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胆囊结石病演变中代谢物变化的特征。

Features of Metabolite Changes in Disease Evolution in Cholecystolithiasis.

机构信息

Shanghai Biotree Biotech Co. Ltd., Shanghai, China.

Institute of Basic Medical Sciences, The Second Hospital of Shandong University, Shandong, 250033, China.

出版信息

Dig Dis Sci. 2024 Jan;69(1):275-288. doi: 10.1007/s10620-023-08134-6. Epub 2023 Nov 9.

Abstract

BACKGROUND

Cholecystolithiasis is defined as a disease caused by complex and changeable factors. Advanced age, female sex, and a hypercaloric diet rich in carbohydrates and poor in fiber, together with obesity and genetic factors, are the main factors that may predispose people to choledocholithiasis. However, serum biomarkers for the rapid diagnosis of choledocholithiasis remain unclear.

AIMS

This study was designed to explore the pathogenesis of cholecystolithiasis and identify the possible metabolic and lipidomic biomarkers for the diagnosis of the disease.

METHODS

Using UHPLC-MS/MS and GC-MS, we detected the serum of 28 cholecystolithiasis patients and 19 controls. Statistical analysis of multiple variables included Principal Component Analysis (PCA). Visualization of differential metabolites was performed using volcano plots. The screened differential metabolites were further analyzed using clustering heatmaps. The quality of the model was assessed using random forests.

RESULTS

In this study, dramatically altered lipid homeostasis was detected in cholecystolithiasis group. In addition, the levels of short-chain fatty acids and amino acids were noticeably changed in patients with cholecystolithiasis. They detected higher levels of FFA.18.1, FFA.20.1, LPC16.0, and LPC20.1, but lower levels of 1-Methyl-L-histidine and 4-Hydroxyproline. In addition, glycine and L-Tyrosine were higher in choledocholithiasis group. Analyses of metabolic serum in affected patients have the potential to develop an integrated metabolite-based biomarker model that can facilitate the early diagnosis and treatment of the disease.

CONCLUSION

Our results highlight the value of integrating lipid, amino acid, and short-chain fatty acid to explore the pathophysiology of cholecystolithiasis disease, and consequently, improve clinical decision-making.

摘要

背景

胆石病是由复杂多变的因素引起的疾病。高龄、女性、高糖高脂饮食、肥胖和遗传因素等是导致胆总管结石的主要因素。然而,用于胆总管结石快速诊断的血清生物标志物仍不清楚。

目的

本研究旨在探讨胆石病的发病机制,寻找可能用于诊断该病的代谢和脂质组学生物标志物。

方法

使用 UHPLC-MS/MS 和 GC-MS 检测了 28 例胆石病患者和 19 例对照者的血清。采用主成分分析(PCA)对多变量进行统计分析。使用火山图对差异代谢物进行可视化。进一步采用聚类热图对筛选出的差异代谢物进行分析。使用随机森林评估模型的质量。

结果

本研究在胆石病组中检测到明显改变的脂质稳态。此外,胆石病患者的短链脂肪酸和氨基酸水平也明显改变。他们检测到更高水平的 FFA.18.1、FFA.20.1、LPC16.0 和 LPC20.1,但 1-甲基-L-组氨酸和 4-羟脯氨酸水平较低。此外,胆石病组中甘氨酸和 L-酪氨酸水平较高。对受影响患者的代谢血清进行分析有可能开发出一种基于综合代谢物的生物标志物模型,从而促进疾病的早期诊断和治疗。

结论

我们的研究结果强调了整合脂质、氨基酸和短链脂肪酸来探索胆石病病理生理学的价值,并由此改善临床决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f345/10787879/d6d825077029/10620_2023_8134_Fig1_HTML.jpg

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