【摘要】 目的 探讨胰岛素生长因子-1 (IGF-1)/胰岛素样生长因子结合蛋白-3 (IGFBP-3)、抗衰老物质Klotho联合细胞周期调节物质p21 waf/cip1对特发性矮小症(ISS)儿童注射用重组人生长激素(rhGH)干预后年生长速率(GV)的预测效能。方法 选取2021年4月至2023年6月南阳市中心医院收治的150例ISS患者进行前瞻性研究，根据rh GH干预后GV分为低(GV<5 cm/年，25例)、中(GV介于5～7 cm/年，34例)、高(GV>7 cm/年，91例) GV组。比较三组患儿治疗前的IGF-1/IGFBP-3、Klotho、p21 waf/cip1水平，采用Pearson相关性分析治疗前IGF-1/IGFBP-3、Klotho、p21 waf/cip1水平与rhGH干预后GV的相关性，消除了其他可能因素的影响后，采用净相关性分析治疗前IGF-1/IGFBP-3、Klotho、p21 waf/cip1水平与rhGH干预后GV的相关性，采用受试者工作特征(ROC)曲线评估治疗前IGF-1/IGFBP-3、Klotho、p21 waf/cip1及其联合检测对rhGH干预后GV的预测效能。结果 治疗前，高GV组患儿的IGF-1/IGFBP-3、Klotho、rhGH干预后GV分别为0.18±0.05、(1 672.20±356.38) pg/mL、(8.79±0.58) cm/年，明显高于低GV组[0.07±0.02、(905.65±281.13) pg/mL、(4.22±0.24) cm/年]和中GV组[0.12±0.04、(1 294.33±327.52) pg/mL、(6.15±0.26) cm/年]，且中GV组明显高于低GV组，差异均有统计学意义(P<0.05)；治疗前，高GV组患儿的p21waf/cip1为(0.16±0.05) pg/mL，明显低于中GV组的(0.23±0.07) pg/mL和低GV组的(0.39±0.13) pg/mL，且中GV组明显低于低GV组，差异均有统计学意义(P<0.05);Pearson相关性分析结果显示，治疗前IGF-1/IGFBP-3、Klotho与rhGH干预后GV呈正相关(P<0.05),p21 waf/cip1与rhGH干预后GV呈负相关(P<0.05)；净相关性分析结果显示，治疗前IGF-1/IGFBP-3、Klotho、p21 waf/cip1水平仍与rhGH干预后GV显著相关(P<0.05);ROC分析结果显示，三者及联合预测rhGH干预后获得中GV的AUC分别为0.799、0.766、0.768、0.931，其中联合的AUC最大；三者及联合预测rhGH干预后获得高GV的AUC分别为0.809、0.740、0.828、0.943，其中联合的AUC亦最大。结论 治疗前IGF-1/IGFBP-3、Klotho、p21 waf/cip1与ISS儿童rhGH干预后GV显著相关，可作为预测rhGH敏感性的标志物，联合检测时能进一步提高预测性能，为临床早期预测rhGH的敏感性提供重要的参考信息。更多还原

【Abstract】 Objective To investigate the predictive efficacy of insulin growth factor-1(IGF-1)/insulin-like growth factor binding protein-3(IGFBP-3), anti-aging substance Klotho, and cell cycle regulatory substance p21 waf/cip1 for the annual growth rate(GV) of children with idiopathic short stature(ISS) after intervention with recombinant human growth hormone(rhGH) injection. Methods A prospective study was conducted on 150 ISS patients admitted to Nanyang Central Hospital from April 2021 to June 2023. After rhGH intervention, the patients were divided into low(GV<5 cm/year, 25 cases), medium(GV between 5-7 cm/year, 34 cases), and high(GV>7 cm/year, 91 cases) GV groups. The levels of IGF-1/IGFBP-3, Klotho, p21 waf/cip1 before treatment were compared among the three groups of children, and Pearson correlation analysis was used to determine the correlation between the levels of IGF-1/IGFBP-3,Klotho, p21 waf/cip1 before treatment and GV after rhGH intervention. After eliminating the influence of other possible factors, net correlation analysis was used to determine the correlation between the levels of IGF-1/IGFBP-3, Klotho,p21 waf/cip1 before treatment and GV after rhGH intervention. Receiver operating characteristic(ROC) curves were used to evaluate the predictive power of IGF-1/IGFBP-3, Klotho, p21 waf/cip1 and their combined detection before treatment for GV after rhGH intervention. Results Before treatment, the IGF-1/IGFBP-3, Klotho, and GV after rhGH intervention in the high GV group were 0.18±0.05,(1 672.20±356.38) pg/mL, and(8.79±0.58) cm/year, respectively,which were significantly higher than 0.07±0.02,(905.65±281.13) pg/mL,(4.22±0.24) cm/year in the low GV group and0.12±0.04,(1294.33±327.52) pg/mL, and(6.15±0.26) cm/year in the medium GV group; the three indexes in the medium GV group were significantly higher than those in the low GV group; the differences were statistically significant(P<0.05). Before treatment, the p21 waf/cip1 of the high GV group was(0.16±0.05) pg/mL, significantly lower than(0.23±0.07) pg/mL of the medium GV group and(0.39±0.13) pg/mL of the low GV group; the p21 waf/cip1 of the medium GV group was significantly lower than that of the low GV group; the differences were statistically significant(P<0.05). Pearson correlation analysis showed that IGF-1/IGFBP-3 and Klotho were positively correlated with GV after rhGH intervention(P<0.05), while p21 waf/cip1 was negatively correlated with GV after rhGH intervention(P<0.05). The results of the net correlation analysis showed that the levels of IGF-1/IGFBP-3, Klotho, and p21 waf/cip1 before treatment were still significantly correlated with GV after rhGH intervention(P<0.05). ROC analysis showed that the AUCs of IGF-1/IGFBP-3, Klotho, and p21 waf/cip1 alone and in combination for predicting medium GV after rhGH intervention were 0.799, 0.766, 0.768, and 0.931, respectively, and the AUC of the combination was the largest. The AUCs of the three alone and in combination for predicting high GV after rhGH intervention were 0.809, 0.740, 0.828, and 0.943, respectively, and AUC of the combination was the largest. Conclusion IGF-1/IGFBP-3, Klotho, and p21 waf/cip1 are significantly correlated with GV after rhGH intervention in children with ISS, which can be used as markers to predict rhGH sensitivity. Combined detection of the three indexes can further improve the predictive performance and provide important reference for early clinical prediction of rhGH sensitivity.更多还原