精神药物的暴露与静脉血栓栓塞症发生风险的研究进展

<正>静脉血栓栓塞症(venous thromboembolism, VTE)包括肺血栓栓塞症(pulmonary thromboembolism, PTE)与深静脉血栓形成(deep venous thrombosis, DVT),是一种常见的疾病，具有显著的发病率和死亡率。越来越多的研究表明VTE与精神药物的使用之间存在联系。一项关于精神病院中VTE发生率的研究显示：精神病院环境中VTE的发病率很高，尤其是在患者入院的最初几天，     

老年人肺栓塞的特点和肺血栓栓塞症诊断策略

一、老年人肺栓塞的特点 肺血栓栓塞症 (pulmonary thromboembolism,PTE)和深静脉血栓形成(deep venous thrombosis,DVT)均属于静脉血栓栓塞症(venous thromboembolism,VTE).在西方国家,总人群PTE的年发病率为0.5%;在美国,每年有200万VTE患者,因DVT和PTE住院患者超过25万,并居于所有死因的第3位,仅次于肿瘤和心肌梗死.PTE是DVT的最严重的并发症,3个月病死率为17%.     

老年人静脉血栓栓塞症的流行病学

<正>静脉血栓栓塞症(venous thromboembolism,VTE)包括肺血栓栓塞症(pulmonary thromboembolism,PTE)和深静脉血栓形成(deep venous thrombosis,DVT)2大类,是同一种疾病在不同部位的2种表现形式。随着病理生理研究的深入和诊断策略的改进,以往对于VTE尤其是PTE"少发病、罕见病"的认识得到了根本的转变,VTE的发病率     

肺血栓栓塞症—深静脉血栓形成的分子流行病学

肺血栓栓塞症(pulmonary thromboembolism，PTE)与深静脉血栓形成(deep venous thrombosis，DVT)共属于静脉血栓栓塞症(venous thromboembolism，VTE)。已公认VTE是一种多基因疾病，抗凝、凝血、纤溶系统以及某些酶类相关基因的异常均可成为其遗传性危险因素(表1)。     

新型口服抗凝药物在肿瘤相关血栓疾病中的应用

正恶性肿瘤与静脉血栓栓塞(venous thromboembolism,VTE)密切相关,VTE包括深静脉血栓形成(deep venous thrombosis,DVT)和肺血栓栓塞症(pulmonary thromboembolism,PTE)。肿瘤病人发生VTE的风险比年龄和性别匹配的对照组高出4～6倍[1],有报道表明高达20%的恶性肿瘤病人发生过VTE[2]。肿瘤分型、肿瘤分期和抗肿瘤药物的使用均与VTE发生相关。肿瘤病人常同时合并数个发生VTE的危险因素,包括手术、住院、中心静脉留置导     

亚甲基四氢叶酸还原酶基因多态性在静脉血栓栓塞症中的研究进展

<正>静脉血栓栓塞症(venous thromboembolism,VTE)包括深静脉血栓(deep vein thrombus,DVT)和肺血栓栓塞症(pulmonary thromboembolism,PTE),是同一种疾病、两个不同阶段的不同临床表现~([1])。VTE在老年人中每年的发病率为1/1 000~([2-3]),病死率高居全球第三,仅次于卒中和缺血性心脏病~([2]),严重危害人类健康。VTE形成涉及多阶段、多基因和基因—环境相互作用~([4]),     

急性脑卒中患者静脉血栓栓塞症调查及危险因素探讨

<正>静脉血栓栓塞症(venous thromboembolism,VTE)包括深静脉血栓形成(deep venous thrombosis,DVT)和肺血栓栓塞症(pulmonary thromboembolism,PTE)。脑卒中患者是VTE发生的高危人群,如果不给予任何干预措施,30%~40%的脑卒中患者会发生DVT,严重     

老年慢性冠状动脉综合征合并静脉血栓栓塞症患者抗栓治疗进展

正老年冠心病合并静脉血栓栓塞症(venous thromboembolism, VTE)的临床发生率逐年增加。虽然,血栓形成导致血管阻塞是其共性病理改变,但是,发生在冠状动脉与静脉部位的不同、血栓机制不同,导致抗栓治疗的药物选择与方法不同,联合抗凝及抗血小板治疗增加出血风险。近年来研究表明,随着新型抗凝药物的广泛应用,冠心病合并VTE患者的综合抗栓治疗研究取得一些临床证据。为此,本研究就不同临床类型冠心病合并VTE患者抗栓治疗研究进展进行     

