急性脑梗塞患者血浆t—PA,PAI及vWF：Ag的检测及其与血脂的关系

本文同时检测了22例急性期脑梗塞患者血浆组织纤溶酶原激活物(t-PA)抑制物(PAI)活性及因子Ⅷ相关抗原(vWF:Ag)含量,结果示三指标与对照组比较,均有显著的增高;并对患者组上述指标与血脂间进行了相关性分析,认为血脂与纤溶系统间的相互联系对动脉粥样硬化、脑血栓形成具有重要意义。     

膀胱癌病人乙酰基转移酶表型的研究

应用ＤＤＳ作为实验药物，采用高效液相色谱法，研究了目前尚存话的有２－萘胺职业接触史的１１名膀胱癌病人、２５名普通膀胱癌病人及２３名接触对照的ＮＡＴ酶表型。结果表明。无论有无２－萘胺职业接触史，膀胱癌病人中慢型乙酰化者所占比例（５２．２％和４５．５％）均高于对照组（１３．０％），且差异有显著性（Ｐ＜０．０５），比值比０Ｒ分别为５．５６（９５％可信限＝１．０２～３０．３）和７．２５（９５％可信限＝１．７０～３０．３），提示慢型乙酰化者若暴露于２－萘胺更易患膀胱肿瘤，乙酰化慢表型是膀胱癌的一个遗传易感因素。     

心血管疾病患者血栓前状态相关指标检测

目的 :探讨血栓前状态 (prethromboticstate ,PTS)相关指标与心血管疾病的关系。 方法 :检测 66例急性心肌梗死 (血栓形成组 ) ,54例心绞痛 (血栓前状态组 )和 30例健康对照者 (对照组 )的血小板P 选择素 (P selectin)、血栓素B2 (TXB2 )、6 酮 前列腺素F1α(6 K PGF1α)、血管性假血友病因子 (vWF)、抗凝血酶 (AT)、组织纤溶酶原激活物抑制物活性 (PAI 1活性 )、D 二聚体 (D dimer)、一氧化氮 (NO)、组织纤溶酶原激活物含量 (t PA含量 )及组织纤溶酶原激活物活性 (t PA活性 )。结果 :与对照组比较 ,血栓前状态组的P selectin、TXB2 、PAI 1活性均显著升高(P <0 .0 5～ 0 .0 0 1 ) ,AT、t PA活性均显著降低 (P <0 .0 5～ 0 .0 0 1 ) ;血栓形成组的P selectin、TXB2 、vWF、PAI 1活性、D dimer、NO、t PA含量均显著升高 (P <0 .0 1～ 0 .0 0 1 ) ,6 K PGF1α、AT、t PA活性均显著降低 (P <0 .0 5～ 0 .0 0 1 )。血栓形成组与血栓前状态组相比 ,血栓形成组的TXB2 、vWF、PAI 1活性、D dimer、NO、t PA含量均显著升高 (P <0 .0 5～ 0 .0 0 1 ) ,6 K PGF1α、AT、t PA活性均显著降低 (P <0 .0 5～ 0 .0 1 )。多元Logistic回归发现 ,TXB2 、P selectin、PAI 1活性、t PA活性变化与PTS最为密切。结论 :TXB2      

Renin inhibition in hypertension

Fifty years ago, investigators identified renin inhibition as the preferred pharmacologic approach to blockade of the renin-angiotensin system. Renin is a monospecific enzyme that catalyzes the rate-limiting step in the synthesis of angiotensin II. Amplified enzymatic activity and additional physiological effects occur when renin and pro-renin bind to the (pro)renin receptor. Until very recently, development of clinically effective renin inhibitors remained elusive. Molecular modeling was used to develop aliskiren, a potent, low-molecular-weight, nonpeptide, direct renin inhibitor with sufficient bioavailability to produce sustained suppression of plasma renin activity after oral administration. In patients with hypertension, aliskiren produces dose-dependent blood pressure (BP) reduction and 24-h BP control up to a dose of approximately 300 mg once daily; at these doses, aliskiren shows placebo-like tolerability. Its antihypertensive potency is approximately equivalent to that of angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and diuretics. After abrupt withdrawal, persistent BP reduction and prolonged suppression of plasma renin activity is observed. When combined with diuretics, fully additive BP reduction is seen. When given with an angiotensin receptor blocker, aliskiren produces significant additional BP reduction indicative of complimentary pharmacology and more complete renin-angiotensin system blockade. Clinical trials are currently underway assessing the effects of aliskiren combined with an angiotensin receptor blocker on intermediate markers of end organ damage, and long-term end point trials are planned. The results of these studies will ultimately determine the place of renin inhibition and aliskiren in the treatment of hypertension and related cardiovascular disorders. The effect of aliskiren on receptor-bound renin and pro-renin is the subject of active investigation.     

