Background: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) -mediated neuroinflammation is linked to neuronal necroptosis in cerebral ischemia-reperfusion (I/R) injury, especially in cerebral ischemic penumbra. This study was designed to investigate the regulation of nuclear factor E2related factor-2 (Nrf2) on NLRP3 inflammasome in necroptosis signal pathway induced by I/R injury. Methods:We investigated the mechanisms of Nrf2-negative regulation in necroptosis signaling pathway by using middle cerebral artery occlusion (MCAO) with Q-VD-OPH injected intraperitoneally. The protein level of the NLRP3 inflammasome was detected by western blot with Nrf2 knockdown and overexpression.NLRP3 inflammasome activation was Reactive oxygen species (ROS) dependent, and the protein level was regulated when N-acetylcysteine (NAC) and adenosine triphosphate (ATP) were selected as tools for regulating ROS.Results: We demonstrated the negative regulation of Nrf2 on NLRP3 inflammasome activation in Q-VD-OPH-induced necroptosis in cerebral artery I/R injury through Lentivirus-mediated RNA Interferenc, which mediated knockdown and overexpression of Nrf2. NLRP3 inflammasome activation was sensitive to both ATP-mediated ROS level increases and NAC-mediated ROS inhibition, suggesting that ROS is associated with the activation of NLRP3 inflammasome in necroptosis. In addition, Nrf2-induced NAD(P) H quinone dehydrogenase 1 (NQO1) was involved in the inhibition of NLRP3 inflammasome activation.These results suggest that Nrf2 regulates NQO1 to attenuate ROS, which negatively regulates NLRP3 inflammasome.Conclusions: Nrf2/NQO1 was an inhibitor of ROS-induced NLRP3 inflammasome activation in Q-VD-OPH-induced necroptosis following cerebral I/R injury. Therefore, NLRP3 inflammasome could be a potential therapeutic target for cerebral ischemia.

Radiodermatitis, inflammatory lesions of skin and mucosa caused by radiation, is a common adverse effect during the radiation therapy of vulvar carcinoma. The incidence of radiodermatitis is affected by various factors, and the purpose of this study was to investigate the risk factors of radiodermatitis in patients with vulvar carcinoma. Patients with vulvar tumors who received radiotherapy from January 2015 to December 2020 were included in this retrospective study. Radiodermatitis was graded according to the grading criteria of the American Center for Radiological Oncology, and then univariate analysis and logistic multivariate regression analysis were used to determine the risk factors of radiodermatitis. A total of 60 eligible patients were enrolled, including 3 (5%), 25 (41.7%), 28 (46.7%), and 4 (6.6%) patients with grade 0, 1, 2, and 3 radiodermatitis, respectively. Univariate analysis showed that the incidence of radiodermatitis was significantly correlated with age, therapeutic strategy, pathological stage and radiotherapy dose (p < .05). Multivariate regression analysis indicated that age, therapeutic strategy and radiotherapy dose were independent risk factors for radiodermatitis (p < .05). In the current study, we identified the independent risk factors for radiodermatitis in patients with vulvar carcinoma were age, therapeutic strategy and radiotherapy dose, which might be conducive to identify high-risk patients, so as to adjust their treatment plan in time and reduce the risk of radiation-induced skin toxicity.