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.     

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。     

脑络通对脑缺血损伤防治作用的实验观察

目的探讨脑络通防治缺血性脑损伤的作用机制。方法采用多因素病证结合的气虚血瘀证脑缺血动物模型。观察脑络通对血浆t-PA(tissue plasminogen activator组织型纤溶酶原激活物)、PAI(plasminogen activator inhibitor组织型纤溶酶原激活物抑制物)及血清IL-1β(interleukin-1β白细胞介素-1β)、IL-6(interleukin-6白细胞介素-6)含量的影响。结果与缺血模型组比较,脑络通可显著提高血浆t-PA活性(p<0.01),降低PAI活性(p<0.01),降低血清IL-1β水平(p<0.01)及IL-6水平(p<0.05),且优于药物对照组。结论在脑缺血急性期,脑络通可通过改善血浆纤维蛋白溶解系统活性,调节炎性介质释放,从多个病理环节阻断缺血性脑损伤,为益气活血的中药复方制剂脑络通防治缺血性脑血管疾病提供了进一步的实验证据。     

经肝动脉小剂量栓塞化疗联合经皮乙酸灭活对巨块型肝癌疗效的评价(附28例报道)

目的评价经肝动脉小剂量栓塞化疗(TACE)联合经皮乙酸注射(PAI)治疗巨块型肝癌的疗效。方法28例巨块型肝癌患者,首次行常规剂量TACE治疗,重复TACE治疗采用小剂量(10mg丝裂霉素与碘油乳化栓塞),术后1周CT复查,依据碘油的充盈状况,对碘油稀疏和缺损区域进行PAI治疗。观察其治疗后的生存率,肿块的变化及术后肝功能、α-FP、副反应情况。结果28例患者术后1a,2a,3a累积生存率分别为96.4%,78.6%,32.1%,全部患者的肿块缩小。结论小剂量TACE联合PAI治疗巨块型肝癌能明显提高患者的生存率,术后肝功能损伤小,副反应少。     

转染siRNA特异性下调人主动脉平滑肌细胞PAI表达

目的转染化学合成siRNA特异性下调人主动脉平滑肌细胞PAI表达。方法人工合成一对互补并编码相应短发夹状PAI小核糖核酸,体外退火;采用电转染方法将小RNA导入人主动脉平滑肌细胞中,采用逆转录聚合酶链反应(RT-PCR)、western blot法分别检测转染细胞PAI mRNA和蛋白的表达变化。结果转染PAI siRNA载体后,人主动脉平滑肌细胞PAI mRNA和蛋白表达均较对照组明显下降(P<0.01)。结论转染人主动脉平滑肌细胞后,并可快速特异性地封闭PAI的表达,为进一步研究PAI作用机制提供了实验基础。