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不同严重程度慢性萎缩性胃炎患者胱天蛋白酶1、NLRP3炎症小体表达差异及对预后的预测价值

Expression of cysteine aspartate-specifi c protease and NLRP3 infl ammasomes in patients with chronic atrophic gastritis of different severity levels and their predictive value for prognosis
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摘要 目的探究胱天蛋白酶1(Caspase-1)、核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3(NLRP3)炎症小体在慢性萎缩性胃炎(CAG)中的表达及其对疾病进展和临床结局的预测价值。方法回顾性选择2022年3月至2024年3月于河北省沧州市中心医院就诊的129例CAG患者作为研究对象,依据胃萎缩分期分级标准分为轻度组(n=35)、中度组(n=66)和重度组(n=28),并根据幽门螺杆菌(Hp)根治情况分为预后良好组(n=95)和预后不良组(n=34)。比较各组患者的一般资料及Caspase-1、NLRP3 mRNA水平,采用LASSO回归分析预后的影响因素并构建logistic回归预测模型,分析Caspase-1、NLRP3 mRNA水平与病情严重程度在不良预后的交互作用,采用限制性立方样条评估Caspase-1、NLRP3 mRNA水平在不同严重程度下与预后不良的剂量-反应关系。结果轻度组、中度组和重度组CAG患者Hp阳性感染占比、肿瘤坏死因子-α(TNF-α)、降钙素原(PCT)、白介素(IL)-1β、IL-6、IL-8、IL-11、转化生长因子-β(TGF-β)、Caspase-1及NLRP3 mRNA水平差异有统计学意义(P<0.05)。预后不良组重度病情、Hp阳性感染、TNF-α、PCT、IL-1β、IL-6、IL-8、IL-11、TGF-β、Caspase-1及NLRP3 mRNA水平均明显高于预后良好组(P<0.05)。LASSO回归及多因素logistic回归显示,重度病情、Hp阳性感染、TGF-β、Caspase-1及NLRP3 mRNA水平增高为预后不良的独立危险因素,据此构建预测模型,受试者操作特征曲线分析显示,其预测患者预后不良的曲线下面积为0.908(95%CI 0.822~0.975),依据约登指数最大值,确定预测界值为175.38,敏感度为89.25%、特异度为94.06%;随着病情严重程度加重,Caspase-1、NLRP3 mRNA水平与预后不良的正相关强度逐渐增强(P<0.05);Caspase-1、NLRP3 mRNA水平在不同严重程度下与预后不良均存在非线性剂量-反应关系(P<0.001)。结论Caspase-1、NLRP3炎症小体表达水平与CAG患者病情严重程度存在正相关性,且二者联合应用对CAG患者预后具有一定的预测价值。 Objective To investigate the expression of cysteine aspartic acid-specifi c protease 1(Caspase-1)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)infl ammasome in chronic atrophic gastritis(CAG),and their predictive value for disease progression and clinical outcomes.Method A total of 129 patients with CAG who visited Cangzhou Central Hospital from March 2022 to March 2024 were selected as the research subjects.According to the gastric atrophy staging and grading criteria,they were divided into the mild group(n=35),the moderate group(n=66),and the severe group(n=28).Additionally,they were classifi ed into the good prognosis group(n=95)and the poor prognosis group(n=34)based on the eradication status of Hp.The general data and mRNA levels of Caspase-1 and NLRP3 in each group were compared.LASSO regression analysis was used to identify the infl uencing factors of prognosis and a Logistic regression prediction model was constructed.The interaction between the mRNA levels of Caspase-1 and NLRP3 and the severity of the disease in the poor prognosis was analyzed.The restricted cubic spline was used to evaluate the dose-response relationship between the mRNA levels of Caspase-1 and NLRP3 and poor prognosis at different severity levels.Result There were statistically signifi cant differences in the proportions of Helicobacter pylori(HP)positive infections,tumor necrosis factor-α(TNF-α),procalcitonin(PCT),interleukin(IL)-1β,IL-6,IL-8,IL-11,transforming growth factor-β(TGF-β),Caspase-1,and NLRP3 mRNA levels among patients with different severity of CAG(P<0.05).The severe disease condition,HP positive infection,TNF-α,PCT,IL-1β,IL-6,IL-8,IL-11,TGF-β,Caspase-1,and NLRP3 mRNA levels in the poor prognosis group were signifi cantly higher than those in the good prognosis group(P<0.05).LASSO regression and multivariate Logistic regression showed that severe disease condition,HP positive infection,TGF-β,Caspase-1,and NLRP3 mRNA levels were independent risk factors for poor prognosis.Based on this,a prediction model was constructed.The receiver operating characteristic curve analysis showed that the AUC for predicting poor prognosis of patients was 0.908(95%CI 0.822~0.975).According to the maximum Youden index,the prediction threshold was determined to be 175.38.When Y≥175.38,the sensitivity was 89.25%and the specifi city was 94.06%.As the severity of the disease increased,the positive correlation strength between Caspase-1,NLRP3 mRNA levels and poor prognosis gradually strengthened(P<0.05).There were nonlinear dose-response relationships between Caspase-1,NLRP3 mRNA levels and poor prognosis at different severity levels(P<0.001).Conclusion The expression levels of Caspase-1 and NLRP3 infl ammasome are positively correlated with the severity of CAG patients’conditions,and the combination of these two factors has certain clinical value in predicting the prognosis of CAG patients.
作者 李立文 王青青 Li Liwen;Wang Qingqing(Department of Gastroenterology,Cangzhou Central Hospital,Cangzhou Hebei 062450,China)
出处 《中国医刊》 2026年第2期156-162,共7页 Chinese Journal of Medicine
基金 2023-2024年沧州市科技计划自筹经费项目(23244102074)。
关键词 慢性萎缩性胃炎 胱天蛋白酶1 炎症小体 预后 Chronic atrophic gastritis Cysteine aspartate-specifi c protease 1 Infl ammasome Prognosis
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