To evaluate circulating IL9 in inflammatory bowel disease and disease-associated anemia/cachexia and assess its potential as a mucosal healing marker.METHODSSerum IL9 as well as other cytokines (IL1β, IL6, IL13, IFN...To evaluate circulating IL9 in inflammatory bowel disease and disease-associated anemia/cachexia and assess its potential as a mucosal healing marker.METHODSSerum IL9 as well as other cytokines (IL1β, IL6, IL13, IFNγ, TNFα, and VEGF-A) were determined in 293 individuals: 97 patients with Crohn’s disease (CD) and 74 with ulcerative colitis (UC) and in 122 apparently healthy controls. The clinical activity of CD and UC was expressed in terms of the Crohn’s Disease Activity Index (CDAI) and the Mayo Scoring System (MDAI), respectively, and the severity of bowel inflammation in UC patients was assessed using Mayo endoscopic score. Cytokine concentrations were measured by a flow cytometry-based method using Luminex xMAP<sup>®</sup> technology. High-sensitive C-reactive protein concentrations (hsCRP) were determined in CD and UC patients using the enhanced immunoturbidimetric method.RESULTSSystemic IL9 was significantly lower in healthy individuals [9 pg/mL (95%CI: 8.2-10)] than in patients with inflammatory bowel disease (IBD): both inactive [14.3 pg/mL (11.9-19.9)] and active [27.6 pg/mL (24.5-32), P < 0.0001]. Cytokine concentrations were significantly higher in active CD [27.4 pg/mL (23.4-32.2)] and in active UC [32.7 pg/mL (27-38.9)] compared to inactive diseases [15.9 pg/mL (10.8-23.4) in CD and 19.4 pg/mL (13.9-27.1) in UC, P = 0.001]. IL9 correlated weakly with CDAI (ρ = 0.32, P = 0.003) and MDAI (ρ = 0.35, P = 0.002) and strongly with endoscopic inflammation in UC (ρ = 0.74, P < 0.0001). As a negative marker of mucosal healing (MH), IL9 had an accuracy superior to hsCRP and IL6 [97% (P < 0.0001), 67% (P = 0.071), and 55% (P = 0.525), respectively]. IL9 was significantly higher in cachectic IBD patients [30.25 pg/mL (24.4-37.5) vs 21.88 pg/mL (18-26.5), P = 0.026] and negatively correlated with hemoglobin concentrations (ρ = -0.27, P < 0.001). Multiple regression showed IL1β and IL13 to be the independent predictors of circulating IL9 in healthy individuals, IFNγ or IL6 in active and inactive UC, respectively, and IL13 and VEGF-A in both active and inactive CD.CONCLUSIONThe systemic IL9 level is higher in IBD and corresponds with endoscopic inflammation, suggesting its possible application as a negative marker of mucosal healing in UC.展开更多
目的探究血清网膜素-1(Omentin-1)、补体/C1q肿瘤坏死因子相关蛋白9(CTRP-9)水平与急性脑梗死(ACI)神经功能康复的相关性。方法选取2022年11月至2024年2月于该院治疗的ACI患者106例作为研究组,其中包括ACI神经功能康复良好患者62例(良好...目的探究血清网膜素-1(Omentin-1)、补体/C1q肿瘤坏死因子相关蛋白9(CTRP-9)水平与急性脑梗死(ACI)神经功能康复的相关性。方法选取2022年11月至2024年2月于该院治疗的ACI患者106例作为研究组,其中包括ACI神经功能康复良好患者62例(良好组)和康复不良患者44例(不良组)。采用酶联免疫吸附试验检测所有研究对象的血清Omentin-1、CTRP-9水平;采用Spearman相关性分析血清Omentin-1、CTRP-9水平与ACI患者入院时的美国国立卫生研究院卒中量表(NIHSS)评分及脑梗死体积的相关性;采用多因素Logistic回归分析ACI患者神经功能康复不良的影响因素;采用受试者工作特征(ROC)曲线分析血清Omentin-1、CTRP-9水平对ACI患者神经功能康复不良的诊断价值。结果良好组血清Omentin-1、CTRP-9水平明显高于不良组(P<0.05),入院时NIHSS评分、脑梗死面积和发病90 d时改良Rankin量表(mRS)评分明显低于不良组(P<0.05);Spearman相关性分析显示,血清Omentin-1、CTRP-9水平与90 d mRS评分呈负相关(r=-0.648,-0.573,均P<0.001);多因素Logistic回归分析结果显示,90 d mRS评分是ACI患者神经功能康复不良的危险因素(P<0.05),血清Omentin-1、CTRP-9水平是ACI患者神经功能康复不良的保护因素(P<0.05);ROC曲线分析结果显示,血清Omentin-1、CTRP-9水平诊断ACI患者神经功能康复不良的曲线下面积(AUC)为0.843、0.828,二者联合诊断的AUC为0.937,明显大于二者单独诊断(Z_(二者联合-Omentin-1)=2.321,P=0.020;Z_(二者联合-CTRP-9)=2.532,P=0.011)。结论ACI神经功能康复不良患者血清Omentin-1、CTRP-9水平明显降低,且Omentin-1、CTRP-9水平与90 d mRS评分呈负相关,与神经功能康复情况密切相关。展开更多
The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multi...The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.展开更多
基金Supported by National Science Center,No.DEC-2011/01/D/NZ5/02835
