目的探讨针灸参与保护、修复造血微环境的可能作用机制。方法40只雄性KM种小鼠随机分为空白组(Con-trol)、模型组(CTX)、针刺干预组(Acu)、艾灸干预组(Mox),每组10只。CTX组、Acu组、Mox组腹腔注射环磷酰胺制备骨髓抑制模型,于造模后24...目的探讨针灸参与保护、修复造血微环境的可能作用机制。方法40只雄性KM种小鼠随机分为空白组(Con-trol)、模型组(CTX)、针刺干预组(Acu)、艾灸干预组(Mox),每组10只。CTX组、Acu组、Mox组腹腔注射环磷酰胺制备骨髓抑制模型,于造模后24h开始Acu组予以针刺干预、Mox组予以艾灸干预,Control、CTX组陪同固定,1次/d,连续5d。取各组小鼠骨髓组织提取RNA,进行高通量转录组测序、分析及Real-time PCR实验验证。结果CTX vs Control、Acu vs CTX、Mox vs CTX这3组转录本的交集差异基因有64个,其中具有较高节点热度的中心基因为CXCL12、VEGFA与KDR。与Control组比,CTX组骨髓组织中CXCL12 mRNA表达水平显著降低(P<0.05),CXCR4(CXCL12的受体)、VEGF、VEG-FR-2 mRNA表达水平显著升高(P<0.05);与CTX组比,Acu组、Mox组骨髓组织中CXCL12 mRNA表达水平显著升高(P<0.05),CXCR4、VEGF、VEGFR-2 mRNA表达水平显著下降(P<0.05);与Acu组相比,Mox组CXCL12、CXCR4、VEGF及VEGFR-2 mRNA表达水平无明显差异(P>0.05)。结论针灸缓解骨髓抑制的作用机制,可能与血管新生、正向调节骨髓基质细胞增殖等缓解、修复造血微环境损伤的生物过程有关。展开更多
Objective:Hepatocellular carcinoma(HCC)presents substantial genetic and phenotypic diversity,making it challenging to predict patient outcomes.There is a clear need for novel biomarkers to better identify high-risk in...Objective:Hepatocellular carcinoma(HCC)presents substantial genetic and phenotypic diversity,making it challenging to predict patient outcomes.There is a clear need for novel biomarkers to better identify high-risk individuals.Long non-coding RNAs(lncRNAs)are known to play key roles in cell cycle regulation and genomic stability,and their dysregulation has been closely linked to HCC progression.Developing a prognostic model based on cell cycle-related lncRNAs could open up new possibilities for immunotherapy in HCC patients.Methods:Transcriptomic data and clinical samples were obtained from the TCGA-HCC dataset.Cell cycle-related gene sets were sourced from existing studies,and coexpression analysis identified relevant lncRNAs(correlation coefficient>0.4,P<0.001).Univariate analysis identified prognostic lncRNAs,which were then used in a LASSO regression model to create a risk score.This model was validated via cross-validation.HCC samples were classified on the basis of their risk scores.Correlations between the risk score and tumor mutational burden(TMB),tumor immune infiltration,immune checkpoint gene expression,and immunotherapy response were evaluated via R packages and various methods(TIMER,CIBERSORT,CIBERSORT-ABS,QUANTISEQ,MCP-COUNTER,XCELL,and EPIC).Results:Four cell cycle-related lncRNAs(AC009549.1,AC090018.2,PKD1P6-NPIPP1,and TMCC1-AS1)were significantly upregulated in HCC.These lncRNAs were used to create a risk score(risk score=0.492×AC009549.1+1.390×AC090018.2+1.622×PKD1P6-NPIPP1+0.858×TMCC1-AS1).This risk score had superior predictive value compared to traditional clinical factors(AUC=0.738).A nomogram was developed to illustrate the 1-year,3-year,and 5-year overall survival(OS)rates for individual HCC patients.Significant differences in TMB,immune response,immune cell infiltration,immune checkpoint gene expression,and drug responsiveness were observed between the high-risk and low-risk groups.Conclusion:The risk score model we developed enhances the prognostication of HCC patients by identifying those at high risk for poor outcomes.This model could lead to new immunotherapy strategies for HCC patients.展开更多
