目的 研究妊娠期糖尿病(GDM)患者血清C-C基序趋化因子配体2(CCL2)、脂质运载蛋白-2(LCN2)水平与糖脂代谢及胰岛素抵抗的相关性。方法 回顾性选取2021年6月至2023年6月在苏州大学附属张家港医院确诊的98例GDM患者作为病例组,选择同期来院...目的 研究妊娠期糖尿病(GDM)患者血清C-C基序趋化因子配体2(CCL2)、脂质运载蛋白-2(LCN2)水平与糖脂代谢及胰岛素抵抗的相关性。方法 回顾性选取2021年6月至2023年6月在苏州大学附属张家港医院确诊的98例GDM患者作为病例组,选择同期来院的98名健康妊娠孕妇作为对照组。收集两组孕妇的一般临床资料[孕周、孕次、孕前身体质量指数(BMI)、收缩压、舒张压、总胆固醇、甘油三酯、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FBG)、餐后1 h血糖(1 h PG)、餐后2 h血糖(2 h PG)、空腹胰岛素(FINS)、糖化血红蛋白(GHb)、稳态模型评估胰岛素抵抗指数(HOMA-IR)];比较对照组和病例组血清CCL2和LCN2表达水平;采用多因素Logistic回归分析对影响GDM的因素进行分析;采用Pearson相关性分析对血清CCL2和LCN2与糖脂代谢及胰岛素抵抗相关指标的相关性进行分析;采用受试者操作特征(ROC)曲线分析血清标志物CCL2、LCN2对GDM患者的诊断价值。结果 两组孕妇的年龄、孕周、孕次等比较,差异均无统计学意义(P > 0.05)。病例组的甘油三酯、总胆固醇、LDL-C、FBG、1 h PG、2 h PG、GHb、FINS、HOMA-IR均显著高于对照组,HDL-C显著低于对照组,差异均有统计学意义(P<0.05)。病例组的血清CCL2、LCN2水平分别为(32.46±6.87)、(23.61±6.26) pg/mL,均显著高于对照组[(26.31±4.37)、(16.78±4.34) pg/m L],差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,血清LDL-C、FINS、甘油三酯、总胆固醇、HOMA-IR、CCL2、LCN2均为GDM的危险因素(P<0.05),而HDL-C是GDM的保护因素(P<0.05)。Pearson相关性分析结果显示,血清CCL2、LCN2水平与FBG、1 h PG、2 h PG、FINS、LDL-C、Hb Alc、甘油三酯、总胆固醇、HOMA-IR均呈正相关(P<0.05),与HDL-C呈负相关(P<0.05)。血清CCL2、LCN2二者联合诊断GDM患者的曲线下面积(AUC)最高,显著高于CCL2、LCN2单独诊断(P<0.05)。结论 GDM患者血清中CCL2和LCN2的表达水平均明显升高,二者与糖脂代谢紊乱和胰岛素抵抗存在密切关联,可作为临床诊断GDM的指标。展开更多
Objective:This study aimed at exploring the effects of the epigenetic regulator,chidamide,on reprogramming the immunosuppressive tumor microenvironment in small cell lung cancer(SCLC),particularly the roles in macroph...Objective:This study aimed at exploring the effects of the epigenetic regulator,chidamide,on reprogramming the immunosuppressive tumor microenvironment in small cell lung cancer(SCLC),particularly the roles in macrophage polarization and angiogenesis.The therapeutic efficacy of combining chidamide with the anti-angiogenic agent,anlotinib,for refractory SCLC was also evaluated.Methods:RNA sequencing and functional validation were performed to assess chidamide’s effects on macrophages.Signal transducer and activator of transcription 4(STAT4)-mediated transcriptional activation of CCL2 was confirmed with ChIP-qPCR.The synergistic efficacy of chidamide in combination with anlotinib was tested in preclinical models.Results:Chidamide enhanced macrophage infiltration and induced macrophage polarization toward the anti-tumor M1 phenotype.Mechanistically,chidamide upregulated CCL2 via STAT4 transcriptional activation,thereby reshaping the tumor immune microenvironment(TIME).Combining chidamide with anlotinib synergistically suppressed tumor growth and remodeled the immunosuppressive TME in SCLC in vivo.Conclusions:Chidamide reshaped the SCLC TIME by activating STAT4/CCL2,thus driving M1 macrophage polarization and enhancing anti-tumor immunity.Our findings highlight coordinated TIME-targeted therapy as a translatable strategy to overcome therapeutic resistance in SCLC and provide a rationale for clinical trials examining epigenetic and anti-angiogenic therapeutics combinations.展开更多
