Exploring the potential of exosomes in diagnosis and drug delivery for pancreatic ductal adenocarcinoma

Pancreatic cancer (PC) is a cancer of the digestive system, and pancreatic ductal adenocarcinoma (PDAC) accounts for approximately 90% of all PC cases. Exosomes derived from PDAC (PDAC-exosomes) promote PDAC development and metastasis. Exosomes are nanoscale vesicles secreted by most cells, which can carry biologically active molecules and mediate communication and cargo transportation among cells. Recent studies have focused on transforming exosomes into good drug delivery systems (DDSs) to improve the clinical treatment of PDAC. This review considers PDAC as the main research object to introduce the role of PDAC-exosomes in PDAC development and metastasis. This review focuses on the following two themes: (a) the great potential of PDAC-exosomes as new diagnostic markers for PDAC, and (b) the transformation of exosomes into potential DDSs.     

Bayesian adaptive lasso for additive hazard regression with current status data

Variable selection is a crucial issue in model building and it has received considerable attention in the literature of survival analysis. However, available approaches in this direction have mainly focused on time-to-event data with right censoring. Moreover, a majority of existing variable selection procedures for survival models are developed in a frequentist framework. In this article, we consider additive hazards model in the presence of current status data. We propose a Bayesian adaptive least absolute shrinkage and selection operator procedure to conduct a simultaneous variable selection and parameter estimation. Efficient Markov chain Monte Carlo methods are developed to implement posterior sampling and inference. The empirical performance of the proposed method is demonstrated by simulation studies. An application to a study on the risk factors of heart failure disease for type 2 diabetes patients is presented.     

非阻塞性冠状动脉粥样硬化患者血管内皮功能与左室舒张功能的关系

目的 探讨非阻塞性冠状动脉粥样硬化患者血管内皮功能与左室舒张功能的关系。方法 选取2013.6～2015.6宣武医院心脏内科收治的因胸痛疑诊冠心病、经冠脉造影检查证实为非阻塞性冠状动脉粥样硬化症（冠状动脉狭窄＜50%）患者119例，其中男性55例，女性64例，年龄31～85岁，平均年龄60岁。专业培训人员采用标准化问卷调查记录患者临床资料，行超声心动图和肱动脉血流介导内皮依赖性血管舒张功能（FMD）检测，分为FMD正常组（FMD＞10%）和减低组（FMD≤10%）。结果 两组人群基本临床资料无显著性差异（P值均＞0.05）。左室结构指标室间隔厚度、左室后壁厚度、左室舒张末内径、左室质量指数两组间比较无显著性差异（P值均＞0.05）。左室收缩功能指标每搏输出量、心输出量、左室短轴缩短率及射血分数组间比较也无显著性差异（P值均＞0.05）。FMD降低组较FMD正常组E/A比值显著减低（P＜0.001）、E/e’比值显著升高（P=0.006），控制年龄等影响因素，偏相关分析显示FMD与E/A比值存在显著正相关（r=0.261，P=0.005），FMD与E/e’呈显著负相关（r=-0.203，P=0.033）。结论 在非阻塞性冠状动脉粥样硬化人群中，内皮功能与左室舒张功能密切相关，内皮功能不全患者左室舒张功能明显减退。     

银杏内酯B对肌萎缩侧索硬化细胞模型的保护作用及其机制

目的:探讨银杏内酯B(ginkgolide B,GB)对肌萎缩侧索硬化细胞模型c-Jun氨基末端激酶(JNK)信号通路及细胞凋亡的影响。方法:通过含过表达人突变超氧化物歧化酶1(SOD1)~(G93A)基因(hSOD1~(G93A))和过表达人野生SODWT基因(hSOD1WT)与空质粒的慢病毒感染NSC34细胞,经一定浓度的嘌呤霉素筛选,倒置荧光显微镜下观察慢病毒的转染效率和细胞形态的变化,蛋白免疫印迹法(Western blot)检验感染细胞是否过表达SOD1蛋白,建立hSOD1~(G93A)-NSC34细胞系后给予GB,细胞培养分组为正常组、模型组、不同浓度GB组(25,50,75,100 mg·L-1)组,48 h后噻唑蓝(MTT)比色法检测细胞存活率,筛选出最佳药物浓度,后续实验分组为以正常组,模型组,75 mg?L~(-1) GB组,SP600125组,75 mg?L-1GB+SP600125组,流式细胞术检测各组细胞的凋亡率,蛋白免疫印迹法(Western blot)检测磷酸化(p-)JNK,c-Jun,p-c-Jun,半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)蛋白的表达。结果:与正常的NSC34细胞比较,hSOD1~(G93A)NSC34组细胞胞体变圆,突触减少、变短,而hSOD1WT NSC34组细胞和空质粒组细胞形态学未发生明显变化,与正常组比较,hSOD1~(G93A)NSC34组,hSOD1WTNSC3组细胞内SOD1蛋白水平显著升高(P0. 01),肌萎缩侧索硬化(ALS)细胞模型成功建立。与正常组比较,模型组细胞存活率显著降低(P0. 01);与模型组比较,给予不同浓度GB后,细胞存活率均显著升高(P0. 01),药物质量浓度为75 mg?L-1时细胞存活率显著升高(P0. 01)。后续实验,与正常组比较,模型组凋亡率,p-JNK,p-c-Jun,cleaved Caspase-3蛋白表达量显著升高(P0. 01);与模型组比较,75 mg?L-1GB组,SP600125组,75 mg?L-1GB+SP600125组凋亡率,p-JNK,p-c-Jun,cleaved Caspase-3蛋白表达明显降低(P0. 05,P0. 01)。结论:GB对肌萎缩侧索硬化细胞模型具有抑制细胞凋亡的保护作用,这种保护作用可能是通过JNK信号通路实现的。     

重庆某贫困县居家康复治疗救助政策实施情况及问题探讨

针对因病致贫的现象,我国健康扶贫的地方创新政策不断涌现。目前健康扶贫的经济扶助政策主要围绕大病住院费用的筹资解决,而少见对大病之后居家康复所维持健康的必要成本,如药品费用予以帮扶。从卫生经济学而言,预防和康复比治疗是对于穷人更有效的卫生投资,也能节省卫生资源开支。围绕大病贫困患者的康复精准帮扶,重庆某贫困县创新"居家康复治疗救助"政策以降低贫困人口医药费用负担。针对执行存在监控力度不足、医方激励不足、患者满意度不够高的问题,围绕大病贫困患者的需求,提出相应对策,包括拓宽补助的多种方式,提高对医生的激励设计,允许报销的合理弹性,加强多部门协同监管。     

Long Noncoding RNA WEE2-AS1 Plays an Oncogenic Role in Glioblastoma by Functioning as a Molecular Sponge for MicroRNA-520f-3p

The long noncoding RNA WEE2 antisense RNA 1 (WEE2-AS1) plays an oncogenic role in hepatocellular carcinoma and triple negative breast cancer progression. In this study, we investigated the expression and roles of WEE2-AS1 in glioblastoma (GBM). Furthermore, the molecular mechanisms behind the oncogenic actions of WEE2-AS1 in GBM cells were explored in detail. WEE2-AS1 expression was detected using quantitative real-time polymerase chain reaction. The roles of WEE2-AS1 in GBM cells were evaluated by the cell counting kit-8 assay, flow cytometric analysis, Transwell cell migration and invasion assays, and tumor xenograft experiments. WEE2-AS1 expression was evidently enhanced in GBM tissues and cell lines compared with their normal counterparts. An increased level of WEE2-AS1 was correlated with the average tumor diameter, Karnofsky Performance Scale score, and shorter overall survival among GBM patients. Functionally, depleted WEE2-AS1 attenuated GBM cell proliferation, migration, and invasion in vitro, promoted cell apoptosis, and impaired tumor growth in vivo. Mechanistically, WEE2-AS1 functioned as a molecular sponge for microRNA- 520f-3p (miR-520f-3p) and consequently increased specificity protein 1 (SP1) expression in GBM cells. A series of recovery experiments revealed that the inhibition of miR-520f-3p and upregulation of SP1 could partially abrogate the influences of WEE2-AS1 downregulation on GBM cells. In conclusion, WEE2-AS1 can adsorb miR-520f-3p to increase endogenous SP1 expression, thereby facilitating the malignancy of GBM. Therefore, targeting the WEE2-AS1–miR-520f-3p–SP1 pathway might be a promising therapy for the management of GBM in the future.     

母乳喂养对宫内发育迟缓儿胰岛素敏感性影响的随访研究

目的 探讨宫内发育迟缓（IUGR）儿胰岛素敏感性和血清脂联素水平，随访研究母乳喂养对胰岛素敏感性的影响。方法 选择2014年10月至2018年10月住院的足月IUGR儿为IUGR组（106例），同期出生足月适于胎龄儿（AGA）为AGA组（90例），记录出生体重、身长，生后7 d检测血清空腹血糖（FG）、三酰甘油（TG）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、胰岛素（INS）和脂联素水平，计算胰岛素抵抗指数（HOMA-IR）。将IUGR组按照实际喂养方式，分为母乳喂养组（37例）和配方奶喂养组（42例），于3月龄、6月龄追踪复测上述血清指标和生长指数。结果 与AGA组比较，IUGR组血清胰岛素、HOMA-IR增高，脂联素水平降低，差异均有统计学意义（P < 0.05）。母乳喂养和配方奶喂养组IUGR儿生后7 d、3月龄、6月龄生长指数、血清FG、TG、LDL和HDL水平差异无统计学意义（P > 0.05）。母乳喂养组血清INS、HOMA-IR水平随母乳喂养时间延长而降低，脂联素水平随母乳喂养时间延长而增高（P < 0.05）。结论 IUGR儿生后早期胰岛素敏感性下降，母乳喂养可改善IUGR儿胰岛素敏感性。