新生儿肺炎患者血清YKL-40，25(OH)D3 和HMGB1 表达水平与感染类型及病情评估的相关性研究

目的 探讨人软骨糖蛋白(human cartilage glycoprotein 39，YKL-40)、25 羟维生素D3[25-hydroxy vitamin D3，25(OH)D3] 和高迁移率族蛋白B1(high mobility group protein B1，HMGB1) 水平在新生儿肺炎(neonatal pneumonia，NP)诊断及病情评估中的应用价值。方法 选取2020 年1 ～ 12 月深圳市龙华区人民医院新生儿科收治的105 例NP 患儿为研究对象，按照感染病原体的不同，分为细菌性肺炎组40 例和非细菌性肺炎组65 例；根据病情严重程度，可分为轻症肺炎组69 例和重症肺炎组36 例，另选取同期85 例健康新生儿为对照组。通过酶联免疫吸附试验法(enzyme-linkedimmunosorbent assay，ELISA) 检测血清YKL-40，25(OH)D3 和HMGB1 水平；ROC 曲线分析YKL-40，25(OH)D3 和HMGB1 单独或联合检测对NP 的诊断价值；Spearman 分析YKL-40，25(OH)D3 和HMGB1 水平与病情程度的相关性。结果 细菌性肺炎组与非细菌性肺炎组血清YKL-40(46.39±8.36 ng/ml，40.28±8.47 ng/ml)和HMGB1(23.38±5.66ng/ml，17.32±4.18 ng/ml)水平均显著高于对照组(30.49±6.35 ng/ml，12.56±3.22 ng/ml)，差异有统计学意义(F=939.480，99.507，均P ＜ 0.05)，血清25(OH)D3(12.76±3.57μg/L，18.33±4.21μg/L)水平显著低于对照组(19.76±4.87μg/L)，差异有统计学意义(F=225.752，P ＜ 0.05)。重症组血清YKL-40(52.56±9.68 ng/ml)和HMGB1(26.74±4.57 ng/ml)水平显著高于轻症组(16.63±5.32 ng/ml，9.63±2.38 ng/ml)和对照组(11.63±3.32 ng/ml，6.34±2.06 ng/ml)，差异均有统计学意义(F=265.331，55.426，均P ＜ 0.05)，而重症组和轻症组血清25(OH)D3(9.76±3.54μg/L ,31.16±5.01μg/L)水平显著低于对照组(35.16±5.88μg/L)，差异有统计学意义(F=55.426，P ＜ 0.05)。Spearman 秩相关性分析结果显示，患儿病情严重程度与血清YKL-40，HMGB1 水平呈正相关(r= 0.727，0.210，均P ＜ 0.05)，而与25(OH)D3 水平呈负相关(r=-0.566，P ＜ 0.05)。ROC 曲线分析结果显示YKL-40，25(OH)D3 和HMGB1 联合检测诊断NP 效能最高，其AUC 为0.912(95%CI:0.864 ～ 0.932)，敏感度和特异度分别为96.34%，85.72%，高于各指标单项检测，差异均有统计学意义(Z=0.746，2.843，3.662，均P ＜ 0.05)；三者联合在新生儿细菌性与非细菌性肺炎的诊断效能最高，其AUC 为0.894(95%CI:0.832 ～ 0.941)，敏感度和特异度分别为97.26%，80.66%，高于各指标单项检测，差异均有统计学意义(Z=1.573，3.228，2.689，均P ＜ 0.05)。结论 血清YKL-40，25(OH)D3 和HMGB1 水平在NP 感染类型诊断和反映患儿病情程度方面有重要的临床应用价值，三者联合检测临床诊断效能更优。

Correlation of Serum YKL-40, 25(OH)D3 and HMGB1 Expression Levels with Infection Types and Disease Assessment in Neonatal Pneumonia

Objective To investigate the serum levels of human cartilage glycoprotein 39 (YKL-40), 25-hydroxy vitamin D3 [25-hydroxy vitamin D3, 25(OH)D3] and high mobility group protein B1 (high mobility group protein B1, HMGB1) level changes in the diagnosis of neonatal pneumonia infection type and the application of disease assessment. Methods A total of 105 children with NP who were admitted to the Department of Neonatology, Longhua District People’s Hospital of Shenzhen from January to December 2020 were selected as the research objects. According to different infectious pathogens, they were divided into a bacterial pneumonia group of 40 cases and a non-bacterial pneumonia group of 65 cases. According to the severity of the disease, they could be divided into 69 cases of mild pneumonia group and 36 cases of severe pneumonia group, and 85 healthy newborns were selected as the control group during the same period. Serum levels of YKL-40, 25(OH)D3 and HMGB1 were detected by enzyme-linked immunosorbent assay. ROC curve was used to analyze the differential diagnosis value of YKL-40, 25(OH)D3 and HMGB1 for NP alone or in combination. Spearman rank correlation was used the relationship between serum YKL-40, 25(OH) D3 and HMGB1 levels and the severity of the disease in children with NP was analyzed. Results The serum levels of YKL-40 (46.39±8.36 ng/ml，40.28±8.47 ng/ml)and HMGB1(23.38±5.66 ng/ml，17.32±4.18 ng/ml) in the bacterial pneumonia groups and non-bacterial pneumonia groups were significantly higher than those in the control group (30.49±6.35 ng/ml，12.56±3.22 ng/ml), and the differences were statistically significant (F=939.480, 99.507, all P ＜ 0.05), while bacterial and non-bacterial pneumonia groups serum 25(OH)D3(12.76±3.57μg/L，18.33±4.21μg/L) levels were significantly lower than those in the control group(19.76±4.87μg/L), and the difference was statistically significant (F=225.752, P ＜ 0.05).The serum levels of YKL-40 (52.56±9.68 ng/ml)and HMGB1(26.74±4.57 ng/ml) in the severe group were significantly higher than those in the mild group(16.63±5.32 ng/ml，9.63±2.38 ng/ml) and the control group(11.63±3.32 ng/ml，6.34±2.06 ng/ml), the differences were all statistical significance (F=265.331，55.426，all P ＜ 0.05) ,and serum 25(OH) D3 (9.76±3.54μg/L ,31.16±5.01μg/L)levels in the severe and mild were significantly lower than control groups (35.16±5.88μg/L) (F=55.426, P ＜ 0.05) . The results of Spearman rank correlation analysis showed that the disease severity was positively correlated with serum YKL-40 and HMGB1 levels (r=0.727, 0.210, all P ＜ 0.05), but negatively correlated with 25(OH)D3 levels (r= -0.566, P ＜ 0.05).The results of ROC curve analysis showed that the combined detection of YKL-40, 25(OH) D3 and HMGB1 had the highest efficacy in diagnosing NP, the AUC was 0.912 (95%CI: 0.864 ～ 0.932), the sensitivity and specificity were 96.34%, 85.72%,respectively. In the single detection of each index, the differences in AUC were statistically significant (Z=0.746, 2.843, 3.662, all P ＜ 0.05).The combined detection of the three had the highest diagnostic efficiency in distinguishing neonatal bacterial pneumonia from non-bacterial pneumonia, and its AUC was 0.894 (95%CI: 0.832 ～ 0.941), the sensitivity and specificity were 97.26%, 80.66%, respectively. Which was higher than the single test of each index, and the difference in AUC was statistically significant (Z=1.573, 3.228, 2.689, all P ＜ 0.05). Conclusion Serum levels of YKL-40, 25(OH) D3 and HMGB1 had important clinical value in diagnosis of NP infection types and in reflecting the severity of children’s disease, the combined detection of the three has better clinical diagnostic performance.