抗CD14PE单克隆抗体标记单核细胞,抗FITCCD42a单克隆抗体标记血小板,流式细胞仪测定各研究条件下PMAs占各自单核细胞总数的百分比。结果在室温和4℃条件下,6h内5mmol/LK2EDTA和0.5%的多聚甲醛不会增加体外PMAs的形成,但它们均能使已形成的PMAs减少。枸橼酸钠抗凝条件下,体外PMAs的形成随时间延长而显著增加,抽血后室温放置30min和抽血后即刻(10min)PMAs测定值之差<3%,分别为6.53%±1.75%和8.80%±2.33%(P<0.05)。结论体外全血PMAs测定易受多种因素影响,抗凝剂枸橼酸钠不影响PMAs的形成及其稳定性,采用枸橼酸钠抗凝需在抽血后短时间内(<30min)测定PMAs。     

血小板与单核细胞聚合物在2型糖尿病患者血管并发症诊断中的意义

目的探讨血小板与单核细胞聚合物（platelet—monocyte aggregates,PMA）在2型糖尿病（type 2 diabetes mellitus,T2DM）患者血管病变诊断中的意义。方法应用荧光标记单抗流式细胞术对94例T2DM患者（按有无血管并发症分为有血管并发症组64例和无血管并发症组30例）和42例健康刘照者血清中PMA表达率及实验室常规检测指标进行分析。结果T2DM患者组血清中的PMA表达率明显高于健康对照组,且差异有统计学意义（P〈0．01）。有血管病发症组患者血清中的PMA表达率高于无血管病发症组,且两组间差异亦有统计学意义（P=0．015）;糖尿病患者血管病变损伤区域数量≥2时,其PMA表达率明显高于无血管病变患者组,且差异均有统计学意义（P均〈0．05）。PMA表达率与RBC、WBC、HGB、高密度脂蛋白胆固醇等均有一定相关性（P均〈0．05）。受试者工作特征曲线显示PMA表达率为24．72％时,对T2DM血管并发症诊断的灵敏度为71．9％,特异性为73．8％,曲线下面积为0．754。结论T2DM患者血清中的PMA表达率明昆升高,日升高的程度与糖尿病血管病变数量有关。     

Tissue factor and IL8 production by P-selectin-dependent platelet–monocyte aggregates in whole blood involves phosphorylation of Lyn and is inhibited by IL10

Summary. Background: P‐selectin and CD40L expressed by activated platelets induce tissue factor (TF) and inflammatory cytokines in monocytes, but little is known of the cellular signaling pathways involved. The anti‐inflammatory cytokine IL10 reduces atherosclerotic plaque formation. Objectives: To evaluate the importance of P‐selectin upon platelet–monocyte aggregate (PMA) formation in thrombin receptor activator peptide (TRAP) stimulated whole blood, the P‐selectin–P‐selectin glycoprotein ligand (PSGL)‐1‐induced cellular signaling pathway, and the effects of IL10 on these functions. Methods: TF, IL8, and monocyte chemotactic protein‐1 (MCP‐1) production, PMAs and phosphorylation of Lyn were analyzed in whole blood, purified monocytes, and vitamin D₃‐differentiated U‐937 cells stimulated with TRAP or P‐selectin with or without IL10. Anti‐P‐selectin or anti‐CD40L antibodies (Abs), Src‐kinases inhibitors, SU6656 or PP2, were added in some experiments. Results: TRAP and P‐selectin increased TF, IL8, and MCP‐1 mRNA in whole blood and purified monocytes. Anti‐P‐selectin Ab reduced TRAP‐induced PMA formation by 80 ± 2% (P = 0.001) and production of TF (P = 0.04) and IL8 (P = 0.01). IL10 and SU6656 had no effect on PMA formation, although both significantly reduced TF (P = 0.002 and P = 0.02) and IL8 (P = 0.009 and P = 0.001) mRNA upon TRAP and P‐selectin stimulation. Induced Lyn phosphorylation in monocytes was diminished by SU6656 (P = 0.02), anti‐P‐selectin Ab (P = 0.02), and IL10 (P = 0.03) upon TRAP or P‐selectin stimulation. These results were confirmed in the vitamin D₃‐differentiated U‐937 cells. Conclusions: The formation of PMAs in whole blood was P‐selectin‐dependent in the long term. P‐selectin–PSGL‐1‐induced TF and IL8 expression through Lyn phosphorylation, and part of the inhibitory effect of IL10 depends on reduced phosphorylation.     

