目的探讨T细胞免疫球蛋白黏蛋白分子(Tim-3)及半乳糖凝集素-9(Galectin-9)的表达与肿瘤T细胞免疫在鼻咽癌中的临床意义。方法在癌症基因组图谱计划(The Cancer Genome Atlas,TCGA)数据库中查找Tim-3在各种肿瘤组织中的表达情况,选取与...目的探讨T细胞免疫球蛋白黏蛋白分子(Tim-3)及半乳糖凝集素-9(Galectin-9)的表达与肿瘤T细胞免疫在鼻咽癌中的临床意义。方法在癌症基因组图谱计划(The Cancer Genome Atlas,TCGA)数据库中查找Tim-3在各种肿瘤组织中的表达情况,选取与鼻咽癌患者免疫密切相关的基因Tim-3及其配体Galectin-9作为研究基因;收集2018年3月~2022年3月广西壮族自治区民族医院收治的65例鼻咽癌患者的肿瘤组织、同期65例鼻咽部炎性标本组织及对应鼻咽癌患者放疗前后应用免疫细胞病理芯片技术检测的外周血T细胞亚群变化的数据,并做随访观察。结果生物信息学分析TCGA数据库中鼻咽癌的测序数据,结果显示,Tim-3在大部分肿瘤组织中呈高表达,在鼻咽癌组织中较癌旁正常组织表达水平显著上调,Tim-3及其配体Galectin-9在癌组织中的表达呈正相关;免疫组化结果显示,鼻咽癌组织中Tim-3和Galectin-9的表达水平均显著高于鼻咽部炎性组织(P<0.05);鼻咽癌组织中Tim-3和Galectin-9高表达与淋巴结受累(P<0.05)以及更晚的TNM分期(P<0.05)紧密相关;Tim-3和Galectin-9的表达水平与患者年龄、性别及EB病毒感染等因素无关(P>0.05);Tim-3和Galectin-9在鼻咽癌中的表达呈正相关(r=0.313,P=0.011);随访发现,Tim-3和Galectin-9的高表达可能与鼻咽癌的不良预后相关;鼻咽癌患者放疗前3天和放疗后7天的T淋巴细胞亚群检测显示,CD4+、CD4+/CD8+较放疗前显著下降(P<0.05),CD3+与CD8+变化差异无统计学意义(P>0.05);Tim-3和Galectin-9蛋白阳性组患者放疗敏感度明显高于于Tim-3和Galectin-9阴性组(P<0.05)。结论Tim-3/Galectin-9信号通路在鼻咽癌发生、发展和转移中起重要作用,T细胞免疫在鼻咽癌治疗中发挥重要作用。联合检测鼻咽癌组织中Tim-3和Galectin-9及T细胞亚群的变化可能为临床评估肿瘤监测病情及肿瘤免疫治疗提供新参数。展开更多
Currently,the BeiDou⁃3(BDS⁃3)precise point positioning(PPP)service(PPP⁃B2b)mostly employs the ionosphere⁃free(IF)combination model for precise timing,which tends to amplify the noise in observation values.To address t...Currently,the BeiDou⁃3(BDS⁃3)precise point positioning(PPP)service(PPP⁃B2b)mostly employs the ionosphere⁃free(IF)combination model for precise timing,which tends to amplify the noise in observation values.To address this issue,this paper proposes a real⁃time BDS⁃3 precise unidirectional timing model based on uncombined(UC)observations using the BDS⁃3 PPP⁃B2b service.This model resolves the challenge of the amplified observation noise inherent in the IF combination model.The experiment involved selecting eight global navigation satellite system(GNSS)observation stations within China and collecting continuous observation data for 15 d.A comparative analy⁃sis with the traditional dual⁃frequency IF combination PPP timing model showed that the BDS⁃3 UC PPP timing based on the BDS⁃3 PPP⁃B2b service can achieve a timing preci⁃sion of 0.5 ns.In addition,it was found that due to global positioning system(GPS)satellite clock products in the BDS⁃3 PPP⁃B2b service not being unified to the standard time,the GPS IF PPP timing method based on the BDS⁃3 PPP⁃B2b service is not recommended for precise timing.In summary,the BDS⁃3 UC PPP timing model proposed in this paper is suitable for precise timing,providing observa⁃tion values with smaller noise,and its timing accuracy is comparable to that of the BDS⁃3 IF PPP,with slightly better frequency stability.展开更多
目的:评估PD1抑制剂(帕博利珠单抗)联合Tim3抑制剂(TSR-022)在复发/难治性多发性骨髓瘤(R/R MM)中的疗效及安全性。方法:纳入2023年1月至2025年3月确诊的120例R/R MM患者,随机分为观察组(PD1+T i m 3抑制剂,n=60)和对照组(标准挽救化疗,...目的:评估PD1抑制剂(帕博利珠单抗)联合Tim3抑制剂(TSR-022)在复发/难治性多发性骨髓瘤(R/R MM)中的疗效及安全性。方法:纳入2023年1月至2025年3月确诊的120例R/R MM患者,随机分为观察组(PD1+T i m 3抑制剂,n=60)和对照组(标准挽救化疗,n=60)。主要终点为总体缓解率(ORR),次要终点包括无进展生存期(PFS)、总生存期(OS)及不良反应。结果:观察组ORR显著高于对照组(P<0.05)。观察组3级以上AE发生率显著低于对照组(P<0.05)。治疗后观察组外周血PD1+Tim3+T细胞比例从基线42.3%降至12.5%(P<0.05),且下降幅度与ORR呈正相关(r=0.62,P=0.003)。结论:PD1联合Tim3抑制剂可显著提升R/R MM患者的缓解率及生存获益,安全性可控,为免疫检查点抑制剂联合治疗提供了新证据。展开更多
