基于CiteSpace可视化分析代谢组学在中医药领域的研究现状及趋势＊

目的 应用可视化方法分析代谢组学在中医药领域的现状及趋势。方法 检索中国知网数据库（CNKI）和Web of Science 核心合集数据库2021年3月15日之前收录的中医药领域代谢组学研究的相关文献，应用CiteSpace软件对纳入的文献进行关键词、作者、研究机构等内容进行可视化分析。结果 共纳入中文文献247篇，英文文献350篇。文献数量在波动中迅速上升。中、英文文献作者合作网络显示，张爱华是中医药领域代谢组学研究发文量最多的作者，并形成了核心研究团队。发文机构显示，中国医学科学院是该领域的重要研究机构，机构间合作紧密。中、英文文献关键词分析显示，研究内容主要集中在核磁共振、代谢标记物、冠心病、质谱技术、代谢通路等相关领域。结论 中医药领域代谢组学研究的热点主要为中医药治疗代谢性疾病的机制研究。研究趋势为卵泡代谢组学研究及中药有效成分的研究。     

Non-invasive metabolic biomarkers for early diagnosis of diabetic nephropathy: Meta-analysis of profiling metabolomics studies

AimDiabetic nephropathy (DN) is one of the worst complications of diabetes. Despite a growing number of DN metabolite profiling studies, most studies are suffering from inconsistency in their findings. The main goal of this meta-analysis was to reach to a consensus panel of significantly dysregulated metabolites as potential biomarkers in DN.Data synthesisTo identify the significant dysregulated metabolites, meta-analysis was performed by “vote-counting rank” and “robust rank aggregation” strategies. Bioinformatics analyses were performed to identify the most affected genes and pathways. Among 44 selected studies consisting of 98 metabolite profiles, 17 metabolites (9 up-regulated and 8 down-regulated metabolites), were identified as significant ones by both the meta-analysis strategies (p-value<0.05 and OR>2 or <0.5) and selected as DN metabolite meta-signature. Furthermore, enrichment analyses confirmed the involvement of various effective biological pathways in DN pathogenesis, such as urea cycle, TCA cycle, glycolysis, and amino acid metabolisms. Finally, by performing a meta-analysis over existing time-course studies in DN, the results indicated that lactic acid, hippuric acid, allantoin (in urine), and glutamine (in blood), are the topmost non-invasive early diagnostic biomarkers.ConclusionThe identified metabolites are potentially involved in diabetic nephropathy pathogenesis and could be considered as biomarkers or drug targets in the disease.Prospero registration numberCRD42020197697.     

Erythrocyte sphingolipid species as biomarkers of Alzheimer's disease

Diagnosing Alzheimer's disease (AD) in the early stage is challenging. Informative biomarkers can be of great value for population-based screening. Metabolomics studies have been used to find potential biomarkers, but commonly used tissue sources can be difficult to obtain. The objective of this study was to determine the potential utility of erythrocyte metabolite profiles in screening for AD. Unlike some commonly-used sources such as cerebrospinal fluid and brain tissue, erythrocytes are plentiful and easily accessed. Moreover, erythrocytes are metabolically active, a feature that distinguishes this sample source from other bodily fluids like plasma and urine. In this preliminary pilot study, the erythrocyte metabolomes of 10 histopathologically confirmed AD patients and 10 patients without AD (control (CTRL)) were compared. Whole blood was collected post-mortem and erythrocytes were analyzed using ultra-performance liquid chromatography tandem mass spectrometry. Over 750 metabolites were identified in AD and CTRL erythrocytes. Seven were increased in AD while 24 were decreased (P<0.05). The majority of the metabolites increased in AD were associated with amino acid metabolism and all of the decreased metabolites were associated with lipid metabolism. Prominent among the potential biomarkers were 10 sphingolipid or sphingolipid-related species that were consistently decreased in AD patients. Sphingolipids have been previously implicated in AD and other neurological conditions. Furthermore, previous studies have shown that erythrocyte sphingolipid concentrations vary widely in normal, healthy adults. Together, these observations suggest that certain erythrocyte lipid phenotypes could be markers of risk for development of AD.     

