目的探讨新生儿呼吸窘迫综合征(NRDS)患儿肿瘤坏死因子α诱导蛋白8样因子2(TIPE2)水平变化及其在呼吸机相关肺炎(VAP)中的潜在作用。方法采取前瞻性研究,收集2023年2月至2025年2月成都市双流区妇幼保健院新生儿科符合纳排标准的118例NRD...目的探讨新生儿呼吸窘迫综合征(NRDS)患儿肿瘤坏死因子α诱导蛋白8样因子2(TIPE2)水平变化及其在呼吸机相关肺炎(VAP)中的潜在作用。方法采取前瞻性研究,收集2023年2月至2025年2月成都市双流区妇幼保健院新生儿科符合纳排标准的118例NRDS患儿。局部加权散点图平滑法(LOWESS)分析TIPE2水平变化与细胞免疫水平的关系。多因素Logistic回归分析TIPE2水平与NRDS新生儿VAP的关联以及不同亚组下两者的关系。受试者操作特征(ROC)曲线分析TIPE2水平对NRDS新生儿VAP的预测价值。限制性立方样条法(RCS)分析TIPE2水平与NRDS新生儿VAP的剂量-反应关系。Bootstrap法分析TIPE2水平与细胞免疫水平对NRDS新生儿VAP的中介效应。结果两组患者1 min及5 min Apgar评分、TIPE2、CD3^(+)T细胞、CD4^(+)T细胞、CD8^(+)T细胞、CD4^(+)/CD8^(+)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)差异明显(P<0.001)。TIPE2水平与CD3^(+)T细胞、CD4^(+)T细胞、CD8^(+)T细胞和CD4^(+)/CD8^(+)均存在明显相关性(P<0.001)。随着TIPE2水平逐渐升高,TIPE2水平与NRDS新生儿VAP风险始终存在独立相关性。不同亚组内,TIPE2水平与NRDS新生儿VAP均存在明显关联(P交互<0.05)。TIPE2水平预测NRDS新生儿VAP是否发生具有中等效能,AUC为0.805(95%CI:0.707~0.854)。TIPE2水平与NRDS新生儿VAP发生风险呈非线性关系(P<0.05)。患儿发生VAP的风险随着TIPE2水平、CD3^(+)T细胞、CD4^(+)T细胞和CD4^(+)/CD8^(+)的升高以及CD8^(+)T细胞的下降而明显下降。TIPE2水平在CD3^(+)T细胞、CD4^(+)T细胞、CD8^(+)T细胞、CD4^(+)/CD8^(+)和VAP情况之间发挥中介效应,中介效应值分别为0.247、0.349、0.211、0.250;中介效应与总效应比分别为41.79%、55.05%、37.61%、35.40%。结论TIPE2通过调节NRDS新生儿的免疫功能促进VAP的发生发展;其表达水平降低与VAP风险增加相关,可作为早期预测VAP的生物标志物,为新生儿VAP早期诊断和干预提供依据。展开更多
The multiple roles of the tumor necrosis factor(TNF)-α-inducible protein 8(TNFAIP8),also named TIPE family of proteins have been shown in tumor and inflammation progression and regulation of cellular autophagy and ap...The multiple roles of the tumor necrosis factor(TNF)-α-inducible protein 8(TNFAIP8),also named TIPE family of proteins have been shown in tumor and inflammation progression and regulation of cellular autophagy and apoptosis.In this review,we found that the TIPE family showed highly homologous sequences and conserved functional domains,such as the death effector domain(DED)-like domain but displayed different roles and mechanisms in different biological activities.For example,while TIPE is primarily associated with tumor progression and antitumor drug resistance,TIPE1 suppresses tumor progression in most instances.TIPE2 has multiple roles in tumor progression regulation,and antitumor drug resistance.Moreover,TIPE2 was also involved in inflammatory response regulation,tumor typing,and staging.A few studies reported that TIPE3 was engaged in tumor development by activating the phosphatidylinositol-3-kinase(PI3K)/protein kinase B(AKT)signaling pathway.The structure,function,and mechanism of the TIPE family in cancer and inflammation have been summarized in this review.This might serve as a reference for further research on the TIPE family and shed new light on the crosstalk among antitumor responses,inflammation,and immunology.展开更多
