基于化学空间和分子对接探讨人参在治疗骨关节炎中发挥抗炎镇痛作用的可行性

目的:探讨人参在治疗骨关节炎(OA)中发挥抗炎镇痛作用的可行性.方法:从中药系统药理数据库及分析平台(TCMSP)中筛选人参中口服生物利用度≥30％和类药性≥0.18的成分,从活性化合物专家网站中检索OA疼痛密切相关白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的抑制剂,在D...     

肿瘤坏死因子样微弱凋亡诱导因子对骨关节炎软骨细胞作用实验研究

目的研究肿瘤坏死因子样微弱凋亡诱导因子（TWEAK）对体外培养骨关节炎（OA）软骨细胞的作用,同时探讨炎性细胞因子白细胞介素-1β（IL-1β）和肿瘤坏死因子α（TNF-α）与TWEAK之间的关系。方法体外培养OA患者原代软骨细胞,分别用TWEAK（75ng/mL）,TWEAK（75ng/mL）和IL-1β（5ng/mL）,TWEAK（75ng/mL）和TNF-α（5ng/mL）作用细胞48h,MTT检测细胞因子对软骨细胞的增殖作用影响;ELISA检测细胞培养上清液中MMP-13、IL-6和Fas的分泌表达。结果 MTT结果表明细胞因子刺激软骨细胞后对细胞增殖无明显影响。TWEAK和IL-1β组诱导MMP-13表达增加（P〈0.05）;TWEAK和IL-1β组,TWEAK和TNF-α组均诱导IL-6表达增加（P〈0.05）。3组Fas分泌表达差异无统计学意义（P〉0.05）。结论 IL-1β与TWEAK,TNF-α与TWEAK分别诱导OA软骨细胞MMP-13和IL-6表达增加,可能参与关节软骨损伤和OA的病程发展。     

右美托咪啶全凭静脉麻醉对老年上腹部手术患者围术期炎性细胞因子的影响

盐酸右美托咪啶（DEX）是新型高选择性以肾上腺索能受体激动剂,具有镇静、抗焦虑、镇痛、稳定血流动力学、呼吸抑制轻等特点,目前已在临床实践中成功应用。本研究拟将DEX作用于老年上腹部手术患者,观察测定炎性因子白细胞介素-α（IL-6）、白细胞介素-β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）等多项指标,探讨其是否具有抑制炎性因子,降低应激反应的作用,并将结果与丙泊酚组的效果进行比较。     

上调microRNA-543表达对大鼠骨关节炎软骨细胞的保护作用

目的：探讨微小RNA-543（microRNA-543, miRNA-5431/miR-543）对大鼠骨关节炎（osteoarthritis, OA）软骨细胞的可能作用及潜在机制。方法：采用膝关节内侧副韧带切断法建立大鼠OA模型,real-time PCR法检测OA模型大鼠软骨组织与正常大鼠软骨组织miR-543的表达差异。体外分离正常膝关节软骨细胞,IL-1β（10 ng/L）共培养24 h模拟体外OA状态,以miR-543 mimics转染软骨细胞,采用MTT、real-time PCR及Western 印迹法观察miR-543过表达对IL-1β诱导下软骨细胞增殖及凋亡相关鼠双微体基因4（murine double minute 4, MDM4）、蛋白激酶B1（protein kinase B1, PKB1/Akt1）、B细胞淋巴瘤/白血病-2（B cell lymphoma/leukemia-2, Bcl-2）和炎症因子肿瘤坏死因子-α（tumor necrosis factor-α, TNF-α）、白细胞介素-6（interleukin-6, IL-6）表达的影响。结果：OA模型大鼠软骨组织较正常大鼠软骨组织miR-543表达明显下调（P<0.05）。与正常软骨细胞相比,IL-1β诱导后软骨细胞存活率降低（P<0.05）,MDM4表达上调,Akt1、Bcl-2表达下调（P<0.05）,炎症因子TNF-α、IL-6释放增加（P<0.05）;转染miR-543 mimics后,IL-1β诱导的软骨细胞存活率明显升高（P<0.05）,MDM4表达下调,Akt1、Bcl-2表达上调（P<0.05）,炎症相关因子TNF-α、IL-6 mRNA表达降低（P<0.05）。结论：OA大鼠软骨组织miR-543表达较正常软骨组织明显降低;上调miR-543表达体外可促进软骨细胞增殖,拮抗IL-1β诱导的软骨细胞损伤,可能与其下调MDM4表达、上调Akt1、Bcl-2表达,减少炎症因子（TNF-α、IL-6）有关。     

