1.Application of cognitive training in improving executive function in patients with mild cognitive impairment
Ruyu ZHANG ; Zixuan JI ; Yanchang WANG ; Wei QIAO ; Haining LIU
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(2):187-192
Mild cognitive impairment(MCI)is a clinical condition that lies between normal aging and dementia and can be considered as the initial stage of dementia development.Executive dysfunction is one of the core symptoms of dementia, the maintenance and improvement of executive function play a central role in delaying the onset of dementia.At present, many studies have shown that cognitive training can improve executive function in MCI patients, but there are few researches and no consensus on the underlying mechanisms.This paper provides a review of the effects of cognitive training on executive function in patients with MCI, explores the impact of executive function deficits and cognitive training on the behavioral and neural levels of executive function in patients with MCI, and points out the limitations of current MCI intervention strategies and potential development directions, with the aim of providing new insights into the intervention and treatment of MCI.
2.Clinical efficacy of one-stage treatment of bilateral kidney stones under flexible ureteroscopy
Wuhe ZHANG ; Yao JIANG ; Yansheng SU ; Shaoyi QIAO ; Jintao JI ; Shuchang ZHOU
China Journal of Endoscopy 2025;31(10):1-6
Objective To explore the efficacy and safety of one-stage flexible ureteroscopic lithotripsy for bilateral kidney stones.Methods Retrospectively analyzed 112 patients with bilateral kidney stones treated by flexible ureteroscopic lithotripsy from January 2018 to October 2023.Based on the treatment procedure,the participants were divided into an observation group and a control group.The observation group(60 cases)underwent one-stage lithotripsy using flexible ureteroscopy for bilateral kidney stones,the control group(52 cases)received staged lithotripsy for bilateral kidney stones.The operation time,intraoperative blood loss,stone clearance rate one month after operation,postoperative hematuria time,duration of lumbar and abdominal pain,creatinine level one day after operation and incidence of postoperative complications were compared between the two groups of patients.Results Findings indicated that the observation group had a mean operation time of(103.68±27.46)min,which was significantly shorter compared to the control group's mean operation time of(132.51±39.74)min,the difference was statistically significant(P<0.01).Additionally,the stone clearance rate after one month post-operation was 91.67%in the observation group and 90.38%in the control group(P=0.920);The average blood loss of the observation group was(15.29±5.15)mL,and the duration of postoperative lumbar and abdominal pain was(6.18±1.40)d,while the average blood loss of the control group was(12.00±3.62)mL,and the duration of postoperative lumbar and abdominal pain was(4.56±1.12)d,with significant difference(P<0.01);The duration of postoperative hematuria in the observation group was(3.07±0.92)d,the incidence of postoperative irritation sign of bladder was 65.00%,the incidence of postoperative moderate and low fever was 25.00%,and the creatinine level on the first day after surgery was(73.47±17.80)μmol/L,while the duration of postoperative hematuria in the control group was(2.73±1.28)d,the incidence of postoperative irritation sign of bladder was 53.85%,the incidence of postoperative moderate and low fever was 17.31%,and the creatinine level on the first day after surgery was(68.61±17.38)μmol/L,the differences were not statistically significant(P>0.05).Conclusion One stage flexible ureteroscopic lithotripsy for bilateral kidney stones is safe and effective,moreover,the surgical outcome is close to that of staged surgery,but postoperative nursing and pain management should be strengthened in order to improve the effect of comprehensive treatment.
