Metabolomic Profiling by UPLC-QTOF/MS Reveals Potential Biomarkers and Metabolic Alterations in Pediatric Septic Shock

利用超高效液相色谱-四极杆飞行时间质谱(UPLC-QTOF/MS)进行代谢组学分析,揭示了儿童脓毒症休克中的潜在生物标志物和代谢改变。

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Abstract

PURPOSE: Septic shock is a major cause of mortality in pediatric intensive care units (PICU). This study aimed to investigate metabolic alterations in PICU patients with septic shock using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) to identify potential biomarkers and unique metabolic pathways for early diagnosis and improved treatment strategies. PATIENTS AND METHODS: Serum and urine samples from septic shock survivors (SS), septic shock non-survivors (SNS), and non-infected systemic inflammatory response syndrome (SIRS) patients were analyzed using UPLC-QTOF/MS. All differential metabolites from serum samples were subjected to multiple regression analysis. Bioinformatics analysis was conducted on metabolite data obtained from urine and serum samples of the SS and SNS groups to further investigate differences in metabolic pathways. RESULTS: Combinational metabolites demonstrated superior diagnostic performance compared with individual metabolites, with an area under the receiver operating characteristic curve (AUC) of 0.925 for SS vs SIRS and 0.901 for SNS vs SIRS. Key metabolic pathways, including glycerophospholipid metabolism, arginine and proline metabolism, were implicated in the development of septic shock. Importantly, alterations in glutamine and glutamate metabolism were associated with survival, suggesting the significant potential for further investigation. CONCLUSION: Metabolomic profiling using UPLC-QTOF/MS represents a promising approach for early diagnosis of pediatric septic shock. The identified biomarkers and metabolic pathways provide insights into the pathogenic mechanisms and may assist in the development of targeted therapeutic strategies. Further validation in larger, prospective cohorts is required before clinical application.

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