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 observe the value of parallel reverse enhance attention network module based on Kolmogorov-Arnold networks(KAN-PrdaModule)for segmenting polyps showed on colonoscopy images.Methods Nine hundred colonoscopy images in Kvasir-SEG dataset and 550 colonoscopy images in CVC-ClinicDB dataset were selected as training set(n=1 450),while 196 colonoscopy images in ETIS dataset,62 in CVC-ClinicDB dataset,380 in CVC-ColonDB dataset and 100 in Kvasir-SEG dataset were enrolled as test set(n=738).KAN-PrdaModule was proposed through improving U-Net,which improved detection accuracy through multi-scale feature fusion,and the value of KAN-PrdaModule for segmenting polyps showed on colonoscopy images was analyzed according to mean Dice similarity coefficient(mDSC),mean intersection over union(mIoU),weighted metric(Fωβ)and structural metric(Sα),and compared with U-Net,U-Net++,stochastic frontier analysis(SFA)and PraNet models.Results Among the above 5 models,the performance of SFA model for segmenting polyps on colonoscopy images was poor,with blurry edges of polyps and some ones were missed.U-Net and U-Net++models had decent performance,which could roughly identify polyps.PraNet model performed well,and the segmented edges of polyps were clear.KAN-PrdaModule had the best performance,showed high similarity to the true value images,with the best overall mDSC,mIoU,Fωβand Sα.Conclusion KAN-PrdaModule could effectively segment polyps showed on colonoscopy images,with segmenting effect better than U-Net,U-Net++,SFA and PraNet models.

Uveal melanoma is the most prominent aggressive intraocular cancer, which threatens the survival and vision of patients.Although the primary tumor can be controlled in various ways, nearly half of patients eventually die from liver metastases.Therefore, it is necessary to explore effective treatment therapies to improve the quality and survival time of patients.Mice model is the most common animal model for uveal melanoma.Several mouse models are available to be selected for different research purposes.Current mouse models of uveal melanoma include allograft models, xenograft models and genetic engineering models.Although the mouse model has been used in the study of uveal melanoma for more than 40 years, there is little literature on the subject at home and abroad due to the diversity of animal models and the complexity of genomic variation in uveal melanoma.This article reviews relevant domestic and international studies on mouse models of uveal melanoma to focus on the advantages, limitations and application range of existing models, providing references for animal studies of uveal melanoma.

Uveal melanoma is the most prominent aggressive intraocular cancer, which threatens the survival and vision of patients.Although the primary tumor can be controlled in various ways, nearly half of patients eventually die from liver metastases.Therefore, it is necessary to explore effective treatment therapies to improve the quality and survival time of patients.Mice model is the most common animal model for uveal melanoma.Several mouse models are available to be selected for different research purposes.Current mouse models of uveal melanoma include allograft models, xenograft models and genetic engineering models.Although the mouse model has been used in the study of uveal melanoma for more than 40 years, there is little literature on the subject at home and abroad due to the diversity of animal models and the complexity of genomic variation in uveal melanoma.This article reviews relevant domestic and international studies on mouse models of uveal melanoma to focus on the advantages, limitations and application range of existing models, providing references for animal studies of uveal melanoma.

Objective To observe the value of parallel reverse enhance attention network module based on Kolmogorov-Arnold networks(KAN-PrdaModule)for segmenting polyps showed on colonoscopy images.Methods Nine hundred colonoscopy images in Kvasir-SEG dataset and 550 colonoscopy images in CVC-ClinicDB dataset were selected as training set(n=1 450),while 196 colonoscopy images in ETIS dataset,62 in CVC-ClinicDB dataset,380 in CVC-ColonDB dataset and 100 in Kvasir-SEG dataset were enrolled as test set(n=738).KAN-PrdaModule was proposed through improving U-Net,which improved detection accuracy through multi-scale feature fusion,and the value of KAN-PrdaModule for segmenting polyps showed on colonoscopy images was analyzed according to mean Dice similarity coefficient(mDSC),mean intersection over union(mIoU),weighted metric(Fωβ)and structural metric(Sα),and compared with U-Net,U-Net++,stochastic frontier analysis(SFA)and PraNet models.Results Among the above 5 models,the performance of SFA model for segmenting polyps on colonoscopy images was poor,with blurry edges of polyps and some ones were missed.U-Net and U-Net++models had decent performance,which could roughly identify polyps.PraNet model performed well,and the segmented edges of polyps were clear.KAN-PrdaModule had the best performance,showed high similarity to the true value images,with the best overall mDSC,mIoU,Fωβand Sα.Conclusion KAN-PrdaModule could effectively segment polyps showed on colonoscopy images,with segmenting effect better than U-Net,U-Net++,SFA and PraNet models.

