RNA helicases and chaperones are the two major classes of RNA remodeling proteins, which function to remodel RNA structures and/or RNA-protein interactions, and are required for all aspects of RNA metabolism. Although some virus-encoded RNA helicases/chaperones have been predicted or identified, their RNA remodeling activities in vitro and functions in the viral life cycle remain largely elusive. Enteroviruses are a large group of positive-stranded RNA viruses in the Picornaviridae family, which includes numerous important human pathogens. Herein, we report that the nonstructural protein 2CATPase of enterovirus 71 (EV71), which is the major causative pathogen of hand-foot-and-mouth disease and has been regarded as the most important neurotropic enterovirus after poliovirus eradication, functions not only as an RNA helicase that 3′-to-5′ unwinds RNA helices in an adenosine triphosphate (ATP)-dependent manner, but also as an RNA chaperone that destabilizes helices bidirectionally and facilitates strand annealing and complex RNA structure formation independently of ATP. We also determined that the helicase activity is based on the EV71 2CATPase middle domain, whereas the C-terminus is indispensable for its RNA chaperoning activity. By promoting RNA template recycling, 2CATPase facilitated EV71 RNA synthesis in vitro; when 2CATPase helicase activity was impaired, EV71 RNA replication and virion production were mostly abolished in cells, indicating that 2CATPase-mediated RNA remodeling plays a critical role in the enteroviral life cycle. Furthermore, the RNA helicase and chaperoning activities of 2CATPase are also conserved in coxsackie A virus 16 (CAV16), another important enterovirus. Altogether, our findings are the first to demonstrate the RNA helicase and chaperoning activities associated with enterovirus 2CATPase, and our study provides both in vitro and cellular evidence for their potential roles during viral RNA replication. These findings increase our understanding of enteroviruses and the two types of RNA remodeling activities.
Objective To compare the efficacy of transjugular intrahepatic portosystemic shunts (TIPS) and endoscopic variceal ligations (EVL) plus propranolol in decreasing rebleeding and improving survival rates in cirrhotic patients with cavernous transformation of the portal vein (CTPV). Methods Cirrhotic patients with CTPV and a history of variceal bleeding who were treated for recurrent variceal bleeding between June 2010 and July 2016 were identified and classified based on the treatment they received (TIPS or EVL plus propranolol). Their characteristics and clinical data were recorded. The rebleeding and long‐term survival rates between the two groups were analyzed. Results A total of 51 patients were included, of whom 25 were treated with TIPS and 26 with EVL plus propranolol. The mean duration of follow up was 21 months (range 1–47 months) in the former group and 27 months (range 6–73 months) in the latter group. The recurrent variceal bleeding‐free rate increased remarkably in the TIPS group compared with the EVL + propranolol group (P = 0.047). Three (14.3%) patients died in the TIPS group, and one (3.8%) in the EVL plus propranolol group (P = 0.305). Hepatic encephalopathy occurred in 14.3% (3/21) of the patients in the TIPS group and in 3.8% (1/26) in the EVL + propranolol group (P = 0.202). Conclusion TIPS appeared to be more effective in preventing rebleeding in cirrhotic patients with CTPV compared with EVL plus propranolol, without improving survival.
BackgroundTo summarize the experiences with the technique of percutaneous biliary stent placement for treatment of malignant biliary obstruction in patients with different types of biliary obstruction.MethodsPercutaneous biliary stent placement was performed in 126 patients with malignant biliary obstruction. The etiology included 56 cases of cholangiocarcinoma, 28 cases of pancreatic cancer, 12 cases of ampullary carcinoma, 10 cases of primary hepatic carcinoma, 8 cases of gastric cancer metastasis, 6 cases of gallbladder carcinoma, and 6 cases of liver metastasis of colon cancer. The obstructed lesion predominantly involved the common bile duct in 42 patients, common hepatic duct in 39 patients, and hilar bile duct in 45 patients. When the bile duct was punctured successfully under fluoroscopy, the guide wire was explored to across the obstruction segment under the assistant of catheter, then the stent was inserted along the super-slippery guide wire. In patients with hilar hepatic duct lesions involving both left and right hepatic ducts, the both ducts were punctured and bilateral stenting was performed. A 8.5 F internal/external drainage catheter was inserted. The liver function test and ultrasound were performed one week after the procedure to observe the decrease of bilirubin and alleviation of biliary obstruction.ResultsA total of 166 stents were implanted in 126 patients. In the 42 patients with common bile duct obstruction, each patient was implanted one stent. In the 39 patients with common hepatic duct obstruction, each patient was impanted one stent. In the 45 patients with hilur bile duct obstruction, 38 patients were placed 2 stents, one patient was placed with 3 stents, and the rest were placed with one stent. The serum total bilirubin decreased from 309.2 ± 158.3 µmol/L before the procedure to148.5 ± 98.0 µmol/L one week after the procedure (P < 0.001). Alkaline phosphatase and alanine aminotransferase significantly decreased (P < 0.001). Five cases died within 1 month (4%) after the procedure. Complications occurred in 9 cases (7.1%). Six patients underwent combined duodenal self-expandable metal stent placement successfully.ConclusionsThe percutaneous biliary stent placement is a safe and effective palliative therapy for malignant biliary obstruction by improving liver function and 1ife quality.
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