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 delineate the epidemiologic profile of rifampicin resistant pulmonary tuberculosis (RR-PTB) among students in Chongqing, so as to provide evidence for effectively controlling RR-PTB outbreaks in schools. Methods: Individual level surveillance records of 395 student RR-PTB cases reported from 2015 to 2024 were extracted from the China Information System for Disease Control and Prevention. The Joinpoint regression analysis was employed to quantify temporal trends in the registration rate of student RR-PTB cases, and the comparison of RR-PTB registration rates with different demographic characteristics and different regions was performed using Chi-square test. Results: From 2015 to 2024, a total of 395 student RR-PTB cases were identified, with the registration rate ranged from 0.07 per 100 000 to 1.47 per 100 000, showed a fluctuating upward trend ( AAPC= 35.22%, t =4.13, P <0.01). A turning point was detected in 2017, rates rose during 2015-2017 (APC=295.23%， t =4.62， P < 0.01 ) and plateaued thereafter (APC=-0.47%， t =-0.12， P =0.91). The proportion of RR-PTB cases occurring among students increased both among all RR-PTB cases (1.54% in 2015, 7.48% in 2024) and all student pulmonary tuberculosis cases (0.20% in 2015, 7.17% in 2024), with significant linear trends ( χ 2 trend =33.55,159.98, both P <0.01). The majority of cases were enrolled in senior high school (50.38%), classified as retreatment (53.92%), of Han ethnicity (75.95%), and diagnosed with multidrug resistant tuberculosis(53.16%). There were significant differences in the composition of different ethnicity, registration category and resistance pattern between different years( χ 2=23.47, 17.23, 59.64，all P <0.05). The South-Eastern Wuling Mountainous Region exhibited the highest notification rate (3.96 per 100 000), whereas the western region had the lowest rate ( 0.47 per 100 000). County level jurisdictions reported higher rates than district level ones (2.16 per 100 000 vs 0.63 per 100 000 ). Statistically significant differences were observed in the RR-PTB reported rates among students across different districts and counties( χ 2=418.05,167.05,both P <0.01). Conclusions From 2015 to 2024, the registration rate of detected student RR-PTB cases in Chongqing showed an increasing trend. Students have become one of the key populations for drug resistant TB prevention and control. Intensified health education and active case finding should be implemented to enhance proactive surveillance capabilities.

Objective By summarizing the literature on the treatment of bronchial asthma with"Tonifying the spleen to help the lung"as the guiding ideology and"tonifying spleen drugs"published in recent 25 years,analyzing the domestic research situation,to understanding the research status of the mechanism of"Tonifying the spleen to help the lung"in the treatment of asthma,so as to provide ideas for the research of traditional Chinese medicine in the treatment of asthma.Methods Taking"Tonifying the spleen to help the lung","tonifying the spleen","strengthening the spleen","transporting the spleen","benefiting the spleen","Shenling Baizhu Powder","Yigong Powder","Ginseng Schisandra Decoction","Maimendong Decoction","Liujunzi Decoction"and"asthma"as the keywords,searching the literature in the Chinese Journal Full-text Database(CNKI),extracting the data recorded in the literature,including prescriptions,drug composition,test indexes and experimental results,and summarize and analyze the data.Results A total of 54 literatures were included in this literature study.The prescriptions of"Tonifying the spleen to help the lung"method in the treatment of asthma are complex.The classic prescriptions often involved include Liujunzi Decoction,Yupingfeng Powder,Yigong Powder,Buzhong yiqi decoction,Shenling baizhu powder,Maimendong decoction,Ginseng Schisandra decoction and Erchen decoction.The commonly used drugs include Atractylodes macrocephala,Astragalus membranaceus,Poria cocos,licorice,tangerine peel,etc.Experimental research mainly involves inflammatory cells,immunoglobulins,cytokines,signaling pathway,T cell subsets,cell receptors,intestinal flora and other aspects,and the specific detection indicators are complex and diverse.Conclusion The method of"Tonifying the spleen to help the lung"is effective in the treatment of bronchial asthma.Many studies show that its effect has a clear scientific basis,but its mechanism is complex and diverse and is gradually becoming clear.

