血中小分子代谢物作为生物标志物对结肠癌诊断价值的评价

目的 分析结肠癌患者血液中小分子代谢产物的水平,并评价其作为结肠癌生物标志物的能力。方法 收集结肠癌患者清晨空腹血液标本299例及性别年龄无显著差异的体检健康人血液标本277例。采用液相色谱-串联质谱法(LC-MS/MS)检测全血中11种氨基酸与31种酰基肉碱,分析结肠癌患者及健康对照血液中小分子代谢物水平的差异。利用ROC曲线分析小分子代谢物对结肠癌的诊断能力。结果 结肠癌患者血液小分子代谢物中1种酰基肉碱显著高于健康组,6种酰基肉碱、9种氨基酸显著低于健康组。经ROC曲线分析,9种氨基酸、7种酰基肉碱及16种指标对结肠癌具有一定的诊断价值,ROC曲线下面积分别为0.789、0.922和0.956。结论 结肠癌患者血液中小分子代谢物的水平与健康人有显著差异,9种氨基酸及7种酰基肉碱组合可作为区分结肠癌与健康人的生物标志物。     

2型糖尿病患者的氨基酸及酰基肉碱代谢水平分析

目的 检测并分析2型糖尿病患者血液中11种氨基酸和31种酰基肉碱的水平,评价小分子代谢物作为2型糖尿病的诊断价值.方法 收集门诊2型糖尿病患者302例,正常对照302例,利用液相串联质谱技术测定血液中的11种氨基酸和31种酰基肉碱的水平并进行比较分析.用ROC曲线判断诊断效能.结果 2型糖尿病患者与对照组的7种氨基酸和21种酰基肉碱水平差异有统计学意义,C2对2型糖尿病有辅助诊断价值,曲线下面积为0.771(95％CI=0.734～0.809),P<0.01,当临界值为12.50μmol/L时,灵敏度和特异性分别为60.3％和82.5％.结论 2型糖尿病患者存在氨基酸和酰基肉碱代谢紊乱,C2可以作为2型糖尿病的辅助诊断指标.     

代谢组学技术对牙周炎生物标志物、病理机制及与全身关系的评价

背景：近年来,代谢组学技术高速发展,研究范围十分广泛,能检测机体整体内的小分子代谢物的总体动态变化,其研究口腔疾病时可检测到机体产生的特异性代谢产物,这使得探索口腔疾病的发病机制、致病过程、早期诊断及预后监测有了新的思路。目的：对近年来代谢组学技术在牙周炎中的应用进展做一综述,同时对存在的问题及改进方法进行了展望,旨在为牙周炎诊疗提供参考依据。方法：由第一作者检索CNKI中国期刊全文数据库、万方数据库、FMRS、Web of Science及PubMed数据库2010年8月至2022年8月中收录的相关文献,中文检索词为“牙周炎,代谢组学,唾液,龈沟液”,英文检索词为“metabolomics,metabonomics,periodontitis,saliva,gingival sulcus fluid”。首先简要阅读文章摘要及主要内容,对文献进行初步筛选,将与文章主题不相关的文献排除,最终纳入的文献数为52篇。结果与结论：目前牙周炎的代谢组学研究样本来源主要为唾液、龈沟液、血清、细菌、尿液、细胞和组织,不同的样本来源均有一定的优劣。代谢组学技术与牙周炎的相关研究结果主要集中在蛋白质、脂...     

液相串联质谱在遗传代谢病高危新生儿检测中运用研究

目的研究液相串联质谱在遗传代谢病高危新生儿检测中的意义。方法留取560例临床疑似遗传代谢病新生儿的干血滤纸片,经含氨基酸、酰基肉碱内标的甲醇萃取,盐酸正丁醇衍生后,进行液相串联质谱分析。结果560例高危新生儿中检测出患儿48例,阳性率8．6％（48／560）,包括脂肪酸代谢病11例（22．9％）;氨基酸代谢病15例（31．3％）;有机酸代谢病22例（45．8％）。结论液相串联质谱可以通过检测血滤纸片中的不同酰基肉碱浓度,一次分析快速检测30多种遗传代谢病,对于遗传代谢病高危新生儿的临床诊断具有重要的价值。     

应用蛋白组学与代谢组学技术筛选狼疮生物标志物的研究进展

系统性红斑狼疮（SLE）是一种以自身抗体产生和免疫复合物形成为特点的自身免疫性疾病。其临床表现多种多样,包括肾小球肾炎、皮肤炎、血栓形成,血管炎,癫痫和关节炎等。复杂的发病机理和多样的临床症状给SLE的诊断和监测带来了巨大的挑战。寻找新的生物标志物仍然是SLE研究的主要目标和挑战之一。但值得注意的是,蛋白质组学和代谢组学为生物标志物的发现为此提供了新的思路和平台。越来越多的证据表明,蛋白质和代谢图谱具有高灵敏度和特异性,能更安全有效的诊断SLE和判断病情。通过对该领域的研究可以更好地理解SLE的发病机理,并对其诊断、治疗和预防提供新的思路。     

