基于网络药理学的大果木姜子油治疗心力衰竭作用机制研究

目的:揭示大果木姜子油治疗心力衰竭的作用机制。方法:首先从动物药理学实验验证疗效,采用异丙肾上腺素(ISO)诱导复制心力衰竭大鼠模型,造模成功后应用大果木姜子油治疗4周,监测血流动力学指标,分析血清BNP水平和心肌组织形态学变化;然后基于文献检索和TCMSP数据库获取大果木姜子油活性成分及作用靶点,从CTD和Drugbank数据库筛选心力衰竭的已知治疗靶点,将疾病治疗靶点与大果木姜子油活性成分作用靶点进行Venn分析,运用SYBYL软件进行分子对接验证,运用STRING数据库分析蛋白互作关系,再利用DAVID数据库进行GO分子功能和KEGG通路富集分析。结果:大果木姜子油可显著升高ISO诱导的心衰大鼠LVSP、±dp/dtmax,降低LVEDP和BNP水平,改善心肌组织形态学变化;获得大果木姜子油20个活性成分,其中7个活性成分(沉香螺旋醇、芳樟醇、萜品烯-4-醇等)可能通过调控一个蛋白互作网络治疗心力衰竭,该网络中的靶点有PTGS1、PTGS2、NOS2、NOS3、GSK3B;由蛋白富集分析发现,这些靶点与前列腺素内过氧化物合酶活性和一氧化氮合酶活性有关。结论:大果木姜子油可改善心衰大鼠的血流动力学紊乱及心肌组织形态学变化;其治疗心力衰竭的机制可能与调控前列腺素内过氧化物合酶活性和一氧化氮合酶活性有关。     

第55届美国血液学会年会骨髓增生异常综合征研究领域新进展：5-氮杂胞苷和地西他滨疗效及治疗方案评述

介绍第55届美国血液学会（ASH）年会有关骨髓增生异常综合征（MDS）研究领域对5-氮杂胞苷和地西他滨的评价和展望.除了较年长的女性患者,自2004年5-氮杂胞苷问世以来,MDS患者的生存期未有明显延长.但是,临床和试验数据提示,随着5-氮杂胞苷和地西他滨应用的不断扩展,会对MDS产生明显的影响.而且,这些药物是相对于传统细胞毒性药物的成功范例,其为进一步开展这方面的研究提供了新的思维和方法.     

"对位对线"补片固定法在腹腔镜造口旁疝Sugarbaker修补术中的应用

目的腹腔镜下Sugarbaker修补手术是造口旁疝的主要手术方式，补片固定是手术的关键技术环节，本研究介绍一种新式补片固定方法，并探讨其在临床上的应用效果。 方法回顾性分析2017年6月至2019年6月在中山大学附属第六医院住院的66例造口旁疝患者临床资料，患者均行腹腔镜造口旁疝修补手术（Sugarbaker术式），根据补片固定方式的不同分为试验组（41例，采用"对位对线"补片固定法）和对照组（25例，采用传统疝钉双圈补片固定方法）。比较两组患者相关指标和治疗效果。 结果两组患者性别、年龄、体质指数、病程以及造口旁疝分型比较，差异均无统计学意义。试验组补片固定时间短于对照组[（32.6±9.0）min vs（38.7±11.0）min，P<0.05]，两组在疝钉固定数量、血清肿、补片感染、术后住院时间指标方面，差异无统计学意义。试验组和对照组的平均随访时间差异无统计学意义[（37.6±14.8）个月vs（38.8±15.2）个月，P=0.687]，试验组的造口旁疝复发率低于对照组（2.4% vs 20.0%，P<0.05），而两组术后慢性疼痛发生率差异无统计学意义（24.2% vs 24.0%，P=0.971）。 结论在腹腔镜造口旁疝Sugarbaker修补术中应用"对位对线"补片固定法，可以缩短补片固定时间并减少术后复发，值得临床上推广使用。     