Objective:To explore the current situation and influencing factors of somatic and psychological symptoms among nursing undergraduate students.Methods:This study was a cross-sectional study. Through snowball sampling and convenience sampling, 806 nursing undergraduate students from East, South, Central, North, Northwest and Southwest China were selected as the research subjects from March to July 2021. A survey was conducted among nursing undergraduate students using the Patient Health Questionnaire-15 (PHQ-15), Patient Health Questionnaire-2 (PHQ-2), and Generalized Anxiety Disorder-2 (GAD-2) .Results:The positive detection rates of somatic symptoms, depression, and anxiety among 806 nursing undergraduate students were 66.5% (536/806), 14.3% (115/806), and 12.9% (104/806), respectively. The results of binomial Logistic regression analysis showed that chronic diseases, perceived health status, and water intake were the influencing factors for psychological and somatic symptoms of nursing undergraduate students ( P<0.05). Nursing undergraduate students' somatic symptoms, depression and anxiety were positively correlated ( P<0.05) . Conclusions:The detection rate of somatic symptoms among nursing undergraduate students is high. Families and universities should pay timely attention to the psychological and somatic health of nursing undergraduate students, and provide targeted psychological support for students with different characteristics.

Objective: To understand the current situation of school tuberculosis prevention and control system and the implementation of daily prevention and control measures, and to provide a reference for strengthening the prevention and control of tuberculosis in schools. Methods: A random sampling method was used to select schools where on site questionnaire survey was carried out, including 156 junior high schools, 78 senior high schools and 6 universities. SPSS 25.0 was used for descriptive analysis and chi square test. Results: The average annual screening rates of junior high school, senior high school and university from 2015 to 2020 were 58.84%, 71.71% and 84.41% respectively, and the difference was statistically significant ( χ 2=61 247.39， P <0.01). The average annual TB detection rates were 8.69/10 5, 50.89/10 5 and 36.51/10 5 respectively, and the difference was statistically significant ( χ 2=101.20， P <0.01). The screening rate of TB screening in 2015-2020 years increased by year( χ 2 trend =70 052.10, 86 182.82 , 22 213.56， P <0.01). The detection rate of TB among junior high schools and high schools has been increasing year by year( χ 2 trend =9.27, 12.23, P <0.01). From 2015 to 2020, the proportion of tuberculosis screening, contact history, PPD and chest screening increased by year in junior high school and senior high school freshmen, and the difference was statistically significant ( χ 2=129.10, 118.10, 206.92, 37.67; 108.79, 84.90, 139.84, 51.82, P <0.01). The proportion of chest X ray screening in universities increased by year( χ 2 trend =18.33， P <0.01). In 2019, poor performance on TB control in universities mainly included, including the school responsibility system for tuberculosis prevention and control, the school s annual TB work plan and absenteeism registration and etiology tracing, the proportion was 50.00 %, 0 and 16.67% respectively, compared with junior high school and senior high school, the difference was statistically significant( P <0.05). The prevalence rates of junior high school, senior high school and university students were 33.75/10 5, 90.10/10 5 and 54.20/10 5 respectively in 2019, and the difference was statistically significant ( χ 2=104.36， P <0.01). Conclusion The proportion of TB screening for freshmen in Chongqing increased significantly during 2015- 2020. High school students are still the focus of school based tuberculosis prevention and control. Improving the proportion of tuberculosis screening，strengthening and standardizing physical examination and screening，and establishing a clear responsibility system for prevention and control are effective means to prevent and control the spread of tuberculosis on campus.