液相色谱-质谱研究高尿酸血症大鼠血清代谢组学

目的利用液相色谱-串联质谱技术,研究高尿酸血症(HUA)大鼠整体代谢谱的改变,筛选与高尿酸血症相关的潜在生物标志物。方法通过腺嘌呤和氧嗪酸钾灌胃3周,同时自由进食含10%酵母膏饲料方法建立高尿酸血症大鼠模型。采用基于超高效液相色谱-质谱(UPLC-MS/MS)的代谢组学方法,运用主成分分析(PCA)和偏最小二乘判别分析(PLS-DA)分析比较模型组与正常大鼠血清的代谢谱差异。结果与对照组大鼠相比,在高尿酸模型组大鼠中发现并鉴定出14种潜在生物标志物,分别为尿酸、次黄嘌呤、尿囊素、肌酐、马尿酸、犬尿氨酸、色氨酸、硫酸吲哚酚、硫酸对甲酚、牛磺酸、棕榈酸、硬脂酸、溶血磷脂酰胆碱(LPC)(17∶0)和LPC(18∶0)。提示,高尿酸血症影响大鼠嘌呤代谢、氨基酸代谢、胆汁酸代谢、脂肪酸代谢及菌群代谢。结论本研究筛选出高尿酸模型大鼠血清中的14种差异代谢物,有助于解释高尿酸血症引起的代谢改变,可望为高尿酸血症的早期筛查、诊断和治疗提供帮助。     

慢性高原病患者血清GC-TOF-MS代谢组学的初步研究

目的:研究慢性高原病患者气相色谱飞行时间质谱(GC-TOF-MS)代谢组学的变化,并鉴定血清代谢图谱的内源性代谢物,探讨青海玉树世居藏族居民潜在的差异性代谢标志物。方法:收集10例青海玉树世居藏族慢性高原病患者(CMS组)和10例世居高原健康藏族居民(control组)血清,利用GC-TOF-MS代谢组学和多元回归分析方法,如主成分分析法(PCA)、偏最小二乘法判别分析(PLS-DA)和正交偏最小二乘法判别分析(OPLS-DA)模式识别分析各代谢物的变化。结果:PCA、PLS-DA和OPLS-DA模式判别分析结果显示,两组血清代谢组均表现出明显聚类型分布。CMS组血清中延胡索酸、肌苷、植烷酸、2,2-二甲基丁二酸、β-酮己二酸、异亮氨酸、甘氨酸、丝氨酸、L-半胱氨酸、瓜氨酸、三甲基赖氨酸、1-磷酸葡萄糖和核糖水平显著高于control组;CMS组血清中下降的代谢物有硫酸、草酸、谷氨酰胺和来苏糖。结论:慢性高原病患者和高原健康藏族居民血清代谢物水平有显著性差异,这些血清代谢物的改变可能参与了慢性高原病的发生与发展。     

脂类代谢组学的发展和应用

脂类代谢组学(lipidomics)是一个刚刚兴起和快速发展的研究领域,是代谢组学研究领域一个分支.随着代谢组学研究技术的快速发展和应用,人们对脂类代谢组学的研究日益广泛和深入.生物膜脂质的研究主要包括磷脂代谢组学(phospholipidomics)和鞘脂类代谢组学(sphingolipidomics);二脂酰甘油(DAG)作为细胞内第二信使发挥信号传导功能,其动态变化与疾病的发生及发展密切相关;脂类介质(如resolvins及protectins)在炎症的发展及消退过程中发挥重要作用,同时阿司匹林的抗炎机制也与resolvins及protectins密切相关.     

基于代谢组学的干细胞研究进展

代谢组学是一种定性和定量分析复杂生物样品中所有小分子代谢物的组学方法,主要考察生物体系受刺激或扰动后内源性代谢物的变化,是系统生物学的重要组成部分.近年来代谢组学在评判细胞功能状态及决定细胞命运的代谢途径的研究中取得了很大的进展.干细胞治疗作为一种再生医学,为各种退行性疾病的治疗带来了新的希望,成为目前的研究热点,本文重点综述了代谢组学在分析各种干细胞研究中的进展.     