红细胞与静脉血栓栓塞症研究进展

<正>静脉血栓栓塞症(venous thromboembolism, VTE)包括深静脉血栓形成和肺栓塞，是严重威胁人类生命健康的疾病。有报道显示，全球每年约有1000万人罹患VTE,其中肺栓塞患者1年死亡率高达25%,30%的深静脉血栓形成患者会出现中至重度血栓后综合征，严重影响生活质量^[1]。VTE是遗传性和获得性危险因素共同作用的全身性疾病，其发病机制十分复杂，经典的理论包括静脉内皮损伤、血流减慢和凝血激活三大要素。     

心肌肌钙蛋白与急性肺栓塞的研究情况

<正>肺栓塞(pulmonary embolism, PE)是以各种栓子阻塞肺动脉或其分支为其发病原因的一组疾病或临床综合征的总称，肺血栓栓塞症(pulmonary thromboembolism, PTE)是其最常见的类型，与深静脉血栓形成是静脉血栓栓塞症(venous thromboembolism, VTE)在不同部位、不同阶段的两种临床表现形式^[1]。     

Regulation of P-selectin binding to the neutrophil P-selectin counter-receptor P-selectin glycoprotein ligand-1 by neutrophil elastase and cathepsin G

In the inflammatory response, leukocyte rolling before adhesion and transmigration through the blood vessel wall is mediated by specific cell surface adhesion receptors. Neutrophil rolling involves the interaction of P-selectin expressed on activated endothelium and its counter-receptor on neutrophils, P-selectin glycoprotein ligand-1 (PSGL-1). Here, it is reported that P-selectin binding to neutrophils is lost under conditions that cause the release of proteinases from neutrophil primary granules. Treatment of neutrophils with the purified neutrophil granule proteinases, cathepsin G and elastase, rapidly abolished their capacity to bind P-selectin. This inactivation corresponded to loss of the N-terminal domain of PSGL-1, as assessed by Western blot analysis. A loss of intact PSGL-1 protein from the surfaces of neutrophils after the induction of degranulation was also detected by Western blot analysis. Cathepsin G initially cleaved near the PSGL-1 N-terminus, whereas neutrophil elastase predominantly cleaved at a more C-terminal site within the protein mucin core. Consistent with this, cathepsin G cleaved a synthetic peptide based on the PSGL-1 N-terminus between Tyr-7/Leu-8. Under conditions producing neutrophil degranulation in incubations containing mixtures of platelets and neutrophils, the loss of PSGL-1, but not P-selectin, from platelet-neutrophil lysates was detected. Cathepsin G- or neutrophil elastase-mediated PSGL-1 proteolysis may constitute a potential autocrine mechanism for down-regulation of neutrophil adhesion to P-selectin.     

P-选择素与肿瘤转移

肿瘤转移是复杂多步骤的肿瘤细胞与宿主相互作用的连续过程 ,包括肿瘤细胞侵袭周围组织、从原发灶脱离进入循环系统、逃避免疫监视以及在远隔器官形成与原发瘤同样类型的转移灶。近年来许多学者发现细胞粘附分子在肿瘤转移中起重要作用。选择素 (ｓｅｌｅｃｔｉｎ)是细胞粘附分子中的一个家族 ,包括Ｌ 选择素、Ｐ 选择素和Ｅ 选择素。研究证明 ,Ｐ 选择素能介导肿瘤细胞与血小板及血管内皮细胞间的粘附 ,促进肿瘤细胞的血道转移和扩散[1] 。本文就Ｐ 选择素及其在肿瘤转移中的有关研究作一综述。一、Ｐ 选择素的分子生物学特点Ｐ 选择素亦称…     

P-selectin glycoprotein ligand-1 supports rolling on E- and P-selectin in vivo

Selectin-dependent rolling is the earliest observable event in the recruitment of leukocytes to inflamed tissues. Several glycoproteins decorated with sialic acid, fucose, and/or sulfate have been shown to bind the selectins. The best-characterized selectin ligand is P-selectin glycoprotein-1 (PSGL-1) that supports P-selectin- dependent rolling in vitro and in vivo. In vitro studies have suggested that PSGL-1 may also be a ligand for E- and L-selectins. To study the in vivo function of PSGL-1, without the influence of other leukocyte proteins, the authors observed the interaction of PSGL-1-coated microspheres in mouse venules stimulated to express P- and/or E-selectin. Microspheres coated with functional recombinant PSGL-1 rolled in surgically stimulated and tumor necrosis factor alpha (TNFalpha)-stimulated mouse venules. P-selectin deficiency or inhibition abolished microsphere rolling in surgically and TNFalpha-stimulated venules, whereas E-selectin deficiency or inhibition increased microsphere rolling velocity in TNFalpha-stimulated venules. The results suggest that P-selectin-PSGL-1 interaction alone is sufficient to mediate rolling in vivo and that E-selectin-PSGL-1 interaction supports slow rolling.     

