Reinstatement of alcohol-seeking by priming injections of alcohol and exposure to stress in rats

 Previous studies using a reinstatement procedure have found that acute reexposure to the self-administered drug and exposure to footshock stress reinstate heroin and cocaine seeking after prolonged drug-free periods. Here we tested whether these findings generalize to alcohol-taking behavior. Male rats were initially allowed to consume alcohol in a two-bottle choice procedure (water versus alcohol) for 30 min/day for 36 days. Rats were then trained for 60 min/day in operant chambers to press a lever for the drug (0.13 ml of 12% w/v of an alcohol solution) for up to 55 days. After stable drug-taking on a fixed-ratio-3 schedule of reinforcement was obtained, lever pressing for alcohol was extinguished by terminating drug delivery for 4–9 days. Reinstatement of drug seeking was then determined after non-contingent priming injections of alcohol (0.24 and 0.48 g/kg; given IP and orally) or exposure to intermittent footshock stress (5 and 15 min; 0.8 mA). Priming injections of alcohol produced a modest dose-dependent reinstatement of drug seeking, whereas footshock stress potently reinstated extinguished alcohol seeking. In contrast, similar parameters of footshock failed to reinstate extinguished sucrose-taking behavior in rats previously trained to lever press for sucrose pellets. These findings extend previous reports on reinstatement of cocaine and heroin seeking by a footshock stressor and by priming drug injections. It also appears that the reinstatement procedure provides an appropriate methodology to study relapse to alcohol-taking behavior in the drug-free state. Received: 9 April 1997 / Final version: 1 August 1997     

消化道肿瘤免疫相关不良事件的临床分析

目的探讨消化系统恶性肿瘤中免疫检查点抑制剂(immune checkpoint inhibitors, ICIs）导致免疫相关不良事件(immune-related adverse events, irAEs)的特征及危险因素。方法 回顾性分析2019年4月至2021年10月北京大学肿瘤医院诊治的95例接受ICIs治疗的消化系统恶性肿瘤患者的临床资料和irAEs发生情况。irAEs、内分泌irAEs危险因素分析采用二元Logistic回归分析。结果 95例患者共应用ICIs治疗458例次,中位应用3例次(范围：1~33例次）。irAEs的发生率为55.8%,3~4级irAEs发生率为9.5%。最常见的irAEs为皮肤irAEs(27.4%）和内分泌irAEs(22.1%）。内分泌irAEs中甲状腺功能减退最常见(16.8%）,肾上腺皮质功能减退(2.1%）和垂体炎(1.1%）少见。多数irAEs发生于免疫治疗初期,78.2%发生于12周内。过敏反应、皮肤irAEs最早发生,中位发生时间分别为2周(范围：0.9～3.1周）和3.8周(范围：0.9～17.9周）,内分泌irAEs中位发生时间为6.9周(范围：3.0～52.1周）。多因素分析显示,女性(OR=5.197, 95%CI：1.166～23.154, P=0.031)和微卫星高度不稳定(microsatellite instability-high,MSI-H） (OR=35.048, 95%CI：2.756～445.787, P=0.006)是内分泌irAEs发生风险增加的独立危险因素,免疫治疗联合化学药物治疗(OR=0.107, 95%CI：0.021～0.412, P=0.001）是内分泌irAEs的独立保护性因素。结论在消化系统恶性肿瘤中应用ICIs具有较好的安全性。女性和MSI-H患者出现内分泌irAEs风险增加,联合化学药物治疗可能降低内分泌irAEs发生风险。     

