结核病分子流行病学特征性研究

目的运用结核病分子生物学手段,对DOTS策略实施效果进行监测和评价。方法对肺结核病人培养阳性痰标本采用MIRU-VNTR分型法技术进行分子流行病学分析和其结核病人流行病学相关性的回顾性调查。结果分子流行病学分析结果2004年成簇率为70%,其中山东基因型簇为22%,山东基因型簇比例较2002年下降了50%(P<0.005);流行病学相关率为32.5%。结论结核病分子生物学研究结果可作为DOTS实施效果监测和评价的客观指标之一。     

胸腔积液患者抗凝血酶Ⅲ活性测定及其临床意义

近年来,我们测定了31例肺癌及23例结核患者的血浆、胸腔积液中AT—Ⅲ的活性,并分别进行了比较。现报告如下。 资料与方法:肺癌组31例,男16例,女15例;年龄35～62岁,平均50岁。均由纤支镜检查或胸腔积液病理检查确诊。本组患者肝肾功能、血小板及出、凝血时间均正常,无心脏病、糖尿病病史。结核病组23例,男11例,女12例;年龄20～73岁,平均48岁。由痰菌检查或胸腔积液检查确诊。正常对照组21例,男10例,女11例;年龄35～62岁,平均21～42     

Expression of p53, p16 and COX-2 in pancreatic cancer with tissue microarray

BACKGROUND: Pancreatic cancer development and progression is driven by the accumulation of genetic changes. In this study we constructed tissue microarray containing specimens from pancreatic cancer, adjacent non-cancer tissue and normal tissue to survey the expression of p53, p16 and cyclooxyganase-2 (COX-2). METHODS: Tissue microarray containing 337 specimens from different stages of pancreatic cancer, adjacent noncancer tissue and normal tissues was constructed, and the expression of p53, p16 and COX-2 was assayed by immunohistochemistry to consecutive formalin-fixed tissue microarray sections. RESULTS: The expression of p53, p16 and COX-2 was significantly higher in tumorous tissues than in non-tumorons ones. A significant relationship was observed between p53 and COX-2, or p16 and COX-2. But no obvious correlation was seen between p53 and p16 expressions. Logistic regression analysis showed p53 and COX-2 as dependent predictors in pancreatic carcinogenesis, and a reciprocal relationship to neoplastic progression between p53 and COX-2. CONCLUSION: Combination analysis of p53 and COX-2 may be useful in predicting pancreatic carcinogenesis.     

急性肺损伤的氧化作用与抗氧化研究进展

急性肺损伤(ALI)是临床常见的呼吸系统急症,发病率高,确切发病机制不甚明确,临床治疗效果欠佳。本文对近几年ALI的氧化作用研究和抗氧化对ALI的治疗作用和相关研究进展,以及抗氧化作用对ALI的治疗前景作一综述。     

针刺对缺血缺氧性脑病神经细胞和神经营养因子的影响

针刺抑制缺血缺氧性脑损伤后的神经元凋亡，促进缺血缺氧性脑损伤后内源性神经干细胞的增殖和各种神经营养因予分泌的机制。     

波生坦治疗特发性肺动脉高压患者的疗效及安全性

目的 观察内皮素受体拮抗剂波生坦治疗中国特发性肺动脉高压患者的有效性、安全性及耐受性.方法 全国多中心Ⅳ期临床试验,共入选79例右心导管等技术确诊的新发特发性肺动脉高压患者,口服波生坦每日2次,每次62.5 mg,治疗4周后增至每日2次,每次125 mg至16周试验结束.分别在基线及治疗16周时记录6分钟步行距离,WHO肺高压功能分级、Borg呼吸困难评分及超声心动图评价资料.结果 波生坦治疗16周后,患者6分钟步行距离从(343.7±93.7)m增至(397.5±104.4)m(P＜0.01),WHO肺高压功能分级显著改善(P＜0.01),Borg呼吸困难评分由3.0±1.5降低至2.5±1.5(P＜0.01),超声心动图估测肺动脉收缩压从(97.8±25.2)mm Hg(1 mm Hg=0.133 kPa)下降至(92.8±29.5)mmHg(P＜0.05).无患者因无法耐受不良反应退出.结论 波生坦能显著改善中国特发性肺动脉高压患者的运动耐量、心功能,且具有良好的安全性和耐受性.

