鞘磷脂类信号通路与动脉粥样硬化的研究进展

动脉粥样硬化是临床常见的冠心病和脑梗死等缺血性心脑血管疾病的主要病理基础,其病因复杂,发病机制尚未完全阐明。近年来,越来越多的研究显示鞘磷脂类信号通路可通过调节脂代谢、炎症和血管内皮功能等影响动脉粥样硬化的发生发展。文章综述了鞘磷脂类信号通路关键分子鞘磷脂、神经酰胺和1-磷酸鞘氨醇与动脉粥样硬化的关系,旨在为防治疾病提供新思路。     

足头向穿刺路径在膈肌下方肝肿瘤消融治疗中的CT模拟测量研究

【摘要】 目的 对足头向穿刺路径进行模拟测量并评价在膈肌下方肝肿瘤热消融治疗中的临床应用价值。方法 重建患者上腹部CT图像，选取有代表性的3个矢状面和1个冠状面作为标准层面，在各层面建立膈下标准病灶模型，并采用足头向穿刺路径进行模拟穿刺。测量各平面上膈肌高度、穿刺路径长度及间距。采用可到达性评价模拟穿刺时穿刺针分布于标准病灶中的最理想的位置情况。结果 纳入86例患者行测量研究，多数患者矢状2、3面的膈肌高度低于2cm，仅分别对平面内1511%的病灶e和813%的病灶f进行了测量。标准病灶a、b、c、d、b’的完全到达比例分别为5243%、6097%、3837%、5294%、6353%，中位路径长度分别为1039cm、1337cm（背侧，腹侧1266cm）、1315cm、888cm、1126cm，中位穿刺路径间距分别为21cm、209cm（背侧，214cm腹侧）、206cm、211cm、2145cm。结论 采用足头向穿刺路径进行穿刺，标准病灶a、b、d、b’有较高的完全到达比例，穿刺宽容度较高，有进一步在临床中应用的价值。标准病灶c的完全到达率不高。标准病灶e、f需要采用该路径穿刺的比例不高。     

Berberine Induces Cell Apoptosis through Cytochrome C/Apoptotic Protease-Activating Factor 1/Caspase-3 and Apoptosis Inducing Factor Pathway in Mouse Insulinoma Cells

Objective: To investigate apoptotic effects of berberine, a significant alkaloids component existing in Rhizoma coptidis, and its possible acting mechanism in insulinoma cells. Methods: Different concentrations of berberine were used to treat mouse insulinoma(MIN6) cells for various period of time. The viability and apoptosis of the cells were analyzed using methylthiazolyldiphenvl-tetrazolium bromide assay, flow cytometry and enzyme-linked immuno sorbent assay. Changes in the relating pro-and anti-apoptosis proteins were detected by western-blotting. Results: The half-maximal inhibitory concentration(IC50) of berberine was 5.7 μmol/L on MIN6 cells viability for 16 h. Berberine caused a 20% reduction(P0.05) in cell number after only 4-h incubation; which reached 50% after 24 h(P0.01). Berberine treatment for 16 h significantly increased the level of DNA fragmentation. The flow cytometry showed the apoptotic rate increased 2.9-and 4.6-fold after treating with berberine(5 μmol/L) for 8 and 16 h, while 3-and 8.7-fold after 10 μmol/L treatment for 8 and 16 h(P0.01). Berberine treatment dramatically elevated the expression ratio of Bax to Bcl-2. Meanwhile, berberine notably increased the apoptosis-inducing factors and cytochrome C transforming from the mitochondria to the cytoplasm. Apoptotic protease-activating factor 1(Apaf-1) was subsequently activated after cytochrome C release. Furthermore, caspase-3 and poly adenosine diphosphate-ribose polymerase were also activated to trigger apoptosis cascade. Conclusion: High concentration(5 and 10 μmol/L) of berberine could induce the apoptosis of MIN6 cells through cytochrome C/Apaf-1/caspase-3 and apoptosis inducing factor(AIF) pathway.     

