[Efficacy and safety of low-dose rasburicase for refractory chronic gouty arthritis].

Objective: To explore the efficacy and safety of low-dose rasburicase for refractory chronic gouty arthritis. Methods: A cohort study. The clinical data of patients with refractory chronic gouty arthritis who were treated with rasburicase at Sun Yat-sen Memorial Hospital, Sun Yat-sen University between January 2021 and July 2022 were retrospectively analyzed. Refractory chronic gouty arthritis was defined as serum uric acid (sUA)>360 µmol/L and urate volume>10 cm3 under dual-energy computed tomography after tolerable maximal oral urate-lowering therapy for at least 3 months. The administration of low-dose rasburicase was applied intravenously with total dosage ranging from 4.5 to 7.5 mg each dose, at 4-week intervals for a maximum of three doses. Efficacy was evaluated by the changes of sUA level, tophus and urate volume. Results: A total of 22 patients were included for analysis, with 95.4% (21/22) male, the mean age was (44±15) years, and the median duration of gout was 11 (6-15) years. The mean sUA at baseline was (667±112) µmol/L. The levels of sUA significantly decreased after each dose of rasburicase (P<0.001), and the median reduction of sUA after each dose of rasburicase was 568 (471-635), 187 (66-335) and 123 (49-207) µmol/L, respectively. At week 12, nine patients (40.9%) exhibited sUA<360 µmol/L and tophus disappeared in one patient. The urate volume significantly decreased at week 12 when compared with that before the first dose of rasburicase in all the patients [40 (16-172) cm3 vs 17 (7-134) cm3, P<0.001], with a median reduction rate of 41.6% (22.9%-58.5%). The everall safety of rasburicase was good, and no serious adverse reactions occurred. Conclusions: Low-dose rasburicase is well-tolerated and effective for decreasing the urate burden in patients with refractory chronic gouty arthritis. Further prospective randomized controlled trials are needed to validate these findings.

Preparation, characterization and luminescence properties of a new hydrous red phosphor CaB3 O5 (OH):Eu3+ with different morphologies.

A new borate phosphor CaB3 O5 (OH):Eu3+ with different morphologies was synthesized using a hydrothermal method and its luminescence properties were studied. The effects of surfactants on the crystal structures, morphologies and luminescence properties of the samples were studied. The results showed that the surfactants play an important role in controlling the morphology and improving the luminescence properties of phosphors. The luminescence intensity and R/O(I615/I592) value were enhanced for the prepared sample by adding PEG4000. The prepared sample exhibited a higher R/O than some anhydrous calcium borate phosphors, indicating that this product could serve as a new potential red phosphor.

Gossypol and an HMT G9a inhibitor act in synergy to induce cell death in pancreatic cancer cells.

The histone methyltransferase G9a is overexpressed in a variety of cancer types, including pancreatic adenocarcinoma, and promotes tumor invasiveness and metastasis. We recently reported the discovery of BRD4770, a small-molecule inhibitor of G9a that induces senescence in PANC-1 cells. We observed that the cytotoxic effects of BRD4770 were dependent on genetic background, with cell lines lacking functional p53 being relatively resistant to compound treatment. To understand the mechanism of genetic selectivity, we used two complementary screening approaches to identify enhancers of BRD4770. The natural product and putative BH3 mimetic gossypol enhanced the cytotoxicity of BRD4770 in a synergistic manner in p53-mutant PANC-1 cells but not in immortalized non-tumorigenic pancreatic cells. The combination of gossypol and BRD4770 increased LC3-II levels and the autophagosome number in PANC-1 cells, and the compound combination appears to act in a BNIP3 (B-cell lymphoma 2 19-kDa interacting protein)-dependent manner, suggesting that these compounds act together to induce autophagy-related cell death in pancreatic cancer cells.