血清蛋白质谱模型对肝癌诊断的应用

目的应用表面增强激光解吸电离飞行时间质谱技术(SELDI-TOF-MS)从肝癌患者血清中筛选标志蛋白,找出最佳的标志蛋白组合模式作为临床诊断指标。方法蛋白组学图谱通过表面增强激光解吸电离飞行时间质谱产生。对20例肝癌患者和60例健康志愿者、20例肝硬化的血清蛋白质谱进行反复分析寻找合理运算规则以确定能区分肝癌和健康志愿者与肝硬化患者的蛋白组学图谱。结果发现肝癌患者和肝硬化患者、健康对照组血清蛋白质指纹图谱之间有5个标志蛋白在肝癌患者血清中高表达,1个标志蛋白在肝癌患者血清中低表达。分析系统筛选出4477Da、8943Da、13761Da、4097Da标志蛋白建立起一个肝癌的诊断模型。结论SELDI-TOF-MS技术的特异性及敏感度远远高于目前所采用的某一单独的标志物的血清学诊断,其结果对进一步研究肝癌的蛋白质组学改变及其临床应用可能具有重要意义。     

结核性胸膜炎患者血清与胸腔积液蛋白质组的初步分析

目的:比较分析结核性胸膜炎患者血清与胸腔积液蛋白质组的异同,为探讨结核性胸膜炎的发生机制和寻找诊断标志物提供实验依据.方法:采用弱阳离子交换蛋白质芯片(WCX2)处理分析样本、应用表面增强激光解析电离飞行时间质谱(SELDI-TOF-MS)技术,以蛋白质/多肽质荷比(m/z)区分不同的蛋白质/多肽,对5例结核性胸膜炎患者血清与胸腔积液蛋白质组进行描述性分析.结果:(1)在5例患者血清中检测到134种血清蛋白质/多肽,其中76种在胸腔积液中未出现;在5例患者胸腔积液中检测到269种蛋白质/多肽,其中211种在血液中未出现.(2)在5例患者血液中均检测到m/z分别为2660、3 191、4208、5 903、7 764、9 287等6种蛋白质/多肽;在5例患者胸腔积液中均检测到m/z分剐为2416、2660、2 900、2 940等4种蛋白质/多肽;在5例患者血液和胸腔积液中均检测到m/z为2 660的蛋白质/多肽.结论:结核性胸膜炎患者胸腔积液蛋白质组远比其血清蛋白质组复杂,对其进行深入研究有助于明晰结核性胸膜炎的发生机制和寻找诊断标志物.     

SELDI—TOF MS室内质量控制的初步研究

目的:表面增强激光解析电离飞行时间质谱(SELDI-TOF MS)是快速、高通量的蛋白质组学分析技术.像所有技术一样,质量控制是SELDI-TOF MS应用于临床的关键.本文就SELDI-TDF MS室内质量控制进行初步研究.方法:收集本院门诊患者血清,对仪器进行内标、外标校准后,采用Biomarker Wizard软件对同一血清样本在不同批次的芯片进行比较.结果:质量CV值小于0.1%,而血清样本的峰值的平均CV值也都控制在30%以内,质控血清也相当稳定.结论:初步建立了SELDI-TOF MS的质控方案.     

两种化学表面芯片对SELDI-TOF MS结果的影响

目的采用标准化芯片操作规程比较弱电离子交换芯片(CM10)、金属离子整合芯片(I MAC)对增强激光解析电离飞行时间质谱(SELDI-TOF MS)检测结果的影响。方法收集1份健康体检者血清,每一个芯片类型都检测8孔。分析质谱峰的数量(S/N5、S/N2.5、S/N10),计算孔间变异系数(CV),通过比较这两个指标来评估两种芯片对血清蛋白组的检测能力。结果在合适的激光能量强度下,S/N5时,IMAC所测得的质谱峰有247个,CM10所测得的质谱峰有167个,两者的质谱峰平均CV值相近,均在20%左右。结论 IMAC有更好的检测能力。     

