clinical and therapeutical implication
肠外肠内营养指南汇总
附录1肠外肠内营养学临床指南中华医学会肠外肠内营养学分会（2006 版）第一章制定指南的“指南”引言制定指南的初级阶段中华医学会肠外肠内营养学分会（Chinese Society of Parenteral and Enteral Nutrition, CSPEN）于2004年12月在京成立。
作为一个多学科学术组织，CSPEN的愿景（vision）是倡导循证营养支持的实践，促进我国肠外肠内营养的合理应用，为患者提供安全、有效和具有良好效价比的营养治疗。
编写、制定与推广临床指南是实现上述目标的重要途径。
指南定义为：按照循证医学原则，以当前最佳证据为依据，按照系统和规范方法，在多学科专家、各级医院的临床医师和护理人员合作下达成的共识。
本指南的宗旨是为临床医师、护理工作者、营养师、药剂师和患者在特定临床条件下，制定和/或接受肠外肠内营养支持方案提供帮助，并为卫生政策的制定者提供决策依据。
2005年1月- 9月，是我们分会制定指南的初级阶段。
CSPEN常委们在中华医学会的直接指导下，组织了我国肠外肠内营养学工作者及儿科、外科、内科等多学科专家成立了第一届《肠外肠内营养指南》编写委员会。
按照循证医学原则，经过参比国内国外的临床研究报告，制定的肠外肠内营养支持的适应症指南。
在2005年9月在北京召开的的“第一届全国临床营养周”大会上公开征求意见后，又做了大范围的修正和大范围的补充，于当年12月完成了第2005版《肠外肠内营养学临床―指南‖系列一：住院患者肠外营养支持的适应证》。
虽然该指南范围窄，仅是住院患者肠外肠内营养支持的适应证的内容，但仍然受到业者的重视。
已经先后在《中国临床营养杂志》、《中华医学杂志》和《中华外科杂志》等三本核心期刊杂志登载。
发表后受到国内同行的关注，也为2006年完善方法学和扩大内容打下了基础。
一、2006年版指南制订过程在2005年适应症指南的基础上，2006年1月CSPEN《肠外和肠内营养临床指南》编委会和支持小组就启动了文献复习工作，在不同场合广泛听取和收集国内同行意见和建议。
贝伐珠单抗联合奥沙利铂和卡培他滨在晚期直肠癌治疗中的效果分析
药物与临床China &Foreign Medical Treatment 中外医疗贝伐珠单抗联合奥沙利铂和卡培他滨在晚期直肠癌治疗中的效果分析石贤清溧阳市人民医院肿瘤内科，江苏常州 213300［摘要］ 目的 分析贝伐珠单抗+奥沙利铂+卡培他滨联合用药方式对于直肠癌晚期患者的临床疗效。
方法 选取2019年1月—2022年1月溧阳市人民医院收治的40例直肠癌晚期患者为研究对象，以随机数表法分为对照组和观察组，每组20例。
对照组使用奥沙利铂+卡培他滨方案，观察组使用奥沙利铂+贝伐珠单抗+卡培他滨方案，对比两组患者的临床效果。
结果 两组各项不良反应总发生率对比，差异无统计学意义（P >0.05）。
观察组实际治疗有效率略高于对照组，但差异无统计学意义（P >0.05）。
观察组患者的血清癌胚抗原水平为（10.81±1.04）ng/mL 低于对照组的（14.96±3.85）ng/mL ，差异有统计学意义（t =4.654，P <0.05）。
观察组CD4+、自然杀伤细胞及CD4+/CD8+水平高于对照组，而CD8+低于对照组，差异有统计学意义（P <0.05）。
结论 将卡培他滨片+奥沙利铂+贝伐珠单作为晚期直肠癌的治疗方案，效果显著。
［关键词］ 贝伐珠单抗；奥沙利铂；卡培他滨；直肠癌晚期［中图分类号］ R735.37 ［文献标识码］ A ［文章编号］ 1674-0742（2023）11(b)-0125-04Effectiveness Analysis of Bevacizumab Combined with Oxaliplatin and Capecitabine in the Treatment of Advanced Rectal CancerSHI XianqingDepartment of Medical Oncology, Liyang People's Hospital, Changzhou, Jiangsu Province, 213300 China[Abstract] Objective To analyze the clinical therapeutic efficacy of the combination of bevacizumab + oxaliplatin + capecitabine for patients with advanced rectal cancer. Methods 40 patients with advanced rectal cancer admitted to Liyang People's Hospital from January 2019 to January 2022 were selected as the study objects. They were randomly divided into a control group and an observation group by the method of chaotic number table, with 20 cases in each group. The control group centered on oxaliplatin + capecitabine treatment program, while the observation group inter⁃vened with the help of oxaliplatin + bevacizumab + capecitabine program, and the clinical effects of the two groups were compared. Results There was no statistically significant difference in the incidence of adverse reactions between the control group and the observation group (P >0.05). The actual treatment efficiency of the observation group was bet⁃ter than that of the control group, but the difference was not statistically significant (P>0.05). The carcinoembryonic antigen level of patients in the observation group was (10.81±1.04) ng/mL, which was lower than (14.96±3.85) ng/mL of the control group, and the difference was statistically significant (t =4.654, P <0.05). The levels of CD4+, natural kill⁃ing cells, and CD4+/CD8+ indexes in the observation group were higher than those in the control group, while CD8+ was lower than that in the control group, and the differences were statistically significant (P <0.05). Conclusion The ap⁃plication of capecitabine tablets + oxaliplatin + bevacizumab as an application program for the treatment of advanced rectal cancer is very effective.[Key words] Bevacizumab; Oxaliplatin; Capecitabine; Advanced rectal cancer直肠癌在临床中有较高的发病率，属于常见的恶性肿瘤，根据以往研究资料显示，直肠癌好发于DOI ：10.16662/ki.1674-0742.2023.32.125[作者简介] 石贤清（1984-），女，硕士，副主任医师，研究方向为胃肠道肿瘤、肺部肿瘤。
clinical investigation plan
clinical investigation planClinical Investigation Plan (CIP)Introduction:The clinical investigation plan (CIP) is a crucial document that outlines the strategy and methodology for conducting clinical trials or studies. It serves as a roadmap for researchers and ensures that the investigation is conducted in an ethical, scientifically rigorous, and transparent manner. This comprehensive plan provides detailed information about the study design, subject selection, data collection, analysis, and reporting.Study Objectives:The CIP begins with a clear statement of the study objectives. These objectives should be specific, measurable, achievable, relevant, and time-bound (SMART). They should address the research question(s) or hypothesis being tested and outline the desired outcomes of the investigation.Background and Rationale:In this section of the CIP, the research context and rationale for conducting the study are provided. This includes a literature review summarizing relevant previous research, the current knowledge gap, and the potential benefits of the proposed investigation. The rationale should address the need for the study and highlight its potential contribution to scientific knowledge or clinical practice. Study Design:The CIP details the study design, which may be observational (e.g., cohort, case-control) or experimental (e.g., randomized controlledtrial). The rationale for choosing a particular design is explained, along with any potential limitations associated with the design choice. The study design section should also include information about the study duration, endpoints, and sample size estimation. Subject Selection:The CIP outlines the criteria for subject selection, ensuring that participants meet specific eligibility criteria. It describes the method of subject recruitment and provides details about the informed consent process, ensuring that participants understand the study purpose, procedures, and potential risks. The plan should include a description of any inclusion or exclusion criteria, as well as the process for randomization (if applicable) and blinding. Data Collection:This section of the CIP describes the data collection procedures, including the tools, instruments, or measurements to be used. It outlines the frequency and duration of assessments and clarifies who will collect the data and how it will be managed, stored, and protected to ensure patient confidentiality.Statistical Analysis:The CIP delineates the statistical methods that will be used to analyze the data. It includes a detailed description of the primary and secondary endpoints, as well as any planned subgroup analyses or exploratory endpoints. The plan should also address how missing data, outliers, or confounding factors will be handled. Safety and Ethical Considerations:The CIP emphasizes the safety of participants and outlines thesteps taken to monitor and manage adverse events. It includes details about the ethical principles, such as informed consent, privacy protection, and data confidentiality. The plan should also specify whether an independent data monitoring committee will be involved and describe its responsibilities.Timeline and Budget:The CIP provides a timeline for the entire investigation, including subject recruitment, data collection, analysis, and reporting. It also includes a budget estimate, covering both direct costs (e.g., personnel, supplies, equipment) and indirect costs (e.g., overhead, administrative fees).Conclusion:A well-written CIP is essential for ensuring that a clinical investigation is conducted efficiently, ethically, and with scientific rigor. It provides a detailed roadmap for researchers and serves as a reference document throughout the study. By addressing study objectives, design, subject selection, data collection, analysis, and ethical considerations, the CIP helps to ensure high-quality research and accurate reporting of study outcomes.。
临床药师参与1例地舒单抗治疗重症骨质疏松患者的药学监护
·药师实践·临床药师参与1例地舒单抗治疗重症骨质疏松患者的药学监护林燕 刘晓琰（上海交通大学医学院附属第九人民医院黄浦分院药剂科 上海 200011）摘要 1例73岁老年女性重症骨质疏松者行髋关节置换术后，采用地舒单抗抗骨质疏松，6 d后主诉下肢有抽搐感，复查血钙2.0 mmol/L。
临床药师结合患者症状和用药史，判断与地舒单抗注射液不良反应有关，及时调整医嘱，加用葡萄糖酸钙颗粒和骨化三醇胶丸促进钙的吸收，纠正低钙血症。
临床药师积极参与治疗方案的制定，提供全程化的药学服务，保证重症高危骨质疏松患者的治疗效果，保障患者用药安全，提高患者的预后和生活质量。
关键词 骨质疏松 地舒单抗 药学监护 临床药师中图分类号：R977.9; R589.9 文献标志码：B 文章编号：1006-1533(2024)05-0070-03引用本文林燕, 刘晓琰. 临床药师参与1例地舒单抗治疗重症骨质疏松患者的药学监护[J]. 上海医药, 2024, 45(5): 70-72.Clinical pharmacist participates in the pharmacological monitoring of a patient with severe osteoporosis treated with denosumabLIN Yan, LIU Xiaoyan(Department of Pharmacy, Huangpu Branch, Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China)ABSTRACT A 73 year old female patient with severe osteoporosis underwent hip arthroplasty and was then treated with denosumab for osteoporosis. After 6 days, the patient complained of convulsions in the lower limbs and her blood calcium content was 2.0 mmol/L after follow-up examination. The clinical pharmacists judged that this adverse reaction was associated with denosumab injection by considering her symptoms and medication history, and promptly adjusted the medical prescription, added calcium gluconate granules and osteotriol gel pills to promote calcium absorption, and her hypocalcaemia was finally corrected.Clinical pharmacists actively participate in the development of treatment plans and provide comprehensive pharmacy services to promote the therapeutic efficacy of patients with severe high-risk osteoporosis, ensure the safety of their medication, and improve their prognosis and quality of life.KEY WORDS osteoporosis; denosumab; pharmacological monitoring; clinical pharmacist近年来，骨质疏松症的发病率显著上升，根据世界卫生组织的统计，骨质疏松症的严重程度仅次于心血管疾病，已成为我国中老年人的一个重要健康问题。
脑小血管病患者轻度认知损害与高同型半胱氨酸的相关性研究进展
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赵瑞华教授临证治疗围绝经期失眠症的经验
２０２３年９月第１０卷第９期Ｓｅｐｔｅｍｂｅｒ．２０２３，Ｖｏｌ．１０，Ｎｏ．９世界睡眠医学杂志ＷｏｒｌｄＪｏｕｒｎａｌｏｆＳｌｅｅｐＭｅｄｉｃｉｎｅ２０４７ 基金项目：北京市西城区第二批中医药传承工程项目（２０１９）；第六批北京市级中医药专家学术经验继承项目（京中医科字〔２０２１〕１６０号）作者简介：李田田（１９８９ ０６—），女，硕士，主治医师，研究方向：中医妇科学，Ｅ ｍａｉｌ：８３６８５９３２６＠ｑｑ ｃｏｍ通信作者：赵瑞华（１９５９ ０８—），女，主任医师，博士，研究方向：中医妇科学，Ｅ ｍａｉｌ：ｚｈａｏｒｕｉｈｕａ＠ｇａｍｙｙ ｃｎ赵瑞华教授临证治疗围绝经期失眠症的经验李田田１ 赵瑞华２（１北京市回民医院妇科，北京，１０００５４；２中国中医科学院广安门医院妇科，北京，１０００５３）摘要 探析赵瑞华教授临证治疗围绝经期失眠症的经验。
赵师认为肾虚致阴阳失调为围绝经期失眠症发病之本，肝虚、肝郁为其主要因素，常兼营卫失和，临证治疗力主整体观念，天人合一，谨守病机，辨证施治，以燮理阴阳为主，注重调神摄眠及健康宣教。
