While acute nociceptive pain is a crucial warning system that protects us from injury or disease,chronic pain is not protective,but a pathological condition.As such,it is now recognized as a disease in its own right,w...While acute nociceptive pain is a crucial warning system that protects us from injury or disease,chronic pain is not protective,but a pathological condition.As such,it is now recognized as a disease in its own right,which major classes refer to inflammatory,neuropathic,and idiopathic pain.It is frequent,with up to a third of the population that may suffer at one point from chronic pain.It is often associated with other pathologies,including sleep disorders,anxiety,depression,and is still difficult to treat.It thus represents a significant burden in terms of health and societal impact(Tracey et al.,2019).The mechanisms of chronic pain involve multiple diverse pathways in both the peripheral and central nervous systems(CNS),reflecting its multifaceted biology.Indeed,research over the past decades has established that central sensitization(enhancement in the function of neurons and circuits in central nociceptive pathways),in particular within the dorsal horn,the first central relay of nociceptive inputs plays a key role in the chronicity of pain(Latremoliere and Woolf,2009).展开更多
目的探讨慢性阻塞性肺疾病(COPD)患者血清G蛋白偶联受体43(GPR43)、甲基转移酶3(METTL3)水平表达与肺功能和气流受限程度的相关性。方法选取2019年1月~2024年5月成都市第六人民医院收治的COPD患者150例(COPD组)和同期健康体检志愿者150...目的探讨慢性阻塞性肺疾病(COPD)患者血清G蛋白偶联受体43(GPR43)、甲基转移酶3(METTL3)水平表达与肺功能和气流受限程度的相关性。方法选取2019年1月~2024年5月成都市第六人民医院收治的COPD患者150例(COPD组)和同期健康体检志愿者150例(对照组)。根据气流受限程度将COPD患者分为轻度组(n=61)、中度组(n=46)和重度/极重度组(n=43)。检测血清GPR43、METTL3水平并测定肺功能[第1秒用力呼气容积(FEV1)/用力肺活量(FVC)、FEV1占预计值%(%pred)]。Spearman相关性分析血清GPR43、METTL3水平与肺功能指标的相关性;通过多元有序Logistic回归分析血清GPR43、METTL3水平与COPD患者气流受限程度的关系,使用受试者工作特征(ROC)曲线分析其评估效能。结果与对照组比较,COPD组血清GPR43水平(5.32±1.07ng/ml vs 7.61±1.59ng/ml),FEV1/FVC比值[54.17(43.77,63.60)%vs 80.78(76.24,88.22)%]和FEV1%pred[72.25(44.94,84.22)%vs 93.06(89.71、95.54)%]显著降低(t/Z=-14.591,-14.247,-14.108),而METTL3水平(41.73±5.27pg/ml vs 31.85±5.03pg/ml)显著升高(t=16.614),差异具有统计学意义(均P<0.001)。重度/极重度组血清GPR43水平低于轻度、中度组(4.57±0.77ng/ml vs 5.98±1.05ng/ml、5.16±0.79 ng/ml),中度组低于轻度组(t=7.474、3.598、4.391),重度/极重度组血清METTL3水平高于轻度组、中度组(45.76±5.24pg/ml vs 38.83±4.20pg/ml、41.82±4.00pg/ml),中度组高于轻度组(t=-7.474、-4.003、-3.722),差异具有统计学意义(均P<0.001)。COPD患者FEV1/FVC比值、FEV1%pred与血清GPR43水平呈正相关(r=0.762、0.768,均P<0.001),与METTL3水平呈负相关(r=-0.758、-0.778,均P<0.001)。GPR43为COPD气流受限的独立保护因素(OR=0.689,Waldχ^(2)=14.064,P<0.05),METTL3为独立危险因素(OR=1.251,Waldχ^(2)=4.500,P<0.05)。血清GPR43与METTL3联合评估COPD重度/极重度气流受限的曲线下面积(AUC)优于GPR43和METTL3单独检测,差异具有统计学意义(Z=3.231、3.374,均P<0.05)。结论COPD患者血清GPR43水平降低、METTL3水平升高,与肺功能降低和气流受限程度加重有关,血清GPR43,METTL3水平联合评估COPD患者重度/极重度气流受限的价值较高。展开更多
基金supported by the grants for Anhui Provincial University Scientific Research Innovation Team(No.2022AH010083)Anhui Provincial Major Science and Technology Project(No.2022AH040215)the Scientific Research and Innovation Team of Bengbu Medical University,China(No.Byycx24018).
