危重症疾病中支链氨基酸非营养代谢作用

严重创伤、烧伤、感染等危重症疾病可诱发全身炎症反应和多器官损伤,此时蛋白质分解增强,尿氮丢失,出现负氮平衡,氨基酸代谢特别是支链氨基酸(BCAA)代谢出现明显紊乱。BCAA对多器官损伤患者不仅具有单纯的营养支持作用,还可通过调控哺乳动物雷帕霉素靶蛋白(m TOR)等信号通路参与炎症反应、氧化应激、免疫调节和体液内分泌等。另外,血中异常水平的BCAA也可以作为疾病的生物标记物。     

尿中性粒细胞明胶酶相关脂质转运蛋白在狼疮肾炎中的研究进展

中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)已被证明是肾脏疾病一种新的生物标记物。大量证据证明,系统性红斑狼疮肾炎(lupus nephritis,LN)患者尿NGAL(urinary neutrophil gelatinase-associated lipocalin,u NGAL)的特异性和灵敏度均高于抗双链DNA抗体。尽管u NGAL能否作为系统性红斑狼疮肾新生物标记物还存在争议,但临床与基础实验均显示u NGAL能促进LN的发生,且与其严重程度及临床活动性密切相关。本文就u NGAL与LN的关系进行综述。     

血清S-100B蛋白和NSE含量变化评估脑损伤程度的意义

目的探讨颅脑损伤后血清S-100B蛋白、神经元特异性烯醇化酶(NSE)水平变化及其在损伤程度的临床意义。方法采用酶联免疫测定法检测90例颅脑损伤患者入院时及入院后6、12、24h和3、7天血清S-100B蛋白、NSE水平,并分析其与颅脑损伤严重程度的关系。同时选择30例健康体检者作为对照组进行比较分析。结果颅脑损伤后血清S-100B蛋白、NSE水平较对照组明显升高(P0.05或P0.01);重型组患者的血清S-100B蛋白和NSE水平明显高于轻、中型组患者(P0.05或P0.01);动态检测结果显示,血清S-100B蛋白在伤后12h达峰值(P0.05),NSE含量在伤后24h达峰值(P0.05),然后缓慢下降。GCS评分与S-100B、NSE浓度呈负相关(分别为r=-0.814,P0.01;r=-0.726,P0.05)。结论颅脑损伤后血清S-100B蛋白、NSE水平升高,其与脑损伤程度有较好的相关性,2种标记物水平对颅脑损伤程度有较高的评估价值。     

结核病血清学检测FolB蛋白(Rv3607c)抗体效果的初步评价

血清学检测是结核病诊断的主要方法之一,Fol B蛋白(Rv3607c)是结核分枝杆菌的一种分泌蛋白,是潜在的血清学检测生物标记物。本研究的目的是评价Fol B蛋白作为生物标记物的特异性和灵敏度。以结核分枝杆菌基因组DNA为模板,通过PCR的方法成功的获得Rv3607c目的基因,克隆到大肠杆菌p ET28a载体上,并在BL21(DE3)中可溶性表达。利用Ni-柱亲和层析系统纯化得到纯度为95%的Fol B蛋白,以此蛋白作为包被抗原,对44例健康人和212例阳性结核患者血清进行了ELISA检测。结果显示Fol B蛋白能区分结核病人和健康对照组,灵敏度和特异性分别为49.3%和90.6%,都比目前公认的临床应用蛋白Pst SI(38 k D)要高,因此Fol B蛋白可以作为一个在结核病临床诊断上有潜在应用意义的生物标记物。     

阿尔茨海默症诊断和监测的唾液生物标记物

阿尔茨海默症(Alzheimer's disease,AD)是全世界老年人群中最常见的神经退行性疾病,也是导致中枢神经系统不可逆和渐进性恶化的疾病.AD病发后尚无治愈手段,而AD的病理表现早于临床发病十多年,在显著的脑损伤出现前疾病修正疗法可能迟滞疾病的进程,因此迫切需要发掘适用的AD生物标记物从而利于早期诊断、预防及...     

