Suppression of the p75 receptor signal attenuates the effect of ephrin-B3 and promotes axonal regeneration of the injured optic nerve

The p75 neurotrophin receptor (p75NTR) is known to transduce the signal from some myelin-associated axon growth inhibitors, including Nogo and myelin-associated glycoprotein. As ephrin-B3, a member of the ephrin family, is also expressed in myelin and inhibits axon growth, the purpose of this study was to assess the possible involvement of p75NTR in ephrin-B3 signaling. Here, we report that p75NTR is required for the inhibitory effect of ephrin-B3 on neurite growth in vitro. While ephrin-B3 inhibited neurite elongation of embryonic cortical neurons, the neurons with p75NTR knockdown or with EphA4 knockdown were less sensitive to ephrin-B3. Although no direct interaction of p75NTR with ephrin-B3 was observed, Pep5, a peptide that specifically inhibits RhoA activation mediated by p75NTR, reduced the effect of ephrin-B3. Therefore, p75NTR functions as a signal transducer for ephrin-B3. Moreover, axonal regeneration in vivo was induced by Pep5 application after optic nerve crush injury in mice. Thus, Pep5 is a promising agent that contributes to axonal regeneration in the central nervous system.     

对比不同类型干细胞对于缺血性脑卒中治疗的研究进展

成人中枢神经系统存在着一定量的神经干细胞,其具有两大关键能力;自我更新和多向分化潜能。缺血性脑卒中是一种由于由脑血流的缺失或减少引起的脑动脉闭塞,进而导致脑组织梗死的脑血管疾病。虽然对于脑损伤的药物治疗已经取得了一定的成果,但目前以干细胞为基础的治疗方法仍成为了研究热点。无论是内源性神经干细胞还是外源性神经干细胞移植均可在脑损伤后向远端损伤区迁移并分化成新的神经细胞,从而在中枢神经系统疾病尤其是脑梗死后进行组织修复和功能恢复。因此在这篇综述中,我们主要探讨不同类型的干细胞对脑梗死介导的脑损伤的应用潜能,对比不同类型干细胞对缺血性脑卒中的治疗优缺点。     

尼莫地平在预防缺血性脑血管事件所引起的认知障碍中的作用

目的:观察尼莫地平治疗预防缺血性脑血管事件所引起的认知障碍中的临床效果。方法:将在我院进行治疗的120例缺血性脑血管事件患者随机分为观察组60例和对照组60例。对照组患者按照常规方法进行治疗,观察组患者在此基础上给予尼莫地平治疗,观察对比两组的治疗效果。结果:观察组总有效率显著高于对照组,差异具有统计学意义(P0.05)。两组患者治疗后MOCA评分和MMSE评分均随着治疗时间的延长而逐渐增加。对照组患者治疗2个月及3个月后MOCA评分与治疗前比较,差异具有统计学意义(P0.05);观察组治疗1个月后MOCA评分与治疗前比较,差异具有统计学意义(P0.05)。观察组每月治疗后MOCA评分显著高于对照组,差异具有统计学意义(P0.05)。两组患者治疗2个月及3个月后MMSE评分与治疗前比较,差异具有统计学意义(P0.05)。观察组患者治疗3个月后MMSE评分显著高于对照组,差异具有统计学意义(P0.05)。随访1年后,观察组MMSS、MOCA评分均显著高于对照组,差异均具有统计学意义(P0.05)。两组患者治疗期间均未出现严重不良反应。结论:尼莫地平对于缺血性脑血管事件所引起的认知障碍的预防有较好疗效,安全性良好,值得推广应用。     

一种基于视网膜主血管方向的视盘定位及提取方法

为分割出眼底图像中的视盘,构建基于眼底图像的计算机辅助诊断系统,提出了一种基于视网膜主血管方向的视盘定位及提取方法。首先,利用Otsu阈值分割眼底图像R通道获取视盘候选区域;然后利用彩色眼底图像的HSV空间的H通道提取视网膜主血管并确定主血管方向;在此基础上,通过在方向图内寻找出对加权匹配滤波器响应值最高的点确定视盘中心位置;最后,利用该位置信息从视盘候选区域中"挑选"出真正的视盘。利用该方法对100幅不同颜色、不同亮度的眼底图像进行视盘分割,得到准确率98%,平均每幅图像处理时间1.3 s。结果表明:该方法稳定可靠,能快速、有效分割出眼底图像中的视盘。     

