目的:探讨血清补体C1q/肿瘤坏死因子相关蛋白(Complement-C1q/tumor necrosis factor-related protein 3,CTRP3)水平与甲状腺功能亢进患者骨代谢的相关性。方法:回顾性收集本院2021年10月至2023年10月期间收治的85例甲状腺功能亢进患者...目的:探讨血清补体C1q/肿瘤坏死因子相关蛋白(Complement-C1q/tumor necrosis factor-related protein 3,CTRP3)水平与甲状腺功能亢进患者骨代谢的相关性。方法:回顾性收集本院2021年10月至2023年10月期间收治的85例甲状腺功能亢进患者的临床资料。依据骨密度检测结果将85例甲状腺功能亢进患者分为合并骨质疏松组(n=20)和未合并骨质疏松组(n=65)。收集两组的基线资料及入院时甲状腺激素指标(游离三碘甲状腺原氨酸、游离四碘甲状腺原氨酸、促甲状腺激素、总三碘甲状腺原氨酸、血清总甲状腺素)、血清CTRP3水平、骨代谢(骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素)。分析血清CTRP3水平与甲状腺功能亢进患者骨代谢指标的相关性。结果:骨质疏松组血清CTRP3水平明显低于未合并骨质疏松组,且血清骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素水平均明显高于未合并骨质疏松组(P<0.05)。经双变量Pearson相关性分析显示,血清CTRP3水平与骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素水平呈负相关(P<0.05)。结论:血清CTRP3水平与甲状腺功能亢进患者与骨代谢指标(骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素)有关。展开更多
目的分析孕早期血清补体C1q/肿瘤坏死因子相关蛋白3(CTRP3)、成纤维细胞生长因子19(FGF-19)对妊娠期糖尿病(GDM)患者不良妊娠结局的预测效能。方法该研究为回顾性研究,研究对象为开封市第三人民医院(祥符区第一人民医院)2022年1月至2023...目的分析孕早期血清补体C1q/肿瘤坏死因子相关蛋白3(CTRP3)、成纤维细胞生长因子19(FGF-19)对妊娠期糖尿病(GDM)患者不良妊娠结局的预测效能。方法该研究为回顾性研究,研究对象为开封市第三人民医院(祥符区第一人民医院)2022年1月至2023年8月收治的115例GDM患者,统计入组患者的不良妊娠结局发生率,并将其分别列为发生组和未发生组,比较两组患者糖脂代谢指标[空腹血糖(FBG)、餐后2 h血糖(2 h PG)、总胆固醇(TC)、甘油三酯(TG)],胰岛素功能指标[空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、人源甘丙肽(GAL)]及血清CTRP3、FGF-19间的差异,分析血清CTRP3、FGF-19与GDM患者糖脂代谢指标,胰岛素功能指标间的相关性,及对GDM患者不良妊娠结局的预测效能。结果经统计,115例GDM中不良妊娠结局发生率为27.83%(32/115);经检测,发生组的FBG、2 h PG、TC、TG、FINS、HOMA-IR、NGAL、GAL分别为(10.45±2.41)mmol/L、(14.66±3.25)mmol/L、(10.23±2.36)mmol/L、(5.81±1.44)mmol/L、(40.24±5.44)pmol/mL、(8.23±1.72)、(425.33±50.36)ng/mL、(142.33±20.45)ng/L,均高于未发生组[(8.35±1.61)mmol/L、(12.44±3.45)mmol/L、(8.39±1.42)mmol/L、(4.77±1.35)mmol/L、(37.44±5.28)pmol/mL、(7.35±1.61)、(380.23±50.44)ng/mL、(127.33±20.26)ng/L],CTRP3、FGF-19分别为(135.33±20.26)ng/L、(18.26±3.15)pg/mL,均低于未发生组[(150.26±20.41)ng/L、(20.33±3.26)pg/mL](t=5.414、3.141、5.113、3.634、2.527、2.502、4.299、3.549、3.523、3.080,P<0.05);经Pearson相关性系数检验,血清CTRP3与FBG、2 h PG、TC、TG、FINS、HOMA-IR、NGAL、GAL呈负相关(r=-0.361、-0.362、-0.348、-0.355、-0.359、-0.360、-0.361、-0.357,P<0.05);血清FGF-19与FBG、2 h PG、TC、TG、FINS、HOMA-IR、NGAL、GAL呈负相关(r=-0.341、-0.345、-0.352、-0.349、-0.348、-0.350、-0.352、-0.347,P<0.05);经受试者操作特征(ROC)曲线检验,血清CTRP3对GDM不良妊娠结局的预测灵敏度、特异度分别为82.44%、80.35%,截断值为142.80 ng/L,曲线下面积(AUC)=0.868(95%CI:0.815~0.904);血清FGF-19对GDM不良妊娠结局的预测灵敏度、特异度分别为81.95%、80.11%,截断值为19.30 pg/mL,AUC=0.865(95%CI:0.802~0.895)。结论孕早期血清CTRP3、FGF-19水平会随GDM患者糖脂代谢紊乱程度及胰岛素抵抗程度加剧而不断降低,动态监测血清CTRP3、FGF-19变化能实现对GDM不良妊娠结局的早期预测。展开更多
Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures.Recent studies have shown that complement component 3(C3)aggravate the neuronal injury in epilepsy.And our previous studies revealed...Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures.Recent studies have shown that complement component 3(C3)aggravate the neuronal injury in epilepsy.And our previous studies revealed that TRPV1(transient receptor potential vanilloid type 1)is involved in epilepsy.Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood.We found that in a mouse model of status epilepticus(SE),complement C3 derived from astrocytes was increased and aggravated neuronal injury,and that TRPV 1-knockout rescued neurons from the injury induced by complement C3.Circular RNAs are abundant in the brain,and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV 1 and exacerbated neuronal injury.Mechanistically,disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury.This study provides support for the hypothesis that the C3-TRFV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.展开更多
Objective:Myeloma bone disease(MBD)is the most common complication of multiple myeloma(MM).Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the seve...Objective:Myeloma bone disease(MBD)is the most common complication of multiple myeloma(MM).Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the severity of bone disease.However,the mechanism of C3 a/C4 a in osteoclasts MM patients remains unclear.Methods:The formation and function of osteoclasts were analyzed after adding C3 a/C4 a in vitro.RNA-seq analysis was used to screen the potential pathways affecting osteoclasts,and the results were verified by Western blot,q RT-PCR,and pathway inhibitors.Results:The osteoclast area per view induced by 1μg/m L(mean±SD:50.828±12.984%)and 10μg/m L(53.663±12.685%)of C3 a was significantly increased compared to the control group(0μg/m L)(34.635±8.916%)(P<0.001 and P<0.001,respectively).The relative m RNA expressions of genes,OSCAR/TRAP/RANKL/cathepsin K,induced by 1μg/m L(median:5.041,3.726,1.638,and 4.752,respectively)and 10μg/m L(median:5.140,3.702,2.250,and 5.172,respectively)of C3 a was significantly increased compared to the control group(median:3.137,2.004,0.573,and 2.257,respectively)(1μg/m L P=0.001,P=0.003,P<0.001,and P=0.008,respectively;10μg/m L:P<0.001,P=0.019,P<0.001,and P=0.002,respectively).The absorption areas of the osteoclast resorption pits per view induced by 1μg/m L(mean±SD:51.464±11.983%)and 10μg/m L(50.219±12.067%)of C3 a was also significantly increased(33.845±8.331%)(P<0.001 and P<0.001,respectively)compared to the control.There was no difference between the C4 a and control groups.RNA-seq analysis showed that C3 a promoted the proliferation of osteoclasts using the phosphoinositide 3-kinase(PI3 K)signaling pathway.The relative expressions of PIK3 CA/phosphoinositide dependent kinase-1(PDK1)/serum and glucocorticoid inducible protein kinases(SGK3)genes and PI3 K/PDK1/p-SGK3 protein in the C3 a group were significantly higher than in the control group.The activation role of C3 a in osteoclasts of MM patients was reduced by the SGK inhibitor(EMD638683).Conclusions:C3 a activated osteoclasts by regulating the PI3 K/PDK1/SGK3 pathways in MM patients,which was reduced using a SGK inhibitor.Overall,our results identified potential therapeutic targets and strategies for MBD patients。展开更多
