Discovery of novel 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives as potent carbonic anhydrase IX inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer.

A novel series of 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives were designed and synthesized as carbonic anhydrase IX (CA IX) inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer (TNBC). The representative compound 9o exhibited more potent inhibitory activity and selective against CA IX over off-target CA II, compared with positive control SLC-0111. Molecular docking study was also performed to gain insights into the binding interactions of 9o in the binding pocket of CAIX. Moreover, compound 9o exhibited superior antitumor activities against breast cancer cells under hypoxia than that of normoxia conditions. Mechanism studies revealed that compound 9o could act as DNA intercalator and effectively suppressed cell migration, arrested the cell cycle at G1/S phase and induced apoptosis in MDA-MB-231 cells, while inducing ferroptosis accompanied by the dissipation of MMP and the elevation intracellular levels of ROS. Notably, in vivo studies demonstrated that 9o effectively inhibited tumor growth and metastasis in a highly metastatic murine breast cancer 4 T1 xenograft model. Taken together, this study suggests that compound 9o represents a potent and selective CA IX inhibitor and ferroptosis inducer for the treatment of TNBC.

Risk factors for portal hypertensive gastropathy.

BACKGROUND: Portal hypertensive gastropathy (PHG) is often underestimated in clinical diagnosis. Gastrointestinal bleeding in cirrhosis of PHG accounts for approximately 10% of upper gastrointestinal bleeding. However, the relationship between PHG and gender, laboratory parameters, liver function and varices is still controversial. In the present study, we aimed to retrospectively evaluate the incidence of PHG and to explore the relationship between PHG and gender, laboratory parameters, liver function and varicose veins. METHODS: A retrospective analysis of 325 patients with cirrhosis who underwent esophagogastroduodenoscopy (EGD) in the Department of Gastroenterology of the Second Hospital of Hebei Medical University from 1 January 2018 to 31 December 2020 was performed. The relationships among age, gender, laboratory parameters, Child-Pugh stage, oesophageal varices (EV), gastric varices (GV) and ascites with PHG were analysed with univariate and multivariate logistic regression. RESULTS: The occurrence of PHG was significantly associated with gender, haemoglobin, platelet count, prothrombin time, albumin, Child-Pugh stage, EV, GV and ascites (P < 0.05). Furthermore, there was a positive correlation between the severity of PHG and the degree of EV, GV and ascites (P < 0.05). Multivariate logistic regression showed that albumin, EV and GV levels were independently associated with the occurrence of PHG. CONCLUSION: The incidence of PHG in cirrhosis was 87.4% in this study. The occurrence of PHG was related to gender, haemoglobin, platelet count, prothrombin time, albumin, Child-Pugh stage, EV, GV and ascites. Albumin, the degree of EV and GV are independent risk factors for the occurrence of PHG.

Risk factors for emergency endoscopic variceal ligation treatment failure of acute variceal bleeding.

OBJECTIVE: To determine the risk factors for emergency endoscopic variceal ligation (EVL) failure in acute variceal bleeding (AVB). METHODS: Data from 161 cirrhosis patients with oesophageal variceal bleeding who underwent emergency EVL treatment at the Second Hospital of Hebei Medical University from January 2018 to May 2021 were retrospectively analysed. Enrolled patients were divided into a successful treatment group and a failed treatment group. The variables studied were demographic, clinical, imaging, laboratory, and endoscopic data from the enrolled patients. RESULTS: Of the enrolled patients, 19 patients experienced emergency EVL failure. Of these patients, nine underwent emergency endoscopic treatment again, six patients were treated with a Sengstaken-Blakemore tube for haemostasis and endoscopic treatment, four patients received drug therapy. The presence of portal vein thrombosis (PVT) in the failure group was higher than that in the success group (p < .05). Active bleeding on endoscopy was associated with emergency EVL failure for patients with Child-Pugh class C (p < .05). CONCLUSIONS: Child-Pugh class C with active bleeding on endoscopy or the presence of PVT could increase the risk of emergency EVL failure. The patient's condition should be fully evaluated before emergency endoscopic treatment to reduce the risk of failure.

Double plastic stent implantation for recurrent acute pancreatitis with incomplete pancreas divisum: a case report and literature review.

Pancreas divisum (PD) is a common pancreatic malformation caused by the failure of fusion between ventral and dorsal pancreatic ducts. There is a small branch of communication between the two systems in incomplete PD, and this variation has an incidence of 15%. A 43-year-old female patient presented to our department with recurrent abdominal pain. Magnetic resonance cholangiopancreatography (MRCP) showed that the ventral pancreatic duct was curved, with a local pouchlike dilatation. Endoscopic ultrasonography supported the diagnosis of incomplete PD and showed a thin branch of communication between ventral and dorsal pancreatic ducts. Endoscopic retrograde cholangiopancreatography (ERCP) and papillotomy of the minor papilla with double plastic stent implantation were performed. One pancreatic plastic stent was inserted across the minor and major papilla over the guide wire, creating a U-shape. The other wire-guided plastic stent was inserted through the minor papilla into the dorsal pancreatic duct. The pancreatic fluid drained smoothly after stent placement. During the 6-month follow-up, the patient remained well, without recurrence of pancreatitis.