非霍奇金淋巴瘤血清蛋白质质谱分析

目的：应用表面增强激光解析电离飞行时间质谱技术检测血清蛋白指纹图,通过差异蛋白组学筛选非霍奇金淋巴瘤（nonhodgkin’s lymphoma,NHL）特有的蛋白标记物,找出最佳的标志蛋白组合模式建立非霍奇金淋巴瘤诊断模型。方法：用Ciphergen公司生产的PBSII／C型蛋白质指纹图谱仪和AuChpi金芯片采集50例NHL患者（NHI。组）、50例淋巴结炎患者（淋巴结炎组）、50例健康志愿者（对照组）血清蛋白质指纹图谱,采用BiomakerWizard3．1版分析软件筛选差异蛋白,建立NHL诊断模型。结果：NHL患者、淋巴结炎患者、健康志愿者血清蛋白质指纹图谱之间有4个标志蛋白在NHL患者血清中高表达,3个标志蛋白在NHL血清中低表达。分析系统筛选出质荷比（M／Z）4966、9278、6633、4222、9216、9237和7714标志蛋白建立NHL诊断模型,该模型对NHL的诊断灵敏度和特异性分别为92％和98％。结论：NHL与淋巴结炎组、对照组比较血清蛋白质表达具有显著差异,筛选其中差异蛋白质可用于建立NHL预测模型。     

血清蛋白指纹技术在冠心病不稳定型心绞痛诊断中的应用

目的采用蛋白质组学新技术筛选冠心病不稳定型心绞痛（unstable angina，UA）患者血清蛋白标志分子，建立诊断不稳定心绞痛的蛋白分类模型。方法冠心病不稳定型心绞痛患者48例，男28例，女20例；正常健康人60例，患者出现症状24h内采血，分离血清。样本分为两组：第一组为训练组，包括UA患者和正常健康人各30例，性别年龄相当；第二组为盲法分析组，包括剩余18例UA患者和26例正常健康人。利用（surface enhanced laser desorption／ionization time of flight mass spectrometry，SELDI—TOF—MS）技术对血清样本进行蛋白质谱分析。采用蛋白飞行质谱仪（PBSⅡ—C型）对结合在WCX2芯片上的血清蛋白进行读取分析。采用Ciphergen Proteinchip 3．1软件分析分组数据及相关性，Biomarker Wizard软件对不同组相同质荷比的蛋白含量进行t检验，P〈0．01时具有统计学意义，用Biomarker Patterns System建立分类树模型。结果UA患者与正常人血清蛋白组比较后发现了25个表达差异蛋白，其中13个蛋白在UA患者血清中高表达，12个低表达。软件分析系统利用上述蛋白建立了一个分类模式，在训练组中敏感性和特异性均为96．6％。盲法分析显示其对UA患者的诊断敏感性为94．4％，特异性为100％，阳性预测值为100％，阴性预测值96．3％。结论SELDI技术能够有效快速地从血清中筛选出UA患者相关的标志蛋白分子，利用蛋白模式分类方法对冠心病患者进行风险评估和冠心病的筛查是一个比较好的方法。     

高发区自然人群贲门癌血清蛋白指纹图诊断模型的建立及临床价值

目的 用表面增强激光解吸离子化飞行时间质谱（SELDI-TOF-MS）分析食管癌高发区自然人群中贲门癌和正常对照血清蛋白表达谱的改变，筛选并建立高发区贲门癌血清蛋白指纹图诊断模型并探究其临床价值。方法 采用CMIO蛋白芯片及SELDI-TOF-MS技术对34例贲门癌和38例正常对照者血清蛋白指纹图谱进行检测，所得结果用ZUCI-蛋白芯片数据分析系统（ZUCI-Protein Chip Data Analyze System）软件包分析，建立贲门癌蛋白指纹图诊断模型，并用留-法交叉验证作为评估模型、判别效果的方法。结果通过软件包运算，用3个质荷比峰（5643．45793、8570．82126、15940．1533m／z）建立了贲门癌蛋白指纹图诊断模型，其准确度93．06％，敏感度85．29％，特异度100％，阳性预测值100％。结论 本组建立的诊断模型可以有效区分贲门癌和健康人，为肿瘤高发区贲门癌的诊断与筛查提供了一条崭新途径。     