阿司匹林对阿尔茨海默病患者脑脊液中细胞因子表达的影响

目的探讨阿尔茨海默病（Alzheimer’s disease，AD）患者脑脊液中白细胞介素-15（IL-15）、生长转化因子β1（TGF-β1）的表达情况及阿司匹林对白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、IL-15和TGF-β1的影响。方法应用ELISA反应体系分别检测AD患者使用阿司匹林前后及对照组脑脊液中的IL-6、IL-15、TGF-β1和TNF-α表达的水平。结果①AD患者IL-15、TGF-β1表达明显升高，与对照组比较均有统计学意义（均P〈0．01）；②阿司匹林可以降低脑脊液中IL-6、IL-15、TGF-β1、TNF-α水平，与治疗前比较均有统计学意义（均P〈0．05）。结论IL-15、TGF-β1参与AD疾病的发生过程；阿司匹林可能通过抑制炎性细胞因子分泌而对AD患者发挥治疗作用。     

心理干预联合硬膜外分娩镇痛对产妇IL-2、IL-6、TNF-α的影响

[目的]探讨心理干预联合硬膜外分娩镇痛对产妇血清白介素-2（IL-2）、白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）的影响.[方法] 选择160 例无相关禁忌的初产妇,ASAⅠ～Ⅱ级,随机分成两组,每组80例,R组为硬膜外分娩镇痛,P组为硬膜外分娩镇痛联合心理干预（呼吸训练法和渐进性肌肉放松法）,比较两组VAS评分、血浆IL-2、IL-6、TNF-α水平.[结果] 镇痛效果（VAS评分）P组明显低于R组 P组产妇胎儿娩出时（T3）、产后24h（T4）与R组比较,IL-6、TNF-α水平有明显的降低,IL-2水平明显升高,差异具有显著性（P〈0.05）.[结论] 心理干预联合硬膜外分娩镇更有效的减轻产时疼痛强度,降低炎性反应,减轻产后免疫功能抑制.     

急性脑梗死患者血清同型半胱氨酸与炎性反应因子IL-1β、TNF—α的临床研究

目的通过检测急性脑梗死患者同型半胱氨酸、白细胞介素-1β（IL-18）和肿瘤坏死因子-α（TNF—α）的血清水平值,探讨同型半胱氨酸、IL-1β、TNF-α在急性脑梗死患者中的发病机制和作用,研究IL-1β、TNF-α与急性脑梗死患者急性发病后的同型半胱氨酸的关系。方法实验分为2组：健康组（N组）与急性脑梗死组。采用酶联免疫吸附试验（ELISA）检测急性脑梗死患者血清IL-1β、TNF-α浓度值,荧光标记免疫法检测血清同型半胱氨酸水平。结果同型半胱氨酸、IL-1β和TNF-α在急性脑梗死患者中明显高于健康对照组,且患者血浆IL-1β与TNF-α呈显著正相关,差异有统计学意义（P〈0．05）;健康对照纽IL-1β与TNF-α无显著相关性（P〉0．05）。急性脑梗死组IL-1β、TNF-α与同型半胱氨酸具有正相关性（P〈0．05）。结论同型半胱氨酸参与了急性脑梗死发生发展的炎性反应过程,急性发病后同型半胱氨酸的浓度增高可能是炎性反应的促发因素。     

