Neurotrophin-3、LncRNA H19与小儿癫痫持续状态严重程度的关系及对预后预测效能研究

A study of the relationship between Neurotrophin-3,LncRNA H19 and the severity of persistent status epilepticus in pediatric patients and its predictive efficacy for prognosis

目的探讨神经营养因子-3(Neurotrophin-3)、长链非编码核糖核酸H19(LncRNA H19)与小儿癫痫持续状态(SE)严重程度的关系及对预后预测效能。方法选取2020年1月—2023年12月山西医科大学附属运城市中心医院儿内科收治的SE患儿152例为SE组,根据儿童癫痫持续状态严重程度评分(STEPSS)分为轻度亚组67例、中度亚组52例、重度亚组33例;根据院内结局分为良好预后亚组91例和不良预后亚组61例。另选取同期医院健康体检儿童60例为健康对照组。采用酶联免疫吸附法检测血清Neurotrophin-3,实时荧光定量聚合酶链反应检测LncRNA H19水平;Spearman法分析血清Neurotrophin-3、LncRNA H19水平与SE患儿STEPSS评分的相关性;多因素Logistic回归分析SE患儿不良预后的影响因素;受试者工作特征(ROC)曲线分析血清Neurotrophin-3、LncRNA H19水平对小儿SE不良预后的预测价值。结果SE组血清Neurotrophin-3水平低于健康对照组,LncRNA H19水平高于健康对照组(t/P=11.877/<0.001、20.966/<0.001);随着病情加重,轻度亚组、中度亚组、重度亚组血清Neurotrophin-3水平依次降低,LncRNA H19水平依次升高(F/P=184.107/<0.001、114.394/<0.001);152例SE患儿不良预后发生率为41.13%(61/152)。不良预后亚组STEPSS评分、SE发作时间≥1 h、全面性发作、气管插管比例、血清LncRNA H19水平高于良好预后亚组,血清Neurotrophin-3水平低于良好预后亚组(χ^(2)/t/P=8.090/<0.001、11.931/0.001、11.566/0.001、8.752/0.003、6.467/<0.001、7.846/<0.001);SE患儿STEPSS评分与血清Neurotrophin-3水平呈负相关,与LncRNA H19水平呈正相关(rs/P=-0.764/<0.001,0.748/<0.001);多因素Logistic回归分析显示,SE发作时间≥1 h、STEPSS评分升高、全面性发作、LncRNA H19升高为小儿SE不良预后的独立危险因素[OR(95%CI)=3.216(1.406~7.354)、2.001(1.366~2.931)、3.970(1.229~11.691)、1.592(1.245~2.034)],Neurotrophin-3升高为独立保护因素[OR(95%CI)=0.943(0.919~0.967)];血清Neurotrophin-3、LncRNA H19水平及二者联合预测SE患儿不良预后的AUC分别为0.808、0.780、0.891,二者联合的AUC大于单独预测(Z/P=3.194/0.001、3.521/<0.001)。结论血清Neurotrophin-3水平降低和LncRNA H19水平升高与SE患儿病情加重和不良预后有关,血清Neurotrophin-3、LncRNA H19水平联合对SE患儿不良预后有较高的预测效能。

Objective To investigate the relationship between Neurotrophin-3,long non-coding ribonucleic acid H19(LncRNA H19)and the severity of pediatric status epilepticus(SE)and the efficacy in predicting prognosis.Methods One hundred and fifty-two children with SE admitted to the Department of Pediatrics of Yuncheng Central Hospital of Shanxi Medical University from January 2020 to December 2023 were selected as the SE group,and the children with SE were classified into 67 cases in the mild subgroup,52 cases in the moderate subgroup,and 33 cases in the severe subgroup according to the status epilepticus in pediatric severity score(STEPSS);according to the in-hospital outcome,children with SE were divided into good prognosis subgroup of 91 cases and poor prognosis subgroup of 61 cases.Another 60 children were selected for health check-ups in hospitals during the same period as healthy control group.The enzyme-linked immunosorbent assay and real-time fluorescence quantitative polymerase chain reaction were used to detect serum Neurotrophin-3 and LncRNA H19 levels;Spearman's method was used to analyze the correlation between serum Neurotrophin-3,LncRNA H19 levels and the STEPSS scores of the children with SE;multifactorial logistic regression analysis was used to analyze the factors influencing poor prognosis in children with SE;the predictive value of serum Neurotrophin-3 and LncRNA H19 levels on poor prognosis of pediatric SE was analyzed using receiver operating characteristic(ROC)curves.Results Serum Neurotrophin-3 levels were lower and LncRNA H19 levels were higher in the SE group than in the healthy control group(t/P=11.877/<0.001,20.966/<0.001);as the disease aggravated,the serum Neurotrophin-3 levels in the mild subgroup,the moderate subgroup,and the severe subgroup decreased in the order of.LncRNA H19 levels increased sequentially(F/P=184.107/<0.001,114.394/<0.001);the incidence of poor prognosis in 152 children with SE was 41.13%(61/152).STEPSS score,SE episode duration≥1h,full-blown seizures,proportion of tracheal intubation,and serum LncRNA H19 levels were higher in the poor prognosis subgroup than in the good prognosis subgroup,and serum Neurotrophin-3 levels were lower than in the good prognosis subgroup(χ^(2)/t/P=8.090/<0.001,11.931/0.001,11.566/0.001,8.752/0.003,6.467/<0.001,7.846/<0.001);STEPSS score in children with SE was negatively correlated with serum Neurotrophin-3 levels and positively correlated with LncRNA H19 levels(r s/P=-0.764/<0.001,0.748/<0.001);multifactorial logistic regression analysis showed that SE episodes lasted for≥1 h,high STEPSS score,full-blown seizures,and high LncRNA H19 were independent risk factors for poor prognosis of pediatric SE[OR(95%CI)=3.216(1.406-7.354),2.001(1.366-2.931),3.970(1.229-11.691),and 1.592(1.245-2.034)],and high Neurotrophin-3 was an independent protective factor[OR(95%CI)=0.943(0.919-0.967)];the AUCs of serum Neurotrophin-3,LncRNA H19 levels and the combination of the two for predicting poor prognosis in children with SE were 0.808,0.780,and 0.891,respectively,and the AUCs of the combination of the two were greater than those predicted by serum Neurotrophin-3 and LncRNA H19 levels alone(Z/P=3.194/0.001,3.521/<0.001).Conclusion Decreased serum Neurotrophin-3 levels and increased LncRNA H19 levels were associated with exacerbation and poor prognosis in children with SE,and the combination of serum Neurotrophin-3 and LncRNA H19 levels had a high predictive efficacy for poor prognosis in children with SE.