PURPOSE: Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients.METHODS: A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed.RESULTS: There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%).CONCLUSIONS: Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.
Adrenal Cortex Hormones ; Asthma ; China ; Comorbidity ; Disease Progression ; Education ; Female ; Food Hypersensitivity ; Hospitalization ; Humans ; Hypertension ; Inpatients ; Medication Adherence ; Mortality ; Multivariate Analysis ; Pulmonary Disease, Chronic Obstructive ; Retrospective Studies ; Risk Factors ; Seasons ; Self Care ; Smoke ; Smoking

Betacoronavirus ; Consensus ; Coronavirus Infections ; complications ; epidemiology ; prevention & control ; Epidemics ; Humans ; Minimally Invasive Surgical Procedures ; Musculoskeletal Diseases ; complications ; therapy ; Pandemics ; prevention & control ; Pneumonia, Viral ; complications ; epidemiology ; prevention & control

To evaluate the effectiveness and safety of Xinling Wan on patients with stable angina pectoris, a randomized, double-blinded, placebo parallel-controlled, multicenter clinical trial was conducted. A total of 232 subjects were enrolled and randomly divided into experiment group and placebo group. The experiment group was treated with Xinling Wan (two pills each time, three times daily) for 4 weeks, and the placebo group was treated with placebo. The effectiveness evaluation showed that Xinling Wan could significantly increase the total duration of treadmill exercise among patients with stable angina pectoris. FAS analysis showed that the difference value of the total exercise duration was between experiment group (72.11±139.32) s and placebo group (31.25±108.32) s. Xinling Wan could remarkably increase the total effective rate of angina pectoris symptom score, and the analysis showed that the total effective rate was 78.95% in experiment group and 42.61% in placebo group. The reduction of nitroglycerin dose was (2.45±2.41) tablets in experiment group and (0.50±2.24) tablets in placebo group on the basis of FAS analysis. The decrease of symptom integral was (4.68±3.49) in experiment group and (3.19±3.31) in placebo group based on FAS analysis. Besides, Xinling Wan could decrease the weekly attack time and the duration of angina pectoris. PPS analysis results were similar to those of FAS analysis. In conclusion, Xinling Wan has an obvious therapeutic effect in treating stable angina pectoris, with a good safety and a low incidence of adverse event and adverse reaction in experiment group.

Objective To observe the influence of down-regulation of HtrA1 expression by small interfering RNA on light-injured human retinal pigment epithelium (RPE) cells.Methods Cultured human RPE cells(8th-12th generations)were exposed to the blue light at the intensity of (2000 ± 500) Lux for 6 hours to establish the light injured model.Light injured cells were divided into HtrA1 siRNA group,negative control group and blank control group.HtrA1 siRNA group and negative control group were transfected with HtrA1 siRNA and control siRNA respectively.The proliferation of cells was assayed by CCK-8 method.Transwell test was used to detect the invasion ability of these three groups.Flow cytometry was used to detect the cell cycle and apoptosis.The expression of HtrA1 and vascular endothelial growth factor (VEGF)-A was detected by real time-polymerase chain reaction and Western blot respectively.Results The mRNA and protein level of HtrA1 in the light injured cells increased significantly compared to that in normal RPE cells (t=17.62,15.09;P＜0.05).Compared with negative control group and blank control group,the knockdown of HtrA1 in HtrA1 siRNA group was associated with reduced cellular proliferation (t=6.37,4.52),migration (t =9.56,12.13),apoptosis (t =23.37,29.08) and decreased mRNA (t=17.36,11.32,7.29,4.05) and protein levels (t=12.02,15.28,4.98,6.24) of HtrA1 and VEGF-A.Cells of HtrA1 siRNA group mainly remained in G0/G1 phase,the difference was statistically significant (t=6.24,4.93;P ＜0.05).Conclusion Knockdown of HtrA1 gene may reduce the proliferation,migration capability and apoptosis of light-injured RPE cells,and decrease the expression of VEGF-A.

Objective To analyze the constituent of the 32 kD protein band and its expression in schizophrenia se?rum. Methods Sixty schizophrenia patients and 58 health controls were recruited. The serum samples were collected and precipitated with 7%PEG. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was used to ob?tain the abnormal 32 kD proteins band in patients. This protein band was cut and then analyzed using mass spectrometric technique. Results The 32 kD protein band was present in 38 schizophrenia patients but not in control and positive rate was 63.33%. The mass spectrometric analysis showed that 32 kD protein band contained 14 proteins ranging from 30 kD to 35 kD, including 6 high-frequency proteins (cDNA coded protein 1 and 2, Apolin protein A-1, Isoform 2 of ficolin-2, Complement factor H and clusterin) and 8 low-frequency proteins (IgG H chain, zinc-alphg-2-glycoprotein, fermitin,family apolin protein L-1, isoform 10 of collectin-1, purine nucleoside, anne xin and cDNA coded protein 3). Three cD?NA coded unknown proteins were highly similar to complement C4-B, β2-glycoprotein and erythrocyte band 7 integral membrane protein. Conclusion There is a unknown specific 32 kD protein that is consisted mainly of fourteen proteins in serum of schizophrenia.