小细胞肺癌分子标记物研究进展

肺癌仍然是现在最常见的恶性肿瘤之一。小细胞肺癌(Smallcelllungcancer,SCLC)是肺癌中恶性程度最高的一种类型,与吸烟密切相关,其较早发生远处转移和播散导致预后差,目前的主要治疗手段有手术、化学治疗、放射治疗。但其具有初始化放疗敏感,却很快耐受的特点,导致了它总体预后不良,生存期短。如何寻求一种有效的疾病预后、疗效判断标记物,显得尤为重要。本文主要介绍近年来在小细胞肺癌中分子标记物的研究进展,包括神经内分泌的相关蛋白、凋亡蛋白抑制剂(Survivin)、相关酶类及膜蛋白,这些分子标记物与小细胞肺癌疾病的进展、预后密切相关,能够为临床的疾病治疗评估提供潜在可行的方法。但是,这些标记物仍存在特异性不高的问题,最终应用于临床实践,仍需要更多的临床研究。     

肾脏疾病检测的现状与应用

肾脏疾病是临床上常见而又十分严重的疾病,若不能及时发现,常引起肾衰,危及生命。随着对肾脏病的研究,肾脏疾病的检测方法也有了很大进步,建立肾损伤早期检测体系成为当务之急,目前这一体系主要包括肾小球早期损伤标志物：尿微量白蛋白(mAlb)和尿转铁蛋白(Tf);肾小管早期损伤标记物：肾小管上皮细胞的各种酶(统称尿酶)、各段肾小管脱落的抗原性物质和低分子量蛋白(LMWP);肾小球滤过率的标志物：胱氨酸蛋白酶抑制剂C(Cystatin C)。     

铁死亡在缺氧相关脑损伤中的研究进展

脑部缺氧经常带来不可逆的中枢神经系统损伤，严重危害着人类健康，对缺氧相关脑损伤机制的深入探索具有重要意义。铁死亡作为一种程序性细胞死亡，主要表现为铁依赖性脂质过氧化物过量积累导致的细胞死亡，与谷胱甘肽代谢、脂质过氧化和铁代谢异常相关，参与多种疾病的发生和发展。研究发现铁死亡在缺氧相关脑损伤中发挥重要作用。本文总结了铁死亡的发生机制，并阐述了其在脑缺血再灌注损伤、新生儿缺氧缺血性脑损伤、阻塞性睡眠呼吸暂停所致脑损伤及高原低氧脑损伤中的研究进展。     

环状RNA: 新型生物标记物与治疗靶点

环状RNA(circular RNAs,circ RNAs)是一类在真核细胞中广泛存在的非编码RNA,具有结构稳定、丰度高及细胞或组织特异性表达等特征,可能通过多种作用方式参与基因表达调控.例如,有些circ RNA富含微小RNA(mi RNAs)结合位点,可充当竞争性内源RNA(ce RNA)结合mi RNA并阻断其对靶基因表达的抑制作用.自2013年以来,circ RNA逐渐成为RNA领域的研究热点并得到广泛关注.最新研究表明,circ RNA的表达及作用与多种疾病的发生发展、生物组织发育及细胞衰老等相关.circ RNA在不同生物样本中的表达差异使其可能成为用于疾病诊断、组织发育鉴定等方面理想的生物标记物,其在疾病中作用方式的逐步阐明,使之具有成为有效治疗靶点的潜力.circ RNA数据库的构建、预测工具的开发及对其作用方式的更深入研究,必将使之具有更广阔的应用前景.     

急性肺损伤的生物标记物

急性呼吸窘迫综合征(ARDS)和急性肺损伤(ALI)多由低氧性呼吸衰竭引起,导致高通透性肺水肿,临床上有较高的发病率与死亡率。近十年来,针对血浆和支气管肺泡灌洗液中相关生物标记物的研究为探索急性肺损伤的病理生理机制指明了新的方向。个别生物标记物已在一些大型、多中心ARDS试验中得到证实。但迄今仍没有一个或一组生物标记物常规应用于临床。随着人类对ALI发病机制理解的进一步深入,或许不久的将来,生物标记物会真正应用于评估疾病的严重程度和预后。本文将概述近年来ALI相关生物标记物的研究进展。     

NICE分型在结直肠癌诊断中的意义

结直肠癌发病率高,早期诊断困难,威胁着全世界人民的健康。近几年窄带成像技术(Narrow Band Imaging,NBI)发展迅速,大大改善了结直肠镜下图像的清晰程度,NBI辅助下的结直肠镜检查在早期诊治肠癌方面具有重要意义。为了进一步优化结直肠镜的诊断效能,多种NBI辅助的结直肠镜下的结直肠病变分型被提出。针对病变的表面形态、颜色分布以及微血管的形态与走形,Sano分型、Jikei分型、Showa分型、Hiroshima分型和NICE(Narrow-Band Imaging International Colorectal Endoscopic)分型相继被提出。其中NICE分型以良好的学习曲线和诊断效能被广泛认可和应用。     