P选择素与炎症性肠病

炎症性肠病(IBD)包括溃疡性结肠炎(UC)和克罗恩病(CD),目前认为血小板功能异常在其发病机制及发展过程中起着重要作用.P选择素是细胞黏附分子中选择素家族成员,介导血小板活化及炎症反应等.研究表明P选择素在炎症性肠病的病理过程中起重要作用.     

血小板膜及血清P选择素在急性冠脉综合征中的临床意义

目的 探讨血小板膜P选择素的表达率及血清P选择素的浓度在急性冠脉综合征(acute coronarysyndrome,ACS)中的临床意义.方法 采用间接免疫荧光流式细胞术和双抗夹心酶联免疫测定法分别检测30例ACS患者、20例稳定型心绞痛(stable angina,SA)患者和25例正常对照者(经冠状动脉造影检查提示冠状动脉正常)血小板膜P选择素表达率和血清P选择素浓度,并进行统计分析.结果 ACS组血小板膜P选择素表达率显著高于SA组[(17.19±8.05)%vs.(13.09±6.25)%,P<0.05],并显著高于对照组[(17.19±8.05)%vs.(10.83±5.76)%,P<0.05],SA组和对照组之间比较,差异无统计学意义(P>0.05).ACS组血清P-选择素的浓度显著高于SA组[(43.98±14.71)ng/ml vs.(36.14±13.42)ng/ml,P<0.05],并显著高于对照组[(43.98±14.71)ng/ml vs.(33.34±11.05)ng/ml,P<0.05],SA组和对照组比较,差异无统计学意义(P>0.05).冠状动脉性心脏病(冠心病)患者血小板膜P选择素表达率与血清P-选择素浓度呈正相关(r=0.295,P=0.017).结论 检测血清P选择素浓度对预测ACS发生、发展有重要的参考价值.     

P-selectin in haemostasis

During the past decade, interrelationships between inflammation and thrombosis have been the subject of extensive works, and it is now commonly recognized that inflammation (notably leucocyte recruitment) directly affects thrombosis, and that thrombosis also constitutes a pro-inflammatory event. This tight link is partly attributable to P-selectin, which is functional not only when expressed on the surface of activated platelets and endothelial cells, but also when shed, generating its soluble form, termed sP-selectin. In this review, we will provide an overview of the relative roles of the different compartments of P-selectin (platelet, endothelial cell, plasma) in haemostasis and vascular pathologies, and the potential therapeutic benefits achievable in targeting this molecule.     

P-选择素与缺血性脑血管病

P-选择素又称CD62,通过介导内皮细胞和血小板的活化以及动脉粥样硬化的形成和发展等过程,促进缺血性脑血管病的发生.多项研究证实,P-选择素在缺血性脑血管病危险因素,如高血压、糖尿病、高胆固醇血症、心脏病、吸烟、酗酒、高纤维蛋白原血症等的发生和发展中起重要作用.P-选择素能否作为独立危险因素预测缺血性脑血管病的发生,尚待进一步研究证实.     

Association between P-selectin gene polymorphisms and soluble P-selectin levels and their relation to coronary artery disease

P-selectin is a cellular adhesion molecule that mediates the interaction of activated endothelial cells or platelets with leukocytes. Increased levels of soluble P-selectin have been reported in various cardiovascular disorders. We measured serum soluble P-selectin levels as well as 3 polymorphisms of the P-selectin gene (C-2123G, A-1969G, and Thr715Pro) in a large cohort of patients with documented coronary artery disease (n=869) and a healthy control group (n=334). The 3 P-selectin polymorphisms were strongly associated with P-selectin levels and altogether explained 7.3% and 18.6% of the P-selectin variability in patients and controls, respectively. Genotype distributions did not significantly differ between patients and controls. P-selectin levels were increased in patients younger than 55 years of age compared with controls (135.2 vs 114.3 ng/mL, P<0.01). On the contrary, patients older than 65 years of age had significantly lower P-selectin levels than did controls (121.5 vs 134.7 ng/mL, P<0.02). In intermediate age groups, P-selectin levels did not significantly differ between the 2 groups. In conclusion, this study revealed a strong association between P-selectin gene polymorphisms and serum P-selectin levels and a complex age-dependent relation between soluble P-selectin levels and coronary artery disease, which suggests that this molecule might have different roles in the atherothrombotic process.