川芎抗动脉粥样硬化作用机制的网络药理学与分子对接技术研究

目的使用网络药理学与分子对接技术探究川芎抗动脉粥样硬化的作用机制。方法运用中药系统药理(TCMSP)数据库筛选川芎的活性成分及质控成分,通过Swiss Target Prediction预测药物靶点。在DrugBank和DisGeNET数据库筛选出动脉粥样硬化的相关靶点。通过STRING构建靶点蛋白互作网络,运用Cytoscape绘制网络并进行拓扑学分析。使用Omicshare对相关靶点进行GO富集分析与KEGG富集分析。运用DockThor进行分子对接。结果获得川芎抗动脉粥样硬化的167个相关治疗靶点,通过网络拓扑分析发现钙敏感受体、丝裂原活化蛋白激酶3等46个靶点为核心靶点。GO富集分析发现川芎在生物过程、分子功能、细胞组成多方面影响动脉粥样硬化的发生发展。KEGG通路富集分析发现,川芎可能通过调节神经活性配体-受体相互作用、钙信号通路等多条代谢通路来发挥抗动脉粥样硬化的作用。结论运用网络药理学的方法证实了川芎抗动脉粥样硬化具有多途径、多靶点作用的特点。预测了川芎抗动脉粥样硬化的可能机制,为其后续基础研究提供了参考和理论依据。     

Cardiovascular therapy in patients with renal insufficiency

Chronic renal failure and arterial hypertension run in parallel. New goal blood pressure levels have been established in 130/85 mmHg and 125/75 mmHg depending on the level of proteinuria being below or above 1 g/day.New and lower threshold BP (>130/85 mmHg) to initiate pharmacologic therapy are required in the presence of renal failure in order to facilitate the strict BP control that is required.Renal insufficiency is accompanied since its initial stages by a marked increase in cardiovascular risk and serum creatinine, its estimated clearance and the presence of proteinuria are very powerful predictors of a bad cardiovascular outcome. Hence, the need to consider that both renal and cardiovascular protection are obtained with such a strict BP control which, otherwise seems to require blockade of angiotensin II effects when proteinuria above 1g/day is present.Prevention of renal failure related to elevated blood pressure requires of strict blood pressure control, usually obtained with combination of two or more antihypertensive agents, one of them capable of blocking angiotensin II. Besides this, strict control of associated cardiovascular risk factors is also required.     

高血压病患者脉压与靶器官损害的关系

目的　探讨脉压与高血压病靶器官损害的关系。方法　回顾性调查近 5年住我院未治疗高血压病患者 696例(男 3 87例 ,女 3 0 9例 ) ,按平均压 <10 7mmHg和≥ 10 7mmHg分为二组 ,再分别以脉压≤ 60mmHg ,60 10 0mmHg分为 4个亚组。分析各亚组的脉压与体重指数 (BMI)、血糖、血脂、BUN、Cr、UA、CCr、LVMI、EF、FS及心脑并发症发生率的相关性。结果　 ( 1)各亚组的高血压病史、吸烟者、饮酒者、BMI、血糖、甘油三酯 (TG)、胆固醇 (TC)、高密度脂蛋白 (HDL)及低密度脂蛋白 (LDL)无明显差别 (P >0 0 5) ;( 2 )脉压与BUN、Cr、UA、年龄、SBP、LVMI呈正相关 (r分别为 0 75,0 60 ,0 70 ,0 48,0 59,0 56,P均 <0 0 5) ,而与CCr、DBP、FS、EF呈负相关 (r分别为 -0 68,-0 52 ,-0 49,-0 51,P均 <0 0 5)。 ( 3 )左室肥厚、冠心病、心功能不全及脑并发症的发生率与患者年龄、收缩压、舒张压和脉压有关 (P均 <0 0 5) ,统计学分析脉压起着更重要的作用。结论　高血压病患者的靶器官损害与年龄、收缩压、舒张压和脉压等因素有关 ,但脉压起着更重要的作用     

2型糖尿病患者治疗3年前后临床疗效对比分析

目的比较和分析2型糖尿病(T2DM)患者治疗3年前后的代谢和血压控制、胰岛B细胞功能变化及其与糖尿病并发症的关系。方法选择1993—2000年解放军第306医院糖尿病中心治疗3年的T2DM患者,测量身高、体重、腰围、臀围、卧立位血压,测定空腹及餐后2h血糖和胰岛素、糖化血红蛋白(HbA1c)、胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、肌酐(Cr)、尿微量白蛋白等和眼底检查,统计分析血糖、血脂和血压治疗达标率及相应的用药情况。结果T2DM患者治疗3年后应用的降血糖药物种类、降血压药物种类、调脂药物及胰岛素使用者的比例明显升高。HbA1c、HDL-C控制理想的病例从3年前的23%、69%升高到3年后的30%、76%;血压、TC、TG和LDL-C情况无明显改变;空腹及餐后胰岛素、胰岛素抵抗指数(HOMA-IR)明显下降,微量白蛋白尿的病例从3年前的15%增加到3年后的23%;眼底病变则由26%升高到33%。结论尽管T2DM患者使用降糖药、调脂药和胰岛素治疗的病例数明显增加,但3年治疗后代谢控制仍不满意,胰岛B细胞功能明显下降,眼底病和肾脏受损在加重,需要进一步重视T2DM治疗的全面达标。     

