静脉血栓栓塞症组织因子途径抑制物C-399T多态性的研究

目的：分析静脉血栓栓塞症（VTE）患者组织因子途径抑制物（tissue factor pathway inhibitor,TFPI）基因C-399T多态性,探讨TFPI基因多态性与VTE的关系。方法：应用聚合酶链反应-限制性片段多态性（PCR—RFLP）的方法检测110例VTE患者（其中深静脉血栓患者75例,肺血栓栓塞症患者35例）,116例正常对照TF—PIC399T基因型频率和等位基因频率。结果：①VTE组和对照组TFPIC-399T基因型频数分布符合Hardy—Weinberg平衡;②VTE组患者TFPIC-399T具有纯合突变型（TT）基因型个体的频数（23．6％）高于正常对照组（12．1％）,差异有统计学意义（Χ^2=5．186,P〈0．05）;③杂合子突变型（CT）和正常纯合子（CC）2组与正常对照组比较均差异无统计学意义（均P〉0．05）。结论：TFPI基因C-399T多态性与VTE易感性有关,纯合突变基因型可能是VTE的重要危险因素。     

p73和p51基因在结直肠癌中的表达和意义

背景：p53基因是一种肿瘤抑制基因，其家族成员p73和p51在结构上与p53具有高度同源性，影响细胞转录和凋亡的功能与p53相似。目的：研究p73和p51基因在结直肠癌中的表达及其与细胞凋亡和肿瘤临床病理特征的关系，探讨两者在结直肠癌发生、发展中的可能作用。方法：以逆转录聚合酶链反应（RT—PCR）检测60例结直肠癌组织和相应癌旁组织中p73、p51mRNA表达，以原位末端标记（TUNEL）法检测细胞凋亡。结果：结直肠癌组织p73、p51AmRNA表达阳性率显著高于相应癌旁组织（p73：71．7％对5．0％，P〈0．01：p51A：46．7％对11．7％，P〈0．01）：p51B mRNA在结直肠癌组织与相应癌旁组织中的相对表达量无明显差异（0．7318±0．3628对0．6836±0．3516，P〉0．05）。p73、p51A mRNA表达阳性者肿瘤细胞凋亡指数分别显著低于p73、p51A mRNA表达阴性者（p73：3．2％±2．5％对5．5％±2．8％．P=0．003；p51A：2．6％±2．3％对4．9％±2．7％，P=0．001）。p73mRNA表达与结直肠癌的分化程度、TNM分期和淋巴结转移相关（P〈0．05），p51A mRNA表达仅与淋巴结转移相关（P〈0．05）。结论：结直肠癌中p73、p51A基因表达上调，两者可能通过抑制肿瘤细胞凋亡而参与了结直肠癌的发生、发展。p73过表达可能与结直肠癌预后不良有关。     

45例老年肺癌合并静脉血栓栓塞症患者的临床观察

目的分析老年肺癌合并静脉血栓栓塞症（VTE）患者的临床危险因素。方法选取我院收治的1026例经确诊的肺癌患者为研究对象,并分析以下相关因素：患者年龄、性别、病理类型、治疗前血小板计数、白细胞介素1（IL-1）、D-二聚体、肿瘤坏死因子（TNF）。结果上述肺癌患者中,45例（4.39%）患者并发静脉血栓栓塞。相关因素方面,血小板计数、IL-1、D-二聚体、TNF水平正常的患者VTE发生率分别为3.71%、0.32%、2.43%和3.26%,而上述水平升高的患者VTE发生率分别为6.27%、19.92%、10.31%和7.81%,差异明显（P〈0.05）。Logistic分析,IL-1、D-二聚体、TNF水平升高是肺癌患者并发静脉血栓栓塞症的临床危险因素（P〈0.05）。结论肺癌患者发生VTE的危险因素为IL-1、D-二聚体和TNF。     

