1.A novel feedback loop: CELF1/circ-CELF1/BRPF3/KAT7 in cardiac fibrosis.
Yuan JIANG ; Bowen ZHANG ; Bo ZHANG ; Xinhua SONG ; Xiangyu WANG ; Wei ZENG ; Liyang ZUO ; Xinqi LIU ; Zheng DONG ; Wenzheng CHENG ; Yang QIAO ; Saidi JIN ; Dongni JI ; Xiaofei GUO ; Rong ZHANG ; Xieyang GONG ; Lihua SUN ; Lina XUAN ; Berezhnova Tatjana ALEXANDROVNA ; Xiaoxiang GUAN ; Mingyu ZHANG ; Baofeng YANG ; Chaoqian XU
Acta Pharmaceutica Sinica B 2025;15(10):5192-5211
Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.
2.Present situation of health education on school myopia prevention and control in primary and middle schools in Beijing
WANG Yao, QIN Tingting, GU Mingyu, YANG Yutong, GUO Junjun, LI Xingming
Chinese Journal of School Health 2024;45(8):1136-1139
Objective:
To investigate the present situation of health education on school myopia prevention and control in primary and middle schools in Beijing, so as to provide scientific basis and suggestions for effective implementation of health education on school myopia prevention and control.
Methods:
From November 6-17, 2023, a total of 551 school doctors and health care teachers from public primary and secondary schools in seven districts of Beijing were investigated by using stratified random cluster sampling method. The contents included basic information, the basic situation of school health work, and the status of myopia prevention and control in schools. The data was described by frequency and proportion. Chisquare test was used to analyze the influencing factors.
Results:
A total of 89.8% of the respondents were found in the school of offering health education courses about myopia prevention and control. Among these respondents, 54.5% were equipped with health education course material of professional myopia prevention and control, and the teachers were primarily class teachers (57.6%), health care teachers (45.5%), and physical education teachers (45.1%), and most of the classes were conducted once a month (33.7%) and once a semester (28.1%). A total of 95.6% of the subjects had health education activities about myopia prevention and control at their schools. The frequency of activities was once a month (38.5%) and once a semester (27.9%). There were statistically significant differences of the report rate in setting up health education courses on myopia prevention and control, and the frequency of activities in different areas and different types of schools (χ2=19.53, 13.15, 34.30, 20.32, P<0.05).
Conclusions
Health education on school myopia prevention and control in primary and middle schools in Beijing is supportive. But health education courses taught by professional teachers should pay attention to the norms of the course material to complete a certain amount of class time, and development of health education activities should be diversified, so as to effectively implement health education of myopia prevention and control at school.
3.Antibiotic-loaded bone cement in treatment of calf compartment syndrome caused by diabetic foot necrotizing fasciitis
Peng XU ; Mingyu XUE ; Yongjun RUI ; Fanyu BU ; Xiaofeng GUO ; Yikai XIE
Chinese Journal of Tissue Engineering Research 2024;28(17):2637-2641
BACKGROUND:At present,the treatment methods for necrotizing fasciitis mostly use negative pressure sealing suction after thorough debridement.This method requires repeated debridement to completely remove necrotic infected tissue,causing serious physical and economic burdens to patients. OBJECTIVE:To introduce a rare clinical case of calf compartment syndrome caused by diabetic foot necrotizing fasciitis,and summarize the clinical experience of using antibiotic-loaded bone cement for treatment and comprehensive management. METHODS:A total of 6 patients with calf compartment syndrome caused by diabetic necrotizing fasciitis admitted to Wuxi 9th Affiliated Hospital of Soochow University from August 2017 to August 2020 were selected,including 5 males and 1 female with an average age of 54 years.During the perioperative period,the patients'general condition was evaluated and systemic nutritional support treatment was given.In the first stage,all patients received complete debridement to control infection,antibiotic-loaded bone cement packing,and negative pressure sealed drainage.In the second stage,bone cement was removed and wound repair was performed.The wound healing,as well as the occurrence of redness,swelling,and exudation was observed during the follow-up. RESULTS AND CONCLUSION:(1)The wounds of four patients were fresh after twice antibiotic-loaded bone cement packing,and the membrane formation was good,and one patient was good after three times of antibiotic-loaded bone cement packing,and the wounds of all five patients healed well after the second stage of skin grafting.Due to the difficulty in maintaining intraoperative blood pressure and infection in all four compartments of the lower leg,a patient underwent emergency knee amputation.Meanwhile,the stump wound was placed with antibiotic-loaded bone cement.The wound was closed directly after the secondary bone cement was removed,and the wound healed in the first stage.(2)The six patients were followed up for 6-24 months after discharge.At the last follow-up,all six patients had good wound healing and no symptoms such as redness,swelling,and exudation.The quality of life of the patients was significantly improved,and all of them were satisfied with the curative effect.(3)The occurrence of calf compartment syndrome should be vigilant when diabetic foot necrotizing fasciitis is highly suspected.Early diagnosis and timely incision decompression are of great importance.Besides,the application of antibiotic-loaded bone cement in the treatment of calf compartment syndrome caused by diabetic necrotizing fasciitis has a good short-term effect.
