BACKGROUND The effects of T-cell immunoglobulin mucin molecule-3(Tim-3),transforming growth factor β(TGF-β),and chemokine-12(CXCL12) expression on the prognosis of patients with diffuse large B-cell lymphoma(DLBCL) ...BACKGROUND The effects of T-cell immunoglobulin mucin molecule-3(Tim-3),transforming growth factor β(TGF-β),and chemokine-12(CXCL12) expression on the prognosis of patients with diffuse large B-cell lymphoma(DLBCL) have not been elucidated.AIM To examine the correlation between Tim-3,TGF-β and CXCL12 expression and DLBCL prognosis.METHODS Lymph node tissues of 97 patients with DLBCL and 93 normal-response hyperplastic lymph node tissues treated from January 2017 to May 2019 were selected as the DLBCL and control groups,respectively.The expression of Tim-3,TGF-β,and CXCL12 was detected immunohistochemically.Patients were followed up for 3 years,and progression-free survival was recorded.Cox mult-ifactorial analysis was performed to analyze the risk factors for poor prognosis.RESULTS The positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in DLBCL tissues than in non-cancerous(control) tissues(P < 0.05).One-year postsurgery,the positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in patients with effective treatment than in those with ineffective treatment(P < 0.05).The 3-year progression-free survival of 97 patients with DLBCL was 67.01%(65/97).Univariate analysis revealed that clinical stage,bone marrow infiltration,International Prognostic Index(IPI) score,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were associated with poor prognosis(P < 0.05).Multivariate Cox regression analysis demonstrated that clinical stage Ⅲ–Ⅳ,bone marrow infiltration,mediate-to-high-risk IPI scores,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were independent risk factors affecting prognosis(P < 0.05).CONCLUSION DLBCL tissues exhibit high positive expression of Tim-3,TGF-β,and CXCL12,and a high expression of all three indicates a poor prognosis.展开更多