Cytoplasmic TRADD Confers a Worse Prognosis in Glioblastoma

Tumor necrosis factor receptor 1 (TNFR1)-associated death domain protein (TRADD) is an important adaptor in TNFR1 signaling and has an essential role in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and survival signaling. Increased expression of TRADD is sufficient to activate NF-κB. Recent studies have highlighted the importance of NF-κB activation as a key pathogenic mechanism in glioblastoma multiforme (GBM), the most common primary malignant brain tumor in adults.We examined the expression of TRADD by immunohistochemistry (IHC) and find that TRADD is commonly expressed at high levels in GBM and is detected in both cytoplasmic and nuclear distribution. Cytoplasmic IHC TRADD scoring is significantly associated with worse progression-free survival (PFS) both in univariate and multivariate analysis but is not associated with overall survival (n = 43 GBMs). PFS is a marker for responsiveness to treatment. We propose that TRADD-mediated NF-κB activation confers chemoresistance and thus a worse PFS in GBM. Consistent with the effect on PFS, silencing TRADD in glioma cells results in decreased NF-κB activity, decreased proliferation of cells, and increased sensitivity to temozolomide. TRADD expression is common in glioma-initiating cells. Importantly, silencing TRADD in GBM-initiating stem cell cultures results in decreased viability of stem cells, suggesting that TRADD may be required for maintenance of GBM stem cell populations. Thus, our study suggests that increased expression of cytoplasmic TRADD is both an important biomarker and a key driver of NF-κB activation in GBM and supports an oncogenic role for TRADD in GBM.     

Effects of Wenyang Zhenshuai Granules on the Expression of Key Mitochondrial Autophagy Proteins in the Doxorubicin-Induced Model of H9c2 Cardiomyocyte Injury

Bulletin of Experimental Biology and Medicine - This study aimed to explore the effects of Wenyang Zhenshuai granules (WZG) on the morphology of cardiomyocytes, cell viability, and the expression...     

Impact of Chronic Total Occlusion in a Noninfarct-related Artery on Clinical Outcomes in Patients With Acute ST-elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

In the setting of primary percutaneous coronary intervention (PCI), encountering with chronic total occlusion (CTO) in a noninfarct-related artery (IRA) is not a rare situation. Limited information on the impact of CTO on clinical outcomes in acute ST-elevation myocardial infarction (STEMI) patients undergoing primary PCI has raised more concerns. The aim of the present study was to evaluate the effect of concurrent CTO in a non-IRA on the clinical outcomes in patients with STEMI undergoing primary PCI.In the present prospective study, 555 consecutive patients with STEMI who underwent early primary PCI from January 2010 to December 2013 were included. The patients were divided into 2 groups: no CTO and CTO. Data on 12 months follow-up was obtained from 449 patients. The primary endpoint was the composite of hospitalization from angina, reinfarction, heart failure, or re-revascularization, and cardiac death at 12 months follow-up.Of the 555 patients, 75 (13.5%) had CTO in a non-IRA. Compared with patients in no CTO group, more patients in CTO group had hypertension (62.7% vs 46.5%, P = 0.009), diabetes (49.3% vs 35.0%, P = 0.024), and 3-vessel disease (52.0% vs 32.3%, P = 0.001). Patients with CTO had a lower left ventricular ejection fraction (LVEF) (40.1% ± 16.8% vs 54.3% ± 12.1%, P = 0.038), more presented with cardiogenic shock on admission (13.3% vs 4.8%, P = 0.008), compared with patients without CTO. Complete revascularization (CR) was less achieved in CTO group than in no CTO group (33.3% vs 49.1%, P = 0.013). The 12-month cardiac mortality rate was 14.5% versus 6.2% (P = 0.039), the incidence of 12-month primary endpoint was 38.7% versus 21.2% (P = 0.003) for CTO and no CTO group, respectively. Multivariate analysis revealed that after correction for baseline differences, CTO in a non-IRA (hazard ratio 4.183, 95% confidence interval 1.940–6.019, P = 0.001), cardiogenic shock on admission (hazard ratio 3.286, 95% confidence interval 1.097–9.845, P = 0.034), and 3-vessel disease (hazard ratio 2.678, 95% confidence interval 1.221–5.874, P = 0.014) remained an independent predictor of 1-year cardiac mortality in patients with STEMI undergoing primary PCI.CTO in a non-IRA in patients with STEMI undergoing primary PCI is associated with a poor prognosis. The presence of CTO in a non-IRA, cardiogenic shock on admission and 3-vessel disease might be an independent risk factor for greater 1-year cardiac mortality in patients with acute STEMI undergoing primary PCI.