目的探究间质性肺疾病(interstitial lung disease,ILD)患者血清和支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中冷诱导RNA结合蛋白(cold-inducible RNA-binding protein,CIRBP)、黏蛋白(mucin,MUC)5AC的水平及临床意义。方...目的探究间质性肺疾病(interstitial lung disease,ILD)患者血清和支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中冷诱导RNA结合蛋白(cold-inducible RNA-binding protein,CIRBP)、黏蛋白(mucin,MUC)5AC的水平及临床意义。方法收集2022年1月—2024年2月在兰州大学第一医院呼吸与危重症医学科住院的ILD患者63例,其中特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)患者22例,结缔组织疾病相关间质性肺疾病(connective tissue disease-interstitial lung disease,CTD-ILD)患者20例,其他类型的ILD患者21例。选取同时间段人口学特征匹配的健康人30例作为健康组。采用酶联免疫吸附试验检测健康组血清和ILD患者血清及BLAF中CIRBP、MUC5AC水平,比较健康组和ILD组血清及不同类型的ILD患者血清和BALF中CIRBP、MUC5AC水平及其与患者的肺功能、血气分析及6分钟步行距离(6-minute walk distance,6MWD)之间的相关性。依据血清CIRBP、MUC5AC水平绘制受试者操作特征曲线,确定其诊断ILD的最佳临界值、敏感性和特异性。结果三组ILD患者血清CIRBP水平均高于健康组(P<0.01),但三组ILD患者间血清CIRBP水平差异无统计学意义(P>0.05);三组ILD患者与健康组以及三组ILD患者间血清MUC5AC水平差异均无统计学意义(P>0.05);三组ILD患者BALF中CIRBP、MUC5AC水平差异均无统计学意义(P>0.05)。IPF患者BALF中CIRBP与6MWD呈负相关,CTD-ILD患者血清CIRBP与动脉血氧分压和氧饱和度均呈负相关,其他ILD患者血清CIRBP与肺总量占预计值百分比(total lung capacity as a percentage of predicted value,TLC%pred)、用力肺活量占预计值百分比(forced vital capacity as a percentage of predicted value,FVC%pred)、一氧化碳弥散量占预计值百分比(diffusion capacity of carbon monoxide of lung as a percentage of predicted value,DLCO%pred)、6MWD均呈负相关,BALF中CIRBP与DLCO%pred呈负相关;IPF患者BALF中MUC5AC与DLCO%pred呈负相关,CTD-ILD患者BALF中MUC5AC与TLC%pred、DLCO%pred及6MWD呈负相关,其他ILD患者血清MUC5AC与FVC%pred、DLCO%pred、6MWD呈负相关。血清CIRBP诊断ILD的敏感性和特异性分别为77.6%、96.7%。血清MUC5AC诊断ILD的敏感性和特异性分别为55.1%、76.7%;将两指标联合诊断ILD的敏感性为87.8%,特异性为86.7%。结论CIRBP和MUC5AC的高水平表达对ILD具有一定的诊断效能和病情评估作用,有可能成为ILD的潜在生物标志物。展开更多
Chronic obstructive pulmonary disease(COPD)has garnered increased attention as a result of its persistent symptoms,which undermine patientsʼquality of life.Fudosteine has substantial advantages in the treatment of COP...Chronic obstructive pulmonary disease(COPD)has garnered increased attention as a result of its persistent symptoms,which undermine patientsʼquality of life.Fudosteine has substantial advantages in the treatment of COPD due to its high efficacy and low adverse effects.In this study,Fudosteine sulfonamide derivatives Series I and amine derivatives Series II were designed and synthesized,and their biological activities were evaluated.The results showed that compound 6f had outstanding anti-inflammatory action with an IC_(50) of 1.08 mmol/L,and a higher antioxidant capacity than the lead molecule.At the same time,molecular docking investigations have revealed that compound 6f establishes hydrogen bonds and hydrophobic contacts with the MUC5AC protein.Furthermore,derivative 1f inhibited PDE4A1 enzyme activity five times more than Fudosteine.2,2-Diphenyl-1-picrylhydrazyl(DPPH)free radical scavenging tests demonstrated that all examined substances had higher antioxidant activity than Fudosteine.This study established a solid foundation for further research into COPD drug therapy.展开更多
Purpose:Acute otitis media caused by gram-negative bacteria is a common otological condition among pediatric patients.Eustachian tube dysfunction(ETD)plays a pivotal role in the delayed resolution of acute otitis medi...Purpose:Acute otitis media caused by gram-negative bacteria is a common otological condition among pediatric patients.Eustachian tube dysfunction(ETD)plays a pivotal role in the delayed resolution of acute otitis media,whereas the precise contribution of SIRT3 in this mechanism remains uncertain.This study aims to reveal the involvement of SIRT3 in murine ETD induced by LPS.Results:Histological analysis showed no baseline differences in ET structure between WT and SIRT3 knockout(SIRT3-KO)mice.However,LPS exposure led to increased goblet cell proliferation and MUC5 AC mucus secretion in both genotypes,with SIRT3-KO exacerbating these effects.The SIRT3-KO group displayed reduced cilia length.Functionally,SIRT3-KO mice showed a significantly higher initial POP and decreased MCC compared to the WT group after LPS exposure.Additionally,the active clearance of negative pressure(ACNP)was significantly reduced in SIRT3-KO mice,indicating compromised ET function.Conclusions:SIRT3-KO increased resistance to ET opening in mice exposed to LPS,and this effect may be related to the upregulated MUC5 AC expression,the increased surface tension of the luminal fluid and the impaired MCC function in mice exposed to LPS.展开更多
