CC:L-GILZ 转录变体 1的高表达与脓毒症患者30天内死亡率的增加有关，且高表达比例可能表明氢化可的松治疗的禁忌

Abstract

Background: Sepsis presents a challenge due to its complex immune responses, where balance between inflammation and anti-inflammation is critical for survival. Glucocorticoid-induced leucine zipper (GILZ) is key protein in achieving this balance, suppressing inflammation and mediating glucocorticoid response. This study aims to investigate GILZ transcript variants in sepsis patients and explore their potential for patient stratification and optimizing glucocorticoid therapy.脓毒症因其复杂的免疫反应而构成挑战，关键在于生存所需的炎症与抗炎之间的平衡。糖皮质激素诱导的亮氨酸拉链蛋白（GILZ）是实现这种平衡的关键，它能够抑制炎症并介导糖皮质激素的反应。本研究旨在调查脓毒症患者中的GILZ转录变体，并探索它们在患者分层和优化糖皮质激素治疗方面的潜力。

Methods: Sepsis patients meeting the criteria outlined in Sepsis-3 were enrolled, and RNA was isolated from whole blood samples. Quantitative mRNA expression of GILZ transcript variants in both sepsis patient samples (n = 121) and the monocytic U937 cell line (n = 3), treated with hydrocortisone and lipopolysaccharides, was assessed using quantitative PCR (qPCR).我们纳入了符合Sepsis-3标准的患者，并从他们的全血样本中分离出RNA。使用定量PCR（qPCR）技术，评估了脓毒症患者样本（n = 121）以及用氢化可的松和脂多糖处理的单核细胞U937细胞系（n = 3）中GILZ转录变体的mRNA表达量。

Results: Elevated expression of GILZ transcript variant 1 (GILZ TV 1) serves as a marker for heightened 30-day mortality in septic patients. Increased levels of GILZ TV 1 within the initial day of sepsis onset are associated with a 2.2-[95% CI 1.2-4.3] fold rise in mortality, escalating to an 8.5-[95% CI 2.0-36.4] fold increase by day eight. GILZ TV1 expression is enhanced by glucocorticoids in cell culture but remains unaffected by inflammatory stimuli such as LPS. In septic patients, GILZ TV 1 expression increases over the course of sepsis and in response to hydrocortisone treatment. Furthermore, a high expression ratio of transcript variant 1 relative to all GILZ mRNA TVs correlates with a 2.3-fold higher mortality rate in patients receiving hydrocortisone treatment.GILZ转录变体1（GILZ TV 1）的高表达是脓毒症患者30天内死亡率增加的标志。脓毒症发作初期GILZ TV 1的水平增加与死亡率上升2.2倍（95% CI 1.2-4.3）有关，并在第八天增加至8.5倍（95% CI 2.0-36.4）。GILZ TV1的表达在细胞培养中可被糖皮质激素增强，但不受如LPS等炎症刺激的影响。在脓毒症患者中，GILZ TV 1的表达随着病程进展和对氢化可的松治疗的反应而增加。此外，与所有GILZ mRNA转录变体相比，转录变体1的高表达比例与接受氢化可的松治疗的患者有2.3倍的更高死亡率相关。

Conclusion: High expression of GILZ TV 1 is associated with a higher 30-day sepsis mortality rate. Moreover, a high expression ratio of GILZ TV 1 relative to all GILZ transcript variants is a parameter for identifying patient subgroups in which hydrocortisone may be contraindicated.GILZ TV 1的高表达与较高的30天脓毒症死亡率相关联。此外，GILZ TV 1相对于所有GILZ转录变体的高表达比例是识别可能不适宜使用氢化可的松治疗的患者亚群的参数。