蛋白芯片技术筛选肝癌血清标志蛋白的初步研究

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。方法采用WCX2芯片及SELDI—TOF—MS技术对34例肝癌患者及34例健康对照组血清进行蛋白质指纹图谱检测分析，所得到的结果采用Biomarker Wizard和Biomarker Pattems System软件分析。结果发现肝癌患者和健康对照组血清蛋白质指纹图谱之间有17个稳定的标志蛋白，其中有6个标志蛋白在肝癌患者血清中高表达，11个标志蛋白在肝癌患者血清中低表达。分析系统筛选出13752Da及11472Da标志蛋白建立起一个肝癌的诊断模型，对肝癌的诊断特异性为97．06％，敏感度为91．18％，及阳性预测率为96．88％。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。     

SELDI-TOF-MS技术筛选鼻咽癌患者血清标志蛋白

目的应用表面增强激光解吸电离飞行时间质谱（SELDI—TOF—MS）技术筛选鼻咽癌（NPC）患者血清中的标志蛋白。方法用CiphergenBiosystem公司生产的PBSⅡ／C型蛋白质指纹图谱仪和GoldChip（金芯片）蛋白芯片检测98例鼻咽癌患者和30例正常人血清的蛋白指纹图谱,采用Biomaker Wizard 3．1软件分析两组的蛋白表达情况筛选差异表达蛋白。结果两组均检出较多蛋白峰,并且有表达明显的蛋白峰（P〈0．01）,在鼻咽癌患者中,低表达的有1个（即m／z为5026Da）,高表达的有4个（即m／z为5934Da,5352Da,6655Da,6675Da）。结论用SELDI—TOF—MS蛋白质芯片技术筛选NPC患者血清中特异性蛋白标志物对鼻咽癌的早期诊断具有较大价值。     

唾液蛋白指纹图谱在乳腺癌诊断中的应用

目的:检测乳腺癌患者唾液蛋白质,筛选特异的蛋白质标记物,构建用于乳腺癌早期诊断的唾液蛋白质指纹图谱模型。方法:应用表面增强激光解吸电离飞行时间质谱(SELDI-TOF-MS)技术测定91例唾液标本(其中乳腺癌47例,健康人44例)的蛋白质质谱,建立乳腺癌诊断模型。结果:乳腺癌患者与健康对照样本检测到311个蛋白质峰,其中32个蛋白质峰在两组间差异有统计学意义。获得分子量为4849.31,5224.96,3439.02和3559.89Da4个蛋白质组成的模板,可将乳腺癌与正常人正确分组,47例乳腺癌有37例被准确诊断,34例健康人被准确排除,灵敏度78.7%(37/47);特异度为77.2%(34/44)。结论:表面增强激光解吸电离飞行时间质谱技术建立乳腺癌癌唾液蛋白质指纹图谱模型为早期筛查及诊断乳腺癌提供了一种特异性强、敏感性高的新方法,值得进一步研究和应用。     

表面增强激光解吸离子化飞行时间质谱在胃炎诊断中的应用研究

胃炎是常见消化道疾病之一。目前确诊主要依赖胃黏膜活检，但这种创伤性诊断会给患者造成痛苦。而现用的诸多实验室方法的假阳性较高。本研究用表面增强激光解吸离子化飞行时间质谱（SELDI-TOF-MS）技术对胃炎患者、胃溃疡、胃癌和健康志愿者血清蛋白质行对比分析，以筛选可用于临床胃炎诊断的特异性生物标志。     

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。     

精神分裂症与急性应激障碍及抑郁症患者血清蛋白质谱初步分析

目的研究精神分裂症、急性应激障碍、抑郁症患者血清蛋白质谱的表达情况，筛选差异表达的标志蛋白并探讨其临床价值。方法采用表面增强激光解吸电离飞行时间质谱技术（SELDI-TOF—MS）对122例精神分裂症、急性应激障碍、抑郁症患者及健康患者血清蛋白质谱图进行检测，用Biomarker Wizard3．1版本软件分析质谱数据，筛选血清差异表达的标志蛋白并评价其临床价值。结果精神分裂症患者与健康者血清有56个差异蛋白质峰，其中5个蛋白质峰作为标志蛋白具有潜在的临床价值；精神分裂症与急性应激障碍者之间差异表达的蛋白质峰有15个；精神分裂症与抑郁症患者血清有21个差异蛋白质峰。结论精神分裂症、急性应激障碍、抑郁症患者血清中具有差异表达的标志蛋白，可能对其鉴别诊断和病因学研究，以及进一步研究蛋白质组学改变及其临床应用具有重要意义。     

