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内皮细胞表型显示出不同的代谢模式,并可预测创伤患者的死亡率。

Endothelial Cell Phenotypes Demonstrate Different Metabolic Patterns and Predict Mortality in Trauma Patients.

机构信息

Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.

CAG Center for Endotheliomics, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark.

出版信息

Int J Mol Sci. 2023 Jan 23;24(3):2257. doi: 10.3390/ijms24032257.

Abstract

In trauma patients, shock-induced endotheliopathy (SHINE) is associated with a poor prognosis. We have previously identified four metabolic phenotypes in a small cohort of trauma patients (N = 20) and displayed the intracellular metabolic profile of the endothelial cell by integrating quantified plasma metabolomic profiles into a genome-scale metabolic model (iEC-GEM). A retrospective observational study of 99 trauma patients admitted to a Level 1 Trauma Center. Mass spectrometry was conducted on admission samples of plasma metabolites. Quantified metabolites were analyzed by computational network analysis of the iEC-GEM. Four plasma metabolic phenotypes (A-D) were identified, of which phenotype D was associated with an increased injury severity score ( < 0.001); 90% (91.6%) of the patients who died within 72 h possessed this phenotype. The inferred EC metabolic patterns were found to be different between phenotype A and D. Phenotype D was unable to maintain adequate redox homeostasis. We confirm that trauma patients presented four metabolic phenotypes at admission. Phenotype D was associated with increased mortality. Different EC metabolic patterns were identified between phenotypes A and D, and the inability to maintain adequate redox balance may be linked to the high mortality.

摘要

在创伤患者中,由休克引起的内皮病变(SHINE)与预后不良相关。我们之前在一小部分创伤患者(N=20)中确定了四种代谢表型,并通过将量化的血浆代谢组学图谱整合到基因组规模的代谢模型(iEC-GEM)中,展示了内皮细胞的细胞内代谢特征。对一家 1 级创伤中心收治的 99 名创伤患者进行了回顾性观察性研究。对入院时的血浆代谢物样本进行了质谱分析。通过 iEC-GEM 的计算网络分析对量化的代谢物进行了分析。确定了四种血浆代谢表型(A-D),其中表型 D 与损伤严重程度评分增加相关(<0.001);在 72 小时内死亡的患者中,有 90%(91.6%)具有这种表型。发现表型 A 和 D 之间的推断 EC 代谢模式存在差异。表型 D 无法维持足够的氧化还原稳态。我们证实,创伤患者在入院时表现出四种代谢表型。表型 D 与死亡率增加相关。在表型 A 和 D 之间确定了不同的 EC 代谢模式,并且无法维持足够的氧化还原平衡可能与高死亡率有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/038a/9916682/67f7277f74bc/ijms-24-02257-g001.jpg

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