文摘目的探讨新生儿呼吸窘迫综合征(NRDS)患儿肿瘤坏死因子α诱导蛋白8样因子2(TIPE2)水平变化及其在呼吸机相关肺炎(VAP)中的潜在作用。方法采取前瞻性研究,收集2023年2月至2025年2月成都市双流区妇幼保健院新生儿科符合纳排标准的118例NRDS患儿。局部加权散点图平滑法(LOWESS)分析TIPE2水平变化与细胞免疫水平的关系。多因素Logistic回归分析TIPE2水平与NRDS新生儿VAP的关联以及不同亚组下两者的关系。受试者操作特征(ROC)曲线分析TIPE2水平对NRDS新生儿VAP的预测价值。限制性立方样条法(RCS)分析TIPE2水平与NRDS新生儿VAP的剂量-反应关系。Bootstrap法分析TIPE2水平与细胞免疫水平对NRDS新生儿VAP的中介效应。结果两组患者1 min及5 min Apgar评分、TIPE2、CD3^(+)T细胞、CD4^(+)T细胞、CD8^(+)T细胞、CD4^(+)/CD8^(+)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)差异明显(P<0.001)。TIPE2水平与CD3^(+)T细胞、CD4^(+)T细胞、CD8^(+)T细胞和CD4^(+)/CD8^(+)均存在明显相关性(P<0.001)。随着TIPE2水平逐渐升高,TIPE2水平与NRDS新生儿VAP风险始终存在独立相关性。不同亚组内,TIPE2水平与NRDS新生儿VAP均存在明显关联(P交互<0.05)。TIPE2水平预测NRDS新生儿VAP是否发生具有中等效能,AUC为0.805(95%CI:0.707~0.854)。TIPE2水平与NRDS新生儿VAP发生风险呈非线性关系(P<0.05)。患儿发生VAP的风险随着TIPE2水平、CD3^(+)T细胞、CD4^(+)T细胞和CD4^(+)/CD8^(+)的升高以及CD8^(+)T细胞的下降而明显下降。TIPE2水平在CD3^(+)T细胞、CD4^(+)T细胞、CD8^(+)T细胞、CD4^(+)/CD8^(+)和VAP情况之间发挥中介效应,中介效应值分别为0.247、0.349、0.211、0.250;中介效应与总效应比分别为41.79%、55.05%、37.61%、35.40%。结论TIPE2通过调节NRDS新生儿的免疫功能促进VAP的发生发展;其表达水平降低与VAP风险增加相关,可作为早期预测VAP的生物标志物,为新生儿VAP早期诊断和干预提供依据。
基金supported by the Medical Scientific Research Foundation of Guangdong Province of China(No.A2021236)2022 Guangdong Provincial Education Science Planning Project(Higher Education Special Project,No.2022GXJK221)+4 种基金the 2021 Open Project Fund of Guangdong Provincial Key Laboratory of Medicinal Functional Gene Research,the National Key Clinical Specialty Construction Project(Clinical Pharmacy)and High-Level Clinical Key Specialty(Clinical Pharmacy)in Guangdong Province,Science and Technology Program of Guangzhou,China(No.202201010154)the Special Fund for the Cultivation of Scientific and Technological Innovation of College Students in Guangdong Province of China(No.pdjh2022b0270)the College Students’Innovation and Entrepreneurship Training Project of Guangdong Province(Nos.202210573054,202210573041)Special Fund for the Cultivation of National Natural Science Foundation of China in School of Clinical Pharmacy,Guangdong Pharmaceutical University(No.SCP2022-03)Jinghua(Zhejiang Province)Science and Technology Research Program Project(No.2021-4-135).
文摘The multiple roles of the tumor necrosis factor(TNF)-α-inducible protein 8(TNFAIP8),also named TIPE family of proteins have been shown in tumor and inflammation progression and regulation of cellular autophagy and apoptosis.In this review,we found that the TIPE family showed highly homologous sequences and conserved functional domains,such as the death effector domain(DED)-like domain but displayed different roles and mechanisms in different biological activities.For example,while TIPE is primarily associated with tumor progression and antitumor drug resistance,TIPE1 suppresses tumor progression in most instances.TIPE2 has multiple roles in tumor progression regulation,and antitumor drug resistance.Moreover,TIPE2 was also involved in inflammatory response regulation,tumor typing,and staging.A few studies reported that TIPE3 was engaged in tumor development by activating the phosphatidylinositol-3-kinase(PI3K)/protein kinase B(AKT)signaling pathway.The structure,function,and mechanism of the TIPE family in cancer and inflammation have been summarized in this review.This might serve as a reference for further research on the TIPE family and shed new light on the crosstalk among antitumor responses,inflammation,and immunology.
