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严重子宫内膜异位症患者的代谢特征:一项前瞻性实验研究。

Metabolic Profile of Patients with Severe Endometriosis: a Prospective Experimental Study.

机构信息

Department of Biomedical Sciences, Unit of Clinic Metabolomics, University of Cagliari, Cagliari, Italy.

Department of Surgical Sciences, Division of Gynecology and Obstetrics, University of Cagliari, Cagliari, Italy.

出版信息

Reprod Sci. 2021 Mar;28(3):728-735. doi: 10.1007/s43032-020-00370-9. Epub 2020 Nov 10.

Abstract

Endometriosis is a common disease affecting women in reproductive age. There are several hypotheses on the pathogenesis of this disease. Often, its lesions and symptoms overlap with those of many other medical and surgical conditions, causing a delay in diagnosis. Metabolomics represents a useful diagnostic tool for the study of metabolic changes during a different physiological or pathological status. We used H-NMR to explore metabolic alteration in a cohort of patients with endometriosis in order to contribute to a better understanding of the pathophysiology of the disease and to suggest new useful biomarkers. Thirty-seven patients were recruited for the metabolomic analysis: 22 patients affected by symptomatic endometriosis and 15 not affected by it. Their serum samples were collected and analyzed with H-NMR. Multivariate statistical analysis was conducted, followed by univariate and pathway analyses. Partial Least Square Discriminant Analysis (PLS-DA) was performed to determine the presence of any differences between the non-endometriosis and endometriosis samples (RX = 0.596, RY = 0.713, Q = 0.635, and p < 0.0001). β-hydroxybutyric acid and glutamine were significantly increased, whereas tryptophan was significantly decreased in the endometriosis patients. ROC curves were built to test the diagnostic power of the metabolites (β-hydroxybutyric acid: AUC = 0.85 CI = 0.71-0.99; glutamine: AUC = 0.83 CI = 0.68-0.98; tryptophan: AUC = 0.75 CI = 0.54-0.95; β-hydroxybutyric acid + glutamine + tryptophan AUC = 0.92 CI = 0.81-1). The metabolomic approach enabled the identification of several metabolic alterations occurring in women with endometriosis. These findings may provide new bases for a better understanding of the pathophysiological mechanisms of the disease and for the discovery of new biomarkers. Trial registration number NCT02337816.

摘要

子宫内膜异位症是一种常见于育龄妇女的疾病。目前有几种关于这种疾病发病机制的假说。通常,其病变和症状与许多其他医学和外科疾病重叠,导致诊断延迟。代谢组学是研究不同生理或病理状态下代谢变化的一种有用的诊断工具。我们使用 H-NMR 探索了一组子宫内膜异位症患者的代谢变化,以期有助于更好地理解疾病的病理生理学,并提出新的有用的生物标志物。我们招募了 37 名患者进行代谢组学分析:22 名患有症状性子宫内膜异位症的患者和 15 名未患有该疾病的患者。采集他们的血清样本并进行 H-NMR 分析。进行了多变量统计分析,随后进行了单变量和途径分析。偏最小二乘判别分析(PLS-DA)用于确定非子宫内膜异位症和子宫内膜异位症样本之间是否存在任何差异(RX=0.596,RY=0.713,Q=0.635,p<0.0001)。子宫内膜异位症患者的β-羟基丁酸和谷氨酰胺显著增加,而色氨酸显著减少。构建 ROC 曲线以测试代谢物的诊断能力(β-羟基丁酸:AUC=0.85 CI=0.71-0.99;谷氨酰胺:AUC=0.83 CI=0.68-0.98;色氨酸:AUC=0.75 CI=0.54-0.95;β-羟基丁酸+谷氨酰胺+色氨酸 AUC=0.92 CI=0.81-1)。代谢组学方法能够识别出在子宫内膜异位症患者中发生的几种代谢变化。这些发现可能为更好地理解疾病的病理生理机制和发现新的生物标志物提供新的基础。试验注册号 NCT02337816。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7764/7862197/e60102d2a9c3/43032_2020_370_Fig1_HTML.jpg

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