The Dynamic Change And Clinical Ignificance Of Plasma Mitochondrial DNA In Children With Sepsis

Background Sepsis is defined as life-threatening organ dysfunction caused by the disorder of the body's response to infection.If the treatment time is missed,sepsis with high morbidity,high mortality and high cost of treatment features can evolve into septic shock,multiple organ dysfunction(MODS).Therefore,early identification of sepsis,clinical diagnosis,disease assessment and effective treatment play an important role in reducing sepsis mortality.However,the current clinical commonly used in the diagnosis and evaluation of sepsis disease biomarkers such as proccalcitonin(PCT),C-reactive protein(CRP),tumor necrosis factor-?(Tumor necrosis factor-?,TNF-?),interleukin-6(IL-6)are insufficient in clinical sepsis early diagnosis,risk stratification and prognosis.It is helpful for the early identification,diagnosis and treatment of children with sepsis to make use of continuous,dynamic and combined biomarker detection methods and integration of its clinical features.Plasma free DNA is a detectable DNA fragment in the extracellular fluid which contains mitochondrial DNA(MtochondrialDNA,mtDNA)and nuclear DNA(n DNA).During sepsis,mt DNA and nDNA are released from the apoptotic and necrotic tissue into the circulation,whose increase in concentration may be caused by the increase of cell release or decreased clearance.Thus,mtDNA finds its favour in doctot's eyes due to the length of short,simple structure,high copy number.At present,numbers of studies have shown that plasma mtDNA concentration increased significantly in patients with sepsis,which is valueable for assessing the severity of sepsis and prognosis,has a high specificity and sensitivity in predicting sepsis mortality.In a word,plasma mtDNA is superior to conventional sepsis detection indicators.However pediatric sepsis is rarely studied.Objective: In this study,prospective research methods was used to observe the dynamic changes of plasma mt DNA in children with sepsis and to explore the clinical value of plasma mt DNA to evaluate the condition of children with sepsisMethods: A total of 37 children with sepsis were enrolled in the Children's Hospital of Hunan Province from June to January 2017,and 27 healthy children with the same age and sex were randomly selected as the experimental control group.All children were draw peripheral venous blood on the 1st,3rd and 7th day of hospitalization.Real-time quantitative PCR was used to detect plasma mt DNA levels on the 1st,3rd and 7th day after hospitalization.The detection of CRP,PCT and otherlaboratory indicators were detected simultaneously.Results:(1)Compared with the normal group,the content of mt DNA in the sepsis group was(3384.4,1368.5-6857.5)pg/ml,which was higher than that in the normal control group(1904.8,1267.9-2395.5),(Z=-2.603,P=0.00).The difference was statistically significant.(2)Plasma mt DNA and disease severity(1)The level of plasma mtDNA in sepsis multiple organ disorder group was higher than that in single organ disorder group and the former's plasma mtDNA levels increased significantly in the first 1,3days.The mtDNA difference was statistically significant at day1(P<0.001),day 3(P<0.001)and day 7(P<0.025).In addition,the plasma mtDNA level of the two groups decreased gradually with the prolongation of time.(2)The level of plasma mtDNA in septic shock group was significantly higher than that in non-shock group,and the former plasma mtDNA levels increased obviously in the first 1,3 days,The mtDNA difference was statistically significant at day 1(P<0.000),day 3(P<0.000)and day 7(P<0.003).What's more,the plasma mtDNA level of the two groups decreased gradually with the prolongation of time.(3)Plasma mt DNA and prognosisThe level of plasma mtDNA in sepsis non-surviving group wassignificantly higher than that in survivors group.The mt DNA difference was statistically significant at day 1(P<0.016)and day 3(P<0.002).But there was no significant difference in mt DNA at day 7(P> 0.05).Besides,the plasma mtDNA level of the two groups decreased gradually with the prolongation of time.(4)ROC curve analysis(1)The diagnosis efficacy of mt DNA and PCT,CRP in predicting sepsis MODSThe mt DNA,PCT and CRP in predicting receiver operating characteristic curve(ROC)of sepsis MODS was analyzed: The ROC curves of plasma mtDNA,CRP and PCT were plotted on the basis of traditional MODS diagnosis.The area under the curve was0.848,0.614,0.775.The difference of plasma mt DNA,PCT in predicting MODS was statistically significant(P<0.005),however CRP was not statistically significant(P>0.05).The optimal cutoff values were2176.2pg/ml,7.24ng/mL respectively.The sensitivity and specificity of mtDNA were 89%,72%,the CRP were 58%,67%,the PCT were 84%,61%.(2)The diagnosis efficacy of mtDNA at different time points in predicting sepsis MODSOn the first day of admission,the area under the plasma mtDNA curve was the largest(P<0.05),suggesting that the accuracy was relativelyhigh.However,the accuracy was relatively low on days 3 and 7.Conclusion:(1)The increase of plasma mtDNA level in children with sepsis was associated with organ dysfunction,indicated that it could be used as one of the biomarkers for the diagnosis of sepsis MODS in children.(2)The level of plasma mtDNA in children with sepsis was significantly higher than that on the first and third day after admission,which was positively correlated with the severity of seizures and had certain value in judging and assessing the severity of sepsis.