脓毒症生物标志物的研究进展

脓毒症是危及患者生命的疾病。生物标志物可用于对脓毒症的诊断、治疗和预后评估。近年来不断有新的脓毒症生物标志物被发现, 迄今已确定的生物标志物超过250种。脓毒症发生过程的复杂性以及各种检测技术灵敏度的提高将会导致新的生物标志物不断涌现。但针对脓毒症, 目前临床上仍缺乏特异性的用于诊断的生物标志物以及有效的治疗方法。因此, 寻找可靠的生物标志物以及评估生物标志物在脓毒症中的运用无疑有助于指导临床决策。该文综述了脓毒症生物标志物的研究现状, 以期加强对目前脓毒症生物标志物的认识, 为生物标志物运用于脓毒症的诊断、治疗和预后评估提供参考。     

脓毒症生物标志物的研究进展

背景 脓毒症是危重症患者的主要死因,早期诊断可以尽量避免治疗的延误.然而由于临床上对该疾病的一些特点难以把握,导致了诊断的延误. 目的 探讨不同的脓毒症生物标志物在脓毒症进程中的作用. 内容 就已有的生物标志物,包括已在临床上应用的C-反应蛋白（C-reactive protein,CRP）、降钙素原（procalcitonin,PCT）等以及新近的生物标志物作一个归纳总结. 趋向 随着对脓毒症的深入研究,越来越多的生物标志物将被发现并应用于临床.     

胰石蛋白在脓毒症早期诊断中应用的研究进展

脓毒症是一种严重危及生命的综合征, 其主要特征是宿主对感染的异常反应, 可迅速演变为脓毒症休克和多器官功能衰竭。脓毒症的治疗依赖于早期识别和诊断以及充分而及时的抗感染和多器官功能支持。近年来, 胰石蛋白作为一种新的脓毒症生物标志物被广泛研究。现有证据表明, 与目前临床上常用的炎症标志物相比, 胰石蛋白对脓毒症的诊断具有更高的敏感度和特异度, 并且能对脓毒症进行早期识别, 可在一定程度上评估脓毒症患者病情的严重程度。该文就胰石蛋白的特征、生物学功能、诊断特点以及临床应用的研究进展作一综述。     

蛋白质肿瘤标志物在胰腺癌早期诊断中的研究进展

胰腺癌是一种病死率极高的消化系统常见的恶性肿瘤,近年来其发病率呈上升趋势,初期症状隐匿,早期诊断困难,根治性切除手术是治疗胰腺癌最为有效的方法,但是此病患者临床确诊时多处于中晚期阶段,往往失去根治性手术机会,故其预后极差.探索研究胰腺癌早期诊断肿瘤标志物可以提高早期诊断率,从而提高该病根治性手术切除率及显著改善患者预后.近年来,随着蛋白质组学及其技术的迅速发展,胰腺癌蛋白质肿瘤标志物领域成为研究热点.本文就蛋白质肿瘤标志物在胰腺癌早期诊断中的研究进展作一综述.     

早期脓毒症生物分子预警的研究进展

背景 脓毒症是ICU患者的主要死亡原因,提高脓毒症预警的准确度并及时进行治疗是脓毒症早期干预的重点.失控的炎性应答可导致促炎反应航炎反应平衡的破坏、患者早期死亡.目前,尚无有效的生物化学技术能够提供快速可信的方法以鉴别脓毒症.目的 归纳目前有助于早期诊断脓毒症的生物学标志物及基于多重PCR的检测方法.内容 归纳C反应蛋白(C-reactin protein,CRP)、降钙素原(procalcitonin,PCT)、IL-6、脂多糖结合蛋白(lipopolysaccharides-binding protein,LBP)、可溶性髓系细胞触发受体-1(soluble triggering receptor expressed on myeloid cells-1, sTREM-1)、尿激酶纤溶酶原激活物(urokinase-type plasminogen activator,uPAR)、高迁移率族蛋白B1(high mobility group box 1 protein,HMGB1)、肾素血管紧张素系统(rennin angiotensin system,RAS)、基于多重PCR的病原体检测对脓毒症早期预警的作用.趋向 尚无一种单一的生物标志物或生物分子技术可以提供准确的预警以有效地鉴别脓毒症.PCT是目前最常用于脓毒症诊断及危重程度判断的唯一实践性生物分子.未来对脓毒症早期预警的研究可更多注重联合使用多种生物学标志物.     