Coronary Calcification and Long-Term Outcomes According to Drug-Eluting Stent Generation

ObjectivesThe aim of this study was to evaluate the long-term impact of coronary artery calcification (CAC) on outcomes after percutaneous coronary intervention and the respective performance of first- and second-generation drug-eluting stents (DES).BackgroundWhether contemporary DES have improved the long-term prognosis after percutaneous coronary intervention in lesions with severe CAC is unknown.MethodsIndividual patient data were pooled from 18 randomized trials evaluating DES, categorized according to the presence of angiography core laboratory–confirmed moderate or severe CAC. Major endpoints were the patient-oriented composite endpoint (death, myocardial infarction [MI], or any revascularization) and the device-oriented composite endpoint of target lesion failure (cardiac death, target vessel MI, or ischemia-driven target lesion revascularization). Multivariate Cox proportional regression with study as a random effect was used to assess 5-year outcomes.ResultsA total of 19,833 patients were included. Moderate or severe CAC was present in 1 or more target lesions in 6,211 patients (31.3%) and was associated with increased 5-year risk for the patient-oriented composite endpoint (adjusted hazard ratio [adjHR]: 1.12; 95% confidence interval [CI]: 1.05 to 1.20) and target lesion failure (adjHR: 1.21; 95% CI: 1.09 to 1.34), as well as death, MI, and ischemia-driven target lesion revascularization. In patients with CAC, use of second-generation DES compared with first-generation DES was associated with reductions in the 5-year risk for the patient-oriented composite endpoint (adjHR: 0.88; 95% CI: 0.78 to 1.00) and target lesion failure (adjHR: 0.73; 95% CI: 0.61 to 0.87), as well as death or MI, ischemia-driven target lesion revascularization, and stent thrombosis. The relative treatment effects of second-generation compared with first-generation DES were consistent in patients with and without moderate or severe CAC, although outcomes were consistently better with contemporary devices.ConclusionsIn this large-scale study, percutaneous coronary intervention of target lesion moderate or severe CAC was associated with adverse patient-oriented and device-oriented adverse outcomes at 5 years. These detrimental effects were mitigated with second-generation DES.     

Insulin binding by a cell line (HT 29) derived from human colonic cancer.

Insulin binding was demonstrated in cultured HT 29 cells originating from a human colon carcinoma. At 37 degrees and in complete medium, the binding of [125I]insulin (1-4x10-10M) reaches a maximum in 40 min and the cell associated radioactivity remains constant for at least 4 h. No degradation of the hormone is observed under these conditions. The binding is proportional to the number of cells and its pH optimum is 7.8. In the presence of excess insulin 50% of the [125I]insulin is dissociated from the complex after 10 min. At equilibrium, insulin binding is specific: proinsulin is 25 times less potent than native insulin in competing with [125I]insulin and related polypeptide hormones are inactive. Scatchard analysis indicates two classes of binding sites (1400 sites/cell of "high affinity" e.g. 4.7 x 108 M-1, and 20 000 sites of "low affinity" e.g. 4 x 107 M-1). The binding of insulin to this non-target cell shows the same kinetic characteristics and specificity as found for insulin in its target cells, except that HT 29 cells do not degrade the hormone. The problem of the correlation between insulin binding and a biological effect in these cells remains to be elucidated.     

Randomized Comparison Between Everolimus-Eluting Bioresorbable Scaffold and Metallic Stent: Multimodality Imaging Through 3 Years

