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:To analyze the influencing factors of pancreatic fistula after pancreaticoduodenectomy (PD), and to construct and evaluate the prediction model of postoperative pancreatic fistula (POPF).Methods:Clinical data of 255 PD patients undergoing PD at the General Surgery Department of the Second Affiliated Hospital of Air Force Military Medical University from January 2016 to January 2023 were retrospectively analyzed as the training set, including 148 males and 107 females, aged 58.0 (52.0, 64.5) years. According to the occurrence of POPF, patiennts were divided into the pancreatic fistula group ( n=65, including grade B and C POPF) and the non-pancreatic fistula group ( n=190). The age, gender, body mass index (BMI), white blood cell (WBC) count and neutrophil/lymphocyte ratio (NLR) before surgery and on the postoperative day (POD) 3, albumin, diameter of pancreatic duct, texture of the pancreas, operation time, and amylase concentration in the drainage fluid on POD3 were compared between the groups. Multivariate logistic regression analyses were conducted to identify the influencing factors of POPF. The nomogram of the pancreatic fistula prediction model was constructed using the rms package. One thousand cases were selected as the test set through the Bootstrap resampling method. And in the test set the receiver operating characteristic (ROC) curve and calibration curve were drawn to evaluate the model. Results:Logistic univariate analysis showed that there were significant differences between the two groups in terms of age, BMI, WBC count and NLR (preoperative and on POD3), the concentration of amylase in drainage fluid on POD3, pancreatic duct diameter, and operation time (all P<0.05). The results of logistic multivariate regression analysis showed age ( OR=1.050, 95% CI: 1.011-1.091), BMI ( OR=1.127, 95% CI: 1.005-1.264) and the amylase concentration of the drainage fluid >367.5 U/L on POD3 ( OR=3.688, 95% CI: 1.849-7.354) were the influencing factors of POPF ( P<0.05). Based on the three influencing factors screened out by multivariate analysis, a histogram for the prediction of pancreatic fistula was constructed using the rms package. The area under the ROC curve of the nomogram for predicting the occurrence of pancreatic fistula after PD was 0.744 (95%CI: 0.679-0.809), with a sensitivity of 69.2% and a specificity of 70.5%. The calibration curve shows that the model's prediction is consistent with the actual situation in the overall trend, indicating a relatively high degree of calibration. Conclusion:Age, BMI and amylase concentration of drainage fluid >367.5 U/L on POD3 are the influencing factors for pancreatic fistula after PD. The nomogram model for predicting pancreatic fistula constructed based on this has good predictive and application value.

Objective To analyze the incidence trend and epidemiological characteristics of pulmonary tuberculosis(PTB)among healthcare workers(HCWs)in Chongqing City from 2019 to 2023,and provide reference for the pre-vention and control of tuberculosis among HCWs.Methods The registered data of PTB cases in Chongqing from 2019 to 2023 were collected from China Information System for Disease Prevention and Control.The three-dimen-sional distribution of registration rate,changing trend,and treatment characteristics of PTB among HCWs were an-alyzed using retrospective descriptive analysis method.Results A total of 646 HCWs PTB cases were registered in Chongqing from 2019 to 2023,and the average annual registration rate was higher than that of the entire population(52.34/100 000 vs 46.00/100 000).The registration rate in 2019-2023 showed an overall downward trend.The average annual registration rate of PTB among HCWs in hospitals was the highest(59.87/100 000),followed by primary medical institutions(41.62/100 000)and other medical institutions(35.21/100 000).The epidemic period of PTB among HCWs was March-June each year,with seasonal indices of 133.75％,100.31％,113.31％,and 117.03％,respectively.The average annual registration rate of PTB among HCWs in the southeast town of Chongqing was the highest(121.21/100 000),followed by the northeast town of Chongqing(89.51/100 000),while the lowest was in the main urban area(34.47/100 000).The registration rate of PTB among HCWs gradually decreased with the increase of age(P＜0.05).Compared with the whole population,the proportions of female PTB cases among HCWs(76.01％),25-＜35 age group(57.89％),pathogen negative(48.14％),active detected ca-ses(5.73％),initial treatment cases(95.82％),and cases using fixed-dose combination of PTB(74.15％)were all higher(all P＜0.05).The delay rate of seeking medical treatment was lower in HCWs than that in the entire popu-lation(52.63％vs 69.12％),and the success rate of treatment was higher(91.49％vs 84.19％)(both P＜0.05).Conclusion The registration rate of PTB among HCWs in Chongqing has been declining year by year,with diffe-rential distribution in different medical institutions and regions,presenting seasonal changes.The majority of cases are aged＜35 years old,and have high pathogen negative rate and high initial treatment rate.Targeted prevention and control strategies need to be developed based on occupational exposure characteristics.