4.Sero-epidemiological study and infection rate evaluation of pertussis in Henan Province
Qian LIU ; Qiaohua DOU ; Lu ZHANG ; Jiangnan KONG ; Yonghao GUO ; Daxing FENG ; Yanfang JI ; Changshuang WANG ; Mingyu ZHANG ; Jin XU ; Yanyang ZHANG
Chinese Journal of Preventive Medicine 2024;58(7):983-991
Objective:To analyze the epidemiological distribution characteristics, influencing factors, and infection rates of pertussis in the population of Henan Province.Methods:From 2022 to 2023, a cross-sectional survey was conducted to investigate the permanent population in Henan Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-pertussis toxin IgG (PT-IgG), analyze the antibody positivity rate (≥20 IU/ml) and median concentration (MC), and estimate the pertussis infection rate based on PT IgG ≥40 IU/ml. The rank sum test was used to compare antibody levels among groups, and the χ2 test was used to compare antibody positive rates and infection rates among groups. Results:A total of 4 810 research subjects were included in this study. The overall positive rate of PT-IgG was 12.10% and MC was 3.04 (0.35, 10.36) IU/ml. There were significant differences both in positive rates and antibody levels of PT-IgG among different regions or age groups (region positive rate: χ2=134.06, P<0.001, MC: H=337.74, P<0.001; age group positive rate: χ2=45.27, P<0.001, MC: H=134.49, P<0.001). Both the positive rate of PT-IgG (25.26%) and MC (8.01 IU/ml) were the highest within one year after completing a full course of vaccination. There were significant differences in positive rates and antibody levels among people receiving different types of pertussis vaccines (positive rate: χ2=12.38, P=0.006, MC: H=17.93, P<0.001). The antibody positivity rate (35.71%) and MC (8.88 IU/ml) of the people who received cell-free pertussis inactivated poliomyelitis influenza type b (combined) vaccine throughout the course were higher than those who received other types of vaccines. The natural infection rate of pertussis was evaluated for individuals aged≥3 years who had no history of pertussis vaccine immunization within the year prior to sampling. With a high vaccination rate, the estimated infection rate of pertussis in the population was 5 757.22/100 000. The infection rates in the 3-year-old (1 940.16/100 000) and 4-year-old (1 765.68/100 000) populations were at a low level among the entire population, reaching their peak at the age of 6 (12 656.71/100 000). Subsequently, although the infection rate continued to decline, it remained at a high level and peaked again at the age of 40-49 years (8 740.39/100 000). There was a statistically significant difference in the estimated infection rate of pertussis among different age groups ( χ2=53.21, P<0.001). Conclusion:The PT-IgG level of pertussis in the population of Henan Province is generally at a low level. The estimated infection rate of pertussis is much higher than the reported incidence rate. A booster dose of pertussis vaccine is recommended at 6 years old.
