High-Fat Diet Aggravates Cerebral Infarct,Hemorrhagic Transformation and Neuroinflammation in a Mouse Stroke Model

Background: Stroke in context of type 2 diabetes (T2D) is associated with a poorer outcome than in non-diabetic conditions. We aimed at creating a new reproducible mouse model of stroke in impaired glucose tolerance conditions induced by high-fat diet. Methods: Adult C57BL6 mice were fed for 2 months with either normal diet (ND) or high-fat diet (HFD). We used a model of Middle Cerebral Artery Occlusion (MCAO) for 90 min. Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT) were used to assess pre-diabetic status. Brain infarct volume, hemorrhagic transformation (HT) as well as systemic and cerebral inflammatory markers were evaluated. Results: HFD was associated with an increased body weight and glycemia following OGTT. The HFD group presented a significant increase in brain infarct volume (38.7 (IQR 30–46.7%) vs. 28.45 (IQR 21–30%); p = 0.016) and HT (HFD: 2 (IQR 1–5) vs. ND: 0 (IQR 0–1); p = 0.012) and higher levels of IL-6 and MCP-1 in infarcted hemisphere compared to the ND group. Conclusion: Two months of HFD in adult mice were sufficient to alter the lipid profile and the control of hyperglycemia. These metabolic perturbations were significantly associated with increased infarct volume and hemorrhagic complications.     

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.     

积极降压对脑小血管病防治策略的影响

2017年,美国心脏病学会和美国心脏协会提出将高血压诊断标准降为130/80 mm Hg (1 mm Hg=0. 133 kPa),这与其他指南有所不同。降压治疗的核心目标在于靶器官的保护,近年来降压治疗与脑小血管病预防的相关问题日益受到临床重视。目前研究结果表明,降压治疗对腔隙性卒中患者的二级预防以及白质病变进展的预防可能有一定积极意义,但确切的降压目标值并未确定。血压与临床结局可能呈现J型关系,血压过低或过高可能均有害,而取得最大获益的降压目标有待进一步探索。     

浅述设备对PCB微孔电镀镀液更新之影响

分析了设备对PCB电镀过程中孔中镀液更新之影响,为有效地利用设备条件改善孔中镀液的更新提供了一些方法及理论数据。     

Effective lightning protection schemes for distribution line

The causes of lightning outage are subdivided into direct lightning strokes and induced lightning strokes, which are identified by the characteristics of the lightning overvoltage. In the past, lightning protection devices were directed mainly toward the latter, and attention has been focused on the installation of lightning protection devices, ground wires, and reinforcement of insulators. However, lightning outages continue to occur. Thus it is extremely important to clarify the fault characteristics of lightning surges and to study the effectiveness of various lightning protection devices by considering both direct lightning stroke and induced lightning stroke in order to prevent lightning outage in the future. In this research, the electromagnetic transients program (EMTP) has been applied to the direct lightning stroke, and the induced lightning outage analysis program for multiple conductor systems has been applied to the induced lightning stroke to study the effectiveness of lightning protection devices provided by combination of various lightning protection devices. The most effective lightning protection schemes are analyzed and evaluated based on verification tests on the full scale models as well as economic considerations.     

Soluble Epoxide Hydrolase Blockade after Stroke Onset Protects Normal but Not Diabetic Mice

Soluble epoxide hydrolase (sEH) is abundant in the brain, is upregulated in type 2 diabetes mellitus (DM2), and is possible mediator of ischemic injury via the breakdown of neuroprotective epoxyeicosatrienoic acids (EETs). Prophylactic, pre-ischemic sEH blockade with 4-[[trans-4-[[(tricyclo[3.3.1.13,7]dec-1-ylamino)carbonyl]amino]cyclohexyl]oxy]-benzoic acid (tAUCB) reduces stroke-induced infarct in normal and diabetic mice, with larger neuroprotection in DM2. The present study tested whether benefit occurs in normal and DM2 mice if tAUCB is administered after stroke onset. We performed 60 min middle cerebral artery occlusion in young adult male C57BL mice divided into four groups: normal or DM2, with t-AUCB 2 mg/kg or vehicle 30 min before reperfusion. Endpoints were (1) cerebral blood flow (CBF) by laser Doppler, and (2) brain infarct at 24 h. In nondiabetic mice, t-AUCB reduced infarct size by 30% compared to vehicle-treated mice in the cortex (31.4 ± 4 vs. 43.8 ± 3 (SEM)%, respectively) and 26% in the whole hemisphere (26.3 ± 3 vs. 35.2 ± 2%, both p < 0.05). In contrast, in DM2 mice, tAUCB failed to ameliorate either cortical or hemispheric injury. No differences were seen in CBF. We conclude that tAUCB administered after ischemic stroke onset exerts brain protection in nondiabetic but not DM2 mice, that the neuroprotection appears independent of changes in gross CBF, and that DM2-induced hyperglycemia abolishes t-AUCB-mediated neuroprotection after stroke onset.     

Focal Ischemic Injury to the Early Neonatal Rat Brain Models Cognitive and Motor Deficits with Associated Histopathological Outcomes Relevant to Human Neonatal Brain Injury

Neonatal arterial ischemic stroke is one of the more severe birth complications. The injury can result in extensive neurological damage and is robustly associated with later diagnoses of cerebral palsy (CP). An important part of efforts to develop new therapies include the on-going refinement and understanding of animal models that capture relevant clinical features of neonatal brain injury leading to CP. The potent vasoconstrictor peptide, Endothelin-1 (ET-1), has previously been utilised in animal models to reduce local blood flow to levels that mimic ischemic stroke. Our previous work in this area has shown that it is an effective and technically simple approach for modelling ischemic injury at very early neonatal ages, resulting in stable deficits in motor function. Here, we aimed to extend this model to also examine the impact on cognitive function. We show that focal delivery of ET-1 to the cortex of Sprague Dawley rats on postnatal day 0 (P0) resulted in impaired learning in a touchscreen-based test of visual discrimination and correlated with important clinical features of CP including damage to large white matter structures.     

从形近字看汉字简化中的不足

由于汉字简化而造成的形近字占形近字总数的22.8%。本文认为产生这些形近字的原因包括3个方面:一是某些汉字的简化符号无规律可循;二是某些汉字简化过程中没有从整体、系统上进行考虑;三是汉字的简化过程单纯考虑汉字的笔划而忽略了区别度。     

副井提升系统安全回路及上位机优化改造

针对煤矿副井提升系统安全回路软硬件及上位机中存在的不足进行了优化改造,改进了过卷试验方式,将闸系统紧停信号引入安全回路,并将安全回路各节点状态信号引入RSView32人机界面,实时显示安全回路状态;根据现场检修需要,在上位机增加了复位显示功能及行程偏差大报警信号。实际应用表明,该优化改造可迅速定位故障节点,实现软硬件互查。