Characterization of the human ventricular cerebrospinal fluid proteome obtained from hydrocephalic patients

The continuing expansion of proteomic technology has been fueled by the potential for discovering novel biomarkers that may be used for the early detection of disease. It has been proposed that human cerebrospinal fluid (CSF), which surrounds and protects the brain and spinal cord from traumatic injury, may be a valuable target for the diagnosis of a variety of conditions such as Alzheimer's disease, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson's disease. The immense complexity of biofluids, however, still requires that considerable development be made in the analytical techniques used so that comprehensive coverage of the proteins present in such samples is achieved. Using a simple separation strategy the protein complement of human ventricular cerebrospinal fluid obtained from patients with hydrocephalus was evaluated. The study resulted in the identification of over 1500 unique proteins that were found within all nine CSF samples that were analyzed. Comparison with the HUPO serum proteome database demonstrated that human ventricular CSF contains a large array of proteins that may be unique to CSF. This analysis greatly increases our knowledge of the protein content of this clinically important biofluid.     

Biomarkers of neurodegenerative disorders： How good are they？

Biomarkers are very important indicators of normal and abnormal biological processes. Specific changes in pathologies,biochemistries and genetics can give us comprehensive information regarding the nature of any particular disease. A good biomarker should be precise and reliable, distinguishable between normal and interested disease, and differentiable between different diseases. It is believed that biomarkers have great potential in predicting chances for diseases, aiding in early diagnosis, and setting standards for the development of new remedies to treat diseases. New technologies have enabled scientists to identify biomarkers of several different neurodegenerative diseases. The followings, for instance,are only a few of the many new biomarkers that have been recently identified: the phosphorylated tau protein and aggregated β-amyloid peptide for Alzheimer‘s disease (AD), α-synuclein contained Lewy bodies and altered dopamine transporter (DAT) imaging for Parkinson‘s disease (PD), SOD mutations for familial amyotrophic lateral sclerosis (ALS), and CAG repeats resulted from Huntington‘s gene mutations in Huntington‘s disease (HD). This article will focus on the most-recent findings of biomarkers belonging to the four mentioned neurodegenerative diseases.     

CSF T-Tau/Aβ42 predicts white matter microstructure in healthy adults at risk for Alzheimer's disease

Cerebrospinal fluid (CSF) biomarkers T-Tau and Aβ(42) are linked with Alzheimer's disease (AD), yet little is known about the relationship between CSF biomarkers and structural brain alteration in healthy adults. In this study we examined the extent to which AD biomarkers measured in CSF predict brain microstructure indexed by diffusion tensor imaging (DTI) and volume indexed by T1-weighted imaging. Forty-three middle-aged adults with parental family history of AD received baseline lumbar puncture and MRI approximately 3.5 years later. Voxel-wise image analysis methods were used to test whether baseline CSF Aβ(42), total tau (T-Tau), phosphorylated tau (P-Tau) and neurofilament light protein predicted brain microstructure as indexed by DTI and gray matter volume indexed by T1-weighted imaging. T-Tau and T-Tau/Aβ(42) were widely correlated with indices of brain microstructure (mean, axial, and radial diffusivity), notably in white matter regions adjacent to gray matter structures affected in the earliest stages of AD. None of the CSF biomarkers were related to gray matter volume. Elevated P-Tau and P-Tau/Aβ(42) levels were associated with lower recognition performance on the Rey Auditory Verbal Learning Test. Overall, the results suggest that CSF biomarkers are related to brain microstructure in healthy adults with elevated risk of developing AD. Furthermore, the results clearly suggest that early pathological changes in AD can be detected with DTI and occur not only in cortex, but also in white matter.     

Proteomics and personalized medicine: a focus on kidney disease

ABSTRACT

Introduction: Inter-individual variability in response to drug treatment has induced an increased demand for decisions via personalize medicine. Also, the contribution of proteomics to the era of personalized medicine would seem to be vital in improving therapeutic outcomes.

Areas covered: We review validated biomarkers discovered by proteomics techniques and their use in personalized medicine with the focus on kidney diseases. We discuss this topic with a special emphasis on recent publications and relevant initiatives and depict some limitations that remain for personalized medicine.

