目的观察六味地黄丸对狼疮肾炎患者糖基化终末产物受体(receptor for advanced glycation end products,RAGE)、单核细胞趋化蛋白1及趋化因子Fractalkine水平的影响,探讨六味地黄丸用于狼疮肾炎的临床疗效,以期为临床上狼疮肾炎的治疗...目的观察六味地黄丸对狼疮肾炎患者糖基化终末产物受体(receptor for advanced glycation end products,RAGE)、单核细胞趋化蛋白1及趋化因子Fractalkine水平的影响,探讨六味地黄丸用于狼疮肾炎的临床疗效,以期为临床上狼疮肾炎的治疗提供参考。方法收集大连大学附属中山医院2014年9月至2016年9月肾内科门诊收治的狼疮肾炎患者46例,其中男性25例,女性21例,按照随机数字表法原则分为观察组和对照组,每组23例,其中对照组给予甲泼尼龙0.5 g/d静脉滴注3 d后口服泼尼松片(0.6 mg·kg^(-1)·d^(-1))治疗,8周后逐渐减量至10 mg/d维持治疗;观察组在常规西医治疗的基础上给予浓缩六味地黄丸辅助治疗,8丸/次,3次/日,均进行8个疗程(16 d为一个疗程)治疗。分别比较2组患者治疗前、后糖基化终末产物受体、单核细胞趋化蛋白1及趋化因子Fractalkine水平以及2组患者的临床疗效进行观察。结果与对照组临床疗效相比,六味地黄丸观察组总有效率为78.3%,高于对照组的70.0%(P<0.05);与对照组治疗后相比,观察组治疗后糖基化终末产物受体、单核细胞趋化蛋白1、趋化因子Fractalkine水平显著低于对照组(P<0.05)。结论六味地黄丸辅助常规西药治疗狼疮肾炎能够降低糖基化终末产物受体、单核细胞趋化蛋白1以及趋化因子Fractalkine的表达,提示六味地黄丸能够通过减轻狼疮肾炎的相关指标对狼疮肾炎具有治疗作用,值得临床进一步推广。展开更多
The anti-tumor effect of anti-PD-1 antibody has long been shown to be strongly related to the tumor immune microenvironment(TIME).This study aimed to mechanistically assess whether Chang Wei Qing(CWQ)Decoction can enh...The anti-tumor effect of anti-PD-1 antibody has long been shown to be strongly related to the tumor immune microenvironment(TIME).This study aimed to mechanistically assess whether Chang Wei Qing(CWQ)Decoction can enhance the anti-tumor effect of PD-1 inhibitor therapy.PD-1 inhibitor therapy showed the significant anti-tumor effect in patients with mismatch repairdeficient/microsatellite instability-high(dMMR/MSI-H)colorectal cancer(CRC),rather than those with mismatch repairproficient/microsatellite stable(pMMR/MSS)CRC.Hence,immunofluorescence double-label staining was utilized to explore the difference in the TIME between dMMR/MSI-H and pMMR/MSS CRC patients.Flow cytometry was used to analyze T-lymphocytes in tumors from mice.Western blot was used to measure the expression of PD-L1 protein in mouse tumors.The intestinal mucosal barrier of mice was evaluated by hematoxylin-eosin staining and immunohistochemistry.16S rRNA-gene sequencing was used to examine the structure of the gut microbiota in mice.Subsequently,Spearman’s correlation analysis was used to analyze the relationship between the gut microbiota and tumor-infiltrating T-lymphocytes.The results showed that dMMR/MSI-H CRC patients had more CD8+T cells and higher expression of PD-1 and PD-L1 proteins.In vivo,CWQ enhanced the anti-tumor effect of anti-PD-1 antibody and increased the infiltration of CD8+and PD-1+CD8+T cells in tumors.Additionally,the combination of CWQ with anti-PD-1 antibody resulted in lower inflammation in the intestinal mucosa than that induced by anti-PD-1 antibody alone.CWQ and anti-PD-1 antibody co-treatment upregulated PD-L1 protein and reduced the abundance of Bacteroides in the gut microbiota but increased the abundance of Akkermansia,Firmicutes,and Actinobacteria.Additionally,the proportion of infiltrated CD8+PD-1+,CD8+,and CD3+T cells were found to be positively correlated with the abundance of Akkermansia.Accordingly,CWQ may modulate the TIME by modifying the gut microbiota and consequently enhance the anti-tumor effect of PD-1 inhibitor therapy.展开更多
基金the Health System Innovation Project of Shanghai Putuo Science and Technology Commission(No.ptkwws202002)the Traditional Chinese Medicine Clinical Key Specialty Construction Project of Shanghai Putuo District(No.ptzyzk2101)the Clinical Specialized Discipline of Health System of Putuo District in Shanghai(No.2021tszk01).
文摘The anti-tumor effect of anti-PD-1 antibody has long been shown to be strongly related to the tumor immune microenvironment(TIME).This study aimed to mechanistically assess whether Chang Wei Qing(CWQ)Decoction can enhance the anti-tumor effect of PD-1 inhibitor therapy.PD-1 inhibitor therapy showed the significant anti-tumor effect in patients with mismatch repairdeficient/microsatellite instability-high(dMMR/MSI-H)colorectal cancer(CRC),rather than those with mismatch repairproficient/microsatellite stable(pMMR/MSS)CRC.Hence,immunofluorescence double-label staining was utilized to explore the difference in the TIME between dMMR/MSI-H and pMMR/MSS CRC patients.Flow cytometry was used to analyze T-lymphocytes in tumors from mice.Western blot was used to measure the expression of PD-L1 protein in mouse tumors.The intestinal mucosal barrier of mice was evaluated by hematoxylin-eosin staining and immunohistochemistry.16S rRNA-gene sequencing was used to examine the structure of the gut microbiota in mice.Subsequently,Spearman’s correlation analysis was used to analyze the relationship between the gut microbiota and tumor-infiltrating T-lymphocytes.The results showed that dMMR/MSI-H CRC patients had more CD8+T cells and higher expression of PD-1 and PD-L1 proteins.In vivo,CWQ enhanced the anti-tumor effect of anti-PD-1 antibody and increased the infiltration of CD8+and PD-1+CD8+T cells in tumors.Additionally,the combination of CWQ with anti-PD-1 antibody resulted in lower inflammation in the intestinal mucosa than that induced by anti-PD-1 antibody alone.CWQ and anti-PD-1 antibody co-treatment upregulated PD-L1 protein and reduced the abundance of Bacteroides in the gut microbiota but increased the abundance of Akkermansia,Firmicutes,and Actinobacteria.Additionally,the proportion of infiltrated CD8+PD-1+,CD8+,and CD3+T cells were found to be positively correlated with the abundance of Akkermansia.Accordingly,CWQ may modulate the TIME by modifying the gut microbiota and consequently enhance the anti-tumor effect of PD-1 inhibitor therapy.