Two novel methods to assess ulnar nerve conduction across the elbow

PurposeNerve conduction studies (NCS) are used as an electrodiagnostic method for diagnosing ulnar neuropathy of the elbow (UNE). The purpose of this study was to determine normal and reliability values of across elbow ulnar nerve conduction velocity using two novel methods.MethodsUlnar nerve conduction studies were performed on both upper extremities of 104 healthy subjects. Two different techniques were used to evaluate ulnar nerve function at the elbow: Technique 1 (W-BE-AE) determined mixed NCV across the elbow indirectly while Technique 2 (BE-AE) measured conduction time directly. Twenty subjects returned within one week for re-testing to generate reliability data.ResultsThe mean NCV for the BE-AE segment using Technique 1 was 59.68 m/s (±8.91 m/s). The mean peak latency for the BE-AE segment using Technique 2 was 2.03 ms (±0.24 ms). The interrater and intrarater reliability intraclass correlation coefficient (ICC) for Technique 1 was 0.454 and 0.756, respectively. For Technique 2, the interrater and intrarater reliability ICC was 0.76 and 0.814, respectively.ConclusionThis study identified normal values for ulnar nerve conduction across the elbow with reliability ranging from poor to good, depending on the technique. These two novel techniques provide alternative methods to traditional techniques to measure ulnar nerve conduction across the elbow.     

普罗布考联合胰激肽原酶对老年糖尿病周围神经病变患者氧化应激反应及血清NSE水平的影响

目的:探讨普罗布考联合胰激肽原酶对老年糖尿病周围神经病变患者氧化应激反应及血清神经元特异性烯醇化酶(NSE)水平的影响。方法:选择2015年8月至2017年8月我院接诊的94例老年糖尿病周围神经病变患者作为本研究对象,通过随机数表法将其分为观察组(n=47)和对照组(n=47)。对照组在常规治疗基础上给予胰激肽原酶治疗,观察组在对照组基础上联合普罗布考治疗,两组均连续治疗12周。比较两组治疗后的临床疗效、治疗前后运动传导速度(MNCV)、感觉传导速度(SNCV)、多伦多临床评分系统(TCSS)评分、血清丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)及NSE水平的变化和不良反应的发生情况。结果:治疗后,观察组临床疗效总有效率为93.62%(44/47),明显高于对照组[70.21%(33/47)](P0.05);两组正中神经、腓总神经MNCV、SNCV较治疗前均显著延长(P0.05),且观察组正中神经、腓总神经MNCV、SNCV均明显高于对照组(P0.05);两组TCSS评分各内容和总分、血清MDA、NSE水平较治疗前均显著降低(P0.05),且观察组TCSS评分中症状评分、反射评分、感觉评分和总分及、血清MDA、NSE水平均明显低于对照组(P0.05);两组血清超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)水平较治疗前均显著升高(P0.05),且观察组血清SOD、CAT、GSH-Px水平均明显比对照组高(P0.05)。两组治疗期间不良反应总发生率分别为10.64%(5/47)、4.26%(2/47),组间比较差异无统计学意义(P0.05)。结论:普罗布考联合胰激肽原酶治疗老年糖尿病周围神经病变患者的效果显著优于单用胰激肽原酶治疗,可更有效改善神经病变程度,其机制可能和缓解氧化应激反应、降低血清NSE水平有关。     

