食管鳞癌血清WCX2蛋白芯片诊断模型的研究

目的　分析食管鳞癌血清蛋白表达谱的改变 ,筛选并建立食管鳞癌血清标志物诊断模型。方法　采用表面增强激光解吸离子化飞行时间质谱 (SELDI TOF MS)技术分析 199例食管鳞癌患者和 10 6名性别、年龄匹配的健康人血清 ,获得WCX2蛋白芯片表达图谱。用BiomarkerPattern软件分析食管癌差异蛋白并初步建立诊断模型。扩大样本量 ,通过盲法分析进一步验证诊断模型。结果　在分子量 0～ 5 0 0 0 0范围内 ,共检测到 92个差异蛋白峰 ,其中 34个差异有显著意义 (P <0 0 5 )。建立了由 12个差异蛋白组成的食管鳞癌诊断模型 ,其敏感性为 91 5 % (5 4 / 5 9) ,特异性为86 9% (5 3/ 6 1)。扩大样本盲法验证结果其敏感性为 85 % (119/ 14 0 )、特异性为 84 4 % (38/ 4 5 )。结论　由 12个差异表达蛋白及其特定组合构成的诊断模型可以区分食管鳞癌与健康人     

血清蛋白质谱与人工神经网络模型诊断卵巢癌的应用性研究

目的 建立筛选卵巢癌血清蛋白质谱与人工神经网络诊断模型的研究。方法 用H4(疏水表面)蛋白芯片结合表面增强激光解吸电离飞行时间质谱(SELDI-TOF-MS)技术检测卵巢癌患者和健康人血清样本的蛋白质谱，同时采用人工神经网络筛选差异蛋白以建立诊断模型。结果 用SELDI-TOF-MS技术和H4蛋白芯片从47例卵巢癌和29名健康人血清中，筛选出4个有明显表达差异的蛋白，其质荷比(m／z)分别为5881、7553、6652和9391。用其中的18名健康人和29例卵巢癌患者样本作训练集和交叉验证后，再用筛选出的4个差异蛋白质建立人工神经网络预测模型。然后，对11名健康人和18例卵巢癌患者样本进行盲法测试，以验证该模型。结果显示，我们建立的诊断模型对卵巢癌检测的敏感性为100％，特异性为90．9％，阳性率为94．7％。结论 血清蛋白质谱与人工神经网络模型对小样本的卵巢癌诊断具有较高的敏感性和特异性，可扩大样本进行深入的应用性研究。     

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。     

脑膜瘤和脑良性肿瘤及脑外伤患者脑脊液蛋白质谱差异表达模型的研究

目的用表面增强激光解吸离子化飞行时间质谱(SELDI-TOF-MS)和生物信息学分析技术寻找脑脊液中能鉴别脑膜瘤和其他脑良性肿瘤及脑外伤诊断的新标志物。方法收集14例脑膜瘤、9例其他脑良性肿瘤和27例轻度脑外伤患者的脑脊液标本，用H4蛋白芯片和SELDI-TOF-MS检测蛋白质谱的表达。用Biomarker PattemsTM Software分析软件进行数据处理，建立区分脑膜瘤和脑外伤患者脑脊液中蛋白质谱差异表达模型和区分脑膜瘤和其他脑良性肿瘤脑脊液中蛋白质谱差异表达模型；并用2个模型对各2例脑膜瘤、其他脑良性肿瘤和脑外伤患者进行盲法交叉验证。结果用5个质荷比峰建立的区分脑膜瘤和脑外伤脑脊液蛋白质谱差异表达模型的准确率为98％(49/50)．敏感性为100％(14/14)，特异性为96．3％(26/27)，阳性预测率为93．3％(14/15)，阴性预测率为100％(27/27)。用4个质荷比峰建立的区分脑膜瘤和其他脑良性肿瘤脑脊液蛋白质谱差异表达模型的准确率为96％(48/50)，敏感性为100％(14/14)，特异性为94．4％(34/36)，阳性预测率为92．3％(14/16)，阴性预测率为100％(34/34)。盲法交叉验证，第一个模型能将脑肿瘤、其他脑良性肿瘤和脑外伤全部正判，第二个模型将1例脑外伤误判。结论用SELDI-TOF-MS技术平台和生物信息学技术初步建立的区分脑膜瘤与脑外伤和其他脑良性肿瘤的脑脊液蛋白差异表达模型，为寻找脑膜瘤中新的肿瘤标志物进行蛋白质组学研究开辟了一条新的途径。     

