Dear Editor,Psoriasis is increasingly recognized as a systemic inflammatory disease associated with several comorbidities,including metabolic syndrome,depression,and malignancies[1].Colorectal cancer(CRC)is the third ...Dear Editor,Psoriasis is increasingly recognized as a systemic inflammatory disease associated with several comorbidities,including metabolic syndrome,depression,and malignancies[1].Colorectal cancer(CRC)is the third most common cancer worldwide and ranks second in mortality among all malignancies.Currently,it has become one of the most severe challenges faced by healthcare systems in many countries[2].A previous study has found that patients with psoriasis have a significantly increased risk of developing CRC[3].展开更多
Objectives:The mechanism by which specific tumor subsets in colorectal cancer(CRC)use alternative metabolic pathways,particularly those modulated by hypoxia and fructose,to alter the tumor microenvironment(TME)remains...Objectives:The mechanism by which specific tumor subsets in colorectal cancer(CRC)use alternative metabolic pathways,particularly those modulated by hypoxia and fructose,to alter the tumor microenvironment(TME)remains unclear.This study aimed to identify these malignant subpopulations and characterize their intercellular signaling networks and spatial organization through an integrative multi-omics approach.Methods:Leveraging bulk datasets,single-cell RNA sequencing,and integrative spatial transcriptomics,we developed a prognostic model based on hypoxia-and fructose metabolism-related genes(HFGs)to delineate tumor cell subpopulations and their intercellular signaling networks.Results:We identified a specific subset of stanniocalcin-2 positive(STC2+)malignant cells spatially enriched within tumor regions and strongly associated with poor prognosis.This subset served as a key signaling hub in the TME,exhibiting increased epithelial–mesenchymal transition activity.STC2+cells engage in two spatially organized ligand–receptor interactions:the growth differentiation factor 15(GDF15)—transforming growth factor beta receptor 2(TGFBR2)pathway targeting endothelial cells and the migration inhibitory factor(MIF)—(cluster of differentiation 74[CD74]+C-X-C motif chemokine receptor 4[CXCR4])pathway targeting macrophages.Conclusion:This study identified a malignant cell state in CRC that is metabolically defined and spatially limited,including liver metastases,and is characterized by elevated STC2 expression and active immune-stromal interactions.Given the interplay between metabolic reprogramming and TME remodeling,STC2+malignant cells are a functionally significant subpopulation and a potential therapeutic target.展开更多
目的:本研究基于前列腺癌、肺癌、CRC和卵巢癌筛查试验(PLCO)的数据,探讨了维生素(Vit) B族亚型(VitB2、B3、B6、B9和B12)摄入量与结直肠癌(CRC)及其不同亚部位发病风险之间的关系。方法:研究纳入98,400名年龄在55至74岁之间的男性和女...目的:本研究基于前列腺癌、肺癌、CRC和卵巢癌筛查试验(PLCO)的数据,探讨了维生素(Vit) B族亚型(VitB2、B3、B6、B9和B12)摄入量与结直肠癌(CRC)及其不同亚部位发病风险之间的关系。方法:研究纳入98,400名年龄在55至74岁之间的男性和女性,使用Cox回归模型评估了Vit摄入量与CRC发病率之间的关联。结果:研究发现,维生素B族亚型摄入量与CRC发病率显著负相关,且作用在不同亚部位表现出差异性。例如,VitB2和VitB6对直肠癌的保护作用显著,VitB9和VitB12则显著降低近端结肠癌的风险。此外,研究还揭示了BMI对Vit保护作用的调节效应,VitB6对BMI较低人群具有更强的保护作用,而VitB9在BMI较高人群中的保护作用更加显著。不吸烟人群中VitB9的保护作用也得到了进一步确认。补充剂来源的VitB9和VitB12与CRC风险显著负相关,而饮食来源的VitB2、B3和B6未表现出显著影响。结论:研究发现支持了VitB族在CRC预防中的潜在作用,并强调了个性化营养干预的重要性,并为CRC的预防策略和健康政策提供了重要依据。Objective: This study, based on data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), explored the relationship between the intake of B-vitamin subtypes (VitB2, B3, B6, B9, and B12) and the risk of colorectal cancer (CRC) and its various subsite incidences. Methods: The study included 98,400 men and women aged 55 to 74. Cox regression models were used to assess the association between vitamin intake and CRC incidence. Results: The study found a significant negative correlation between B-vitamin intake and CRC incidence, with varying effects across different subsites. For instance, VitB2 and VitB6 were significantly protective against rectal cancer, while VitB9 and VitB12 were significantly associated with reduced risk of proximal colon cancer. Additionally, the study revealed a moderating effect of BMI on the protective role of vitamins. VitB6 showed stronger protective effects in individuals with lower BMI, while VitB9 exhibited a more pronounced protective effect in those with higher BMI. The protective effect of VitB9 in non-smokers has also been further confirmed. Supplement-derived VitB9 and VitB12 were significantly negatively associated with CRC risk, while dietary VitB2, B3, and B6 showed no significant effects. Conclusion: The study supports the potential role of B-vitamins in CRC prevention, emphasizing the importance of personalized nutritional interventions. It provides crucial evidence for CRC prevention strategies and health policies.展开更多