Chronic pain,frequently comorbid with neuropsychiatric disorders,significantly impairs patients’quality of life and functional capacity.Accumulating evidence implicates the chemokine CCL2 and its receptor CCR2 as key...Chronic pain,frequently comorbid with neuropsychiatric disorders,significantly impairs patients’quality of life and functional capacity.Accumulating evidence implicates the chemokine CCL2 and its receptor CCR2 as key players in chronic pain pathogenesis.This review examines the regulatory mechanisms of the CCL2/CCR2 axis in chronic pain processing at three hierarchical levels:(1)Peripheral Sensitization:CCL2/CCR2 modulates TRPV1,Nav1.8,and HCN2 channels to increase neuronal excitability and CGRP signaling and calcium-dependent exocytosis in peripheral nociceptors to transmit pain.(2)Spinal Cord Central Sensitization:CCL2/CCR2 contributes to NMDAR-dependent plasticity,glial activation,GABAergic disinhibition,and opioid receptor desensitization.(3)Supraspinal Central Networks:CCL2/CCR2 signaling axis mediates the comorbidity mechanisms of pain with anxiety and cognitive impairment within brain regions,including the ACC,CeA,NAc,and hippocampus,and it also increases pain sensitization through the descending facilitation system.Current CCL2/CCR2-targeted therapeutic strategies and their development status are discussed,highlighting novel avenues for chronic pain management.展开更多
文摘目的 研究妊娠期糖尿病(GDM)患者血清C-C基序趋化因子配体2(CCL2)、脂质运载蛋白-2(LCN2)水平与糖脂代谢及胰岛素抵抗的相关性。方法 回顾性选取2021年6月至2023年6月在苏州大学附属张家港医院确诊的98例GDM患者作为病例组,选择同期来院的98名健康妊娠孕妇作为对照组。收集两组孕妇的一般临床资料[孕周、孕次、孕前身体质量指数(BMI)、收缩压、舒张压、总胆固醇、甘油三酯、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FBG)、餐后1 h血糖(1 h PG)、餐后2 h血糖(2 h PG)、空腹胰岛素(FINS)、糖化血红蛋白(GHb)、稳态模型评估胰岛素抵抗指数(HOMA-IR)];比较对照组和病例组血清CCL2和LCN2表达水平;采用多因素Logistic回归分析对影响GDM的因素进行分析;采用Pearson相关性分析对血清CCL2和LCN2与糖脂代谢及胰岛素抵抗相关指标的相关性进行分析;采用受试者操作特征(ROC)曲线分析血清标志物CCL2、LCN2对GDM患者的诊断价值。结果 两组孕妇的年龄、孕周、孕次等比较,差异均无统计学意义(P > 0.05)。病例组的甘油三酯、总胆固醇、LDL-C、FBG、1 h PG、2 h PG、GHb、FINS、HOMA-IR均显著高于对照组,HDL-C显著低于对照组,差异均有统计学意义(P<0.05)。病例组的血清CCL2、LCN2水平分别为(32.46±6.87)、(23.61±6.26) pg/mL,均显著高于对照组[(26.31±4.37)、(16.78±4.34) pg/m L],差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,血清LDL-C、FINS、甘油三酯、总胆固醇、HOMA-IR、CCL2、LCN2均为GDM的危险因素(P<0.05),而HDL-C是GDM的保护因素(P<0.05)。Pearson相关性分析结果显示,血清CCL2、LCN2水平与FBG、1 h PG、2 h PG、FINS、LDL-C、Hb Alc、甘油三酯、总胆固醇、HOMA-IR均呈正相关(P<0.05),与HDL-C呈负相关(P<0.05)。血清CCL2、LCN2二者联合诊断GDM患者的曲线下面积(AUC)最高,显著高于CCL2、LCN2单独诊断(P<0.05)。结论 GDM患者血清中CCL2和LCN2的表达水平均明显升高,二者与糖脂代谢紊乱和胰岛素抵抗存在密切关联,可作为临床诊断GDM的指标。
基金supported in part by grants from National Natural Science Foundation of China(Grant Nos.82172635,82272686,and 82203628)the Natural Science Foundation of Tianjin(Grant Nos.23JCZDJC00200 and 21JCYBJC01000)the Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-010A).