中枢神经系统氧感受神经元的研究进展

中枢神经系统内从丘脑到延髓的整个脑干区域分布着许多氧化学感受器,并组成了一个复杂的感受氧气的网络,它们在氧浓度变化的过程中对心血管与呼吸系统起着重要的调节作用.目前关于中枢氧感受器化学传递过程的细胞机制中,仅有颈动脉体血管球细胞和肺血管平滑肌细胞的保护机制,而中枢性氧感受神经元需要何种的离子通道和氧感受器传导缺氧的机制目前还不很清楚,本文主要对此方面目前的相关研究作简要综述.     

Ultrastructural Characterization of Oligodendroglial-like Cells in Central Nervous System Tumors

Cells with uniform, small-round nucleus and clear cytoplasm (oligodendroglial-like cell, OLC) are commonly observed in central nervous system (CNS) neoplasm of glial and neuronal lineage, such as oligodendroglioma, clear-cell ependymoma, and central neurocytoma. Immunohistochemistry does not always contribute to the characterization of OLC because of (1) loss of antigen expression; (2) lack of specific markers for oligodendrogliomas; and (3) occasional coexpression of neuronal and glial antigens. An ultrastructural analysis associated with an immunohistochemical study of 20 cases of CNS tumors largely constituted by OLCs has been performed. Neurocytomas (12 cases), medullocytomas (2 cases), cerebral neuroblastoma (1 case), and ganglioglioma (1 case) showed OLCs with ultrastructural features of neuronal differentiation (neu-ritic processes, dense-core granules, synaptic structures). Oligodendroglioma (3 cases) OLCs were characterized by mitochondrial-rich cytoplasm, and ependymoma (1 case) OLCs showed microrosettes and scattered cilia. The electron microscopic analysis can provide a more precise diagnosis of these OLC-containing tumors despite their uniform morphological appearance.     

Coagulase-negative Staphylococci: Emerging Pathogen in Central Nervous System Shunt Infection

Central nervous system (CNS) shunts are commonly used to treat patients with hydrocephalus. Its placement is associated with increased risk of infection. The study was intended to evaluate infection rate associated with CNS shunt surgeries and identify risk factors for shunt infection. The frequency and characterisation of aetiological agents along with their antibiotic resistance pattern were also studied. A prospective study of 86 patients who underwent 97 surgeries over a period of 18 months was conducted. One hundred seventy-six cerebrospinal fluid samples and 44 shunt tips obtained were processed using standard microbiological techniques. Of 86 patients, 39 (45.35%) operated for shunt revision were infected while 47 patients operated for shunt insertion were not found to be infected. Methicillin-resistant Staphylococcus epidermidis was the predominant isolate. 57.58% isolates of Staphylococci were found to be biofilm producers. Mortality of 15% was observed among infected patients. Shunt infection remains a serious issue in the patients undergoing shunt surgery. Accurate diagnosis, treatment and prevention of infection are essential in such patients.     

ASBMT Statement on Routine Prophylaxis for Central Nervous System Recurrence of Acute Lymphoblastic Leukemia following Allogeneic Hematopoietic Cell Transplantation

Hematologic malignancies treated with allogeneic hematopoietic cell transplantation (allo-HCT) have a variable incidence of post-transplantation central nervous system (CNS) relapse, with acute lymphoblastic leukemia (ALL) representing the most common disease histology. Although data supporting post-transplantation CNS prophylaxis for ALL in the pre-CNS penetrant systemic therapy era established this as standard practice, controversy exists regarding the role of post-transplantation CNS prophylaxis in the contemporary era. Here we review the most relevant (albeit exclusively retrospective) literature to date on the role of post-transplantation CNS prophylaxis in ALL. Given the paucity of data supporting the routine practice of post-transplantation CNS prophylaxis for ALL in the contemporary era, this position statement is anticipated to further stoke controversy and discussion within the transplantation community. Ultimately, only well-designed prospective clinical studies will elucidate the role of routine post-transplantation CNS prophylaxis.     

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia Patients with Central Nervous System Involvement

Central nervous system (CNS) involvement in adult acute myeloid leukemia (AML) is rare and associated with poor outcomes. Therefore, CNS involvement in AML is an indicator for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the impact of CNS involvement in AML on the outcome of allo-HSCT remains unclear. We performed a large-scale nationwide retrospective analysis to elucidate the outcomes of allo-HSCT on AML with CNS involvement (CNS+AML). Clinical data were collected from a registry database of the Japan Society for Hematopoietic Cell Transplantation. CNS involvement was defined as the infiltration of leukemia cells into the CNS or myeloid sarcoma in the CNS identified at any time from diagnosis to transplantation. One hundred fifty-seven patients with CNS+AML underwent allo-HSCT between 2006 and 2011. The estimated overall survival, cumulative incidence of relapse and nonrelapse mortality at 2 years for CNS+AML (51.2%, 30.2%, and 14.5%, respectively) were comparable with those for AML without CNS involvement (48.6%, 27.4%, and 22.0%, respectively). Univariate and multivariate analyses indicated that the development of chronic graft-versus-host disease, disease status, and cytogenetic risk category were independent prognostic factors for overall survival for CNS+AML. These results suggest that allo-HSCT may improve outcomes in patients with CNS+AML.     