Objective: To provide the evidence for tuberculosis pvevalence for high school freshmen by analyzing data of entrance physical exarnination of Chongqing in 2018. Methods: The TB information management system of schools in Chongqing was used to collect the data of TB physical examination for high school freshmen in 2018. Excel 2007 was used to establish database, SPSS 25.0 software was used for statistical analysis, including descriptive analysis, chi square test. Results: In 2018, a total of 118 370 freshmen from 146 general education high schools and a total of 30 842 freshmen from 30 secondary vocational schools had TB screening during physical examination for freshmen. The proportion of school and freshmen participating in the TB examination was 40.09% and 44.28% respectively. The rates of school (57.03%) and freshmen (58.81%) participating in the examination of tuberculosis in senior high school students of general education were higher than those in secondary vocational education schools(16.39%, 22.73%), the difference was statistically significant(χ2=73.38, 42 744.64, P<0.01). 84 cases of active pulmonary tuberculosis (APTB) were detected in the physical examination of high school freshmen, mainly smear negative patients (92.86%)，and there was no significant difference in the prevalence of tuberculosis among the freshmen with different education, school and screening methods(P>0.05). The detection rates of TB among freshmen in general education and vocational education were 49.00/100 000 and 54.62/100 000 respectively. The detection rates of tuberculosis among freshmen in public schools and private schools were 50.29/100 000 and 124.88/100 000 respectively(χ2=5.42, 10.92, P<0.05). The detection rate of direct chest X-ray examination was 62.90/100 000. The first screening method was PPD test and the detection rate of chest X-ray examination was 84.30/100 000 for those with strong positive PPD test, the differences was no significant(χ2=0.29, P>0.05). Conclusion The tuberculosis screening program for high school freshmen is of great significance to the prevention and control of tuberculosis. Effective screening methods should be adopted and strengthened in secondary vocational schools.

OBJECTIVETo assess the association of CYP2C19 gene polymorphisms with the incidence of ischemic stroke among patients receiving clopidogrel therapy following coronary stenting for coronary artery disease.

METHODSClinical data of patients receiving clopidogrel therapy after coronary stenting were retrospectively studied. For a case-control study, 137 patients with acute cerebral infarction and 122 non-stroke patients were selected. Based on the variants of the CYP2C19 gene detected by a DNA microarray assay, the patients were further divided into the wild-type group(CYP2C19*1/*1) and mutant group(defined by the presence of at least one loss-of-function allele, including CYP2C19*1/*2, CYP2C19*1/*3, CYP2C19*2/*2, CYP2C19*2/*3 and CYP2C19*3/*3). The incidences of ischemic stroke in the two groups were compared through a chi-square analysis. The influence of CYP2C19 gene polymorphisms and clopidogrel therapy on the incidence of ischemic stroke was analyzed through multivariable logistic regression.

RESULTSA total of 259 patients were enrolled. The case and control groups showed no difference in terms of gender and age. There were 123 cases (47.5%) in the CYP2C19 wild-type group and 136 cases (52.5%) in the mutant group. The incidence of ischemic stroke of mutant group was significantly higher than that of wild-type group (59.9% vs. 44.3%, X2=6.398, P=0.042). Multivariate analysis revealed that loss-of-function polymorphisms of the CYP2C19 gene carried a 1.13 times greater risk for ischemic stroke compared to wild-type genotype (OR=2.13, 95%CI: 1.23-3.71).

CONCLUSIONThe efficacy of clopidogrel for the prevention of ischemic stroke in post-coronary stent patients may be reduced by the insufficiency of the CYP2C19 gene. The dosage of clopidogrel therapy should be adjusted based on its polymorphisms.

Brain Ischemia ; prevention & control ; Cytochrome P-450 CYP2C19 ; genetics ; Genotype ; Humans ; Percutaneous Coronary Intervention ; adverse effects ; Platelet Aggregation Inhibitors ; therapeutic use ; Polymorphism, Genetic ; Stents ; adverse effects ; Stroke ; prevention & control ; Ticlopidine ; analogs & derivatives ; therapeutic use

Chronic hepatitis B virus (HBV) carriers are facing the risk of progression to liver fibrosis,liver cirrhosis,and hepatocellular carcinoma.However,due to low risk,slow disease progression,and unsatisfactory short-term effect of antiviral treatment,controversy still exists over whether such patients should be given antiviral treatment.This article reviews the research advances in the necessity and feasibility of antiviral therapy for chronic hepatitis B virus carriers,so as to provide a reference for clinical practice.