Objective To analyze the incidence trend and epidemiological characteristics of pulmonary tuberculosis(PTB)among healthcare workers(HCWs)in Chongqing City from 2019 to 2023,and provide reference for the pre-vention and control of tuberculosis among HCWs.Methods The registered data of PTB cases in Chongqing from 2019 to 2023 were collected from China Information System for Disease Prevention and Control.The three-dimen-sional distribution of registration rate,changing trend,and treatment characteristics of PTB among HCWs were an-alyzed using retrospective descriptive analysis method.Results A total of 646 HCWs PTB cases were registered in Chongqing from 2019 to 2023,and the average annual registration rate was higher than that of the entire population(52.34/100 000 vs 46.00/100 000).The registration rate in 2019-2023 showed an overall downward trend.The average annual registration rate of PTB among HCWs in hospitals was the highest(59.87/100 000),followed by primary medical institutions(41.62/100 000)and other medical institutions(35.21/100 000).The epidemic period of PTB among HCWs was March-June each year,with seasonal indices of 133.75％,100.31％,113.31％,and 117.03％,respectively.The average annual registration rate of PTB among HCWs in the southeast town of Chongqing was the highest(121.21/100 000),followed by the northeast town of Chongqing(89.51/100 000),while the lowest was in the main urban area(34.47/100 000).The registration rate of PTB among HCWs gradually decreased with the increase of age(P＜0.05).Compared with the whole population,the proportions of female PTB cases among HCWs(76.01％),25-＜35 age group(57.89％),pathogen negative(48.14％),active detected ca-ses(5.73％),initial treatment cases(95.82％),and cases using fixed-dose combination of PTB(74.15％)were all higher(all P＜0.05).The delay rate of seeking medical treatment was lower in HCWs than that in the entire popu-lation(52.63％vs 69.12％),and the success rate of treatment was higher(91.49％vs 84.19％)(both P＜0.05).Conclusion The registration rate of PTB among HCWs in Chongqing has been declining year by year,with diffe-rential distribution in different medical institutions and regions,presenting seasonal changes.The majority of cases are aged＜35 years old,and have high pathogen negative rate and high initial treatment rate.Targeted prevention and control strategies need to be developed based on occupational exposure characteristics.

Objective To investigate the diagnostic value of serum bromodomain-containing pro-tein 4(BRD4)combined with gastrin-17(G-17)in Helicobacter pylori(Hp)-positive early gastric cancer.Methods A total of 88 patients with Hp-positive early gastric cancer admitted to our hospital from September 2021 to September 2023 were selected as early gastric cancer group.Meanwhile,92 patients with Hp-positive precancerous lesions and 80 patients with Hp-positive gastritis admitted dur-ing the same period were selected as precancerous lesion group and gastritis group,respectively.En-zyme-linked immunosorbent assay(ELISA)was used to detect the serum levels of BRD4 and G-17.Multivariate logistic regression analysis was performed to screen the influencing factors of Hp-positive early gastric cancer.Receiver operating characteristic(ROC)curve analysis was used to evaluate the diagnostic value of serum BRD4 and G-17 in Hp-positive early gastric cancer.Results Compared with the gastritis group,the levels of BRD4 and G-17 in the precancerous lesion group and early gastric cancer group were significantly increased(P＜0.05).Furthermore,compared with the precancerous le-sion group,the levels of BRD4 and G-17 in the early gastric cancer group were also significantly elevated(P＜0.05).The proportion of patients with a family history of gastric cancer,those who preferred hot food,cold food,or high-salt food,as well as the levels of PG Ⅱ,BRD4,and G-17 were signifi-cantly higher in the early gastric cancer group than in the non-gastric cancer group,while the level of pepsinogen(PG)Ⅰ was significantly lower(P＜0.05).Logistic regression analysis revealed that preference for hot food,high-salt food,PG Ⅱ,BRD4,G-17,and PG Ⅰ were all influencing factors for Hp-positive early gastric cancer(P＜0.05).The area under the curve(AUC)values for serum BRD4,G-17,and their combination in diagnosing Hp-positive early gastric cancer were 0.793,0.830,and 0.912,respectively.The diagnostic efficacy of the combined detection was superior to that of single detection(P＜0.05).Conclusion The serum levels of BRD4 and G-17 are elevated in patients with Hp-positive early gastric cancer,and both exhibit certain diagnostic value for Hp-positive early gastric cancer,suggesting their potential as serum biomarkers for the diagnosis of Hp-positive early gastric cancer.

Objective To optimize the processing technology of Curculigo orchioides Gaertn.Methods On the basis of single factor experiment,the ratio of material to liquid,frying temperature and frying time were taken as the influencing factors,and the comprehensive scores of appearance traits,curculigoside,orcinol glucoside and orcinol gentiobioside were taken as the evaluation indexes.The optimal processing technology was optimized by Box-Behnken response surface method combined with analytic hierarchy process,and the process verification was carried out.Results The optimal process was as follows:the raw C.orchioides pieces were mixed with the same amount of Evodia rutaecarpa juice,placed in a closed container,moistened until the juice was completely absorbed,stir-fried at 130 ℃ for 6 min,taken out and dried at 60 ℃.For each 100 kg of Curculigo,10 kg of Evodia rutaecarpa was used.Evodia rutaecarpa juice preparation method:10 kg of Evodia rutaecarpa was soaked in 12 times the amount of water for 60 min,decocted for 50 min,extracted for 3 times,combined with the filtrate,and concentrated to 100 kg to obtain Evodia rutaecarpa juice.Conclusion The optimal processing technology of Curculigo orchioides Gaertn.is stable and feasible.