血清炎症因子与膝骨关节炎MRI影像学特征有一定的相关性

  目的  探讨血清炎症因子与膝骨关节炎（KOA）MRI影像学特征的相关性。  方法  选取2020年1月~2021年5月于我院收治的膝骨关节炎患者120例作为研究组,另选取同期健康体检人员90例作为对照组。根据是否有滑膜炎将研究组分为Ⅰ组（滑膜炎,n=71）和Ⅱ组（无滑膜炎,n=49）。比较所有患者MRI影像学表现和血清炎症因子[肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）]水平,并对KOA患者MRI影像学特征与血清炎症因子相关性进行分析。  结果  Ⅰ组所有患者均存在软骨病变,且66.20%为2级软骨病变,而Ⅱ组患者有5例无软骨病变,病变患者59.18%为1级。Ⅰ组软骨厚度低于Ⅱ组（P < 0.05）。血清中IL-1β、IL-6和TNF-α表达水平对照组 < Ⅱ组 < Ⅰ组（P < 0.05）,IL-10表达水平Ⅱ组 < Ⅰ组 < 对照组（P < 0.05）;Ⅰ组血清炎性细胞因子中IL-1β、IL-6和TNF-α与MRI软骨分级呈正相关关系（r=0.387、0.289、0.426,P < 0.05）,IL-10无相关性（P > 0.05）;Ⅱ组血清炎性细胞因子中仅IL-1β与MRI软骨分级呈正相关关系（r=0.509,P < 0.05）,IL-6、IL-10和TNF-α均无相关性（P > 0.05）;KOA合并滑膜炎患者MRI滑膜厚度与血清炎性细胞因子中IL-1β、IL-6和TNF-α呈正相关（r=0.497、0.425、0.506,P < 0.05）;MRI软骨厚度与血清炎性细胞因子中IL-1β和TNF-α呈负相关（r=-0.503、-0.313,P < 0.05）。  结论  KOA患者MRI可见明显异常,与血清炎性因子有一定的相关性,膝关节影像学特征与血清炎性因子水平结合可对KOA临床诊断及治疗提供指导价值。      

抗β2GPI/β2GPI复合物激活THP-1细胞表达炎性相关因子

目的探讨抗β2糖蛋白I(抗β2GPI)自身抗体与β2糖蛋白I(β2GPI)复合物刺激单核细胞株THP-1表达炎性因子IL-6、IL-8、TNF-α及可能机制。方法用荧光定量PCR法检测抗β2GPI/β2GPI复合物刺激THP-1细胞不同时间(0.5、1、1.5、2、6 h)后IL-6、IL-8、TNF-αmRNA表达,用免疫荧光染色法及western blot观察THP-1细胞表达IL-6、IL-8、TNF-α蛋白的情况。荧光定量PCR及western blot观察Toll样受体4(TLR4)途径抑制物(TAK-242)干预抗β2GPI/β2GPI复合物对THP-1细胞的刺激作用。结果抗β2GPI/β2GPI复合物(100μg/mL)刺激THP-1细胞不同时间,可使细胞表达IL-6、IL-8及TNF-αmRNA水平逐渐上升,于刺激2 h时IL-6、IL-8及TNF-α达到峰值(P<0.01),免疫荧光染色及western blot证实细胞表达IL-6、IL-8及TNF-α蛋白水平也明显增加。TAK-242(5μmol/L)可显著抑制抗β2GPI/β2GPI复合物诱导的细胞IL-6、IL-8及TNF-α表达。结论抗β2GPI/β2GPI复合物通过TLR4途径,激活THP-1细胞表达炎性细胞因子IL-6、IL-8及TNF-α,参与抗磷脂综合征的病理机制。     

