OBJECTIVE:To uncover the biological foundation of the prevailing TCM syndrome in individuals with Esophageal squamous cell carcinoma(ESCC),Zhengxu Xieshi(ZXXS),which is characterized by a deficiency in vital Qi and an...OBJECTIVE:To uncover the biological foundation of the prevailing TCM syndrome in individuals with Esophageal squamous cell carcinoma(ESCC),Zhengxu Xieshi(ZXXS),which is characterized by a deficiency in vital Qi and an excess in evil Qi.METHODS:We investigated shifts in vital Qi by quantifying systemic metabolic changes in the peripheral blood.Serum metabolomic profiling was conducted on the ESCC cohort 1 along with a matched healthy control cohort.Additionally,we assessed changes in evil Qi by examining metabolic perturbations in ESCC tissues.This analysis involved metabolomic and proteomic surveys of ESCC tissues and paired normal adjacent tissues as controls in an independent ESCC cohort 2.RESULTS:Serum metabolomic profiling highlighted the prevalent downregulation of differentially expressed metabolites in patient sera,in contrast to the upregulation observed in ESCC tissues,compared to their respective controls.Remarkably,the group of differential metabolites in the ESCC tissues was predominantly composed of amino acids.Thus,we focused on amino acid metabolism.Our integrative analysis showed the downregulation of a significant majority of disturbed amino acids in patient sera relative to the upregulation of an overwhelming proportion of perturbed amino acids within ESCC tissues.Enrichment analysis of these amino acids revealed seven metabolic pathways that contribute to the metabolism of antioxidants,energy intermediates,and biosynthetic precursors.Interestingly,these pathways displayed attenuation in patient sera but augmentation in ESCC tissues.Similarly,the proteomic data confirmed the activation of these pathways in ESCC tissues.CONCLUSION:This study presents a new perspective on the prevalence of ZXXS syndrome in patients with ESCC,contextualized within the realm of metabolic reprogramming.Specifically,diminished amino acid metabolism in the circulating blood corresponds to a deficiency in vital Qi.Conversely,hyperactive amino acid metabolism in ESCC tissues signifies an augmentation of local evil Qi.These findings hold potential to enrich the current medical framework and offer a deeper understanding of ESCC management by integrating the principles of ZXXS syndrome.展开更多
目的现代研究表明免疫细胞在缺血性中风(IS)发生发展过程中具有重要作用,当前对于中医正邪理论的内在机制尚未阐明,不少研究认为免疫细胞介导的免疫平衡可能是中医正邪理论的重要机制之一。利用孟德尔随机化(MR)分析验证免疫细胞对IS的...目的现代研究表明免疫细胞在缺血性中风(IS)发生发展过程中具有重要作用,当前对于中医正邪理论的内在机制尚未阐明,不少研究认为免疫细胞介导的免疫平衡可能是中医正邪理论的重要机制之一。利用孟德尔随机化(MR)分析验证免疫细胞对IS的因果关系,并进一步探讨正邪理论的内在机理。方法基于公开的遗传数据,将免疫细胞作为工具变量进行双样本MR分析,探索731个免疫细胞表型与IS患病风险之间的因果关系。将逆方差加权(IVW)方法作为主要方法用作标准分析,使用加权中位数、MR-Egger、Simple mode和Weighted mode作为补充,Cochrans Q检验异质性、MR-Egger截距检验测试水平多效性。结果经FDR校正后,发现仍有11个免疫细胞表型具有统计学意义(经FDR校正的p<0.05):其中CD27 on memory B cell、CD27 on sw mem、CD27 on CD24^(+)CD27^(+)、CD27 on IgD^(-)CD38^(dim)、CD27 on IgD^(-)CD38-、CD27 on IgD^(-)CD38br、CD25 on IgD^(+)和CD25 on IgD^(+)CD38^(dim)对IS的起危险作用;CD40 on CD14-CD16^(+)monocyte、CD40 on CD14^(+)CD16-monocyte、CD40 on CD14^(+)CD16^(+)monocyte对IS起保护作用。其中8个在B细胞组,3个在单核细胞组。以B细胞上的CD27、CD25和单核细胞上的CD40为显著。结论通过遗传学手段证实了免疫细胞在IS中发挥关键作用,为阐明正邪理论的内在机理提供一定的参考。展开更多
基金Supported by Natural Science Foundation-funded Project:Establishment of Syndrome-Disease Warning System and Investigation of the Clinical Features and Evolution Patterns of Traditional Chinese Medicine Syndromes in Esophageal Cancer under Modern Medical Diagnosis and Treatment(2023YFC3503200,2023YFC3503201)Biological Basis of the Pathogenesis of Cancer Toxin in Traditional Chinese Medicine(2022YFC3500200,2022YFC3500202)+12 种基金Natural Science Foundation-funded Project:Mechanistic Study of the Nucleolar Methyltransferase Fibrillarin to Promote Neoplastic Growth of Esophageal Squamous Cell Carcinoma via Activating Nucleoside Synthesis(No.32170778)Mechanistic Study of Renal Cancer Neoplastic Growth Driven by Glucose Transporter 5-Mediated Fructose Metabolism Reprogramming(No.31970708)Mechanistic Study of Methionine Cycle Modulating the Growth of Esophageal Squamous Cell Carcinoma through"DNA Methylation-DNA Stability-p53/p21-cell Cycle"Pathway(No.82002953)the Antitumor Mechanism of Oleanolic Acid via Autophagy by Regulating Adenosine Monophosphate-Activated Protein Kinase-Mammalian Target of Rapamycin-Unc51 Like Kinase 1 Pathway and Inhibiting Purine Salvage Pathway(No.82004177)USP14 Cooperates with Ubiquitin C-Terminal Hydrolase L5 to Regulate Constitutive Photomorphogenic 9 Signalosome-mediated Programmed Death-Ligand 1 Deubiquitination and Promote Immune Evasion in Hepatocellular Carcinoma.