BACKGROUND The treatment of difficult common bile duct stones(CBDS)remains a big challenge around the world.Biliary stenting is a widely accepted rescue method in patients with failed stone extraction under endoscopic...BACKGROUND The treatment of difficult common bile duct stones(CBDS)remains a big challenge around the world.Biliary stenting is a widely accepted rescue method in patients with failed stone extraction under endoscopic retrograde cholangiopancreatography.Fully covered self-expanding metal stent(FCSEMS)has gained increasing attention in the management of difficult CBDS.AIM To manufacture a drug-eluting FCSEMS,which can achieve controlled release of stone-dissolving agents and speed up the dissolution of CBDS.METHODS Customized covered nitinol stents were adopted.Sodium cholate(SC)and disodium ethylene diamine tetraacetic acid(EDTA disodium,EDTA for short)were used as stone-dissolving agents.Three different types of drug-eluting stents were manufactured by dip coating(Stent I),coaxial electrospinning(Stent II),and dip coating combined with electrospinning(Stent III),respectively.The drugrelease behavior and stone-dissolving efficacy of these stents were evaluated in vitro to sort out the best manufacturing method.And the selected stonedissolving stents were further put into porcine CBD to evaluate their biosecurity.RESULTS Stent I and Stent II had obvious burst release of drugs in the first 5 d while Stent III presented controlled and sustainable drug release for 30 d.In still buffer,the final stone mass-loss rate of each group was 5.19%±0.69%for naked FCSEMS,20.37%±2.13%for Stent I,24.57%±1.45%for Stent II,and 33.72%±0.67%for Stent III.In flowing bile,the final stone mass-loss rate of each group was 5.87%±0.25%for naked FCSEMS,6.36%±0.48%for Stent I,6.38%±0.37%for Stent II,and 8.15%±0.27%for Stent III.Stent III caused the most stone mass-loss no matter in still buffer or in flowing bile,which was significantly higher than those of other groups(P<0.05).In vivo,Stent III made no difference from naked FCSEMS in serological analysis(P>0.05)and histopathological examination(P>0.05).CONCLUSION The novel SC and EDTA-eluting FCSEMS is efficient in diminishing CBDS in vitro.When conventional endoscopic techniques fail to remove difficult CBDS,SC and EDTA-eluting FCSEMS implantation may be considered a promising alternative.展开更多
Matrine （MT）, the effective component of Sophora fla- vescens Air, has been shown to have anti-inflammation, immune-suppressive, anti-tumor, and anti-hepatic fibrosis activities. However, the pharmacological effects...Matrine （MT）, the effective component of Sophora fla- vescens Air, has been shown to have anti-inflammation, immune-suppressive, anti-tumor, and anti-hepatic fibrosis activities. However, the pharmacological effects of MT still need to be strengthened due to its relatively low efficacy and short half-life. In the present study, we report a more effective thio derivative of MT, MD-1, and its inhibitory effects on the activation of hepatic stellate cells （HSCs） in both cell culture and animal models. Cytological experiments showed that MD-1 can inhibit the proliferation of HSC-T6 cells with a half-maximal inhibitory concentration （ICs0） of 62 pmollL. In addition, MD-1 more strongly inhibits the migration of HSC-T6 cells compared to MT and can more effectively induce G0/G1 arrest and apoptosis. Investigating the biological mechanisms underlying anti-hepatic fibrosis in the presence of MD-I, we found that MD-I can bind the epidermal growth factor receptor （EGFR） on the surface of HSC-T6 cells, which can further inhibit the phospho- rylaUon of EGFR and its downstream protein kinase B （Akt）, resulting in decreased expression of cyclin D1 and eventual inhibition of the activation of HSC-T6 cells. Furthermore, in rats with dimethylnitrosamine （DMN）- induced hepatic fibrosis, MD-1 slowed the development and progression of hepatic fibrosis, protecting hepatic parenchymal cells and improving hepatic functions. Therefore, MD-1 is a potential drug for anti-hepatic fibrosis.展开更多
基金the National Natural Science Foundation of China,No.81470904and Shanghai Committee of Science and Technology,No.14411963000
文摘BACKGROUND The treatment of difficult common bile duct stones(CBDS)remains a big challenge around the world.Biliary stenting is a widely accepted rescue method in patients with failed stone extraction under endoscopic retrograde cholangiopancreatography.Fully covered self-expanding metal stent(FCSEMS)has gained increasing attention in the management of difficult CBDS.AIM To manufacture a drug-eluting FCSEMS,which can achieve controlled release of stone-dissolving agents and speed up the dissolution of CBDS.METHODS Customized covered nitinol stents were adopted.Sodium cholate(SC)and disodium ethylene diamine tetraacetic acid(EDTA disodium,EDTA for short)were used as stone-dissolving agents.Three different types of drug-eluting stents were manufactured by dip coating(Stent I),coaxial electrospinning(Stent II),and dip coating combined with electrospinning(Stent III),respectively.The drugrelease behavior and stone-dissolving efficacy of these stents were evaluated in vitro to sort out the best manufacturing method.And the selected stonedissolving stents were further put into porcine CBD to evaluate their biosecurity.RESULTS Stent I and Stent II had obvious burst release of drugs in the first 5 d while Stent III presented controlled and sustainable drug release for 30 d.In still buffer,the final stone mass-loss rate of each group was 5.19%±0.69%for naked FCSEMS,20.37%±2.13%for Stent I,24.57%±1.45%for Stent II,and 33.72%±0.67%for Stent III.In flowing bile,the final stone mass-loss rate of each group was 5.87%±0.25%for naked FCSEMS,6.36%±0.48%for Stent I,6.38%±0.37%for Stent II,and 8.15%±0.27%for Stent III.Stent III caused the most stone mass-loss no matter in still buffer or in flowing bile,which was significantly higher than those of other groups(P<0.05).In vivo,Stent III made no difference from naked FCSEMS in serological analysis(P>0.05)and histopathological examination(P>0.05).CONCLUSION The novel SC and EDTA-eluting FCSEMS is efficient in diminishing CBDS in vitro.When conventional endoscopic techniques fail to remove difficult CBDS,SC and EDTA-eluting FCSEMS implantation may be considered a promising alternative.
文摘Matrine （MT）, the effective component of Sophora fla- vescens Air, has been shown to have anti-inflammation, immune-suppressive, anti-tumor, and anti-hepatic fibrosis activities. However, the pharmacological effects of MT still need to be strengthened due to its relatively low efficacy and short half-life. In the present study, we report a more effective thio derivative of MT, MD-1, and its inhibitory effects on the activation of hepatic stellate cells （HSCs） in both cell culture and animal models. Cytological experiments showed that MD-1 can inhibit the proliferation of HSC-T6 cells with a half-maximal inhibitory concentration （ICs0） of 62 pmollL. In addition, MD-1 more strongly inhibits the migration of HSC-T6 cells compared to MT and can more effectively induce G0/G1 arrest and apoptosis. Investigating the biological mechanisms underlying anti-hepatic fibrosis in the presence of MD-I, we found that MD-I can bind the epidermal growth factor receptor （EGFR） on the surface of HSC-T6 cells, which can further inhibit the phospho- rylaUon of EGFR and its downstream protein kinase B （Akt）, resulting in decreased expression of cyclin D1 and eventual inhibition of the activation of HSC-T6 cells. Furthermore, in rats with dimethylnitrosamine （DMN）- induced hepatic fibrosis, MD-1 slowed the development and progression of hepatic fibrosis, protecting hepatic parenchymal cells and improving hepatic functions. Therefore, MD-1 is a potential drug for anti-hepatic fibrosis.
