Correlation Between Serum NF-κB，S1P1，and SOCS3 Levels and Disease Severity in Children with Bacterial Infectious Pneumonia，and Their Prognostic Predictive Value
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摘要:
目的 探究细菌感染性肺炎患儿血清核因子κB（nuclear factor-kappa B，NF-κB）、1-磷酸鞘氨醇受体1（sphingosine-1-phosphate 1，S1P1）、细胞因子信号转导抑制因子3（suppressor of cytokine signaling 3，SOCS3）水平与病情程度的相关性及其对患儿预后的预测价值。 方法 选取2022年1月至2024年12月西安国际医学中心医院收治的200例细菌感染性肺炎患儿，分为轻症组（n = 120）和重症组（n = 80），另选120例体检健康儿童为对照组。ELISA法检测三组血清NF-κB、S1P1、SOCS3水平，采用Spearman和Pearson相关性分析其与患儿病情指标和临床指标的相关性。对细菌感染性肺炎患儿随访6个月，分为预后良好组（n = 131）和预后不良组（n = 69），采用Logistic回归分析预后不良因素。采用ROC曲线评估血清NF-κB、S1P1、SOCS3水平对预后的预测价值。采用DCA曲线评估血清NF-κB、S1P1、SOCS3的临床净获益。 结果 轻症组、重症组血清NF-κB、SOCS3、C反应蛋白（C-reactive protein，CRP）、白细胞计数（white blood cell count，WBC）、临床肺部感染评分（clinic pulmonary infection score，CPIS）高于对照组，S1P1、收缩压、舒张压低于对照组（P < 0.05）；重症组血清NF-κB、SOCS3、CRP、WBC、CPIS评分高于轻症组，S1P1低于轻症组，心率高于对照组和轻症组（P < 0.05）。病情、CPIS评分、CRP、WBC与血清NF-κB、SOCS3水平呈正相关，与S1P1水平呈负相关（P < 0.05）。预后不良组血清NF-κB、SOCS3、CRP、WBC、CPIS评分高于预后良好组，S1P1低于预后良好组（P < 0.05）。NF-κB、SOCS3、CRP、WBC、CPIS评分升高以及S1P1降低是影响细菌感染性肺炎患儿预后不良的危险因素（P < 0.05）。血清NF-κB、S1P1、SOCS3联合预测细菌感染性肺炎患儿预后不良的AUC和净获益高于单项预测（P < 0.05）。 结论 细菌感染性肺炎患儿血清NF-κB、SOCS3水平升高，S1P1水平降低，三者与患儿病情严重程度和预后密切相关，对预后不良具有较高的预测价值和临床净获益。 -
关键词:
- 细菌感染性肺炎 /
- 核因子κB /
- 1-磷酸鞘氨醇受体1 /
- 细胞因子信号转导抑制因子3 /
- 病情程度 /
- 预后
Abstract:Objective To investigate the correlation between serum nuclear factor-kappa B （NF-κB）, sphingosine-1-phosphate 1 （S1P1）, suppressor of cytokine signaling 3 （SOCS3） levels and disease severity in children with bacterial infectious pneumonia, and to evaluate their predictive value for patient prognosis. Methods A total of 200 children with bacterial infectious pneumonia admitted to Xi'an International Medical Center Hospital from January 2022 to December 2024 were enrolled and divided into mild pneumonia group （n=120） and severe pneumonia group （n=80）. Additionally, 120 healthy children from routine physical examinations served as the control group. Serum levels of NF-κB, S1P1, and SOCS3 in all three groups were detected using ELISA. Spearman and Pearson correlation analyses were performed to assess the correlations between these markers and disease indicators and clinical parameters. Children with bacterial infectious pneumonia were followed up for 6 months and categorized into favorable prognosis group （n = 131） and unfavorable prognosis group （n = 69）. Logistic regression analysis was used to identify risk factors for poor prognosis. ROC curves were employed to evaluate the predictive value of serum NF-κB, S1P1, and SOCS3 levels for prognosis. Decision curve analysis （DCA） was used to assess the clinical net benefit of these biomarkers. Results Serum NF-κB, SOCS3, C-reactive protein （CRP）, white blood cell count （WBC）, and clinical pulmonary infection score （CPIS） in both mild and severe pneumonia groups were higher than in the control group, while S1P1, systolic blood pressure, and diastolic blood pressure were lower than in the control group （P < 0.05）. Serum NF-κB, SOCS3, CRP, WBC, and CPIS scores in the severe group were higher than in the mild group, S1P1 was lower, and heart rate was higher than in both the control and mild groups （P < 0.05）. Disease severity, CPIS score, CRP, and WBC showed positive correlations with serum NF-κB and SOCS3 levels, and negative correlations with S1P1 levels （P < 0.05）. Serum NF-κB, SOCS3, CRP, WBC, and CPIS scores in the unfavorable prognosis group were higher than in the favorable prognosis group, while S1P1 was lower （P < 0.05）. Elevated NF-κB, SOCS3, CRP, WBC, CPIS scores, as well as decreased S1P1, were identified as risk factors for poor prognosis in children with bacterial infectious pneumonia （P < 0.05）. The AUC and net benefit of serum NF-κB, S1P1, and SOCS3 for poor prognosis were superior to individual predictors （P < 0.05）. Conclusion Serum NF-κB and SOCS3 levels are elevated in children with bacterial pneumonia, while S1P1 level is decreased. The three factors are closely related to disease severity and prognosis, and have high predictive value and clinical net benefit for poor prognosis. -
