1.Chemical knockdown of Keap1 and homoPROTAC-ing allergic rhinitis.
Jianyu YAN ; Tianyu WANG ; Ruizhi YU ; Lijuan XU ; Hongming SHAO ; Tengfei LI ; Zhe WANG ; Xudong CHA ; Zhenyuan MIAO ; Chengguo XING ; Ke XU ; Huanhai LIU ; Chunlin ZHUANG
Acta Pharmaceutica Sinica B 2025;15(8):4137-4155
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 homoPROTACKEAP1. 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 homoPROTACKEAP1 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.
2.Epidemiological characteristics of rifampicin resistant pulmonary tuberculosis among students in Chongqing during 2015-2024
Chinese Journal of School Health 2025;46(12):1771-1775
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.
3.Optimization of ethanol extraction process for Yihuang powder by orthogonal experiment combined with AHP and GA-BP neural network
Wei WANG ; Wujie YANG ; Yu HAN ; Yueyan AN ; Ji HAO ; Qiang ZHANG ; Chengguo JU
China Pharmacy 2024;35(3):327-332
OBJECTIVE To optimize ethanol extraction process of Yihuang powder. METHODS An orthogonal experiment was designed by reflux extraction with ethanol volume fraction, liquid-to-material ratio, and extraction time as investigation factors. The parameters used were the contents of hesperidin, nobiletin, tangeretin, gallic acid, chebulagic acid, chebulinic acid, liquiritin, glycyrrhizin, eugenol, and the paste-forming rate. The analytic hierarchy process (AHP) was used to calculate the comprehensive score. The optimal ethanol extraction process parameters of Yihuang powder were determined by verifying the results predicted by orthogonal experiment and genetic algorithm (GA)-back propagation neural network (BP neural network). RESULTS The optimal ethanol extraction process parameters, as optimized by orthogonal experiment, were as follows: ethanol volume fraction of 60%, liquid-solid ratio of 14∶1 (mL/g), extraction time of 90 min, and extraction for 2 times. The comprehensive score obtained by verification was 79.19. Meanwhile, the optimal ethanol extraction process parameters, optimized by GA-BP neural network, were ethanol volume fraction of 65%, liquid-solid ratio of 14∶1 (mL/g ), extraction time of 60 min, and extraction for 2 times. The comprehensive score obtained by verification was 85.30, higher than the results obtained from orthogonal experiment. CONCLUSIONS The optimization method of orthogonal experiment combined with GA-BP neural network is superior to the traditional orthogonal experiment optimization method. The optimized ethanol extraction process of Yihuang powder is stable and reliable.
4.The development of a health-promoting lifestyle scale for patients with polycystic ovary syndrome and the test of its reliability and validity
Ning ZHANG ; Xiaoling SUN ; Jing WANG ; Yingjie WANG ; Haiming YANG ; Shanmei SHEN ; Shan LU ; Caiqi LIU ; Chengguo ZHANG ; Fangfang MENG
Chinese Journal of Nursing 2024;59(4):438-446
Objective To develop a health-promoting lifestyle scale for women with polycystic ovary syndrome(PCOS),and to test its reliability and validity,and preliminarily apply it.Methods Based on the Pender health promotion model,the item pool of the scale was constructed through literature research,semi-structured interviews and group discussions.After 2 rounds of Delphi expert consultation and pre-survey,the initial scale was formed.From April to July 2022,316 patients with PCOS in the health management center,reproductive medicine center and endocrinology department of a tertiary hospital in Nanjing were selected for item analysis,exploratory factor analysis and reliability test,respectively.From August to October 2022,358 PCOS patients were selected for confirmatory factor analysis.From November 2022 to February 2013,294 PCOS patients were selected,and the scale was used to investigate the status of health-promoting lifestyle in PCOS patients.Results The health-promoting lifestyle scale for PCOS patients included 5 dimensions and 33 items.The total content validity index of the scale was 0.942,and the content validity index of each item was 0.810-1.000.5 common factors were extracted by 2 exploratory factor analyses,and the cumulative variance contribution rate was 62.399%.Confirmatory factor analysis showed that the model fit was good.The Cronbach's a coefficient of the total scale was 0.930;the split-half reliability was 0.842;the test-retest reliability was 0.888.The preliminary application results showed that the total score of health-promoting lifestyle in PCOS patients was(96.925±14.273),and the average score of items was(2.937±0.433),which was at a medium level.Conclusion The health-promoting lifestyle scale for PCOS patients has good reliability and validity,which can be used as a tool for medical staff to assess the level of health-promoting lifestyle of PCOS patients,and can help nurses to quickly identify the level and dimensions of health-promoting lifestyle of patients,so as to formulate individualized precise health management plans.