文摘目的:探讨血清补体C1q/肿瘤坏死因子相关蛋白(Complement-C1q/tumor necrosis factor-related protein 3,CTRP3)水平与甲状腺功能亢进患者骨代谢的相关性。方法:回顾性收集本院2021年10月至2023年10月期间收治的85例甲状腺功能亢进患者的临床资料。依据骨密度检测结果将85例甲状腺功能亢进患者分为合并骨质疏松组(n=20)和未合并骨质疏松组(n=65)。收集两组的基线资料及入院时甲状腺激素指标(游离三碘甲状腺原氨酸、游离四碘甲状腺原氨酸、促甲状腺激素、总三碘甲状腺原氨酸、血清总甲状腺素)、血清CTRP3水平、骨代谢(骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素)。分析血清CTRP3水平与甲状腺功能亢进患者骨代谢指标的相关性。结果:骨质疏松组血清CTRP3水平明显低于未合并骨质疏松组,且血清骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素水平均明显高于未合并骨质疏松组(P<0.05)。经双变量Pearson相关性分析显示,血清CTRP3水平与骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素水平呈负相关(P<0.05)。结论:血清CTRP3水平与甲状腺功能亢进患者与骨代谢指标(骨特异性碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基前肽、碱性磷酸酶、N端骨钙素)有关。
文摘目的分析孕早期血清补体C1q/肿瘤坏死因子相关蛋白3(CTRP3)、成纤维细胞生长因子19(FGF-19)对妊娠期糖尿病(GDM)患者不良妊娠结局的预测效能。方法该研究为回顾性研究,研究对象为开封市第三人民医院(祥符区第一人民医院)2022年1月至2023年8月收治的115例GDM患者,统计入组患者的不良妊娠结局发生率,并将其分别列为发生组和未发生组,比较两组患者糖脂代谢指标[空腹血糖(FBG)、餐后2 h血糖(2 h PG)、总胆固醇(TC)、甘油三酯(TG)],胰岛素功能指标[空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、人源甘丙肽(GAL)]及血清CTRP3、FGF-19间的差异,分析血清CTRP3、FGF-19与GDM患者糖脂代谢指标,胰岛素功能指标间的相关性,及对GDM患者不良妊娠结局的预测效能。结果经统计,115例GDM中不良妊娠结局发生率为27.83%(32/115);经检测,发生组的FBG、2 h PG、TC、TG、FINS、HOMA-IR、NGAL、GAL分别为(10.45±2.41)mmol/L、(14.66±3.25)mmol/L、(10.23±2.36)mmol/L、(5.81±1.44)mmol/L、(40.24±5.44)pmol/mL、(8.23±1.72)、(425.33±50.36)ng/mL、(142.33±20.45)ng/L,均高于未发生组[(8.35±1.61)mmol/L、(12.44±3.45)mmol/L、(8.39±1.42)mmol/L、(4.77±1.35)mmol/L、(37.44±5.28)pmol/mL、(7.35±1.61)、(380.23±50.44)ng/mL、(127.33±20.26)ng/L],CTRP3、FGF-19分别为(135.33±20.26)ng/L、(18.26±3.15)pg/mL,均低于未发生组[(150.26±20.41)ng/L、(20.33±3.26)pg/mL](t=5.414、3.141、5.113、3.634、2.527、2.502、4.299、3.549、3.523、3.080,P<0.05);经Pearson相关性系数检验,血清CTRP3与FBG、2 h PG、TC、TG、FINS、HOMA-IR、NGAL、GAL呈负相关(r=-0.361、-0.362、-0.348、-0.355、-0.359、-0.360、-0.361、-0.357,P<0.05);血清FGF-19与FBG、2 h PG、TC、TG、FINS、HOMA-IR、NGAL、GAL呈负相关(r=-0.341、-0.345、-0.352、-0.349、-0.348、-0.350、-0.352、-0.347,P<0.05);经受试者操作特征(ROC)曲线检验,血清CTRP3对GDM不良妊娠结局的预测灵敏度、特异度分别为82.44%、80.35%,截断值为142.80 ng/L,曲线下面积(AUC)=0.868(95%CI:0.815~0.904);血清FGF-19对GDM不良妊娠结局的预测灵敏度、特异度分别为81.95%、80.11%,截断值为19.30 pg/mL,AUC=0.865(95%CI:0.802~0.895)。结论孕早期血清CTRP3、FGF-19水平会随GDM患者糖脂代谢紊乱程度及胰岛素抵抗程度加剧而不断降低,动态监测血清CTRP3、FGF-19变化能实现对GDM不良妊娠结局的早期预测。
基金by the National Natural Science Foundation of China(81571481 and 82060588)the Natural Science Foundation of Hubei Province,China(2017CFA017)+1 种基金the Wuhan Science and Technology Project(2019020701011444)the Medical Science Advancement Program of Wuhan University(TFJC2018001 and TFLC2018001).
