STUB1与幽门螺旋杆菌感染的肥胖儿童并发非酒精性脂肪性肝病的关系

Relationship of STUB1 with NAFLD in Obese Children Infected with Hp.

目的探究STIP1同源性和包含U-box蛋白1(STUB1)与幽门螺旋杆菌(Hp)感染的肥胖儿童并发非酒精性脂肪性肝病(NAFLD)的关系。方法选择2019年2月至2020年7月就诊的387例Hp感染的肥胖儿童作为研究对象,根据是否合并NAFLD分为肥胖组(n=118)和NAFLD组(n=269)。收集年龄、性别、体质指数(BMI)、糖脂代谢和肝酶指标等;用Ficoll密度梯度离心法分离出外周血中单个核细胞;用蛋白质免疫印迹法检测单个核细胞中STUB1表达水平。用受试者工作特征(ROC)曲线评价STUB1判断Hp感染的肥胖儿童并发NAFLD的效能;用限制性立方样条拟合Logistic回归分析STUB1与Hp感染的肥胖儿童并发NAFLD的关系;用Lasso回归分析Hp感染的肥胖儿童并发NAFLD的风险因素;构建列线图回归模型判断Hp感染的肥胖儿童是否并发NAFLD,用一致性指数(C-index)、校准曲线和决策树分析(DCA)评估模型的临床价值。结果肥胖组儿童BMI、空腹血糖(FBG)、胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)水平均低于NAFLD组(P<0.05);STUB1水平高于NAFLD组(P<0.05)。STUB1判断Hp感染的肥胖儿童并发NAFLD的受试者工作特征(ROC)曲线下面积、敏感度和特异度分别为0.813,83.64%和66.95%。STUB1与Hp感染的肥胖儿童并发NAFLD呈线性关系。FBG、TC、TG和LDL-C均是Hp感染的肥胖儿童并发NAFLD的独立危险因素,STUB1是Hp感染的肥胖儿童并发NAFLD的独立保护因素。由FBG、TC、TG、LDL-C和STUB1构建的列线图回归模型的C-index和平均绝对误差值分别为0.975和0.014,该模型判断Hp感染的肥胖儿童并发NAFLD的净收益较高。结论STUB1水平低提示Hp感染的肥胖儿童并发NAFLD的风险高。基于STUB1构建的列线图回归模型有很高的区分度、精准度及临床应用价值,可辅助判断Hp感染的肥胖儿童并发NAFLD。

Objective To explore the relationship between STIP1 homology and U-box containing protein 1(STUB1)and non-alcoholic fatty liver disease(NAFLD)in obese children with Helicobacter pylori(Hp)infection.Methods From February 2019 to July 2020,387 obese children with Hp infection were selected as research objects.According to whether they were combined with NAFLD,they were divided into obesity group(n=118)and NAFLD group(n=269).Age,sex,body mass index(BMI),glucolipid metabolism and liver enzyme indices were collected.Ficoll density gradient centrifugation was used to isolate mononuclear cells in peripheral blood.Western blotting was used to detect STUB1 in mononuclear cells.Efficacy of STUB1 in determining NAFLD in obese children with Hp infection was evaluated using receiver operating characteristic(ROC)curves.Relationships between STUB1 and NAFLD in obese children with Hp infection were analyzed using restricted cubic spline fiting logistic regression.Risk factors for NAFLD in obese children with Hp infection were analyzed using lasso regression.Nomogram regression models were constructed to determine whether obese children with Hp infection had NAFLD,and clinical values of model were assessed using consistency index(C-index),calibration curves and decision tree analysis(DCA).Results BMI,fasting blood glucose(FBG),fasting insulin(FINS),homeostasis model assessment of insulin resist(HOMA-IR),total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in obese group were lower than those in NAFLD group(P<0.05).And STUB1 was higher than that in NAFLD group(P<0.05).Area under the receiver operating characteristic(ROC)curve,sensitivity and specificity of STUB1 to diagnose NAFLD in obese children with Hp infection were 0.813,83.64%and 66.95%,respectively.STUB1 had a linear relationship with NAFLD in obese children with Hp infection.FBG,TC,TG and LDL-C were all independent risk factors for NAFLD in obese children with Hp infection,and STUB1 was an independent protective factor for NAFLD in obese children with Hp infection.C-index and mean absolute error values of nomogram regression model constructed by FBG,TC,TG,LDL-C and STUB1 were 0.975 and 0.014,respectively,and model judged net benefit of NAFLD in obese children with Hp infection to be higher.Conclusion Low STUB1 could indicate that obese children with Hp infection is at high risk of NAFLD.The nomogram regression model would construct that STUB1 has high discrimination,accuracy and clinical application value,and could assist in judging NAFLD in obese children with Hp infection.