5.Comparison of clinical effects of different doses of meropenem in the treatment of septic shock
Ze PING ; Jianjun ZHANG ; Jinrong WANG ; Chengguo CHAI ; Ning LI
China Pharmacy 2024;35(13):1624-1627
OBJECTIVE To compare the clinical effects of different doses of meropenem in the treatment of septic shock. METHODS One hundred and six patients with septic shock were randomly divided into standard-dose group and high-dose group, with 53 cases in each group. Patients in the standard-dose group were given standard dose of meropenem (initial intravenous injection of 1 g meropenem more than 30 minutes, followed by 1 g meropenem intravenously every 8 hours, each time for more than 3 hours); patients in the high-dose group were given high dose of meropenem (initial intravenous injection of 2 g meropenem more than 30 minutes, followed by 2 g meropenem intravenously every 8 hours, each time for more than 3 hours); other treatment measures were determined based on the specific conditions of the patients. The main observation indicators were the increments of sequential organ failure assessment (SOFA) scores and simplified acute physiology score Ⅱ (SAPS Ⅱ) after 3, 5 and 7 days of treatment in both groups. Secondary observation indicators included in-hospital mortality, 90-day all-cause mortality, 7-day microbial cure rate, 7-day clinical cure rate, serum procalcitonin (PCT) and C-reactive protein (CRP) levels after 3, 5 and 7 days of treatment, hospitalization days in the intensive care unit, ventilator treatment days, the highest dose of norepinephrine. The occurrence of adverse drug reaction in the two groups was observed. RESULTS The increments of SOFA scores and SAPS Ⅱ after 7 days of treatment, the levels of PCT and CRP after 5 and 7 days of treatment as well as the 90-day all-cause mortality in the high- dose group were significantly lower than the standard-dose group (P<0.05). There were no statistically significant differences in other indicators between the two groups (P>0.05). CONCLUSIONS High-dose meropenem treatment for septic shock has better clinical effects and is safer than standard-dose meropenem.
6.Optimization of honey processing technology of Phellinus igniarius by multi-index comprehensive score combined with analytic hierarchy process
Yidan HONG ; Wei WANG ; Liqiang ZHANG ; Yimei ZHANG ; Lihua LI ; Chengguo JU
China Pharmacy 2024;35(11):1309-1314
OBJECTIVE To optimize the honey processing technology of Phellinus igniarius. METHODS The key factors of honey processing technology of P. igniarius (honey-water ratio, the mass ratio of honey-water to P. igniarius, the frying temperature and the frying time) were investigated by orthogonal test combined with analytic hierarchy process to determine the optimal technological parameters, using the internal quality (the contents of ergosterol, protocatechuic aldehyde and protocatechuic acid) and appearance traits as evaluation indexes. RESULTS The optimal process of honey-roasting P. igniarius was to take raw P. igniarius (1 cm3 square block), add the appropriate amount of auxiliary materials (with 25 kg of refined honey and water for every 100 kg of P. igniarius), mix well, moisten for 2 h until the auxiliary materials were completely absorbed; put it in a frying container, fry at the frying temperature of 130-140 ℃ for 5 min; take it out, put it in an oven at 50 ℃ for 2 h; take it out, and let it cool. The RSD of the results of three validation experiments was 0.68%. CONCLUSIONS The optimized honey processing technology of P. igniarius is stable and feasible.
7.Optimization of honey processing technology of Phellinus igniarius by multi-index comprehensive score combined with analytic hierarchy process
Yidan HONG ; Wei WANG ; Liqiang ZHANG ; Yimei ZHANG ; Lihua LI ; Chengguo JU
China Pharmacy 2024;35(11):1309-1314
OBJECTIVE To optimize the honey processing technology of Phellinus igniarius. METHODS The key factors of honey processing technology of P. igniarius (honey-water ratio, the mass ratio of honey-water to P. igniarius, the frying temperature and the frying time) were investigated by orthogonal test combined with analytic hierarchy process to determine the optimal technological parameters, using the internal quality (the contents of ergosterol, protocatechuic aldehyde and protocatechuic acid) and appearance traits as evaluation indexes. RESULTS The optimal process of honey-roasting P. igniarius was to take raw P. igniarius (1 cm3 square block), add the appropriate amount of auxiliary materials (with 25 kg of refined honey and water for every 100 kg of P. igniarius), mix well, moisten for 2 h until the auxiliary materials were completely absorbed; put it in a frying container, fry at the frying temperature of 130-140 ℃ for 5 min; take it out, put it in an oven at 50 ℃ for 2 h; take it out, and let it cool. The RSD of the results of three validation experiments was 0.68%. CONCLUSIONS The optimized honey processing technology of P. igniarius is stable and feasible.