Slow-onset and Fast-onset Symptom Presentations In Acute Coronary Syndrome (ACS): New Perspectives on Prehospital Delay in Patients with ACS

Background

Patient decision delay is the main reason why many patients fail to receive timely medical intervention for symptoms of acute coronary syndrome (ACS).

Study Objectives

This study examines the validity of slow-onset and fast-onset ACS presentations and their influence on ACS prehospital delay times. A fast-onset ACS presentation is characterized by sudden, continuous, and severe chest pain, and slow-onset ACS pertains to all other ACS presentations.

Methods

Baseline data pertaining to medical profiles, prehospital delay times, and ACS symptoms were recorded for all ACS patients who participated in a large multisite randomized control trial (RCT) in Dublin, Ireland. Patients were interviewed 2–4 days after their ACS event, and data were gathered using the ACS Response to Symptom Index.

Results

Only baseline data from the RCT, N = 893 patients, were analyzed. A total of 65% (n = 577) of patients experienced slow-onset ACS presentation, whereas 35% (n = 316) experienced fast-onset ACS. Patients who experienced slow-onset ACS were significantly more likely to have longer prehospital delays than patients with fast-onset ACS (3.5 h vs. 2.0 h, respectively, t = −5.63, df 890, p < 0.001). A multivariate analysis of delay revealed that, in the presence of other known delay factors, the only independent predictors of delay were slow-onset and fast-onset ACS (β = −.096, p < 0.002) and other factors associated with patient behavior.

Conclusion

Slow-onset ACS and fast-onset ACS presentations are associated with distinct behavioral patterns that significantly influence prehospital time frames. As such, slow-onset ACS and fast-onset ACS are legitimate ACS presentation phenomena that should be seriously considered when examining the factors associated with prehospital delay.     

Serum levels of leptin and proinflammatory cytokines in patients with gastrointestinal cancer

The aim was to investigate the serum levels of leptin, TNF-alpha, IL-1 beta, IL-6, insulin, and growth hormone in patients with upper gastrointestinal cancer and cachexia. A total of 39 patients with various advanced stage (stage IV) gastrointestinal malignancies were enrolled. These cancer patients were divided into two groups according to the presence or absence of cachexia. Fifteen healthy adults were recruited as the control group. Body mass index (BMI; kg/m2) was calculated. Serum leptin, tumour necrosis factor (TNF)-alpha interleukin (IL)-1 beta, interleukin (IL)-6, growth hormone, insulin, glucose, triglyceride, total protein, albumin, erythrocyte sedimentation rate, and CRP were measured. In both cancer groups (cachectic and non-cachectic) body mass index and serum leptin levels were lower than controls (p < 0.001). Serum IL-1 beta, IL-6, and growth hormone levels were higher in both cachectic and non-cachectic groups than those of controls (p < 0.05). Serum TNF-alpha level in non-cachectic group was also significantly higher than in control group (p < 0.01). There is no significant difference between three groups in terms of insulin resistance as assessed by HOMA index. Our results showed that some proinflammatory cytokine levels were increased and leptin level was decreased due to upper gastrointestinal cancers. Increased cytokine levels may lead to decreased food intake and caused a weight loss.     

