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夜班期间医护人员基因表达的变化:对免疫反应和健康风险的影响。

Changes in gene expression in healthcare workers during night shifts: implications for immune response and health risks.

作者信息

Nukiwa Ryota, Oda Sayaka, Matsumoto Hisatake, Al Kadi Mohamad, Murao Shuhei, Matsubara Tsunehiro, Nakao Shunichiro, Okuzaki Daisuke, Ogura Hiroshi, Oda Jun

机构信息

Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Department of Emergency and Critical Care Medicine, Hachinohe City Hospital, Aomori, Japan.

出版信息

J Intensive Care. 2025 Mar 11;13(1):14. doi: 10.1186/s40560-024-00769-5.

Abstract

BACKGROUND

Shift work is common in healthcare, especially in emergency and intensive care, to maintain the quality of patient care. Night shifts are linked to health risks such as cardiovascular disease, metabolic disorders, and poor mental health. It has been suggested that inflammatory responses due to the disruption of circadian rhythm may contribute to health risks, but the detailed mechanisms remain unclear. This study aimed to analyze changes in gene expression in whole blood of healthcare workers before and after a night shift and investigate the molecular pathogenesis of these changes and their impact on health.

METHODS

This was a single-center, prospective, observational study of four medical doctors working night shifts in the emergency department. Blood samples from the subjects were collected before and after the night shift, and RNA sequencing was performed to analyze changes in gene expression in whole blood. The data obtained were analyzed via Ingenuity Pathway Analysis (IPA) core analysis that included canonical pathway analysis, upstream regulator analysis, and functional network analysis. RNA bulk deconvolution was performed to estimate the relative abundance of immune cells. The IPA analysis match feature was also used to assess similarities of gene expression patterns with other diseases.

RESULTS

We identified 302 upregulated and 78 downregulated genes (p < 0.05, |log2-fold change|> 0.5) as genes whose expression changed after the night shift. Canonical pathway analysis revealed that Toll-like receptors and other innate immune response pathways were activated. Upstream regulator analysis and functional network analysis also consistently indicated a predicted activation of innate immune and inflammatory responses. RNA bulk deconvolution showed changes in the proportions of several immune cells. IPA analysis match indicated that gene expression patterns after night shifts were highly correlated with several diseases, including major depressive disorder, in terms of immune and inflammatory responses.

CONCLUSION

The results revealed that innate immune and inflammatory responses are elicited after night shifts in healthcare workers and that gene expression patterns correlate with several diseases in terms of immune and inflammatory responses. These findings suggest that shift work may affect health risks through innate immune and inflammatory responses.

摘要

背景

轮班工作在医疗保健领域很常见,尤其是在急诊科和重症监护室,以维持患者护理质量。夜班与心血管疾病、代谢紊乱和心理健康不佳等健康风险有关。有人认为,昼夜节律紊乱引起的炎症反应可能导致健康风险,但其详细机制尚不清楚。本研究旨在分析医护人员夜班前后全血中基因表达的变化,探讨这些变化的分子发病机制及其对健康的影响。

方法

这是一项针对急诊科四名值夜班的医生的单中心、前瞻性观察性研究。在夜班前后采集受试者的血样,并进行RNA测序以分析全血中基因表达的变化。通过Ingenuity Pathway Analysis(IPA)核心分析对获得的数据进行分析,该分析包括经典通路分析、上游调节因子分析和功能网络分析。进行RNA整体反卷积以估计免疫细胞的相对丰度。IPA分析匹配特征也用于评估基因表达模式与其他疾病的相似性。

结果

我们确定了302个上调基因和78个下调基因(p < 0.05,|log2倍变化|> 0.5)为夜班后表达发生变化的基因。经典通路分析显示Toll样受体和其他先天免疫反应通路被激活。上游调节因子分析和功能网络分析也一致表明先天免疫和炎症反应的预测激活。RNA整体反卷积显示几种免疫细胞的比例发生变化。IPA分析匹配表明,夜班后的基因表达模式在免疫和炎症反应方面与包括重度抑郁症在内的几种疾病高度相关。

结论

结果显示,医护人员夜班后会引发先天免疫和炎症反应,并且基因表达模式在免疫和炎症反应方面与几种疾病相关。这些发现表明,轮班工作可能通过先天免疫和炎症反应影响健康风险。

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