AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was adminis...AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was administered intraperitoneally in CCl4-treated mice.Fibrosis was assessed by histology and Masson staining.The activation of hepatic stellate cells(HSCs) was investigated by analysis of α-smooth muscle actin expression.The frequencies of T helper(Th) 22 cells,Th17 cells and Th1 cells,the expression of inflammatory cytokines [IL-22,IL-17 A,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),IL-6,IL-1b] and transcription factors [aryl hydrocarbon receptor(AHR),RAR-related orphan receptor(RORγt),T-bet] m RNA in the liver were investigated.In addition,the plasma levels of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6 and IL-1b were evaluated.RESULTS:Significant elevations in circulating Th22 cells,Th17 cells,Th1 cells,IL-22,IL-17 A,and IFN-γ were observed in the hepatic fibrosis group compared with the control group(P < 0.01).Treatment with rm IL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis,which was confirmed by lower hepatic fibrosis pathological scores(P < 0.01).Rm IL-22 decreased the frequencies of Th22 cells(6.71% ± 0.97% vs 8.09% ± 0.74%,P < 0.01),Th17 cells(4.34% ± 0.37% vs 5.71% ± 0.24%,P < 0.01),Th1 cells(3.09% ± 0.49% vs 4.91% ± 0.73%,P < 0.01),and the levels of IL-22(56.23 ± 3.08 vs 70.29 ± 3.01,P < 0.01),IL-17A(30.74 ± 2.77 vs 45.68 ± 2.71,P < 0.01),and IFN-γ(74.78 ± 2.61 vs 124.89 ± 2.82,P < 0.01).Down-regulation of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6,IL-1b,AHR RORγt,and T-bet gene expression in the liver was observed in the rm IL-22 group(P < 0.01).CONCLUSION:The frequencies of Th22,Th17 andTh1 cells are elevated in hepatic fibrosis.Rm IL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines,thereby ameliorating liver fibrogenesis.展开更多
通过欧拉-拉格朗日(Coupled Eulerian-Lagrangian,CEL)大变形有限元对不考虑应变软化的T形触探仪(T-bar)承载力系数进行计算,其计算结果与已有塑性理论解和RITSS(Remeshing and Interpolation with Small Strain,即在小变形有限元的基...通过欧拉-拉格朗日(Coupled Eulerian-Lagrangian,CEL)大变形有限元对不考虑应变软化的T形触探仪(T-bar)承载力系数进行计算,其计算结果与已有塑性理论解和RITSS(Remeshing and Interpolation with Small Strain,即在小变形有限元的基础上通过网格重剖分和应力插值技术实现大变形有限元分析)的计算结果均吻合较好,验证了CEL计算模型的可靠性。在ABAQUS有限元平台的基础上进行二次开发,编写应变软化子程序计算出考虑应变软化的T-bar承载力系数,其计算结果与RITSS吻合较好,验证了应变软化子程序的可靠性。对T-bar周围土体的软化程度和流动机制分析发现,应变软化使土体抗剪强度减小的同时还改变了土体的流动机制,这两个因素的综合作用导致T-bar的承载力系数减小,从而揭示了应变软化对T-bar承载力系数的影响机理。展开更多
目的:观察乙型肝炎相关原发性肝癌患者(hepatitis B virus-related primary liver cancer,H B V-P L C)发生和进展过程中外周血T、N K、B细胞数量的变化,并初步探讨T淋巴细胞减少与胸腺功能的联系.方法:收集在首都医科大学附属北京地坛...目的:观察乙型肝炎相关原发性肝癌患者(hepatitis B virus-related primary liver cancer,H B V-P L C)发生和进展过程中外周血T、N K、B细胞数量的变化,并初步探讨T淋巴细胞减少与胸腺功能的联系.方法:收集在首都医科大学附属北京地坛医院住院的73例HBV-PLC患者,50例乙型肝炎肝硬化患者(liver cirrhosis,LC),37例慢性乙型肝炎(chronic hepatitis B,CHB)患者.收集3组患者一般资料和临床生化指标.采用流式方法检测3组患者外周血中CD3^+T淋巴细胞、CD4^+T、CD8^+T、CD3-CD16^+CD56^+NK、CD3-CD19^+B的分布情况,并检测了T淋巴细胞表面CD31、CD45RA分子的表达水平.结果:与CHB和LC患者相比,HBV-PLC患者外周血中性粒细胞升高,淋巴细胞减少(P<0.001);与CHB患者相比,HBV-PLC患者外周血NK细胞计数减少(P=0.011),T淋巴细胞、CD4^+T、C D8^+T、B细胞计数减少,纯真CD4^+和CD8^+T细胞表面CD31表达降低(P<0.001).在肝癌Child、Okuda、BCLC分期中晚期比早期淋巴细胞计数、T、CD4^+T、CD8^+T计数均降低(P<0.05).结论:随着肝癌的发生和进展,HBV-PLC患者外周血抗肿瘤免疫细胞减少,这种减少与胸腺迁出功能降低有关.展开更多