关键词 围绝经期失眠症；燮理阴阳；经验；赵瑞华ＰｒｏｆｅｓｓｏｒＺｈａｏＲｕｉｈｕａ′ｓＥｘｐｅｒｉｅｎｃｅｉｎＣｌｉｎｉｃａｌＴｒｅａｔｍｅｎｔｏｆＰｅｒｉｍｅｎｏｐａｕｓａｌＩｎｓｏｍｎｉａＬＩＴｉａｎｔｉａｎ１，ＺＨＡＯＲｕｉｈｕａ２（１ＢｅｉｊｉｎｇＨｕｉｍｉｎｈｏｓｐｉｔａｌ，Ｂｅｉｊｉｎｇ１０００５４，Ｃｈｉｎａ；２Ｇｕａｎｇ′ａｎｍｅｎＨｏｓｐｉｔａｌ，ＣｈｉｎｅｓｅＡｃａｄｅｍｙｏｆｔｒａｄｉｔｉｏｎａｌＣｈｉｎｅｓｅｍｅｄｉｃｉｎｅ，Ｂｅｉｊｉｎｇ１０００５３，Ｃｈｉｎａ）Ａｂｓｔｒａｃｔ ＥｘｐｌｏｒｉｎｇＰｒｏｆｅｓｓｏｒＺｈａｏＲｕｉｈｕａ′ｓｅｘｐｅｒｉｅｎｃｅｉｎｃｌｉｎｉｃａｌｔｒｅａｔｍｅｎｔｏｆｐｅｒｉｍｅｎｏｐａｕｓａｌｉｎｓｏｍｎｉａ ＰｒｏｆｅｓｓｏｒＺｈａｏｂｅｌｉｅｖｅｓｔｈａｔｋｉｄｎｅｙｄｅｆｉｃｉｅｎｃｙｌｅａｄｉｎｇｔｏｙｉｎａｎｄｙａｎｇｉｍｂａｌａｎｃｅｉｓｔｈｅｒｏｏｔｃａｕｓｅｏｆｔｈｅｄｉｓｅａｓｅ，ｗｈｉｌｅｌｉｖｅｒｄｅｆｉｃｉｅｎｃｙａｎｄｌｉｖｅｒｄｅ ｐｒｅｓｓｉｏｎａｒｅｔｈｅｍａｉｎｆａｃｔｏｒｓ Ｓｈｅｏｆｔｅｎｃｏｎｃｕｒｒｅｎｔｌｙｅｎｇａｇｅｓｉｎｔｈｅｄｉｓｈａｒｍｏｎｙｏｆｈｅａｌｔｈａｎｄｈｙｇｉｅｎｅ Ｈｅｒｃｌｉｎｉｃａｌｔｒｅａｔｍｅｎｔｅｍ ｐｈａｓｉｚｅｓａｈｏｌｉｓｔｉｃｃｏｎｃｅｐｔ，ｕｎｉｔｙｏｆｈｅａｖｅｎａｎｄｍａｎ，ａｄｈｅｒｅｎｃｅｔｏｔｈｅｐａｔｈｏｇｅｎｅｓｉｓ，ｄｉａｌｅｃｔｉｃａｌｔｒｅａｔｍｅｎｔ，ａｎｄｍａｉｎｌｙｆｏｃｕｓｅｓｏｎＣｏｏｒｄｉｎａｔｉｎｇｙｉｎａｎｄｙａｎｇ，ｆｏｃｕｓｉｎｇｏｎｒｅｇｕｌａｔｉｎｇｔｈｅｍｉｎｄ，ｒｅｇｕｌａｔｉｎｇｓｌｅｅｐ，ａｎｄｈｅａｌｔｈｅｄｕｃａｔｉｏｎ．Ｋｅｙｗｏｒｄｓ Ｐｅｒｉｍｅｎｏｐａｕｓａｌｉｎｓｏｍｎｉａ；ＣｏｏｒｄｉｎａｔｉｎｇＹｉｎＹａｎｇ；Ｅｘｐｅｒｉｅｎｃｅ；ＺＨＡＯＲｕｉｈｕａ中图分类号：Ｒ３３８ ６３；Ｒ２７１ １９；Ｒ２７１文献标识码：Ａｄｏｉ：１０．３９６９／ｊ．ｉｓｓｎ．２０９５－７１３０．２０２３．０９．０１７ 围绝经期失眠症（ＰｅｒｉｍｅｎｏｐａｕｓａｌＩｎｓｏｍｎｉａ，ＰＭＩ）是指女性在绝经期前后，伴随烦躁、盗汗等一系列围绝经期综合征出现的以睡眠失常为主的一类症状性疾病，以入睡困难、睡后易醒、醒后难以再次入睡、早醒为主要表现［１］，我国ＰＭＩ的发病率近８０％［２］。
ClinicalPharmacy临床药学英文版课件
Goal
to promote the correct and appropriate use of medicinal products and devices.
These activities aim at: maximising the clinical effect of medicines minimising the risk of treatment-induced
adverse events minimising the expenditures for
Patient care
Knowledge of laboratory
and diagnostic skills
Drug Information Skills
Communication skills
Physical assessment
skills
Patient monitoring
skills
Education
How does clinical pharmacy differ from pharmacy?
The discipline of pharmacy embraces the knowledge on synthesis, chemistry and preparation of drugs
Clinical pharmacy is more oriented to the analysis of population needs with regards to medicines, ways of administration, patterns of use and drugs effects on the patients.
不同分期恶性肿瘤患者外周血凝血功能指标、NLR检测及其临床意义
病变的相关性分析[J].医学临床研究,2020,37(5):680-682.[17]Medina-Leyte DJ,Zepeda-García O,Domínguez-Pérez M,et al.En-dothelial dysfunction,inflammation and coronary artery disease:po-tential biomarkers and promising therapeutical approaches [J].Int J Mol Sci,2021,22(8):3850.[18]Kwon Y ,Kim M,Kim Y ,et al.EGR3-HDAC6-IL -27axis mediatesallergic inflammation and is necessary for tumorigenic potential of cancer cells enhanced by allergic inflammation-promoted cellular in-teractions [J].Front Immunol,2021,12(1):680441.[19]Nie F,Zhang Q,Ma J,et al.Schizophrenia risk candidate EGR3is anovel transcriptional regulator of RELN and regulates neurite out-growth via the Reelin signal pathway in vitro [J].J Neurochem,2021,157(6):1745-1758.[20]Shin SH,Kim I,Lee JE,et al.Loss of EGR3is an independent riskfactor for metastatic progression in prostate cancer [J].Oncogene,2020,39(36):5839-5854.[21]Hua Y ,Wang H,Ye Z,et al.An integrated pan-cancer analysis ofidentifying biomarkers about the EGR family genes in human carci-nomas [J].Comput Biol Med,2022,148(1):105889.(收稿日期：2023-09-18)不同分期恶性肿瘤患者外周血凝血功能指标、NLR 检测及其临床意义赵娜1，赵宁2，申晓楠1，苗雨莉11.通用环球西安西航医院检验科，陕西西安710021；2.西安医学院药学院，陕西西安710021【摘要】目的探讨不同分期恶性肿瘤患者外周血凝血功能指标、中性粒细胞/淋巴细胞比值(NLR)检测及其临床意义。
小细胞肺癌的生物学研究及其临床治疗进展
据统计，2012年全球新发肺癌病例数为180万， 占全部癌症新发人数12.9%，死亡病例数为160万，占 全部癌症死亡人数19.6%[1]。在中国，根据全国肿瘤 登记中心公布的2015年数据[2]，中国肺癌每年新发病 例数约73.33万，其每年死亡病例数约60.02万。小细 胞肺癌（SCLC）占肺癌病例数的13%~15%，每年新发 病 例 数 约 25万 ， 为 癌 症 相 关 死 亡 第 6大 病 因 。 [3-5] SCLC是 一 种 侵 袭 性 强 的 神 经 内 分 泌 癌 ， 生 长 速 度 快，在诊断早期可短时间内发生广泛转移；预后极 差，其生存期不到10月，5年生存率1%~5%[5]。在近 30年里，SCLC一线治疗方法无重大突破，仍以化疗 为主，辅以胸部放疗、预防性脑部放疗（PCI）等治疗。 在肺癌几个主要分型中，公认与吸烟关系最为密切 的 是 SCLC[6]。 目 前 有 研 究 者 认 为 是 烟 草 可 导 致 SCLC患者体细胞内基因突变，且基因突变负荷量非
摘要：肺癌是全球几大恶性肿瘤之一，在我国居于恶性肿瘤发病及死亡首位。小细胞肺癌是肺内分泌肿瘤的一种，具有侵袭 性强、易复发、易转移、预后不良等特征。而临床上小细胞肺癌的一线治疗方案仍未取得突破性的进展，主要仍以化疗为主， 辅以放疗等综合治疗。虽然，小细胞肺癌对化疗反应敏感，但80%局限期小细胞肺癌及几乎所有广泛期小细胞肺癌都会发生 肿瘤复发及进展，且化疗的毒副作用大。生物信息学及分子生物技术的发展为癌症的诊治提供更为广泛的空间，其中生物治 疗方法为近年研究的热点之一，尤其是免疫治疗，特别是研究一些免疫检查点抑制剂以达到抗癌的作用。本文旨在阐述小细 胞肺癌生物学研究及其治疗进展。 关键词：小细胞肺癌；放化疗；免疫治疗；免疫检查点抑制剂
常 高 。 [7] SCLC基 因 突 变 负 荷 高 为 广 大 学 者 研 究 SCLC新疗法法提供契机。近几年SCLC治疗方法有 所改变，研究较为热门是免疫治疗，包括细胞因子疗 法、肿瘤疫苗、免疫检查点抑制剂治疗；以免疫检查 点抑制剂为热点。目前已经进入临床试验主要为 CTLA-4抑制剂及PD-1/PD-L1抑制剂。
国外常见英文医学杂志影响因子及网址
国外常见英文医学杂志影响因子及网址<综合>1、期刊名称：Nature Medicine影响因子：大约31网络版地址：.nature./nm/journal/v14/n5/index.html#af有提前公布的文摘，但是时间不定：.nature./nm/journal/vaop/ncurrent/index.html2、期刊名称：NEJM New England Journal of Medicine （新英格兰医学杂志）影响因子：44点多（05年）网络版地址：/3、期刊名称：British medical journal （BMJ）影响因子：9.245（2006）网络版地址：.bmj./4、期刊名称：PNAS影响因子：9.6(2006)网络版地址：/——也可以免费获得全文5、期刊名称：lancet影响因子：网络版地址：.thelancet./6、期刊名称：Science影响因子：网络版地址：/7、期刊名称： Nature影响因子：网络版地址：.nature./8、期刊名称:Nature Genetics网址：.nature./ng/index.htm<生命科学>1、期刊名称：《Cell》影响因子：大约28(2005),29(2006)网络版地址：.cell./Online First版本：.cell./content/current2、期刊名称：stem cells影响因子：7.924(2006)网络版地址：.stemcells./view/0/index.html——该期刊所有文章PDF全文全部可在上述网址获得，而且更新很快3、期刊名称：科学家影响因子：网络版地址：.the-scientist./<细胞生物>1、期刊名称：journal of cell Science影响因子：6.427网络版地址：/2、期刊名称：Current Biology影响因子：10.988网络版地址：.current-biology./3、期刊名称：Molecular Cell影响因子：14.033网络版地址：/4、期刊名称：Nature review molecular cell biology影响因子：31.354网络版地址：.nature./nrm/5、期刊：fertility sterility影响因子：3.220（3点多）网址：.sciencedirect./science/journal/00150282<消化>1、期刊名称：journal of hepatology影响因子：6.64网络版地址：.jhep-elsevier./2、期刊名称：gut影响因子：9.02网络版地址：gut.bmj./Online First版本（如果有，请列出）：gut.bmj./onlinefirst.dtl3、期刊名称：hepatology影响因子：10.77网络版地址：.interscience.wiley./journal/hepatology4、期刊名称：gastroenterology影响因子：约13网络版地址：/<消化镜方向>1、杂志名称：GIEIF:5.8网址：/2、杂志名称：EndoscopyIF：4.1网址：.thieme.de/fz/index.html<呼吸>下面4本杂志比较偏重临床，可读性强——1、期刊名称：《American journal of respiratory and critical care medicine 》影响因子：大约8网络版地址：/Online First版本：/articlesinpress.shtml2、期刊名称：Thorax影响因子：网络版地址：thorax.bmj./content/vol52/suppl_2/3、期刊名称：ERJ欧洲呼吸杂志影响因子：网络版地址：erj.ersjournals./4、期刊名称：Chest（有中文版）影响因子：网络版地址：/下列杂志也比较出名，但偏重基础——5、期刊名称：American Journal of Respiratory Cell and Molecular Biology （AJRCMB ）影响因子：网络版地址：/6、期刊名称： American Journal of Physiology－《Lung Cellular and Molecular Physiology 》影响因子：网络版地址：/以下两个杂志的哮喘文献很有影响——7、期刊名称：Allergy影响因子：网络版地址：.blackwellpublishing./journal.asp?ref=0105-45388、期刊名称：Clinical & Experimental Allergy影响因子：网络版地址：.blackwellpublishing./journal.asp?ref=0954-7894<危重症>1、期刊名称：《American Journal of Respiratory and Critical Care Medicine》影响因子：8.123网址：2、期刊名称：Critical Care Medicine影响因子：约7网络版地址：.ccmjournal.——创刊于1973年，为月刊，2006年IF=6.599。
胸腺鳞状细胞癌-相关
全部翻完Thymic Squamous Cell Carcinomas作为关键词的19页结果。
差不多是case 居多，还有症状，自己看看吧，应该已包含全部有该完整关键词的文章！可能有漏，觉得不够你也可以自己翻。
不过建议不要浪费时间再翻，可以搜其他关键词。
祝你研究顺利Alles Gute. 看到我眼睛痛！！！！p.s 每篇上面的是链接，不过我都是全部复制过来，建议如果你觉得这个作者说的有道理可以点开查看相关介绍的链接。
如果觉得差不多就不用每个点开了。
希望能帮到你！加油！！晚期的多峰性治疗胸腺癌link:/pubmed/25311849Gen Thorac Cardiovasc Surg. 2015 Mar;63(3):159-63. doi: 10.1007/s11748-014-0486-7. Epub 2014 Oct 14.Multimodality treatment for advanced thymic carcinoma: outcomes of induction therapy followed by surgical resection in 16 cases at a single institution.Shintani Y1, Inoue M, Kawamura T, Funaki S, Minami M, Okumura M.Author information•1Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, 2-2-L5 Yamadaoka, Suita, Osaka, 565-0871, Japan, yshintani@thoracic.med.osaka-u.ac.jp.AbstractOBJECTIVE:We reviewed our institutional experience with cases of multimodality treatment foradvanced thymic carcinoma to determine patient outcomes and prognostic indicators.METHODS:Between 1998 and 2014, 16 patients with a Masaoka stage III or IV thymic carcinomaunderwent surgical resection after induction therapy at Osaka University Hospital. These were considered to have great vessel invasion or metastasis to the mediastinal or intrathoracic lymph nodes based on the preoperative workup findings, and received induction therapy.RESULTS:Complete tumor resection was achieved in 11 (69 %) after the induction therapy. Pathological findings revealed that 10 patients had Masaoka stage III disease, 1 had IVa, and 5 had IVb. The histological diagnosis was squamous cell carcinoma in 13, neuroendocrine carcinoma in 2, and undifferentiated carcinoma in 1. The 5-year survival rate for all patients was 71 %. Survival was significantly better in patients who underwent a complete resection (R0 disease) as compared to those with incompletely resected tumors (R1 or R2 disease).CONCLUSIONS:Multimodality treatment offers encouraging results and complete resection provides high survival rate for patients with advanced thymic carcinoma.link: /pubmed/25629460Long-Term Outcomes of Surgery for Thymic Carcinoma: Experience of 25 Cases at a Single Institution.Tagawa T1, Suzuki H1, Nakajima T1, Iwata T1, Mizobuchi T1, Yoshida S1, Yoshino I1. Author informationAbstractBackground Thymic carcinoma, a relatively rare entity, often presents as locally advanced disease, and sometimes as distant metastatic disease. The treatment strategy, long-term surgical outcomes and clinical prognostic factors have yet to be fully elucidated. Methods Clinical charts of 25 patients who underwent surgery for thymic carcinoma at our institution from 1991 to 2014 were retrospectively reviewed. Results The Masaoka stage was stage I in three patients (12%), II in eight (32%), III in four (16%), IVa in four (16%), and IVb in six (24%). Histologic subtypes weresquamous cell carcinoma in 12 patients, well-differentiated neuroendocrine carcinoma in 5, undifferentiated carcinoma in 3, adenocarcinoma in 1, and others in 4. Three patients had paraneoplastic syndrome including myasthenia gravis, multiple endocrine neoplasia type 1 (MEN1), and Cushing syndrome. Neoadjuvant chemotherapy was administered to five patients (20%). Complete resection was achieved in 17 patients (68%). There were no perioperative deaths. Twelve patients received postoperative therapy. The 5- and 10-year overall survival rates were 76.2 and 63.5%, respectively. The 5- and 10-year survival rates of patients with Masaoka stage I-III were 88.9 and 74.1%, respectively, whereas the 5-year survival rate of stage IV was 50.0%. The 5- and 10-year survival rates of 17 patients who underwent complete resection were 88.9 and 71.1%, respectively. Of the 17 patients with complete resection, 3 patients experienced recurrence including lung and supraclavicular lymph node. Conclusion Even for this highly malignant disease, surgery could contribute to favorable long-term outcomes in the setting of multimodality therapy.Georg Thieme Verlag KG Stuttgart · New York.link: /pubmed/24427739Anti-Apoptotic Signaturein Thymic Squamous Cell Carcinomas - Functional Relevance of Anti-Apoptotic BIRC3 Expression inAuthor informationAbstractThe molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and TCs, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymicsquamous cell carcinomas (TSCCs) with a custom-made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC.KEYWORDS:MTCH2; apoptosis; gene expression; myasthenia gravis; targetedtherapy; thymic carcinoma; thymoma; thymuslink: /pubmed/23866799Surgical treatment and prognosis of thymic squamousMETHODS:From February 2003 to December 2010, 105 consecutive surgical patients were enrolled in this study with pathologic confirmed thymic squamous cell carcinoma in Shanghai Chest Hospital. Clinical and pathologic data were retrospectively reviewed. Survival analysis was performed using the Kaplan-Meier and log rank tests. Multivariate analysis was performed using the Cox regression model.RESULTS:The squamous cell subtype made up 73.4% of the thymic carcinomas and 16.1% oftotalthymic tumors. Four patients (3.8%) presented with myasthenia gravis. The 5-year overall survival rate and the disease-free survival rate were 59.5% and 57.6%, respectively. On multivariate analysis, only the completeness of resection (hazard ratio 3.692; 95% confidenceinterval: 1.827 to 7.464; p=0.001) was found to have significant impact on overall survival. Completeness of resection (hazard ratio 2.361; 95% confidence interval: 1.226 to 4.547; p=0.010) and chemotherapy (hazard ratio 0.307; 95% confidence interval: 0.134 to 0.704; p=0.005) were associated with disease-free survival.CONCLUSIONS:Complete resection not only predicts better overall survival but also extends disease-free interval after resection of thymic squamous cell carcinoma. Our results provide additional evidence supporting an alternative clinical stage specific for thymic carcinoma.Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved. link: /pubmed/23639785Identification of novel mutations of TP53, ALK and RET gene in metastatic thymic squamous cell carcinoma andAuthor informationAbstractThymic carcinomas are rare epithelial malignancies with marked invasive tendency which can metastasize to distant organs, most commonly to the lung, bone, liver, kidney and extra-thoracic lymph nodes. Central nervous system metastasis is extremely rare and only 45 such cases have been reported in the English literature. We reported a 42-year-old male with thymic squamous cell carcinoma and lung and bones metastases. He underwent thymomectomy and pulmonarylobectomy with concurrent chemo-radiotherapy. Based on the clinical symptoms of severeheadache and vomiting and the results of brain computed tomography and magnetic resonance imaging scans, 2 metastatic tumors with a cystic component were diagnosed. We resected the metastatic tumors and the signs of increased intracranial pressure subsided immediately after the operation. The patient underwent continuous chemotherapy systemically and whole brainirradiation for disease control. This presentation suggests that surgical resection with concurrent chemo-radiotherapy is the treatment of choice for thymic carcinomas with brain metastases.link: /pubmed/19967491Thymic squamous cell carcinoma producing granulocyte colony-stimulating factor associated with a high serum•Int J Clin Oncol. 2010 Feb;15(1):116.AbstractGranulocyte colony-stimulating factor (G-CSF)-producing thymic carcinoma is extremely rare.A-66-year-old man presented with an anterior mediastinal mass, and underwent surgical biopsy. He had marked leukocytosis, and his serum levels of G-CSF and interleukin-6 were elevated.Histologically, the tumor consisted of squamous cell carcinoma, which showed positiveimmunoreactivity for G-CSF. He was treated with thoracic radiotherapy, and chest imagingrevealed a marked reduction of tumor size. He was doing well at 8 months after tumor diagnosis.Thymic squamous cell carcinoma producing parathyroid hormone-related protein and CYFRA 21-1.Yoshiike F1, Koizumi T, Yoneyama A, Komatu M, Yamaguchi S, Hanaoka M, Kubo K, Eda S.Author informationAbstractA 54-year-old man was admitted to our hospital because of dyspnea. Radiographic examination showed an anterior mediastinal mass and pericardial effusion. Serum calcium and parathyroid hormone-related protein (PTHrP) levels were elevated, and serum CYFRA 21-1 level was extremely high. Results of percutaneous needle biopsy under computed tomography guidance led to a diagnosis of moderately differentiated squamous cell carcinoma. Immunohistological staining showed the tumor cells to be positive for PTHrP and cytokeratin monoclonal antibodies. Postmortem findings were considered to indicate thymic carcinoma. Thymic carcinoma is rare, but our case indicates that thymicsquamous cell carcinoma can be identified in terms of paraneoplastic hypercalcemia./pubmed/7773875Squamous cell carcinoma of the thymus with paraneoplastic hypercalcemia.与上同Negron-Soto JM1, Cascade PN.Author informationAbstractPrimary thymic carcinoma is a rare neoplasm that in contradistinction to thymoma, is not supposed to be associated with a paraneoplastic syndrome. A 73-year-old man, with new onset of disorientation, was found to have an elevated serum calcium level as the cause. Computed tomography demonstrated a mediastinal mass, pericardial invasion, and metastases to the lung. Examination of a biopsy specimen revealed thymic squamous cell carcinoma. Thus, a paraneoplastic syndrome, in this case hypercalcemia, does not exclude primary carcinoma ofthe thymus.link: /pubmed/15084623PATIENTS AND METHODS:Two hundred twenty-eight patients were followed for up to 21 years (median, 60 months; range, 1 to 252 months) after primary surgery. Forty-two patients received adjuvant radiotherapy (mean dose, 53 Gy), and 33 patients received adjuvant chemotherapy.RESULTS:Seventy-six (88%) of 86 patients with WHO type A, AB, and B1 thymomas were treated by surgery alone, with three tumor relapses after 3 to 10 years (median, 3.4 years). Twelve of 67 patients with WHO type B2 and B3 thymomas in Masaoka stages I and II were treated by adjuvant radiotherapy without evidence of tumor recurrence after 1 to 12 years (median, 4 years). Among 75 patients with B2 and B3 thymomas with incomplete resection or a tumor stage III or higher, the recurrence rate was 34% (n = 23) after 0.5 to 17 years (median, 5 years) in patients receiving adjuvant radiochemotherapy, compared to 78% (seven of nine patients) in patients without adjuvant radiochemotherapy. Incomplete tumor resection was associated with a high recurrence rate (65%) and a poor prognosis (P <.01).CONCLUSION:The long-term outcome of TET patients is related to tumor stage, WHO histotype, completeness of surgical removal, and type of treatment. Prospective trials are warranted to formally address the efficacy of adjuvant therapy in the treatment of localized and advanced malignant TETs./pubmed/12795160[Thymic carcinoma (mixedsmall cell undifferentiated squamous cell carcinoma); report of a case].[Article in Japanese]/pubmed/12413013Interleukin-6-producing thymic squamous cell carcinoma associated with Castleman's disease and/pubmed/10513141A long-term survival case of thymic squamous cell carcinoma, performed complete extirpation with vascular reconstruction of the superior vena cava.Shinkai K1, Hisano H, Shibasaki S, Yano H, Nomura M, Ayabe H.Author informationAbstractA 59-year-old woman who complained of anterior chest pain exhibited an abnormal shadow on chest X ray and was admitted to our hospital. The chest X ray showed a demarcated tumor at the anterosuperior mediastinum and she was diagnosed as having a mediastinal tumor. After the midsternotomy was performed, the mediastinal tumor derived from the thymic tissues was discovered to have invaded the right upper lung, pericardium and superior vena cava. After excising the tumor, anastomosis between the right brachiocephalic vein and superior vena cava, followed by that between the left brachiocephalic vein and right cardiac auricle was performed using expanded polytetrafluoroethylene-ringed vascular grafts (phi 10 mm) for reconstruction. The tumor was diagnosed as a thymic carcinoma (squamous cell carcinoma) pathologically. After surgery, she was treated by cobalt irradiation. One month and again 3 months after the operation, venography showed patency. The patient has not demonstrated recurrence for 9 years and 6 months./pubmed/9838398只有名没有内容Long-term survival of renal transplantationwith thymic squamous-cell carcinoma after successful radiation therapy.link /pubmed/8538098[A case of thymic squamous cell carcinoma successfullyas possible, it was not capsular invasion and mediastinal lymph nodes metastasis and complete curative resection was able to perform. Additional radiation therapy was done, post-operative course was uneventful./pubmed/7666619[A case of thymic carcinoma successfully controlled by combined chemotherapy and irradiation].[Article in Japanese]Beppu H1, Nodera H, Atarashi K, Yoshimura N, Tsukimoto K, Nagashima Y.Author informationAbstractThere is no well established therapeutic protocol for advanced thymic carcinoma, although chemotherapy and irradiation can apparently be used to control the malignancy. Here we report a case of advanced thymic carcinoma successfully controlled by combination of treatment with systemic chemotherapy and irradiation. A 79-year-old man was admitted to the Hiratsuka Kyosai Hospital with complaints of productive cough and dyspnea. Chest roentgenogram and computerized tomography on admission revealed a tumorous lesion in the anterior mediastinum and on accumulation of left pleural and pericardial effusion fluid. The tumor was diagnosed asa thymic squamous cell carcinoma, after percutaneous needle biopsy. Because of extension to the left pleura and cardiac sac, the tumor was considered to be unresectable and systemic chemotherapy (CDDP + VDS + MMC) was begun. After drainage of the pericardial effusion fluid, intrapericardial injection of MMC was also done. The anterior mediastinum was irradiated. The patient has been doing well, with regression of the thymic tumor for 48 months after irradiation. This case provides important information that can be used to establish an effective therapeutic regimen for advanced thymic carcinoma.Myasthenia gravis and primary squamous cellIn the case described, a 43-year-old man had an asymptomatic mass involving the right hilar and superior mediastinum. At surgery, the tumor was found to have invaded the right middle lobe of the lung and the pericardium. The mass was found to be a thymic squamous cell carcinoma, a rare tumor. Two serum tumor markers--lipid-associated sialic acid and squamous cellcarcinoma antigen--were elevated. The patient underwent postoperative radiation therapy and has responded favorably to treatment. He had no clinical evidence of metastasis or recurrence as of 43 months postoperatively./pubmed/602973Squamous cell carcinoma of the thymus. An analysis of eight cases.Shimosato Y, Kameya T, Nagai K, Suemasu K.AbstractEight cases of squamous cell carcinoma of the anterior mediastinum, most likely derived from thethymus, are presented. Seven were male and one female ranging in age from 39 to 65 years; the average was 55.5 years. There were no cases associated with any paraneoplastic syndromes. They possessed common morphological characteristics. Grossly, the tumors resembled malignant thymoma. Invasion of the lung and metastases to regional lymph nodes were frequent. Often observed microscopically were foci of sharply defined keratinization resembling Hassall's corpuscles, no radial arrangement of tumor cells at the periphery of nests, and broad, fibrotic, or hyalinized stroma. Admixture of a few lymphoid cells and some features transitional to thymoma were also observed in some parts of tumors. However, undoubtedly carcinomatous areas were present in some or large parts of all the tumors, where individual cells possessed a vesicular nucleus and a prominent round nucleolus. These features were distinct from those of bronchogenic squamous cell carcinoma and other thymic tumors, although they appeared to be related to thymoma. Treatment of choice is radical surgery and postoperative radiotherapy, because of relatively high radiosensitivity. Prognosis of patients was relatively good. From analyses of cases it is concluded that squamous cell carcinoma of the thymus should be separated from ordinary thymoma of the epithelial type, and that squamous cell carcinoma involving boththe thymus and lungs should be carefully examined for the primary site of growth.。
