AIM To compare the outcomes of transcatheter superior mesenteric artery(SMA) urokinase infusion and transjugular intrahepatic portosystemic shunt(TIPS) for acute portal vein thrombosis(PVT) in cirrhosis.METHODS From J...AIM To compare the outcomes of transcatheter superior mesenteric artery(SMA) urokinase infusion and transjugular intrahepatic portosystemic shunt(TIPS) for acute portal vein thrombosis(PVT) in cirrhosis.METHODS From January 2013 to December 2014, patients with liver cirrhosis and acute symptomatic PVT who met the inclusion criteria were randomly assigned to either an SMA group or a TIPS group. The two groups accepted transcatheter selective SMA urokinase infusion therapyand TIPS, respectively. The total follow-up time was24 mo. The primary outcome measure was the change in portal vein patency status which was evaluated by angio-computed tomography or Doppler ultrasound.Secondary outcomes were rebleeding and hepatic encephalopathy.RESULTS A total of 40 patients were enrolled, with 20 assigned to the SMA group and 20 to the TIPS group. The symptoms of all patients in the two groups improved within 48 h. PVT was improved in 17(85%) patients in the SMA group and 14(70%) patients in the TIPS group. The main portal vein(MPV) thrombosis was significantly reduced in both groups(P < 0.001), and there was no significant difference between them(P= 0.304). In the SMA group, superior mesenteric vein(SMV) thrombosis and splenic vein(SV) thrombosis were significantly reduced(P = 0.048 and P = 0.02),which did not occur in the TIPS group. At 6-, 12-,and 24-mo follow-up, in the SMA group and the TIPS group, the cumulative rates free of the first episode of rebleeding were 80%, 65%, and 45% vs 90%, 80%,and 60%, respectively(P = 0.320); the cumulative rates free of the first episode of hepatic encephalopathy were 85%, 80%, and 65% vs 50%, 40%, and 35%,respectively(P = 0.022).CONCLUSION Transcatheter selective SMA urokinase infusion and TIPS are safe and effective for acute symptomatic PVT in cirrhosis.展开更多
Human Notum(hNotum)inhibitors could be used for treating Wnt signalling-associated diseases including colorectal cancer.Herein,two series of chalcone derivatives were designed and synthesized aiming to find selective ...Human Notum(hNotum)inhibitors could be used for treating Wnt signalling-associated diseases including colorectal cancer.Herein,two series of chalcone derivatives were designed and synthesized aiming to find selective and potent hNotum inhibitors.Structure–activity relationship(SAR)studies showed that 2-methoxyl and 5-bromine substitutions on A-ring significantly enhanced anti-hNotum effect,while 4’-ethoxyl and 3’-alkyl substitutions on B-ring were beneficial for hNotum inhibition.Among all tested chalcones,B11 displayed the most potent anti-Notum effect(IC_(50)=3.6 nmol/L),good selectivity,excellent chemical stability and suitable metabolic stability.Further investigations showed that B11 acted as a competitive inhibitor of hNotum,while this agent(5μmol/L)significantly weaken the migration abilities of colorectal cancer cells.Collectively,this study deciphers the SARs of chalcones as hNotum inhibitors and reports a novel and potent hNotum inhibitor with the anti-migration effect on colorectal cancer cells,which offers a promising lead compound to develop novel anti-cancer agents.展开更多
基金Supported by the National Natural Science Foundation of China,No.81572888
文摘AIM To compare the outcomes of transcatheter superior mesenteric artery(SMA) urokinase infusion and transjugular intrahepatic portosystemic shunt(TIPS) for acute portal vein thrombosis(PVT) in cirrhosis.METHODS From January 2013 to December 2014, patients with liver cirrhosis and acute symptomatic PVT who met the inclusion criteria were randomly assigned to either an SMA group or a TIPS group. The two groups accepted transcatheter selective SMA urokinase infusion therapyand TIPS, respectively. The total follow-up time was24 mo. The primary outcome measure was the change in portal vein patency status which was evaluated by angio-computed tomography or Doppler ultrasound.Secondary outcomes were rebleeding and hepatic encephalopathy.RESULTS A total of 40 patients were enrolled, with 20 assigned to the SMA group and 20 to the TIPS group. The symptoms of all patients in the two groups improved within 48 h. PVT was improved in 17(85%) patients in the SMA group and 14(70%) patients in the TIPS group. The main portal vein(MPV) thrombosis was significantly reduced in both groups(P < 0.001), and there was no significant difference between them(P= 0.304). In the SMA group, superior mesenteric vein(SMV) thrombosis and splenic vein(SV) thrombosis were significantly reduced(P = 0.048 and P = 0.02),which did not occur in the TIPS group. At 6-, 12-,and 24-mo follow-up, in the SMA group and the TIPS group, the cumulative rates free of the first episode of rebleeding were 80%, 65%, and 45% vs 90%, 80%,and 60%, respectively(P = 0.320); the cumulative rates free of the first episode of hepatic encephalopathy were 85%, 80%, and 65% vs 50%, 40%, and 35%,respectively(P = 0.022).CONCLUSION Transcatheter selective SMA urokinase infusion and TIPS are safe and effective for acute symptomatic PVT in cirrhosis.
基金financially supported by the National Natural Science Foundation of China(Nos.82104281,81922070,81973286,81801818 and 82273897)Shanghai Municipal Health Commission’s TCM research project(No.2022CX005)+1 种基金Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202004)Three-year Action Plan for Shanghai TCM Development and Inheritance Program[No.ZY(2021–2023)-0401]。
文摘Human Notum(hNotum)inhibitors could be used for treating Wnt signalling-associated diseases including colorectal cancer.Herein,two series of chalcone derivatives were designed and synthesized aiming to find selective and potent hNotum inhibitors.Structure–activity relationship(SAR)studies showed that 2-methoxyl and 5-bromine substitutions on A-ring significantly enhanced anti-hNotum effect,while 4’-ethoxyl and 3’-alkyl substitutions on B-ring were beneficial for hNotum inhibition.Among all tested chalcones,B11 displayed the most potent anti-Notum effect(IC_(50)=3.6 nmol/L),good selectivity,excellent chemical stability and suitable metabolic stability.Further investigations showed that B11 acted as a competitive inhibitor of hNotum,while this agent(5μmol/L)significantly weaken the migration abilities of colorectal cancer cells.Collectively,this study deciphers the SARs of chalcones as hNotum inhibitors and reports a novel and potent hNotum inhibitor with the anti-migration effect on colorectal cancer cells,which offers a promising lead compound to develop novel anti-cancer agents.
