基于网络药理学探讨搜风愈喘方拆方“祛宿痰方”调控儿童哮喘的作用机制＊

目的 基于“伏风暗瘀宿痰”小儿哮喘病机新说，采用网络药理学及实验验证的方法，探索搜风愈喘方拆方“祛宿痰方”治疗儿童哮喘的作用机制，验证中医“宿痰”病机与西医细胞外基质改变病理之间的交通性。方法 通过TCMSP数据库建立“祛宿痰方”的有效成分和靶点数据集，利用OMIM、GeneCards、DrugBank、TTD疾病数据库建立哮喘疾病靶点数据集，利用Cytoscape软件取交集并构建“祛宿痰方”与哮喘的蛋白质互作网络，筛选关键靶点蛋白。利用Metascape数据库进行基因本体（Gene ontology，GO）分析以及京都基因和基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）富集分析。复制卵蛋白（OVA）诱导的哮喘大鼠模型，对核心通路及关键靶点进行实验验证。结果 共得到“祛宿痰方”治疗哮喘的靶点98个，包括IL-13、TP53、TGF-β1、VEGF-A、MMP9等，KEGG得到与哮喘相关的通路287条（P＜0.05），包括NF-κB信号通路、PI3K-AKT信号通路、IL-17信号通路等。GO结果显示与哮喘相关生物进程包括炎症反应、细胞外基质调控、氧化应激、血管生成等。动物实验证实“祛宿痰方”可下调大鼠肺组织中p-NF-κB-P65磷酸化水平，抑制NF-κB信号通路的激活，降低IL-13、TGF-β1 mRNA表达量（P<0.05），减少哮喘大鼠肺组织中炎症细胞浸润、黏液产生，从而延缓哮喘的进程。结论 “祛宿痰方”可抑制NF-κB信号通路的激活，降低肺组织中IL-13、TGF-β1 mRNA表达量，可能通过抑制炎症反应、调控细胞外基质等途径作用于哮喘，中医“宿痰”病机与西医细胞外基质改变病理之间存在一定的的交通性。     

Neural Correlates of Failed Inhibitory Control as an Early Marker of Disordered Eating in Adolescents

BackgroundBinge eating and other forms of disordered eating behavior (DEB) are associated with failed inhibitory control. This study investigated the neural correlates of failed inhibitory control as a potential biomarker for DEB.MethodsThe study used prospective longitudinal data from the European IMAGEN study adolescent cohort. Participants completed baseline assessments (questionnaires and a brain scan [functional magnetic resonance imaging]) at 14 years of age and a follow-up assessment (questionnaires) at 16 years of age. Self-reported binge eating and/or purging were used to indicate presence of DEB. Neural correlates of failed inhibition were assessed using the stop signal task. Participants were categorized as healthy control subjects (reported no DEB at both time points), maintainers (reported DEB at both time points), recoverers (reported DEB at baseline only), and developers (reported DEB at follow-up only). Forty-three individuals per group with complete scanning data were matched on gender, age, puberty, and intelligence (N = 172).ResultsAt baseline, despite similar task performance, incorrectly responding to stop signals (failed inhibitory control) was associated with greater recruitment of the medial prefrontal cortex and anterior cingulate cortex in the developers compared with healthy control subjects and recoverers.ConclusionsGreater recruitment of the medial prefrontal and anterior cingulate regions during failed inhibition accords with abnormal evaluation of errors contributing to DEB development. As this precedes symptom onset and is evident despite normal task performance, neural responses during failed inhibition may be a useful biomarker of vulnerability for DEB. This study highlights the potential value of prospective neuroimaging studies for identifying markers of illness before the emergence of behavior changes.     