药物涂层球囊治疗下肢动脉硬化闭塞症的应用进展
药物涂层球囊治疗下肢动脉硬化闭塞症的应用进展杨祖尉;余朝文【摘要】经皮腔内血管成形术(PTA)或支架置入术已被公认是治疗下肢动脉硬化闭塞症(LEASO)的重要方法,但术后再狭窄的发生限制了其疗效.药物涂层球囊(DCB)含有抗增殖药物,可以抑制新生血管内膜增生,降低再狭窄发生,从而克服了经皮腔内血管成形术的局限性.近年来的临床试验显示,DCB在治疗股腘动脉的初次病变及支架内再狭窄方面,可明显提高一期通畅率(PP),降低晚期管腔损失(LLL),但DCB在膝下动脉(BTK)中的治疗作用仍不明确.本文对DCB在治疗LEASO病变中的应用进展进行综述.【期刊名称】《大连医科大学学报》【年(卷),期】2019(041)002【总页数】8页(P167-174)【关键词】经皮腔内血管成形术;动脉硬化闭塞症;下肢;药物涂层球囊;再狭窄【作者】杨祖尉;余朝文【作者单位】蚌埠医学院第一附属医院血管外科,安徽蚌埠233000;蚌埠医学院第一附属医院血管外科,安徽蚌埠233000【正文语种】中文【中图分类】R654.3下肢动脉硬化闭塞症(lower extremity arteriosclerosis obliterans，LEASO) 是动脉粥样硬化在下肢的主要表现，是外周动脉疾病和慢性动脉闭塞性疾病的重要组成部分。
下肢动脉硬化闭塞症病理变化表现为大、中动脉退行性病变。
动脉内膜或中层细胞、纤维间质、脂质和组织碎片的异常沉积，可导致继发性血栓形成[1]，临床上可出现间歇性跛行、严重肢体缺血、溃疡和坏疽。
1964 年，Charles Dotter[2]首次采用经皮腔内血管成形术(percutaneous transluminal angioplasty, PTA)成功治疗1例LEASO患者，标志着治疗外周动脉疾病新时代的到来[3]。
然而，PTA也存在一些不足，如：具有较高的再狭窄率，有报道PTA 治疗后60%以上会出现再狭窄[4]。
芪苈强心胶囊联合尼可地尔治疗慢性肺心病伴冠心病心衰患者的效果
2023年11月 第9卷 第11期芪苈强心胶囊联合尼可地尔治疗慢性肺心病伴冠心病心衰患者的效果熊云志1，罗宗梅2，徐菱31.深圳市盐田区人民医院心血管内科，广东深圳 518081；2.贵州省贵阳市第二人民医院心血管内科，贵州贵阳 550081；3.深圳市罗湖区人民医院妇科，广东深圳 518005摘要 目的 综合分析芪苈强心胶囊联合尼可地尔治疗慢性肺源性心脏病（简称慢性肺心病）伴冠心病心力衰竭的临床治疗效果。
方法 回顾性选取2021年10月—2022年12月深圳市盐田区人民医院收治的60例慢性肺心病伴冠心病心力衰竭患者的临床资料。
按照患者入院顺序分为对照组（30例，应用尼可地尔治疗）和研究组（30例，在对照组基础上应用芪苈强心胶囊治疗），比较两组患者的临床治疗有效率、心功能指标及生存质量。
结果 与对照组比较，研究组临床治疗总有效率（90.00%）更高，差异有统计学意义（χ2=4.706，P <0.05）；治疗后，研究组左室射血分数、每搏输出量高于对照组，左室舒张末期内径低于对照组，差异有统计学意义（P <0.05）；治疗后，研究组生存质量评分均高于对照组，差异有统计学意义（P <0.05）。
结论 芪苈强心胶囊联合尼可地尔治疗慢性肺心病伴冠心病心力衰竭患者的临床治疗效果显著。
关键词 芪苈强心胶囊；尼可地尔；慢性肺心病伴冠心病心力衰竭；临床治疗效果；心功能；生存质量中图分类号 R 541541..5 文献标志码 Adoi10.11966/j.issn.2095-994X.2023.09.11.39Qili Qiangxin Capsule Combined with Nicorandil in the Treatment of Patients with Chronic Pulmonary Heart Disease Accompanied by Coronary Heart Disease and Heart FailureXIONG Yunzhi 1, LUO Zongmei 2, XU Ling 31.Department of Cardiovascular Medicine, Yantian District People's Hospital, Shenzhen, Guangdong Province, 518081 China;2.Depart⁃ment of Cardiovascular Medicine, Guiyang Second People's Hospital, Guiyang, Guizhou Province, 550081 China;3.Department of Gynecol⁃ogy, Luohu District People's Hospital, Shenzhen, Guangdong Province, 518005 ChinaAbstract Objective To comprehensively analyze the clinical therapeutic effect of Qili Qiangxin capsule combined with nicorandil in the treat⁃ment of chronic pulmonary heart disease (referred to as chronic pulmonary heart disease) with coronary heart failure. Methods The clinical data of 60 patients with chronic pulmonary heart disease with CHD and heart failure treated in Yantian District People's Hospital of Shenzhen from October 2021 to December 2022 were retrospectively selected. Patients were divided into control group (30 cases, treatment with nicodil) and study group (30 cases, treatment with Qiliqiangxin capsule on the basis of control group) according to the order of admission. Clinical treatment effectiveness, cardiac function indexes, quality of life of the two groups were compared. Results Compared with the control group, the total effective rate of the study group (90.00%) was higher, the difference was statistically significant (χ2=4.706, P <0.05).After treatment, the left ventricular ejection fraction and output per beam in the study group were higher than those in the control group, and the left ventricu⁃lar end-diastolic diameter was lower than that in the control group, the differences were statistically significant (P <0.05). After treatment, the quality of life score of the study group was higher than that of the control group, and the difference was statistically significant (P <0.05). Con⁃clusion The clinical therapeutic effect of Qili Qiangxin capsule combined with nicorandil in the treatment of patients with chronic pulmonary* 中西医结合研究 *收稿日期：2023-09-02；修回日期：2023-09-23作者简介：熊云志（1982-），男，本科，主治医师，研究方向为心血管病。
thernostics under review
thernostics under reviewTitle: Understanding and Analyzing the Role of TheragnosticsIntroduction:Theragnostics, an emerging field in medicine, combines therapeutics and diagnostics to provide personalized treatment options for patients. It revolutionizes the healthcare industry by tailoring treatment plans for individuals based on their unique genetic makeup, disease characteristics, and response to treatment. This article aims to explore the concept, development, challenges, and potential applications of theragnostics.I. Defining Theragnostics:Theragnostics, often referred to as theranostics, is a fusion of therapeutics and diagnostics. It encompasses the integration of diagnostic tools, such as medical imaging and biomarker analysis, with targeted therapy interventions. By integrating diagnosis and therapy, theragnostics ensures a more precise and individualized approach to healthcare.II. Evolution of Theragnostics:The concept of theragnostics can be traced back to the late 1990swhen researchers recognized the need for personalized medicine. Advances in genomics, proteomics, and imaging techniques laid the groundwork for the development of theragnostics. It was a paradigm shift from the traditional one-size-fits-all approach to a patient-centric model.III. Key Diagnostic Modalities in Theragnostics:a. Medical Imaging: Various imaging techniques, including positron emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI), are used to visualize and diagnose diseases. Imaging agents tagged with radioisotopes or paramagnetic substances enable accurate detection and localization of targets for subsequent therapy.b. Biomarkers: These are molecular indicators that provide specific information about a disease or its response to treatment. Biomarkers play a vital role in tailoring therapies for patients.IV. Therapeutic Approaches in Theragnostics:a. Targeted Drug Delivery: Theragnostics helps in delivering drugs directly to tumor sites, minimizing side effects. This is achieved through nanoparticles, liposomes, or antibody-drug conjugates, which are designed to specifically recognize and delivertherapeutics to diseased tissues.b. Radiopharmaceutical Therapy: Radioactive isotopes are attached to specific molecules, which selectively target cancer cells. Once targeted, the radioactive isotopes emit radiation, killing or damaging cancer cells while sparing healthy tissues.V. Challenges in Theragnostics:a. Regulatory Approval: Developing and validating tests, imaging agents, and therapeutic compounds is a complex process that requires regulatory approval. Ensuring accuracy, safety, and efficacy of theragnostics is essential for widespread adoption.b. Cost and Affordability: Theragnostics, being a relatively new and advanced field, can be expensive. Widespread adoption may be hindered due to high costs, especially in resource-constrained settings.c. Technology Integration: Integration of diagnostic and therapeutic approaches requires coordination between different disciplines, including radiology, pathology, and pharmaceuticals. Coordinated efforts are essential for seamless implementation and realization of its potential.VI. Potential Applications:a. Cancer Treatment: Theragnostics plays a crucial role in identifying tumor markers, determining response to treatment, and providing targeted therapy options. It aids in monitoring treatment response and adjusting therapies accordingly.b. Neurological Disorders: Theragnostics has the potential to help in early diagnosis and monitoring the progression of neurodegenerative diseases. It enables targeted drug delivery to specific brain regions, minimizing off-target effects.c. Cardiovascular Diseases: By identifying high-risk patients, tracking disease progression, and providing personalized treatment plans, theragnostics can significantly impact cardiovascular healthcare.Conclusion:Theragnostics represents an innovative approach revolutionizing personalized medicine. By integrating diagnostics with targeted therapeutics, theragnostics provides valuable opportunities for accurate disease diagnosis, prognosis, and treatment. Further research, technological advancements, and widespread adoption are necessary for maximizing its potential and improving patient outcomes.。
伴先天易感因素和复杂基因突变的难治复发儿童急性髓系白血病一例并文献复习重点
单独伴 AML1-ETO 阳性的 AML 通常预后较好， 但本例患 儿无初诊时其他可辅助预后判断的基因突变指标，无法回顾性 评估其预后。 该患儿在临床上表现为难治复发的病程，在 2 次 复发后呈现出复杂染色体核型异常，并具有显著的克隆异质性
万方数据
和克隆演变迹象， 提示存在基因组不稳定因素。 另外， 部分 DNA 拓扑异构酶抑制剂类药物可能与遗传易感因素一起促进 了染色体异常事件的发生。
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白血病·淋巴瘤 2016 年 12 月第 25 卷第 12 期 Journal of Leukemia & Lymphoma, December 2016, Vol. 25, No. 12
（q21；p24），add （22）（q13）［1］／45，idem，del （15）（q22）［1］／ 45，X，-Y，t （3；5）（q27；q13），del （5）（q31），inv （7）（q22； q36），（ t 8；21）（q22；q22）［1］／46，XY［1］（图 1）。 AML1-ETO 定 量（实时荧光定量聚合酶链反应法［4］）结果为 143.26 %（AML1ETO／ABL1）。
总之， 本例患儿资料提示儿童 AML 患者可能有较强的遗 传易感因素，初诊时即比较全面地进行基因突变组分析有助于 早期制订更合理的治疗方案。 对于染色体不稳定因素较多的患 者，应尽量减少使用拓扑异构酶抑制剂类化疗药物。 利益冲突 无
参考文献
［1 ］ 陈雪， 刘红星. 血液肿瘤的遗传易感因素值得重视： 第 56 届美 国血液学会年会报道［J］. 白血病·淋巴瘤， 2015， 24（2）： 65-70. DOI：10.3760/cma.j.issn.1009-9921.2015.02.001. Chen X， Liu HX. Inherited and congenital predisposition to hematologic malignancies： reports from the 56th American Society of Hematology annual meeting ［J］. Journal of Leukemia & Lymphoma， 2015， 24（2）： 65-70. DOI：10.3760/cma.j.issn.1009-9921.2015.02. 001.