Objective To optimize the processing technology of Curculigo orchioides Gaertn.Methods On the basis of single factor experiment,the ratio of material to liquid,frying temperature and frying time were taken as the influencing factors,and the comprehensive scores of appearance traits,curculigoside,orcinol glucoside and orcinol gentiobioside were taken as the evaluation indexes.The optimal processing technology was optimized by Box-Behnken response surface method combined with analytic hierarchy process,and the process verification was carried out.Results The optimal process was as follows:the raw C.orchioides pieces were mixed with the same amount of Evodia rutaecarpa juice,placed in a closed container,moistened until the juice was completely absorbed,stir-fried at 130 ℃ for 6 min,taken out and dried at 60 ℃.For each 100 kg of Curculigo,10 kg of Evodia rutaecarpa was used.Evodia rutaecarpa juice preparation method:10 kg of Evodia rutaecarpa was soaked in 12 times the amount of water for 60 min,decocted for 50 min,extracted for 3 times,combined with the filtrate,and concentrated to 100 kg to obtain Evodia rutaecarpa juice.Conclusion The optimal processing technology of Curculigo orchioides Gaertn.is stable and feasible.

Objective:To analyze the influencing factors of pancreatic fistula after pancreaticoduodenectomy (PD), and to construct and evaluate the prediction model of postoperative pancreatic fistula (POPF).Methods:Clinical data of 255 PD patients undergoing PD at the General Surgery Department of the Second Affiliated Hospital of Air Force Military Medical University from January 2016 to January 2023 were retrospectively analyzed as the training set, including 148 males and 107 females, aged 58.0 (52.0, 64.5) years. According to the occurrence of POPF, patiennts were divided into the pancreatic fistula group ( n=65, including grade B and C POPF) and the non-pancreatic fistula group ( n=190). The age, gender, body mass index (BMI), white blood cell (WBC) count and neutrophil/lymphocyte ratio (NLR) before surgery and on the postoperative day (POD) 3, albumin, diameter of pancreatic duct, texture of the pancreas, operation time, and amylase concentration in the drainage fluid on POD3 were compared between the groups. Multivariate logistic regression analyses were conducted to identify the influencing factors of POPF. The nomogram of the pancreatic fistula prediction model was constructed using the rms package. One thousand cases were selected as the test set through the Bootstrap resampling method. And in the test set the receiver operating characteristic (ROC) curve and calibration curve were drawn to evaluate the model. Results:Logistic univariate analysis showed that there were significant differences between the two groups in terms of age, BMI, WBC count and NLR (preoperative and on POD3), the concentration of amylase in drainage fluid on POD3, pancreatic duct diameter, and operation time (all P<0.05). The results of logistic multivariate regression analysis showed age ( OR=1.050, 95% CI: 1.011-1.091), BMI ( OR=1.127, 95% CI: 1.005-1.264) and the amylase concentration of the drainage fluid >367.5 U/L on POD3 ( OR=3.688, 95% CI: 1.849-7.354) were the influencing factors of POPF ( P<0.05). Based on the three influencing factors screened out by multivariate analysis, a histogram for the prediction of pancreatic fistula was constructed using the rms package. The area under the ROC curve of the nomogram for predicting the occurrence of pancreatic fistula after PD was 0.744 (95%CI: 0.679-0.809), with a sensitivity of 69.2% and a specificity of 70.5%. The calibration curve shows that the model's prediction is consistent with the actual situation in the overall trend, indicating a relatively high degree of calibration. Conclusion:Age, BMI and amylase concentration of drainage fluid >367.5 U/L on POD3 are the influencing factors for pancreatic fistula after PD. The nomogram model for predicting pancreatic fistula constructed based on this has good predictive and application value.

OBJECTIVE: We aimed to understand the willingness and barriers to the acceptance of tuberculosis (TB) preventive treatment (TPT) among people with latent TB infection (LTBI) in China. METHODS: A multicenter cross-sectional study was conducted from May 18, 2023 to December 31, 2023 across 10 counties in China. According to a national technical guide, we included healthcare workers, students, teachers, and others occupations aged 15-65 years as our research participants. RESULTS: Overall, 17.0% (183/1,077) of participants accepted TPT. There were statistically significant differences in the acceptance rate of TPT among different sexes, ages, educational levels, and occupations ( P < 0.05). The main barriers to TPT acceptance were misconceptions that it had uncertain effects on prevention (57.8%, 517/894), and concerns about side effects (32.7%, 292/894). CONCLUSION An enhanced and comprehensive understanding of LTBI and TPT among people with LTBI is vital to further expand TPT in China. Moreover, targeted policies need to be developed to address barriers faced by different groups of people.
Humans ; China/epidemiology* ; Adult ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Young Adult ; Adolescent ; Aged ; Latent Tuberculosis/prevention & control* ; Patient Acceptance of Health Care ; Tuberculosis/prevention & control* ; Antitubercular Agents/therapeutic use* ; Health Knowledge, Attitudes, Practice