Glibenclamide for the Treatment of Ischemic and Hemorrhagic Stroke

Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1–transient receptor potential melastatin 4 (Sur1–Trpm4) channels and, in some cases, microglial K_ATP (Sur1–Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke.     

Implications of enolase in the RANKL-mediated osteoclast activity following spinal cord injury

Spinal Cord Injury (SCI) is a debilitating condition characterized by damage to the spinal cord, resulting in loss of function, mobility, and sensation. Although increasingly prevalent in the US, no FDA-approved therapy exists due to the unfortunate complexity of the condition, and the difficulties of SCI may be furthered by the development of SCI-related complications, such as osteoporosis. SCI demonstrates two crucial stages for consideration: the primary stage and the secondary stage. While the primary stage is suggested to be immediate and irreversible, the secondary stage is proposed as a promising window of opportunity for therapeutic intervention. Enolase, a metabolic enzyme upregulated after SCI, performs non-glycolytic functions, promoting inflammatory events via extracellular degradative actions and increased production of inflammatory cytokines and chemokines. Neuron-specific enolase (NSE) serves as a biomarker of functional damage to neurons following SCI, and the inhibition of NSE has been demonstrated to reduce signs of secondary injury of SCI and to ameliorate dysfunction. This Viewpoint article involves enolase activation in the regulation of RANK-RANKL pathway and summarizes succinctly the mechanisms influencing osteoclast-mediated resorption of bone in SCI. Our laboratory proposes that inhibition of enolase activation may reduce SCI-induced inflammatory response and decrease osteoclast activity, limiting the chances of skeletal tissue loss in SCI.     

基于多通道的ICU脑血管疾病死亡风险预测模型

死亡风险预测指根据病人临床体征监测数据来预测未来一段时间的死亡风险。对于ICU病患，通过死亡风险预测可以有针对性地对病人做出临床诊断，以及合理安排有限的医疗资源。基于临床使用的MEWS和Glasgow昏迷评分量表，针对ICU病人临床监测的17项生理参数，提出一种基于多通道的ICU脑血管疾病死亡风险预测模型。引入多通道概念应用于BiLSTM模型，用于突出每个生理参数对死亡风险预测的作用。采用Attention机制用于提高模型预测精度。实验数据来自MIMIC [Ⅲ]数据库，从中提取3?080位脑血管疾病患者的16?260条记录用于此次研究，除了六组超参数实验之外，将所提模型与LSTM、Multichannel-BiLSTM、逻辑回归（logistic regression）和支持向量机（support vector machine, SVM）四种模型进行了对比分析，准确率Accuracy、灵敏度Sensitive、特异性Specificity、AUC-ROC和AUC-PRC作为评价指标，实验结果表明，所提模型性能优于其他模型，AUC值达到94.3%。     

我国煤矿安全事故统计分析及预测

为分析我国煤矿死亡事故发生的规律和准确判断未来我国煤矿的整体安全生产形势,根据2009—2018年我国煤矿死亡事故统计数据,从煤矿事故发生级别、事故类型2个维度对我国的煤矿生产安全事故进行了研究。通过SPSS 25.0软件建立Brown线性趋势模型,并对我国2009—2018年煤矿百万吨死亡率进行验证,最后预测2019—2021年我国煤矿百万吨死亡率。结果表明2009—2018年煤矿事故起数和死亡人数处于持续下降趋势,我国煤矿安全形势持续稳定向好;在事故发生级别上,一般事故发生的事故起数最多,累计造成的人员死亡也是最高,其次是较大事故和重大事故,特别重大事故发生起数在2016年出现了回升,造成了大量人员伤亡,但是2017年出现回落,没有发生特大事故;在事故类型中,顶板事故发生频率最高,瓦斯事故是一次伤害造成死亡人数最多的;Brown线性趋势模型对2009—2018年煤矿百万吨死亡率验证表明,相对误差基本上都在30%以内,R^2=0.931,接近于1,均方根误差(RMSE)和正态化的BIC均较小,表明Brown线性趋势模型模型的拟合效果比较好,预测精度较高。对我国煤矿事故发生规律的研究和煤矿百万吨死亡率的预测验证分析,使煤矿企业制定完备的安全管理措施和避免煤矿事故的发生具有重要意义。     

