中国云南基层医院远程卒中的有效性和安全性研究

目的远程卒中指导基层医院脑梗死静脉溶栓国外已经很成熟,但国内鲜有报道。该研究以上海九院中心与祥云中心建立7×24小时远程卒中合作,由九院中心指导祥云中心进行脑梗死静脉溶栓。方法利用远程卒中前瞻性收集1年内九院中心与祥云中心急性脑梗死病例,统计其静脉溶栓质控和随访情况,对比两中心静脉溶栓率、3小时静脉溶栓率、就诊到静脉溶栓时间(DTN)、发病到静脉溶栓时间(OTT)、3个月随访改良生活能力评分(mRS)及出血、死亡率。结果远程卒中后1年九院中心静脉溶栓率27. 04%,祥云中心静脉溶栓率7. 73%,差异有统计学意义(P=0. 000)。九院中心DTN为(62. 76±26. 41) min,祥云中心DTN为(70. 55±28. 51) min,差异无统计学意义(P 0. 05)。3个月随访两中心mRS评分、出血和死亡率,差异均无统计学意义(P 0. 05)。结论远程卒中指导下祥云中心静脉溶栓预后及安全性不差于九院中心,远程卒中是改善农村基层医院静脉溶栓的有效方法之一。     

In Vitro Examination of the Thrombolytic Efficacy of Desmoteplase and Therapeutic Ultrasound Compared with rt-PA

The aim of the study described here was to evaluate the thrombolytic efficacy of combined treatment with the fibrin-selective plasminogen activator desmoteplase (DSPA) and therapeutic ultrasound (sonothrombolysis [STL]) compared with conventional rt-PA (recombinant tissue plasminogen activator) treatment in vitro. Lysis rates were determined by the weight loss of platelet-rich plasma (PRP) clots treated with rt-PA (60 kU/mL) or DSPA (2 μg/mL) combined with pulsed wave ultrasound (2 MHz, 0.179 W/cm²). To reveal the individual effects of medication and ultrasound, lysis rates were also determined for DSPA monotherapy and for combined treatment with rt-PA and ultrasound. Clots solely placed in plasma served as the control group. Lysis increased significantly with rt-PA (26.5 ± 7.8%) and DSPA (30.5 ± 6%) compared with the control group (18.2 ± 5.9%) (each p < 0.001). DSPA lysis was more effective than rt-PA lysis (without STL: p = 0.015, with STL: p = 0.01). Combined treatment with DSPA and 2-MHz STL significantly exceeded rt-PA lysis (32.8% vs. 26.5%, p < 0.001).     

Reduction of intracerebral hemorrhage by rivaroxaban after tPA thrombolysis is associated with downregulation of PAR‐1 and PAR‐2

This study aimed to assess the risk of intracerebral hemorrhage (ICH) after tissue‐type plasminogen activator (tPA) treatment in rivaroxaban compared with warfarin‐pretreated male Wistar rat brain after ischemia in relation to activation profiles of protease‐activated receptor‐1, ‐2, ‐3, and ‐4 (PAR‐1, ‐2, ‐3, and ‐4). After pretreatment with warfarin (0.2 mg/kg/day), low‐dose rivaroxaban (60 mg/kg/day), high‐dose rivaroxaban (120 mg/kg/day), or vehicle for 14 days, transient middle cerebral artery occlusion was induced for 90 min, followed by reperfusion with tPA (10 mg/kg/10 ml). Infarct volume, hemorrhagic volume, immunoglobulin G leakage, and blood parameters were examined. Twenty‐four hours after reperfusion, immunohistochemistry for PARs was performed in brain sections. ICH volume was increased in the warfarin‐pretreated group compared with the rivaroxaban‐treated group. PAR‐1, ‐2, ‐3, and ‐4 were widely expressed in the normal brain, and their levels were increased in the ischemic brain, especially in the peri‐ischemic lesion. Warfarin pretreatment enhanced the expression of PAR‐1 and PAR‐2 in the peri‐ischemic lesion, whereas rivaroxaban pretreatment did not. The present study shows a lower risk of brain hemorrhage in rivaroxaban‐pretreated compared with warfarin‐pretreated rats following tPA administration to the ischemic brain. It is suggested that the relative downregulation of PAR‐1 and PAR‐2 by rivaroxaban compared with warfarin pretreatment might be partly involved in the mechanism of reduced hemorrhagic complications in patients receiving rivaroxaban in clinical trials. © 2016 Wiley Periodicals, Inc.     