ObjectivesThe aim of this study was to investigate the vascular responses and fates of the scaffold after bioresorbable vascular scaffold (BVS) implantation using multimodality imaging.BackgroundSerial comprehensive image assessments after BVS implantation in the context of a randomized trial have not yet been reported.MethodsIn the ABSORB Japan trial, 400 patients were randomized to a BVS (n = 266) or a cobalt-chromium everolimus-eluting stent (n = 134). Through 3 years, patients underwent serial angiography and intravascular ultrasound or optical coherence tomography (OCT).ResultsLuminal dimension at 3 years was consistently smaller with the BVS than with the cobalt-chromium everolimus-eluting stent (mean angiographic minimal luminal diameter 2.04 ± 0.63 mm vs. 2.40 ± 0.56 mm, mean difference −0.37 mm [95% confidence interval: −0.50 to −0.24 mm]; p < 0.001), mainly because of smaller device area (6.13 ± 2.03 mm² vs. 7.15 ± 2.16 mm², mean difference −1.04 mm² [95% confidence interval: −1.66 to −0.42 mm²]; p < 0.001), and larger neointimal area (2.10 ± 0.61 mm² vs. 1.86 ± 0.64 mm², mean difference 0.24 mm² [95% confidence interval: 0.06 to 0.43 mm²]; p = 0.01) by OCT. BVS-treated vessels did not show previously reported favorable vessel responses, such as positive vessel remodeling, late luminal enlargement, and restoration of vasomotion, although the OCT-based healing score was on average zero (interquartile range: 0.00 to 0.00). At 3 years, intraluminal scaffold dismantling (ISD) was observed in 14% of BVS. On serial OCT, ISD was observed in 6 lesions at 2 years, where the struts had been fully apposed at post-procedure, while ISD was observed in 12 lesions at 3 years, where 8 lesions were free from ISD on 2-year OCT. In 5 cases of very late scaffold thrombosis, strut discontinuities were detected in all 4 cases with available OCT immediately before reintervention.ConclusionsIn this multimodality serial imaging study, luminal dimension at 3 years was smaller with the BVS than with the cobalt-chromium everolimus-eluting stent. ISD, suspected to be one of the mechanisms of very late BVS thrombosis, was observed in a substantial proportion of cases at 3 years, which developed between post-procedure and 2 years and even beyond 2 years. (AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 [Absorb™ BVS] in Japanese Population [ABSORB JAPAN]; NCT01844284)     

Long-Term Outcomes After PCI or CABG for Left Main Coronary Artery Disease According to Lesion Location

ObjectivesThe aim of this study was to investigate the impact of lesion site (ostial or shaft vs. distal bifurcation) on long-term outcomes after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for left main coronary artery (LMCA) disease.BackgroundLong-term comparative data after PCI and CABG for LMCA disease according to lesion site are limited.MethodsPatients from the MAIN-COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty Versus Surgical Revascularization) registry were analyzed, comparing adverse outcomes (all-cause mortality [a composite outcome of death, Q-wave myocardial infarction, or stroke] and target vessel revascularization) between PCI and CABG according to LMCA lesion location during a median follow-up period of 12.0 years.ResultsIn overall population, the adjusted risks for death and serious composite outcome were higher after PCI than after CABG for distal bifurcation disease, which was mainly separated beyond 5 years. These outcomes were not different for ostial or shaft disease. When comparing drug-eluting stents (DES) and CABG, the adjusted risks for death and serious composite outcome progressively diverged beyond 5 years after DES compared with CABG for distal bifurcation disease (death: hazard ratio: 1.78; 95% confidence interval: 1.22 to 2.59; composite outcome: hazard ratio: 1.94; 95% confidence interval: 1.35 to 2.79). This difference was driven mainly by PCI with a 2-stent technique for distal bifurcation. In contrast, the adjusted risks for these outcomes were similar between DES and CABG for ostial or shaft disease.ConclusionsAmong patients with distal LMCA bifurcation disease, CABG showed lower mortality and serious composite outcome rates compared with DES beyond 5 years. However, there were no between-group differences in these outcomes among patients with ostial or shaft LMCA disease.     

The overall effectiveness of prophylaxis in severe haemophilia

The aim of this retrospective review was to assess the overall effectiveness of prophylaxis when compared with on-demand treatment of haemophilic patients. Twenty-five children (22 with severe haemophilia A and three with severe haemophilia B) were evaluated. Five haemophilia A patients received primary prophylaxis (instituted before the onset of any joint bleed) while the other 17 haemophilia A and all three haemophilia B patients were on secondary prophylaxis. We compared factor usage, number of bleeding episodes, emergency room (ER) visits and hospitalizations while on prophylaxis to those while on demand therapy. All subjects were male, the median age at time of review was 11.4 years and at start of prophylaxis was 4.5 years. Thirteen of the 25 patients (52%) required indwelling venous catheters for access, seven of these had one or more (one-six) episodes of line sepsis. Haemophilia A patients received an average of 23.8 U kg(-1) (20-30 U kg(-1)) of recombinant factor VIII three times a week while haemophilia B patients received 50 U kg(-1) recombinant FIX twice weekly. There was a significant reduction in the mean number of major bleeds on prophylaxis from 15.5 to 1.9 per year and a significant decrease in target joints, ER visits and hospitalizations. Although factor usage per year was higher on prophylaxis, there was an overall reduction in number of bleeds and resultant decrease in hospitalizations and ER visits. By preventing new target joints, prophylaxis can lead to reduction in long-term morbidity and a better quality of life despite increased central lines and higher factor usage.