文摘目的探讨T细胞免疫球蛋白黏蛋白分子(Tim-3)及半乳糖凝集素-9(Galectin-9)的表达与肿瘤T细胞免疫在鼻咽癌中的临床意义。方法在癌症基因组图谱计划(The Cancer Genome Atlas,TCGA)数据库中查找Tim-3在各种肿瘤组织中的表达情况,选取与鼻咽癌患者免疫密切相关的基因Tim-3及其配体Galectin-9作为研究基因;收集2018年3月~2022年3月广西壮族自治区民族医院收治的65例鼻咽癌患者的肿瘤组织、同期65例鼻咽部炎性标本组织及对应鼻咽癌患者放疗前后应用免疫细胞病理芯片技术检测的外周血T细胞亚群变化的数据,并做随访观察。结果生物信息学分析TCGA数据库中鼻咽癌的测序数据,结果显示,Tim-3在大部分肿瘤组织中呈高表达,在鼻咽癌组织中较癌旁正常组织表达水平显著上调,Tim-3及其配体Galectin-9在癌组织中的表达呈正相关;免疫组化结果显示,鼻咽癌组织中Tim-3和Galectin-9的表达水平均显著高于鼻咽部炎性组织(P<0.05);鼻咽癌组织中Tim-3和Galectin-9高表达与淋巴结受累(P<0.05)以及更晚的TNM分期(P<0.05)紧密相关;Tim-3和Galectin-9的表达水平与患者年龄、性别及EB病毒感染等因素无关(P>0.05);Tim-3和Galectin-9在鼻咽癌中的表达呈正相关(r=0.313,P=0.011);随访发现,Tim-3和Galectin-9的高表达可能与鼻咽癌的不良预后相关;鼻咽癌患者放疗前3天和放疗后7天的T淋巴细胞亚群检测显示,CD4+、CD4+/CD8+较放疗前显著下降(P<0.05),CD3+与CD8+变化差异无统计学意义(P>0.05);Tim-3和Galectin-9蛋白阳性组患者放疗敏感度明显高于于Tim-3和Galectin-9阴性组(P<0.05)。结论Tim-3/Galectin-9信号通路在鼻咽癌发生、发展和转移中起重要作用,T细胞免疫在鼻咽癌治疗中发挥重要作用。联合检测鼻咽癌组织中Tim-3和Galectin-9及T细胞亚群的变化可能为临床评估肿瘤监测病情及肿瘤免疫治疗提供新参数。
基金The Basic Science Center Project of the National Natural Science Foundation of China(No.42388102)the Jiangsu Province Natural Resources Science and Technology Project(No.JSZRKJ202404).
文摘Currently,the BeiDou⁃3(BDS⁃3)precise point positioning(PPP)service(PPP⁃B2b)mostly employs the ionosphere⁃free(IF)combination model for precise timing,which tends to amplify the noise in observation values.To address this issue,this paper proposes a real⁃time BDS⁃3 precise unidirectional timing model based on uncombined(UC)observations using the BDS⁃3 PPP⁃B2b service.This model resolves the challenge of the amplified observation noise inherent in the IF combination model.The experiment involved selecting eight global navigation satellite system(GNSS)observation stations within China and collecting continuous observation data for 15 d.A comparative analy⁃sis with the traditional dual⁃frequency IF combination PPP timing model showed that the BDS⁃3 UC PPP timing based on the BDS⁃3 PPP⁃B2b service can achieve a timing preci⁃sion of 0.5 ns.In addition,it was found that due to global positioning system(GPS)satellite clock products in the BDS⁃3 PPP⁃B2b service not being unified to the standard time,the GPS IF PPP timing method based on the BDS⁃3 PPP⁃B2b service is not recommended for precise timing.In summary,the BDS⁃3 UC PPP timing model proposed in this paper is suitable for precise timing,providing observa⁃tion values with smaller noise,and its timing accuracy is comparable to that of the BDS⁃3 IF PPP,with slightly better frequency stability.
文摘目的:评估PD1抑制剂(帕博利珠单抗)联合Tim3抑制剂(TSR-022)在复发/难治性多发性骨髓瘤(R/R MM)中的疗效及安全性。方法:纳入2023年1月至2025年3月确诊的120例R/R MM患者,随机分为观察组(PD1+T i m 3抑制剂,n=60)和对照组(标准挽救化疗,n=60)。主要终点为总体缓解率(ORR),次要终点包括无进展生存期(PFS)、总生存期(OS)及不良反应。结果:观察组ORR显著高于对照组(P<0.05)。观察组3级以上AE发生率显著低于对照组(P<0.05)。治疗后观察组外周血PD1+Tim3+T细胞比例从基线42.3%降至12.5%(P<0.05),且下降幅度与ORR呈正相关(r=0.62,P=0.003)。结论:PD1联合Tim3抑制剂可显著提升R/R MM患者的缓解率及生存获益,安全性可控,为免疫检查点抑制剂联合治疗提供了新证据。