图 1 细菌感染性肺炎患儿预后的影响因素
Figure 1. Influencing Factors on prognosis of bacterial pneumonia in children
图 2 血清NF-κB、S1P1、SOCS3对预后不良的ROC曲线
Figure 2. ROC curves for serum NF-κB，S1P1，and SOCS3 in predicting poor prognosis
图 3 血清NF-κB、S1P1、SOCS3预测预后的DCA曲线
Figure 3. Diagnostic c-curve for serum NF-κB，S1P1，and SOCS3 in predicting prognosis
表 1 三组一般资料[（$ \bar x \pm s $）/n（%）]
Table 1. General data among three groups [（$ \bar x \pm s $）/n（%）]
组别 n 年龄（岁） 性别 BMI（kg/m2） 男 女 对照组 100 6.18 ± 1.04 65（65.00） 35（35.00） 18.56 ± 3.09 轻症组 120 6.05 ± 1.01 69（57.50） 51（42.50） 18.33 ± 3.05 重症组 80 6.18 ± 1.03 44（55.00） 36（45.00） 18.52 ± 3.08 F/χ2 0.579 2.121 0.176 P 0.561 0.346 0.839 
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表 2 三组其他临床资料（$ \bar x \pm s $）
Table 2. Other clinical data among the three groups （$ \bar x \pm s $）
组别 对照组（n = 100） 轻症组（n = 120） 重症组（n = 80） F P NF-κB（ng/mL） 4.15 ± 0.76 5.07 ± 0.85△ 6.55 ± 0.99△# 173.382 <0.001* S1P1（ng/mL） 11.81 ± 2.02 10.76 ± 1.79△ 7.14 ± 1.12△# 175.479 <0.001* SOCS3（pg/mL） 214.17 ± 40.55 276.93 ± 46.12△ 355.58 ± 59.24△# 190.406 <0.001* 心率（次/分） 89.72 ± 14.48 91.48 ± 15.75 101.15 ± 17.51△# 13.156 <0.001* CRP（mg/L） 6.23 ± 2.05 31.45 ± 5.91△ 41.30 ± 6.73△# 1117.656 <0.001* WBC（×109/L） 6.52 ± 1.53 10.17 ± 1.74△ 13.81 ± 2.33△# 345.325 <0.001* 收缩压（mmHg） 105.05 ± 17.52 93.37 ± 15.44△ 90.94 ± 15.08△ 21.204 <0.001* 舒张压（mmHg） 70.38 ± 11.76 61.18 ± 10.31△ 59.93 ± 9.72△ 27.913 <0.001* CPIS评分（分） 2.03 ± 0.17 6.08 ± 1.02△ 7.98 ± 1.33△# 950.966 <0.001* *P < 0.05；与对照组比较，△P < 0.05；与轻症组比较，#P < 0.05。
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表 3 细菌感染性肺炎患儿血清NF-κB、S1P1、SOCS3水平与病情、炎症指标的相关性
Table 3. Correlation between serum NF-κB，S1P1，and SOCS3 levels and disease severity and inflammatory markers in children with bacterial infectious pneumonia
项目 NF-κB S1P1 SOCS3 r P r P r P 病情 0.552 <0.001* −0.528 <0.001* 0.563 <0.001* CPIS评分 0.549 <0.001* −0.540 <0.001* 0.558 <0.001* CRP 0.562 <0.001* −0.554 <0.001* 0.576 <0.001* WBC 0.502 <0.001* −0.508 <0.001* 0.520 <0.001* *P < 0.05。
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表 4 预后良好组与预后不良组临床资料比较[（$ \bar x \pm s $）/n（%）]
Table 4. 4 Comparison of clinical data between the favorable prognosis group and the unfavorable prognosis group [（$ \bar x \pm s $）/n（%）]
组别 预后良好组（n = 131） 预后不良组（n = 69） t/χ2 P 年龄（岁） 6.12 ± 1.03 6.06 ± 1.00 0.396 0.693 性别 0.087 0.768 男 75（57.25） 38（55.07） 女 56（42.75） 31（44.93） BMI（kg/m2） 18.34 ± 3.14 18.52 ± 2.92 0.395 0.694 NF-κB（ng/mL） 5.16 ± 0.89 6.64 ± 0.98 10.793 <0.001* S1P1（ng/mL） 10.41 ± 2.07 7.22 ± 1.15 11.864 <0.001* SOCS3（pg/mL） 285.53 ± 55.17 351.80 ± 58.52 7.907 <0.001* 心率（次/min） 93.89 ± 17.34 98.13 ± 16.41 1.674 0.096 CRP（mg/L） 32.39 ± 6.66 41.07 ± 6.86 8.671 <0.001* WBC（×109/L） 10.50 ± 2.05 13.75 ± 2.41 10.021 <0.001* 收缩压（mmHg） 93.50 ± 15.55 90.29 ± 14.71 1.414 0.159 舒张压（mmHg） 60.71 ± 10.35 60.62 ± 9.61 0.060 0.952 CPIS评分（分） 6.24 ± 1.22 7.97 ± 1.25 9.453 <0.001* 病程（d） 3.25 ± 1.08 3.38 ± 1.15 0.791 0.430 入院时体温（℃） 38.41 ± 0.53 38.56 ± 0.58 1.841 0.067 *P < 0.05。
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表 5 血清NF-κB、S1P1、SOCS3对预后不良的预测价值
Table 5. Predictive value of serum NF-κB，S1P1，and SOCS3 for poor prognosis
变量 AUC 截断值 95% CI 灵敏度（%） 特异度（%） Youden指数 NF-κB（ng/mL） 0.795 5.792 0.731～0.860 73.91 73.28 0.472 S1P1（ng/mL） 0.798 8.665 0.735～0.860 72.46 74.81 0.473 SOCS3（pg/mL） 0.793 299.802 0.723～0.864 73.91 74.81 0.487 联合 0.907 0.864～0.949 92.75 72.53 0.653
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