HSV-1糖蛋白B和糖蛋白D的T细胞表位重组核酸疫苗的构建及其免疫原性

目的 构建Ⅰ型单纯疱疹病毒(HSV-1)糖蛋白B(gB)和糖蛋白D(gD)的T细胞表位重组核酸疫苗,并研究其作为核酸疫苗的免疫原性.方法 登录免疫表位数据库(IEDB),查阅已发表的无症状表位,联合运用SYFPEITHI、IEDB等生物信息学软件,预测潜在的HSV-1 gB和gD的T细胞表位.将已知表位和预测表位串联,...     

基于混合核函数的PSO-SVM分类算法

在数据挖掘中,支持向量机是被广泛应用的一种分类算法,其核函数的选择及参数的设定没有有效的标准。本文采用混合核函数构造兼顾学习能力和泛化性能的支持向量机算法,并利用粒子群算法来确定支持向量机的参数。应用基于混合核函数的PSO SVM算法对一个经典的分类测试数据集进行分类,将该算法与单一核函数支持向量机算法的分类结果进行比较,结果表明所提出的算法的分类性能有明显提升。     

EB病毒gp350/220抗原T-B联合表位生物信息学预测

为预测EB病毒(EBV)gp350/220抗原T-B联合表位,采用在线软件IEDB和SYFPEITHIT分别预测gp350/220抗原B细胞表位和T细胞表位,寻找该抗原B细胞和T细胞共同的区域即T-B联合表位。gp350/220抗原存在潜在的T-B联合表位区域:28-43、49-55、59-64、69-79、85-91、99-111、119-129、135-144。本文运用生物信息学方法确定了gp350/220分别存在5个T细胞抗原表位﹑6个B细胞表位和3个T-B细胞联合表位区域,为进一步研发gp350/220高价优势表位疫苗奠定基础。     

结核分枝杆菌clpP2抗原表位预测与分析

【摘要】 目的 预测结核分枝杆菌酪蛋白酶蛋白水解亚基单位2（clpP2）的抗原表位,为结核病疫苗、药物研制等提供新的靶点。方法 以clpP2蛋白的氨基酸序列为基础,采用生物信息软件DNA Star预测二级结构;运用SWISS-MODEL在线软件进行同源建模;运用VaxiPred软件综合预测T 细胞抗原表位,用ABCpred、COBEPro和BepiPredPred 软件综合预测其B 细胞抗原表位;采用DNA Star Protean、SignalP、TMHMM在线软件和NCBI数据库分析其免疫学相关信息。结果 clpP2蛋白结构丰富,含有较多潜在细胞毒性T细胞和辅助T细胞表位; 也含有较多的B细胞线性和构象优势表位,这些区域亲水性、表面可能性和柔韧性指数都较高。结论 clpP2蛋白具有诱导免疫应答的潜能,可以作为结核监测、治疗、预防的新靶点。     

靶向人端粒酶逆转录酶T细胞表位肽的治疗性癌症疫苗研究进展

人端粒酶逆转录酶(hTERT)是人端粒酶的催化亚单位,正常成熟组织中基本无表达,而在多数恶性肿瘤中高表达,而使其成为恶性肿瘤特异性疫苗免疫治疗的首选抗原.T细胞表位肽疫苗是用抗原的T细胞表位制备的疫苗,在肿瘤免疫治疗中有其独特的优势.hTERT的T细胞表位肽疫苗可诱导机体产生特异性免疫应答,在小鼠体内显示了抗肿瘤效应,并已进入人体试验阶段,显示出较好的应用前景.文中就hTERT的T细胞表位肽疫苗在恶性肿瘤中的免疫治疗的研究进展作一综述.     