黄龙止咳颗粒联合小儿消积止咳口服液治疗痰湿蕴肺型儿童慢性咳嗽的临床研究
黄龙止咳颗粒联合小儿消积止咳口服液治疗痰湿蕴肺型儿童慢性咳嗽的临床研究龚平华① 张晓磊① 【摘要】 目的：探讨痰湿蕴肺型儿童慢性咳嗽使用黄龙止咳颗粒联合小儿消积止咳口服液治疗的临床效果。
方法：选取2022年1月—2023年1月常熟市第一人民医院儿科收治的100例痰湿蕴肺型儿童慢性咳嗽患儿作为研究对象，根据治疗方法不同分为联合组50例和参照组50例。
参照组给予常规对症治疗联合黄龙止咳颗粒，联合组在参照组基础上给予小儿消积止咳口服液。
比较两组疗效、临床症状消失时间、不良反应发生率。
结果：联合组治疗总有效率为96.00%，高于参照组的84.00%，差异有统计学意义（P<0.05）；联合组咳嗽消失时间、喘息消失时间、肺啰音消失时间均早于参照组，差异有统计学意义（P<0.05）；联合组不良反应发生率为6.00%，与参照组的8.00%比较，差异无统计学意义（P>0.05）。
结论：痰湿蕴肺型儿童慢性咳嗽采用黄龙止咳颗粒联合小儿消积止咳口服液治疗，可有效提升治疗效果，缩短症状改善时间。
【关键词】 痰湿蕴肺型儿童慢性咳嗽 黄龙止咳颗粒 小儿消积止咳口服液 doi：10.14033/ki.cfmr.2023.23.034 文献标识码 B 文章编号 1674-6805（2023）23-0134-04 Clinical Study of Huanglong Zhike Granules Combined with Xiao’er Xiaoji Zhike Oral Liquid in the Treatment of Chronic Cough in Children with Phlegm Dampness and Lung Accumulation/GONG Pinghua, ZHANG Xiaolei. //Chinese and Foreign Medical Research, 2023, 21(23): 134-137 [Abstract] Objective: To investigate the clinical therapeutic effect of Huanglong Zhike Granules combined with Xiao’er Xiaoji Zhike Oral Liquid in the treatment of chronic cough in children with phlegm dampness and lung accumulation. Method: A total of 100 children with chronic cough in children with phlegm dampness and lung accumulation who admitted to the Department of Pediatrics, the First People's Hospital of Changshu from January 2022 to January 2023 were selected as the research objects. According to different treatment methods, they were divided into the combined group (n=50) and the reference group (n=50). The reference group was treated with conventional symptomatic treatment combined with Huanglong Zhike Granules, and the combined group was treated with Xiao’er Xiaoji Zhike Oral Liquid on the basis of the reference group. The efficacy, disappearance time of clinical symptoms and incidence of adverse reactions were compared between two groups. Result: The total effective rate of the combined group was 96.00%, which was higher than 84.00% of the reference group, the difference was statistically significant (P<0.05). The cough disappearance time, wheezing disappearance time and lung rale disappearance time in the combined group were earlier than those in the reference group, the differences were statistically significant (P<0.05). The incidence of adverse reactions in the combined group was 6.00%, which was compared with 8.00% in the reference group, the difference was not statistically significant (P>0.05). Conclusion: Huanglong Zhike Granules combined with Xiao’er Xiaoji Zhike Oral Liquidin in the treatment of chronic cough in children with phlegm dampness and lung accumulation can effectively improve the therapeutic effect and shorten the time of symptom improvement. [Key words] Chronic cough in children with phlegm dampness and lung accumulation Huanglong Zhike Granules Xiao’er Xiaoji Zhike Oral Liquid First-author's address: The First People's Hospital of Changshu, Changshu 215500, China 14岁以下儿童肺部影像学检查无异常，且病程超过4周的咳嗽通常被定义为儿童慢性咳嗽[1]。
Patient or client If in doubt, ask
Peter C. Wing, MB, ChB
Abstract DO PEOPLE SEEKING HEALTH CARE prefer to be called “patients” or “clients”? To try and answer this question the author surveyed 101 people attending a back-pain clinic and found that most (74) preferred “patient.” Given the implicit assumptions inherent in the use of specific labels, the author advises clinicians to evaluate carefully the attitudinal implications of using a particular term and to ensure that preferences are respected. Résumé LES PERSONNES À LA RECHERCHE DE SOINS DE SANTÉ préfèrent-elles se voir comme des «patients» ou comme des «clients»? Pour essayer de répondre à cette question, l’auteur a interrogé 101 personnes à une clinique de soins du dos et a constaté que la plupart (74) préféraient le mot «patient». Étant donné les hypothèses inhérentes au qualificatif choisi, l’auteur conseille aux cliniciens d’évaluer attentivement les répercussions sur les attitudes de l’utilisation de certains termes et de s’assurer qu’on respecte les préférences des intéressés.
“一证一品”专科护理模式在肿瘤病房
中西医结合护理Chinese Journal of Integrative Nursing2021年第7卷第7期Vol.7，No.7，2021“一证一品”专科护理模式在肿瘤病房疼痛管理中的应用关丽1，魏书婷1，郝丽2（首都医科大学附属北京中医医院1.肿瘤科；2.护理部，北京，100010）摘要：目的探讨“一证一品”专科护理模式在肿瘤病房疼痛症状管理中的应用效果。
方法以项目实施的时间为分界线，采用便利抽样方法选取2017年1月—12月收入科室的50例肿瘤患者为对照组，2018年1月12月收入科室的50例肿瘤患者为试验组。
在肿瘤疼痛症状管理中体现“病与证”、“施治与施护”、“中医药与中医护理”相结合，采用中医外治法及情志护理，将品质护理贯穿全程。
比较项目实施前后患者疼痛改善时间、对疼痛的认知水平及患者满意度的变化。
结果与对照组相比，试验组患者的疼痛改善时间缩短（P ＜0.05）。
试验组患者疼痛相关自我护理知识知晓率100.00%，满意度为90.00%（45/50）。
结论通过“一证一品”专科护理示范病房建设，在肿瘤患者疼痛症状管理中可以有效的帮助肿瘤患者缓解疼痛，提高疼痛自我护理知识知晓率，进而提高患者的满意度，提升护理服务质量。
关键词：疼痛；肿瘤；中医护理；中医辨证中图分类号：R 473.5文献标志码：A文章编号：2618-0219（2021）07-0042-06Application of “One Syndrome and One product ”specialized nursing plan for pain managementin the oncology wardGUAN Li 1，WEI Shuting 1，HAO Li 2（1.Department of Oncology ；2.Department of Nursing ，Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University ，Beijing ，100010）ABSTRACT ：Objective To explore the application effect of “One Syndrome and One Product ”specialized nursing plan for pain management in the oncology ward.Methods Taking the imple⁃mentation time of the project as the dividing line ，50cancer patients with hospital admission be⁃tween Jan.2017and Dec.2017were included as the control group ，and another 50cancer patients with hospital admission between Jan.2018and Dec.2018were included as the study group.In the management of cancer pain symptoms ，the combination of disease and syndrome ，treatment and nursing ，Traditional Chinese Medicine （TCM ）and TCN nursing were reflected ，the external treatment of TCM and emotional nursing were adopted ，and the quality nursing ran through the whole process.The time to pain relief ，the cognitive level of pain and patients ’satisfaction were compared before and after the implementation of the project.Results After the implementation of the “One Syndrome and One Product ”nursing project ，the time to pain relief of patients in the study group shortened remarkably compared with that in the control group （P ＜0.05）.The rate of patient awareness on pain related self -care knowledge was 100.00%，and rate of patient satisfac⁃tion was 90.00%.Conclusion Through the construction of specialized care ward based on “OneDOI ：10.12209/j.issn 2709-1961.202107068·"一证一品"专栏·收稿日期：2021-04-26第一作者简介：关丽，副主任护师，首都医科大学附属北京中医医院肿瘤科护士长，肿瘤、静疗专业护士，从事肿瘤护理21年。
临床医学（ClinicalMedicine）_考研英语作文
临床医学(Clinical Medicine)to strive to be among the top 100 in my field has always been my aspiration. for the materialization of this aspiration, i have dedicated all my enthusiasm and energy to my academic endeavors—both my studies and research—over the past few years. however, to my dismay, the unsatisfactory research conditions in china have caused the research and the therapeutic level in the field of my specialization, namely clinical medicine /gastroenterology, to lag behind those of the developed countries in the west by at least 10 years. many of the original ideas that i have developed on certain issues in my field cannot be fully put into practice on account of the limitations in personnel, experimental facilities and research funds. consequently, i strongly wish that i can be admitted into your esteemed university to undertake an advanced degree program in clinical medicine & gastroenterology.i have cherished a deep and long yearning for a chance to study at your university. as early as the years when i was an undergraduate at the department of medicine of (provincial) medical university, i had a chance to read the book the reach of helicobacter pylori edited by some professors of your university which influenced me to take up the study of digestive diseases as my area of specialization. later, during my master’s program, i focused on the development of the chronic stomach disease (gastrosia) and the incidence of the gastric cancer. the comprehensive research and practice that i have performed in this area further reinforce my determination to seek advanced studies at your university when there should be an opportunity. this is because your esteemed university enjoys a very highacademic reputation for the research work you have carried out in the field of digestive disease study. this ensures that if i can be admitted into your program i will be part of your well-respected program and i will be able to undertake in-depth study and develop a close understanding of the most updated theories and technical developments in this field. by working together and exchanging experiences with the world’s leading experts in this field, i will be exposed to wholly novel ideas of research and significantly broaden my academic vision.at the same time, as china is a country with a high incidence of hepatopathy (liver disease), i believe that i can make important contributions to the relevant research projects of your university with my rich clinical experience in this field. of course, i am fully aware that, to be able to enroll in your prestigious and time-honored university, i will be inevitably confronted with fierce competitions from other elitist students the world over. but i have full confidence in myself as a worthy candidate for your program based on my past education, research and clinical experience, as well as my aspiration to develop myself into a leading expert in china in my chosen area.at the department of medicine and the graduate school of medical university, i respectively completed my bachelor’s program and my master’s program in internal medicine. through my academic endeavors, i have not only laid a firm yet comprehensive groundwork in medical theories, becoming well-read in classic medical literature, but also developed a sound ability in rigorous yet flexible logical thinking and a sense of scientific commitment. i am relatively strong at probing, from a micro perspective, into the etiopathologic and developmental mechanisms, at theoretically deducing the process of the genesisof a pathological state, and at demonstrating it through well-designed experiments. during heated classroom discussions, i could always convince my classmates with my eloquent presentation, rigorous logical analysis and detailed experimental statistics. in addition to that, i have also won general recognition from the teachers and professors who taught me.my research capacity, creative thinking and experimental skills experienced further improvement