文摘目的探究间质性肺疾病(interstitial lung disease,ILD)患者血清和支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中冷诱导RNA结合蛋白(cold-inducible RNA-binding protein,CIRBP)、黏蛋白(mucin,MUC)5AC的水平及临床意义。方法收集2022年1月—2024年2月在兰州大学第一医院呼吸与危重症医学科住院的ILD患者63例,其中特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)患者22例,结缔组织疾病相关间质性肺疾病(connective tissue disease-interstitial lung disease,CTD-ILD)患者20例,其他类型的ILD患者21例。选取同时间段人口学特征匹配的健康人30例作为健康组。采用酶联免疫吸附试验检测健康组血清和ILD患者血清及BLAF中CIRBP、MUC5AC水平,比较健康组和ILD组血清及不同类型的ILD患者血清和BALF中CIRBP、MUC5AC水平及其与患者的肺功能、血气分析及6分钟步行距离(6-minute walk distance,6MWD)之间的相关性。依据血清CIRBP、MUC5AC水平绘制受试者操作特征曲线,确定其诊断ILD的最佳临界值、敏感性和特异性。结果三组ILD患者血清CIRBP水平均高于健康组(P<0.01),但三组ILD患者间血清CIRBP水平差异无统计学意义(P>0.05);三组ILD患者与健康组以及三组ILD患者间血清MUC5AC水平差异均无统计学意义(P>0.05);三组ILD患者BALF中CIRBP、MUC5AC水平差异均无统计学意义(P>0.05)。IPF患者BALF中CIRBP与6MWD呈负相关,CTD-ILD患者血清CIRBP与动脉血氧分压和氧饱和度均呈负相关,其他ILD患者血清CIRBP与肺总量占预计值百分比(total lung capacity as a percentage of predicted value,TLC%pred)、用力肺活量占预计值百分比(forced vital capacity as a percentage of predicted value,FVC%pred)、一氧化碳弥散量占预计值百分比(diffusion capacity of carbon monoxide of lung as a percentage of predicted value,DLCO%pred)、6MWD均呈负相关,BALF中CIRBP与DLCO%pred呈负相关;IPF患者BALF中MUC5AC与DLCO%pred呈负相关,CTD-ILD患者BALF中MUC5AC与TLC%pred、DLCO%pred及6MWD呈负相关,其他ILD患者血清MUC5AC与FVC%pred、DLCO%pred、6MWD呈负相关。血清CIRBP诊断ILD的敏感性和特异性分别为77.6%、96.7%。血清MUC5AC诊断ILD的敏感性和特异性分别为55.1%、76.7%;将两指标联合诊断ILD的敏感性为87.8%,特异性为86.7%。结论CIRBP和MUC5AC的高水平表达对ILD具有一定的诊断效能和病情评估作用,有可能成为ILD的潜在生物标志物。
文摘Chronic obstructive pulmonary disease(COPD)has garnered increased attention as a result of its persistent symptoms,which undermine patientsʼquality of life.Fudosteine has substantial advantages in the treatment of COPD due to its high efficacy and low adverse effects.In this study,Fudosteine sulfonamide derivatives Series I and amine derivatives Series II were designed and synthesized,and their biological activities were evaluated.The results showed that compound 6f had outstanding anti-inflammatory action with an IC_(50) of 1.08 mmol/L,and a higher antioxidant capacity than the lead molecule.At the same time,molecular docking investigations have revealed that compound 6f establishes hydrogen bonds and hydrophobic contacts with the MUC5AC protein.Furthermore,derivative 1f inhibited PDE4A1 enzyme activity five times more than Fudosteine.2,2-Diphenyl-1-picrylhydrazyl(DPPH)free radical scavenging tests demonstrated that all examined substances had higher antioxidant activity than Fudosteine.This study established a solid foundation for further research into COPD drug therapy.
基金supported by the National Natural Science Foundation of China(Grant NO.82071057,82101229)National Key Research and Development Program of China(Grant NO.2023YFC2508001)。
文摘Purpose:Acute otitis media caused by gram-negative bacteria is a common otological condition among pediatric patients.Eustachian tube dysfunction(ETD)plays a pivotal role in the delayed resolution of acute otitis media,whereas the precise contribution of SIRT3 in this mechanism remains uncertain.This study aims to reveal the involvement of SIRT3 in murine ETD induced by LPS.Results:Histological analysis showed no baseline differences in ET structure between WT and SIRT3 knockout(SIRT3-KO)mice.However,LPS exposure led to increased goblet cell proliferation and MUC5 AC mucus secretion in both genotypes,with SIRT3-KO exacerbating these effects.The SIRT3-KO group displayed reduced cilia length.Functionally,SIRT3-KO mice showed a significantly higher initial POP and decreased MCC compared to the WT group after LPS exposure.Additionally,the active clearance of negative pressure(ACNP)was significantly reduced in SIRT3-KO mice,indicating compromised ET function.Conclusions:SIRT3-KO increased resistance to ET opening in mice exposed to LPS,and this effect may be related to the upregulated MUC5 AC expression,the increased surface tension of the luminal fluid and the impaired MCC function in mice exposed to LPS.