食管癌血清蛋白质谱揩纹图分析及人工神经网络诊断模型研究

目的利用高通量和高灵敏的表面激光解析电离飞行时间质涪技术（SELDI—TOF—MS）寻找食管癌患者血清中微量的标志性差异蛋白质组,为探索食管癌发生与基因转录的蛋白调控机制,基因治疗以及早期诊断提供参考数据,方法用SELDI—TOF—MS检测食管癌及其相关人群的血清蛋白质谱指纹图,用Biomarkex Wizaid Software软件筛选出差异蛋白,选择具有标志性的差异蛋白质组建立人工神经网络诊断模型,使用SPSS分析其诊断效能。结果在食管癌患者血清中发现89个差异蛋白（P〈0．05）。其中有显著差异（P〈0.001）的蛋白质如下：在食管癌患者血清中表达增高的蛋白（5017．6Da,7458、5Da,7908,1Da,8111.9Da,8577,8Da）和表达降低的蛋白（4215.8Da,5890.9Da,7749.3Da）。利用筛选出8个有明显表达差并的蛋白质组建立食管癌人工神经网络筛查模型和诊断模型,其灵敏度达到93．2％和96.3％,特异度分别为95．6％和97．2％,经大样本盲法验证的灵敏度为75.4％和75.8％,特异度分别为84．8%和86．7％,经蛋白组数据库检索发现两种蛋白分别为血清淀粉样蛋白A和子宫球蛋白。结论血清蛋白质谱指纹图结合人工神经网络技术进行蛋白组学数据挖掘对食管癌的筛查和诊断以及探索其基因和蛋白调控机制具有重要的临床意义。     

利用SELDI-TOF-MS技术分析喉癌患者血清蛋白质谱变化

目的筛选喉癌特异性血清蛋白质标志物,建立用于喉癌诊断的分类树模型。方法采集喉癌患者57例与正常人64例的血清,用表面增强激光解吸/电离-飞行时间-质谱分别检测其蛋白表达谱,用Biomarker Wizard软件筛选出差异蛋白,再用Biomarker Patterns软件建立喉癌诊断模型,另采集15例喉癌患者及20名正常人的血清对该模型进行盲法验证。结果通过对喉癌患者术前血清与正常人血清蛋白质谱分析,发现有24个蛋白的表达有明显差异(P0.05),并建立了由质荷比(M/Z)分别为4 2066、6238、928和9 424 Da的4种蛋白质组成的分类树诊断模型,准确率为95.0%(115/121),敏感性和特异性分别为94.7%(54/57)、95.3%(61/64)。盲法验证其敏感性为86.7%(13/15),特异性为85.0%(17/20)。分析喉癌患者手术前后血清蛋白质谱的变化,发现术前高表达的8种蛋白质术后表达明显下调。结论喉癌血清蛋白质谱诊断模型具有一定的优越性,为喉癌的早期诊断及预后标志物的筛选提供了新途径。     

SELDI在筛选从慢性活动性肝炎到早期肝硬化两阶段血清标记物中的应用

目的比较慢性活动性肝炎患者和早期肝硬化患者血清蛋白标记物并建立相关筛选模型。方法用表面加强激光解析／电离飞行时间质谱技术（SELDI．TOF—MS）及CM10蛋白芯片对28例慢性活动性肝炎患者、26例早期肝硬化患者血清样本进行分析，将获得的血清蛋白质指纹图谱，用计算机软件进行比较分析，建立慢性活动性肝炎与早期肝硬化患者的比较筛选模型。结果慢性活动性肝炎组与早期肝硬化组共有26个差异有统计学意义的蛋白峰；建立诊断模型的灵敏度92％（24／26），特异度86％（24／28），准确率为89％（48／54）。结论建立的血清蛋白质指纹图谱模型能够区分慢性活动性肝炎患者与早期肝硬化患者，SELDI技术在诊断及特异性蛋白生物标志分子的筛选等方面具有较好的临床应用前景。     