Expert opinion: The development of highly accurate biomarkers is essential for optimizing the management of kidney diseases. Various biomarkers of kidney diseases have been identified using proteomic techniques. However, only a few of these biomarkers showed the potential to be used in clinical practice concerning personalized medicine. Therefore, it becomes evident that the combination of multiple biomarkers confers higher accuracy and the ability to depict complex pathophysiological conditions, a prerequisite for personalized treatment. CKD273, a multimarker panel for early CKD detection may serve as a first example for personalized medicine in nephrology. Based on this successful example, proteomics is expected to develop into the key technology to guide personalized intervention.     

天冬酰胺内肽酶和胶质细胞在创伤性脑损伤中的激活

摘要 目的：创伤性脑损伤（traumatic brain injury, TBI）缺乏安全有效的治疗手段,亟须寻找新的干预靶点。天冬酰胺内肽酶 (asparaginyl endopeptidase, AEP)在免疫和神经系统疾病中起重要作用,本研究观察了小鼠TBI模型中AEP的激活和变化,探讨AEP对脑损伤和修复的意义。方法：控制性皮层撞击法在小鼠右脑半球制作TBI损伤,在造模后的不同时间点,测定受损脑组织内的乳酸含量和AEP的活性变化,免疫荧光化学染色观察TBI之后3天的胶质细胞活化,以及AEP在其中的表达。结果：TBI造成乳酸在受损脑组织内逐渐堆积,导致小胶质细胞和星形胶质细胞的反应性活化和增生,AEP的上调和激活出现在TBI的继发性脑损伤阶段,AEP在小胶质细胞和星形胶质细胞内均出现上调。结论：AEP有可能参与调控TBI引发的胶质细胞活化,在神经损伤和修复中发挥重要作用。     

NBI及AFE在喉癌早期诊断中的应用

研究表明,喉癌的早期诊断、及时治疗不仅可以提高治愈率,而且也减少了患者的手术创伤和经济负担。积极开展喉癌的早期诊断研究具有重要的临床和社会意义。发现早期喉癌常规方法主要有电子喉镜、纤维喉镜、颈部CT及MRI检查,但并不能明显有效提高早期诊断率。而窄带成像(narrow band imaging,NBI)及自体荧光内镜(autofluorescence endoscopy AFE)是近几年用于喉癌早期诊断的两种新颖的内镜技术。NBI是一种通过变窄光波的波长,使粘膜上皮内乳头样毛细血管袢及粘膜下静脉的结构形成鲜明的对比,从而提高组织表面细微结构的对比度,便于发现病灶。而AFE技术是一种利用自发荧光聚集于病变组织的某个区域产生的差异强度,来区别正常组织与肿瘤性病变,从而用于肿瘤的早期诊断及识别癌前病变。因此,对NBI及AFE的进一步研究及认识对喉癌早期诊断提供非常重要的临床应用价值。     

Evidence that a panel of neurodegeneration biomarkers predicts vasospasm, infarction, and outcome in aneurysmal subarachnoid hemorrhage

Biomarkers for neurodegeneration could be early prognostic measures of brain damage and dysfunction in aneurysmal subarachnoid hemorrhage (aSAH) with clinical and medical applications. Recently, we developed a new panel of neurodegeneration biomarkers, and report here on their relationships with pathophysiological complications and outcomes following severe aSAH. Fourteen patients provided serial cerebrospinal fluid samples for up to 10 days and were evaluated by ultrasonography, angiography, magnetic resonance imaging, and clinical examination. Functional outcomes were assessed at hospital discharge and 6-9 months thereafter. Eight biomarkers for acute brain damage were quantified: calpain-derived α-spectrin N- and C-terminal fragments (CCSntf and CCSctf), hypophosphorylated neurofilament H,14-3-3 β and ζ, ubiquitin C-terminal hydrolase L1, neuron-specific enolase, and S100β. All 8 biomarkers rose up to 100-fold in a subset of patients. Better than any single biomarker, a set of 6 correlated significantly with cerebral vasospasm, brain infarction, and poor outcome. Furthermore, CSF levels of 14-3-3β, CCSntf, and NSE were early predictors of subsequent moderate-to-severe vasospasm. These data provide evidence that a panel of neurodegeneration biomarkers may predict lasting brain dysfunction and the pathophysiological processes that lead to it following aSAH. The panel may be valuable as surrogate endpoints for controlled clinical evaluation of treatment interventions and for guiding aSAH patient care.