文摘本研究旨在探讨脂质运载蛋白2(lipocalin-2,LCN2)基因敲除(LCN2KO)对盲肠结扎与穿孔(cecal ligation and perforation,CLP)诱导的脓毒症小鼠肺损伤和铁死亡的作用,进一步明确Toll样受体4(Toll-like receptor 4,TLR4)/核因子-κB(nuclear factorκB,NF-κB)通路在其中的可能作用。用LCN2KO小鼠建立CLP模型,用ELISA检测小鼠血清中白介素6(interleukin-6,IL-6)和IL-1β含量,用试剂盒检测肺组织丙二醛(malondialdehyde,MDA)和谷胱甘肽(glutathione,GSH)含量,用DHE荧光探针检测肺组织中活性氧(reactive oxygen species,ROS)水平,用Western blot检测肺组织中铁死亡相关蛋白的表达水平。结果显示,相对野生型(wild type,WT)-Sham组,WT-CLP组小鼠肺组织明显受损,血清IL-6和IL-1β含量升高,肺组织MDA含量增加,GSH含量降低,ROS水平显著升高,LCN2和TLR4蛋白表达水平显著上调,p-P65/P65比值显著升高,铁死亡抑制蛋白1(ferroptosis suppressor protein 1,FSP1)和谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)蛋白表达水平显著下调。LCN2KO可以逆转脓毒症小鼠的上述变化。TLR4抑制剂TAK-242和NF-κB抑制剂PDTC均可下调脓毒症小鼠肺组织中LCN2蛋白表达水平;与LCN2KO的作用相似,二者均可逆转脓毒症诱导的铁死亡和肺损伤。以上结果提示,LCN2KO可能通过调控TLR4/NF-κB信号通路减轻铁死亡,从而改善脓毒症小鼠肺损伤。
基金Institut National de la Santéet de la Recherche Médicale(Inserm)UniversitéClermont Auvergne(France)+2 种基金CHU Clermont-Ferrand(to RD)the French government IDEX-ISITE initiative 16-IDEX-0001(to RD)The Fondation pour la Recherche Médicale(FRM)(to SM).
文摘While acute nociceptive pain is a crucial warning system that protects us from injury or disease,chronic pain is not protective,but a pathological condition.As such,it is now recognized as a disease in its own right,which major classes refer to inflammatory,neuropathic,and idiopathic pain.It is frequent,with up to a third of the population that may suffer at one point from chronic pain.It is often associated with other pathologies,including sleep disorders,anxiety,depression,and is still difficult to treat.It thus represents a significant burden in terms of health and societal impact(Tracey et al.,2019).The mechanisms of chronic pain involve multiple diverse pathways in both the peripheral and central nervous systems(CNS),reflecting its multifaceted biology.Indeed,research over the past decades has established that central sensitization(enhancement in the function of neurons and circuits in central nociceptive pathways),in particular within the dorsal horn,the first central relay of nociceptive inputs plays a key role in the chronicity of pain(Latremoliere and Woolf,2009).
文摘目的探讨慢性阻塞性肺疾病(COPD)患者血清G蛋白偶联受体43(GPR43)、甲基转移酶3(METTL3)水平表达与肺功能和气流受限程度的相关性。方法选取2019年1月~2024年5月成都市第六人民医院收治的COPD患者150例(COPD组)和同期健康体检志愿者150例(对照组)。根据气流受限程度将COPD患者分为轻度组(n=61)、中度组(n=46)和重度/极重度组(n=43)。检测血清GPR43、METTL3水平并测定肺功能[第1秒用力呼气容积(FEV1)/用力肺活量(FVC)、FEV1占预计值%(%pred)]。Spearman相关性分析血清GPR43、METTL3水平与肺功能指标的相关性;通过多元有序Logistic回归分析血清GPR43、METTL3水平与COPD患者气流受限程度的关系,使用受试者工作特征(ROC)曲线分析其评估效能。结果与对照组比较,COPD组血清GPR43水平(5.32±1.07ng/ml vs 7.61±1.59ng/ml),FEV1/FVC比值[54.17(43.77,63.60)%vs 80.78(76.24,88.22)%]和FEV1%pred[72.25(44.94,84.22)%vs 93.06(89.71、95.54)%]显著降低(t/Z=-14.591,-14.247,-14.108),而METTL3水平(41.73±5.27pg/ml vs 31.85±5.03pg/ml)显著升高(t=16.614),差异具有统计学意义(均P<0.001)。重度/极重度组血清GPR43水平低于轻度、中度组(4.57±0.77ng/ml vs 5.98±1.05ng/ml、5.16±0.79 ng/ml),中度组低于轻度组(t=7.474、3.598、4.391),重度/极重度组血清METTL3水平高于轻度组、中度组(45.76±5.24pg/ml vs 38.83±4.20pg/ml、41.82±4.00pg/ml),中度组高于轻度组(t=-7.474、-4.003、-3.722),差异具有统计学意义(均P<0.001)。COPD患者FEV1/FVC比值、FEV1%pred与血清GPR43水平呈正相关(r=0.762、0.768,均P<0.001),与METTL3水平呈负相关(r=-0.758、-0.778,均P<0.001)。GPR43为COPD气流受限的独立保护因素(OR=0.689,Waldχ^(2)=14.064,P<0.05),METTL3为独立危险因素(OR=1.251,Waldχ^(2)=4.500,P<0.05)。血清GPR43与METTL3联合评估COPD重度/极重度气流受限的曲线下面积(AUC)优于GPR43和METTL3单独检测,差异具有统计学意义(Z=3.231、3.374,均P<0.05)。结论COPD患者血清GPR43水平降低、METTL3水平升高,与肺功能降低和气流受限程度加重有关,血清GPR43,METTL3水平联合评估COPD患者重度/极重度气流受限的价值较高。