社区传染性疾病技能培训问题调查

背景 社区卫生服务机构作为传染病防控工作的最基层单位,是传染病防治的前沿阵地和重要关口,基层医务工作者承担着辖区内疫情监测、预防接种、健康宣传及协助疾控部门调查处置暴发疫情和突发公共卫生事件等职责,在疾病群防群控、易感人群保护、传染源控制及健康宣教等方面发挥着积极作用,同时对有效防控传染病发挥关键作用。目的 了解基层医务工作者社区传染病的诊治能力,分析存在的问题和薄弱方面,有针对性地设计及开展传染病相关系列培训,提高基层传染病防控能力。方法 2021年11月—2022年3月以香港大学深圳医院全科医学科在2021年11月举办的国家级社区传染性疾病继续教育会议的所有参会者为研究对象。会前、会后通过问卷星二维码向参会者发放调查问卷,会前问卷内容包括参会者人口学特征,工作后是否参加过社区传染病培训,社区传染病诊治开展情况,社区传染病防治的主观态度（是否愿意管理社区传染病、对自己传染病诊治能力满意度）,传染病防治专业知识及会议内容相关知识,对慢性乙型肝炎的态度。会后问卷内容主要为会议内容相关知识、对慢性乙型肝炎的态度以及对本次线上会议满意度调查。会前共有301名基层医务工作者完成调查问卷,会前及...     

血浆TPO水平变化与血小板减少疾病的关系

目的:探讨血浆血小板生成素(Thrombopoietin,TPO)水平变化与血小板减少疾病的关系。方法:采用多抗夹心酶联免疫吸附法对68例各种不同原因致血小板减少患者通过应用白介素-11(rhIL-11)来动态检测TPO水平,rhIL-11剂量为25μg/(kg.d),皮下注射,连用10天。结果:(1)急性白血病(Acute leukemia,AL)化疗后血小板减少患者TPO水平低于正常对照组;再生障碍性贫血(Aplastic anemia,AA)及骨髓增生异常综合征(Myelodysplastic syndrome,MDS)患者TPO水平高于正常对照组;原发性血小板减少性紫癜(Idiopathic thrombocytopenic purpura,ITP)及肝硬化(Liver cirrhosis)患者TPO水平与正常对照组无明显差异。而其中的白血病化疗后血小板减少患者和AA患者的骨髓巨核细胞数较TPO正常组显著降低。(2)上述疾病患者用rhIL-11有效者TPO水平趋于正常,无效或疗效欠佳者,则TPO无变化。有效者TPO水平与血小板计数呈负相关。结论:血浆TPO检测,有助于临床鉴别各种血小板减少疾病的病因,对血小板减少患者合理应用rhIL-11提供理论的依据。     

抗早孕因子单克隆抗体的制备与鉴定

目的建立分泌抗EPF(Early pregnancy factor,早孕因子)单克隆抗体的杂交瘤细胞株,纯化单抗并鉴定.方法用本实验室已纯化的早孕和肿瘤源性EPF作为抗原刺激Balb/c小鼠,用免疫后的小鼠脾细胞与同系小鼠骨髓瘤细胞(NS-1)融合,经4次克隆化,获得可稳定分泌抗EPF单克隆抗体的细胞株,注入Balb/c小鼠腹腔制备腹水型单抗,Protein-A亲和层析纯化,SDS电泳和Western-blot等方法分析纯化结果.结果融合后获得一株稳定分泌抗EPF抗体的细胞株(C3D11),克隆化后,获得稳定分泌抗EPF单克隆抗体的细胞株,将增殖后的细胞注射Balb/c小鼠腹腔获得腹水型单抗,以亲和层析法纯化,SDS-PAGE分析显示纯化后去掉了大部分杂蛋白,免疫印迹分析抗体纯度较高,与抗原匹配性良好.结论本研究制备的EPF单克隆抗体为特异性抗EPF抗体.     

Increased mast cell density during the infection with velogenic Newcastle disease virus in chickens

In addition to their well-characterized role in allergic inflammation, recent data confirm that mast cells play a more extensive role in a variety of viral infections. The contribution of mast cells to Newcastle disease pathogenesis has not been investigated. We evaluated mast cell activity after Newcastle disease virus (NDV) infection in specific pathogen free chickens using cytochemical and immunocytochemical analyses. The results were as follows. Severe tissue damage was observed in the proventriculus, duodenum, jejunum and caecal tonsil, and NDV antigens were detected and presented extensively in these tissues. Second, in the NDV-infected group, the mast cell population was increased markedly in the proventriculus, duodenum, jejunum and caecal tonsil at 24, 48, 72 and 96 h after infection (P<0.01). However, very few mast cells were observed in those same tissues in the control. More intriguingly, the greatest number of mast cells was found in the proventriculus, which also showed the greatest level of NDV antigens. Third, the content of tryptase was significantly higher (P<0.01) in the NDV-infected group compared with the control from 24 to 96 h post infection). Furthermore, as an important protease released by mast cells, tryptase had a positive correlation with mast cell distribution. These data indicated that mast cells were involved in the response to NDV. Our results also suggested that the broad range of mast cell mediators might have a role in the pathology of Newcastle disease.     