文摘目的探讨针灸参与保护、修复造血微环境的可能作用机制。方法40只雄性KM种小鼠随机分为空白组(Con-trol)、模型组(CTX)、针刺干预组(Acu)、艾灸干预组(Mox),每组10只。CTX组、Acu组、Mox组腹腔注射环磷酰胺制备骨髓抑制模型,于造模后24h开始Acu组予以针刺干预、Mox组予以艾灸干预,Control、CTX组陪同固定,1次/d,连续5d。取各组小鼠骨髓组织提取RNA,进行高通量转录组测序、分析及Real-time PCR实验验证。结果CTX vs Control、Acu vs CTX、Mox vs CTX这3组转录本的交集差异基因有64个,其中具有较高节点热度的中心基因为CXCL12、VEGFA与KDR。与Control组比,CTX组骨髓组织中CXCL12 mRNA表达水平显著降低(P<0.05),CXCR4(CXCL12的受体)、VEGF、VEG-FR-2 mRNA表达水平显著升高(P<0.05);与CTX组比,Acu组、Mox组骨髓组织中CXCL12 mRNA表达水平显著升高(P<0.05),CXCR4、VEGF、VEGFR-2 mRNA表达水平显著下降(P<0.05);与Acu组相比,Mox组CXCL12、CXCR4、VEGF及VEGFR-2 mRNA表达水平无明显差异(P>0.05)。结论针灸缓解骨髓抑制的作用机制,可能与血管新生、正向调节骨髓基质细胞增殖等缓解、修复造血微环境损伤的生物过程有关。
文摘Objective:Hepatocellular carcinoma(HCC)presents substantial genetic and phenotypic diversity,making it challenging to predict patient outcomes.There is a clear need for novel biomarkers to better identify high-risk individuals.Long non-coding RNAs(lncRNAs)are known to play key roles in cell cycle regulation and genomic stability,and their dysregulation has been closely linked to HCC progression.Developing a prognostic model based on cell cycle-related lncRNAs could open up new possibilities for immunotherapy in HCC patients.Methods:Transcriptomic data and clinical samples were obtained from the TCGA-HCC dataset.Cell cycle-related gene sets were sourced from existing studies,and coexpression analysis identified relevant lncRNAs(correlation coefficient>0.4,P<0.001).Univariate analysis identified prognostic lncRNAs,which were then used in a LASSO regression model to create a risk score.This model was validated via cross-validation.HCC samples were classified on the basis of their risk scores.Correlations between the risk score and tumor mutational burden(TMB),tumor immune infiltration,immune checkpoint gene expression,and immunotherapy response were evaluated via R packages and various methods(TIMER,CIBERSORT,CIBERSORT-ABS,QUANTISEQ,MCP-COUNTER,XCELL,and EPIC).Results:Four cell cycle-related lncRNAs(AC009549.1,AC090018.2,PKD1P6-NPIPP1,and TMCC1-AS1)were significantly upregulated in HCC.These lncRNAs were used to create a risk score(risk score=0.492×AC009549.1+1.390×AC090018.2+1.622×PKD1P6-NPIPP1+0.858×TMCC1-AS1).This risk score had superior predictive value compared to traditional clinical factors(AUC=0.738).A nomogram was developed to illustrate the 1-year,3-year,and 5-year overall survival(OS)rates for individual HCC patients.Significant differences in TMB,immune response,immune cell infiltration,immune checkpoint gene expression,and drug responsiveness were observed between the high-risk and low-risk groups.Conclusion:The risk score model we developed enhances the prognostication of HCC patients by identifying those at high risk for poor outcomes.This model could lead to new immunotherapy strategies for HCC patients.
