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尿液外泌体mRNAs评分指导坏死性小肠结肠炎患儿手术时机相关研究
Value of urinary exosome mRNA score in guiding surgical timing in children with necrotizing enterocolitis
- 重庆医科大学学报 2026年51卷第3期 页码：431-438
- 作者机构：
江西省妇幼保健院/江西省儿童医学中心，南昌 330000
- 作者简介：
吴 岳，Email：wu00yue@163.com，研究方向：小儿外科。
陶俊峰，Email：304733369@qq.com。
- 基金信息：
DOI：10.13406/j.cnki.cyxb.003845
中图分类号： R722.1收稿：2024-10-22，
修回：2025-03-03，
录用：2025-03-05，
纸质出版：2026-03-28
- 稿件说明：
移动端阅览
吴岳,陶俊峰,刘钟等.尿液外泌体mRNAs评分指导坏死性小肠结肠炎患儿手术时机相关研究[J].重庆医科大学学报,2026,51(03):431-438.
Wu Yue,Tao Junfeng,Liu Zhong,et al.Value of urinary exosome mRNA score in guiding surgical timing in children with necrotizing enterocolitis[J].Journal of Chongqing Medical University,2026,51(03):431-438.
吴岳,陶俊峰,刘钟等.尿液外泌体mRNAs评分指导坏死性小肠结肠炎患儿手术时机相关研究[J].重庆医科大学学报,2026,51(03):431-438. DOI： 10.13406/j.cnki.cyxb.003845.
Wu Yue,Tao Junfeng,Liu Zhong,et al.Value of urinary exosome mRNA score in guiding surgical timing in children with necrotizing enterocolitis[J].Journal of Chongqing Medical University,2026,51(03):431-438. DOI： 10.13406/j.cnki.cyxb.003845.
摘要
目的
2
探索坏死性小肠结肠炎（necrotizing enterocolitis，NEC）患儿尿液外泌体（exosomes，Exo）mRNAs表达特征。构建mRNAs评分用于指导NEC患儿手术时机。
方法
2
选取本院2021年1月至2024年3月收治的196例NEC患儿作为研究对象。根据是否进行手术干预分为手术组和非手术组。对4例手术组患儿和4例非手术组患儿尿液Exo-mRNAs进行微阵列数据分析。使用Metascape在线数据库进行京都基因和基因组（kyoto encyclopedia of genes and genomes，KEGG）信号通路分析。通过拓扑特征分析筛选核心基因并在临床队列中利用酶联免疫吸附法验证核心基因表达特征。通过logistic回归分析构建尿液Exo-mRNAs评分。通过受试者工作特征（receiver operating characteristic，ROC）曲线分析和比较风险变量曲线下面积（area under the curve，AUC）。
结果
2
196例患儿中，需要手术干预患儿48例（32.4 %）。手术组和非手术组患儿尿液Exo-mRNAs微阵列数据分析识别出565个差异表达基因，其中441个基因表达上调，124个基因表达下调。KEGG信号通路主要富集在细胞色素P450、胆汁分泌和脂肪消化吸收等信号通路中。2次拓扑特征分析发现11个核心基因：前列腺素内过氧化物合酶2（prostaglandin-endoperoxide Synthase 2，PTGS2）、白细胞介素-1β（interleukin-1 beta，IL-1β）、白细胞介素-6（interleukin-6，IL-6）、基质金属蛋白酶9（matrix metalloproteinase-9，MMP9）、细胞色素P450 3A4（cytochrome P450 family 3 subfamily A member 4，CYP3A4）、Toll样受体2（toll-like receptor 2，TLR2）、钙黏蛋白1（cadherin 1，CDH1）、细胞色素P450 2C9（cytochrome P450 family 2 subfamily C member 9，CYP2C9）、细胞色素P450 2C19（cytochrome P450 family 2 subfamily C member 19，CYP2C19）、CXC基序趋化因子配体8（C-X-C motif chemokine ligand 8，CXCL8）和载脂蛋白C-3（apolipoprotein C-Ⅲ，APOC3）。手术组患儿尿液Exo中PTGS2、IL-1β、MMP9和TLR2表达量增加，CYP3A4、CDH1和CYP2C9表达量降低（
P<
0.05）。Exo-mRNAs评分公式为0.704×PTGS2
表达量
+0.426×IL-1β
表达量
+0.198×TLR2
表达量
-1.166×CYP3A4
表达量
。多因素logistic回归分析显示，Exo-mRNAs评分、胎龄和肠脂肪酸结合蛋白（I-FABP）是NEC患儿手术干预风险独立影响变量（
P
<
0.05）。ROC曲线分析结果显示，Exo-mRNAs评分预测手术干预风险的AUC为0.888（0.836-0.929），均高于单独Exo-mRNA、胎龄和I-FABP的AUC。
结论
2
尿液Exo-mRNAs评分可作为指导NEC患儿手术时机的非侵入性标志物，为NEC患儿积极早期干预和治疗提供理论依据。
Abstract
Objective
2
To investigate the expression characteristics of urinary exosome（Exo） mRNAs in children with necrotizing enterocolitis（NEC），and to construct an mRNA score for guiding surgical timing in children with NEC.
