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基于蛋白质组学的院外心脏骤停后人体蛋白质表达的血清变化:自主循环恢复(ROSC)后第1天幸存者与非幸存者预后的初步研究

Proteomics-Based Serum Alterations of the Human Protein Expression after Out-of-Hospital Cardiac Arrest: Pilot Study for Prognostication of Survivors vs. Non-Survivors at Day 1 after Return of Spontaneous Circulation (ROSC).

作者信息

Hinkelbein Jochen, Kolaparambil Varghese Johnson Lydia, Kiselev Nikolai, Schmitz Jan, Hellmich Martin, Drinhaus Hendrik, Lichtenstein Theresa, Storm Christian, Adler Christoph

机构信息

Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, University Hospital Cologne, 50937 Cologne, Germany.

Faculty of Medicine and Surgery, Università degli Studi di Perugia, 05100 Terni, Italy.

出版信息

J Clin Med. 2022 Feb 14;11(4):996. doi: 10.3390/jcm11040996.

Abstract

BACKGROUND

Targeted temperature management (TTM) is considered standard therapy for patients after out-of-hospital cardiac arrest (OHCA), cardiopulmonary resuscitation (CPR), and return of spontaneous circulation (ROSC). To date, valid protein markers do not exist to prognosticate survivors and non-survivors before the end of TTM. The aim of this study is to identify specific protein patterns/arrays, which are useful for prediction in the very early phase after ROSC.

MATERIAL AND METHODS

A total of 20 adult patients with ROSC (19 male, 1 female; 69.9 ± 9.5 years) were included and dichotomized in two groups (survivors and non-survivors at day 30). Serum samples were drawn at day 1 after ROSC (during TTM). Three panels (organ failure, metabolic, neurology, inflammation; OLINK, Uppsala, Sweden) were utilised. A total of four proteins were found to be differentially regulated (>2- or <-0.5-fold decrease; -test). Bioinformatic platforms were utilised to analyse pathways and identify signalling cascades and to screen for potential biomarkers.

RESULTS

A total of 276 proteins were analysed and revealed only 11 statistically significant protein alterations (Siglec-9, LAYN, SKR3, JAM-B, N2DL-2, TNF-B, BAMBI, NUCB2, STX8, PTK7, and PVLAB). Following the Bonferroni correction, no proteins were found to be regulated as statistically significant. Concerning the protein fold change for clinical significance, four proteins (IL-1 alpha, N-CDase, IL5, CRH) were found to be regulated in a clinically relevant context.

CONCLUSIONS

Early analysis at 1 day after ROSC was not sufficiently possible during TTM to prognosticate survival or non-survival after OHCA. Future studies should evaluate protein expression later in the course after ROSC to identify promising protein candidates.

摘要

背景

目标温度管理(TTM)被认为是院外心脏骤停(OHCA)、心肺复苏(CPR)及自主循环恢复(ROSC)后患者的标准治疗方法。迄今为止,在TTM结束前,尚无有效的蛋白质标志物可用于预测幸存者和非幸存者。本研究的目的是识别特定的蛋白质模式/阵列,这些模式/阵列有助于在ROSC后的极早期进行预测。

材料与方法

共纳入20例ROSC成年患者(19例男性,1例女性;年龄69.9±9.5岁),并分为两组(30天时的幸存者和非幸存者)。在ROSC后第1天(TTM期间)采集血清样本。使用了三个检测板(器官衰竭、代谢、神经学、炎症;OLINK,瑞典乌普萨拉)。共发现四种蛋白质存在差异调节(>2倍或<-0.5倍降低;检验)。利用生物信息学平台分析通路、识别信号级联反应并筛选潜在生物标志物。

结果

共分析了276种蛋白质,仅发现11种具有统计学意义的蛋白质改变(唾液酸结合免疫球蛋白样凝集素9、层黏连蛋白、SKR3、连接黏附分子B、N2DL-2、肿瘤坏死因子β、BAMBI、核苷结合蛋白2、 syntaxin-8、蛋白酪氨酸激酶7和PVLAB)。经过Bonferroni校正后,未发现有蛋白质具有统计学意义的调节。关于具有临床意义的蛋白质倍数变化,发现四种蛋白质(白细胞介素-1α)、N-环糊精酶、白细胞介素5、促肾上腺皮质激素释放激素)在临床相关背景下存在调节。

结论

在TTM期间,ROSC后第1天进行早期分析不足以预测OHCA后的生存或非生存情况。未来的研究应在ROSC后的病程后期评估蛋白质表达,以确定有前景的蛋白质候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f6/8874966/4d6aa65219aa/jcm-11-00996-g001.jpg

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