摘要
目的探讨肠道组织蛋白酶D(CAD)、S-100蛋白、蛋白酶激活受体-1(PAR-1)与先天性巨结肠(HSCR)患儿病情分型的相关性及预测预后的价值。方法选取2020年1月至2023年9月郑州大学第一附属医院收治的195例HSCR患儿开展前瞻性研究。术中取病变组织、病变旁正常组织检测CAD、S-100蛋白、PAR-1表达水平,比较患儿的病变组织和病变旁正常组织CAD、S-100蛋白、PAR-1表达水平,并比较不同病情分型患儿的病变组织CAD、S-100蛋白、PAR-1表达水平,采用Spearman相关性分析HSCR患儿病变组织CAD、S-100蛋白、PAR-1表达水平与病情分型的相关性。对患儿进行术后12个月随访,比较预后不良组、预后良好组患儿的一般资料及病变组织CAD、S-100蛋白、PAR-1表达水平,采用Logistic多因素回归分析预后不良的影响因素,应用受试者工作特征曲线(ROC)分析病变组织CAD、S-100蛋白、PAR-1预测HSCR患儿预后不良的价值。结果HSCR患儿的病变组织CAD表达水平为0.46±0.12,明显低于病变旁正常组织的1.35±0.28,S-100蛋白、PAR-1表达水平分别为5.37±1.28、15.81±4.16,明显高于病变旁正常组织的4.19±0.93、6.74±1.95,差异均有统计学意义(P<0.05);长段型和全结肠型HSCR患儿的病变组织CAD表达水平为0.31±0.09,明显低于常见型的0.44±0.10、短段型的0.56±0.15,S-100蛋白、PAR-1表达水平分别为6.83±1.78、20.57±4.64,明显高于常见型的5.52±1.26、16.25±4.08、短段型的4.46±1.04、12.93±3.25,且常见型HSCR患儿的病变组织CAD表达水平明显低于短段型,S-100蛋白、PAR-1表达水平明显高于短段型,差异均有统计学意义(P<0.05);Spearman相关性分析结果显示,HSCR患儿病变组织CAD表达水平与病情分型呈负相关(r=-0.615,P<0.05),S-100蛋白、PAR-1表达水平与病情分型呈正相关(r=0.504、0.553,P<0.05);预后不良组患儿的术后遵医嘱排便训练者占比、病变组织CAD表达水平明显低于预后良好组,病情分型(短段型/常见型/长段型和全结肠型)、术前营养不良者占比、小肠结肠炎者占比、术后伤口感染者占比、肠管切除长度、病变组织S-100蛋白、PAR-1表达水平明显高于预后良好组,差异均有统计学意义(P<0.05);Logistic多因素回归分析结果显示,术前营养不良、术前小肠结肠炎、术后伤口感染、肠管切除长度、病变组织S-100蛋白、PAR-1是HSCR患儿预后不良的独立危险因素(P<0.05),术后遵医嘱排便训练、病变组织CAD是独立保护因素(P<0.05);ROC分析显示,病变组织CAD、S-100蛋白、PAR-1联合预测预后不良的曲线下面积(AUC)为0.856,大于各指标单独预测的AUC,差异均有统计学意义(P<0.05)。结论HSCR患儿病变组织CAD、S-100蛋白、PAR-1表达水平与病情分型密切相关,有助于预测患儿预后,联合应用可为临床识别预后不良高风险患儿提供可靠临床依据。
Objective To investigate relationships of intestinal cathepsin D(CAD),S-100 protein,and prote-ase-activated receptor-1(PAR-1)with disease typing in children with Hirschsprung's disease(HSCR)and to evaluate their value in predicting postoperative prognosis.Methods A prospective study was conducted on 195 pediatric pa-tients with HSCR admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to September 2023.During the operation,lesion tissues and normal tissues adjacent to the lesion were collected to detect the expres-sion levels of CAD,S-100 protein,and PAR-1.The expression levels of CAD,S-100 protein,and PAR-1 were com-pared between the lesion tissues and normal tissues adjacent to the lesion,and the levels in the lesion tissues were com-pared among different disease types.Spearman correlation analysis was used to assess correlations between the expres-sion levels of CAD,S-100 protein,and PAR-1 in the lesion tissues of pediatric patients with HSCR and disease typing.Follow-up visits were conducted 12 months after surgery to compare general information and expression levels of CAD,S-100 protein,and PAR-1 in the lesion tissues of patients with poor and good prognoses.Multivariate logistic regression analysis was used to identify the factors influencing poor prognosis,and receiver operating characteristic(ROC)curves were generated to evaluate the predictive value of CAD,S-100 protein,and PAR-1 in lesion tissues for poor prognosis in pediatric patients with HSCR.Results The expression level of CAD in the lesion tissues of children with HSCR was 0.46±0.12,significantly lower than 1.35±0.28 in the normal tissues adjacent to the lesions,whereas the expression levels of S-100 protein and PAR-1 were 5.37±1.28 and 15.81±4.16,respectively,both significantly higher than corresponding 4.19±0.93 and 6.74±1.95 in the normal tissues adjacent to the lesions(all P<0.05).In children with long-segment and to-tal colonic HSCR,the expression level of CAD in the lesion tissues was 0.31±0.09,which was significantly lower than 0.44±0.10 in the common type and 0.56±0.15 in the short-segment type.The expression levels of S-100 protein and PAR-1 were 6.83±1.78 and 20.57±4.64,respectively,which were significantly higher than corresponding 5.52±1.26 and 16.25±4.08 in the common type and corresponding 4.46±1.04 and 12.93±3.25 in the short-segment type.Furthermore,the expression level of CAD in the lesion tissues of children was lower,and S-100 protein and PAR-1 were higher in the common type than in the short-segment type(all P<0.05).Spearman analysis showed a negative correlation between CAD expression and disease classification in the lesion tissues of children with HSCR(r=-0.615,P<0.05)and positive correlations for S-100 protein(r=0.504)and PAR-1(r=0.553)(both P<0.05).Compared with the good-prognosis group,the poor-prognosis group had lower rates of postoperative defecation training adherence and lower CAD expression,but higher proportions of disease typing(short segment type/common type/long segment type and total colonic type),preop-erative malnutrition,enterocolitis,postoperative wound infection,greater bowel-resection length,and higher S-100 pro-tein and PAR-1 levels(all P<0.05).Multivariate logistic regression identified preoperative malnutrition,preoperative en-terocolitis,postoperative wound infection,length of resected intestinal tube,and elevated S-100 protein and PAR-1 as in-dependent risk factors for poor prognosis,while adherence to postoperative defecation training and higher CAD expres-sion were independent protective factors(all P<0.05).The combined ROC curve for the combined prediction of poor prognosis using CAD,S-100 protein,and PAR-1 yielded an area under the curve(AUC)of 0.856,significantly greater than that of any single indicator.(P<0.05).Conclusion The expression levels of CAD,S-100 protein,and PAR-1 in le-sion tissues of children with HSCR are closely related to disease typing,which can help predict the prognosis of the chil-dren.The combined application of these markers can provide reliable clinical evidence for identifying children at high risk of poor prognosis in clinical practice.
作者
张宁
岳铭
袁宇航
ZHANG Ning;YUE Ming;YUAN Yu-hang(Department of Pediatric Surgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 455000,Henan,CHINA)
出处
《海南医学》
2025年第13期1895-1900,共6页
Hainan Medical Journal
基金
河南省科技厅科技攻关项目(编号:222102310292)。