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UPLC-QTOF/MS based metabolomics reveals metabolic alterations associated with severe sepsis

机译:基于UPLC-QTOF / MS的代谢组语揭示了与严重败血症相关的代谢改变

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Severe sepsis (SS) remains among the leading causes of death in both developed and developing countries. There is an urgent need for accurate biomarkers for early diagnosis of SS. Non-targeted mass-spectrometry was used to characterize sensitive and economical peripheral biomarker(s) associated with the serum metabolome from SS patients. In this study, serum samples were obtained from healthy controls and age-matched patients with SS. Multivariate statistical analysis was performed, and the metabolites identified were studied in relation to subsequent intervention procedures by receiver operating characteristic curve analysis. Metabolic differences among SS and control subjects were identified based on orthogonal signal correction-partial least squares discriminant analysis. Sphingosine, 5-methylcytidine, 3-dehydrocarnitine, 4-acetamido-2-aminobutanoic acid and phenyllactic acid in the SS subjects were significantly different from the controls. Three metabolites comprising sphingosine, 5-methylcytidine and 3-dehydrocarnitine were selected as candidate biomarkers and validated in separate, independent patient cohorts. These metabolite markers hold great potential for further development of SS early diagnostic markers. These findings suggest mass-spectrometry serum metabolomics may possess great potential for early diagnosis of SS patients.
机译:严重的败血症(SS)仍然是发达国家和发展中国家的主要死因之一。迫切需要准确的生物标志物进行SS的早期诊断。非靶向质谱法用于表征与SS患者血清代谢物相关的敏感和经济的外周生物标志物。在本研究中,血清样品从健康对照和年龄匹配的SS患者中获得。进行多变量统计分析,并通过接收器操作特征曲线分析研究了与随后的干预程序相关的代谢物。基于正交信号校正部分最小二乘判别分析来识别SS和控制受试者之间的代谢差异。 SS受试者中的鞘氨醇,5-甲基胞苷,3-甲基氨基甲酸,4-乙酰氨基-2-氨基丁酸和苯乳酸与对照显着不同。选择包含鞘氨醇,5-甲基胞苷和3-脱氢氨基的三种代谢物作为候选生物标志物,并在单独的独立患者群体中验证。这些代谢物标记具有巨大的潜力,可以进一步发展SS早期诊断标志物。这些发现表明质谱血清代谢组学可能具有巨大诊断SS患者的潜力。

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