卵巢癌患者血清蛋白指纹图谱检测及其临床意义

目的 运用SELDI-TOF-MS技术（表面增强激光解吸电离飞行时间质谱技术）检测卵巢癌患者、良性卵巢囊肿和正常健康妇女的血清蛋白质指纹图谱，初步探讨筛选出的肿瘤标志物建立的诊断模型在卵巢癌诊断中的临床意义。方法 用SELDI-TOF-MS技术及WCX2芯片检测55例卵巢癌患者和60例对照纽的血清蛋白指纹图谱，并运用SPSS10.0软件判别分析处理数据和筛选标志物，以建立诊断模型。结果 6个蛋白质峰（11500、11650、11800、15800、16000、16250m／z）组合构建的诊断模型1鉴别卵巢癌和对照组的敏感性为94、5％（52／55），特异性为93．3％（56160）。6个蛋白质峰（11590、11700、12000、14800、15500、15900m／z）组合构建的诊断模型Ⅱ鉴别Ⅰ期卵巢癌和对照组的敏感性为82．45％（14／17），特异性为90．0％（54／60）。5个蛋白质峰（11600、11750、16100、16150、16200m／z）组合构建的诊断模型Ⅲ鉴别Ⅰ期卵巢癌患者和Ⅱ～Ⅳ期卵巢癌患者的敏感性为92．1％（35／38），特异性为94．1％（16／17）。结论 SELDI-TOF-MS技术是一种快速、准确、高通量、高灵敏度的蛋白质分析方法，能够直接检测出卵巢癌患者血清中相对特异的肿瘤标志物，其对于卵巢癌的早期诊断具有一定的临床意义。     

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。     

血清AFP、AFU、CA19—9联合检测对原发性肝癌的诊断价值

本对260例原发性肝癌(gLC)进行血清甲胎蛋白(AFP)、a—L一岩藻糖苷酶(AnI)、糖抗原19—9(CA19—9)联合检测。结果表明，肝癌组与肝硬化组及正常对照组比较，其含量均有显差异(P<0．001)。肝癌纽血清AFP、AFU、CA19—9单项检测及三项联合检测．其敏感性分别为63．5％、71．2％、61．5％及94.2％。血清AFP、AFU、CA19—9诊断肝癌的特异性分别为95．1％、87.8％、90．2％；准确率分别为77．4％、74．2％、75.2％。在95例AFP阴性的肝癌患中血清AFU、CA19—9的敏感性分别为57.9％(55,,'95)、73．7％(70／95)。结果表明AFP、AFU、CA19—9三项联合检测可明显提高肝癌诊断的敏感性、准确率．县有重要的临床意义。     

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.     

Interprofessional approaches to creating safe,high quality health care

Three supplementary perspectives are presented arguing that interprofessional collaboration is both necessary and desirable. Nonetheless, there are often too many serious intra-professional barriers and obstacles to interprofessional collaboration to make it successful. Some of these barriers, it is argued and illustrated, are found in the multiple ways in which professional identity is tacitly acquired and embodied in the practitioners' habitual, everyday practice. The paper then explores ways in which reflection, especially Second order reflection, can help to elucidate and overcome these obstacles, as well as increasing professional adaptability and competence.     

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.     

