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。     

Primary fatty amides in plasma associated with brain amyloid burden,hippocampal volume,and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort

IntroductionA critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers.MethodsThis study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis.ResultsEight metabolites were associated with amyloid β and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory.DiscussionPFAMs have been found increased and associated with amyloid β burden in CSF and clinical measures.     

子痫前期孕妇血清代谢组学分析

目的 比较妊娠子痫前期（PE）患者分娩前后血清代谢轮廓的变化，建立疾病区分模型并筛选出具有潜在临床应用价值的特征代谢物。方法 收集2017年9月至2018年3月于天津市第三中心医院住院的孕妇共45例，其中PE孕妇（PE组）20例（44.4%），正常孕妇（对照组）25例（55.6%），应用超高效液相色谱与质谱联用仪（UPLC-MS）分别检测PE组分娩前、分娩后以及对照组的血清标本，筛选出差异性特征代谢物并进行分析。 结果 构建了妊娠PE组血清代谢轮廓模型，共筛选出溶血磷脂酰胆碱类物质LPC 18:0、LPC 22:6、14-甲基十六烷酸、二十二酸和1,25-二羟基维生素D3-26，23内酯共5种差异性代谢产物，且溶血磷脂酰胆碱类物质LPC 18:0、LPC 22:6和14-甲基十六烷酸3种物质在PE分娩前与分娩后的差异有显著性统计学意义（P＜0.05）。结论 构建代谢轮廓模型具有很强的区分PE患者分娩前后及正常孕妇的能力，筛选出特征代谢物能够反映患者代谢水平的变化趋势，为PE的预测、诊治提供参考和帮助。     

Role of high mobility group box-1 protein in pathogenesis of acute kidney injury induced by heat stroke in mice

Objective To observe the differential expression of high mobility group box-1 protein (HMGB1) in renal tissues of heat stroke mice models, and to explore its role in the pathogenesis of heat stroke associated acute kidney injury(HS-associated AKI). Methods According to random number table, 20 healthy male C57BL/6J mice were randomly divided into 2 groups, including normal control (n=10) and heat stroke group (n=10). The mice in heat stroke group were given with a 2-hour-exposure in biological simulation chamber (temperature 41℃, humidity 70%). Heat stroke was defined as anal temperature lasting more than 40 degrees Celsius. A 18F-deoxyglucose nuclide labeled vivo imaging was conducted with micro- positron emission tomography(PET)/computer tomography (CT). Serum creatinine was examined with blood example. In order to evaluate the pathological changes, HE stain was conducted with kidney tissue, and mitochondrial morphological changes in kidney tissue were observed by transmission electron microscopy. The expressions of HMGB1 and apoptosis inducing factor mitochondria associated 2 (Aifm2) were examined by immunohistochemical method, and the levels of HMGB1 and RAGE were examined by Western blotting. The cell apoptosis of renal tissue was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). The metabolomics of kidney tissue in mice were detected by liquid chromatography-mass spectrometry (LC-MS), and the pathway enrichment analysis was carried out by KEEG database. Results (1) The body temperature of the mice in heat shock group was significantly higher than that in normal control group 45 min after model establishment (P＜0.05). The level of serum creatinine in heat shock group was significantly higher than that in normal control group (P＜0.05), and the levels of 18F-deoxyglucose increased in skeletal muscle and visceral tissue of the mice in heat-shock group. (2) HE staining showed hemorrhage in collecting duct and tubular endothelial cell swelling, and mitochondrial swelling and deformation were observed by transmission electron microscopy in kidney tissue of the heat shock group. (3)Immunohistochemical method showed that the levels of Aifm2 and HMGB1 in heat shock group were higher (P＜0.05). (4) Western blotting showed that the levels of HMGB1 and RAGE in heat shock group were higher than those in normal control group (P＜0.05). (5) TUNEL showed that the number of cells with positive stain in kidney tissue of the heat shock group was higher than that in normal control group (P＜0.05). (6) Between normal control group and heat shock group, 136 differential metabolites were detected in kidney tissues. After analysis by KEGG database, pathway abnormalities such as unsaturated fatty acid metabolism disorder may be associated with HS-associated AKI, and many differential metabolites such as adrenic acid may be important regulatory points in the pathogenesis. Conclusion Acute kidney injury is a common complication of heat shock. It may be related to the dysfunction of renal mitochondria and activation of apoptotic pathway caused by systemic hypercatabolism, which may be related to the disorder of unsaturated fatty acid metabolism and activation of HMGB1. Some differential metabolites may be of high value in HS- associated AKI studies.     

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。