Background:This study investigated the role of polydatin in regulating macrophage-epithelial cell(EC)interactions during asthma.An asthma model was induced in BALB/c mice using ovalbumin(20μg).Methods:The therapeutic...Background:This study investigated the role of polydatin in regulating macrophage-epithelial cell(EC)interactions during asthma.An asthma model was induced in BALB/c mice using ovalbumin(20μg).Methods:The therapeutic effects of polydatin(20 and 40 mg/kg)were evaluated in this asthmatic mouse model.To assess the underlying mechanisms,Bronchial Epithelium Adenovirus 12-SV402B(BEAS-2B)cells were cocultured with Tohoku Hospital for Pediatrics-1(THP-1)macrophages,in which toll-like receptor 4(TLR4)was either overexpressed or knocked down,and subsequently stimulated with lipopoly-saccharide(LPS)and ATP.THP-1 cells underwent a 1-h pretreatment with polydatin(50 and 100μmol/L),Class Lipid Inhibitor-095(CLI-095,TLR4 inhibitor,1μg/mL),or A438079(P2X7R antagonist,10μmol/L)prior to LPS/ATP challenge.Results:Findings from Western blotting,enzyme-linked immunosorbent assay,flow cytometry,real-time polymerase chain reaction,and immunofluorescence assays demonstrated that modulating TLR4 expression significantly altered interleukin-1β(IL-1β)secretion from THP-1 macrophages and mitochondrial reactive oxygen species(mtROS)production in BEAS-2B ECs.In the mouse asthma model,polydatin significantly alleviated airway inflammation,oxidative stress,and apoptosis,likely by interfering with TLR4/P2X7R-mediated signaling and suppressing the activation of the NOD-like receptor protein inflammasome.Additionally,polydatin significantly reduced IL-1βand IL-18 levels and inhibited the infiltration of macrophages and eosinophils.Correspondingly,polydatin significantly attenuated TLR4/P2X7R signaling in THP-1 cells stimulated with ATP and LPS,thereby reducing IL-1βand IL-18 secretion,calcium influx,mtROS production,and apoptosis in BEAS-2B ECs.Conclusions:Polydatin is a promising therapeutic candidate for asthma,possibly by targeting macrophage-epithelium cross-talk via the TLR4/P2X7R axis.Future formulations as capsules or sprays may effectively alleviate airway inflammation and remodeling.展开更多
目的 旨在构建基于列线图的肺癌术后感染预测模型,并评估4R危机管理模式在高风险患者中的应用效果。方法 纳入2022年1月至2024年12月在本院接受肺癌根治术的108例患者,收集年龄、性别、BMI、手术类型、术中出血量、术后机械通气时间、...目的 旨在构建基于列线图的肺癌术后感染预测模型,并评估4R危机管理模式在高风险患者中的应用效果。方法 纳入2022年1月至2024年12月在本院接受肺癌根治术的108例患者,收集年龄、性别、BMI、手术类型、术中出血量、术后机械通气时间、术前肺功能(FEV1%)、术后PaO2、术后炎症指标(CRP)等临床变量。采用Cox回归分析筛选术后肺部感染的独立预测因素,并构建预测列线图模型,使用Bootstrap重采样进行内部验证。基于预测模型的风险评分,选取前30%患者(高风险组),随机分为4R危机管理模式干预组(4R组)和常规护理组。4R组实施早期感染风险识别、快速响应、强化术后恢复护理及肺功能重建等干预措施,而常规护理组接受标准术后护理。主要终点为术后肺部感染发生率,次要终点包括住院时间、病死率、术后恢复情况(6MWD活动耐量、SF-36生活质量评分)及术后认知功能(MMSE评分)。结果 多因素Cox回归分析显示,年龄、BMI、手术方式、术中出血量、术后机械通气时间、术前FEV1%预测值、术后PaO2、CRP水平均为术后肺部感染的独立预测因素(P<0.05)。基于独立预测因素构建列线图预测模型,模型评估显示C-statistic为0.87,ROC曲线AUC值0.900(95%CI:0.860-0.940),敏感性85.3%,特异性78.2%,具有良好的预测能力。4R组术后感染发生率显著低于常规护理组(8.33%vs. 22.22%,P=0.008),术后住院时间缩短(9.7±2.5 d vs. 12.8±3.1 d,P<0.001)。CT影像学检查显示,4R组术后第7天CT评分低于常规护理组(3.0±1.0 vs. 4.6±1.3,P=0.041)。术后1个月,4R组患者的6MWD活动耐量评分(320.4±42.1 m vs. 278.3±37.8 m,P=0.034)及SF-36生活质量评分(75.4±8.6 vs. 60.3±9.2,P=0.028)均显著改善。术后1个月和6个月的MMSE评分在4R组较常规护理组显著提高(25.4±2.7 vs. 22.8±3.4,P=0.048;27.1±2.3 vs. 23.2±3.1,P=0.039)。30 d病死率在4R组和常规护理组分别为0.13%vs. 0.70%(P=0.180),差异无统计学意义。结论 基于列线图的肺癌术后感染预测模型具有较高的准确性,可有效识别高风险患者。4R危机管理模式能够显著降低高风险患者术后肺部感染发生率,缩短住院时间,改善术后肺功能及认知恢复,为肺癌术后感染的精准护理管理提供了有效策略。展开更多