结核分枝杆菌RD12区T细胞表位分布情况预测及分析

目的预测并分析结核分枝杆菌（MTB）RD12区4个抗原的CD4^＋T和CD8^＋T细胞表位分布情况。方法在NCBI数据库上查询并获得各个抗原的氨基酸序列,用Blast分析其与MTB复合群及人类蛋白的同源性。利用SYFPEITHI、NETCTL、BIMAS和NetMHC数据库预测并分析MTB的RDl2区抗原CD8^＋T细胞表位的分布情况;利用NetMHC数据库预测并分析MTB的RD12区抗原的CD4^＋T细胞表位的分布情况。然后,综合CD4与CD8表位预测,筛选出优势表位肽段。结果通过预测与分析,初步筛选出MTB的RD12区4个抗原的CD8^＋T细胞候选表位16个;CD4^＋T细胞的强结合候选表位234个,弱结合候选表位505个,综合CD4与CD8表位预测并分析,最终筛选出13个优势表位肽段。结论预测出来的T细胞候选表位将为结核病的特异性诊断及新的抗结核多表位疫苗的研究奠定基础。     

现有乙型肝炎多表位疫苗在中国人群中的理论免疫效果评价

目的预测现有乙型肝炎（HBV）多表位疫苗在中国的理论免疫应答率,并做出评价。方法利用“中国多表位疫苗设计的HLA Ⅰ积累表型频率空间预测系统”计算现有的HBV表位DNA疫苗所涉及的HLA A、B限制性表位组合在中国人群中的累积表型频率（CPF）,得出理论免疫应答率,并绘制CPF预测等值线图,给出评价。结果现有各HBV多表位疫苗对中国人群的理论免疫应答率偏低,仅较多表位组合的疫苗理论免疫应答率高。现有HBV多表位疫苗存在不同方面的问题：大部分此类疫苗对中国人群的理论免疫应答率低;少数此类疫苗理论免疫应答率高,但为较多表位的组合,不符合多表位疫苗设计的原则,并没有用最少的表位组合达到最高的免疫应答率。结论现有的几种主要的HBV多表位疫苗并不能较好地符合中国人群的特点,效果不佳。     

结核杆菌抗原Ag85C的HLA-A*0201限制性CD8+CTL表位的预测及鉴定

目的:预测及鉴定结核杆菌(Mycobacterium tuberculosis, Mtb)抗原Ag85C的HLA-A*0201限制性CD8 CTL表位,为基于表位的结核疫苗研究提供依据.方法:应用SYFPEITHI数据库预测结核杆菌抗原Ag85C序列中可能存在的HLA-A*0201限制性T细胞表位,利用T2细胞株分析各预测的抗原肽与HLA-A*0201分子的亲合力,选取高亲合力肽诱导特异性CTL细胞,检测各高亲合力肽刺激其特异性CTL细胞分泌的IFN-γ水平、在体外的CTL增殖反应以及细胞杀伤毒性,逐步鉴定出Ag85C的HLA-A*0201限制性CD8 CTL表位.结果:SYFPEITHI数据库从Ag85C序列中预测到14条能够结合HLA-A*0201分子的抗原肽,其中3个抗原肽(170～178 aa、317～325 aa和144～153 aa)显示与T2细胞上HLA-A*0201分子有高结合力,而抗原肽FLTREMPAWL(144～153 aa)能够诱导大多数HLA-A*0201阳性结核患者及PPD( )健康志愿者产生特异性CTL细胞,并分泌大量的IFN-γ,能够诱导CTL体外发生增殖,能够产生特异性杀伤活性.结论:成功鉴定出抗原肽FLTREMPAWL(144～153 aa)结核杆菌抗原Ag85C的HLA-A*0201限制性CD8 CTL表位,可作为结核疫苗设计的候选表位,为进一步研发新型有效的抗结核疫苗奠定了基础.     

基于GIS的中国人群乙肝多表位疫苗的预测

目的预测可能的HLA Ⅰ类限制性HBV特异性CTL表位组合在中国人群的理论免疫应答率,旨在指导乙型肝炎（HBV）多表位疫苗的研制和应用。 方法利用“中国多表位疫苗设计的HLA Ⅰ积累表型频率空间预测系统”计算HLA A、B限制性HBV特异性CTL表位组合在中国人群中的累积表型频率（CPF）,得出理论免疫应答率,并绘制CPF预测等值线图,比较结果。 结果HLA A或B单一超型组合针对中国人群的理论免疫应答率普遍偏低。HLA A和B超型组合针对中国人群的理论免疫应答率相对较好。 结论根据不同HLA组分组合设计的多表位疫苗（或DNA疫苗）在中国各地人群中的免疫效果不同,根据中国人HLA分布特点,进行疫苗理论免疫应答率预测研究,可以指导制备适合中国人群的HBV特异性CTL多表位疫苗,应用前景广阔,有重要的指导意义。     