5.Surveillance and analysis of leptospirosis in Zhejiang Province in 2023
Song GUO ; Wenwu YAO ; Ying LIU ; Xuguang SHI ; Jiangping REN ; Rong ZHANG ; Mingyu LUO ; Zhangnyu YANG ; Jimin SUN
Chinese Journal of Endemiology 2024;43(7):559-563
Objective:The epidemiological and host animal pathogen data of leptospirosis in the population of Zhejiang Province in 2023 were analyzed, providing scientific basis for formulating prevention and control strategies of leptospirosis.Methods:The data of human leptospirosis in the population were collected from the China Information System for Disease Control and Prevention, and analyzed using descriptive epidemiological methods. The data on isolation, culture, and nucleic acid testing of Leptospira pathogens from mouse kidneys, frog kidneys, pig kidneys, and duck kidneys as well as duck serum antibody data were collected from Zhejiang Provincial Center for Disease Control and Prevention "Leptospirosis Surveillance Project of Zhejiang Province". The carrying and changing status of Leptospira epidemic microbiota in populations and host animals were analyzed. Results:In 2023, a total of 83 cases of leptospirosis were reported in Zhejiang Province, with a incidence rate of 0.126 2/ 100 000, aged (62.66 ± 11.31) years, including 68 males and 15 females. Leptospirosis cases were reported in 11 cities, mainly concentrated in the southern cities of Wenzhou City, Lishui City and Taizhou City(a total of 68 cases), accounting for 81.93% of the total number of cases. August to October were high incidence months for leptospirosis (a total of 70 cases), accounting for 84.34% of the total number cases. The male to female ratio of patients was 4.53 ∶ 1.00, and all were adults ≥20 years old, the middle and old people aged 45 - 79 years were the high-risk population (a total of 77 cases), accounting for 92.77% of the total number of cases. The patient's occupation was mainly farmers, with a total of 54 cases, accounting for 65.06% of the total number cases. The shortest time from onset to initial diagnosis for patients with leptospirosis was 0 day, and the longest was 13 days. The shortest time from initial diagnosis to confirmed diagnosis was 0 day, and the longest was 16 days. The 72.29% of the leptospirosis cases (60 cases) had a history of field labor or suspected contact with contaminated water within one month before the onset of the disease, and 18.07% of the leptospirosis cases (15 cases) had a history of contact with animals such as mice, frogs, pigs, cows, dogs, fish or ducks, or their excreta within one month before the onset of the disease. The average nucleic acid positive rate of host animals with leptospirosis was 5.92% (31/524) in mouse kidney, 6.74% (36/534) in frog kidney, and 0.66% (1/151) in pig kidney. The isolation and culture of leptospirosis from duck kidney, nucleic acid detection, and antibody detection in duck blood were all negative. The leptospirosis bacteria detected in human population were serogroup Icterohaemorrhagiae (3 samples) and Hebdomadis (4 samples), and the bacteria group detected in host animals was serogroup Icterohaemorrhagiae (3 samples). Conclusions:The outbreak of leptospirosis in Zhejiang Province mainly occurs in the summer and autumn, with the affected areas mainly concentrated in the southern region of Zhejiang Province. The affected population is mainly middle-aged and elderly males, and the population carrying Leptospira is still mainly composed of the serogroup Icterohaemorrhagiae and the Hebdomadis, with the host animal being the serogroup Icterohaemorrhagiae.