8.Survey of uranium concentrations in drinking water in Inner Mongolia autonomous region
Shuai ZHANG ; Qi CHEN ; Xiao XU ; Zhichao SUN ; Yulong BAO ; Chengguo WANG
Chinese Journal of Radiological Medicine and Protection 2024;44(8):663-668
Objective:To investigate of the concentrations of uranium in drinking water in Inner Mongolia Autonomous Region for providing theoretical basis for the health protection of local residents and the assessment of nuclear emergency.Methods:During the dry season and wet water season, tap water and well water samples were collected from 12 cities in Inner Mongolia, 644 unfiltered water samples and 34 filtered water samples were collected, and the uranium concentrations in drinking water was measured using a trace uranium analyzer.Results:During dry and wet seasons the uranium concentration were 0.85-23.61 μg/L and 0.98-23.65 μg/L in tap water, 3.74-88.28 μg/L and 3.68-95.36 μg/L in well water, respectively.Conclusions:The levels of uranium concentrations in drinking water in Inner Mongolia has been preliminarily ascertained, and the installation of filtration devices can significantly reduce the content of uranium in drinking water.
9.Barriers to the Acceptance of Tuberculosis Preventive Treatment: A Multicenter Cross-sectional Study in China.
Jingjuan REN ; Fei HUANG ; Haifeng CHEN ; Huimin ZHANG ; Jianwei SUN ; Ahui ZHAO ; Zuhui XU ; Liqin LIU ; Huizhong WU ; Lanjun FANG ; Chengguo WU ; Qingya WANG ; Wenqian ZHANG ; Xinhua SUN ; Xiaoping LIU ; Jizheng YUAN ; Bohan CHEN ; Ni WANG ; Yanlin ZHAO
Biomedical and Environmental Sciences 2024;37(11):1303-1309
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
10.Optimization of processing methods for Terminalia chebula based on fingerprint,antioxidant spectrum-effect correlation and multi-component contents
Wujie YANG ; Ji HAO ; Chengguo JU ; Qiang ZHANG ; Yueyan AN ; Wei WANG
China Pharmacy 2023;34(19):2371-2377
OBJECTIVE To compare the similarities and differences between raw and different preparations of Terminalia chebula based on fingerprint, antioxidant spectrum-effect correlation and multi-component contents, and to provide a reference for searching for modern processing methods of T. chebula that are similar to classical ancient methods. METHODS Ten batches of raw and different preparations of T. chebula (single stir-fried products, bran-roasted products, sand-scorched products, ash-roasted products, stir-fried charcoal products, and wine-steamed products) were used as test samples. The high-performance liquid chromatography (HPLC) fingerprints of different samples were established by using the Similarity Evaluation System for Chromatographic Fingerprint of TCM (2012 edition), the chromatographic peaks were identified, and chemometrics analysis was carried out. At the same time, HPLC method was used to determine the contents of 8 identified components. The antioxidant capacity of raw and different preparations of T. chebula was determined by DPPH free radical scavenging method, and the spectrum- effect relationship was analyzed. RESULTS A total of 20 common peaks were identified in the fingerprints of the raw and different preparations of T. chebula, and the similarity of each sample was >0.9. Nine common peaks were identified from the raw and different preparations of T. chebula, including chromatographic peak 2 (chebulic acid), 3 (gallic acid), 6 (punicalagin A), 8 (punicalagin B), 12 (corilagin), 15 (chebulagic acid), 18 (ellagic acid), 19 (1,2,3,4,6-O-pentagalloyl glucose), 20 (chebulinic acid), etc. Compared with crude drug, the contents of the above 8 components (punicalagin A and B are recorded as punicalagin) in different preparations of T. chebula were changed, and the changes of the contents of the stir-fried charcoal and wine-steamed products were more obvious than those of other processed products. Chemometric analysis showed that the fingerprints of stir-fried charcoal and wine-steamed products of T. chebula were obviously distinguished from other processed products, and the fingerprint information of raw products and other processed products of T. chebula was partially overlapped. Four main differential components (chebulinic acid, chebulagic acid, gallic acid, ellagic acid) were obtained between raw and processed products of T. chebula; and four main effective components (chebulinic acid, chebulagic acid, gallic acid, corilagin) were obtained by analyzing the spectrum-effect relationship of antioxidant activity. The single stir-fried product of T. chebula showed the strongest antioxidant activity. CONCLUSIONS The single stir-frying method is a modern processing method of T. chebula which is similar to the classical ancient method and is more excellent.


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