as i joined a research group at the research institute of digestive diseases to undertake a research project for my master’s program. under the leadership of prof. , the most celebrated specialist on digestion, i participated in the project the development of chronic stomach disease (gastrosia) & the mechanism of cancerization sponsored by provincial bureau of public health. in this project, i focused my research on the mechanism of action and the cellular immunity of the catalyst subunit telomerase in cancerization and investigated, through a microscopic approach, the clinical significance that those two factors may produce on the diagnosis, treatment and prognosis of the gastric cancer. my thesis, entitled the expression of htert mrna and cellular immunity in gastric cancer and precancerosis won high evaluations from prof. and prof. and other specialists from union hospital and the no. 1 clinical medical institute of university. they rated my thesis as “demonstrating originality in conception and effective methodology, enriching relevant theories and having marked clinical significance.”i have accumulated much practical clinical experience since i started working at the no. 2 hospital of medical university which is classified as the “grade-a class-iii” hospital (t he highest ranking for a hospital in china). based on my research during the master’s program, i expanded my research area to include thestudy on gastric cancer. i have published a total of six papers (please refer to my resume for more detailed information), including the latest the expression and the clinical implication of the catalyst subunit telomerase in gastric cancer and precancerosis, in the world journal of gastroenterology and other leading journals in china and collected into science citation index-expanded index medicus /medline and chemical abstracts. some of those papers were designated to be presented at annual conference on digestion in and province.while undertaking research, i have received formal and comprehensive training as resident physician of internal medicine and obtained national doctor license. through the training program i have grasped the pathogenetic mechanisms of gastrointestinal and liver diseases, cardiovascular diseases, endocrinopathy, pulimonary and connectiv tissue diseases and their corresponding diagnosis and treatment. in less than two years after working at the hospital, i passed the national-level qualifying examination to have achieved the qualifications as the physician-in-charge in digestive internal medicine.helicobacter pylori has been regarded as the key factor in the incidence of gastric diseases and the contributing factor in cancerization. the research in this field has reached the molecular level. i have a good foundation of academic research in this aspect. china has a high incidence of liver diseases and a large proportion of patients i deal with in my daily work are those of hepatitis, allowing me to acquire abundance clinical experience and deep understanding concerning the genesis of the hepatitis and the disease-causing mechanism of the viruses. those two fields will be the area of focus in my prospective program at your university. ideally, i hope to achieve some breakthroughtheoretically and technically.for too many times, i have witnessed the enfeeblement of the otherwise robust life of patients due to their physiological conditions. the horror of seeing the gradual dwindling of a strong-willed life is simply beyond description. but i have largely transmuted this horror into a motivation behind all my academic endeavors and professional practices. for me, success has only one meaning, that is, to unravel the mysteries of the diseases pestering human beings and to contribute to the well-being of my patients.。
人脂肪组织基质血管组分的分离培养
人脂肪组织基质血管组分的分离培养作者：庄伟, 谢良地, 黄杰, 许昌声【关键词】脂肪组织; 细胞外基质；细胞,培养的ABSTRACT: Objective To establish a method for the isolation and culture of stromal vascular fraction(SVF) of human adipose tissue in vitro, which has the characteristics of stem cells. Methods Normal human abdominal subcutaneous adipose tissue was digested with collagenase Ⅰand precipitated by centrifuge. The lowest layer cells were suspended and cultured with DMEM F12. Immunofluorescence assay was used to determine the presence of the surface molecule marker CD31 and CD34. Results Immunofluorescence assay showed that about 70％ of the 2nd generation of cultured SVF cells were CD34 positive, but CD31 negative. Conclusion A rapid reproducible method was set up for the isolation and culture of SVF with the characteristics of stem cells from human adiposetissue, which possess clinical and research implication of stem cells.KEY WORDS: adipose tissue; extracellular matrix; cells, cultured传统的干细胞多取材于胚胎、骨髓和脐血,在伦理和供体来源方面受到一定限制。
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371 Virokines and viroceptors — viral immunomodulators with clinical and therapeutical implicationKontsek P, Kontsekova EVirokíny a viroceptory — imunomodulátory vírusov s klinickýma terapeutickým dosah omAbstractKontsek P, Kontsekova E:Virokines and viroceptors — viral immunomodulators with clinical and therapeutic implicationBratisl Lek Listy 2000; 101 (7): 371–382During evolution viruses have developed variety of sophistica-ted strategies for interactions with the immune system of the host. One of the defense strategies that counteract the immune responses of the infected organism exploits viral proteins that directly interfere with the host’s cytokine system. Among such immunomodulatory molecules are classed also viral homologs of cytokines (virokines) and viral homologs of cytokine recep-tors (viroceptors), produced and secreted by the virus-infected cell. Virokines and viroceptors are encoded by large DNA viru-ses — herpesviruses and poxviruses. The respective genes have been obviously “stolen” by viruses from the host genomes and then have been modified. Detailed characterization of these vi-ral elements, which induce or subvert the host’s cytokine res-ponses against viral infection, may contribute to a better under-standing of the mechanisms which help the viruses to escape immune surveillance. Such knowledge have potential implica-tions for viral epidemiology, treatment or prevention of viral and inflammatory diseases, and for the development of safer vaccines. Examples of viruses indicate, that “capturing” of the immunomodulatory genes may be a more general strategy used also by other types of pathogenic or parasitic organisms to eva-de the immune responses of their hosts. (Tab. 2, Fig. 2, Ref. 73.) Key words: viroceptors, virokines, cytokines, immunomodu-lation, herpesviruses, poxviruses.AbstraktKontsek P., Kontseková E.:Virokíny a viroceptory — imunomodulátory vírusov s klinic-kým a terapeutickým dosahomBratisl. lek. Listy, 101, 2000, è. 7, s. 371–382Vírusy si poèas evolúcie vyvinuli rozmanité sofistikované straté-gie pre interakcie s imunologickým systémom hostite¾ov. Jednou z obranných stratégií, ktoré zasahujú do imunologických reakciíinfikovaného organizmu využíva vírusový proteín, ktorý priamo interferuje s cytokínovým systémom. Medzi tieto cytokínové re-ceptory sú zaradené i vírusové homológy cytokínov (virokíny) a vírusové homológy cytokínových receptorov (viroceptory) produkované a vyluèované bunkou infikovanou vírusom. Viro-kíny a vireceptory sú zakódované ve¾kými DNA herpes a poxví-rusmi. Príslušné gény boli zjavne …ukradnuté“ vírusmi z hostite-¾ovho genómu a následne zmodif ikované. Podrobnácharakteristika týchto vírusových elementov, ktoré indukujú ale-bo subvertujú hostite¾ovu cytokínovú reakciu na vírusovú infek-ciu, môžu prispie• k lepšiemu pochopeniu mechanizmu, ktorýpomáha vírusom uniknú• imunologickej surveillance. Táto zna-los• má potenciálne vplyv na vírusovú epidemiológiu, lieèbu alebo prevenciu vírusových zápalových ochorení a pre rozvoj bezpeènejších vakcín. Príklady vírusov indikujú, že vychytáva-nie imunomodulaèných génov môže by• všeobecnejšou straté-giou používanou i inými typmi patogénnych alebo parazitárnych organizmov na vyhnutie sa imunologickej reakcii ich hostite¾a. (Tab. 2, obr. 2, lit. 73.)K¾úèové slová: viroceptory, virokíny, cytokíny, imunomodulácia, herpesvírusy, poxvírusy.Institut of Neuroimmunology, Slovak Academy of Sciences, Bratislava. bll@fmed.uniba.skDepartment of Microbiology and Virology, Faculty of Natural Sciences, Comenius University, BratislavaAddress for correspondence: P. Kontsek, Institute of Neuroimmunolo-gy SA V, Dubravska cesta 9, SK-842 45 Bratislava 4, Slovakia. Phone: +421.7.5478 8100, Fax:Neuroimunologický ústav Slovenskej akadémie vied v Bratislave a Ka-tedra mikrobiológie a virológie Prírodovedeckej fakulty Univerzity Ko-menského v BratislaveAdresa: P. Kontsek, Neuroimunologický ústav SA V, Dúbravská cesta 9, 842 45 Bratislava 4.Unikanie mechanizmom imunityKoevolúcia vírusov so svojimi hostite¾mi poskytla dostatok èasu pre vytvorenie komplexných vzájomných vz•ahov. Vírusy sú schopné efektívne sa množi• v cicavcoch aj napriek prirodze-nej obrannej odpovedi hostite¾a na infekciu. Preto vírusy musia ma• mechanizmy, ktorými sa chránia pred imunitnou odpoveïou infikovaného organizmu. Spôsob obrany vírusov pred imunit-372BRATISL LEK LISTY 2000; 101 (7): 371–382nými reakciami hostite¾a môže by• pasívny alebo aktívny. Prí-klady pasívnej obrany pozorujeme napr. pri vírusoch chrípky a HIV , ktoré sa vyhýbajú už existujúcej imunite proti urèitým kmeòom týchto agensov prostredníctvom antigénnej variability.Iné, najmä herpetické vírusy, sú schopné navodzova• latentnéinfekcie, pri ktorých sa môžu …ukry•“ pred imunitným systémom.Okrem pasívnych mechanizmov používajú mnohé vírusy prote-íny, ktoré blokujú, alebo neutralizujú zložky hostite¾ovej imuni-ty, a tak unikajú jeho obrane. Viaceré vírusy kódujú proteíny homologické s imunologickými regulaènými molekulami, ktorékontrolujú prezentáciu antigénov, úèinkujú ako cytokíny alebo cytokínové receptory, inhibujú apoptózu, alebo prerušujú kom-plementovú kaskádu (preh¾adne 1). Takúto aktívnu obranu majúnajdokonalejšie vyvinutú ve¾ké DNA vírusy schopné obsiahnu•vo svojich genómoch aj gény, ktoré nie sú nevyhnutné pre mno-ženie vírusu in vitro , ale sa využívajú pri boji s imunitným sys-témom in vivo .Fyziologickú homeostázu v mnohobunkových organizmoch riadia extracelulárne signály, vo