血浆线粒体DNA水平与脓毒症患儿病情严重程度及预后的相关性

Correlation between Plasma Mitochondrial DNA Level and Disease Severity and Prognosis in Children with Sepsis

目的:分析血浆线粒体DNA(mt-DNA)水平与脓毒症患儿病情严重程度及预后的相关性,寻找有价值的生物标志物。方法:选择我院2021年1月至2022年3月儿童重症监护室(ICU)脓毒症患儿103例作为研究对象,根据严重程度分为脓毒症组57例,重度脓毒症组46例;同期性别、年龄匹配的ICU感染患儿50例设为感染组,同期性别、年龄匹配的健康儿童作为对照组,比较各组血浆mt-DNA、降钙素原(PCT)、C反应蛋白(CRP)、乳酸(Lac)水平。比较脓毒症组57例,重度脓毒症组患儿危重症评分(PCIS)、第2代小儿器官功能障碍评分(PELOD-2)、第三代小儿死亡风险评分(PRISMⅢ),并分析血浆mt-DNA与PCT、CRP、Lac水平及PCIS等评分的相关性。根据患儿入院后28d转归情况,分为存活组和死亡组,比较两组血浆mt-DNA、PCT、CRP、Lac水平,建立ROC曲线,分析血浆mt-DNA、PCT、CRP、Lac对脓毒症患儿预后的预测价值。结果:各组mt-DNA、PCT、CRP、Lac水平比较差异均有统计学意义(P<0.05)。组间mt-DNA水平两两比较:重度脓毒症组高于脓毒症组、感染组、对照组;脓毒症组高于感染组、对照组;感染组高于对照组,差异均有统计学意义(P<0.05)。组间PCT、CRP、Lac水平两两比较:重度脓毒症组高于脓毒症组、感染组、对照组;脓毒症组、感染组高于对照组,脓毒症组Lac水平高于感染组,差异均有统计学意义(P<0.05)。脓毒症组与感染组PCT、CRP水平比较差异无统计学意义(P>0.05)。重度脓毒症组患儿PCIS评分低于脓毒症组,PELOD-2、PRISMIII评分高于脓毒症组,差异均有统计学意义(P<0.05)。血浆mt-DNA与PCT、CRP、Lac及PELOD-2、PRISMⅢ评分呈正相关(r=0.877、0.904、0.875、0.923、0.870,P均=0.000)。血浆mt-DNA与PCIS评分呈负相关(r=-0.841,P=0.000)。死亡组患儿血浆mt-DNA、PCT、CRP、Lac水平均高于存活组,差异均有统计学意义(P<0.05)。建立ROC曲线,血浆mt-DNA、PCT、CRP、Lac水平的Cut-off为1124.28pg/mL、18.49ng/mL、27.38mg/L、3.04mmoL/L时,Youden最高,AUC分别为0.817、0.716、0.607、0.759。血浆mt-DNA预测脓毒症预后的敏感度为80.95%,明显高于PCT、CRP、Lac的71.43%、66.67%、76.19%;血浆mt-DNA预测脓毒症预后的特异度为93.90%,明显高于PCT、CRP、Lac的81.71%、75.61%、74.39%,差异均有统计学意义(P<0.05)。结论:mt-DNA在不同严重程度及不同预后的脓毒症患儿中存在显著差异,检测血浆mt-DNA有助于脓毒症患儿病情严重程度及预后的评估,可作为脓毒症患儿早期诊断的生物标志物。

Objective:To analyze the correlation between plasma mitochondrial DNA(mt-DNA)levels and the severity and prognosis of children with sepsis,and to find valuable biomarkers.Methods:A total of 103 children with sepsis in the pediatric intensive care unit(ICU)of our hospital from January 2021 to March 2022 were selected as the research subjects.According to the severity,they were divided into the sepsis group with 57 cases and the severe sepsis group with 46 cases.50 cases of ICU infected children matched by gender and age during the same period were set as the infection group,and healthy children matched by gender and age during the same period were used as the control group.Plasma mt-DNA,calcitoninogen(PCT),C-reactive protein(CRP)and lactate(Lac)levels were compared between the groups.The critical illness score(PCIS),the 2nd generation Paediatric Organ Dysfunction Score(PELOD-2)and the 3rd generation Paediatric Risk of Mortality Score(PRISM III)of 57 cases in the sepsis group were compared,and the correlation between plasma mt-DNA and PCT,CRP,Lac levels and PCIS scores was analysed.According to the outcome 28 days after admission,the children were divided into a survival group and a death group.The plasma mt-DNA,PCT,CRP and Lac levels were compared between the two groups,and ROC curves were established to analyse the predictive value of plasma mt-DNA,PCT,CRP and Lac on the prognosis of children with sepsis.Results:There were significant differences in the levels of mt-DNA,PCT,CRP and Lac among the groups(P<0.05).Pairwise comparison of mt-DNA levels between groups:the severe sepsis group was higher than the sepsis group,the infection group and the control group;the sepsis group was higher than the infection group and the control group;the infection group was higher than the control group,the differences were all Statistical significance(P<0.05).Pairwise comparison of PCT,CRP and Lac levels between groups:the severe sepsis group was higher than the sepsis group,the infection group and the control group;the sepsis group and the infection group were higher than the control group,and the Lac level in the sepsis group was higher than In the infection group,the difference was statistically significant(P<0.05).There was no significant difference in the levels of PCT and CRP between the sepsis group and the infection group(P>0.05).The PCIS score in the severe sepsis group was lower than that in the sepsis group,the PELOD-2 and PRISMIII scores were higher than those in the sepsis group,and the differences were statistically significant(P<0.05).Plasma mt-DNA was positively correlated with PCT,CRP,Lac,PELOD-2 and PRISMⅢscores(r=0.877,0.904,0.875,0.923,0.870,all P=0.000).Plasma mt-DNA was negatively correlated with PCIS score(r=-0.841,P=0.000).The plasma levels of mt-DNA,PCT,CRP and Lac in the death group were higher than those in the survival group,and the differences were statistically significant(P<0.05).The ROC curve was established.When the cut-off of plasma mt-DNA,PCT,CRP,and Lac levels were 1124.28 pg/mL,18.49ng/mL,27.38mg/L,and 3.04 mmoL/L,Youden was the highest,with AUCs of 0.817 and 0.716,,0.607,0.759 respectively.The sensitivity of plasma mt-DNA in predicting the prognosis of sepsis was 80.95%,which was significantly higher than 71.43%,66.67%and 76.19%of PCT,CRP and Lac;the specificity of plasma mt-DNA in predicting the prognosis of sepsis was 93.90%.It was significantly higher than 81.71%,75.61%and 74.39%of PCT,CRP and Lac,and the differences were statistically significant(P<0.05).Conclusion:There are significant differences in mt-DNA in children with sepsis of different severity and prognosis.Plasma mt-DNA can be used as a biomarker for the early diagnosis of sepsis as it can help to assess the severity and prognosis of septic children.