Objective To evaluate the effects of prevention and control measures on coal-burning endemic fluorosis in Wulong County of Chongqing.Methods At a county level investigation,seven of the disease affected villages were investigated to evaluate the effectiveness of prevention and control measures on coal-burning endemic fluorosis in Wulong County from October 2012 to April 2013.Dental fluorosis of all children aged 8-12 was examined in every selected village.Urine samples of 50 children were collected and urinary iodine level was determined.The installed improved stoves,the drying of corn and pepper were investigated in every household surveyed.Ten samples of corn and pepper were collected and iodine level was determined.At a city level survey,seven of the disease affected villages were investigated to evaluate the effectiveness of prevention and control measures on coal-burning endemic fluorosis in April 2013.Dental fluorosis of all children aged 8-12 was examined in all villages.Ten households were selected for investigation of the installation of improved stoves,drying of corn and pepper.Children dental fluorosis was diagnosed based on the standard for Diagnosis of Dental FIuorosis (WS/T 208-2011).The fluoride concentration of children's urine was measured according to the standard for Urine-determination of Fluoride-ion Specific Electrode Method (WS/T 89-1996).The fluoride concentration of corn and pepper was measured by the method of fluoride-ion selective electrode.Results The field survey results at the county level showed that the prevalence rate of dental fluorosis of children aged 8-12 was 8.01％ (44/549).The qualified rate of installed improved stoves was 99.56％(3 186/3 200) and the rate of correct usage of improved stoves was 99.78％(3 179/3 186).The correct drying rates of corn and pepper were all 100.00％(2 390/2 390).Three hundred and fourteen urine samples were collected and the fluoride content was 0.25 mg/L.Fifty-eight corn and 58 pepper samples were collected.The fluoride contents of corn and pepper were 0.70,2.09 mg/kg,respectively.At the field survey at city level,seven of the disease affected villages were investigated,the prevalence rate of dental fluorosis of children was 11.28％ (38/337).Seventy households were surveyed for the improved stoves.The qualified rate of installation of improved stoves and the rate of correct usage of improved stoves were all 100.00％(70/70,70/70).The drying of 56 corn and 58 pepper samples was surveyed.The correct drying rates of corn and pepper were all 100.00％(56/56,58/58).Conchsion All villages have reached the elimination criteria of coal-burning endemic fluorosis areas in Wulong County.

Objective To investigate the association between nutrition and peripheral artery disease (PAD) in continuous ambulatory peritoneal dialysis (CAPD) patients.Methods One hundred and two stable CAPD patients from a single center were enrolled in this cross-sectional study.Automatic ankle-brachial index (ABI) measuring system was applied to examine ABI.Patients were divided into PAD group (ABI ＜ 0.9) and non-PAD group (ABI≥0.9).Clinical data were collected.Biochemical parameters were detected.Nutritional status was evaluated by serum albumin,handgrip strength (HGS) and subjective global assessment (SGA).Logistic regression analysis was performed to estimate the association of PAD with each nutritional marker as well as other potential risk factors.Results The incidence of PAD was 23.53％ (24/102).ABI was significantly lower in patients with malnutrition as compared to those without malnutrition [(0.72 ± 0.21) vs (1.04 ± 0.14),P＜0.01].Compared with non-PAD patients,serum albumin (P ＜ 0.01),HGS (P ＜ 0.01),diastolic blood pressure (P ＜ 0.05),serum creatine (P ＜ 0.05)、blood urine nitrogen (P ＜ 0.01) were significantly decreased,but age (P ＜ 0.01),the incidence of malnutrition [SGA,P ＜ 0.01],diabetic status (P ＜ 0.01),cardiovascular disease history (P ＜ 0.01) were significantly increased in PAD patients.Logistic regression analysis showed that serum albumin (OR=0.762,95％ CI:0.611-0.948,P=0.015),HGS (OR=0.988,95％ CI:0.979-0.997,P=0.013) were independent protective factors for PAD,malnutrition [(SGA),OR=21.101,95％ CI:5.008-88.901,P＜0.01] was independent risk factor for PAD in CAPD patients.Conclusions The PAD incidence of CAPD patients in our center is 23.53％.Nutrition is independent factor associated with PAD in CAPD patients.