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 evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

Objective To investigate the value of salivagram in the diagnosis of pediatric pulmonary aspiration.Methods A total of 469 pediatric patients (age:6 weeks-16 years,average age (4.5±3.1) years;229 males,240 females) underwent salivagram.Signed informed consents were obtained.99Tcm-SC (11.1 MBq,100 μl) was dropped into the root of tongue.After the dropping,the posterior dynamic acquisition was started for 60 min,and then the anterior and posterior static images were acquired for 5 min.All patients were followed up for 3-6 months after the salivagram,and the salivagram results were analyzed.If radioactivity was shown in the main bronchus or bilateral lung fields,the pulmonary aspiration was diagnosed.Results Salivagram demonstrated positive results in 20.7％ (97/469) of the patients.However,3 patients with pulmonary aspiration showed negative results.There was no false positive result on salivagram.Conclusion Salivagram shows good results in the diagnosis of pediatric pulmonary aspiration.

Objective To study the correlations of VDR FokⅠgene polymorphism with type 2 diabetes in postmenopausal women of Han nationality in south Sichuan. Methods 160 patients with type 2 diabetes (T2DM) and 190 healthy cases were enrolled in the study. The VDR FokⅠgene polymorphisms were detected using RFLP-PCR and DNA sequencing. Results The FF, Ff and ff genotype frequencies were 32.5%, 47.5%and 20% in the T2DM group and 15.8%, 53.7%, 30.5% in the control group, respectively (P < 0.05). The allele frequencies were 56.3%, 43.8% in the T2DM group and 42.6%, 57.4% in the control group, respectively (P < 0.05). The risk of T2DM in the FF genotype people was 2.568 times higher than Ff/ff genotype (adjusted OR = 2.568, 95%CI = 1.246 ~ 5.292, P < 0.05). The levels of 2 h PG and HbA1C in the FF genotype people were significantly higher than those of the Ff/ff genotype people (P<0.05). Conclusions There was an association between the VDR FokⅠgene polymorphism and type 2 diabetes incidence in the postmenopausal women in south Sichuan area.

BACKGROUND AND PURPOSE: PET scanning with fluorodeoxyglucose (FDG-PET) is a non-invasive method that measures regional glucose metabolic rate. Phenylalanine (Phe) and its metabolites appear to impair several aspects of brain energy metabolism. 1) To evaluate brain glucose metabolism with FDG-PET imaging in phenylketonuria (PKU) patients before and 4 months after sapropterin therapy; 2) to evaluate neurodevelopmental changes, blood Phe levels and dietary Phe tolerance before and after sapropterin therapy; 3) to generate pilot data to assess the feasibility of evaluating brain glucose metabolism with FDG-PET imaging and to explore potential trends resulting from the administration of sapropterin therapy. METHODS: We enrolled 5 subjects, ranged in age from 22 years to 51 years, with PKU. Subjects underwent FDG-PET brain imaging, blood tests for Phe and tyrosine levels, and neurocognitive evaluations before and 4 months after sapropterin therapy (20 mg/kg/day). All subjects' Phe and tyrosine levels were monitored once a week during the study. Subjects kept 3 day diet records that allow calculation of Phe intake. RESULTS: None of the subjects responded to sapropterin therapy based on 30% decrease in blood Phe level. The data show that glucose metabolism appeared depressed in the cerebellum and left parietal cortex while it was increased in the frontal and anterior cingulate cortices in all five subjects. In response to sapropterin therapy, relative glucose metabolism showed significant increases in left Broca's and right superior lateral temporal cortices. Interestingly, there was corresponding enhanced performance in a phonemic fluency test performed during pre- and postneurocognitive evaluation. CONCLUSIONS: Further studies with a larger sample size are needed to confirm the above changes in both sapropterin non-responsive and responsive PKU patients.
Biopterin ; Brain ; Cerebellum ; Diet Records ; Electrons ; Energy Metabolism ; Glucose ; Hematologic Tests ; Humans ; Neuroimaging ; Phenylalanine ; Phenylketonurias ; Pilot Projects ; Positron-Emission Tomography ; Sample Size ; Tyrosine

OBJECTIVETo evaluate the efficacy and safety of vardenafil on men with erectile dysfunction (ED) of various etiologies.

METHODSA total of 88 men with mild to severe erectile dysfunction were enrolled in the randomized, double-blind, placebo-controlled, fixed-dose trial of 12 weeks of treatment with either placebo or 5, 10 and 20 mg of vardenafil.

RESULTSThis study indicated that vardenafil dosages of 5, 10 and 20 mg were significantly superior to placebo for the treatment of ED, on the basis of the primary study endpoints of the EF domain score of the IIEF, diary-recorded success rates for penetration and maintenance of erection during the intercourse and the GAQ. Vardenafil was well tolerated. The incidence of adverse events was higher for vardenafil than for placebo.

CONCLUSIONOral vardenafil therapy has a high efficacy and a low incidence of adverse events for ED patients with mixed etiologies.

Administration, Oral ; Adult ; Aged ; Double-Blind Method ; Erectile Dysfunction ; drug therapy ; Humans ; Imidazoles ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Phosphodiesterase Inhibitors ; adverse effects ; therapeutic use ; Piperazines ; adverse effects ; therapeutic use ; Sulfones ; adverse effects ; therapeutic use ; Triazines ; adverse effects ; therapeutic use ; Vardenafil Dihydrochloride