Background:Yanhusuo powder,also known as Xuanhusuo powder,is a long-standing Chinese herbal formula mainly used in the treatment of osteoarthritis.Although the clinical effectiveness of Yanhusuo powder has long been a...Background:Yanhusuo powder,also known as Xuanhusuo powder,is a long-standing Chinese herbal formula mainly used in the treatment of osteoarthritis.Although the clinical effectiveness of Yanhusuo powder has long been acknowledged,its mechanism of action and bioactive components remain unknown.Methods:A novel analytical method combining the use of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultra-performance liquid chromatography-triple quadrupole mass spectrometry was applied to profile the formula and absorbed prototype components in plasma after oral administration of Yanhusuo powder.Then,the absorbed constituents were subjected to network pharmacology to predict targets and pathways.AutoDock software was then used for molecular docking studies to screen for potential pharmacodynamic substances.Results:A total of 34 in vitro formula components and 20 in vivo prototype compounds from the various relevant species were successfully separated and identified for the first time.Compound-target-pathway analysis revealed that 20 absorbed constituents,42 target genes and 42 pathways are probably related to the efficacy of Yanhusuo powder against osteoarthritis.The efficacy of Yanhusuo powder mainly involves AKT1,fibronectin 1 and matrix metalloproteinase 9 targets and apoptosis,as well as PI3K-AKT and mitogen-activated protein kinases signaling pathways.According to the results of the molecular docking studies,it can be preliminarily judged that protopine,dehydrocorybulbine and angelicin may be the pharmacologically active substances of Yanhusuo powder.Conclusion:The results provide a scientific basis for understanding the bioactive compounds and the pharmacological mechanism of Yanhusuo powder.展开更多
Background:Inflammatory and nutritional indicators are established prognostic factors in patients with various types of solid tumors.However,it remains unclear whether differences in the baseline and early dynamic cha...Background:Inflammatory and nutritional indicators are established prognostic factors in patients with various types of solid tumors.However,it remains unclear whether differences in the baseline and early dynamic changes in these factors can predict the prognosis of immunotherapy in patients with advanced biliary tract carcinoma(aBTC).Methods:Data were retrospectively collected from 74 consecutive patients who were diagnosed with aBTC and received immunother-apy.Peripheral blood cell counts and other laboratory tests were performed at baseline and after two cycles of immunotherapy.The skeletal muscle index was measured using computed tomography/magnetic resonance imaging scans.Analyses of the relationship be-tween clinicopathological characteristics and survival outcomes were conducted using Kaplan-Meier curves and Cox regression models.Results:Seventy-four patients were enrolled in the study,with 42(56.8%)being male.The median age at diagnosis for all participants was 61 years(range,35–77 years).In the univariate analysis,six baseline indices were associated with survival,namely,lactate dehy-drogenase(LDH),carbohydrate antigen 199,neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio,Prognostic Nutritional Index,and Controlling Nutritional Status score.In the multivariable analysis,an elevated baseline NLR(HR:3.363,95%CI:1.600–7.070,P=0.001)and elevated baseline LDH(HR:2.030,95%CI:1.122–3.670,P=0.019)were independent risk factors for a shorter overall survival.Sarcopenia was not correlated with the overall survival(P>0.05).A persistently high NLR,platelet-to-lymphocyte ratio,and Controlling Nutritional Status score and low Prognostic Nutritional Index indicated a worse prognosis.Conclusions:Elevated baseline NLR and LDH values are independent negative prognostic factors in patients with aBTC receiving im-munotherapy.Patients with persistently high inflammation and poor nutritional status experience a poorer prognosis.展开更多
基金The work was supported by the National Natural Science Foundation of China(No.81373942)the Key Science and Technology Research Projects of Tibet Autonomous Region of China(No.XZ201801-GA-16).
文摘Background:Yanhusuo powder,also known as Xuanhusuo powder,is a long-standing Chinese herbal formula mainly used in the treatment of osteoarthritis.Although the clinical effectiveness of Yanhusuo powder has long been acknowledged,its mechanism of action and bioactive components remain unknown.Methods:A novel analytical method combining the use of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultra-performance liquid chromatography-triple quadrupole mass spectrometry was applied to profile the formula and absorbed prototype components in plasma after oral administration of Yanhusuo powder.Then,the absorbed constituents were subjected to network pharmacology to predict targets and pathways.AutoDock software was then used for molecular docking studies to screen for potential pharmacodynamic substances.Results:A total of 34 in vitro formula components and 20 in vivo prototype compounds from the various relevant species were successfully separated and identified for the first time.Compound-target-pathway analysis revealed that 20 absorbed constituents,42 target genes and 42 pathways are probably related to the efficacy of Yanhusuo powder against osteoarthritis.The efficacy of Yanhusuo powder mainly involves AKT1,fibronectin 1 and matrix metalloproteinase 9 targets and apoptosis,as well as PI3K-AKT and mitogen-activated protein kinases signaling pathways.According to the results of the molecular docking studies,it can be preliminarily judged that protopine,dehydrocorybulbine and angelicin may be the pharmacologically active substances of Yanhusuo powder.Conclusion:The results provide a scientific basis for understanding the bioactive compounds and the pharmacological mechanism of Yanhusuo powder.
基金funded by the Jiangsu Province 333 High-level Talents Project.
文摘Background:Inflammatory and nutritional indicators are established prognostic factors in patients with various types of solid tumors.However,it remains unclear whether differences in the baseline and early dynamic changes in these factors can predict the prognosis of immunotherapy in patients with advanced biliary tract carcinoma(aBTC).Methods:Data were retrospectively collected from 74 consecutive patients who were diagnosed with aBTC and received immunother-apy.Peripheral blood cell counts and other laboratory tests were performed at baseline and after two cycles of immunotherapy.The skeletal muscle index was measured using computed tomography/magnetic resonance imaging scans.Analyses of the relationship be-tween clinicopathological characteristics and survival outcomes were conducted using Kaplan-Meier curves and Cox regression models.Results:Seventy-four patients were enrolled in the study,with 42(56.8%)being male.The median age at diagnosis for all participants was 61 years(range,35–77 years).In the univariate analysis,six baseline indices were associated with survival,namely,lactate dehy-drogenase(LDH),carbohydrate antigen 199,neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio,Prognostic Nutritional Index,and Controlling Nutritional Status score.In the multivariable analysis,an elevated baseline NLR(HR:3.363,95%CI:1.600–7.070,P=0.001)and elevated baseline LDH(HR:2.030,95%CI:1.122–3.670,P=0.019)were independent risk factors for a shorter overall survival.Sarcopenia was not correlated with the overall survival(P>0.05).A persistently high NLR,platelet-to-lymphocyte ratio,and Controlling Nutritional Status score and low Prognostic Nutritional Index indicated a worse prognosis.Conclusions:Elevated baseline NLR and LDH values are independent negative prognostic factors in patients with aBTC receiving im-munotherapy.Patients with persistently high inflammation and poor nutritional status experience a poorer prognosis.