ve¾kej miere zabezpeèované cy-tokínmi. Cytokíny sa významne zúèastòujú aj na kontrole imu-nitnej odpovede voèi infekèným mikroorganizmom. Prispievajúk proliferácii a diferenciácii lymfocytov a iných terèových bu-niek, usmeròujú zápal a priebeh bunkovej i humorálnej imunit-nej odpovede. Preto neprekvapuje, že vírusy pre ovládnutie bu-niek hostite¾a zrejme …ukradli“ niektoré gény ich cytokínového systému, ktoré v upravenej podobe využívajú ako …navodzova-èe“ alebo …prerušovaèe“ cytokínovej signalizácie. Takýmto spô-sobom vírusy priamo inhibujú, alebo brzdia poèetné antivíruso-vé procesy spúš•ané cytokínmi, prípadne mobilizujú bunky hos-tite¾a s cie¾om zvýšenia efektívnosti množenia vírusu (preh¾ad-ne 1, 2). V tomto preh¾adnom èlánku sa budeme zaobera•vírusovými proteínmi, ktoré sú homologické cytokínom alebo cytokínovým receptorom a v súèasnosti sa oznaèujú ako virokí-ny a viroceptory.Charakterizácia virokínov a viroceptorovTermín virokín vznikol roku 1988 ako oznaèenie pre vírusovéproteíny sekretované z infikovaných buniek, ktoré napodobòujúimunitné regulaèné molekuly (napr. proteín viažuci komplement)alebo cytokíny (3). Názov viroceptor sa objavil roku 1991 a zahr-òoval solubilné vírusové proteíny, ktoré sú homológmi bunkových receptorov pre cytokíny (4).Virokíny a viroceptory sa nevyskytujú pri všetkých typoch vírusov. Dosia¾ sa našli len u dvoch èe¾adí ve¾kých DNA vírusov — u poxvírusov a herpesvírusov (obr. 1). Herpetické vírusy súfylogeneticky starou rodinou ve¾kých dvojvláknových DNA víru-sov, ktoré sa množia v jadre buniek. Tieto vírusy nenavodzujúakútnu infekciu prejavujúcu sa mobilizáciou zápalových a proti-vírusových cytokínov, ale vyvolávajú latenciu umožòujúcu unik-nú• imunitnému systému a dlhodobo perzistova• v hostite¾ovi (5).Poxvírusy patria medzi najväèšie eukaryotické dvojvláknové DNA vírusy, ktoré majú schopnos• množenia v cytoplazme infikova-ných buniek. Spôsobujú akútne cytolytické infekcie mobilizujúce zápalové a antivírusové zložky hostite¾ovej imunity (6). Pri her-pesvírusoch sa èastejšie stretávame s virokínmi, kým pri poxvíru-soch sú bežnejšie viroceptory. Táto skutoènos• odráža podstatnéodlišnosti v životnom cykle oboch vírusových èe¾adí.Jeden vírus môže súèasne kódova• aj nieko¾ko rozdielnych virokínov a/alebo viroceptorov. V o všeobecnosti majú virokíny vyššiu aminokyselinovú zhodu (približne 25—50 %) so svojimi bunkovými homológmi ako viroceptory (15—30 %). Štruktúrna homológia sa nemusí prejavova• v celej dåžke porovnávaných ví-rusových a bunkových molekúl, ale èastejšie zahròuje iba urèitépolypeptidové domény, ktoré sú však rozhodujúce pre interakciu s cytokínovým receptorom alebo s cytokínom.Ako a kedy získali vírusy gény pre virokíny a virocepto-ry? Vo všeobecnosti sa predpokladá, že tieto gény boli pôvod-ne bunkovými génmi hostite¾a. V priebehu evolúcie DNA ví-rusy tieto bunkové gény získali a následne štruktúrne optima-lizovali z h¾adiska vlastných potrieb. Pretože väèšina víruso-vých homológov bunkových génov neobsahuje intróny, boli pravdepodobne získané mechanizmom zahròujúcim reverznútranskripciu. Herpesvírusy mohli získa• hostite¾ove gény po-èas množenia vírusov v jadre. Naproti tomu poxvírusy však nemajú žiadnu nukleárnu rastovú fázu, ani nekódujú reverznútranskriptázu. Možno, že niektoré hostite¾ské imunomodulaè-né molekuly (napr. IFN typu I) sa pôvodne získali z víruso-vých genómov (7).Fig. 1. Virokines and viroceptors produced by cells infected with herpesviruses and poxviruses. Virokines: vC4bBP — viral C4b bin-ding protein, vIL6 — viral IL6, vIL8 — viral IL8, vIL10 — viral IL10, vIL17 — viral IL17, vGF — viral growth factor, vMIP1a —viral macrophage inhibitory protein 1a, vMIP1b — viral macrop-hage inhibitory protein 1b, vRANTES — viral RANTES. Virocep-tors: vCCR — viral membrane receptor for CC chemokines, vCXCR — viral membrane receptor for CXC chemokines, vCSF-1R — vi-ral receptor for colony stimulating factor 1, vIFNalpha/beta/ome-ga-R — viral receptor for type I IFN, vIFNgamma-R — viral re-ceptor for type II IFN, vILbeta-R — viral receptor for IL-1beta,vCKBP — viral chemokine binding protein, vTNF-R — viral re-ceptor for TNF.Obr. 1. Virokíny a viroceptory produkované bunkami po infekcii herpesvírusmi a poxvírusmi. Virokíny: vC4bBP — vírusový C4b viažuci proteín, vIL6 — vírusový IL6, vIL8 — vírusový IL8, vIL10— vírusový IL10, vIL17 — vírusový IL17, vGF — vírusový rasto-vý faktor, vMIP1a — vírusový makrofágy inhibujúci proteín 1a,vMIP1b — vírusový makrofágy inhibujúci proteín 1b, vRANTES — vírusový RANTES. Viroceptors: vCCR — vírusový membráno-vý receptor pre CC chemokíny, vCXCR — vírusový membránovýreceptor pre CXC chemokíny, vCSF-1R — vírusový receptor pre faktor stimulujúci rast kolónií, vIFNalfa/beta/omega-R — víruso-vý receptor pre IFN typu I, vIFNgama-R — vírusový receptor pre IFN typu II, vILbeta-R — vírusový receptor pre IL-1beta, vCKBP — vírusový proteín viažuci chemokín, vTNF-R — vírusový recep-tor pre TNF.373KONTSEK P, KONTSEKOVA E: VIROKINES AND VIROCEPTORS — VIRAL ...VirokínyV súèasnosti rozumieme pod pojmom virokíny hlavne víru-sové homológy cytokínov, ktoré po väzbe na príslušný cytokínovýreceptor navodia v terèových bunkách biologické úèinky. Niektorévirokíny po naviazaní na membránový receptor nevyvolajú signa-lizáciu, ale pôsobia ako antagonisty cytokínov. Preh¾ad doteraz známych virokínov je v tabu¾ke 1.Vírusový interleukín-6 (vIL-6)IL-6 je cytokín sekretovaný mnohými typmi buniek, ktorý riadi funkciu lymfocytov B a T, hematopoézu a reakcie akútnej fázy.¼udský herpesvírus 8 (HHV -8 alebo KSHV — Kaposi’s sarco-ma-associated herpes virus) je gamaherpesvírus, ktorý sa dokázal v léziách Kaposiho sarkómov všetkých typov. Bunky infikovanés HHV -8 vyluèujú proteín podobný ¾udskému IL-6 (8). Vírusom kódovaný homológ IL-6 má in vitro biologické úèinky podobnéúèinkom ¾udského IL-6. Je možné, že vIL-6 vyvoláva in vivo aj procesy analogické procesom navodzovaným endogénnym IL-6,ktoré môžu ma• úlohu pri vzniku Kaposiho sarkómu alebo Castle-manovej choroby, èi iných malignancií. Potenciálna úloha vIL-6pri Kaposiho sarkóme by mohla by• sprostredkovaná expresiou tohto proteínu poèas buï latentnej alebo lytickej infekcie napad-nutých tkanív (9).Vírusový interleukín-10 (vIL-10)IL-10 je cytokín produkovaný subpopuláciami pomocných T -lymfocytov, ktorý brzdí aktiváciu syntézy cytokínov lymfocytmi TH1, aktivuje monocyty a stimuluje proliferáciu buniek B, tymo-cytov i žírnych buniek. Vírus Epsteina a Barrovej (EBV) je ve¾mi rozšírený ¾udský gamaherpetický vírus, ktorého tkanivový tropiz-mus je ohranièený na B-lymfocyty a epitelové bunky primátov.Produkt génu BCRF1 tohto vírusu má ve¾mi vysokú 89 % amino-kyselinovú identitu s maturovaným ¾udským IL-10 (10) a dokáže aktivova• cicavèí receptor pre IL-10 s následnou inhibíciou pro-dukcie zápalových cytokínov bunkami TH1. Vírusový IL-10 máspoloèné mnohé biologické úèinky s ¾udským IL-10: tlmí syntézu IFN-gama a kostimuluje proliferáciu a protilátkovú sekréciu ¾ud-skými B-bunkami. Tento virokín s najväèšou pravdepodobnos•ou napomáha EBV vyhnú• sa antivírusovému pôsobeniu IFN-gama v organizme a súèasne napomáha replikácii EBV alebo transfor-mácii B-buniek aktiváciou ich vnútrobunkového metabolizmu (11).Aj ïalší gamaherepsvírus — konský herpesvírus 2 (konský HV -2)— kóduje proteín s vysokou homológiou s ¾udským a myším IL-10, èi produktom BCRF1 (12). Úloha tohto vIL-10 pri vírusovej patogenéze u koní sa dosia¾ nesledovala.Proteín homologický s cicavèími a vírusovými IL-10 kóduje aj poxvírus orf, ktorý infikuje ovce, kozy aj ¾udí a vyvoláva akút-ne nákazlivé kožné ochorenie (13). Štruktúrna homológia víruso-vého proteínu naznaèuje, že jeho gén sa získal poèas evolúcie z ov-ce. Vírusový IL-10 vyvoláva biologické úèinky identické s úèin-kami ovèieho IL-10.Vírusové homológy IL-10 sú pravdepodobne úèinnými sup-resormi zápalu. Aký je predpokladaný mechanizmus ich úèinkov?Jedným zo spôsobov zníženia zápalovej odpovede je zmena po-meru medzi bunkami TH1 a TH2. Kým bunky TH1 prostredníc-tvom produkovaných prozápalových cytokínov IL-2 a IFN-gama stimulujú zápalovú (bunkovú) odpoveï, bunky TH2 a nimi pro-dukované cytokíny bunkovú imunitu znižujú a stimulujú humo-rálnu odpoveï. IL-10 sekretovaný bunkami TH2 potláèa zápal,protivírusovú odpoveï a efektorové funkcie buniek TH1. Zníže-nie syntézy prozápalových cytokínov úèinkom vIL-10 by potomTab. 1. Virokines encoded by herpesviruses and poxviruses.Tab. 1. Virokíny kódované herpetickými vírusmi a poxvírusmi.374BRATISL LEK LISTY 2000; 101 (7): 371–382mohlo ochráni• infikované bunky pred zápalovou odpoveïou, cy-tolýzou NK-bunkami a apoptózou poèas prvých štádií vírusovej infekcie (13).Vírusový interleukín-17 (vIL-17)IL-17 je cytokín produkovaný aktivovaným T -lymfocytmi CD4+, stimuluje fibroblasty k sekrécii IL-6 a IL-8. Herpesvírus saimiri (HVS) je T -lymfotropný gamaherpesvírus navodzujúci asymptomatickú infekciu u opíc maèiakov, no infekcia primátov …Nového sveta“ vedie k fatálnym lymfoproliferatívnym ochore-niam. HVS dokáže transformova• ¾udské T -bunky, ktoré si udržia viaceré funkcie primárne aktivovaných T -lymfocytov. HVS obsa-huje gén, ktorý v infikovaných bunkách navodzuje sekréciu pro-teínu homologickému s ¾udským IL-17 (14). Vírusový aj cicavèíIL-17 stimulujú sekréciu IL-6, kostimulujú proliferáciu T -lymfo-cytov a stimulujú transkripèný faktor NF kapa B. Tento virokín je príkladom toho, ako môžu vírusové imunomodulaèné proteíny prispie• k odhaleniu dovtedy neznámych komponentov cytokíno-vého systému u hostite¾ov — umožnil objavenie bunkového re-ceptora pre IL-17 u èloveka (14).Vírusové chemokínyPrílev špecializovaných populácií leukocytov do miest víru-sovej infekcie a zápalu je prevažne usmeròovaný ve¾korodinou chemoatraktantových cytokínov — chemokínov. Chemokíny sa delia pod¾a poètu a priestorového usporiadania prvých dvoch kon-zervovaných cysteínových rezíduí do dvoch ve¾kých podrodín CXC (prerušený motív CC) a CC (neprerušený motív), a najnovšie boli opísané nové dve podrodiny s jediným zástupcom - CX 3C (frak-talkín) a C (lymfotaktín) (15). Ich zadelenie pribbližne koreluje s populáciami terèových buniek, na ktoré pôsobia. CXC chemo-kíny, ako napr. IL-8, sú vo všeobecnosti aktivátory a chemoatrak-tanty pre neutrofily. Naproti tomu CC chemokíny (napr. RAN-TES — regulated activation normal T expressed and secreted) pri-•ahujú