重症急性胰腺炎并发肺损伤促/抗炎症因子的变化及大黄附子汤的干预研究

目的观察大黄附子汤对重症急性胰腺炎并肺损伤（SAP-ALI）时血清促/抗炎症因子的影响。方法健康长白猪,体重25～30kg,13头,随机分成三组：对照组（n=4）、重症急性胰腺炎肺损伤组（模型组,n=4）、大黄附子汤治疗组（治疗组,n=5）。其中模型组采用主胰管内逆行注入4%牛磺胆酸钠（1ml/kg）诱导SAP-ALI模型。三组均于术后即刻、术后6h、12h、24h、48h、72h取血,ELISA法动态检测血清中促炎因子（TNF-α和IL-1β）、抗炎因子（IL-4）浓度变化,同时动态比浊法测定血清内毒素（LPS）含量。术后72h处死动物,计算肺组织湿/干重比,观察胰腺与肺病理形态学变化。结果模型组6～72h血清淀粉酶、内毒素、TNF-α、IL-1β浓度及肺病理组织学评分均较对照组明显升高（P〈0.05）,IL-4浓度在术后24h开始较对照组逐渐升高（P〈0.05）。治疗组各时间点血清淀粉酶、内毒素、TNF-α、IL-1β浓度均较模型组明显下降（P〈0.05）,但血清IL-4浓度于术后12h出现明显升高,48h达到峰值。结论促炎因子（TNF-α、IL-1β）、抗炎因子（IL-4）及内毒素等共同参与了SAP-ALI的发病过程。大黄附子汤通过降低血清LPS水平,进而下调血清TNF-α及IL-1β表达,上调IL-4表达,减轻SAP-ALI的程度。     

创伤高血糖与感染和MODS早期诊断和干预

本文详细介绍了创伤后血糖应激适度理论,以及高血糖与感染和多器官功能不全综合征的关系;提出涉及胰岛B细胞功能不全的MODS实验诊断新方案和极化液个体化干预新措施,可早期发现创伤MODS、降低感染率及MODS发生率和病死率。     

腹膜后纤维化与肾积水发生关系的临床研究

目的：探讨腹膜后纤维化（RPF）导致肾积水的原因及诊治经验。方法：回顾分析2004年1月—2010年12月24例腹膜后纤维化致肾积水患者的诊治资料。结果：（1）RPF患者常见首发症状为腰背痛或腹痛（69.2%）;（2）红细胞沉降率（ESR）增快和血清IgG4升高最常见。超声检查仅提示上尿路积水。RPF的静脉肾盂造影（IVP）和CT尿路成像（CTU）表现具有特征性。IVP肾盂输尿管显影不良时,CTU能较清晰的显示上尿路影像。CT扫描发现腹膜后软组织肿块9例（37.5%）,优于超声检查;（3）输尿管松解和腹腔化手术治疗22例;行肾切除术1例;行输尿管置双J管术1例。最终确诊为继发性RPF8例,其中4例为术前诊断,3例为术中腹膜后软组织肿块冷冻活检证实,1例为术后病理证实;（4）特发性RPF手术后肾积水均获长期缓解,而继发性RPF的预后取决于原发疾病及其治疗方案。结论：影像学检查是诊断RPF的重要手段,CTU优于超声检查和IVP。输尿管松解和腹腔化手术可以使特发性RPF输尿管梗阻得到长期的缓解,术中对肿块进行冷冻活检有助于鉴别特发性和继发性RPF,及时调整治疗方案。     

Migraine and genetic and acquired vasculopathies

It is remarkable that migraine is a prominent part of the phenotype of several genetic vasculopathies, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), retinal vasculopathy with cerebral leukodystrophy (RVCL) and hereditary infantile hemiparessis, retinal arteriolar tortuosity and leukoencephalopahty (HIHRATL). The mechanisms by which these genetic vasculopathies give rise to migraine are still unclear. Common genetic susceptibility, increased susceptibility to cortical spreading depression (CSD) and vascular endothelial dysfunction are among the possible explanations. The relation between migraine and acquired vasculopathies such as ischaemic stroke and coronary heart disease has long been established, further supporting a role of the (cerebral) blood vessels in migraine. This review focuses on genetic and acquired vasculopathies associated with migraine. We speculate how genetic and acquired vascular mechanisms might be involved in migraine.     

