An oncolytic adenoviral vector of Smac increases antitumor activity of TRAIL against HCC in human cells and in mice

Hepatocellular carcinoma (HCC) displays a high resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cell death. To increase sensitivity of HCC cells to TRAIL, we have constructed an oncolytic adenoviral vector (ZD55) and used this vector to deliver second mitochondria-derived activator of caspases (Smac) and TRAIL genes (ZD55-Smac and ZD55-TRAIL, respectively) into HCC cells. Our data showed that human HCC cells express high levels of inhibitor of apoptosis proteins (IAPs). Transfected HCC cells expressing exogenous X-linked IAPs (XIAPs) displayed more resistance to TRAIL. The expression of Smac led to rapid and potent activation of apoptosis in HCC cells after infection with ZD55-Smac. The activation of caspases and induction of apoptosis could be enhanced further through coinfection with ZD55-TRAIL. The combined treatment of ZD55-Smac and ZD55-TRAIL resulted in significant reduction of XIAP expression levels. In addition, our in vivo data in mice showed only a partial response in the established tumor treated either by ZD55-Smac or ZD55-TRAIL alone. By contrast, complete tumor regression was observed by combination of ZD55-Smac and ZD55-TRAIL in all treated animals. This strong antitumoral activity achieved by this combination was due to a dramatic induction of tumor cell apoptosis in the treated tumors. In conclusion, our data indicate that Smac antagonizes the IAPs in HCC tumor cells and enhances tumor cell death induced by TRAIL in the oncolytic adenoviral vector. The combination of Smac and TRAIL delivered by way of the oncolytic adenoviral vector would provide a useful strategy for therapy of HCC and might also be applied to other IAPs abundant in cancers.     

大剂量阿托伐他汀预防对比剂肾病

Objective To compare the efficacy of high and low dose atorvastatin on preventing contrast induced nephropathy (CIN) in patients underwent diagnostic and therapeutic coronary intervention. Methods All patients received atorvastatin 10 mg/d on the basis of hydrated therapy (n =100) and high dose group received additional atorvastatin 80 nag at 12 to 24 hours before procedure (n =50). Scr, Ccr, blood β2-M, urine NAG/Cr, and urine osmolality before and after the procedure were compared between the groups. Results Baseline demographic characteristics and nephropathy risk factors were similar between groups. Cer was significantly reduced while blood β2-M and uric NAG/Cr were significantly increased in low dose group (all P ＜ 0.05) . Blood β2-M in the high dose group was significantly lower than that in the low dose group at day 1 [(2.35±0.52) mg/L vs. (2.67±0.64) mg/L, P =0.008], day 3[(2.49±0.55)mg/L vs. (2.80±0.64) mg/L,P =0.011] and day 5[(2.29±0.53) mg/L vs. (2.56±0.66) nag/L, P = 0.026] post-procedure respectively; urine NAG/Cr in the high dose group was also significantly lower than that in the low dose group at day 1 [(1.19±0.30) U/mmol vs. (1.46±0.34) U/mmol, P ＜ 0.001], day 3 [(1.30±0.30) U/mmol vs. (1.59±0.33) U/mmol, P ＜ 0.001], and day 5 [(1.10±0.30) U/mmol vs. (1.34±0.35) U/mmol, P = 0.001] post-procedure respectively;Cer in the high dose group was significantly higher than that in the low dose group at day 1 [(73.69±20.99) mL/min vs. (65.19±18.72) mL/min,P =0.035], day 3[(64.04±15.82) ml/min vs. (56.79±14.50)ml/min,P =0.019] post-procedure respectively. Conclusion High dose atorvastatin use before angiography is superior than low dose atorvastatin on attenuating contrast induced renal dysfunction.     

血清总胆红素对老年女性ST段抬高型心肌梗死患者介入术后造影剂肾病的预测价值

目的探究血清总胆红素(TBIL)对老年女性ST段抬高型心肌梗死(STEMI)患者接受直接PCI后造影剂肾病(CIN)的预测价值。方法回顾性分析我院心脏内科接受直接PCI的老年女性STEMI患者579例,分为CIN组48例和非CIN组531例;收集患者一般临床资料,计算估算的肾小球滤过率(eGFR),检测TBIL水平。结果与非CIN组比较,CIN组年龄、高血压、糖尿病、肌酐、尿素、空腹血糖、白细胞计数、血小板计数明显升高,eGFR、TBIL、血红蛋白水平明显降低,差异有统计学意义(P<0.05,P<0.01)。logistic回归分析模型结果显示,低TBIL是CIN的独立危险因素(OR=1.430,95%CI:1.217~1.834,P=0.024);年龄、糖尿病、基线肌酐、基线eGFR也均为CIN的独立危险因素(P<0.05,P<0.01)。结论低TBIL是老年女性STEMI患者PCI术后CIN的独立危险因素,TBIL可能有助于及早且准确地识别CIN高危患者,为临床治疗决策的制定提供一定的依据。     

Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in Drosophila

Hunger elicits diverse, yet coordinated, adaptive responses across species, but the underlying signaling mechanism remains poorly understood. Here, we report on the function and mechanism of the Drosophila insulin-like system in the central regulation of different hunger-driven behaviors. We found that overexpression of Drosophila insulin-like peptides (DILPs) in the nervous system of fasted larvae suppressed the hunger-driven increase of ingestion rate and intake of nonpreferred foods (e.g., a less accessible solid food). Moreover, up-regulation of Drosophila p70/S6 kinase activity in DILP neurons led to attenuated hunger response by fasted larvae, whereas its down-regulation triggered fed larvae to display motivated foraging and feeding. Finally, we provide evidence that neural regulation of food preference but not ingestion rate may involve direct signaling by DILPs to neurons expressing neuropeptide F receptor 1, a receptor for neuropeptide Y-like neuropeptide F. Our study reveals a prominent role of neural Drosophila p70/S6 kinase in the modulation of hunger response by insulin-like and neuropeptide Y-like signaling pathways.     

Medical humanities education in China: an exploratory cross-sectional study

Background

Governmental policies in China have strengthened education in the medical humanities. Previous publications have highlighted the inadequacy of medical humanities education in China and have promoted their advancement and evaluation. Medical disputes and mistrust between doctors and patients in China have been ascribed to a paucity of proper medical humanities education at the medical student level. However, no studies to date have specifically examined the frequency, structure, and characteristics of the medical humanities curricula at all Chinese medical schools, making it difficult to draw a comprehensive understanding of its current state. We therefore aim to provide such an understanding of the current role of the medical humanities at Chinese medical schools.

解读《中国高血压防治指南(2005年修订版)》(三)24小时动态血压监测的临床应用

动态血压监测(ambulatory blood pressure moni-toring,ABPM)技术经过30多年的不断发展和完善,目前已逐渐应用于临床。动态血压监测不仅真实地反映了各时间点的血压状况,而且揭示了高血压患者血压波动特点及昼夜变化规律,较偶测血压有诸多优点,有助于筛选临界高血压及轻度高血压,鉴别“白大衣高血压”,预示靶器官损害程度,还能更好地评价降压药的疗效,指导合理降压治疗[1],但是动态血压不能取代诊所血压测量。1动态血压仪器动态血压监测技术包括直接(动脉内)和间接(无创性)动态血压记录两种。1966年Bevan等设计了动脉内直接测压的方法:经…     

心力衰竭病人心肌组织血管紧张素Ⅱ受体基因表达与心肌重塑

目的：了解不同程序充血性心力衰竭（CHF）病人心肌细胞血管紧张素Ⅱ型受体（AT1）、AT2的mRNA表达与心肌重塑和心功能的关系。方法：通过手术取材,采用RT－PCR技术测定31例瓣膜病所致CHF病人不同心功能组与5例正常人心肌细胞AT1和AT2的mRNA表达。结果：瓣膜病所致心力衰竭（心衰）病人心肌组织呈心肌重塑的病理改变。轻度心衰病人心肌细胞AT1mRNA表达较正常人增高,中重度心衰组AT1mRNA表达明显降低,AT2mRNA表达差异无显著性,但AT1／AT2比值明显降低。结论：心肌细胞AT1在轻度心衰病人增高可能与心肌肥厚的发生有关,重度心衰病人心肌细胞占优势的受体亚型从AT1转变为AT2,其功能意义可能是对心衰的局部保护机制,也可能通过AT2诱导心肌细胞凋亡,致心功能进一步恶化。     

非瓣膜性心房颤动患者凝血-纤溶系统活性的变化及临床意义

目的:探讨非瓣膜性心房颤动患者凝血-纤溶系统改变及其意义.方法:选择慢性非瓣膜性心房颤动患者(心房颤动组)54例,其中男28例,女26例,平均年龄(58.4±12.3)岁;存在相同心血管疾病(高血压或冠心病)的窦性心律者(窦性心律组)40例,男20例,女20例,平均年龄(57.6±11.7)岁;健康体检者35例为对照组,其中男17例,女18例,平均年龄(52.4±18.5)岁.测定以上3组患者血浆纤维蛋白原、D-二聚体、组织纤溶酶原激活剂、组织纤溶酶原抑制剂水平及凝血酶原时间、凝血酶时间和部分凝血活酶时间.结果:非瓣膜性心房颤动患者血浆纤维蛋白原、D-二聚体和组织纤溶酶原抑制剂水平显著升高,血浆组织纤溶酶原激活剂水平显著降低.凝血酶原时间、凝血酶时间和部分凝血活酶时间则无显著变化.结论:非瓣膜性心房颤动患者存在高凝和低纤溶状态.     

阻塞性睡眠呼吸暂停低通气综合征患者体内炎症因子与血管内皮细胞

阻塞性睡眠呼吸暂停低通气综合征（obstructive sleep apnea-hypopnea syndrome,OSAHS）是一种常见的慢性睡眠呼吸疾患,该病有较高的心脑血管并发症。OSAHS患者炎症因子分泌异常,炎症因子可通过各种机制参与血管病变。以下就OSAHS患者炎症因子对血管内皮细胞的作用作一综述。