Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

Esophageal submucosal hematoma is rarely seen in clinical practice and its clinical presentations are untypical.Gastroscopy might injure the esophageal mucosa and cause bleeding.Computed tomography had the advantages of quick examination and formation of imaging,as well as non-invasiveness,which is helpful for the diagnosis and differential diagnosis of the esophageal submucosal hematoma.The clinical data of 9 patients with esophageal submucosal hematoma who were admitted to the Yueqing People's Hospital,the First Affiliated Hospital of Wenzhou Medical University,the First Affiliated Hospital of the Zhengzhou University and the Third People's Hospital of Wenzhou from July 2005 to February 2014 were retrospectively analyzed.The features of computed tomography examination of esophageal submocosal hematoma include the range of the esophageal submucosal hematoma exceeds 2 parts of the esophagus,the rip of the esophageal mucosa begins and ends at the physiological narrowing of the esophagus,thickening of the esophageal wall,stricture of the esophagus,annular thickening and eccentric thickening of the esophageal wall,crescent,spot or gas shadows of the esophageal cavity,the density of the hematoma decreases as the time passed by.These features of computed tomography are of great importance for the diagnosis of esophageal submucosal hematoma.