6.Sero-epidemiological study and infection rate evaluation of pertussis in Henan Province
Qian LIU ; Qiaohua DOU ; Lu ZHANG ; Jiangnan KONG ; Yonghao GUO ; Daxing FENG ; Yanfang JI ; Changshuang WANG ; Mingyu ZHANG ; Jin XU ; Yanyang ZHANG
Chinese Journal of Preventive Medicine 2024;58(7):983-991
Objective:To analyze the epidemiological distribution characteristics, influencing factors, and infection rates of pertussis in the population of Henan Province.Methods:From 2022 to 2023, a cross-sectional survey was conducted to investigate the permanent population in Henan Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-pertussis toxin IgG (PT-IgG), analyze the antibody positivity rate (≥20 IU/ml) and median concentration (MC), and estimate the pertussis infection rate based on PT IgG ≥40 IU/ml. The rank sum test was used to compare antibody levels among groups, and the χ2 test was used to compare antibody positive rates and infection rates among groups. Results:A total of 4 810 research subjects were included in this study. The overall positive rate of PT-IgG was 12.10% and MC was 3.04 (0.35, 10.36) IU/ml. There were significant differences both in positive rates and antibody levels of PT-IgG among different regions or age groups (region positive rate: χ2=134.06, P<0.001, MC: H=337.74, P<0.001; age group positive rate: χ2=45.27, P<0.001, MC: H=134.49, P<0.001). Both the positive rate of PT-IgG (25.26%) and MC (8.01 IU/ml) were the highest within one year after completing a full course of vaccination. There were significant differences in positive rates and antibody levels among people receiving different types of pertussis vaccines (positive rate: χ2=12.38, P=0.006, MC: H=17.93, P<0.001). The antibody positivity rate (35.71%) and MC (8.88 IU/ml) of the people who received cell-free pertussis inactivated poliomyelitis influenza type b (combined) vaccine throughout the course were higher than those who received other types of vaccines. The natural infection rate of pertussis was evaluated for individuals aged≥3 years who had no history of pertussis vaccine immunization within the year prior to sampling. With a high vaccination rate, the estimated infection rate of pertussis in the population was 5 757.22/100 000. The infection rates in the 3-year-old (1 940.16/100 000) and 4-year-old (1 765.68/100 000) populations were at a low level among the entire population, reaching their peak at the age of 6 (12 656.71/100 000). Subsequently, although the infection rate continued to decline, it remained at a high level and peaked again at the age of 40-49 years (8 740.39/100 000). There was a statistically significant difference in the estimated infection rate of pertussis among different age groups ( χ2=53.21, P<0.001). Conclusion:The PT-IgG level of pertussis in the population of Henan Province is generally at a low level. The estimated infection rate of pertussis is much higher than the reported incidence rate. A booster dose of pertussis vaccine is recommended at 6 years old.
7.Tanshinone ⅡA ameliorates energy metabolism dysfunction of pulmonary fibrosis using 13C metabolic flux analysis
Shan BAIXI ; Zhou HAOYAN ; Guo CONGYING ; Liu XIAOLU ; Wu MINGYU ; Zhai RAO ; Chen JUN
Journal of Pharmaceutical Analysis 2024;14(2):244-258
Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis(PF).It is considered as a promising ther-apeutic target anti-PF.The well-documented against PF properties of Tanshinone ⅡA(Tan ⅡA)have been primarily attributed to its antioxidant and anti-inflammatory potency.Emerging evidence suggests that TanⅡA may target energy metabolism pathways,including glycolysis and tricarboxylic acid(TCA)cycle.However,the detailed and advanced mechanisms underlying the anti-PF activities remain obscure.In this study,we applied[U-13C]-glucose metabolic flux analysis(MFA)to examine metabolism flux disruption and modulation nodes of Tan ⅡA in PF.We identified that Tan ⅡA inhibited the glycolysis and TCA flux,thereby suppressing the production of transforming growth factor-β1(TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro.We further revealed that Tan ⅡA inhibited the expression of key metabolic enzyme hexokinase 2(HK2)by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxia-inducible factor 1α(HIF-1α)pathway activities,which decreased the accumulation of abnormal metabolites.Notably,we demonstrated that Tan ⅡA inhibited ATP citrate lyase(ACLY)activity,which reduced the collagen synthesis pathway caused by cytosol citrate consumption.Further,these results were validated in a mouse model of bleomycin-induced PF.This study was novel in exploring the mechanism of the occurrence and develop-ment of Tan ⅡA in treating PF using 13C-MFA technology.It provided a novel understanding of the mechanism of Tan ⅡA against PF from the perspective of metabolic reprogramming.
8.Does the homologous booster with the inactivated coronavirus disease 2019 vaccine work for the omicron variant? Real-world evidence from Jilin, China.