Prospects for the control of neglected tropical diseases by mass drug administration

The prospects for the control of neglected tropical diseases, including soil-transmitted helminthiasis, shistosomiasis, lymphatic filariasis, onchocerciasis and trachoma, through mass drug administration, are exemplified by the elimination of the trachoma as a public-health problem in Morocco. In spite of this and other striking successes, mass drug administration programs are faced with major challenges resulting from suboptimal coverage and lack of efficacy. At current suboptimal coverage rates, programs may need prolongation for an extended period, increasing costs and undermining sustainability. Community participation through health education and information appears to be crucial to improve coverage and to achieve sustainability. Implementation of complementary measures, such as vector control, improved hygiene and environmental sanitation, are important to further control transmission and to prevent re-emergence of the infection and, again, may only be achieved effectively through community-based initiatives. To reduce costs and to relieve pressure on the health system, combining neglected tropical disease programs in areas where diseases coexist and integration with existing control programs for malaria, tuberculosis and HIV/AIDS is advocated. The risk of developing drug resistance is of particular concern in view of the lack of alternative drugs, and reduced treatment efficacy due to emerging resistance is evident for the soil-transmitted helminths and onchocerciasis. Given the risk for the development of drug resistance and the need for a high degree of participation, close attention should be paid to the monitoring of the coverage and efficacy of the different program components.     

Bacterial meningitis: an update of new treatment options

The outcome of bacterial meningitis critically depends on the rapid initiation of bactericidal antibiotic therapy and adequate management of septic shock. In community-acquired meningitis, the choice of an optimum initial empirical antibiotic regimen depends on the regional resistance patterns. Pathogens resistant to antibacterials prevail in nosocomial bacterial meningitis. Dexamethasone is recommended as adjunctive therapy for community-acquired meningitis in developed countries. In comatose patients, aggressive measures to lower intracranial pressure <20 mmHg (in particular, external ventriculostomy, osmotherapy and temporary hyperventilation) were effective in a case–control study. Although many experimental approaches were protective in animal models, none of them has been proven effective in patients. Antibiotics, which are bactericidal but do not lyse bacteria, and inhibitors of matrix metalloproteinases or complement factor C5 appear the most promising therapeutic options. At present, vaccination is the most efficient method to reduce disease burden. Palmitoylethanolamide appears promising to enhance the resistance of the brain to infections.     

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.     

Imaging choices in occult hip fracture

Background: Hip fracture is a common injury, with an incidence rate of > 250,000 per year in the United States. Diagnosis is particularly important due to the high dependence on the integrity of the hip in the daily life of most people. Objectives: In this article we review the literature focused on hip fracture detection and discuss advantages and limitations of each major imaging modality. Discussion: Plain radiographs are usually sufficient for diagnosis as they are at least 90% sensitive for hip fracture. However, in the 3–4% of Emergency Department (ED) patients having hip X-ray studies who harbor an occult hip fracture, the Emergency Physician must choose among several methods, each with intrinsic limitations, for further evaluation. These methods include computed tomography, scintigraphy, and magnetic resonance imaging. Conclusion: We present an evidence-based algorithm for the evaluation of a patient suspected to have an occult hip fracture in the ED. Also outlined are future directions for research to distinguish more effective techniques for identifying occult hip fractures.     

Systematic Reviews Published in the April 2012 Issue of the Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD but monthly online. The April 2012 issue (second DVD for 2012) contains 5045 complete reviews, 2182 protocols for reviews in production, and 17,084 short summaries of systematic reviews published in the general medical literature. In addition, there are citations of 674,000 randomized controlled trials, and 15,400 cited papers in the Cochrane methodology register. The health technology assessment database contains just over 11,000 citations. One hundred and seventeen new reviews have been published in the last 3 months of which 12 have potential relevance for practitioners in pain and palliative medicine. The impact factor of the Cochrane Library stands at 6.186. Readers are encouraged to access the full report for any articles of interest as only a brief commentary is provided.     

Platelets,thrombosis, coagulation,and atherosclerosis

When I first got the invitation to join a medical delegation going to Moldova, I thought for a moment that our destination was the fictional country in the old Marx Brothers movie Duck Soup. On further checking, it turns out that entertaining place was called Freedonia. I now know that Moldova is indeed a real country, bordered on the west by Romania and on the other three sides by the Ukraine. It is a proud country, rich with traditions, and its people are warm, giving, eager to learn ways to improve their healthcare system, and deeply appreciative of our attempts to help them in the task.