Macrophage migration inhibitory factor stimulated by Helicobacter pylori increases proliferation of gastric epithelial cells

AIM: Helicobacter pylori ( H pylorl) is associated with increased gastric inflammatory and epithelial expression of macrophage migration inhibitory factor (MIF) and gastric epithelial cell proliferation. This study aimed at determining whether H pyloridirectly stimulates release of MIF in monocytes, whether the cag pathogenicity island (PAI) is involved for this function, and whether MIF stimulated by H pylori increases gastric epithelial cell proliferation in vitro. METHODS: A cytotoxic wild-type Hpyloristrain (TN2), its three isogenic mutants (TN2Acag, TN2AcagA and TN2AcagE) were co-cultured with cells of a human monocyte cell line, THP-1, for 24 h at different organism/cell ratios. MIF in the supernatants was measured by an ELISA. Cells of a human gastric cancer cell line, MKN45, were then co-cultured with the supernatants, with and without monoclonal anti-MIF antibody for 24 h. The cells were further incubated for 12 h after addition of 3H-thymidine, and the levels of incorporation of 3H-thymidine were measured with a liquid scintillation counter. RESULTS: The wild-type strain and the isogenic mutants, TN2ΔcagA and TN2ΔcagE, increased MIF release at organism/cell ratios of 200/1 and 400/1, but not at the ratios of 50/1 and 100/1. However, the mutant TN2Δcag did not increase the release of MIF at any of the four ratios.^ 3H-thymidine readings for MKN-45 cells were significantly increased with supernatants derived from the wild-type strain and the mutants TN2ΔcagA and TN2ΔcagE, butnot from the mutant TN2A cag. Moreover, in the presence of monoclonal anti-MIF antibody, the stimulatory effects of the wild-type strain on cell proliferation disappeared. CONCLUSION: H pylori stimulates MIF release in monocytes, likely through its cag PAI, but not related to cagA or cagE. H pylori-stimulated monocyte culture supernatant increases gastric cell proliferation, which is blocked by anti-MIF antibody, suggesting that MIF plays an important role in H pylori-induced gastric epithelial cell proliferation.     

Targets of Immune Regeneration in Rheumatoid Arthritis

Many of the aging-related morbidities, including cancer, cardiovascular disease, neurodegenerative disease, and infectious susceptibility, are linked to a decline in immune competence with a concomitant rise in proinflammatory immunity, placing the process of immune aging at the center of aging biology. Immune aging affects individuals older than 50 years and is accelerated in patients with the autoimmune disease rheumatoid arthritis. Immune aging results in a marked decline in protective immune responses and a parallel increase in tissue inflammatory responses. By studying immune cells in patients with rheumatoid arthritis, several of the molecular underpinnings of the immune aging process have been delineated, such as the loss of telomeres and inefficiencies in the repair of damaged DNA. Aging T cells display a series of abnormalities, including the unopposed up-regulation of cytoplasmic phosphatases and the loss of glycolytic competence, that alter their response to stimulating signals and undermine their longevity. Understanding the connection between accelerated immune aging and autoimmunity remains an area of active research. With increasing knowledge of the molecular pathways that cause immunosenescence, therapeutic interventions can be designed to slow or halt the seemingly inevitable deterioration of protective immunity with aging.     

幽门螺杆菌cag致病岛CagⅠ蛋白的生物信息学分析

目的用生物信息学分析方法对幽门螺杆菌(HP)cag致病岛中的CagⅠ蛋白进行综合分析,推断其结构和功能,并探索其在HP致病中的作用。方法用antherprot V5.0软件和网络数据库等分析预测其结构,BLAST程序搜索其同源序列;用PROSITE SCAN和Fingerprint服务器分析推测其潜在的功能。结果 CagⅠ蛋白有361个氨基酸残基,分子量(Mr)为39 370,理论等电点为5.56;N'端20个氨基酸残基为信号肽,有三段跨膜区,二级结构和三级结构中螺旋结构为主体(约80%);CagⅠ为稳定的疏水蛋白,保守性很强,有N-糖基化作用位点、蛋白激酶C磷酸化位点、酪蛋白激酶Ⅱ磷酸化位点和豆蔻酰化作用位点;存在膜蛋白、菌毛蛋白、转运蛋白、ATP/GTP酶、转录调节因子、分泌系统蛋白等多个蛋白质标签。结论 CagⅠ蛋白定位于HP外膜,是Ⅳ型分泌系统重要组成蛋白质,在信号转导和物质转运过程中充当信使或载体,可能具有水解酶及ATP/GTP酶活性。     

血清水平预测老年髋关节术后下肢深静脉血栓的价值研究

目的：探索血清D-二聚体(D-dimer,D-D)、纤维蛋白原(fibrinogen,FIB)、血小板(platelet,PLT)、C反应蛋白(C-reactive protein,CRP)联合组织型纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor-1,PAI-1)水平预测老年髋关节术后下肢深静脉血栓(deep vein thrombosis,DVT)的价值。方法：回顾性分析2020年2月至2022年5月收治的165例老年髋关节术患者,男89例,女76例;年龄60~75(66.43±5.48)岁;股骨颈骨折102例,股骨头坏死63例。所有患者入院24 h内均进行血清D-D、FIB、PLT、CRP、PAI-1检测,根据患者是否发生DVT分为DVT组和非DVT组。结果：DVT组患者的D-D、FIB、PLT、CRP、PAI-1水平均高于非DVT组(P＜0.001);Spearman分析结果显示,DVT与PLT、CRP、D-D、FIB、PAI-1水平均呈正相关性(r=0.382,0.213,0.410,0.310,0.353,均P＜0.001);二分类Logistic回归分析结果显示,D-D、PLT是影响DVT发生的独立因素(OR=0.038,0.960,P=0.032,0.011);D-D、FIB、PLT、CRP、PAI-1及五项联合预测DVT的曲线下面积(area under curve,AUC)分别为0.843、0.692、0.871、0.780、0.819、0.960,五项联合预测的AUC均高于单项预测(P＜0.05)。结论：D-D、FIB、PLT、CRP、PAI-1在预测老年髋关节术后发生DVT中具有一定效能,五项联合预测效能更高。