背景:类风湿性关节炎是自身免疫性疾病,传统治疗方法很难有效解决患者免疫耐受机制缺失的问题。随着干细胞再生医学的发展,应用干细胞治疗免疫性疾病成为热点。目前国内外对于细胞移植治疗类风湿性关节炎少有报道。目的:探讨脐带间充质...背景:类风湿性关节炎是自身免疫性疾病,传统治疗方法很难有效解决患者免疫耐受机制缺失的问题。随着干细胞再生医学的发展,应用干细胞治疗免疫性疾病成为热点。目前国内外对于细胞移植治疗类风湿性关节炎少有报道。目的:探讨脐带间充质干细胞对类风湿性关节炎患者Th1/Th2、Treg变化的影响,为类风湿性关节炎寻找新的治疗方法。方法:180例类风湿性关节炎患者,其中27例为对照组,给予非类固醇抗炎药和抗风湿药,153例为治疗组,静脉输注细胞数为4×107的脐带间充质干细胞40 m L,用药方案与对照组相同,76例患者在第1次细胞治疗的三四个月后接受了2次脐带间充质干细胞治疗。随访治疗后3,6个月进行临床有效性评估(DAS28、HAQ、ACR20)、类风湿因子、抗CCP抗体、T细胞亚群、Th细胞因子检测。部分2次细胞治疗患者随访至8个月检测Treg、T细胞亚群。结果与结论:1随访3个月时,细胞治疗组DAS28评分、HAQ评分、ACR20较对照组下降明显,差异有非常显著性意义(P<0.01)。2脐带间充质干细胞治疗3,6个月的DAS28评分、HAQ评分较治疗前明显下降(P<0.01),2次治疗较1次治疗继续下降(P<0.01)。3治疗后3,6个月γ-干扰素水平较治疗前变化不明显,治疗后6个月白细胞介素4水平较治疗前逐渐上升(P<0.05)。4治疗后3,6个月Treg较治疗前明显上升(P<0.01),同时治疗后Treg升高与ACR明显相关,尤其是ACR70百分率(P<0.05);治疗后3个月CD4+Treg比率明显升高(P<0.05),6,8个月时与治疗前相比也是升高趋势,但差异无显著性意义(P>0.05)。5治疗后6个月B细胞水平明显下降(P<0.05);治疗后3,6个月类风湿因子较治疗前均明显下降(P<0.05)。6治疗后3,6个月抗CCP抗体和白细胞介素17水平变化不大。结果表明类风湿性关节炎患者给予脐带间充质干细胞治疗后Th1/Th2趋于平衡、Treg升高与临床实验指标及症状的缓解直接相关。因此按风湿病指南用药的同时,协同使用脐带间充质干细胞可改善类风湿性关节炎患者免疫网络效应、调整免疫耐受、改善病情。展开更多
基金Supported by National Natural Science Foundation of China,No.81260083Grants from the Guangxi Natural Science Foundation of China,No.2014jj AA40237
文摘AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was administered intraperitoneally in CCl4-treated mice.Fibrosis was assessed by histology and Masson staining.The activation of hepatic stellate cells(HSCs) was investigated by analysis of α-smooth muscle actin expression.The frequencies of T helper(Th) 22 cells,Th17 cells and Th1 cells,the expression of inflammatory cytokines [IL-22,IL-17 A,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),IL-6,IL-1b] and transcription factors [aryl hydrocarbon receptor(AHR),RAR-related orphan receptor(RORγt),T-bet] m RNA in the liver were investigated.In addition,the plasma levels of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6 and IL-1b were evaluated.RESULTS:Significant elevations in circulating Th22 cells,Th17 cells,Th1 cells,IL-22,IL-17 A,and IFN-γ were observed in the hepatic fibrosis group compared with the control group(P < 0.01).Treatment with rm IL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis,which was confirmed by lower hepatic fibrosis pathological scores(P < 0.01).Rm IL-22 decreased the frequencies of Th22 cells(6.71% ± 0.97% vs 8.09% ± 0.74%,P < 0.01),Th17 cells(4.34% ± 0.37% vs 5.71% ± 0.24%,P < 0.01),Th1 cells(3.09% ± 0.49% vs 4.91% ± 0.73%,P < 0.01),and the levels of IL-22(56.23 ± 3.08 vs 70.29 ± 3.01,P < 0.01),IL-17A(30.74 ± 2.77 vs 45.68 ± 2.71,P < 0.01),and IFN-γ(74.78 ± 2.61 vs 124.89 ± 2.82,P < 0.01).Down-regulation of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6,IL-1b,AHR RORγt,and T-bet gene expression in the liver was observed in the rm IL-22 group(P < 0.01).CONCLUSION:The frequencies of Th22,Th17 andTh1 cells are elevated in hepatic fibrosis.Rm IL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines,thereby ameliorating liver fibrogenesis.