文摘Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures.Recent studies have shown that complement component 3(C3)aggravate the neuronal injury in epilepsy.And our previous studies revealed that TRPV1(transient receptor potential vanilloid type 1)is involved in epilepsy.Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood.We found that in a mouse model of status epilepticus(SE),complement C3 derived from astrocytes was increased and aggravated neuronal injury,and that TRPV 1-knockout rescued neurons from the injury induced by complement C3.Circular RNAs are abundant in the brain,and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV 1 and exacerbated neuronal injury.Mechanistically,disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury.This study provides support for the hypothesis that the C3-TRFV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.
基金supported by the National Natural Science Foundation of China(Grant Nos.81770110,81900131,and 82000219)the Anticancer Major Special Project of Tianjin(Grant No.12ZCDZSY18000)+4 种基金the Tianjin Municipal Natural Science Foundation(Grant Nos.18JCYBJC27200 and 18JCQNJC80400)the Tianjin Education Commission Research Project(Grant Nos.2018KJ043 and 2018KJ045)the Tianjin Health and Family Planning Commission(Grant No.15KG150)the Youth Incubation Fund of Tianjin Medical University General Hospital(Grant No.ZYYFY2019020)the Tianjin Science and Technology Planning Project(Grant No.20YFZCSY00060)。
文摘Objective:Myeloma bone disease(MBD)is the most common complication of multiple myeloma(MM).Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the severity of bone disease.However,the mechanism of C3 a/C4 a in osteoclasts MM patients remains unclear.Methods:The formation and function of osteoclasts were analyzed after adding C3 a/C4 a in vitro.RNA-seq analysis was used to screen the potential pathways affecting osteoclasts,and the results were verified by Western blot,q RT-PCR,and pathway inhibitors.Results:The osteoclast area per view induced by 1μg/m L(mean±SD:50.828±12.984%)and 10μg/m L(53.663±12.685%)of C3 a was significantly increased compared to the control group(0μg/m L)(34.635±8.916%)(P<0.001 and P<0.001,respectively).The relative m RNA expressions of genes,OSCAR/TRAP/RANKL/cathepsin K,induced by 1μg/m L(median:5.041,3.726,1.638,and 4.752,respectively)and 10μg/m L(median:5.140,3.702,2.250,and 5.172,respectively)of C3 a was significantly increased compared to the control group(median:3.137,2.004,0.573,and 2.257,respectively)(1μg/m L P=0.001,P=0.003,P<0.001,and P=0.008,respectively;10μg/m L:P<0.001,P=0.019,P<0.001,and P=0.002,respectively).The absorption areas of the osteoclast resorption pits per view induced by 1μg/m L(mean±SD:51.464±11.983%)and 10μg/m L(50.219±12.067%)of C3 a was also significantly increased(33.845±8.331%)(P<0.001 and P<0.001,respectively)compared to the control.There was no difference between the C4 a and control groups.RNA-seq analysis showed that C3 a promoted the proliferation of osteoclasts using the phosphoinositide 3-kinase(PI3 K)signaling pathway.The relative expressions of PIK3 CA/phosphoinositide dependent kinase-1(PDK1)/serum and glucocorticoid inducible protein kinases(SGK3)genes and PI3 K/PDK1/p-SGK3 protein in the C3 a group were significantly higher than in the control group.The activation role of C3 a in osteoclasts of MM patients was reduced by the SGK inhibitor(EMD638683).Conclusions:C3 a activated osteoclasts by regulating the PI3 K/PDK1/SGK3 pathways in MM patients,which was reduced using a SGK inhibitor.Overall,our results identified potential therapeutic targets and strategies for MBD patients。