Fibrinogen and fibrin structure and functions

Fibrinogen molecules are comprised of two sets of disulfide-bridged Aalpha-, Bbeta-, and gamma-chains. Each molecule contains two outer D domains connected to a central E domain by a coiled-coil segment. Fibrin is formed after thrombin cleavage of fibrinopeptide A (FPA) from fibrinogen Aalpha-chains, thus initiating fibrin polymerization. Double-stranded fibrils form through end-to-middle domain (D:E) associations, and concomitant lateral fibril associations and branching create a clot network. Fibrin assembly facilitates intermolecular antiparallel C-terminal alignment of gamma-chain pairs, which are then covalently 'cross-linked' by factor XIII ('plasma protransglutaminase') or XIIIa to form 'gamma-dimers'. In addition to its primary role of providing scaffolding for the intravascular thrombus and also accounting for important clot viscoelastic properties, fibrin(ogen) participates in other biologic functions involving unique binding sites, some of which become exposed as a consequence of fibrin formation. This review provides details about fibrinogen and fibrin structure, and correlates this information with biological functions that include: (i) suppression of plasma factor XIII-mediated cross-linking activity in blood by binding the factor XIII A2B2 complex. (ii) Non-substrate thrombin binding to fibrin, termed antithrombin I (AT-I), which down-regulates thrombin generation in clotting blood. (iii) Tissue-type plasminogen activator (tPA)-stimulated plasminogen activation by fibrin that results from formation of a ternary tPA-plasminogen-fibrin complex. Binding of inhibitors such as alpha2-antiplasmin, plasminogen activator inhibitor-2, lipoprotein(a), or histidine-rich glycoprotein, impairs plasminogen activation. (iv) Enhanced interactions with the extracellular matrix by binding of fibronectin to fibrin(ogen). (v) Molecular and cellular interactions of fibrin beta15-42. This sequence binds to heparin and mediates platelet and endothelial cell spreading, fibroblast proliferation, and capillary tube formation. Interactions between beta15-42 and vascular endothelial (VE)-cadherin, an endothelial cell receptor, also promote capillary tube formation and angiogenesis. These activities are enhanced by binding of growth factors like fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), and cytokines like interleukin (IL)-1. (vi) Fibrinogen binding to the platelet alpha(IIb)beta3 receptor, which is important for incorporating platelets into a developing thrombus. (vii) Leukocyte binding to fibrin(ogen) via integrin alpha(M)beta2 (Mac-1), which is a high affinity receptor on stimulated monocytes and neutrophils.     

Telemedicine and teleradiology technologies and applications

Summary. Telemedicine and teleradiology hold the key for improving future health care delivery. In this paper we first review current communication and computer technologies used in telemedicine and teleradiology. Five examples in teleradiology applications are given including hospital-integrated picture archiving and communication systems, tele-neuro-imaging, telemammography, university consortium teleradiology service, and teleradiology for second opinion. Parameters important to teleradiology applications like costs, image quality, system reliability, and turn around time are considered. Data security is discussed, including patient confidentiality and image authenticity-which will be a major issue in future teleradiology applications.     