Hedgehog signaling inhibitors in solid and hematological cancers

BackgroundThe hedgehog signaling pathway is normally tightly regulated. Mutations in hedgehog pathway components may lead to abnormal activation. Aberrantly activated hedgehog signaling plays a major role in the development of solid and hematological cancer. In recent years, inhibitors have been developed that attenuate hedgehog signaling; 2 have been approved for use in basal cell carcinoma (BCC), while others are under development or in clinical trials. The aim of this review is to provide an overview of known hedgehog inhibitors (HHIs) and their potential for the treatment of hematological cancers and solid tumors beyond BCC.DesignPublished literature was searched to identify articles relating to HHIs in noncutaneous cancer. Both preclinical and clinical research articles were included. In addition, relevant clinical trial results were identified from www.clinicaltrials.gov. Information on the pharmacology of HHIs is also included.ResultsHHIs show activity in a variety of solid and hematological cancers. In preclinical studies, HHIs demonstrated efficacy in pancreatic cancer, rhabdomyosarcoma, breast cancer, and acute myeloid leukemia (AML). In clinical studies, HHIs showed activity in medulloblastoma, as well as prostate, pancreatic, and hematological cancers. Current clinical trials testing the efficacy of HHIs are underway for prostate, pancreatic, and breast cancers, as well as multiple myeloma and AML.ConclusionsAs clinical trial results become available, it will be possible to discern which additional tumor types are suited to HHI mono- or combination therapy with other anticancer agents. The latter strategy may be useful for delaying or overcoming drug resistance.     

Adaptive response of resistant cancer cells to chemotherapy

Despite advances in cancer therapeutics and the integration of personalized medicine, the development of chemoresistance in many patients remains a significant contributing factor to cancer mortality. Upon treatment with chemotherapeutics, the disruption of homeostasis in cancer cells triggers the adaptive response which has emerged as a key resistance mechanism. In this review, we summarize the mechanistic studies investigating the three major components of the adaptive response, autophagy, endoplasmic reticulum (ER) stress signaling, and senescence, in response to cancer chemotherapy. We will discuss the development of potential cancer therapeutic strategies in the context of these adaptive resistance mechanisms, with the goal of stimulating research that may facilitate the development of effective cancer therapy.     

大补元煎通过上调BDNF/TrkB/CREB信号通路改善APP/PS1双转基因痴呆小鼠海马突触可塑性

目的:观察大补元煎对APP/PS1痴呆小鼠海马突触可塑性及脑源性神经营养因子(BDNF)/酪氨酸蛋白激酶受体B(TrkB)/环磷酸腺苷反应元件结合蛋白(CREB)信号通路的作用,并探讨其改善突触可塑性的可能机制。方法:将APP/PS1小鼠36只分为模型组、多奈哌齐组(6.5×10~(-4)g·kg~(-1)·d~(-1))和大补元煎组(13.2 g·kg~(-1)·d~(-1)),野生鼠12只设为正常组,正常组和模型组给予等体积生理盐水,各组连续灌胃30 d。应用Morris水迷宫检测各组小鼠的学习记忆能力,应用尼氏染色和高尔基染色观察海马区神经元和突触的病理形态变化,应用免疫荧光(IF)观察海马突触后致密蛋白95(PSD95)及突触素(SYN)的蛋白表达水平,采用蛋白免疫印迹法(Western blot)检测海马中BDNF,TrkB,CREB及磷酸化CREB(p-CREB)的蛋白表达水平。结果:与空白组比较,模型组小鼠平台潜伏期和游泳总路程增加(P0.01),穿越平台次数和目标象限停留时间减少(P0.01),小鼠海马CA3区神经元胞内尼氏体减少或消失,小鼠海马CA3区神经元及树突分支数量、树突棘密度减少(P0.01),小鼠海马SYN,PSD95,BDNF,TrkB及p-CREB的蛋白表达水平减少(P0.01)。与模型组比较,多奈哌齐组和大补元煎组小鼠平台潜伏期和游泳总路程减少(P0.05,P0.01),穿越平台次数和目标象限停留时间增加(P0.05,P0.01),小鼠海马CA3区神经元胞内尼氏体数量增多,小鼠海马CA3区神经元及树突分支数量,树突棘密度增加(P0.05,P0.01),小鼠海马SYN,PSD95,BDNF,TrkB及p-CREB的蛋白表达水平增加(P0.05,P0.01)。结论:大补元煎改善APP/PS1双转基因小鼠突触可塑性的机制可能与其上调小鼠海马中BDNF/TrkB/CREB信号通路有关。     

重症烧伤患者急救期输液及营养的路径护理

目的讨论研究对重症烧伤患者实行急救期输液及营养的路径护理的临床疗效与意义。方法选择医院烧伤科重症烧伤患者100例随机分组委观察组与对照组各50例。对照组给予急救期输液及营养常规护理。观察组提供急救期营养及输液路径护理。比较两组患者不同护理方式后营养状况、不良反应人数及护理满意度。结果治疗后观察组各项营养指标均显著优于对照组(P<0.05);观察组不良反应发生人数较少,护理服务满意程度较高。结论为重症烧伤患者提供急救期输液与营养路径护理可降低不良反应发生率并为患者加强营养支持,增强免疫力,有助于帮助其有效度过危险期,可促进患者后期治疗与恢复,更有助于拉近护患距离,提升医疗护理服务满意度。