Binding of factor VIIa to tissue factor permits rapid antithrombin III/heparin inhibition of factor VIIa

Because free factor VIIa is inactivated only very slowly by a plasma concentration of antithrombin III (AT III) even in the presence of heparin, it has been assumed that AT III plays no significant role in regulating the initiation of tissue factor-dependent blood coagulation. However, in the present study, we present evidence that factor VIIa bound to tissue factor, unlike free factor VIIa, is readily inactivated by AT III in the presence of heparin. In a reaction mixture containing calcium ions and approximately equimolar concentrations of relipidated tissue factor (8.9 nmol/L) and factor VIIa (10 nmol/L), AT III (100 micrograms/mL) plus heparin (1 U/mL) inhibited 50% of the factor VIIa coagulant activity of the reaction mixture within 5 minutes. AT III/heparin was also shown to inhibit the catalytic activity towards factor X of factor VIIa/tissue factor complexes formed on monolayers of an ovarian carcinoma cell line (OC-2008) that constitutively expresses surface membrane tissue factor. AT III, even in the absence of exogenously added heparin, substantially inhibited the functional activity of factor VIIa/cell surface tissue factor complexes on intact monolayers. AT III alone and AT III/heparin, to a greater extent, also inhibited factor VIIa on "nonfunctional" factor VIIa/tissue factor complexes on intact monolayers, with resultant inhibition of their expression of factor VIIa/tissue factor catalytic activity toward factor X after cell lysis. The potential physiologic significance of these findings is discussed.     

Beta 2-integrin and L-selectin are obligatory receptors in neutrophil aggregation [see comments]

We have recently found that antibodies to L-selectin, the homing receptor on neutrophils, are as effective as those to beta 2-integrin at blocking formyl peptide-stimulated aggregation. Therefore, we investigated the requirements for expression of L-selectin and beta 2- integrin on adjacent cells during aggregation. Fluorescence flow cytometry allowed characterization of aggregates on the basis of size and color, as well as antibody binding to these two adhesive molecules. Formyl peptide-stimulated aggregate formation was measured for individual populations fluorescently labeled red (LDS-751) or green (CD44-FITC), and interpopulation red-green cell conjugates. Blocking either the beta 2-integrin or L-selectin adhesive epitope with monoclonal antibody on individual cell populations resulted in an approximately 50% reduction in two-color aggregation as compared with that in unblocked samples. Shedding the L-selectin on a cell population by preincubation with complexes of lipopolysaccharide and its plasma membrane binding protein also decreased aggregation to a control population by approximately 50%. We examined the aggregation of neutrophils from patients genetically deficient in beta 2-integrin and clinically leukocyte adhesion deficient (LAD). LAD adhesion to normal neutrophils was dependent on the expression of L-selectin on LAD cells and beta 2-integrin on normal cells. Thus, the minimum requirement for adhesion between two mixed populations of neutrophils was that one population expressed the beta 2-integrin and the other expressed the L- selectin adhesive epitope.     

２６２例中国人黑色素瘤Ｃ-ＫＩＴ基因扩增分析

目的　分析中国人黏膜、肢端和非肢端皮肤黑色素瘤Ｃ-ＫＩＴ基因扩增情况。方法　采用Real time Quantitative PCR SYBR green染料法检测２６２例中国人恶性黑色素瘤（ＭＭ）Ｃ-ＫＩＴ基因拷贝数变异;存在Ｃ-ＫＩＴ基因扩增的病例,采用ＰＣＲ扩增和基因测序的方法检测其第９、１１、１３、１７和１８外显子突变情况,免疫组化方法检测ＣＤ１１７表达情况。结果　２１例患者肿瘤组织中Ｃ-ＫＩＴ基因存在明显扩增,黏膜、肢端和非肢端皮肤黑色素瘤Ｃ-ＫＩＴ基因扩增比例分别为１０.２０％（１０／９８）、８.２４％（７／８５）和５.０６％（４／７９）;其中２例Ｃ-ＫＩＴ基因扩增同时伴突变;Ｃ-ＫＩＴ基因扩增与ＣＤ１１７表达无明显相关性。结论 在中国两种最常见的黑色素瘤亚型肢端和黏膜黑色素瘤患者中,部分患者黑色素瘤组织存在Ｃ-ＫＩＴ基因扩增,提示针对这种扩增的特异靶向药物有可能成为该类患者个体化治疗的选择。     