Abstract：

Objective To investigate the efficacy, safety and tolerance of bosentan, a dual endothelin receptor antagonist, in Chinese patients with idiopathic pulmonary arterial hypertension (IPAH).Methods Totally 79 IPAH patients (hemodynamic criteria confirmed by right heart catheterization) were included in this open-label, prospective multicenter study. Patients received 62. 5 mg of bosentan twice daily for the first 4 weeks, and then up-titrated to 125 mg twice daily for another 12 weeks. The primary end point was the change in exercise capacity showed by six-minute walk distance (6MWD) from baseline to 16 weeks. Secondary end points included the change in World Health Organization (WHO) functional class,Borg dyspnoea scale and systolic pulmonary artery pressure measured by echocardiography. Results The 6MWD increased from (343. 7 ± 93.7) meters at baseline to (397.5 ± 104. 4) meters after 16 weeks ( P ＜0. 01 ), WHO functional class and Borg dyspnoea scale were also significantly improved after 16 weeks therapy compared to baseline levels (all P ＜0. 01 ). Furthermore, the systolic pulmonary artery pressure was significantly decreased from (97.8±25.2) mm Hg (1 mm Hg=0. 133 kPa) to (92.8 ±29.5) mm Hg (P ＜0. 05) after 16 weeks bosentan treatment. There was no patient withdrawal from this study for safety consideration. Conclusion Bosentan therapy is well tolerated and can improve the exercise capacity and WHO functional class in Chinese IPAH patients.     

乙型肝炎肝衰竭中医证候数据库的建立

目的建立乙型肝炎肝衰竭证候研究数据库,用以收集、分析患者的临床资料,并探讨该系统的应用价值。方法选择全国十八家传染病院中西医结合科或综合性中医院肝病科住院的乙型肝炎肝衰竭患者,通过数据库进行在线数据收集管理及分析处理。结果制定一套规范的乙型肝炎肝衰竭前瞻性证候研究信息采集表、纳入标准、排除标准和病例剔出标准。数据平台可以实现任意条件查询,获取相应患者资料信息并创建报表;进行全面数据分析。结论成功建立了乙型肝炎肝衰竭患者中医四诊信息数据库,为进一步明确中医证候分布特点,完善辨证论治方法和优化防治方案提供了研究平台。     

Coronary collateral circulation: Effects on outcomes of acute anterior myocardial infarction after primary percutaneous coronary intervention

Background To investigate the effects of collateral coronary circulation on the outcome of the patients with anterior myocardial infarction (MI) with left anterior desending artery occlusion abruptly. Methods Data of 189 patients with acute anterior MI who had a primary percutaneous coronary intervention (PCI) in the first 12 h from the onset of symptoms between January 2004 and December 2008 were retrospective analyzed. Left anterior descending arteries (LAD) of all patients were occluded. LADs were reopened with primary PCI. According to the collateral circulation, all patients were classified to two groups: no collateral group (n = 111), patients without angiographic collateral filling of LAD or side branches (collateral index 0) and collateral group (n = 78), and patients with angiographic collateral filling of LAD or side branches (collateral index 1, 2 or 3). At one year’s follow-up, the occurrence of death, reinfarction, stent thrombosis (ST), target vessel revascularization and readmission because of heart failure were observed. Results At one year, the mortality was lower in patients with collateral circulation compared with those without collateral circulation (1% vs. 8%, P = 0.049), whereas there were no differences in the occurrence of reinfarction, ST, target vessel revascularization and readmission because of heart failure. The occurrence of composite of endpoint was lower in patients with collateral circulation compared with those without collateral circulation (12% vs. 26%; P = 0.014). Conclusions Pre-exist collateral circulation may prefigure the satisfactory prognosis to the patients with acute anterior MI after primary PCI in the first 12 h of MI onset.     