结肠癌蛋白质组学研究进展

结肠癌是一种常见的致死性疾病,发病率逐年上升.蛋白质组学已经成为当今研究结肠癌发病机制、早期诊断、治疗及预后的热点之一,并取得了很大进展.近年来,运用蛋白组学技术发现了越来越多的结肠癌相关的生物标志物.本文就结肠癌蛋白质组学研究进展作一综述.     

急性肾损伤生物标志物的研究现状及进展

急性肾损伤（acute kidney injury,AKI）是住院患者尤其是危重症患者中的常见病.尽管对其研究和认识已不断深入,但其病死率仍居高不下.影响其预后的一个主要原因是缺乏早期诊断的生物标志物.迄今为止,在一些研究中已先后发现了多种具有潜力的AKI生物标志物,并有不少研究结果显示这些生物标志物可能在AKI的早期诊断、病情及疗效监测、预后评估中具有重要意义,有望改善AKI患者预后.     

蛋白质指纹图谱技术及其在骨科中的应用

蛋白质组学从整体角度分析细胞内动态变化的蛋白质组成成分、表达水平与修饰状态,了解蛋白质之间的相互作用与联系。蛋白质组学研究技术主要以分离技术和生物质谱技术为支撑平台,生物信息学为桥梁,对蛋白质表达进行研究分析,通过肿瘤患者体液中蛋白质组的变化,发现特异的肿瘤标志物,以达到对肿瘤的早期诊断;对早期状态的肿瘤蛋白质组学分析,可进一步了解肿瘤早期发生,并为发现早期诊断的候选标志物提供可能;分析体液的蛋白质指纹图谱技术(SELDI-TOF-MS)的研究,可为骨肿瘤的早期发现、骨关节疾病及创伤骨科疾病的疗效判断提供有力依据。     

应用二维电泳及质谱法筛选胰腺癌血清标志物

在中国,胰腺癌发病率逐渐增加,目前其肿瘤相关致死率已跃居第6位[1].早期发现是胰腺癌得以及时治疗的前提之一.目前缺乏理想的胰腺癌血清学标志物.蛋白质组学为肿瘤研究提供了新的思维和技术平台[2].在本研究中,我们初步探讨了二维电泳及质谱法筛选胰腺癌血清标志物中的应用,并希望发现一些与胰腺癌相关的标志物,为胰腺癌的早期诊断提供线索.     

应用二维电泳及质谱法筛选胰腺癌血清标志物

在中国,胰腺癌发病率逐渐增加,目前其肿瘤相关致死率已跃居第6位[1].早期发现是胰腺癌得以及时治疗的前提之一.目前缺乏理想的胰腺癌血清学标志物.蛋白质组学为肿瘤研究提供了新的思维和技术平台[2].在本研究中,我们初步探讨了二维电泳及质谱法筛选胰腺癌血清标志物中的应用,并希望发现一些与胰腺癌相关的标志物,为胰腺癌的早期诊断提供线索.     

Clinical application of sepsis biomarkers

Sepsis is one of the leading causes of death in the critically ill. Early diagnosis is important to avoid delay in instituting appropriate treatment. However, diagnosis can be delayed because of difficulty in interpreting clinical features. Sepsis biomarkers can aid early diagnosis. This article reviews the application of readily available biomarkers for diagnosis of sepsis, for predicting prognosis, and for antibiotic stewardship. 178 biomarkers are described in the literature—ranging from specimen cultures, which lack sensitivity and specificity for early diagnosis of sepsis, to biomarkers such as C-reactive protein, procalcitonin, and genetic biomarkers, which have their own limitations. Future research will mainly focus on use of more than one biomarker, but the main problem in sepsis biomarker research seems to be a lack of a recommended biomarker.     