Dear Editor,This letter presents an improved repetitive controller(IRC) that uses a complex-coefficient filter to enhance the tracking performance of a system for periodic signals. Compared with the low-pass filter us...Dear Editor,This letter presents an improved repetitive controller(IRC) that uses a complex-coefficient filter to enhance the tracking performance of a system for periodic signals. Compared with the low-pass filter used in the conventional repetitive controller(CRC), the complex-coefficient filter causes less change in the phase and amplitude of a signal at the frequencies of the periodic signal, especially at the fundamental frequency, when the two filters have the same cutofffrequency.展开更多
Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its wid...Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse reactions.Venetoclax,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against CRC.This study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating CRC.Methods and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against tumors.Then we employed various techniques to evaluate different aspects of the experimental outcomes.Immunohistochemistry was used to detect cell proliferation and angiogenesis in tumor tissues.Western blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor tissues.Moreover,immunofluorescence was employed to measure cytokine levels.Results:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug use.Venetoclax was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell infiltration.Conclusion:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune microenvironment.Our study presents the justification for utilizing the fruquintinib and venetoclax combination in treating CRC.Venetoclax holds promise in being assimilated into anticancer medications for CRC.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82373475).
文摘Dear Editor,Psoriasis is increasingly recognized as a systemic inflammatory disease associated with several comorbidities,including metabolic syndrome,depression,and malignancies[1].Colorectal cancer(CRC)is the third most common cancer worldwide and ranks second in mortality among all malignancies.Currently,it has become one of the most severe challenges faced by healthcare systems in many countries[2].A previous study has found that patients with psoriasis have a significantly increased risk of developing CRC[3].
基金supported by the Joint Project of the Chongqing Science and Technology Commission(2025MSXM040).
文摘Objectives:The mechanism by which specific tumor subsets in colorectal cancer(CRC)use alternative metabolic pathways,particularly those modulated by hypoxia and fructose,to alter the tumor microenvironment(TME)remains unclear.This study aimed to identify these malignant subpopulations and characterize their intercellular signaling networks and spatial organization through an integrative multi-omics approach.Methods:Leveraging bulk datasets,single-cell RNA sequencing,and integrative spatial transcriptomics,we developed a prognostic model based on hypoxia-and fructose metabolism-related genes(HFGs)to delineate tumor cell subpopulations and their intercellular signaling networks.Results:We identified a specific subset of stanniocalcin-2 positive(STC2+)malignant cells spatially enriched within tumor regions and strongly associated with poor prognosis.This subset served as a key signaling hub in the TME,exhibiting increased epithelial–mesenchymal transition activity.STC2+cells engage in two spatially organized ligand–receptor interactions:the growth differentiation factor 15(GDF15)—transforming growth factor beta receptor 2(TGFBR2)pathway targeting endothelial cells and the migration inhibitory factor(MIF)—(cluster of differentiation 74[CD74]+C-X-C motif chemokine receptor 4[CXCR4])pathway targeting macrophages.Conclusion:This study identified a malignant cell state in CRC that is metabolically defined and spatially limited,including liver metastases,and is characterized by elevated STC2 expression and active immune-stromal interactions.Given the interplay between metabolic reprogramming and TME remodeling,STC2+malignant cells are a functionally significant subpopulation and a potential therapeutic target.
