【摘要】 目的 探讨血清颗粒蛋白前体(PGRN)、白细胞介素(IL)-21、4-羟基壬烯醛(4-HNE)水平与重症肺炎(SP)患儿病情程度、预后的相关性及对患儿预后不良的预测价值。方法 选取2022年1月至2023年1月该院收治的110例SP患儿作为SP组，另随机选取该院同期收治的55例轻症肺炎患儿作为轻症组、55例健康儿童作为对照组。比较3组血清PGRN、IL-21、4-HNE、常规炎症因子[C-反应蛋白(CRP)、IL-6、降钙素原(PCT)]水平。比较SP组不同病情程度[采用小儿危重症评分(PCIS)评估]患儿血清PGRN、IL-21、4-HNE水平。比较SP组治疗后3个月不同预后患儿治疗前后血清PGRN、IL-21、4-HNE、CRP、IL-6、PCT水平及变化值(以△表示对应指标治疗前后变化值的绝对值)。采用Pearson相关分析血清PGRN、IL-21、4-HNE水平与CRP、IL-6、PCT水平、PCIS的相关性。绘制受试者工作特征(ROC)曲线分析△PGRN、△IL-21、△4-HNE、△CRP、△IL-6、△PCT对SP患儿预后不良的预测价值。采用净重新分类指数(NRI)、综合判别改善指数(IDI)评价新预测方案(△PGRN、△IL-21、△4-HNE、△CRP、△IL-6、△PCT联合预测)与常规预测方案(△CRP、△IL-6、△PCT联合预测)对SP患儿预后不良的预测价值。结果 SP组血清PGRN、IL-21、4-HNE、CRP、IL-6、PCT水平均高于轻症组与对照组，且轻症组血清PGRN、IL-21、4-HNE、CRP、IL-6、PCT水平均高于对照组，差异均有统计学意义(P<0.05)。SP组中，极危重患儿3例，危重26例，非危重81例。危重或极危重患儿血清PGRN、IL-21、4-HNE水平均高于非危重患儿，差异均有统计学意义(P<0.05)。Pearson相关分析结果显示，SP组血清PGRN、IL-21、4-HNE水平与血清CRP、IL-6、PCT水平均呈正相关(P<0.05),与PCIS均呈负相关(P<0.05)。SP组中，预后不良25例，预后良好85例；两组治疗后血清PGRN、IL-21、4-HNE、CRP、IL-6、PCT水平均低于同组治疗前，差异均有统计学意义(P<0.05)。预后不良患儿治疗前后血清PGRN、IL-21、4-HNE、CRP、IL-6、PCT水平均高于预后良好患儿，△PGRN、△IL-21、△4-HNE、△CRP、△IL-6、△PCT均小于预后良好患儿，差异均有统计学意义(P<0.05)。ROC曲线分析结果显示，△PGRN、△IL-21、△4-HNE、△CRP、△IL-6、△PCT预测SP患儿预后不良的曲线下面积(AUC)分别为0.786、0.754、0.764、0.794、0.777、0.754,各指标单独预测SP患儿预后不良的AUC比较，差异均无统计学意义(P>0.05)。新预测方案预测预后不良的AUC为0.956(95%CI:0.899～0.986),预测灵敏度、特异度分别为92.00%、90.59%;常规预测方案预测预后不良的AUC为0.849(95%CI:0.768～0.910),预测灵敏度、特异度分别为88.00%、78.82%;与常规预测方案比较，新预测方案的AUC明显增大(Z=2.302,P<0.05),且新预测方案与常规预测方案比较，NRI为0.029(95%CI:0.021～0.039,P<0.05)、IDI为0.047(95%CI:0.035～0.064,P<0.05)。结论 SP患儿血清PGRN、IL-21、4-HNE水平与CRP、IL-6、PCT、病情程度均呈正相关，且治疗期间监测血清PGRN、IL-21、4-HNE水平变化对预测SP患儿预后不良具有良好应用价值。更多还原

【Abstract】 Objective To investigate the correlation of serum levels of Granuloprotein precursor(PGRN),IL-21 and 4-hydroxynonenal(4-HNE) with the severity and prognosis of children with severe pneumonia(SP),and the predictive value of poor prognosis.Methods A total of 110 children with SP admitted to the hospital from January 2022 to January 2023 were selected as the SP group.In addition, 55 children with mild pneumonia admitted to the hospital during the same period were randomly selected as the mild group and 55 healthy children as the control group.The serum levels of PGRN,IL-21,4-HNE,and conventional inflammatory factors [C-reactive protein(CRP),IL-6,procalcitonin(PCT)] were compared among the three groups.The serum levels of PGRN,IL-21,and 4-HNE in children with different severity of illness [Pediatric Critical illness score(PCIS) was used for evaluation] in SP group were compared.The serum levels and changes of PGRN,IL-21,4-HNE,CRP,IL-6,and PCT before and after treatment(the absolute value of the changes of the corresponding indexes before and after treatment was expressed as △) in children with different prognosis 3 months after treatment in the SP group were compared.Pearson correlation analysis was used to analyze the correlation between serum PGRN,IL-21,4-HNE levels and CRP,IL-6,PCT levels, PCIS.The receiver operating characteristic(ROC) curve was drawn to analyze the predictive value of △PGRN,△IL-21,△4-HNE,△CRP,△IL-6,and △PCTSP for poor prognosis in children with SP.The net reclassification index(NRI) and comprehensive discrimination improvement index(IDI) were used to evaluate the predictive value of the new prediction scheme(△PGRN,△IL-21,△4-HNE,△CRP,△IL-6,△PCT combined prediction) and the conventional prediction scheme(△CRP,△IL-6,△PCT combined prediction) for poor prognosis of children with SP.Results The SP group had significantly higher serum levels of PGRN,IL-21,4-HNE,CRP,IL-6 and PCT than the mild group and the control group(P<0.05),and the mild group had significantly higher serum levels of PGRN,IL-21,4-HNE,CRP,IL-6 and PCT than the control group(P<0.05).In the SP group, 3 cases were extremely critical, 26 cases were critical, and 81 cases were non-critical.The serum levels of PGRN,IL-21 and 4-HNE in critical or extremely critical children were significantly higher than those in non-critical children(P<0.05).Pearson correlation analysis showed that the serum levels of PGRN,IL-21 and 4-HNE in the SP group were positively correlated with the serum levels of CRP,IL-6 and PCT(P<0.05),and negatively correlated with PCIS(P<0.05).In the SP group, 25 cases had poor prognosis and 85 cases had good prognosis.The levels of serum PGRN,IL-21,4-HNE,CRP,IL-6 and PCT in the two groups after treatment were lower than those before treatment, and the differences were statistically significant(P<0.05).The serum levels of PGRN,IL-21,4-HNE,CRP,IL-6 and PCT in children with poor prognosis were higher than those in children with good prognosis before and after treatment, and the serum levels of △PGRN,△IL-21,△4-HNE,△CRP,△IL-6 and △PCT in children with poor prognosis were lower than those in children with good prognosis, and the differences were statistically significant(P<0.05).ROC curve analysis showed that the area under the curve(AUC) of △PGRN,△IL-21,△4-HNE,△CRP,△IL-6 and △PCT for predicting poor prognosis in children with SP were 0.786,0.754,0.764,0.794,0.777 and 0.754 respectively.There was no significant difference in AUC predicted by each index alone(P>0.05).The AUC of the new prediction scheme for poor prognosis of SP was 0.956(95%CI:0.899-0.986),and the predictive sensitivity and specificity were 92.00% and 90.59% respectively.The AUC of the conventional prediction scheme for poor prognosis was 0.849(95%CI:0.768-0.910),and the predictive sensitivity and specificity were 88.00% and 78.82%,respectively.Compared with the conventional prediction scheme, the AUC of the new prediction scheme was significantly increased(Z=2.302,P<0.05).Compared with the conventional prediction scheme, the NRI of the new prediction scheme was 0.029(95%CI:0.021-0.039,P<0.05),and the IDI was 0.047(95%CI:0.035-0.064,P<0.05).Conclusion The serum levels of PGRN,IL-21 and 4-HNE in SP children are positively correlated with CRP,IL-6,PCT and disease severity, and monitoring the changes of serum levels of PGRN,IL-21 and 4-HNE during treatment has good application value in predicting the poor prognosis of SP children.更多还原