SELDI技术在食管癌诊断和治疗监测中的应用

目的用蛋白质质谱分析法寻找食管癌诊断、治疗监测以及预后的生物指标。方法采用弱阳离子结合芯片(CM-10)及表面增强激光解吸/电离飞行时间质谱仪(SELDI-TOF-MS)检测食管癌149例、100例正常人的血清蛋白质谱,将获得的图谱采用Ciphergen公司的Biomarker Wizard软件分析。结果食管癌患者与正常人之间有16个差异峰,其中蛋白峰M/Z5622、7750、5322的诊断效能较高。M/Z值为3820的蛋白峰可能为食管淋巴结转移指标,M/Z5622蛋白峰可能与食管癌的远处脏器转移有关。结论该方法可快速、准确检测食管癌,简便易行,是一种有效的筛查手段。且在作为食管癌临床疗效监测及预后方面均有广阔的应用前景。     

几种分枝杆菌Middlebrook 7H9早期培养滤液蛋白质/多肽谱初步分析

目的:初步了解分枝杆菌Middlebrook 7H9早期培养滤液中蛋白质/多肽的存在状况,为进一步探讨其致病性、药物作用靶点、诊断标志物等问题打下基础.方法:利用表面增强激光解析电离飞行时间质谱技术对结核分枝杆菌(ATCC 27294)、胞内分枝杆菌(ATCC 13950)、堪萨斯分枝杆菌(ATCC 12478)、龟分枝杆菌(ATCC19977)、瘰疬分枝杆菌(ATCC 19981)、浅黄分枝杆菌(ATCC 43909)、不产色分枝杆菌(ATCC 19530)、海分枝杆菌(ATCC 927)、耻垢分枝杆菌(ATCC 19420)和戈登分枝杆菌(ATCC 14470)等10种分枝杆菌Middlebrook 7H9的第7天培养滤液进行蛋白质多肽谱分析.结果:与Middlebrook 7H9培养液蛋白质多肽谱相比,其7 d早期培养滤液分别存在有144、89、87、59、72、53、120、68、83和81种独特的早期培养滤液蛋白质多肽;结核分枝杆菌与其他分枝杆菌相比有47种独特的早期培养滤液蛋白质多肽.结论:每种分枝杆菌有其独特的早期培养滤液蛋白质多肽谱,其中某些蛋白质多肽可能与细菌的致病性相关.     

特发性肺纤维化患者支气管肺泡灌洗液中特异性蛋白标记物研究

目的 分析特发性肺纤维化(IPF)患者支气管肺泡灌洗液(BALF)中蛋白质谱变化,寻找特异性蛋白标记物,评价这些标记物对IPF的诊断价值及临床应用前景.方法 收集IPF患者及对照组BALF标本,应用表面增强激光解析/电离飞行时间质谱(SELDI-TOF-MS)技术筛选差异蛋白.通过非线性支持向量机方法建立诊断模型,并留一交叉验证法评估各模型的预测效果.结果 IPF患者BALF中筛选出8个表达有显著差异的蛋白质峰,其中检测效率最高的4个低表达蛋白质峰质荷比(m/z)分别为1947.634、1975.519、2488.535及4950.230.以这4个蛋白质峰组合建立诊断模型,其特异性和敏感性均为100%.结论 应用SELDI-TOF-MS技术分析获得的低分子量蛋白质峰在诊断中具有较高的灵敏度和特异性,这些小分子可能在IPF发病中起重要作用.     

