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血清蛋白质组学分析对心脏骤停后神经预后有预测价值的新型血清蛋白。

Serum proteomic analysis of novel predictive serum proteins for neurological prognosis following cardiac arrest.

机构信息

Department of Emergency, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.

Nanjing Jiangbei New Area Biopharmaceutical Public Service Platform Co. Ltd, Nanjing, Jiangsu, China.

出版信息

J Cell Mol Med. 2021 Jan;25(2):1290-1298. doi: 10.1111/jcmm.16201. Epub 2020 Dec 18.

Abstract

Early prognostication of neurological outcome in comatose patients after cardiac arrest (CA) is vital for clinicians when assessing the survival time of sufferers and formulating appropriate treatment strategies to avoid the withdrawal of life-sustaining treatment (WLST) from patients. However, there is still a lack of sensitive and specific serum biomarkers for early and accurate identification of these patients. Using an isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic approach, we discovered 55 differentially expressed proteins, with 39 up-regulated secreted serum proteins and 16 down-regulated secreted serum proteins between three comatose CA survivors with good versus poor neurological recovery. Then, four proteins were selected and were validated via an enzyme-linked immunosorbent assay (ELISA) approach in a larger-scale sample containing 32 good neurological outcome patients and 46 poor neurological outcome patients, and it was confirmed that serum angiotensinogen (AGT) and alpha-1-antitrypsin (SERPINA1) were associated with neurological function and prognosis in CA survivors. A prognostic risk score was developed and calculated using a linear and logistic regression model based on a combination of AGT, SERPINA1 and neuron-specific enolase (NSE) with an area under the curve of 0.865 (P < .001), and the prognostic risk score was positively correlated with the CPC value (R = 0.708, P < .001). We propose that the results of the risk score assessment not only reveal changes in biomarkers during neurological recovery but also assist in enhancing current therapeutic strategies for comatose CA survivors.

摘要

心脏骤停 (CA) 后昏迷患者的神经预后早期预测对于临床医生评估患者的存活时间和制定适当的治疗策略以避免对患者进行生命支持治疗 (WLST) 至关重要。然而,目前仍然缺乏用于早期和准确识别这些患者的敏感和特异性血清生物标志物。使用基于相对和绝对定量 (iTRAQ) 的蛋白质组学方法,我们发现了 55 种差异表达的蛋白质,其中 39 种上调的分泌性血清蛋白和 16 种下调的分泌性血清蛋白在 3 名昏迷 CA 幸存者中表现出良好与不良神经恢复之间存在差异。然后,我们选择了 4 种蛋白质,并通过包含 32 名神经功能良好的患者和 46 名神经功能不良的患者的更大样本的酶联免疫吸附测定 (ELISA) 方法进行验证,证实血清血管紧张素原 (AGT) 和α-1-抗胰蛋白酶 (SERPINA1) 与 CA 幸存者的神经功能和预后相关。使用基于 AGT、SERPINA1 和神经元特异性烯醇化酶 (NSE) 的线性和逻辑回归模型开发并计算了预后风险评分,曲线下面积为 0.865 (P <.001),且预后风险评分与 CPC 值呈正相关 (R = 0.708, P <.001)。我们提出,风险评分评估的结果不仅揭示了神经恢复过程中生物标志物的变化,还可以帮助增强昏迷 CA 幸存者的当前治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943d/7812277/7000b1373e0d/JCMM-25-1290-g001.jpg

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