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.

OBJECTIVE:To explore optimization method and effect of clinical pharmacists on anticoagulants therapy plan for cancer patient with venous thromboembolism(VTE). METHODS:Clinical pharmacists participated in the whole process of antico-agulant therapy for one case of breast cancer complicated with VTE. Clinical pharmacists suggested patient to initially take low mo-lecular weight heparin sodium 0.6 ml,sc,qd;and then take Warfarin sodium tablet 3 mg,po,qd;initial plan and oral dosage form plan superimposed and alternated,and pharmaceutical care and medication education were also provided for the patient. RESULTS:Physicians adopted clinical pharmacist's suggestions,and the patient received anticoagulant therapy for 27 days and paclitaxel che-motherapy once. Coagulation function INR was 2.71;the patient didn't felt discomfort and then discharged from hospital. CON-CLUSIONS:The participation of clinical pharmacists in the optimization of individualized anticoagulant therapy and pharmaceutical care is able to promote rational drug use,prevent severe ADR in the clinic,guarantee the safety of drug use and improve medica-tion compliance.

Aged ; Humans ; Kidney Neoplasms ; pathology ; Male ; Neoplasm Metastasis ; Paranasal Sinus Neoplasms ; secondary