脑心通对脑缺血再灌注损伤细胞外信号调节激酶活化的影响

目的:观察大鼠局灶性脑缺血/再灌注((ischemia/reperfusion,I/R)后信号转导介质细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)的活化情况以及脑心通对其影响。方法:雄性成年Wistar大鼠90只,随机分成3组:假手术组、对照组和脑心通组(每组30只),分别于缺血前6日每日用生理盐水4mL、生理盐水4mL和脑心通0.48g/kg(脑心通用4mL生理盐水溶解)灌胃。采用线栓法致大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)模型,在脑缺血再灌注后的3h、6h、24h、48h和72h分别处死大鼠(各组每个时间点6只),将脑组织进行免疫组织化学、TTC染色,TUNEL法观察细胞凋亡。结果:脑缺血诱导ERK活化,第6h达高峰,并持续到72h。脑心通组ERKs活化明显较对照组增强,而且各时间点ERK免疫反应阳性细胞数脑心通组显著较对照组增多(P<0.01)。脑心通组TTC染色梗死体积及凋亡细胞数较对照组明显较少(P<0.01)。结论:局灶性脑缺血再灌注可诱导缺血脑细胞部分ERK活化,脑心通干预可使缺血大脑海马ERK活化增强,减轻细胞的缺血性损伤。     

胃粘膜相关淋巴组织型淋巴瘤MAPK和Stat3磷酸化及cyclinD1蛋白表达的意义

目的:研究胃粘膜相关淋巴组织型(MALT)淋巴瘤MAPK和Stat3磷酸化与cyclinD1蛋白表达及其意义。方法:利用免疫组织化学方法检测了45例胃MALT淋巴瘤MAPK和Stat3磷酸化及cyclinD1蛋白的表达。结果:在胃MALT淋巴瘤中p-MAPK、p-Stat3及cyclinD1蛋白的阳性率分别为73.3%(33/45)、64.4%(29/45)和68.9%(31/45);低度恶性组p-MAPK和cyclinD1蛋白的阳性表达强度明显高于高度恶性组(P<0.01),而p-Stat3表达强度无明显差异(P>0.05);在低度和高度恶性胃MALT淋巴瘤中p-MAPK和cyclinD1蛋白的阳性信号强度均呈明显的正相关(r=0.6572和0.6823,P<0.01),而p-Stat3与cyclinD1蛋白表达未见明显相关性(r=0.1927,P>0.05)。结论:提示MAPK磷酸化在胃MALT淋巴瘤中发生及演进过程中起重要作用,但Stat3的磷酸化可能与该肿瘤的恶性演进关系不明显;在胃MALT淋巴瘤的发生与发展中,p-MAPK可诱导cyclinD1过度表达,从而促使该肿瘤细胞维持高增殖状态。     

一种滑移式微动振幅测量装置的设计

根据微动滑移振幅具有小位移的特点，设计制作了一种弓形传感装置，该装置能把小幅位移信号转换为电信号，并通过示波器实时显示出来，用这种测试装置来测量滑移式微动振幅具有测试方法简单而测试精度较高的优点。     

112例脑动脉系统微栓子监测的临床研究

目的　研究脑动脉系统微栓子 (MES)的产生机制及其相关因素。方法　将 112例 MES监测的临床资料进行总结分析。结果　本组微栓子检出率为 33.93% ,且全部见于有明显脑卒中症状者 ;脑梗死 MES检出率为35 .87%且以原发性大面积梗死为主 ;MES阳性与病程有明显相关 ,病程 <72 h易检出微栓子 ,阳性率为 4 7.72 % ;颅内血管狭窄是微栓子产生的主要原因 ;颈动脉异常与正常组微栓子出现率无明显差异 ,但发现本组病例中微栓子出现以左侧为主 ,与颈动脉病变部位一致率为 5 5 .5 5 % ;确定微栓子来源于有病变的颅外颈动脉 2例 ,来源于有病变的颅内颈动脉系 5例 ,来源于同时伴有颅内外血管病变 12例 ,表明颅内外动脉同时伴有病变时微栓子检出率增高 ;MES的阳性率与血液成分无相关性 ,但在血液成分异常组中血粘度增高以及血小板聚集降低 MES阳性率明显增高。结论　脑动脉系统中监测到微栓子说明患者有活动的栓子来源 ,易发生或复发脑梗死 ,TCD能正确的监测、判断脑循环中微栓子 ,确定其发生率、性质、来源以及与疾病的联系     

Raf-1 kinase,epidermal growth factor receptors,and mutant ras proteins in colonic carcinomas

Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr).