Effect of inflammation on endothelial cells induced by poly-L-lactic acid degradation in vitro and in vivo

Abstract

As a promising candidate, biodegradable Poly-L-lactic Acid (PLLA) has been extensively used in coronary artery stents. In our previous reports, PLLA stents implanted in porcine coronary arteries showed safety without stent thrombosis. However, inflammatory responses were observed, which needed further study. In this study, human aortic endothelial cells (HAEC) were treated with different volume percentages of extract of pre-degraded PLLA (extract of PLLA) in vitro, and the cell growth curve and morphological changes were examined. The expression of inflammatory cytokines such as NF-κB, VEGF and VCAM-1 were also observed by ELISA. In addition, PLLA stent was implanted in porcine coronary artery to examine morphological changes, functional marker eNOS and inflammatory responses. The extract of PLLA caused significant growth inhibition and release of NF-κB, VEGF and VCAM-1 in HAEC with volume percentage-dependence. Although re-endothelialization and expression of eNOS was observed, expression of NF-κB and lymphocytes surrounding PLLA were also found after PLLA stents were implanted in the artery. This study demonstrated the effects of inflammation on endothelial cells induced by PLLA degradation in vitro and showed the inflammation in vivo, suggesting that anti-inflammatory strategy is necessary for PLLA stent implantation in the artery.     

Cajal间质细胞的研究进展

Cajal间质细胞(interstitial cells of Cajal,ICC)是一类主要分布于胃肠道的间质细胞,是胃肠道的起搏细胞(pacemaker cell)和信号传导细胞,与肌细胞以及末梢神经元有着紧密的关系,具有激发和促进胃肠蠕动的作用.借助于电子显微镜技术,清楚观察到了ICC位置分布和内部精细结构;应用免疫荧光等生化技术,发现了其特殊表达的C-kit蛋白;利用电生理技术,得知多种胃肠动力障碍疾病也与其异常有关.多年来,学者逐渐在胃肠道、胆道、膀胱、子宫等部位发现了ICC的踪迹,并试图阐述其与某些疾病的发生机制.本文就ICC的起源、形态学、受体和功能、以及与其相关的疾病等作一综述.     

Towards clinical data-driven eligibility criteria optimization for interventional COVID-19 clinical trials

ObjectiveThis research aims to evaluate the impact of eligibility criteria on recruitment and observable clinical outcomes of COVID-19 clinical trials using electronic health record (EHR) data.Materials and MethodsOn June 18, 2020, we identified frequently used eligibility criteria from all the interventional COVID-19 trials in ClinicalTrials.gov (n = 288), including age, pregnancy, oxygen saturation, alanine/aspartate aminotransferase, platelets, and estimated glomerular filtration rate. We applied the frequently used criteria to the EHR data of COVID-19 patients in Columbia University Irving Medical Center (CUIMC) (March 2020–June 2020) and evaluated their impact on patient accrual and the occurrence of a composite endpoint of mechanical ventilation, tracheostomy, and in-hospital death.ResultsThere were 3251 patients diagnosed with COVID-19 from the CUIMC EHR included in the analysis. The median follow-up period was 10 days (interquartile range 4–28 days). The composite events occurred in 18.1% (n = 587) of the COVID-19 cohort during the follow-up. In a hypothetical trial with common eligibility criteria, 33.6% (690/2051) were eligible among patients with evaluable data and 22.2% (153/690) had the composite event.DiscussionBy adjusting the thresholds of common eligibility criteria based on the characteristics of COVID-19 patients, we could observe more composite events from fewer patients.ConclusionsThis research demonstrated the potential of using the EHR data of COVID-19 patients to inform the selection of eligibility criteria and their thresholds, supporting data-driven optimization of participant selection towards improved statistical power of COVID-19 trials.     

An Embryonic Diapause-like Adaptation with Suppressed Myc Activity Enables Tumor Treatment Persistence

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基于知识图谱构建和定性访谈法探析张忠德教授辨治间质性肺病临床特征与方药规律＊

目的 构建个性化知识图谱技术和定性访谈法结合，进一步挖掘张忠德教授辨治间质性肺疾病临证特征与用药规律。方法 采用回顾性分析，系统收集张忠德教授广东省中医院门诊2010年8月至2020年8月治疗间质性肺疾病病历，按照诊断标准、纳入标准、排除标准，严格筛选后，通过广东省中医院大数据挖掘团队中医药大数据智能处理与知识服务系统进行数据挖掘分析，并通过多元化视觉定性访谈法，将定量与定性分析有效结合。结果 共筛选出347首方，共141味药物，常用药物频次 ≥ 84次的药物有10味，其中党参、麦芽、黄芪、紫菀、白术等为核心用药，通过症状与药物推理知识地图显示，党参、炒麦芽、黄芪、大枣、太子参、山萸肉、巴戟天等为主要治疗用药；临证遣方用药知识关联分析，得知咳嗽、耳鸣、心悸、水肿、头痛、胸闷、恶寒等为多见，针对咳嗽，首选紫苏子、橘红、桂枝等温肺降气通阳之品等；频繁聚集显示，常用药对炒麦芽-炒白术、黄芪-党参、黄精-菟丝子、前胡-紫菀、炙枇杷叶-浙贝母等；聚类分析结果得到4组关系密切的聚类新药物组合；以脾为中轴，肺肾共扶为主的“平调五脏论”，分期阶梯辨治间质性肺疾病。结论 张忠德教授认为间质性肺疾病，虚实夹杂为多见，应从肺、脾、肾着手，采用平调五脏论分期阶梯辨治，用药配伍精简，以和为贵，以平为期。     

The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength

Lgr5 was originally discovered as a common Wnt target gene in adult intestinal crypts and colon cancer. It was subsequently identified as an exquisite marker of multiple Wnt-driven adult stem cell types. Lgr5 and its homologs, Lgr4 and Lgr6, constitute the receptors for R-spondins, potent Wnt signal enhancers and stem cell growth factors. The Lgr5/R-spondin complex acts by neutralizing Rnf43 and Znrf3, two transmembrane E3 ligases that remove Wnt receptors from the stem cell surface. Rnf43/Znrf3 are themselves encoded by Wnt target genes and constitute a negative Wnt feedback loop. Thus, adult stem cells are controlled by an intricate interplay of potent Wnt agonists, antagonists, and anti-antagonists.     

Binocular form deprivation influences the visual cortex

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors are considered to play a crucial role in synaptic plasticity in the developing visual cortex. In this study, we established a rat model of binocular form deprivation by suturing the rat binocular eyelids before eye-opening at postnatal day 14. During development, the decay time of excitatory postsynaptic currents mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors of normal rats became longer after eye-opening; however, the decay time did not change significantly in binocular form deprivation rats. The peak value in the normal group became gradually larger with age, but there was no significant change in the binocular form deprivation group. These findings indicate that binocular form deprivation influences the properties of excitatory postsynaptic currents mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in the rat visual cortex around the end of the critical period, indicating that form stimulation is associated with the experience-dependent modification of neuronal synapses in the visual cortex.