粉尘螨Der f 38的结构与免疫优势表位的生物信息学预测分析

目的：分析粉尘螨过敏原Der f 38的理化性质及结构特征，并综合生物信息学工具预测其免疫优势B、T细胞表位。方法：从世界卫生组织/国际免疫学联合会的过敏原数据库中获取Der f 38的氨基酸序列信息，利用ProtParam对Der f 38的理化性质特征进行分析。通过SWISS-MODEL、AlphaFold2及GalaxyRefine对Der f 38的三维结构模型进行综合构建、优化得到最佳的蛋白模型。利用DNAStar Protean、Bepipred 2.0、ElliPro、DiscoTop、TepiTool进行Der f 38蛋白的B细胞线性、构象型表位以及T细胞表位的综合预测。结果：Der f 38为分子量13.99kDa且等电点为9.08,总平均亲水性为-0.337,不稳定指数为31.79。通过多种生物信息学工具综合分析，共得到4个优势B细胞线性表位、8个B细胞构象表位和8个T细胞表位。结论：Der f 38属于碱性蛋白，具有一定的亲水性和稳定性，含有多个免疫优势的B细胞和T细胞抗原表位，为进一步针对该蛋白的疫苗和过敏原特异性免疫疗法的设计与开发提供理论参考。     

总量均衡区间与提高宏观调控精度问题

现代市场经济条件下，由于供给方调整供给数量须耗费调节成本，因而传统分析中的“总量均衡中心点”两侧便分别存在着“低位临界点”与“高位临界点”，这两点界定了一个特殊的“总量均衡区间”。总量均衡区间的存在，导致按传统理论进行的宏观调控必然出现一种系统性偏差，从而直接影响宏观调控的精度。为消除这一偏差、提高调控精度与质量，在宏观调控过程的控制上有必要确立与遵循“临界点原则”。     

推拿手法实践操作综合考核体系的构建--以湖南中医药大学为例

推拿手法实践操作考核是推拿手法考核的重要组成部分,是真实、客观、公平、公正的评价学生动手能力的一种有效的方法和手段。探索出适合现代推拿手法教学和考核的方式是推拿教师必须积极面对的一个重要课题。湖南中医药大学针灸推拿学院推拿教学科研人员经过多年的思考及5年的探索和不断改进,建立了一套利用目测法、体测法和机测法在推拿手法考核中适合本、专科不同专业层次人才的推拿手法实践操作综合考核体系。     

Interpretation of single progesterone measurement in diagnosis of anovulation and defective luteal phase: observations on analysis of the normal range

Single serum progesterone determinations were made in 79 apparently normal women with a regular menstrual cycle. A normal range (40 subjects) was derived from the concentrations in the follicular phase and used to define an "anovular" range for luteal phase values (nine out of 39 subjects). The remaining luteal phase values were used to construct an "ovular" range for the luteal phase and, within this range, to define a group of values (less than the 20th centile) which could be described as a "defective luteal phase." The cut off limits between ovular and anovular and between normal and defective luteal phases were respectively two and four times the follicular phase median. It is proposed that the numerical findings of this study may be used as a rule of thumb for defining normality and abnormality from a single serum progesterone determination.     

Admitting a patient "to" observation or "for" observation--what is the difference?

Coding and billing of a patient placed in "observation" status can be confusing, especially in a busy Emergency Department. If physicians know the rules related to observation status, they can avoid denials or accusations of false claims. Documenting either "admit to observation" or "admit for observation" can be interpreted differently for admission status and billing services. From a billing prospective, writing "admit for observation" would be interpreted as an inpatient admission (if the documentation throughout the medical record is consistent with inpatient status). If the order states "admit to observation," this normally would be interpreted as an order for outpatient observation. Physicians are encouraged to write admission orders that clearly state the level of services intended; for example, wording such as "place in outpatient observation" or "admit as inpatient," to clearly convey the physician's intent.     