Methods
2
A total of 196 children with NEC who were admitted to our hospital from January 2021 to March 2024 were enrolled as subjects，and according to whether surgical intervention was performed，they were divided into surgical group and non-surgical group. A microarray data analysis was performed for the urinary Exo-mRNAs of four children in the surgical group and four in the non-surgical group. Metascape online database was used to perform the Kyoto Encyclopedia of Genes and Genomes（KEGG） signaling pathway analysis. Topological characterization was performed to identify core genes，and ELISA was used to validate the expression profiles of core genes. A logistic regression analysis was used to construct the urinary Exo-mRNAs score. The receiver operating characteristic（ROC） curve was used to analyze and compare the area under the ROC curve（AUC） of risk variables.
Results
2
Among the 196 children，48（32.4%） required surgical intervention. The microarray data analysis of urinary Exo-mRNAs identified 565 differentially expressed genes between the surgical group and the non-surgical group，among which there were 441 upregulated genes and 124 downregulated genes. The KEGG signaling pathways were mainly enriched in the signaling pathways such as cytochrome P450，bile secretion，and fat digestion and absorption. Two sessions of topological characterization identified 11 core genes，i.e.，prostaglandin-endoperoxide synthase 2（PTGS2），interleukin-1β（IL-1β），interleukin-6，matrix metallopeptidase 9（MMP9），cytochrome p450 3A4（CYP3A4），toll-like receptor 2（TLR2），cadherin-1（CDH1），cytochrome p450 2C9（CYP2C9），cytochrome p450 2C19，C-X-C motif chemokine ligand 8，and apolipoprotein C-3. For the children in the surgical group，there were significant increases in the expression levels of PTGS2，IL-1β，MMP9，and TLR2 and significant reductions in the expression levels of CYP3A4，CDH1，and CYP2C9 in urinary Exo（
P
<
0.05）. The formula for Exo-mRNAs scoring was 0.704×PTGS2
expression
+ 0.426×IL-1β
expression
+ 0.198×TLR2
expression
- 1.166×CYP3A4
expression
. The multivariate logistic regression analysis showed that Exo-mRNAs score，gestational age，and intestinal fatty acid-binding protein（I-FABP） were independent influencing variables for the risk of surgical intervention in children with NEC（
P
<
0.05）. The ROC curve analysis showed that Exo-mRNAs score had an AUC of 0.888（0.836-0.
929） in predicting the risk of surgical intervention，with a significantly higher AUC than Exo-mRNA，gestational age，and I-FABP alone.
Conclusion
2
Urinary Exo-mRNAs score can be used as a noninvasive marker for guiding surgical timing in children with NEC，which provides a theoretical basis for the early intervention and treatment of children with NEC.
关键词
Keywords
references
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