2008奥运会羽毛球馆弦支穹顶预应力张拉模拟施工过程分析研究

对于大跨度弦支穹顶结构,预应力张拉施工过程实际上是几何体系由机构(准机构)变为可承担设计荷载的结构体系过程。该类结构体系的安全控制有别于常规结构体系,它需要对结构的设计状态即最终使用状态进行控制,同时应研究预应力张拉施工过程中结构的力学性能,并对结构几何成形过程中的安全性进行控制。本文以2008奥运会羽毛球馆弦支穹顶屋盖为研究对象,应用分步一次加载法和单元生死法两种不同的计算方法对弦支穹顶结构的预应力施工进行全过程模拟计算,分析了在预应力施工过程中结构位移、环索内力和径向拉杆内力变化规律,确认了张拉施工过程的安全性;得出分步一次加载法时结构力学响应大于单元生死法时结构力学响应的结论;证明弦支穹顶整体结构设计采用分步一次加载法是偏安全的。     

Transport in regional science: The “death of distance” is premature

Transport costs have always been an important dimension in regional science. It is therefore remarkable that regional science and transport economics have developed in a rather unconnected way. Although being distinct, the routes of the two were parallel, and there are signs that the two fields will get closer to each other. This paper further discusses long run trends in transport costs and the potential spatial consequences. The main conclusion is that although in terms of money and time, the performance of transport has improved enormously, many economic activities have not become footloose to the extent as expressed by the notion of death of distance. One of the reasons discussed is the role of transaction costs, some being clearly related with distance.JEL Classification: R0, R4The authors thank the guest-editors and an anonymous referee for helpful comments.     

我国地铁施工事故统计分析与研究

城市化进程的快速推进,促进一些城市地铁的建设发展,建设过程中由于各种因素,导致我国地铁施工安全事故居高不下。通过文献查阅、施工单位访问、网络搜索、专家访问等方式,对我国内地 2003~2017 年近 15 年间地铁施工过程中发生的 322 起事故,按照不同事故类型进行数据统计与分析,结合地理环境、历年天气等因素,揭示数据反映出的事故规律;比较不同省市死亡人数占伤亡人数比重,分析其与地铁施工安全管理水平之间的关系。从数据中分析当前地铁施工过程中存在的普遍性特征及其内在规律,并结合福州某工区的地铁施工建设,提出相应的对策与建议。     

应许之地

面对海平面持续上升的危机,本文提出了新型可持续发展城市建设模式,以供参考。     

Cardiac Arrhythmias and Sleep-Disordered Breathing in Patients with Heart Failure

The relationship between heart failure (HF), sleep-disordered breathing and cardiac arrhythmias is complex and poorly understood. Whereas the frequency of predominantly obstructive sleep apnea in HF patients is low and similar or moderately higher to that observed in the general population, central sleep apnea (CSA) has been observed in approximately 50% of HF patients, depending on the methods used to detect CSA and patient selection. Despite this high prevalence, it is still unclear whether CSA is merely a marker or an independent risk factor for an adverse prognosis in HF patients and whether CSA is associated with an increased risk for supraventricular as well as ventricular arrhythmias in HF patients. The current review focuses on the relationship between CSA and atrial fibrillation as the most common atrial arrhythmia in HF patients, and on the relationship between CSA and ventricular tachycardia and ventricular fibrillation as the most frequent cause of sudden cardiac death in HF patients.     

Autophagic Cell Death and Cancer

Programmed cell death (PCD) is a crucial process required for the normal development and physiology of metazoans. The three major mechanisms that induce PCD are called type I (apoptosis), type II (autophagic cell death), and type III (necrotic cell death). Dysfunctional PCD leads to diseases such as cancer and neurodegeneration. Although apoptosis is the most common form of PCD, recent studies have provided evidence that there are other forms of cell death. One of such cell death is autophagic cell death, which occurs via the activation of autophagy. The present review summarizes recent knowledge about autophagic cell death and discusses the relationship with tumorigenesis.