乙型肝炎病毒免疫逃避株表面抗原决定簇编码区的序列分析

应用聚合酶链反应（ＰＣＲ）产物直接测序，在国内首次发现１例持续高滴度乙型肝炎表面抗原（ＨＢｓＡｇ）和抗一ＨＢｓ共存者携带的乙型肝炎病毒ＤＮＡ第５３２位碱基Ａ被Ｇ取代，推导其“ａ”决定簇中第１２６位苏氨酸被丙氨酸取代，提示该株“ａ”决定簇第一个结构环疏水性增加，由此可能导致其抗原性改变，而诱发免疫逃避株形成。     

The impact of fine-needle aspiration biopsy on surgery for single thyroid nodules

Biopsy by fine-needle aspiration has emerged as the most effective single technique for the investigation of single thyroid nodules. A comparison was made of patients who underwent surgery for single nodules in 1979 (before the introduction of fine-needle aspiration biopsy to this Department) and in 1984, after this technique had become fully established. Biopsy by fine-needle aspiration proved to be reliable in the selection of patients for surgery. The incidence of malignancy in each category was: malignant, 83%; atypical, 26%; inadequate, 7%; and benign, none. This contrasted with nuclear scanning and ultrasound techniques that were in use over that period, where the malignancy rate of nodules that showed no uptake of radioisotope was 11% and that of an ultrasound scan that demonstrated a "solid" or "cystic/solid" was 16%. Similarly, nodules that showed an uptake of radioisotope or an ultrasound scan that demonstrated a "cystic" image did not exclude malignancy reliably. As a result of fine-needle aspiration biopsy, there was a 60% reduction in the number of thyroidectomies for single nodules during its use with a higher yield, but no change in the absolute number, of patients with malignancy of the thyroid gland.     

Kant, curves and medical learning practice: a reply to Le Morvan and Stock

In a recent paper published in the Journal of Medical Ethics, Le Morvan and Stock claim that the kantian ideal of treating people always as ends in themselves and never merely as a means is in direct and insurmountable conflict with the current medical practice of allowing practitioners at the bottom of their "learning curve" to "practise their skills" on patients. In this response, I take up the challenge they issue [corrected] and try to reconcile this conflict. The kantian ideal offered in the paper is an incomplete characterisation of Kant's moral philosophy, and the formula of humanity is considered in isolation without taking into account other salient kantian principles. I also suggest that their argument based on "necessary for the patient" assumes too narrow a reading of "necessary". This reply is intended as an extension to, rather than a criticism of, their work.     

浅谈实验动物饲养管理和使用计划中 “灾难计划”的制定与实施

作为一个健全的实验动物饲养管理和使用计划的必须组成部分,"灾难计划(disaster plan)"的制定对任何研究机构均是非常重要的。目前,国内多数实验动物饲养和使用机构均会制定一份突发事件下的紧急预案(emergency operation plan,EOP),但多数机构均没有制定完善的运营连续性计划(business continuity plan,BCP)。本文将就"灾难计划"中"灾难"的定义、如何制定和实施完善的"紧急预案"、如何制定和实施完善的"运营连续性计划"等内容分别进行浅述,以期呈现一个完整并专业的实验动物饲养管理和使用计划中的"灾难计划"。     

Database Reusability in Intelligent Medical Systems

Reuse or reusability is not a specific, algorithmic, heuristic or only a simple set of guidelines. Database reuse means the use of an existing component—a database entity—in a new context, either elsewhere in the same system or in another system. According to different definitions, an intelligent system is a power tool for thinking; but on the other side it is only a kind of information system with built-in knowledge to support decisions made by human experts. Similar conclusions could be made for intelligent medical systems and introduce the database reusability in this environment with a purpose to increase the quality of an intelligent medical system. In the paper the problem of the database reusability will be presented more in detail, especially its integration in an intelligent medical system. Finally, the results of such integration and the benefits for the medicine will be discussed.     

医疗"红包"的监督博弈分析

医生收取“红包”的问题近年来成为严重破坏医患关系的主要不良因素,为此,有关部门采取了相应的措施以加大对“红包”问题的治理力度。本文从博弈论的角度对有关政策的合理性进行了分析,指出了政策的目标与结果之间的“激励的悖论”现象。同时,对“红包”产生的经济学本质做了简单的介绍,并对其治理提出了相应的建议。