Plasminogen activator inhibitor-1 is an aggregate response factor with pleiotropic effects on cell signaling in vascular disease and the tumor microenvironment

In hemostasis, the serine protease inhibitor (serpin) plasminogen activator inhibitor-1 (PAI-1) functions to stabilize clots via inhibition of tissue plasminogen activator (tPA) with subsequent inhibition of fibrinolysis. In tissues, PAI-1 functions to inhibit extracellular matrix degradation via inhibition of urokinase plasminogen activator (uPA). Elevated levels of PAI-1 in the vasculature and in tissues have long been known to be associated with thrombosis and fibrosis, respectively. However, there is emerging evidence that PAI-1 may participate in the pathophysiology of a number of diseases such as atherosclerosis, restenosis, and cancer. In many of these disease states, the canonical view of PAI-1 as an inhibitor of tPA and uPA cannot fully account for a mechanism whereby PAI-1 contributes to the disease. In these cases, one must consider recent data, which indicates PAI-1 can directly promote pro-proliferative and anti-apoptotic signaling in a variety of cell types. Given the wide variety of inflammatory, hormonal, and metabolic signals that increase PAI-1 expression, it is important to consider mechanisms by which PAI-1 can directly participate in disease etiology.     

Expression of urokinase-type plasminogen activator in the mucosal lesions of inflammatory bowel disease

The expression of plasminogen activators was analysed in mucosal homogenates from inflammatory bowel disease patients to determine whether the urokinase-type (u-PA) is implicated in the pathogenesis of mucosal tissue injury. Homogenates of mucosal biopsy tissue from ulcerative colitis, Crohn's disease, infectious colitis and normal control patients were subjected to polyacrylamide gel electrophoresis. The types of plasminogen activator present were detected by zones of lysis in a fibrin-agarose gel overlay. All the tissues studied displayed tissue plasminogen activator activity (t-PA). In ulcerative colitis, 18 of the 19 diseased colon biopsies, but none of six biopsies from uninvolved areas of the same colon, showed u-PA activity. Similar results were found in 12 Crohn's disease patients. Biopsies from the infectious colitis group and from radiation colitis patients also showed both u-PA and t-PA activity. The age, sex, duration of disease, and presence and type of treatment did not affect u-PA expression in the inflamed mucosa. The results suggest that u-PA may be implicated in the mediation of tissue injury in the inflamed intestinal mucosa.     

氯吡格雷联合溶栓治疗急性心肌梗死的疗效评价

目的探讨和研究氯吡格雷联合溶栓治疗急性心肌梗死的临床疗效。方法选取2012年1月—2013年5月之间该院收治的50例急性心肌梗死患者作为研究对象,根据入院编号进行随机分组,分为观察组和对照组,各25例,对照组单纯采用重组人组织型纤溶酶原激酶衍生物进行溶栓治疗,观察组患者则在溶栓治疗基础上加用氯吡格雷联合治疗,对比两组患者的疗效及心肌酶谱变化。结果观察组患者总有效率92.0%,显著高于对照组患者的76.0%,差异有统计学意义(P<0.05);治疗前两组患者的肌酸激酶、肌酸激酶同工酶对比差异无统计学意义,治疗后观察组显著低于对照组,差异有统计学意义(P<0.05)。结论氯吡格雷联合溶栓治疗急性心肌梗死的疗效确切,相较于单纯溶栓治疗更具优势,能够有效降低心肌酶水平,提高疗效,值得在临床上推广和应用。