文摘通过欧拉-拉格朗日(Coupled Eulerian-Lagrangian,CEL)大变形有限元对不考虑应变软化的T形触探仪(T-bar)承载力系数进行计算,其计算结果与已有塑性理论解和RITSS(Remeshing and Interpolation with Small Strain,即在小变形有限元的基础上通过网格重剖分和应力插值技术实现大变形有限元分析)的计算结果均吻合较好,验证了CEL计算模型的可靠性。在ABAQUS有限元平台的基础上进行二次开发,编写应变软化子程序计算出考虑应变软化的T-bar承载力系数,其计算结果与RITSS吻合较好,验证了应变软化子程序的可靠性。对T-bar周围土体的软化程度和流动机制分析发现,应变软化使土体抗剪强度减小的同时还改变了土体的流动机制,这两个因素的综合作用导致T-bar的承载力系数减小,从而揭示了应变软化对T-bar承载力系数的影响机理。
文摘目的:观察乙型肝炎相关原发性肝癌患者(hepatitis B virus-related primary liver cancer,H B V-P L C)发生和进展过程中外周血T、N K、B细胞数量的变化,并初步探讨T淋巴细胞减少与胸腺功能的联系.方法:收集在首都医科大学附属北京地坛医院住院的73例HBV-PLC患者,50例乙型肝炎肝硬化患者(liver cirrhosis,LC),37例慢性乙型肝炎(chronic hepatitis B,CHB)患者.收集3组患者一般资料和临床生化指标.采用流式方法检测3组患者外周血中CD3^+T淋巴细胞、CD4^+T、CD8^+T、CD3-CD16^+CD56^+NK、CD3-CD19^+B的分布情况,并检测了T淋巴细胞表面CD31、CD45RA分子的表达水平.结果:与CHB和LC患者相比,HBV-PLC患者外周血中性粒细胞升高,淋巴细胞减少(P<0.001);与CHB患者相比,HBV-PLC患者外周血NK细胞计数减少(P=0.011),T淋巴细胞、CD4^+T、C D8^+T、B细胞计数减少,纯真CD4^+和CD8^+T细胞表面CD31表达降低(P<0.001).在肝癌Child、Okuda、BCLC分期中晚期比早期淋巴细胞计数、T、CD4^+T、CD8^+T计数均降低(P<0.05).结论:随着肝癌的发生和进展,HBV-PLC患者外周血抗肿瘤免疫细胞减少,这种减少与胸腺迁出功能降低有关.
文摘背景:类风湿性关节炎是自身免疫性疾病,传统治疗方法很难有效解决患者免疫耐受机制缺失的问题。随着干细胞再生医学的发展,应用干细胞治疗免疫性疾病成为热点。目前国内外对于细胞移植治疗类风湿性关节炎少有报道。目的:探讨脐带间充质干细胞对类风湿性关节炎患者Th1/Th2、Treg变化的影响,为类风湿性关节炎寻找新的治疗方法。方法:180例类风湿性关节炎患者,其中27例为对照组,给予非类固醇抗炎药和抗风湿药,153例为治疗组,静脉输注细胞数为4×107的脐带间充质干细胞40 m L,用药方案与对照组相同,76例患者在第1次细胞治疗的三四个月后接受了2次脐带间充质干细胞治疗。随访治疗后3,6个月进行临床有效性评估(DAS28、HAQ、ACR20)、类风湿因子、抗CCP抗体、T细胞亚群、Th细胞因子检测。部分2次细胞治疗患者随访至8个月检测Treg、T细胞亚群。结果与结论:1随访3个月时,细胞治疗组DAS28评分、HAQ评分、ACR20较对照组下降明显,差异有非常显著性意义(P<0.01)。2脐带间充质干细胞治疗3,6个月的DAS28评分、HAQ评分较治疗前明显下降(P<0.01),2次治疗较1次治疗继续下降(P<0.01)。3治疗后3,6个月γ-干扰素水平较治疗前变化不明显,治疗后6个月白细胞介素4水平较治疗前逐渐上升(P<0.05)。4治疗后3,6个月Treg较治疗前明显上升(P<0.01),同时治疗后Treg升高与ACR明显相关,尤其是ACR70百分率(P<0.05);治疗后3个月CD4+Treg比率明显升高(P<0.05),6,8个月时与治疗前相比也是升高趋势,但差异无显著性意义(P>0.05)。5治疗后6个月B细胞水平明显下降(P<0.05);治疗后3,6个月类风湿因子较治疗前均明显下降(P<0.05)。6治疗后3,6个月抗CCP抗体和白细胞介素17水平变化不大。结果表明类风湿性关节炎患者给予脐带间充质干细胞治疗后Th1/Th2趋于平衡、Treg升高与临床实验指标及症状的缓解直接相关。因此按风湿病指南用药的同时,协同使用脐带间充质干细胞可改善类风湿性关节炎患者免疫网络效应、调整免疫耐受、改善病情。
