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综合分析代谢组学特征对慢性砷暴露引起的健康损伤:一项代谢组学研究。

Comprehensive analysis of the metabolomic characteristics on the health lesions induced by chronic arsenic exposure: A metabolomics study.

机构信息

Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China; Taizhou Hospital of Zhejiang Province, Taizhou, Zhejiang, China; Center on Evidence-Based Medicine & Clinical Epidemiological Research, School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China; Center on Evidence-Based Medicine & Clinical Epidemiological Research, School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China.

出版信息

Int J Hyg Environ Health. 2019 Apr;222(3):434-445. doi: 10.1016/j.ijheh.2018.12.010. Epub 2019 Feb 19.

Abstract

Early detection of the health lesions induced by chronic arsenic exposure (HLICAE) are crucial to prevent permanent arsenic-induced damage. If HLICAE can be identified in time, appropriate preventive and therapeutic measures may be provided without various avoidable lesions. The present study aims to assess the probability of HLICAE early recognition with metabolomics. Applying a case-control study, 94 participants with HLICAE (cases) and other 94 subjects without HLICAE (controls) were matched with gender and age (±1 year), coming from a previous chronic arsenic exposure cohort. Serum metabolomic profiles were assessed by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and analyzed with univariate and multivariate statistics. A total of 210 and 364 features were detected in positive and negative ion modes (ESI/ESI), respectively. The altered metabolic pathways included lipid and amino acid metabolisms. 28 metabolomics-based biomarkers were significantly associated with HLICAE and provided areas under the curve (AUC, 95% confidence interval) of 0.898 (0.836, 0.960) and 0.908 (0.855, 0.960) in the discovery phase, 78.6% and 86.4% of positive predictive values in the validation phase, in distinguishing HLICAE from controls in ESI/ESI, respectively. This study provides novel insights on mechanisms of health effects probably induced by chronic arsenic exposure, and these biomarkers may be applied in HLICAE early detection.

摘要

早期发现慢性砷暴露引起的健康损伤(HLICAE)对于预防永久性砷诱导损伤至关重要。如果能够及时发现 HLICAE,可以在没有各种可避免损伤的情况下提供适当的预防和治疗措施。本研究旨在应用代谢组学评估早期识别 HLICAE 的可能性。采用病例对照研究,从先前的慢性砷暴露队列中匹配了 94 例 HLICAE(病例)和 94 例无 HLICAE(对照)的参与者,匹配性别和年龄(±1 岁)。采用超高效液相色谱-四极杆飞行时间质谱(UPLC-QTOF-MS)评估血清代谢组学谱,并进行单变量和多变量统计分析。在正负离子模式(ESI/ESI)下分别检测到 210 和 364 个特征。改变的代谢途径包括脂质和氨基酸代谢。基于 28 种代谢组学的生物标志物与 HLICAE 显著相关,在发现阶段提供了 0.898(0.836,0.960)和 0.908(0.855,0.960)的曲线下面积(AUC,95%置信区间),在验证阶段,ESI/ESI 分别为 78.6%和 86.4%的阳性预测值,用于区分 HLICAE 与对照组。本研究为慢性砷暴露可能引起的健康影响机制提供了新的见解,这些生物标志物可能应用于 HLICAE 的早期检测。

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