(No.81972214)National Scientific and Technological Major Special Project of China:Shuang Huang Sheng Bai Oral Liquid:Efficacy and Safety Evaluation of Traditional Chinese Medicine Compound Based on Systems Biology Approaches(2019ZX09201004-002-013)A special clinical research initiative for the health business sponsored by the Shanghai Municipal Health Commission(No.202040155)Shanghai Municipal Science and Technology Commissions Special Biomedical Technology Support Plan(No.20S31904100)Shanghai"Science and Technology Innovation Action Plan"Medical Innovation Research Project--Shanghai Clinical Research Center of Traditional Chinese Medicine Oncology(21MC1930500)Shanghai 13th Five-Year Plan Key Specialty of Traditional Chinese Medicine Oncology(shslczdzk03701)Tracking Programme for Eastern Scholar at Shanghai Institutions of Higher LearningShanghai High-level Talent Leadership Programme of Traditional Chinese Medicine[ZY(2021-2023)-0403]Scientific Research Project of Industry Development Center of Shanghai University of Traditional Chinese Medicine(602076D)。
文摘OBJECTIVE:To uncover the biological foundation of the prevailing TCM syndrome in individuals with Esophageal squamous cell carcinoma(ESCC),Zhengxu Xieshi(ZXXS),which is characterized by a deficiency in vital Qi and an excess in evil Qi.METHODS:We investigated shifts in vital Qi by quantifying systemic metabolic changes in the peripheral blood.Serum metabolomic profiling was conducted on the ESCC cohort 1 along with a matched healthy control cohort.Additionally,we assessed changes in evil Qi by examining metabolic perturbations in ESCC tissues.This analysis involved metabolomic and proteomic surveys of ESCC tissues and paired normal adjacent tissues as controls in an independent ESCC cohort 2.RESULTS:Serum metabolomic profiling highlighted the prevalent downregulation of differentially expressed metabolites in patient sera,in contrast to the upregulation observed in ESCC tissues,compared to their respective controls.Remarkably,the group of differential metabolites in the ESCC tissues was predominantly composed of amino acids.Thus,we focused on amino acid metabolism.Our integrative analysis showed the downregulation of a significant majority of disturbed amino acids in patient sera relative to the upregulation of an overwhelming proportion of perturbed amino acids within ESCC tissues.Enrichment analysis of these amino acids revealed seven metabolic pathways that contribute to the metabolism of antioxidants,energy intermediates,and biosynthetic precursors.Interestingly,these pathways displayed attenuation in patient sera but augmentation in ESCC tissues.Similarly,the proteomic data confirmed the activation of these pathways in ESCC tissues.CONCLUSION:This study presents a new perspective on the prevalence of ZXXS syndrome in patients with ESCC,contextualized within the realm of metabolic reprogramming.Specifically,diminished amino acid metabolism in the circulating blood corresponds to a deficiency in vital Qi.Conversely,hyperactive amino acid metabolism in ESCC tissues signifies an augmentation of local evil Qi.These findings hold potential to enrich the current medical framework and offer a deeper understanding of ESCC management by integrating the principles of ZXXS syndrome.
文摘目的现代研究表明免疫细胞在缺血性中风(IS)发生发展过程中具有重要作用,当前对于中医正邪理论的内在机制尚未阐明,不少研究认为免疫细胞介导的免疫平衡可能是中医正邪理论的重要机制之一。利用孟德尔随机化(MR)分析验证免疫细胞对IS的因果关系,并进一步探讨正邪理论的内在机理。方法基于公开的遗传数据,将免疫细胞作为工具变量进行双样本MR分析,探索731个免疫细胞表型与IS患病风险之间的因果关系。将逆方差加权(IVW)方法作为主要方法用作标准分析,使用加权中位数、MR-Egger、Simple mode和Weighted mode作为补充,Cochrans Q检验异质性、MR-Egger截距检验测试水平多效性。结果经FDR校正后,发现仍有11个免疫细胞表型具有统计学意义(经FDR校正的p<0.05):其中CD27 on memory B cell、CD27 on sw mem、CD27 on CD24^(+)CD27^(+)、CD27 on IgD^(-)CD38^(dim)、CD27 on IgD^(-)CD38-、CD27 on IgD^(-)CD38br、CD25 on IgD^(+)和CD25 on IgD^(+)CD38^(dim)对IS的起危险作用;CD40 on CD14-CD16^(+)monocyte、CD40 on CD14^(+)CD16-monocyte、CD40 on CD14^(+)CD16^(+)monocyte对IS起保护作用。其中8个在B细胞组,3个在单核细胞组。以B细胞上的CD27、CD25和单核细胞上的CD40为显著。结论通过遗传学手段证实了免疫细胞在IS中发挥关键作用,为阐明正邪理论的内在机理提供一定的参考。