基金National Natural Science Foundation of China,Grant/Award Number:82260007Jilin Province Health Commission,Grant/Award Number:2024A062+1 种基金Jilin Provincial Department of Education,Grant/Award Number:JJKH20240698KJJilin Province Science and Technology Department,Grant/Award Number:20240404025ZP and 20240602100RC。
文摘Background:This study investigated the role of polydatin in regulating macrophage-epithelial cell(EC)interactions during asthma.An asthma model was induced in BALB/c mice using ovalbumin(20μg).Methods:The therapeutic effects of polydatin(20 and 40 mg/kg)were evaluated in this asthmatic mouse model.To assess the underlying mechanisms,Bronchial Epithelium Adenovirus 12-SV402B(BEAS-2B)cells were cocultured with Tohoku Hospital for Pediatrics-1(THP-1)macrophages,in which toll-like receptor 4(TLR4)was either overexpressed or knocked down,and subsequently stimulated with lipopoly-saccharide(LPS)and ATP.THP-1 cells underwent a 1-h pretreatment with polydatin(50 and 100μmol/L),Class Lipid Inhibitor-095(CLI-095,TLR4 inhibitor,1μg/mL),or A438079(P2X7R antagonist,10μmol/L)prior to LPS/ATP challenge.Results:Findings from Western blotting,enzyme-linked immunosorbent assay,flow cytometry,real-time polymerase chain reaction,and immunofluorescence assays demonstrated that modulating TLR4 expression significantly altered interleukin-1β(IL-1β)secretion from THP-1 macrophages and mitochondrial reactive oxygen species(mtROS)production in BEAS-2B ECs.In the mouse asthma model,polydatin significantly alleviated airway inflammation,oxidative stress,and apoptosis,likely by interfering with TLR4/P2X7R-mediated signaling and suppressing the activation of the NOD-like receptor protein inflammasome.Additionally,polydatin significantly reduced IL-1βand IL-18 levels and inhibited the infiltration of macrophages and eosinophils.Correspondingly,polydatin significantly attenuated TLR4/P2X7R signaling in THP-1 cells stimulated with ATP and LPS,thereby reducing IL-1βand IL-18 secretion,calcium influx,mtROS production,and apoptosis in BEAS-2B ECs.Conclusions:Polydatin is a promising therapeutic candidate for asthma,possibly by targeting macrophage-epithelium cross-talk via the TLR4/P2X7R axis.Future formulations as capsules or sprays may effectively alleviate airway inflammation and remodeling.
文摘目的 旨在构建基于列线图的肺癌术后感染预测模型,并评估4R危机管理模式在高风险患者中的应用效果。方法 纳入2022年1月至2024年12月在本院接受肺癌根治术的108例患者,收集年龄、性别、BMI、手术类型、术中出血量、术后机械通气时间、术前肺功能(FEV1%)、术后PaO2、术后炎症指标(CRP)等临床变量。采用Cox回归分析筛选术后肺部感染的独立预测因素,并构建预测列线图模型,使用Bootstrap重采样进行内部验证。基于预测模型的风险评分,选取前30%患者(高风险组),随机分为4R危机管理模式干预组(4R组)和常规护理组。4R组实施早期感染风险识别、快速响应、强化术后恢复护理及肺功能重建等干预措施,而常规护理组接受标准术后护理。主要终点为术后肺部感染发生率,次要终点包括住院时间、病死率、术后恢复情况(6MWD活动耐量、SF-36生活质量评分)及术后认知功能(MMSE评分)。结果 多因素Cox回归分析显示,年龄、BMI、手术方式、术中出血量、术后机械通气时间、术前FEV1%预测值、术后PaO2、CRP水平均为术后肺部感染的独立预测因素(P<0.05)。基于独立预测因素构建列线图预测模型,模型评估显示C-statistic为0.87,ROC曲线AUC值0.900(95%CI:0.860-0.940),敏感性85.3%,特异性78.2%,具有良好的预测能力。4R组术后感染发生率显著低于常规护理组(8.33%vs. 22.22%,P=0.008),术后住院时间缩短(9.7±2.5 d vs. 12.8±3.1 d,P<0.001)。CT影像学检查显示,4R组术后第7天CT评分低于常规护理组(3.0±1.0 vs. 4.6±1.3,P=0.041)。术后1个月,4R组患者的6MWD活动耐量评分(320.4±42.1 m vs. 278.3±37.8 m,P=0.034)及SF-36生活质量评分(75.4±8.6 vs. 60.3±9.2,P=0.028)均显著改善。术后1个月和6个月的MMSE评分在4R组较常规护理组显著提高(25.4±2.7 vs. 22.8±3.4,P=0.048;27.1±2.3 vs. 23.2±3.1,P=0.039)。30 d病死率在4R组和常规护理组分别为0.13%vs. 0.70%(P=0.180),差异无统计学意义。结论 基于列线图的肺癌术后感染预测模型具有较高的准确性,可有效识别高风险患者。4R危机管理模式能够显著降低高风险患者术后肺部感染发生率,缩短住院时间,改善术后肺功能及认知恢复,为肺癌术后感染的精准护理管理提供了有效策略。