文摘目的:本研究基于前列腺癌、肺癌、CRC和卵巢癌筛查试验(PLCO)的数据,探讨了维生素(Vit) B族亚型(VitB2、B3、B6、B9和B12)摄入量与结直肠癌(CRC)及其不同亚部位发病风险之间的关系。方法:研究纳入98,400名年龄在55至74岁之间的男性和女性,使用Cox回归模型评估了Vit摄入量与CRC发病率之间的关联。结果:研究发现,维生素B族亚型摄入量与CRC发病率显著负相关,且作用在不同亚部位表现出差异性。例如,VitB2和VitB6对直肠癌的保护作用显著,VitB9和VitB12则显著降低近端结肠癌的风险。此外,研究还揭示了BMI对Vit保护作用的调节效应,VitB6对BMI较低人群具有更强的保护作用,而VitB9在BMI较高人群中的保护作用更加显著。不吸烟人群中VitB9的保护作用也得到了进一步确认。补充剂来源的VitB9和VitB12与CRC风险显著负相关,而饮食来源的VitB2、B3和B6未表现出显著影响。结论:研究发现支持了VitB族在CRC预防中的潜在作用,并强调了个性化营养干预的重要性,并为CRC的预防策略和健康政策提供了重要依据。Objective: This study, based on data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), explored the relationship between the intake of B-vitamin subtypes (VitB2, B3, B6, B9, and B12) and the risk of colorectal cancer (CRC) and its various subsite incidences. Methods: The study included 98,400 men and women aged 55 to 74. Cox regression models were used to assess the association between vitamin intake and CRC incidence. Results: The study found a significant negative correlation between B-vitamin intake and CRC incidence, with varying effects across different subsites. For instance, VitB2 and VitB6 were significantly protective against rectal cancer, while VitB9 and VitB12 were significantly associated with reduced risk of proximal colon cancer. Additionally, the study revealed a moderating effect of BMI on the protective role of vitamins. VitB6 showed stronger protective effects in individuals with lower BMI, while VitB9 exhibited a more pronounced protective effect in those with higher BMI. The protective effect of VitB9 in non-smokers has also been further confirmed. Supplement-derived VitB9 and VitB12 were significantly negatively associated with CRC risk, while dietary VitB2, B3, and B6 showed no significant effects. Conclusion: The study supports the potential role of B-vitamins in CRC prevention, emphasizing the importance of personalized nutritional interventions. It provides crucial evidence for CRC prevention strategies and health policies.
基金supported in part by the National Natural Science Foundation of China(61873348,6230 3266,62273200)JSPS(Japan Society for the Promotion of Science) KAKENHI(22H03998,23K25252)
文摘Dear Editor,This letter presents an improved repetitive controller(IRC) that uses a complex-coefficient filter to enhance the tracking performance of a system for periodic signals. Compared with the low-pass filter used in the conventional repetitive controller(CRC), the complex-coefficient filter causes less change in the phase and amplitude of a signal at the frequencies of the periodic signal, especially at the fundamental frequency, when the two filters have the same cutofffrequency.
基金supported by the National Natural Science Foundation of China(82072675,82273197,82173933)Fundamental Research Funds for the Central Universities(020814380160).
文摘Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse reactions.Venetoclax,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against CRC.This study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating CRC.Methods and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against tumors.Then we employed various techniques to evaluate different aspects of the experimental outcomes.Immunohistochemistry was used to detect cell proliferation and angiogenesis in tumor tissues.Western blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor tissues.Moreover,immunofluorescence was employed to measure cytokine levels.Results:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug use.Venetoclax was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell infiltration.Conclusion:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune microenvironment.Our study presents the justification for utilizing the fruquintinib and venetoclax combination in treating CRC.Venetoclax holds promise in being assimilated into anticancer medications for CRC.