五藤冲剂联合甲氨蝶呤治疗类风湿关节炎的临床研究

目的:观察自拟五藤冲剂联合甲氨蝶呤治疗类风湿关节炎的临床疗效及安全性。方法:将102例类风湿关节炎患者随机分为治疗组52例,观察组50例,观察组口服甲氨蝶呤片,治疗组在观察组基础上加口服自拟五藤冲剂,疗程12周,观察治疗前后患者的症状、体征及实验室相关指标的变化。结果 治疗组总有效率96.00%,观察组总有效率81.63%,二者比较有统计学差异（P＜0.05）;治疗后两组在压痛关节数、压痛指数、肿胀指数、晨僵时间、握力、HAQ评分方面均有显著性差异（P＜0.01）,在肿胀关节数、DAS28评分、CRP方面有统计学差异（P＜0.05）,在VAS评分、ESR方面无统计学差异（P＞0.05）。结论 自拟五藤冲剂联合甲氨蝶呤治疗类风湿关节炎可显著改善患者症状、体征及炎性指标,显著优于单用甲氨蝶呤。     

奥拉西坦联合尼莫地平治疗重症脑挫裂伤的临床观察

目的观察奥拉西坦联合尼莫地平治疗重症脑挫裂伤的临床疗效。方法选取新疆医科大学第二附属医院2010年11月—2014年10月收治的重症颅脑损伤患者130例,随机分为对照组(68例)和治疗组(62例)。两组患者术后均转入ICU监护并给予等常规治疗,对照组给予尼莫地平注射液4 mg/次,加入到250 m L生理盐水中静脉滴注,1次/d。治疗组在对照组基础上加用注射用奥拉西坦,4 g/次,加入到250 m L生理盐水中缓慢静滴,1次/d。两组均连续治疗14 d。比较两组的临床疗效,同时比较两组治疗前,治疗第3、7、14天神经功能缺损(NIHSS)评分、颅内压、GCS评分、脑电图快慢波比值、大脑中动脉(Mc A)平均血流速度、双侧平均肌力的变化。结果对照组和治疗组总有效率分别为61.76%、80.65%,两组比较差异有统计学意义(P0.05)。对照组NIHSS评分从治疗第7天,治疗组从治疗第3天开始显著下降,同组比较差异有统计学意义(P0.01)。从治疗第3天开始治疗组NIHSS评分显著低于对照组,两组比较差异有统计学意义(P0.05、0.01)。两组颅内压均从治疗第3天开始降低,GCS评分、Mc A平均血流速度、双侧平均肌力从治疗第3天开始升高,同组治疗前后差异有统计学意义(P0.01)。治疗组从治疗第3天开始,GCS评分、Mc A平均血流速度高于对照组,治疗组在治疗第3、7天颅内压低于对照组,在治疗第7天快慢波比值低于对照组,在治疗第3、14天双侧平均肌力高于对照组,两组比较差异有统计学意义(P0.05、0.01)。结论奥拉西坦联和尼莫地平治疗重症脑挫裂伤术后患者具有较好的临床疗效,可促进患者神经功能恢复,提高患者生存质量,为进一步探索和治疗重症脑挫裂伤患者提供明确的思路。     

化疗栓塞联合冷冻对肝癌患者免疫功能的影响

目的：探讨肝动脉化疗栓塞（TACE）联合冷冻消融对中晚期肝癌患者免疫功能的影响及临床意义。方法：搜集59例中晚期原发性肝细胞癌（经影像学检查显示无远处转移）患者资料,依据接受治疗方式不同分为两组：TACE联合冷冻消融治疗组27例为研究组;单纯接受TACE 32例为对照组;研究组在TACE术后2～3周行冷冻消融术。两组分别于治疗前1周、治疗后1月取外周血,测定AFP、T淋巴细胞亚群（CD3^＋、CD4^＋、CD8^＋、CD4^＋/CD8^＋、Treg）水平变化;术后1个月采用增强CT、MRI评价肿瘤坏死程度。结果：两组治疗后甲胎蛋白（AFP）均下降,差异均具有统计学意义（P〈0.01）。研究组肿瘤坏死率（53.9%）较对照组（32.8%）高,差异具有统计学意义（P〈0.01）。研究组调节T细胞（Treg细胞）比例由（8.43±2.58）%下降至（7.33±2.56）%,治疗前后差异具有统计学意义（P〈0.01）;CD3^＋、CD4^＋细胞比例及CD4^＋/CD8^＋分别由（49.07±6.59）%、（46.51±8.17）%、1.23±0.32上升至（52.16±6.44）%、（50.63±8.27）%、1.52±0.46,治疗前后差异均具有统计学意义（P〈0.01）;CD8^＋由（39.15±6.54）%下降至（34.79±6.16）%,治疗前后差异具统计学意义（P〈0.01）。对照组治疗后Treg细胞、CD8^＋比例略有增加,CD4^＋细胞比例及CD4^＋/CD8^＋略有下降,但治疗前后差异均无统计学意义（P〉0.05）。结论：TACE联合冷冻消融治疗中晚期肝癌能提高肿瘤坏死率,降低Treg细胞比例,改善患者细胞免疫抑制状态,增强机体的抗肿瘤免疫效应。     