文摘To evaluate circulating IL9 in inflammatory bowel disease and disease-associated anemia/cachexia and assess its potential as a mucosal healing marker.METHODSSerum IL9 as well as other cytokines (IL1β, IL6, IL13, IFNγ, TNFα, and VEGF-A) were determined in 293 individuals: 97 patients with Crohn’s disease (CD) and 74 with ulcerative colitis (UC) and in 122 apparently healthy controls. The clinical activity of CD and UC was expressed in terms of the Crohn’s Disease Activity Index (CDAI) and the Mayo Scoring System (MDAI), respectively, and the severity of bowel inflammation in UC patients was assessed using Mayo endoscopic score. Cytokine concentrations were measured by a flow cytometry-based method using Luminex xMAP<sup>®</sup> technology. High-sensitive C-reactive protein concentrations (hsCRP) were determined in CD and UC patients using the enhanced immunoturbidimetric method.RESULTSSystemic IL9 was significantly lower in healthy individuals [9 pg/mL (95%CI: 8.2-10)] than in patients with inflammatory bowel disease (IBD): both inactive [14.3 pg/mL (11.9-19.9)] and active [27.6 pg/mL (24.5-32), P < 0.0001]. Cytokine concentrations were significantly higher in active CD [27.4 pg/mL (23.4-32.2)] and in active UC [32.7 pg/mL (27-38.9)] compared to inactive diseases [15.9 pg/mL (10.8-23.4) in CD and 19.4 pg/mL (13.9-27.1) in UC, P = 0.001]. IL9 correlated weakly with CDAI (ρ = 0.32, P = 0.003) and MDAI (ρ = 0.35, P = 0.002) and strongly with endoscopic inflammation in UC (ρ = 0.74, P < 0.0001). As a negative marker of mucosal healing (MH), IL9 had an accuracy superior to hsCRP and IL6 [97% (P < 0.0001), 67% (P = 0.071), and 55% (P = 0.525), respectively]. IL9 was significantly higher in cachectic IBD patients [30.25 pg/mL (24.4-37.5) vs 21.88 pg/mL (18-26.5), P = 0.026] and negatively correlated with hemoglobin concentrations (ρ = -0.27, P < 0.001). Multiple regression showed IL1β and IL13 to be the independent predictors of circulating IL9 in healthy individuals, IFNγ or IL6 in active and inactive UC, respectively, and IL13 and VEGF-A in both active and inactive CD.CONCLUSIONThe systemic IL9 level is higher in IBD and corresponds with endoscopic inflammation, suggesting its possible application as a negative marker of mucosal healing in UC.
文摘目的探究血清网膜素-1(Omentin-1)、补体/C1q肿瘤坏死因子相关蛋白9(CTRP-9)水平与急性脑梗死(ACI)神经功能康复的相关性。方法选取2022年11月至2024年2月于该院治疗的ACI患者106例作为研究组,其中包括ACI神经功能康复良好患者62例(良好组)和康复不良患者44例(不良组)。采用酶联免疫吸附试验检测所有研究对象的血清Omentin-1、CTRP-9水平;采用Spearman相关性分析血清Omentin-1、CTRP-9水平与ACI患者入院时的美国国立卫生研究院卒中量表(NIHSS)评分及脑梗死体积的相关性;采用多因素Logistic回归分析ACI患者神经功能康复不良的影响因素;采用受试者工作特征(ROC)曲线分析血清Omentin-1、CTRP-9水平对ACI患者神经功能康复不良的诊断价值。结果良好组血清Omentin-1、CTRP-9水平明显高于不良组(P<0.05),入院时NIHSS评分、脑梗死面积和发病90 d时改良Rankin量表(mRS)评分明显低于不良组(P<0.05);Spearman相关性分析显示,血清Omentin-1、CTRP-9水平与90 d mRS评分呈负相关(r=-0.648,-0.573,均P<0.001);多因素Logistic回归分析结果显示,90 d mRS评分是ACI患者神经功能康复不良的危险因素(P<0.05),血清Omentin-1、CTRP-9水平是ACI患者神经功能康复不良的保护因素(P<0.05);ROC曲线分析结果显示,血清Omentin-1、CTRP-9水平诊断ACI患者神经功能康复不良的曲线下面积(AUC)为0.843、0.828,二者联合诊断的AUC为0.937,明显大于二者单独诊断(Z_(二者联合-Omentin-1)=2.321,P=0.020;Z_(二者联合-CTRP-9)=2.532,P=0.011)。结论ACI神经功能康复不良患者血清Omentin-1、CTRP-9水平明显降低,且Omentin-1、CTRP-9水平与90 d mRS评分呈负相关,与神经功能康复情况密切相关。
基金supported by the National Natural Science Foundational of China(Key Program),No.U24A20692(to CJZ)the National Natural Science Foundational of China,Nos.82101414(to MLJ),82371355(to CJZ)+4 种基金the National Natural Science Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)The Innovation and Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)Funding for Distinguished Young Scholars of Sichuan Provincial People’s Hospital,No.30420230005(to CJZ)Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(to CJZ)。
文摘The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.