生脉注射液联合曲美他嗪治疗缺血性心肌病合并肾功能不全的临床疗效分析

目的:研究生脉注射液联合曲美他嗪治疗缺血性心肌病合并肾功能不全的临床疗效。方法:选取2015年3月至2017年3月我院收治的100例缺血性心肌病合并肾功能不全患者,按照随机数表法分为观察组(n=50)和对照组(n=50)。对照组采用曲美他嗪治疗,观察组采用生脉注射液联合曲美他嗪治疗。观察和比较两组的治疗疗效、治疗前后心功能指标(左心室射血分数(LVEF)、左室收缩末径(LVESD)、左室舒张末期内径(LVEDD))、肾功能指标(血肌酐(Scr),尿素氮(BUN))、心肌损伤标志物(血清胱抑素(Cys C)、同型半胱氨酸(HCY)、脑钠肽(BNP))水平的变化。结果:治疗后,观察组总有效率显著高于对照组[92.30%(48/52) vs.70.83%(34/48)](P0.05),LVEDD、LVESD水平均显著低于对照组[(51.21±8.54)mm vs.(56.63±10.83)mm,(42.91±6.30)mm vs.(45.86±7.32)mm](P0.05),LVEF水平均显著高于对照组[(46.02±7.85)%vs.(41.20±8.84)%](P0.05),Scr、BUN水平均显著低于对照组[(164.30±17.95)μmol/L vs.(211.75±19.31)μmol/L;(8.12±0.76)mmol/L vs.(11.74±1.72)mmol/L](P0.05)。血清Cys C、HCY、NT-Pro BNP水平均显著低于对照组[(0.90±0.21)mg/L vs 1.52±0.34)mg/L (12.34±3.89)μmol/L vs.(20.86±5.28)μmol/L,(298.47±78.41)ng/L vs.(402.35±92.76)ng/L](P0.05)。结论:生脉注射液联合曲美他嗪治疗缺血性心肌病合并肾功能不全的的临床疗效显著优于单用曲美他嗪治疗,其可有效改善患者心、肾功能,减轻心肌细胞损伤。     

Discovery and evaluation of novel FAAH inhibitors in neuropathic pain model

Conceptual design and modification of urea moiety in chemotype PF-3845/04457845, the bench marking irreversible inhibitor of fatty acid amide hydrolase (FAAH), led to discovery of a novel nicotinamide-based lead 12a having reversible mechanism of action. Focused SAR around the pyridine heterocycle (Ar) in 12a (Tables 1 and 2) resulted into four shortlisted compounds, (?)-12a, (?)-12i, (?)-12l–m. The required (?)-enantiomers were obtained via diastereomeric resolution of a novel chiral dissymmetric intermediate 15. Based on comparative profile of FAAH potency, metabolic stability in liver microsome, liability of inhibiting major hCYP450 isoforms, rat PK, and brain penetration ability, two SAR optimized compounds, (?)-12l and (?)-12m, were selected for efficacy study in rat model of chemotherapy-induced peripheral neuropathy (CIPN). Both the compounds exhibited dose related antihyperalgesic effects, when treated with 3–30?mg/kg po for 7?days. The effects at 30?mg/kg are comparable to that of PF-04457845 (10?mg/kg) and Tramadol (40?mg/kg).     

Emerging roles of long non‐coding RNAs in neuropathic pain

Neuropathic pain, a type of chronic and potentially disabling pain resulting from primary injury/dysfunction of the somatosensory nervous system and spinal cord injury, is one of the most intense types of chronic pain, which incurs a significant economic and public health burden. However, our understanding of its cellular and molecular pathogenesis is still far from complete. Long non‐coding RNAs (lncRNAs) are important regulators of gene expression and have recently been characterized as key modulators of neuronal functions. Emerging evidence suggested that lncRNAs are deregulated and play pivotal roles in the development of neuropathic pain. This review summarizes the current knowledge about the roles of deregulated lncRNAs (eg, KCNA2‐AS, uc.48+, NONRATT021972, MRAK009713, XIST, CCAT1) in the development of neuropathic pain. These studies suggested that specific regulation of lncRNAs or their downstream targets might provide novel therapeutic avenues for this refractory disease.     

Nucleus Isthmi Is Required to Sustain Target Pursuit during Visually Guided Prey-Catching

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