游离脂肪酸对人脐静脉内皮细胞eNOSmRNA及ET-1mRNA表达水平的影响

目的研究游离脂肪酸（FFA）对离体培养人血管内皮细胞（HUVEC）eNOS mRNA和ET-1mRNA表达水平的影响。方法用不同的FFA培养HUVEC，分为C16：0、C18：0、C18：1、C18：2、C24：0及对照组，每组选用4个浓度，孵育24h，用RT—PCR方法，半定量测定eNOS mRNA和ET-1mRNA的表达。结果①C18：1、C18：2组（t≥200μmol／L）eNOS mRNA表达值低于对照组（P〈0．05）且呈浓度依赖性，而C18：2组eNOS mRNA表达值比C18：1组低（P〈0．05）。②C18：1组以及C18：2组ET-1mRNA表达值低于对照组（P〈0．05），呈浓度依赖性。③C16：0、C18：0、C24：0组（≥200μmol／L），ET-1mRNA表达值增高（P〈0．05），呈浓度依赖性。④C18：0、C18：1、C18：2各组相同FFA水平相比较，ET-1mRNA表达水平依次降低（P〈0．05）。⑤C18：1、C18：2组eNOS mRNA与ET-1mRNA表达值之比高于对照组（P〈0．05）。C16：0、C18：0、C24：0各组此比值低于对照组（P〈0．05）。C18：0、C18：1、C18：2各组同浓度FFA条件下此比值依次升高（P〈0．05）。C16：0、C18：0、C24：0各组同浓度FFA条件下此比值无显著差异（P〉0．05）。结论①FFA对内皮细胞eNOS mRNA表达水平的影响与链长无关，而与FFA饱和程度有一定关系。②不饱和脂肪酸（UFA）降低eNOS mRNA以及ET-1mRNA表达；提示UFA倾向于维护血管舒张功能。③饱和脂肪酸（SFA）呈浓度依赖性促进ET-1mRNA表达可能是导致内皮功能障碍的部分原因。     

皮肤鳞癌组织中FHIT基因表达及其意义

应用免疫组织化学S-P法检测脆性组氨酸三联体（FHIT）在27例皮肤鳞癌患者（SCC组）癌组织及11例正常人（对照组）皮肤组织中的表达。结果SCC组FHIT蛋白阳性表达率（44．4％）显著低于对照组（90．9％），P〈0．05。高中分化SCC患者FHIT蛋白阳性表达率（50．0％）显著高于低分化者（38．5％），P〈0．05；有淋巴结转移者FHIT蛋白阳性表达率（42．1％）显著低于无淋巴转移者（50．0％），P〈0．05。提示FHIT基因在SCC的发生、发展中起重要作用，其水平可作为SCC发生及转移能力的一项客观指标。     

T-bet、GATA-3在慢性特发性血小板减少性紫癜患者外周血中的表达及意义

目的进一步探讨慢性特发性血小板减少性紫癜（CITP）的发病机制。方法选择25例CITP患者（CITP组）及25例健康体检者（正常对照组）,采用ELISA法检测外周血Th细胞因子IFN-γ、IL-10表达;采用RT—PCR检测外周血淋巴细胞中转录因子T-bet、GATA-3mRNA表达。结果与正常对照组相比,CITP组IFN—γ表达显著升高、IL-10表达显著降低（P〈0．01）,T—betmRNA表达明显升高、GATA-3mRNA表达明显下降（P〈0．05）。结论T-bet、GATA-3表达异常在CITP发生、发展过程中发挥重要作用,可能机制为增强TM细胞功能、抑制Th2细胞功能。     

血浆肌钙蛋白I对急性肺血栓栓塞症预后的评价

目的：探讨血浆肌钙蛋白I（ScTnI）对急性肺血栓栓塞症（Acute pulmonary thromboembolism，APTE）预后的评价。方法：选择我院近3年确诊APTE并行ScTnI检查的患者共54例，分为ScTnI〈0．05ng／mL组（n=25）及ScTnI≥0．05ng／mL组（n=29），分析ScTnI水平与右心室功能及预后的关系。结果：ScTnl〈0．05ng／mL组中大面积肺血栓栓塞1例，次大面积9例，小面积15例；合并心源性休克者1例；无1例死亡。ScTnI≥0．05ng／mL组中大面积肺血栓栓塞7例，次大面积19例，小面积3例；合并心源性休克者7例；5例住院期间死亡。2组间右心室功能及心源性休克发生率及病死率存在差异有统计学意义（P〈0．05）。结论：APTE ScTnl≥0．05ng／mL者，住院期间心源性休克发生率及病死率显著升高，ScTnI可用于APTE的危险分层。     