Binding of alpha-thrombin to surface-anchored platelet glycoprotein Ib(alpha) sulfotyrosines through a two-site mechanism involving exosite I

The involvement of exosite I in α-thrombin (FIIa) binding to platelet glycoprotein Ibα (GPIbα), which could influence interactions with other substrates, remains undefined. To address the problem, we generated the GPIbα amino terminal domain (GPIbα-N) fully sulfated on three tyrosine residues and solved the structure of its complex with FIIa. We found that sulfotyrosine (Tys) 278 enhances the interaction mainly by establishing contacts with exosite I. We then evaluated how substituting tyrosine with phenylalanine, which cannot be sulfated, affects FIIa binding to soluble or surface-immobilized GPIbα-N. Mutating Tyr(276), which mostly contacts exosite II residues, markedly reduced FIIa interaction with both soluble and immobilized GPIbα-N; mutating Tyr(278) or Tyr(279), which mostly contact exosite I residues, reduced FIIa complexing in solution by 0-20% but affinity for immobilized GPIbα-N 2 to 6-fold, respectively. Moreover, three exosite I ligands--aptamer HD1, hirugen, and lepirudin--did not interfere with soluble FIIa complexing to GPIbα-N, excluding that their binding caused allosteric effects influencing the interaction; nonetheless, all impaired FIIa binding to immobilized GPIbα-N and platelet GPIb nearly as much as aptamer HD22 and heparin, both exosite II ligands. Bound HD1 and hirugen alter Trp(148) orientation in a loop near exosite I preventing contacts with the sulfate oxygen atoms of Tys(279). These results support a mechanism in which binding occurs when the two exosites of one FIIa molecule independently interact with two immobilized GPIbα molecules. Through exosite engagement, GPIbα may influence FIIa-dependent processes relevant to hemostasis and thrombosis.     

Does insulin resistance, visceral adiposity, or a sex hormone alteration underlie the metabolic syndrome? Studies in women

Insulin resistance, obesity, and a sex hormone alteration have each been suggested as the underlying link for the constellation of risk factors for myocardial infarction (MI) commonly referred to as the metabolic syndrome or the insulin resistance syndrome. In an attempt to identify in women which of these variables is the most likely link, insulin, adiposity variables, sex hormones, and risk factors for MI were measured and their relationships analyzed statistically in 58 premenopausal and 20 postmenopausal healthy women. On controlling for age, visceral adipose tissue (VAT) correlated more strongly with risk factors for MI, insulin, and free testosterone (FT) than did total adipose tissue or subcutaneous adipose tissue. VAT, therefore, was used as the adiposity variable for further data analysis. Waist circumference was a better surrogate of VAT than was waist-hip ratio, which was a poor surrogate of VAT. VAT correlated positively with insulin, FT, triglyceride, and glucose, and negatively with high-density lipoprotein and sex hormone-binding globulin. On controlling for age, FT and insulin correlated with risk factors for MI and with each other, but on controlling for age and VAT, all of their correlations lost statistical significance except for FT-triglyceride and FT-insulin in the postmenopausal women. In conclusion, VAT accumulation in women, independently of other measures of adiposity, may largely explain the correlations of insulin, obesity, and sex hormones with risk factors for MI and may be the immediate underlying factor that links risk factors for MI to form the metabolic syndrome. Insulin resistance, which has been generally accepted to be the underlying factor, may be a component of the syndrome rather than its underlying link. We hypothesize that in women FT may effect preferential VAT accumulation and induce insulin resistance directly, as well as via VAT accumulation, so that a sex hormone alteration may underlie VAT accumulation and thus ultimately underlie the metabolic syndrome (with insulin resistance as a component).