Guns and Knives in New Mexico: Patterns of Penetrating Trauma, 1978–1993

Objective: To identify patterns of nonfatal and fatal penetrating trauma among children and adults in New Mexico using ED and medical examiner data.
Methods: The authors retrospectively sampled in 5-year intervals all victims of penetrating trauma who presented to either the state Level-1 trauma center or the state medical examiner from a 16-year period (1978–1993). Rates of nonfatal and fatal firearm and stabbing injury were compared for children and adults.
Results: Rates of nonfatal injury were similar (firearm, 34.3 per 100,000 person-years; stabbing, 35.1). However, rates of fatal injury were significantly different (firearm, 21.9; stabbing, 2.7; relative risk: 8.2; 95% confidence interval: 5.4, 12.5). From 1978 to 1993, nonfatal injury rates increased for children (p = 0.0043) and adults (p < 0.0001), while fatal penetrating injury remained constant. The increase in nonfatal injury in children resulted from increased firearm injury rates. In adults, both stabbing and firearm nonfatal injury rates increased.
Conclusions: Nonfatal injury data suggest that nonfatal violence has increased; fatal injury data suggest that violent death rates have remained constant. Injury patterns vary by age, mechanism of trauma, and data source. These results suggest that ED and medical examiner data differ and that both are needed to guide injury prevention programs.     

Systematic Reviews Published in the January 2011 Issue of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD and monthly online. The January 2011 issue (first quarterly DVD for 2011) contains 4515 complete reviews, 1985 protocols for reviews in production, and 13,521 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 641,000 randomized controlled trials, and 14,018 cited papers in the Cochrane methodology register. The health technology assessment database contains over 9300 citations. One hundred and seven new reviews have been published in the last 3 months, of which five have potential relevance for practitioners in pain and palliative medicine.     

Prise en charge des entorses externes de cheville : étude clinique préliminaire sur l’efficacité du dispositif Myolux™

Ankle sprains are the most common injury of the musculoskeletal system and are associated with significant societal and economic impacts. It has been proven that classical therapeutic strategies may not be effective in preventing recurrent injuries: the recurrence rates reported in the literature can reach 73%. In order to provide an effective rehabilitation solution, a destabilizing orthosis was developed. This device is equipped with a mechanical articulator reproducing the subtalar mechanics and placed under the heel. In this paper, we present the main results of a preliminary clinical study conducted between 2004 and 2007. All subjects included in this study were treated with the abovementioned orthosis during 10 rehabilitation sessions of 30 minutes each. Data show a relatively low recurrence rate of 12% for the overall population. Moreover, it's of primary importance to note that this satisfactory ratio is largely reduced (3% of recurrence rate) for the 29 patients who performed one training session per month after the 10th initial rehabilitation sessions. Hence, the destabilizing orthosis appears to be an effective solution to prevent recurrent ankle sprains. However, joint protection requires long-term and regular training sessions. This result has motivated the development of a similar device allowing patients to perform training sessions at home. Finally, data obtained in this study are promising awaiting the final results of the comparative, multicentric and independent clinical trials currently managed by the Hospices Civils de Lyon.     

Clinical Trial Updates and Hotline Sessions presented at the European Society of Cardiology Congress 2007

This article provides information and commentaries on trials which were presented at the Hotline and Clinical Trial Update Sessions at the European Society of Cardiology Congress 2007 in Vienna. The key presentations were performed by leading experts in the field with relevant positions in the trials or registries. It is important to note that unpublished reports should be considered as preliminary data, as the analysis may change in the final publications. The comprehensive summaries have been generated from the oral presentation and the webcasts of the European Society of Cardiology and should provide the readers with the most comprehensive information of relevant publications.     

Balance and Boundaries in Grief Counseling: An Intervention Framework for Volunteer Training

Volunteers or paraprofessional counselors are commonly used to provide supportive care to the bereaved. These counselors generally are trained in basic listening skills, providing a generic, nonspecific approach to intervention that remains to be proven effective. The present paper outlines a framework that provides paraprofessionals with a broader model for intervention with the bereaved. Attention to boundaries as a helper and balance in the grief recovery are central to the model. Interventions are described that provide the paraprofessional counselor with more options for tailoring their counseling strategy to the individual. These include techniques that are presumed to be more specific to the enhancement of grief recovery.     