系统性红斑狼疮合并静脉血栓栓塞症临床相关危险因素分析

目的探讨系统性红斑狼疮（SLE）合并发生静脉血栓栓塞症（VTE）的临床相关危险因素。方法回顾性连续收集2008年1月至2012年2月期间在解放军总医院住院治疗的27例SLE并发VTE的患者入血栓组,并募集同期27例与血栓组性别、年龄、体质量指数（BMI）、生活方式等环境因素相匹配的不伴有VTE的SLE患者作为对照组,利用单因素统计学分析两组患者的静脉血栓形成相关临床危险因素（血小板计数、免疫功能、补体、合并低蛋白血症、狼疮肾炎、肾功能不全、肾病综合征、肾性高血压、蛋白尿、血尿等）及实验室诊断指标[C-反应蛋白（CRP）、D-二聚体,白细胞计数、活化部分凝血活酶时间（APTT）、血浆凝血酶原时间（PT）、血浆纤维蛋白原（FIB）1的差异。结果与对照组相比,血栓组合并低蛋白血症（70．37％）、狼疮肾炎（74．07％）、肾功能不全（70．37％）、肾病综合征（55．56％）、肾性高血压（66．67％）的发生率均显著升高（P值分别为0．003,0．000,0．000,0．027,O．029）。血栓组患者的实验室检测指标CRP（7．19±9．23）mg／L和D．二聚体（6．32±5．75）mg／L均显著高于对照组（P值分别为0．004,0．000）。结论低蛋白血症、狼疮肾炎、肾功能不全、肾病综合征及肾性高血压可能是SLE合并VTE的临床相关危险因素;CRP及D-二聚体可能成为SLE合并VTE的实验室诊断指标。     

TGF-β1、p15在食管鳞癌中的表达及其生物学意义

目的探讨转化生长因子β1（TGF-β1）、p15基因及其蛋白在食管鳞癌中的表达与食管鳞癌发生的关系。方法采用免疫组化SP法和原位杂交技术检测48例食管鳞癌组织，18例癌旁不典型增生组织和10例切缘正常组织中TGF-β1，与p15 mRNA及其蛋白的表达。结果食管鳞癌组织中TGF-β1的阳性表达率（62．5％）低于正常组织（100％），P〈0．05；食管鳞癌组织中p15 mRNA和p15蛋白的阳性表达率分别为56．3％和47．9％，二者表达明显相关（X^2=22，P〈0．05），均低于在正常组织和不典型增生组织中的表达（P〈0．05）；食管鳞癌组织中TGF-β1的表达与p15 mRNA的表达明显相关（X^2=23．84，P〈0．05）。结论食管鳞癌组织中TGF-β1对p15基因及其蛋白的转录可能有正向调节作用TGF-β1、p15基因及其蛋白的低表达可能与食管鳞癌的发生有关。     

缬沙坦对血管衰老中凋亡调控基因Bcl-2、Bax表达的影响

目的探讨缬沙坦对血管衰老中凋亡调控基因Bcl-2、Bax表达的影响。方法健康Wistar大鼠分为青年组、衰老组及缬沙坦组，测定血浆丙二醛（MDA）、超氧化物歧化酶（SOD）水平，同时采用恒速注人流体方法测定各组大鼠颈动脉血管的顺应性，利用免疫组织化学染色法、RT—PCR法和Western印迹法分析各组大鼠凋亡调控基因Bcl-2、Bax的mRNA及蛋白表达水平。结果与衰老组相比，缬沙坦组MDA浓度显著降低（P〈0．05），SOD浓度显著升高（P〈0．05），颈动脉血管的顺应性增高，其中弹性面积有显著性差异（P〈0．05），Bcl-2的mRNA及蛋白表达水平明显增高（P〈0．05），Bax的mRNA及蛋白表达水平降低（P〈0．05）。结论血管衰老有其特征性生理改变，Bcl-2、Bax的mRNA及蛋白表达的失衡可能是血管衰老的重要分子机制之一，缬沙坦有一定的逆转血管衰老的作用。     

人工关节置换术后下肢深静脉血栓形成的危险因素分析

目的：探讨下肢深静脉血栓形成的危险因素.方法：对我院接受髋关节置换（THA）或膝关节置换（TKA）的185例患者的临床资料进行回顾性分析,以术后发生下肢深静脉血栓（DVT）的患者58例为DVT组,未发生DVT的127例患者为无DVT对照组.结果：185例关节置换手术患者中DVT发生率为31.4％ （58/185）,其中21例接受THA手术（21/118,17.8％）,37例接受TKA手术（37/67,55.2％）;血栓形成部位：腓肠肌静脉血栓38例,胫后静脉20例.x2检验显示两组年龄≥65岁,人体质量指数（BMI）≥25kg/m2,膝关节置换术,全身麻醉,有静脉血栓栓塞症（VTE）家族史者有显著差异（P＜0.05～＜0.01）;Logistic多因素分析显示年龄（OR=8.352,P=0.006）,BMI （OR=4.639,P=0.011）,麻醉方式（OR=7.345,P=0.008）,手术方式（OR=3.235,P=0.018）,VTE家族史（OR=7.749,P=0.007）均为DVT独立危险因素.结论：为降低关节置换手术的下肢深静脉血栓风险,应注意降低体重,改进麻醉和手术方式.     