环孢素A固体分散体的制备及体外研究

 目的利用固体分散技术改善环孢素A(CsA)的溶解性能,提高其体外溶出速率。方法以Poloxamer188为载体,溶剂熔融法制备不同比例组成的环孢素A固体分散体,考察体外溶出速率及不同转速和不同溶出介质对溶出的影响,并配合X-射线粉末衍射分析药物在载体中的存在状态。对溶出度结果用Weibull分布模型进行拟合,计算体外溶出主要参数t_d和t₅₀,并进行方差分析。结果CsA在药物-载体比例为1:4或1:6的固体分散体中呈非晶态。固体分散体的溶出速率与相应物理混合物及原料药间存在极显著差异(P<0.01),溶出介质对药物溶出无显著性影响(P>0.05)。结论制成固体分散体能显著提高CsA的溶出速率。     

针刀松解法改善膝骨关节炎疼痛症状的随机对照临床研究

[目的]评价针刀松解法缓解膝骨关节炎疼痛症状的疗效和安全性。[方法]180例膝骨关节炎患者随机分入针刀组和电针组,每组各90例,分别给予针刀松解法和电针干预,共3周。采用日常生活活动能力（ADL）评分法评价两组治疗前、治疗后及治疗后6月随访时行走疼痛和上下楼梯疼痛的疗效,同时评价治疗期间的安全性。[结果]两组治疗后和随访时行走疼痛和上下楼梯疼痛评分均较治疗前升高,差异有统计学意义（P〈0.01）;组间比较治疗后和随访时ADL评分与治疗前的差值,针刀组在两个时间点的行走疼痛和上下楼梯疼痛评分差值均大于电针组,差异有统计学意义（P〈0.01）;组间比较治疗后及随访时疗效等级分布,差异有统计学意义（P〈0.01）,针刀组的疗效优于电针组。[结论]针刀松解法对缓解膝骨关节炎疼痛症状安全有效。     

侵及颈总动脉病变的手术治疗

目的探讨侵及颈总动脉病变的手术方法及注意事项。方法分析11例资料完整的患者资料,包括喉癌喉3/4切除术后复发1例,结核性颈总动脉瘤破裂大出血1例,医源性颈总动脉瘤1例,颈动脉体瘤3例,甲状腺癌侵及颈总动脉1例,颈部肿瘤侵及颈总动脉2例,颈总动脉离断伤1例,气性坏疽1例。结果上述病例中,2例完成肿瘤切除,颈总动脉重建;2例术中应用Shunt转流管,完成肿瘤切除;1例颈外伤,行颈总动脉结扎;1例医源性颈总动脉瘤患者,行动脉瘤切除,颈总动脉修补;甲状腺癌患者分离颈总动脉并切除部分气管侧壁完成肿瘤切除及应用颈前肌气管修补;2例颈部肿瘤保留颈总动脉切除肿瘤;1例气性坏疽患者颈部切开减压。结论侵及颈总动脉病变的手术治疗,主要有下列3种形式：①切除肿瘤及颈总动脉、颈动脉重建;②切除肿瘤及颈总动脉,颈总动脉结扎;③分离颈总动脉切除肿瘤。     

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窝沟封闭作为一种无痛、无害、无创伤的技术,是预防窝沟龋的有效方法。操作步骤包括:清洁、酸蚀、冲洗和干燥、涂布封闭剂、固化、检查。窝沟封闭的防龋效果与封闭剂的保留率直接相关,窝沟封闭的相关操作技术、材料的性能都是与窝沟封闭效果密切相关的因素。