Jun GUO ; Lei ZHA ; Kai ZENG ; Mingyu SHAO ; Dan CHEN ; Bing WANG ; Yun ZHOU ; Gang YANG ; Xue ZHANG ; Xia ZOU ; Yan ZHANG ; Yan KANG
Chinese Medical Journal 2023;136(23):2892-2894
10.Establishment and validation of nomogram for predicting prostate biopsy results based on pre-biopsy inflammatory markers
Mingyu GUO ; Baoling ZHANG ; Shangrong WU ; Yang ZHANG ; Mingzhe CHEN ; Xiong XIAO ; Xingkang JIANG ; Hongtuan ZHANG ; Yong XU ; Ranlu LIU
Chinese Journal of Urology 2023;44(10):752-760
Objective:To explore the predictive value of pre-biopsy serum inflammatory markers on positive prostate biopsy results, establish a nomogram model based on pre-biopsy inflammatory markers combined with other parameters, and evaluate its predictive ability for prostate biopsy results.Methods:The clinical data of 601 patients undergoing transperineal prostate biopsy who were admitted to the Second Hospital of Tianjin Medical University from August 2019 to August 2021 were retrospectively analyzed. The median age was 68(35, 89)years, and the median tPSA was 9.56(4.01, 19.95)ng/ml. The median fPSA was 1.36(0.88, 2.02)ng/ml, the median PSAD was 0.16(0.11, 0.26)ng/ml 2, and the median platelet-to-lymphocyte ratio(PLR)was 129.90(98.95, 169.89). PI-RADS v2.1 score<3 points in 189 cases(31.45%), 3 points in 174 cases(28.95%), 4 points in 190 cases(31.61%), and 5 points in 48 cases(7.99%). A simple randomization method was used to obtain 421 cases(70.00%)in the modeling group and 180 cases(30%)in the validation group.There was no significant difference in the clinical data between the two groups ( P>0.05). Univariate and multivariate logistic regression analysis were performed in the modeling group to screen independent influencing factors for the prediction of positive prostate biopsy results. A nomogram model was established and internal verification was conducted. External validation of the model was performed in the validation group. Receiver operating characteristic(ROC)curve was used to verify model discrimination, Hosmer-Lemeshow goodness-of-fit test was used to verify model calibration, and decision curve analysis (DCA) was used to evaluate the net benefit and clinical utility of the predictive model. Results:The results of univariate analysis showed that the age( OR=1.060, P<0.01), histological inflammation( OR=0.312, P<0.01), the number of biopsy needles( OR=0.949, P=0.009), f/tPSA( OR=0.954, P=0.003), PV( OR=0.973, P<0.01), PSAD( OR=29.260, P<0.01), PI-RADS v2.1 score(3-point OR=3.766, P=0.001; 4-point OR=11.800, P<0.01; 5-point OR=57.033, P<0.01), lymphocyte count( OR=1.535, P=0.013), NLR( OR=0.848, P=0.044), PLR( OR=0.994, P=0.005)and SII( OR=0.999, P=0.009)were statistically different between the prostate patients and non-prostate cancer patients in the modeling group; Multivariate analysis showed that age( OR=1.094, P<0.001), fPSA( OR=0.605, P=0.002), histological inflammation ( OR=0.241, P<0.001), PSAD ( OR=7.57, P=0.013), PLR ( OR=0.994, P=0.005) and PI-RADS v2.1 Score(3-point OR=2.737, P=0.016; 4-point OR=8.621, P<0.001; 5-point OR=47.65, P<0.001) was an independent influencing factor for prostate cancer at initial biopsy; a nomogram model based on age, fPSA, PSAD, PLR and PI-RADS v2.1 scores was established. The AUC of the modeling group was 0.849(95% CI 0.810-0.888), and the sensitivity was 80.9%, and the specificity was 76.1%; the AUC of the validation group was 0.862(95% CI 0.809-0.915), and the sensitivity was 91.9%, and the specificity was 67.8%, suggesting that the diagnostic prediction model had a good discrimination. The calibration curve showed that the prediction model was well calibrated ( χ2=6.137, P=0.632). The decision curve analysis (DCA) of the modeling and validation groups indicated a larger net benefit of the predictive model. Conclusions:The nomogram model established in this study based on age, fPSA, PSAD, PLR and PI-RADS v2.1 score showed good predictive efficacy for prostate biopsy in patients with PSA between 4-20 ng/ml.


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