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血清外泌体 microRNAs 预测严重社区获得性肺炎患者急性呼吸窘迫综合征事件。

Serum Exosomal MicroRNAs Predict Acute Respiratory Distress Syndrome Events in Patients with Severe Community-Acquired Pneumonia.

机构信息

Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Department of Laboratory, Qihe People's Hospital, Dezhou, 251100, China.

出版信息

Biomed Res Int. 2019 Aug 5;2019:3612020. doi: 10.1155/2019/3612020. eCollection 2019.

Abstract

BACKGROUND

Severe community-acquired pneumonia (SCAP) requiring intensive care unit (ICU) treatment commonly causes acute respiratory distress syndrome (ARDS) with high mortality. This study was aimed at evaluating whether microRNAs (miRNAs) in circulating exosomes have the predictive values for patients at risk of developing ARDS due to SCAP.

METHODS

ARDS/ALI-relevant miRNAs were obtained by literature search. Exosomes in serum were isolated by ultracentrifugation method and identified by Transmission Electron Microscopy. Then the miR profiling in the exosomes using real-time PCR was analyzed in SCAP patients with or without ARDS. Moreover, multivariate Cox proportional regression analysis was performed to estimate the odds ratio of miRNA for the occurrence of ARDS and prognosis. The receiver operating characteristics (ROC) curves were calculated to discriminate ARDS cases. Finally, the Kaplan-Meier curve using log-rank method was performed to test the equality for survival distributions with different miRNA classifiers.

RESULTS

A total of 53 SCAP patients were finally recruited. Ten miRNAs were picked out. Further, a subset of exosomal miRNAs, including the miR-146a, miR-27a, miR-126, and miR-155 in ARDS group exhibited significantly elevated levels than those in non-ARDS group. The combined expression of miR-126, miR-27a, miR-146a, and miR-155 predicted ARDS with an area under the curve of 0.909 (95 % CI 0.815 -1). Only miR-126 was selected to have potential to predict the 28-day mortality (OR=1.002, P=0.024) with its median value classifier.

CONCLUSIONS

The altered levels of circulating exosomal microRNAs may be useful biologic confirmation of ARDS in patients with SCAP.

摘要

背景

需要重症监护病房(ICU)治疗的严重社区获得性肺炎(SCAP)常导致急性呼吸窘迫综合征(ARDS),死亡率高。本研究旨在评估循环外泌体中的 microRNAs(miRNAs)是否对因 SCAP 而有发生 ARDS 风险的患者具有预测价值。

方法

通过文献检索获得 ARDS/ALI 相关 miRNAs。采用超速离心法分离血清中外泌体,透射电子显微镜鉴定。然后用实时 PCR 分析 SCAP 患者伴或不伴 ARDS 时外泌体中的 miR 谱。此外,采用多变量 Cox 比例风险回归分析估计 miRNA 发生 ARDS 和预后的比值比。计算受试者工作特征(ROC)曲线以区分 ARDS 病例。最后,采用对数秩检验方法的 Kaplan-Meier 曲线检验不同 miRNA 分类器的生存分布是否相等。

结果

共纳入 53 例 SCAP 患者。挑选出 10 个 miRNAs。此外,在 ARDS 组中,一组外泌体 miRNAs,包括 miR-146a、miR-27a、miR-126 和 miR-155 的表达水平明显高于非 ARDS 组。miR-126、miR-27a、miR-146a 和 miR-155 的联合表达预测 ARDS 的曲线下面积为 0.909(95%CI 0.815-1)。只有 miR-126 被选择用于预测 28 天死亡率(OR=1.002,P=0.024),其中位数分类器。

结论

循环外泌体 miRNAs 的改变水平可能是 SCAP 患者 ARDS 的有用生物学确认。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c406/6699276/6f7e0087716a/BMRI2019-3612020.001.jpg

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