利用SELDI-TOF-MS蛋白质指纹图谱技术建立肺腺癌诊断模型

目的:寻找肺腺癌患者血浆(清)蛋白特异性生物标志物,用最佳的标志蛋白组合建立肺腺癌诊断模型,并探讨其用于肺腺癌筛查的可行性.方法:应用表面增强激光解吸电离飞行时间质谱(SELDI-TOF-MS)技术及CM10芯片,检测45例肺腺癌患者和40例正常人血清蛋白质指纹图谱,用Biomark Wizrd和Biomark Patterns Software软件对结果进行分析,建立肺腺癌诊断模型:双盲法分析另外19例肺腺癌和20例正常人血清的SELDI质谱数据,验证该模型诊断肺腺癌的准确度.结果:肺腺癌患者和正常人血清蛋白质指纹图谱间有31个差异蛋白(P<0.05),其中以分子量为11.66 kD的蛋白在两组血清中的差异最为显著(P<10-7),该蛋白对诊断肺腺癌有很强的敏感性和特异性;软件自动筛选出分子量为11.66 kD的标志蛋白为主根结点,联合3882.9、4673.2、3158.2和2047.2等4个标志蛋白建立了最佳的肺腺癌诊断模型,对肺腺癌诊断(盲法)的敏感性为84.2%(16/19),特异性为90.0%(18/20).结论:SELDI-TOF-MS技术建立的肺腺癌血清检测法,快速、简单、特异和敏感,为肺腺癌诊断和筛查提供了一个可行的途径和方法.     

食管癌血清蛋白质谱指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谱技术(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Biomarker Wizard 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个有明显表达差异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和子宫珠蛋白.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.     

SELDI技术在乳腺癌淋巴结转移诊断中的应用研究

目的应用表面增强激光解析/电离飞行时间质谱(SELDI-TOF-MS)技术和蛋白芯片从乳腺癌患者血清中筛选出乳腺癌淋巴结转移的特异性蛋白标志物,为预测淋巴结转移提供更早且简单易行的方法。方法用SELDI-TOF-MS技术及IMAC-30蛋白芯片检测了39例发生淋巴结转移和45例未发生转移的乳腺癌患者的血清蛋白指纹图谱,采用Ciphergen Biomaker Wizard软件筛选差异表达蛋白,用SPSS17.0软件对数据进行统计分析。结果乳腺癌发生淋巴结转移组与未转移组相比共有31个差异蛋白峰(P<0.05),判别分析选出质荷比为4781、5329、5895、6012和8918的5个差异蛋白并评价其诊断效能,其中质荷比为4781的蛋白的诊断效能最高,灵敏度为84.62%,特异度为88.89%。结论 SELDI蛋白质谱技术在预测乳腺癌患者的淋巴结转移诊断方面具有一定的价值。     

应用蛋白质芯片技术筛选直肠癌患者

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)从直肠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。方法采用WCX2芯片及SELDI-TOF-MS技术对98例直肠癌患者及40例对照组血清进行蛋白质指纹图谱检测分析,所得到的结果采用Biomarker Wizard和Biomarker Patterns System软件分析。结果直肠癌组与对照组共有26个蛋白质差异有显著性(P<0.05);以其中4个蛋白质生物标志物(质/荷比9295、3730、3938和4095)组建筛选模型,经盲法验证,其敏感度为95.0%(57/60),特异性为93.4%(45/48);CEA敏感度为68.3%(41/60),特异性为77.1%(37/48);CA199敏感度为58.3%(35/60),特异性为75%(36/48)。结论SELDI-TOF-MS技术的敏感度和特异性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直肠癌的蛋白质组学改变及其临床应用可能具有重要意义。     

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.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

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.     

Modified micro-superior percutaneously-assisted total hip: early experiences & case reports

Because of the extensile nature and familiarity of the standard posterior-lateral approach to the hip, a family of "micro-posterior" approaches has been developed. This family includes the Percutaneously-Assisted Total Hip (PATH) approach, the Supercapsular (SuperCap) approach and a newer hybrid approach, the Supercapsular Percutaneously-Assisted Total Hip (SuperPATH) approach. Such approaches should ideally provide a continuum for the surgeon: from a "micro" (external rotator sparing) posterior approach, to a "mini" (external rotator sacrificing) posterior approach, to a standard posterior approach. This could keep a surgeon within his comfort zone during the learning curve of the procedure, while leaving options for complicated reconstructions for the more practiced micro-posterior surgeons. This paper details one author's experiences utilizing this combined approach, as well as permutations of this entire micro-posterior family of approaches as applied to more complex hip reconstructions.     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

Structure and function of "metalloantibiotics"

Although most antibiotics do not need metal ions for their biological activities, there are a number of antibiotics that require metal ions to function properly, such as bleomycin (BLM), streptonigrin (SN), and bacitracin. The coordinated metal ions in these antibiotics play an important role in maintaining proper structure and/or function of these antibiotics. Removal of the metal ions from these antibiotics can cause changes in structure and/or function of these antibiotics. Similar to the case of "metalloproteins," these antibiotics are dubbed "metalloantibiotics" which are the title subjects of this review. Metalloantibiotics can interact with several different kinds of biomolecules, including DNA, RNA, proteins, receptors, and lipids, rendering their unique and specific bioactivities. In addition to the microbial-originated metalloantibiotics, many metalloantibiotic derivatives and metal complexes of synthetic ligands also show antibacterial, antiviral, and anti-neoplastic activities which are also briefly discussed to provide a broad sense of the term "metalloantibiotics."