A new method for the simultaneous analysis of unmodified and modified urinary nucleosides and nucleobases by high performance liquid chromatography

Details are given of a new, rapid and simple pre-fractionation method and an isocratic high performance liquid chromatography system suitable for parallel analysis of nucleosides and nucleobases from urine and other biological fluids. The quantitative recovery and excellent reproducibility of the method is demonstrated by analysis of representative standard RNA catabolites. The advantage of this new method for application to biological samples is discussed.     

Adsorption of Charged Non-albumin Bound Drugs by Amorphous Silica

We investigated the in vitro drug adsorption of PQ 10150 sodium silicate gel (AIS, Santa Clara, CA) with particle size of 230 um and surface area of 400 nr/g. We observed 99% to 88% adsorption of gentamicin; a mean 91 % of disopyramide; a mean 89% of quinidine at low concentration, falling to 75% at higher concentration. Insulin was 88% adsorbed at low concentrations but less so (65%) at higher concentrations. We observed a mean 83 % adsorption of procainamide, a mean 84% of N-acetyl procainamide, 74% oflidocaine, 73% of amitriptyline; and 44% of desipramine. We found an average 14% reduction of total digoxin concentration when serum containing digoxin (2 to 33 ng/mL) was exposed to sodium silicate, while the reduction in free digoxin concentration was 16%. Five percent ethosuximide was also removed. The adsorption of theophylline, phenobarbital, acetaminophen, phenytoin, ethylene glycol, methotrexate, salicylate, thiocyanate and diazepam was minimal and not significant. We conclude that significant amounts of charged, non-albumin bound drugs can be removed by PQ 10150 sodium silicate gel.     

自动化酸碱平衡图在急诊社区获得性肺炎诊治中的应用

目的 探讨自动化酸碱平衡图在急诊科社区获得性肺炎(CAP)患者诊断中的价值.方法 根据病史、肺功能测定结果、慢性阻塞性肺疾病(COPD)诊断标准,将111例CAP患者分为单纯CAP组(56例)和COPD合并CAP组[即慢性阻塞性肺疾病急性加重(AECOPD)组,55例].询问患者病史后即刻抽取动脉血测血气并进行自动化酸碱平衡图分析.结果 血气分析结果显示,AECOPD组动脉血二氧化碳分压(PaCO2,kPa)、HCO3- (mmol/L)、剩余碱(BE,mmol/L)均显著高于CAP组(PaCO2:7.714±2.414比5.896±1.308,HCO3-:30.767±7.185比25.014±3.043,BE:4.345±5.371比-0.354±3.180,均P＜0.01).自动化酸碱平衡图分析结果显示,AECOPD组患者酸碱平衡紊乱高达89.1％,CAP组为66.1％.将AECOPD组和CAP组患者中正常(10.9％、33.9％)、急性呼吸性酸中毒(急性呼酸,12.7％、14.3％)、慢性呼吸性酸中毒(慢性呼酸,49.1％、10.7％)、呼吸性碱中毒(呼碱,7.3％、14.3％)、代谢性酸中毒(代酸,12.7％、17.9％)、代谢性碱中毒(代碱,12.7％、8.9％)综合进行x2分析,差异有统计学意义(x2=24.421,P=0.001),而将正常、急性呼酸、呼碱、代酸及代碱进行x2分析,差异无统计学意义(x2=5.280,P=0.260),提示AECOPD患者慢性呼酸的发生率较单纯CAP患者显著增加.结论 自动化酸碱平衡图能帮助急诊科医师快速识别CAP患者是否存在多重酸碱平衡紊乱,并可快速识别急、慢性呼吸系统疾病.