代谢组学在肾脏疾病中的研究进展

目前肾脏疾病的准确诊断最终仍需要肾穿刺活检技术。代谢组学可以定性和定量分析生物机体包括系统、器官或细胞在受到外界因素影响下引起的内源性代谢产物的变化；肾脏疾病的发生发展会受到生物体内外多种因素的影响，与机体代谢异常密切相关，表现为各类代谢产物的变化。近年来，代谢组学为肾脏疾病的研究做出了很多贡献，本文就代谢组学在肾脏疾病中的研究进展作以综述，希望为肾脏病发生发展及诊断提供新的研究思路和方向。     

Small molecule biomarkers for neonatal hypoxic ischemic encephalopathy

Hypoxic Ischemic Encephalopathy (HIE) is one of the most deleterious conditions in the perinatal period and the access to small molecule biomarkers aiding accurate diagnosis and disease staging, progress monitoring, and early outcome prognosis could provide relevant advances towards the development of personalized therapies. The emergence of metabolomics, the “omics” technology enabling the holistic study of small molecules, for biomarker discovery employing different analytical platforms, animal models and study populations has drastically increased the number and diversity of small molecules proposed as candidate biomarkers. However, the use of very few compounds has been implemented in clinical guidelines and authorized medical devices. In this work we review different approaches employed for discovering HIE-related small molecule biomarkers. Their role in associated biochemical disease mechanisms as well as the way towards their translation into the clinical practice are discussed.     

刺络联合舒利迭吸入疗法防治小儿哮喘的疗效观察

目的:探讨刺络联合舒利迭吸入疗法治疗小儿哮喘的临床疗效,并观察其用药前后的代谢组学变化。方法:选取2013年10月至2015年9月上海市宝山区中西医结合医院收治的哮喘患儿50例作为研究对象,按照随机数字表法随机分为对照组和观察组,每组25例。对照组采用沙美特罗替卡松粉吸入剂治疗,观察组在对照组治疗的基础上针刺四缝和少商穴位以及耳尖放血,间隔1 d进行1次,周期90 d。采集患儿用药前0 d,用药30 d,用药60 d,用药90 d的尿液,采用气相色谱-质谱联用技术(GC-MS)检测尿液内源性代谢物,观察治疗前后2组患儿临床症状评分、免疫指标以及代谢谱的变化情况。结果:观察组总有效率高于对照组,2组比较差异有统计学意义(P<0.05);与治疗前比较,2组患儿各项中医症候均明显减轻,观察组改善程度比对照组更为显著,差异有统计学意义,2组免疫学指标与治疗前比较均显著降低(P<0.05),与对照组比较(90 d),观察组(90 d)各指标降低程度更为明显,差异均有统计学意义(P<0.05)。采用有监督的分析-OPLS分析了治疗前对照组和观察组(0 d),治疗后(90 d)对照组和观察组的尿液代谢谱,结果显示4组代谢谱分离良好,鉴定了21个相关代谢标志物。结论:刺络联合舒利迭吸入疗法治疗小儿哮喘的临床效果确切,可改善患儿症状,降低免疫指标,其作用机制可能与丙氨酸,天冬氨酸和谷氨酸代谢、乙醛酸和二羧酸代谢和组氨酸代谢等代谢异常有关。     

A metabolomic data fusion approach to support gliomas grading

Magnetic resonance imaging (MRI) is the current gold standard for the diagnosis of brain tumors. However, despite the development of MRI techniques, the differential diagnosis of central nervous system (CNS) primary pathologies, such as lymphoma and glioblastoma or tumor‐like brain lesions and glioma, is often challenging. MRI can be supported by in vivo magnetic resonance spectroscopy (MRS) to enhance its diagnostic power and multiproject‐multicenter evaluations of classification of brain tumors have shown that an accuracy around 90% can be achieved for most of the pairwise discrimination problems. However, the survival rate for patients affected by gliomas is still low. The High‐Resolution Magic‐Angle‐Spinning Nuclear Magnetic Resonance (HR‐MAS NMR) metabolomics studies may be helpful for the discrimination of gliomas grades and the development of new strategies for clinical intervention. Here, we propose to use T₂‐filtered, diffusion‐filtered and conventional water‐presaturated spectra to try to extract as much information as possible, fusing the data gathered by these different NMR experiments and applying a chemometric approach based on Multivariate Curve Resolution (MCR). Biomarkers important for glioma's discrimination were found. In particular, we focused our attention on cystathionine (Cyst) that shows promise as a biomarker for the better prognosis of glioma tumors.     