正常人参数性数字n-back工作记忆任务的去激活网络:fMRI研究

目的:探讨工作记忆任务诱发去激活(Task induced deactivation,TID)脑区及其意义。方法:正常受试者35名,采用参数性数字n-back任务(n为1、2、3)行fMRI,0back作为对照任务。根据受试者在实验过程中3back任务的行为学表现,将准确率为≥85%的受试者纳入高执行表现正常受试者(High performing normal subjects,HPNS)组。采用SPM2软件进行功能数据预处理、统计分析和结果显示。结果:HPNS中TID脑区包括:前额叶皮层内侧部(medialprefrontal cortex,MPFC);扣带;右侧额下回(BA47);双侧颞叶多个脑区。在2back负载水平之内,随着负载增加,TID脑区去激活程度增加,但在2back负载之后,大多TID脑区的去激活呈平台期表现。结论:TID网络的存在对WM任务的正确执行是必须的。     

广州地区围产儿脏器重量及大小测量的研究

目的　探讨广州地区围产儿脏器重量及大小的发育规律 .方法　选择 6 2 5例胎龄准确的单胎 ,除外明显浸软、IUGR、水肿儿、巨大胎、有胸腹水者 ,新生儿除外先天性心脏病及有明显疾病的脏器 .根据胎龄分为 6组 ,分别测量围产儿体重、身长和各脏器重量、长度 .进行统计分析 .结果　胰腺、肺发育最早 ,肾脏与肺发育最快 ,出生后脑增长最少而胰腺增长最快 ,肠变异最大等规律 .结论　围产儿脏器资料用于围产儿病理研究有一定意义     

Springer Link及其收录的医学期刊分析

目的：向图书馆员和用户介绍Springer Link，对其收录的医学期刊进行深入分析，使该数据库得到更好的利用。方法利用《外国报刊目录》和美国《医学索引》(IM)的《引用期刊一览表》等对Springer Link收录的英文医学期刊从权威性、出版地分布、学科分布和收藏年限等方面进行考查。结果86％的期刊被IM引用，欧洲——尤其是德国的期刊较多，医学各学科都有相应的期刊被收录，但数量分布不均，有所偏重，72．7％的期刊可以保证至少近5年或自创刊以来的文献。结论Springer Link所提供的全文医学期刊服务质量较上乘，并有自己的特色。     

“Smart” Materials for Biosensing Devices: Cell-Mimicking Supramolecular Assemblies and Colorimetric Detection of Pathogenic Agents

Mimicking cell membrane and the biomolecular recognition associated with membranes represents a great technical challenge, yet it has opened doors to innovative diagnostic and therapeutic methods. Our work has focused on design and synthesis of a class of smart materials exploiting biological principals for use in biosensors: these materials are functional polymeric assemblies that mimic the cell membrane and conveniently report the presence of pathogens with a color change. Biologically active cell membrane components are incorporated into conjugated polymers with desirable optical properties and the binding of the target molecules onto the material triggers conformational and electronic shifts that are reflected in a chromatic change (a so-called biochromic shift) that is conveniently observed and recorded. Langmuir–Blodgett thin films and vesicle bilayers provide ideal configurations for precise delivery of the biological binding entity to the sensing interface, and for control of molecular orientation for effective biomolecular interaction. Polydiacetylenic membrane-mimicking materials containing cell surface receptor gangliosides and sialic acid residues, respectively were formulated into these architectures and used for colorimetric detection of bacterial toxins and influenza virus. One advantage of these biochromic conjugated polymer (BCP) sensors is that their molecular recognition and signal transduction functionalities are resident in a single functional unit, making them amenable to convenient microfabrication and use.