Measurement and clinical significance of circulating PAPP-A in ACS patients

BACKGROUND: The rupture of coronary atherosclerotic plaque and subsequent thrombus formation are major events underlying acute coronary syndromes (ACS). Pregnancy associated plasma protein A (PAPP-A), a biomarker of plaque rupture, has been studied in patients with ACS. This review aimed to provide an overview of clinical utility of PAPP-A in ACS patients and analytical issues adhering to immunological PAPP-A measurement. METHODS: The literature relating to PAPP-A in ACS, the molecular structure and immunodetection of PAPP-A was reviewed. PubMed was used to search the relevant articles published from 1974 to 2006. RESULTS: Higher PAPP-A concentrations have been found in patients with ACS than in patients with stable angina and subjects without coronary artery disease. Elevated PAPP-A concentrations have also been shown to associate with adverse cardiac events in ACS patients. The prognostic value of PAPP-A appears to be independent of cardiac troponins. Noteworthy, the PAPP-A form that accounts for increase in ACS is uncomplexed with the proform of eosinophil major basic protein (proMBP). However, PAPP-A assays applied in clinical studies published thus far detect total PAPP-A. Consequently, the clinical value may be non-optimal when total PAPP-A is measured in ACS patients. In addition, the clinical value can also be affected by the analytical factors that exert an effect on the performance of PAPP-A assays. CONCLUSIONS: PAPP-A appears to be a very promising biomarker useful in the clinical management of ACS patients. However, more prospective and interventional studies with carefully established immunoassays are required to validate its clinical utility.     

不同程度手足口病患儿血清细胞因子及免疫球蛋白水平变化探讨

目的探讨不同程度手足口病患儿血清细胞因子及免疫球蛋白水平的变化。方法将2015年6月至2016年6月该院收治的手足口病患儿84例纳入该研究,据临床病情程度将上述患儿分为普通组46例和重症组38例。另选取同期于该院体检的健康幼儿35例作为对照组,检测并比较各组血清细胞因子的水平,主要包括白细胞介素(IL)-6、IL-10、肿瘤坏死因子-α(TNF-α)以及免疫球蛋白(IgA、IgG、IgM)。结果重症组的IL-6、IL-10、TNF-α水平分别为(61.81±20.17)ng/L、(174.25±60.41)ng/L、(469.33±168.23)ng/L,均高于普通组和对照组(P0.05);普通组的IL-6、IL-10、TNF-α水平分别为(15.75±3.41)ng/L、(33.80±12.11)ng/L、(78.22±58.57)ng/L,高于对照组,但差异无统计学意义(P0.05);重症组的IgA、IgG、IgM水平分别为(0.82±0.26)g/L、(6.87±1.38)g/L、(0.76±0.15)g/L,普通组的IgA、IgG、IgM水平分别为(1.10±0.29)g/L、(8.26±1.05)g/L、(1.12±0.22)g/L,重症组与普通组的免疫球蛋白水平均低于对照组(P0.05),重症组的免疫球蛋白水平均低于普通组,差异有统计学意义(P0.05)。结论手足口病患儿存在细胞因子失衡及免疫功能降低且以重症患儿最为明显,采用细胞因子及体液免疫检测有助于临床判断病情。     

H-FABP、NT-proBNP、CRP、cTnT在ACS患者预后中的评估价值

目的探讨分析H-FABP、NT-proBNP、CRP、cTnT在ACS患者预后中的评估价值。方法 96例ACS患者根据随访1年内患者是否发生不良心血管事件将所有患者分为预后不良组（35例）与对照组（61例）。于患者入院后检测H-FABP、NT-proBNP、CRP、cTnT四项指标的水平,并于出院后进行为期1年的随访,绘制受试者工作特性曲线来测定上述四项指标对ACS患者预后评估的准确性,并找出出院后发生不良心血管事件的危险因素。结果入院时预后不良组H-FABP、NT-proBNP、CRP、cTnT水平均明显高于对照组（P〈0.05）;H-FABP、NT-proBNP、CRP、cTnT检测对预测心血管不良事件的ROC曲线下面积与临界值分别为0.811、40.95μg/L,0.749、1342.98ng/L,0.788、9.69mg/L,0.812、0.78μg/L;COX单因素回归分析显示H-FABP、NT-proBNP、CRP及cTnT水平的升高是ACS患者发生心血管不良事件的危险因素（P〈0.05）。结论 H-FABP、NT-proBNP、CRP、cTnT对ACS患者的预后有着较高的评估价值,值得推广。