a aktivujú monocyty, bazofily, eozinofily a niektoré T -bunky.Vírus Marekovej choroby (Marek’s disease virus — MDV) je onkogénny alfaherpesvírus vyvolávajúci nádorové ochorenia u hy-diny. V jeho genóme sa našiel gén s tromi intrónmi, ktorý kóduje proteín štruktúrne homologický s CXC chemokínom IL-8 (16).Vírusový polypeptid obsahuje vysokokonzervovaný motív CXC,ktorý sa zúèastòuje na väzbe s bunkovým receptorom, chýba však sekvencia ELR, konzervovaná vo všetkých molekulách IL-8. Je možné, že vIL-8 sa môže viaza• na bunkový receptor, ale nenavo-dzuje prenos signálu, takže funguje ako antagonista hostite¾ovho IL-8. Alternatívou je hypotéza, že vIL-8 usmeròuje prílev kura-cích B-buniek do miesta infekcie, èo je kritický krok pre navode-nie poèiatoènej fázy infekcie s MDV (16).Mnohé herpetické vírusy obsahujú gény homologické génom pre CC chemokíny (preh¾adne 17). To naznaèuje, že ovplyvnenie chemokínovej signalizaènej dráhy môže ma• významnú úlohu v pa-togenéze týchto vírusov. ¼udský herpesvírus 6 (HHV -6) patriaci do podèe¾ade betaherpesvírusov infikuje in vitro hlavne T -lymfo-cyty a navodzuje u èloveka akútne a latentné infekcie. Genóm HHV-6 obsahuje gén U83 kódujúci proteín príbuzný CC chemo-kínom (18). Kým funkèná aminoterminálna oblas• vírusovej mo-lekuly je konzervovaná, jej karboxyterminálna èas• je výrazne zmenená. Preto maturovaný proteín preukazuje len miernu ami-nokyselinovú identitu s ¾udskými CC chemokínmi. Virokín sek-retovaný z infikovanej bunky je biologicky aktívny, ale jeho bun-kový receptor nebol ešte identifikovaný (19). Uvažuje sa o úlohe virokínu pri množení HHV -6 in vivo aktiváciou a usmeròovaním buniek do miesta vírusovej infekcie.¼udský gamaherpesvírus HHV -8 kóduje až tri elementy štruk-túrne podobné ¾udským CC chemokínom (20). Dva z nich (vMIP-1A a vMIP-1B) (MIP — macrophage inflammatory protein) vznik-li zrejme duplikáciou génu, ktorý sa získal od jedného hostite¾a,kým gén pre tretí vírusový chemokín BCK (beta-chemokine) bol asi získaný nezávisle (preh¾adne 17). Èlenovia CC chemokínovej rodiny MIP/RANTES bránia vstupu HIV -1 do bunky zábranou väzby s chemokínovým receptorom CCR5. Aj vírusový MIP-1A a MIP-1B sú schopné blokova• infekciu makrofágotropným kme-òom HIV cez tento receptor. Syntetický vMIP-1B redukoval aj infekènos• subtypov HIV , ktoré využívajú pre vstup do bunky re-ceptory CCR3 a CXCR4 (8, 9, 21). Vírusový MIP-1B bol charak-terizovaný ako univerzálny inhibítor chemokínov viažúcich sa na receptory CCR1, CCR2, CCR5, CXCR4 ale nie na receptory CXCR1 a CXCR2 (21). Syntetický vMIP-1B však prekvapujúco pri väzbe na bunkový receptor CC3R navodil biologické úèinky v ¾udských eozinofiloch. Je možné, že vMIP-1B umožòuje na-hromadenie buniek, ktoré nesú receptor CC3R (TH2-bunky, eozi-nofily a bazofily), a tým mení lokálnu imunitnú odpoveï z anti-vírusovej typu TH1 na menej úèinnú typu TH2 (preh¾adne 17).Funkcia BCK nebola zatia¾ charakterizovaná. Myšací cytomega-lovírus (betaherpesvírus) navodzuje v infikovaných bunkách tvor-bu a sekréciu vírusového proteínu (MCK-1), ktorého karboxyter-minálna èas• je homologická s rôznymi cicavèími CC chemokín-mi (22). Predpokladaná úloha MCK-1 (mouse cytomegalovirus K-1) v patogenéze by mohla spoèíva• v jeho úèinku ako chemo-taktického agonistu alebo antagonistu, prípadne vo vyvolávanízmien pri aktivácii alebo diferenciácii buniek, ako sú makrofágy.Vírus molluscum contagiosum je ¾udský tumorigénny poxví-rus. Spôsobuje asymptomatické kožné nádory u detí a sexuálne aktívnych dospelých, ako aj ochorenia asociované s AIDS. Vírus kóduje proteín štruktúrne patriaci do rodiny CC chemokínov a vy-kazujúci sekvenènú homológiu s ¾udským MIP-1ß (23). Tomuto virokínu chýba aminoterminálny segment, ktorý je pri chemokí-noch potrebný pre navodenie biologickej aktivity. Preto sa predo-kladá, že funguje ako chemokínový antagonista a mohol by inhi-bova• zápal. T ýmto sa vysvet¾uje chýbajúca alebo oneskorená zá-palová odpoveï pri kožných léziách vyvolaných týmto vírusom.Aký je predpokladaný biologický význam vírusových chemo-kínov? Usudzuje sa, že by mohli do miesta infekcie privádza• …èer-stvé“ leukocyty pre následnú infekciu vírusom a napomáha• jeho rozšíreniu v organizme. Uvažuje sa aj o možnosti, že vírusovéchemokíny sekretované z infikovaných buniek presmerujú lokál-nu imunitnú odpoveï od rastúcej antivírusovej typu TH1, tým že hromadia bunky, ktoré preferujú menej úèinnú odpoveï typu TH2,a teda napomáhajú proliferácii vírusov. Vírusové chemokíny pô-sobiace ako antagonisty chemokínových receptorov môžu bráni•špecifickému prísunu niektorých populácií leukocytov (napr. an-tivírusových NK-buniek) do miest infekcie (preh¾adne 17).Vírusové rastové faktoryRastové faktory sú cytokíny, ktoré po väzbe na bunkový re-ceptor spúš•ajú signalizaènú kaskádu zahròujúcu fosforyláciu ty-375KONTSEK P, KONTSEKOVA E: VIROKINES AND VIROCEPTORS — VIRAL ...rozínov a aktiváciu systému sekundárnych mesengerov. Najèas-tejšou biologickou odpoveïou terèovej bunky je proliferácia. Bun-ky infikované vírusom vakcínie vyluèujú glykoproteín (VGF —vaccinia virus growth factor), ktorý je štruktúrne príbuzný epider-málnemu rastovému faktoru (EGF) a transformujúcemu rastové-mu faktoru (TGF) (24). VGF sa viaže na bunkový receptor pre EGF , indukuje jeho autofosforyláciu a stimuluje mitózu (25,26).Vírusové rastové faktory štruktúrne príbuzné s rodinou EGF sa našli aj pri ïalších poxvírusoch (vírus varioly, vírus myxomatózy,vírus fibrómu králikov) (preh¾adne 27, 28). Rastový faktor vírusu myxomatózy, ktorý je homologický s VGF , má aktivity podobnéúèinkom EGF a transformujúcemu rastovému faktoru (TGF)-alfa.Inaktivácia génov pre tieto virokíny pri leporipoxvírusoch (vírus myxomatózy, vírus fibrómu králikov) redukovala virulenciu mu-tantných vírusov u králikov a zabraòovala hyperplázii charakte-ristickej pre patológiu poxvírusov (preh¾adne 28).Ïalší poxvírus orf (parapoxvírus) kóduje proteíny príbuznés cicavèími vaskulárnymi endotelovými rastovými faktormi (VEGF) (29). VEGF má dôležitú úlohu pri angiogenéze a jeho vírusový analóg má v podmienkach in vitro mitogénne úèinky,ktorý sa zrejme uplatòuje aj v podmienkach in vivo. Poxvírusy kódujúce homológy VEGF totiž spôsobujú v infikovanom hosti-te¾ovi (ktorým môže by• aj èlovek) pustulárne kožné lézie, ktorésa prejavujú vaskulárnou endotelovou proliferáciou (29).Pri všetkých troch podèe¾adiach herpesvírusov (alfa, beta,gama) sa dokázala schopnos• navodi• v infikovaných bunkách tvor-bu malých sekretovaných molekúl, ktoré majú podobné biologic-ké úèinky ako rastové faktory (30—32). Tieto vírusové produkty však dosia¾ neboli dostatoène charakterizované na molekulovej úrovni. RR 1 (subjednotka ribonukleotidreduktázy HSV2 má akti-vitu fosfokinázy.Existuje viacero hypotéz vysvet¾ujúcich význam vírusových rastových faktorov pre množenia vírusov v tkanivách hostite¾ských stavovcov. Funkcia týchto virokínov by mohla spoèíva• v stimulá-cii metabolickej aktivity a proliferácie neinfikovaných buniek, èo by umožnilo úèinnejšie množenie vírusu, a tým prispelo k jeho patogénnosti (28).Vírusový komplementový kontrolný proteínKomplementový systém je jeden zo základných výkonných systémov vrodenej humorálnej imunity. Pri niektorých vírusoch sa našli proteíny, ktoré sú homologické s rodinou cicavèích prote-ínov regulujúcich aktiváciu komplementu. Proteín kontrolujúci komplement kódovaný vírusom vakcínie (VCP — vaccinia virus control protein) bol prvým solubilným vírusovým proteínom s do-kázanou imunomodulaènou funkciou a viedol k vzniku termínu virokín (3). Štruktúrne je VCP najviac podobný ¾udskému proteí-nu viažucim komplementovú zložku C4b a má najvyššiu funkènúpríbuznos• s ¾udským komplementovým receptorom CR1 (3, 33).Gén kódujúci proteín homologický s VCP sa zistil aj pri ïalšom ortopoxvíruse — víruse varioly (34). Podobný virokín oznaèenýIMP (inflammation modulatory protein) kóduje aj príbuzný po-xvírus kráv. IMP má dôležitú úlohu pri modulácii komplementom aktivovanej zápalovej odpovede hostite¾a (35). Vírusové proteíny kontrolujúce komplement boli v porovnaní s pôvodnými bunko-vými proteínmi výrazne modifikované a skrátené tak, aby si udr-žali funkène najvýznamnejšie úseky proteínov. Napr. proteín via-žuci C4b je ve¾ká molekula pozostávajúca z nieko¾kých reaktív-nych podjednotiek, ale nie je taká úèinná ako IMP (35). Sekreto-vaný glykoproteín príbuzný C4b-viažucemu proteínu sa dokázal aj pri herpetických vírusoch (herpesvírus saimiri) (36). Vírusovéproteíny kontrolujúce komplement pôsobia ako solubilné inhibí-tory komplementovej kaskády. VCP aj IMP môžu blokova• klasic-kú aj alternatívnu cestu aktivácie komplementu prostredníctvom väzby na tretí (C3b) a štvrtý (C4b) komponent tohto systému.Takáto interakcia znižuje tvorbu chemotaktických faktorov C3a,C5a, a tým tlmí prísun imunitných buniek do miesta infekcie (33).VCP zvyšuje aj virulenciu vírusu in vivo tým, že bráni komple-mentom podnietenej od protilátky závislej neutralizácii vírusu (38).Virokíny napodobòujúce proteín viažuci C4b nemajú žiadnu štruktúrnu homológiu s cytokínmi. Z h¾adiska mechanizmu ich inhibiènej funkcie majú tieto vírusové produkty bližšie k virocep-torom ako k virokínom.ViroceptoryMnohé vírusy indukujú v dôsledku infekcie tvorbu protivíru-sových a prozápalových cytokínov, ako sú interferóny (IFN) typu I a II, IL-1, TNF a chemokíny. Cytokíny navodzujú svoje úèinky po interakcii so špecifickými receptormi na povrchu terèových buniek. Mnohé membránové cytokínové receptory, tvorené jed-noduchým transmembránovým polypeptidom, sa èasto vyskytujúv sekretovanej forme. Takéto solubilné receptory sú tvorené len extracelulárnou ligand viažucou doménou, chýba im však trans-membránová oblas• a cytoplazmatická signalizaèná doména (obr.2). Viroceptory sú homológy cytokínových receptorov, ktoré súsekretované z buniek infikovaných vírusmi. Pôsobia ako inhibí-tory cytokínov tým, že viažu cytokíny a bránia ich väzbe s bun-kovými receptormi. Na rozdiel od virokínov sa viroceptory vy-znaèujú nižšou (prípadne žiadnou) sekvenènou homológiu so svo-jimi bunkovými homológmi. Poxvírusy sú jedinou vírusovou èe-¾aïou produkujúcou sekretované verzie homológov alebo analógovcytokínových receptorov (preh¾adne 39). V súèasnosti však po-Fig. 2. Comparison of the two structural types of cytokine receptors.Obr. 2. Porovnanie dvoch štruktúrnych typov cytokínových receptorov.。