探讨儿童慢性顽固性咳嗽与支原体感染的关系及临床治疗观察

目的探讨儿童慢性顽固性咳嗽与肺炎支原体（MP）感染的关系及临床疗效观察。方法采用回顾性研究方法对于现将2005年3月至2008年3月在我院的55例确诊慢性顽固性咳嗽患儿,主要表现为肺炎支原体感染为临床特点进行分析,并进一步临床治疗研究。结果①临床特点：在55例确诊慢性咳嗽的患儿中,以慢性顽固性咳嗽为主要症状。58％（32／55）的病例无肺部体征;②外周血：85％（47／55）的病例外周血变化不大,WBC（4—10）×10 9／L之间,嗜酸性粒细胞增多;③特别检查：47．27％（26／55）肺炎支原体IgM（MP—IgM）抗体阳性,83．64％（46／55）PeR技术检测肺炎支原体特异性DNA;④X光报告为多种形式。结论肺炎支原体（MP）感染是引起儿童慢性顽固性咳嗽的病因之一,对儿童慢性咳嗽,特别是顽固性咳嗽的诊治中应更加重视。     

Physician and Nurse Practitioner Teamwork and Job Satisfaction: Gender and Profession

Designing interprofessional primary care teams composed of physicians and nurse practitioners (NPs) is a national priority. We assessed how profession and gender affect teamwork and job satisfaction among primary care physicians and NPs by using survey data from 186 physicians and 398 NPs practicing in New York State. Our regression models show profession (NP vs physician) moderates the associations of gender with teamwork and job satisfaction. Among NPs, men had higher job satisfaction than women. Among physicians, women had higher job satisfaction than men. Our results can benefit interprofessional primary care teams to optimize their professional and gender mix.     

VEGF和NSE在良恶性嗜铬细胞瘤中的表达及意义

目的探讨肿瘤标志物血管内皮生长因子（VEGF）和神经元特异性烯醇化酶（NSE）在良、恶性嗜铬细胞瘤组织中的表达,分析其可能的临床价值及病理学意义,为临床鉴别良、恶性嗜铬细胞瘤提供辅助依据。方法应用免疫组化（SP法）检测16例恶性嗜铬细胞瘤、18例良性嗜铬细胞瘤及17例正常肾上腺髓质组织中细胞因子VEGF和NSE表达情况,显微镜下判断组织切片的染色结果。结果①恶性嗜铬细胞瘤VEGF表达明显强于正常肾上腺髓质和良性嗜铬细胞瘤（P〈0.01）。良性肿瘤和正常肾上腺髓质的VEGF表达差异无统计学意义（P〉0.05）。恶性嗜铬细胞瘤强阳性率明显高于良性嗜铬细胞瘤（P〈0.01）。②良、恶性嗜铬细胞瘤NSE表达差异有统计学意义（P〈0.05）,良性嗜铬细胞瘤NSE的表达高于正常肾上腺髓质的NSE表达（P〈0.05）。恶性嗜铬细胞瘤强阳性率高于良性嗜铬细胞瘤（P〈0.05）。③VEGF和NSE共同阳性表达在良、恶性嗜铬细胞瘤之间差异有统计学意义（P=〈0.01）。结论临床上检测VEGF和NSE可能为鉴别良、恶性嗜铬细胞瘤提供辅助依据,共同检测VEGF和NSE可能提高良、恶性嗜铬细胞瘤鉴别的敏感性。     

Acetaminophen and acetylcysteine dose and duration: Past,present and future

Abstract

Acetylcysteine has been utilized successfully in the treatment of acetaminophen overdose since the 1970s. Although prospective trials as to efficacy and safety of acetylcysteine were conducted, there were no randomized controlled trials. This commentary addresses the reasons for this, and the background to choice of dose of acetylcysteine utilized in the oral and IV dosing regimens. Nomograms to predict possible hepatotoxicity based upon time of ingestion of acetaminophen were developed from a relatively arbitrary definition of toxicity as an aspartate aminotransferase/alanine aminotransferase (ALT/AST) greater than 1000 IU/L. While these have proved generally useful, patients still continue to develop hepatic damage after acetaminophen overdose, particularly if they present late after ingestion. The optimum management of these patients remains unclear, and one area of uncertainty is the dose and duration of acetylcysteine in various circumstances. This article discusses the issues that need to be elucidated to better target changes in acetylcysteine dose. The potential for measurements of other markers to improve treatment selection is the subject of further research.