Cardiovascular dysfunction in sepsis

Besides adequate and early antimicrobial therapy, goal-directed haemodynamic in-terventions are crucial for survival of severe sepsis and septic shock. Although cardiac output often is restored in the early phase of sepsis syndrome significant left- and right ventricular impairment may already be present. Clinical presentation, invasive blood pressure tracing and echocardiographic evaluation are pivotal for early recognition, diagnosis and monitoring of therapeutic interventions.     

Prediction about severity and outcome of sepsis by pro-atrial natriuretic peptide and pro-adrenomedullin

Objective： Measurement of biomarkers is a potential approach to early prediction of the risk of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of pro-atrial natriuretic peptide （pro-ANP） and pro-adrenomedullin （pro- ADM） levels in a cohort of medical intensive care patients and to compare it with that of other known biomarkers and physiological scores. Methods： Blood samples of 51 consecutive critically ill patients admitted to the intensive care unit and 53 age-matched healthy control people were evaluated in this prospective study. The prognostic value ofpro-ANP and pro-ADM levels was compared with that of acute physiology and chronic health evaluation （APACHE） II scores and various biomarkers such as C-reactive protein, interleukin-6 and procalcitonin. Pro-ANP and pro-ADM were detected by a new sandwich immunoassay. Results： On admission, 25 patients had systemic inflammatory response syndrome （SIRS）, 12 sepsis, 9 severe sepsis and 5 septic shock. At that time, the median levels （ng/ml） of pro-ANP and pro-ADM were 87.22 and 0.34 respectively in patients with SIRS, 1533.30 and 2.23 in those with sepsis, 1098.73 and 4.57 in those with severe sepsis, and 1933.94 and 8.21 in those with septic shock. With the increasing severity of disease, the levels of pro- ANP and pro-ADM were gradually increased. On admission, the circulating levels ofpro-ANP and pro-ADM in patients with sepsis, severe sepsis, or septic shock were significantly higher in non-survivors than in survivors （P〈0.05）. In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the areas under the curve （AUCs） for pro-ANP and pro-ADM were 0.89 and 0.87 respectively, which was similar to the AUCs for procalcitonin and APACHE II scores. Conclusion： Pro-ANP and pro-ADM are valuable biomarkers for prediction of severity of septic patients.     

Biomarkers predicting sepsis in polytrauma patients: Current evidence

Introduction

Major trauma still represents one of the leading causes of death in the first four decades of life. Septic complications represent the predominant causes of late death (45% of overall mortality) in polytrauma patients. The ability of clinicians to early differentiate between systemic inflammatory response syndrome (SIRS) and sepsis is demonstrated to improve clinical outcome and mortality. The identification of an “ideal” biomarker able to early recognize incoming septic complications in trauma patients is still a challenge for researchers.

Aim

To evaluate the existing evidence regarding the role of biomarkers to predict or facilitate early diagnosis of sepsis in trauma patients, trying to compile some recommendations for the clinical setting.

Methods

An Internet-based search of the MEDLINE, EMBASE and Cochrane Library databases was performed using the search terms: “Biomarkers”, “Sepsis” and “Trauma” in various combinations. The methodological quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies Checklist (QUADAS). After data extraction, the level of evidence available for each bio-marker was rated and presented using the “best-evidence synthesis” method, in line with the US Agency for Healthcare Research and Quality.

Results

Thirty studies were eligible for the final analysis: 13 case–control studies and 17 cohort studies. The “strong evidence” available demonstrated the potential use of procalcitonin as an early indicator of post-traumatic septic complications and reported the inability of c-reactive protein (CRP) to specifically identify infective complications. Moderate, conflicting and limited evidence are available for the other 31 biomarkers.

Conclusion

Several biomarkers have been evaluated for predicting or making early diagnosis of sepsis in trauma patients. Current evidence does not support the use of a single biomarker in diagnosing sepsis. However, procalcitonin trend was found to be useful in early identification of post-traumatic septic course and its use is suggested (Recommendation Grade: B) in clinical practice.     