Metabolomics study on the therapeutic effect of traditional Chinese medicine Xue-Fu-Zhu-Yu decoction in coronary heart disease based on LC-Q-TOF/MS and GC-MS analysis

The present study aims is to investigate the metabolic mechanism of Xue-Fu-Zhu-Yu decoction (XFZYD) in the treatment of blood-stasis syndrome in Coronary Heart Disease (CHD). To that end, 30 CHD patients with Blood-Stasis Syndrome (BSS) and 20 healthy subjects were enrolled. LC-Q-TOF/MS analysis determined that in comparison between CHD with BSS patients (Group A) and healthy subjects (Group C), 59 significantly differential metabolites in the positive mode and 18 significantly differential metabolites in the negative mode. The metabolite constituents in the plasma of 30 CHD with BSS patients before (group A) and after 30 days of treatment (Group B), and 20 healthy subjects (Group C) were analyzed using LC-Q-TOF/MS and GC-MS. Based on multivariate statistical analysis (PCA, PLS-DA and OPLS-DA), we determined 69 differential metabolites. The levels of hemorheology indexes were significantly down-regulated after treatment. Metabolic pathway attribution analysis showed that lipid metabolism, amino acid metabolism and bile acid metabolism pathways are involved. Our study identifies the metabolic networks of CHD and demonstrates the efficacy of this metabolomics approach to systematically study the therapeutic effect of XFZYC on CHD.     

基于代谢组学探讨艾灸关元穴对老年大鼠肾能量代谢的影响＊

目的 通过UHPLC-Q-TOF-MS代谢组学探讨艾灸关元穴对老年大鼠肾代谢物的影响，进而为艾灸关元穴的作用机制提供参考。方法 将8月龄SD雄性大鼠设为成年对照组（8只），21月龄SD雄性大鼠随机分为老年对照组（8只）、老年金匮肾气丸组（7只）、老年艾灸组（8只）。老年金匮肾气丸组每日按体重给药，老年艾灸组每日艾灸关元穴15 min，均每周5天。实验持续13周后检测大鼠肾组织线粒体呼吸耗氧速率、琥珀酸脱氢酶（SDH）活性以及血清肾功能指标，观察肾脏病理变化，结合UHPLC-Q-TOF-MS技术对大鼠的肾组织进行代谢轮廓分析，筛选代谢差异物并进行鉴定。结果 与老年对照组比较，老年艾灸组大鼠肾线粒体的呼吸耗氧速率和SDH酶的活力显著提高（P<0.01）。代谢组学结果显示，肾组织中筛选出13个共同差异化合物，分别是丁酸十二烷基酯、亚油酰胺、5-甲基四氢叶酸、PC（16∶0/22∶5（7Z，10Z，13Z，16Z，19Z））、6，8-二羟基嘌呤、1，2，3-丙烷三羧酸、3-（4-甲氧基苯基）-2-氧代丙酸、吲哚-3-乙酰甘氨酸、亚麻油酸、9，10-环氧十八烷酸、二十二碳五烯酸（22n-6）、牛磺胆酸、LysoPS （18∶0/0∶0）。结论 艾灸关元穴可通过调控老年大鼠的牛磺酸和亚牛磺酸代谢、α-亚麻酸代谢、亚油酸代谢、甘油磷脂代谢来调节肾的能量代谢。     

Chemical isotope labeling liquid chromatography mass spectrometry for investigating acute dietary effects of cow milk consumption on human urine metabolome

Biomarker discovery has been increasingly important in the field of metabolomics for the detection and understanding of diseases. Of the many biofluids available for metabolomics, urine is a preferred option as it is non-invasive to collect and contains a wide range of metabolites reflective of the health status of the testing individual. However, urine also contains many exogenous metabolites which are introduced through various sources such as diet. This complicates the data interpretation when searching the metabolome for disease-related endogenous metabolites. Since diet is difficult to control, this work aims to study the acute effects of diet (particularly cow milk) consumption on the human urine amine/phenol submetabolome by utilizing differential chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS). LC-MS analysis of 62 urine samples collected before and after (1 hour and 2 hours) milk intake resulted in the detection of 4985 metabolites with an average of 3815 ± 206 (n = 62) detected per sample. The work aims to differentiate the exogenous “food” metabolites from the endogenous metabolite pool and to determine any dietary effects from milk intake on the human urine metabolome.