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     

Prevalence of venous thromboembolism in neurosurgical patients

This study was conducted to clarify the prevalence of venous thromboembolism (VTE) in neurosurgical patients. Prospective study for venous thromboembolism screening after neurosurgery was conducted. Thirty-seven patients were screened by ultrasonography for deep vein thrombosis in the lower extremities at an average of 12 days postoperatively. All patients received standard thromboprophylaxis using graded compression stocking with/without intermittent pneumatic compression following the VTE prevention guidelines. Definitive diagnosis of venous thromboembolism was made by contrast-enhanced whole-body computed tomography. Prevalence of deep vein thrombosis of the lower legs was 13.5% (5/37). Incidence of pulmonary embolism was 60% (3/5) in patients having deep vein thrombosis. All patients having venous thromboembolism were asymptomatic. In high-risk patients, VTE prevalence after neurosurgery was high even under mechanical prophylaxis. Additional pharmacological prophylaxis should be considered for patients with high risk of VTE.     

Prevention of venous thromboembolism in medical patients with thrombocytopenia or with platelet dysfunction: a review of the literature

Current guidelines for venous thromboembolism (VTE) primary prophylaxis are based on randomized clinical trials that exclude subjects at a potentially high bleeding risk. Thus no specific recommendation/algorithm for pharmacological prophylaxis in patients with thrombocytopenia and/or platelet dysfunction is available. Because at least 25% of subjects admitted to medical departments exhibit these conditions, information on this subject is provided here to optimize their VTE prophylaxis. Low platelet number/function and clotting abnormalities are common in patients with liver cirrhosis. However, these patients have a high incidence of portal and idiopathic venous thromboses, implying that cirrhotic coagulopathy does not protect against thrombosis. At variance with severe thrombocytopenia (< 50,000/μL), mild/moderate thrombocytopenia (> 50,000/μL) should not interfere with VTE prevention decisions. In severe thrombocytopenia, prophylaxis should be considered on an individual basis, however. In patients with antiphospholipid antibodies and thrombocytopenia, a thrombotic tendency is usually associated rather than a bleeding risk. VTE prophylaxis in high-risk conditions is thus suggested in these patients. Except in cases with contraindications to anticoagulation, antithrombotic prophylaxis should be always considered in hospitalized cancer patients with thrombocytopenia, especially in those with hematologic malignancies and multiple VTE risk factors. Aspirin treatment is not as effective as heparins in lowering the risk of VTE. Studies in stroke suggest that thromboprophylaxis with heparins is safe in patients with ischemic stroke undergoing aspirin treatment. The need for VTE prophylaxis in patients on chronic treatment with aspirin and/or clopidogrel should be evaluated after assessing the individual risk-benefit ratio.     

Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism

OBJECTIVES: The purpose of this research was to determine the levels of platelet, leukocyte, and endothelial activation and markers of cellular interactions in patients with venous thromboembolism (VTE). BACKGROUND: The details of interactions between endothelium, platelets, and leukocytes in VTE are not well understood. METHODS: We studied 25 patients with VTE and compared 25 healthy controls. We used flow cytometry to measure: 1) endothelial microparticles (EMP) identified by CD31+/CD42b- (EMP(31)) or E-selectin (EMP(62E)); 2) platelet microparticles (CD31+/CD42b+); 3) surface expression of P-selectin in platelets and CD11b in leukocytes; 4) EMP-monocyte conjugates (percentage of monocytes positive for E-selectin); and 5) platelet-leukocyte conjugates (PLC) expressed as percentage of leukocytes positive for CD41. RESULTS: Patients with VTE had marked elevations of EMP(31) (2,193 vs. 383 counts/microl; p = 0.003), EMP(62E) (368 vs. 223 counts/microl; p = 0.001), and EMP-monocyte conjugates (3.3% vs. 2.5%; p = 0.002), as well as increased activation of platelets (35.2 vs. 5.0 fluorescence intensity units for P-selectin; p < 0.0001) and leukocytes (13.9 vs. 7.7 U for CD11b; p = 0.004). Also elevated in VTE were PLC (61.7% vs. 39.6%; p = 0.01). Expression of CD11b in leukocytes strongly correlated with PLC (r = 0.74; p < 0.0001). CONCLUSIONS: Marked activation of endothelium, platelets, and leukocytes occurs in VTE, and VTE, or the accompanying inflammatory process, involves the release of EMP and formation of EMP-monocyte conjugates and PLC. These findings support prior studies suggesting that release of EMP and their binding to monocytes are key events in thrombogenesis. Our findings also support the concept that the formation of PLC regulates leukocyte activation and participates in linking thrombosis with inflammation.     