文摘Objective:This study aimed at exploring the effects of the epigenetic regulator,chidamide,on reprogramming the immunosuppressive tumor microenvironment in small cell lung cancer(SCLC),particularly the roles in macrophage polarization and angiogenesis.The therapeutic efficacy of combining chidamide with the anti-angiogenic agent,anlotinib,for refractory SCLC was also evaluated.Methods:RNA sequencing and functional validation were performed to assess chidamide’s effects on macrophages.Signal transducer and activator of transcription 4(STAT4)-mediated transcriptional activation of CCL2 was confirmed with ChIP-qPCR.The synergistic efficacy of chidamide in combination with anlotinib was tested in preclinical models.Results:Chidamide enhanced macrophage infiltration and induced macrophage polarization toward the anti-tumor M1 phenotype.Mechanistically,chidamide upregulated CCL2 via STAT4 transcriptional activation,thereby reshaping the tumor immune microenvironment(TIME).Combining chidamide with anlotinib synergistically suppressed tumor growth and remodeled the immunosuppressive TME in SCLC in vivo.Conclusions:Chidamide reshaped the SCLC TIME by activating STAT4/CCL2,thus driving M1 macrophage polarization and enhancing anti-tumor immunity.Our findings highlight coordinated TIME-targeted therapy as a translatable strategy to overcome therapeutic resistance in SCLC and provide a rationale for clinical trials examining epigenetic and anti-angiogenic therapeutics combinations.
基金supported by grants from the Ministry of Science and Technology of China(2021ZD0203205 and 2021ZD0203104)the National Natural Science Foundation of China(82371225,82171212,82571386,82330036 and 82221001)+2 种基金National Key Research and Development Program of China(2024YFC2510102)the Excellent Youth Science Foundation of Shaanxi Province(2025JC-JCQN-103)Shaanxi Province Sanqin Talent Program.
文摘Chronic pain,frequently comorbid with neuropsychiatric disorders,significantly impairs patients’quality of life and functional capacity.Accumulating evidence implicates the chemokine CCL2 and its receptor CCR2 as key players in chronic pain pathogenesis.This review examines the regulatory mechanisms of the CCL2/CCR2 axis in chronic pain processing at three hierarchical levels:(1)Peripheral Sensitization:CCL2/CCR2 modulates TRPV1,Nav1.8,and HCN2 channels to increase neuronal excitability and CGRP signaling and calcium-dependent exocytosis in peripheral nociceptors to transmit pain.(2)Spinal Cord Central Sensitization:CCL2/CCR2 contributes to NMDAR-dependent plasticity,glial activation,GABAergic disinhibition,and opioid receptor desensitization.(3)Supraspinal Central Networks:CCL2/CCR2 signaling axis mediates the comorbidity mechanisms of pain with anxiety and cognitive impairment within brain regions,including the ACC,CeA,NAc,and hippocampus,and it also increases pain sensitization through the descending facilitation system.Current CCL2/CCR2-targeted therapeutic strategies and their development status are discussed,highlighting novel avenues for chronic pain management.