糖尿病肾病的蛋白质组学研究进展

糖尿病肾病(DN)是糖尿病最常见的微血管并发症,也是导致终末期肾病(ESRD)的重要原因。微量白蛋白尿作为预测DN进展的指标并不可靠,寻找DN早期生物学标志物以及对DN早期肾脏病变的机制研究为目前研究的重点。蛋白质组学技术近年来飞速发展,对DN患者的尿液、血液以及肾组织的蛋白质组学研究可能会为我们早期诊治DN提供新的希望。本文对蛋白质组学主要技术及DN蛋白质组学研究的近期研究进展进行综述。     

Clinical proteomics and breast cancer

BackgroundBreast cancer is a heterogeneous disease. Yet, many molecular players and mechanisms behind the complexity of its clinical behaviour remain unknown, and advances in biomedical research are expected to unravel novel molecular discoveries in breast and other cancers. Clinical proteomics is currently experiencing rapid advances in technology that promise new means to improve breast cancer early diagnosis, stratification, and treatment response.MethodsWe reviewed recent literature adopting clinical proteomics in breast cancer research.FindingsThis review highlights the principles, advantages, limitations, discoveries and future prospects of recent clinical proteomics discovery efforts in breast cancer research.ConclusionNumerous proteomic studies of breast cancer have been accomplished aiming to aid the development of personalised therapies, increase understanding of post treatment relapse, and help improve prediction of patient prognosis. This has led to the possible identification of profiles refining breast cancer subtypes and the discovery of novel biomarkers pointing towards diagnostic and prognostic potential.     

Review article: Acute kidney injury in critical illness

Purpose

This review provides a focused and comprehensive update on emerging evidence related to acute kidney injury (AKI).

Principal findings

Acute kidney injury is a significant clinical problem that increasingly complicates the course of hospitalization and portends worse clinical outcome for sick hospitalized patients. The recent introduction of consensus criteria for the diagnosis of AKI (i.e., RIFLE/AKIN classification) have greatly improved our capacity not only to standardize the diagnosis and classification of severity of AKI, but also to facilitate conducting comparative epidemiologic studies in an effort to better understand the burden of adult and pediatric AKI and its syndromes (i.e., septic, cardio-renal, hepato-renal). The characterization of several novel AKI-specific biomarkers (i.e., neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and interleukin-18) is extending our understanding of the pathophysiology of AKI. Moreover, these biomarkers appear to have clinical relevance for early detection and they provide prognostic value. These innovations are aiding in the design of epidemiologic surveys and randomized trials of therapeutic interventions. Strategies for prevention and conservative management of AKI across a range of clinical settings are discussed, including sepsis, hepato-renal syndrome, cardio-renal syndrome, rhabdomyolysis and in the perioperative setting.

Conclusions

Acute kidney injury is an escalating clinical problem in hospitalized patients. Recent advances in AKI have improved knowledge of its pathogenesis, diagnosis, and prognosis; however, considerable research effort is needed. There are still relatively few interventions proven to alter the natural history of established AKI in hospitalized settings, and its development foretells less favourable outcomes.     

Diagnostic approach to sepsis - state of the art

Early diagnosis of the different severities of septic inflammation is important for early implementation of specific therapies. Sepsis and severe sepsis are accompanied by clinical and laboratory signs of systemic inflammation. However, patients suffering from non-infectious inflammation may present with similiar signs and symptoms making it difficult to diagnose infection based on clinical findings alone. Bacteriological evidence of sepsis, though definitive and specific, may not be obtainable, is time-consuming and even may not occur concurrently with clinical signs of sepsis. It is therefore important to identify markers, which, by enabling an early diagnosis of sepsis and organ dysfunction, would allow early specific therapeutic interventions. Wheras C-reactive Protein is a more sensitive parameter for the diagnosis of non-systemic infections, Procalcitonin seems to be a useful parameter to improve the diagnosis and monitoring of therapy in patients with severe sepsis and septic shock.