ARFI评估肝硬化并发食管胃底静脉曲张患者出血和门静脉血栓的价值分析*

目的 探讨采用声脉冲辐射力弹性成像（ARFI）评估肝硬化并发食管胃底静脉曲张（EGV）患者出血或发生门静脉血栓的价值。方法 2015年4月~2017年6月我院收治的87例肝硬化并发EGV患者,采用AEFI测量肝实质剪切波速度（LSWV）和脾脏剪切波速度（SSWV）。采用二元Logistic回归分析影响患者发生门静脉血栓的危险因素。应用受试者工作特征曲线（ROC）下面积（AUC）分析LSWV和SSWV诊断患者出血或发生门静脉血栓的效能。结果 在随访的3个月内,发生消化道出血34例,未出血53例;EGV出血组LSWV和SSWV分别为（2.6±0.5） m/s和（3.3±0.5） m/s,显著高于EGV未出血组[分别为（1.9±0.4） m/s和（2.5±0.3） m/s,P<0.05];在87例患者中25例（28.7%）并发门静脉血栓,单因素和多因素分析显示,Child分级、门静脉内径、血小板计数、感染、腹水、肝性脑病、LSWV、SSWV、EGV分级和EGV出血为EGV患者发生门静脉血栓的危险因素;联合检测LSWV和SSWV诊断EGV患者并发门静脉血栓的AUC为0.893（0.829~0.946）,诊断效能较高。结论 采用ARFI测量LSWV和SSWV可以帮助判断肝硬化并发EGV患者门静脉血栓的发生,对临床具有一定的指导意义。     

The role of inflammation in venous thromboembolism and the link between arterial and venous thrombosis.

During the last decade, the role of inflammation in the etiopathogenesis of arterial thrombosis has been elucidated. However, little is known about the relationship between inflammation and venous thrombosis. Recently, inflammation has been accepted as a possible mechanism through which different risk factors trigger thrombus formation in veins. The data indicate that inflammation of the vessel wall initiates thrombus formation in an intact vein and that inflammation and coagulation systems are coupled by a common activation pathway. The first event in thrombus formation is most probably activation of endothelial cells, platelets and leucocytes, with initiation of inflammation and formation of microparticles that trigger the coagulation system through the induction of a tissue factor. Therefore, the key event in the initiation of venous thrombus formation is most probably vein wall inflammation. However, expected relationship between inflammatory markers as indicators of inflammatory process and clinical venous thromboembolism (VTE) has not yet been elucidated. C-reactive protein does not appear to be useful in predicting future venous thrombosis or to be useful in the diagnosis of VTE. Recently, it was demonstrated that probable association between VTE and several other markers of inflammation such as: interleukin (IL)-6, IL-8 and tumor necrosis factor-a exists. While these markers of inflammation were studied during or after acute venous thrombosis, further prospective studies are needed to determine the predictive value of inflammatory markers for VTE. The identification and elucidation of inflammatory markers relevant to venous thrombosis could provide targets for future therapy. That inflammation is the basic etiopathogenetic process of VTE is also supported by the relation of some risk factors to both arterial and venous thrombosis: age, increased body mass index, hypercholesterolemia, hypertension, lupus anticoagulant and hyperhomocysteinemia. A relation was also found between preclinical and clinical atherosclerotic disease and VTE. Also in line with these arguments are the preventive effects of aspirin and statins in both arterial and venous disease.     

Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism

OBJECTIVE: Despite the endogenous coagulopathy of cirrhosis, some patients with cirrhosis experience thrombophilic states. This study aims to determine the incidence and predictors of venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism, in hospitalized patients with cirrhosis. METHODS: A retrospective case-control study was performed in a tertiary-care teaching hospital over an 8-yr period. A total of 113 hospitalized patients with cirrhosis with a documented new VTE were compared to controls. Risk factors for VTE were determined using univariate and multivariate statistical analyses. RESULTS: Approximately 0.5% of all hospitalized patients with cirrhosis had a VTE. Traditional markers of coagulation such as INR and platelet count were not predictive of VTE. In the univariate analysis, serum albumin level was significantly lower in cases than controls (2.85 vs. 3.10 g/dL, respectively, p = 0.01). In the multivariate analysis, serum albumin remained independently predictive of VTE, with an odds ratio of 0.25 (95% CI 0.10-0.56). CONCLUSIONS: Approximately 0.5% of admissions involving cirrhosis patients resulted in a new thromboembolic event. Low serum albumin was strongly predictive of increased risk for developing VTE, independent of international normalized ratio or platelet count. Serum albumin deficiency may indicate low levels of endogenous anticoagulants.