干细胞与中枢神经系统损伤的修复

内源性神经干细胞，外源性神经干细胞以及胚胎干细胞具有分化为各种神经细胞的能力，神经细胞的再生在恢复中枢神经系统受损伤的功能时起着关键作用。将近年来神经干细胞和胚胎干细胞对中枢神经系统损伤的修复研究作一综述。     

便携(折叠)式中枢神经传导通路电子模型控制器的研制

介绍了折叠式中枢神经传导通路电子模型控制器的组成及工作原理,用此控制器制作的中枢神经传导通路电子模型,能以6种方式分别显示中枢神经系统的8条传导通路路径。此模型可折叠、便携、显示清晰、操作简单等。     

788例疑似中枢神经系统感染病例相关病毒IgM抗体检出率的统计分析

目的 统计分析2013年8月至2015年2月天坛医院神经内科门诊及住院患者中疑似中枢神经系统病毒感染病例的血清及脑脊液(cerebrospinal fluid,CSF)标本的病毒IgM抗体检出情况.方法 采用描述性流行病学方法对上述脑脊液及血清标本中的病毒IgM抗体检出率差异进行统计分析.结果 ①血液标本中,病毒抗体检出率由高到低依次为EB病毒(Epstein-Barr virus,EBV)抗体、单纯疱疹病毒(herpes simplex virus,HSV)抗体和风疹病毒(rubella virus,RUB)抗体,检出率分别为6.0％、5.2％和2.2％,余下病毒抗体检出率约为1％.而脑脊液中检出率最高的为HSV抗体,为4.7％,占所有检出抗体的92.5％.②病毒抗体在血清中检出率高于在其对应的脑脊液中.统计表明:单纯疱疹病毒抗体在血清中检出例数高于其在对应的脑脊液样本,差异具有统计学意义(P＜0.01).同样,相比脑脊液标本,在血清中EB病毒和柯萨奇病毒IgM抗体检出率也较高,其P值分别为P＜0.01和0.039.③病毒抗体检出以春、秋、冬三季多见,夏季检出率相对较低.④不同年龄段的患者病毒抗体检出率无差别.结论 单纯疱疹病毒仍是我院疑似中枢神经系统病毒感染病例的主要病原体,该病毒IgM抗体在患者血液和脑脊液中均具有较高的检出率.该病毒在血液标本中的检出率仅次于EB病毒.以上两种病毒是引起中枢神经系统感染的主要病毒,临床诊断中需引起足够的重视.     

100例中枢神经系统肿瘤的胶质纤维酸性蛋白免疫组化观察

对100例中枢神经系统肿瘤进行GFAP免疫组化观察。结果表明,GFAP主要分布于各种类型的星形细胞瘤,多形性胶质母细胞瘤,混合性胶质瘤及部分室管膜瘤。GFAP染色强度与瘤细胞分化程度有关。本文还探讨了室管膜瘤与少突胶质瘤存在GFAP问题。研究表明GFAP可作为诊断神经胶质瘤的一种有用标记物。     

Diagnostic Ultrastructure of Listeria monocytogenes in Human Central Nervous Tissue

The pathogenesis of Listeria monocytogenes infection of the human central nervous system is poorly understood and ultrastructural aspects are not documented. A case of fatal human L. monocytogenes meningoencephalitis is described, in which diagnosis was confirmed by blood culture and in which special staining (Brown's) showed slender gram-positive bacilli in inflamed areas of the brainstem at autopsy. Electron microscopy of blocks rescued from formalin revealed rods, up to 2.5 μm long × 0.4 μm in diameter, with grampositive type cell walls and distinctive conic ends, the latter being apparent in axial section only. The organism was either free within the cytoplasm or within endosomes or phagosomes of macrophages, smooth muscle cells, and endothelial cells. In one instance, one was seen adhering to the luminal aspect of the vascular endothelium. Central nervous system parenchymal cell infection was suspected but not confirmed. Intracytoplasmic bacteria were surrounded by an electron-transparent halo and, beyond that, a cloud of host-derived microfilaments, as previously described by others in vitro and in animals. The morphology of L. monocytogenes is compared with that of other intracellular pathogens and is found to be distinctive, suggesting the value of ultrastructural study in diagnosis. Such work could also help to solve outstanding pathogenetic questions of central nervous system invasion and spread.