目的探讨EBV mi R-BART17-3p影响原发免疫性血小板减少症(ITP)患儿Treg/Th17平衡的机制。方法收集ITP患儿(ITP组,20例)和健康儿童(对照组,20例)外周血并分离CD_(4)^(+)T细胞。采用实时荧光定量聚合酶链式反应法、Western blot法、酶联...目的探讨EBV mi R-BART17-3p影响原发免疫性血小板减少症(ITP)患儿Treg/Th17平衡的机制。方法收集ITP患儿(ITP组,20例)和健康儿童(对照组,20例)外周血并分离CD_(4)^(+)T细胞。采用实时荧光定量聚合酶链式反应法、Western blot法、酶联免疫吸附法检测EBV mi R-BART17-3p、T细胞免疫球蛋白黏蛋白3(Tim-3)、叉头框蛋白P3(Fox P3)、白细胞介素17A(IL-17A)和转化生长因子-β(TGF-β)的m RNA、蛋白表达水平及含量。采用双荧光素酶报告基因实验考察EBV mi R-BART17-3p对Tim-3表达水平的影响。将15只BALB/C小鼠随机分为空白对照组、模型组、观察组,各5只。腹腔注射抗血小板抗体MWReg30以复制ITP小鼠模型,建模4 d后观察组小鼠予尾静脉注射携带EBV mi R-BART17-3p inhibitor的腺病毒载体。细胞染色并观察形态,检测外周血中TGF-β、IL-17A含量及血小板计数,采用流式细胞仪分别检测CD_(4)^(+)T细胞中Th17和Treg水平,并计算二者百分比。结果与对照组比较,ITP组患儿外周血EBV mi R-BART17-3p表达水平显著升高,Tim-3和TGF-βm RNA表达水平显著降低(P<0.05);Tim-3 m RNA表达水平与EBV mi R-BART17-3p表达水平呈显著负相关(r=-0.732,P<0.001)。Tim-3慢病毒载体p LKO.1-sh-Tim-3(sh-Tim-3)可显著降低Tim-3、Fox P3、TGF-β水平(P<0.05)。mi R-BART17-3p mimic显著升高了CD_(4)^(+)T细胞中mi R-BART17-3p的表达水平,并显著降低了Tim-3、Fox P3、TGF-βm RNA和蛋白表达水平(P<0.05);mi R-BART17-3p mimic可显著降低TGF-β含量,Tim-3+mi R-BART17-3p过表达逆转了mi R-BART17-3p mimic对TGF-β的抑制作用。动物实验结果显示,沉默EBV mi R-BART17-3p可促进Treg分化,减少脾脏和骨髓组织中的巨核细胞计数,并显著增加外周血中血小板计数。结论EBV mi R-BART17-3p可通过Fox P3/Tim-3途径调节ITP患儿Treg/Th17的免疫失衡。展开更多
目的探讨T细胞免疫球蛋白和黏蛋白结构域分子3(T cell immunoglobulin and mucin domain protein 3,Tim-3)在晚期血吸虫病患者外周血CD56+自然杀伤细胞(NK细胞)表面的表达及其与肝纤维化指标的关系。方法采用流式细胞术检测28例临床晚...目的探讨T细胞免疫球蛋白和黏蛋白结构域分子3(T cell immunoglobulin and mucin domain protein 3,Tim-3)在晚期血吸虫病患者外周血CD56+自然杀伤细胞(NK细胞)表面的表达及其与肝纤维化指标的关系。方法采用流式细胞术检测28例临床晚期血吸虫病患者和30例健康者CD56+NK细胞表面Tim-3的表达,应用全自动化学发光免疫分析仪检测肝纤维化血清学三型前胶原N端肽(PIIIP N-P)、层黏连蛋白(LN)、IV型胶原(CIV)和透明质酸(HA)等4项指标,ELISA检测血清中γ-干扰素(IFN-γ)和白细胞介素-4(IL-4)水平,Fibroscan仪检测肝硬度值(LSM)反映肝纤维化程度。统计分析Tim-3表达水平与IL-4和IFN-γ水平、肝脏纤维化程度以及肝纤维化血清指标的相关性。结果流式细胞分析结果显示,晚期血吸虫病患者外周血CD56+NK细胞表面Tim-3表达水平为(62.3±11.4)%,高于健康对照组的(52.1±6.5)%(P<0.01)。晚期血吸虫病患者和健康对照组的PIIIP N-P水平分别为(86.5±29.5)ng/ml和(22.0±7.8)ng/ml,LN分别为(49.3±21.5)ng/ml和(20.4±6.3)ng/ml,CIV分别为(67.5±22.3)ng/ml和(22.0±3.9)ng/ml,HA分别为(645.9±483.1)ng/ml和(54.7±27.7)ng/ml,两组各指标差异均具有统计学意义(P<0.05)。晚期血吸虫病患者和健康对照组IFN-γ水平分别为(93.9±20.1)ng/L和(107.7±24.6)ng/L,IL-4分别为(46.6±11.8)ng/L和(28.9±8.9)ng/L,两组差异均具有统计学意义(P<0.05)。Spearman非参数相关分析结果显示患者CD56+NK细胞表达的Tim-3水平与患者肝纤维化指标LSM、PIIIP N-P、LN、CIV和IL-4水平呈正相关(r=0.528~0.834,P<0.01),与IFN-γ水平呈负相关(r=-0.501,P<0.01),而与HA水平无明显相关性(r=0.352,P>0.05)。结论晚期血吸虫病患者外周血CD56+NK细胞Tim-3表达呈上调,并与患者肝纤维化指标LSM、PIIIP N-P、LN、CIV和IL-4水平呈正相关。展开更多
基金Supported by Ningbo Science and Technology Program,No.2019A6-10312.
文摘BACKGROUND The effects of T-cell immunoglobulin mucin molecule-3(Tim-3),transforming growth factor β(TGF-β),and chemokine-12(CXCL12) expression on the prognosis of patients with diffuse large B-cell lymphoma(DLBCL) have not been elucidated.AIM To examine the correlation between Tim-3,TGF-β and CXCL12 expression and DLBCL prognosis.METHODS Lymph node tissues of 97 patients with DLBCL and 93 normal-response hyperplastic lymph node tissues treated from January 2017 to May 2019 were selected as the DLBCL and control groups,respectively.The expression of Tim-3,TGF-β,and CXCL12 was detected immunohistochemically.Patients were followed up for 3 years,and progression-free survival was recorded.Cox mult-ifactorial analysis was performed to analyze the risk factors for poor prognosis.RESULTS The positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in DLBCL tissues than in non-cancerous(control) tissues(P < 0.05).One-year postsurgery,the positive expression rates of Tim-3,TGF-β,and CXCL12 were higher in patients with effective treatment than in those with ineffective treatment(P < 0.05).The 3-year progression-free survival of 97 patients with DLBCL was 67.01%(65/97).Univariate analysis revealed that clinical stage,bone marrow infiltration,International Prognostic Index(IPI) score,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were associated with poor prognosis(P < 0.05).Multivariate Cox regression analysis demonstrated that clinical stage Ⅲ–Ⅳ,bone marrow infiltration,mediate-to-high-risk IPI scores,Tim-3 positivity,TGF-β positivity,and CXCL12 positivity were independent risk factors affecting prognosis(P < 0.05).CONCLUSION DLBCL tissues exhibit high positive expression of Tim-3,TGF-β,and CXCL12,and a high expression of all three indicates a poor prognosis.
文摘目的探讨EBV mi R-BART17-3p影响原发免疫性血小板减少症(ITP)患儿Treg/Th17平衡的机制。方法收集ITP患儿(ITP组,20例)和健康儿童(对照组,20例)外周血并分离CD_(4)^(+)T细胞。采用实时荧光定量聚合酶链式反应法、Western blot法、酶联免疫吸附法检测EBV mi R-BART17-3p、T细胞免疫球蛋白黏蛋白3(Tim-3)、叉头框蛋白P3(Fox P3)、白细胞介素17A(IL-17A)和转化生长因子-β(TGF-β)的m RNA、蛋白表达水平及含量。采用双荧光素酶报告基因实验考察EBV mi R-BART17-3p对Tim-3表达水平的影响。将15只BALB/C小鼠随机分为空白对照组、模型组、观察组,各5只。腹腔注射抗血小板抗体MWReg30以复制ITP小鼠模型,建模4 d后观察组小鼠予尾静脉注射携带EBV mi R-BART17-3p inhibitor的腺病毒载体。细胞染色并观察形态,检测外周血中TGF-β、IL-17A含量及血小板计数,采用流式细胞仪分别检测CD_(4)^(+)T细胞中Th17和Treg水平,并计算二者百分比。结果与对照组比较,ITP组患儿外周血EBV mi R-BART17-3p表达水平显著升高,Tim-3和TGF-βm RNA表达水平显著降低(P<0.05);Tim-3 m RNA表达水平与EBV mi R-BART17-3p表达水平呈显著负相关(r=-0.732,P<0.001)。Tim-3慢病毒载体p LKO.1-sh-Tim-3(sh-Tim-3)可显著降低Tim-3、Fox P3、TGF-β水平(P<0.05)。mi R-BART17-3p mimic显著升高了CD_(4)^(+)T细胞中mi R-BART17-3p的表达水平,并显著降低了Tim-3、Fox P3、TGF-βm RNA和蛋白表达水平(P<0.05);mi R-BART17-3p mimic可显著降低TGF-β含量,Tim-3+mi R-BART17-3p过表达逆转了mi R-BART17-3p mimic对TGF-β的抑制作用。动物实验结果显示,沉默EBV mi R-BART17-3p可促进Treg分化,减少脾脏和骨髓组织中的巨核细胞计数,并显著增加外周血中血小板计数。结论EBV mi R-BART17-3p可通过Fox P3/Tim-3途径调节ITP患儿Treg/Th17的免疫失衡。