3.The effect of bufalin on extracellular matrix synthesis in renal tubular epithelial cells induced by high glucose
Chen GAO ; Yunyang QIAO ; Jialing JI ; E WANG ; Ying HUO ; Aiqing ZHANG
Tianjin Medical Journal 2025;53(10):1009-1015
Objective To investigate the effect and underlying mechanism of bufalin regulating ferroptosis on extracellular matrix synthesis in renal tubular epithelial cells(RTECs)under high glucose(HG)conditions.Methods RTECs were cultured in vitro and exposed to HG.The experimental groups included:the control group,the HG group,the HG+dimethyl sulfoxide(DMSO)group,the HG+bufalin group,the HG+ferrostatin-1(Fer-1)group,the HG+bufalin+DMSO group and HG+bufalin+erastin group.The expression levels of fibronectin(FN),type Ⅰ collagen(Col Ⅰ),acyl-CoA synthetase long-chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)were detected using Western blot assay and quantitative real-time PCR(qRT-PCR).The potential molecular targets of bufalin were predicted using SwissTargetPrediction,and functional enrichment analysis was conducted using Metascape.FerrDb was employed to analyze ferroptosis-related gene sets.The levels of ferrous ions(Fe2+),malondialdehyde(MDA)and glutathione(GSH)were measured using micro-methods to evaluate the occurrence of ferroptosis.Results Compared with the control group,the mRNA and protein relative expression levels of FN,Col Ⅰand ACSL4 were increased in the HG group,while the mRNA and protein expression levels of GPX4 and SLC7A11 were decreased(P<0.05).Compared with the HG+DMSO group,the mRNA and protein expression levels of FN,Col Ⅰand ACSL4,as well as levels of Fe2+and MDA were decreased in the HG+bufalin group,while the mRNA and protein expression levels of GPX4 and SLC7A11,and the level of GSH were increased(P<0.05).In the HG+Fer-1 group,the mRNA and protein expression levels of GPX4 and SLC7A11 were increased,while the mRNA and protein expression levels of ACSL4,FN and Col Ⅰ were decreased(P<0.05).The SwissTargetPrediction database and Metascape analysis function showed that the downstream functions of bufalin were closely related to lipid metabolism,inflammatory response,programmed cell death and ferroptosis-related pathways.The FerrDb analysis results indicated that the target sites of bufalin were closely related to ferroptosis markers.Compared with the HG+bufalin+DMSO group,the mRNA and protein expression levels of GPX4 and SLC7A11 were decreased in the HG+bufalin+Erastin group,while the mRNA and protein expression levels of ACSL4,FN and Col Ⅰ were increased(P<0.05).Conclusion Bufalin attenuates extracellular matrix synthesis in HG-induced RTECs by inhibiting ferroptosis.
4.Application of cognitive training in improving executive function in patients with mild cognitive impairment
Ruyu ZHANG ; Zixuan JI ; Yanchang WANG ; Wei QIAO ; Haining LIU
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(2):187-192
Mild cognitive impairment(MCI)is a clinical condition that lies between normal aging and dementia and can be considered as the initial stage of dementia development.Executive dysfunction is one of the core symptoms of dementia, the maintenance and improvement of executive function play a central role in delaying the onset of dementia.At present, many studies have shown that cognitive training can improve executive function in MCI patients, but there are few researches and no consensus on the underlying mechanisms.This paper provides a review of the effects of cognitive training on executive function in patients with MCI, explores the impact of executive function deficits and cognitive training on the behavioral and neural levels of executive function in patients with MCI, and points out the limitations of current MCI intervention strategies and potential development directions, with the aim of providing new insights into the intervention and treatment of MCI.
5.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
6.National bloodstream infection bacterial resistance surveillance report 2023: Gram-positive bacteria
Chaoqun YING ; Jinru JI ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Jiangqin SONG ; Hui DING ; Yanyan LI ; Yuanyuan DAI ; Haifeng MAO ; Pengpeng TIAN ; Lu WANG ; Yongyun LIU ; Yizheng ZHOU ; Jiliang WANG ; Yan JIN ; Donghong HUANG ; Hongyun XU ; Peng ZHANG ; Xinhua QIANG ; Hong HE ; Lin ZHENG ; Junmin CAO ; Zhou LIU ; Ying HUANG ; Yan GENG ; Haiquan KANG ; Dan LIU ; Guolin LIAO ; Lixia ZHANG ; Fenghong CHEN ; Yanhong LI ; Baohua ZHANG ; Haixin DONG ; Xiaoyan LI ; Donghua LIU ; Qiuying ZHANG ; Xuefei HU ; Liang GUO ; Sijin MAN ; Dijing SONG ; Rong XU ; Youdong YIN ; Kunpeng LIANG ; Aiyun LI ; Zhuo LI ; Hongxia HU ; Guoping LU ; Jinhua LIANG ; Qiang LIU ; Yinqiao DONG ; Jilu SHEN ; Shuyan HU ; Liang LUAN ; Jian LI ; Ling MENG ; Dengyan QIAO ; Xiusan XIA ; Bo QUAN ; Dahong WANG ; Chunhua HAN ; Xiaoping YAN ; Fei LI ; Shifu WANG ; Ping SHEN ; Yunbo CHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2025;18(2):118-132
Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System(BRICS)during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute(CLSI). Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus( n=1 544,35.2%),coagulase-negative Staphylococci( n=1 441,32.9%), Enterococcus faecium( n=574,13.1%), Enterococcus faecalis( n=385,8.8%),and α-hemolytic Streptococci( n=187,4.3%). The prevalence of methicillin-resistant Staphylococcus aureus(MRSA)and methicillin-resistant coagulase-negative Staphylococci(MRCNS)was 26.2%(405/1 544)and 69.8%(1 006/1 441),respectively. Notably,all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility(>97.0%)to cephalobiol,rifampicin,trimethoprim-sulfamethoxazole,linezolid,minocycline,tigecycline,and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium(resistance to vancomycin and teicoplanin:both 1.7%)compared to Enterococcus faecalis(both 0.3%). The detection rates of MRSA and MRCNS exhibited significant regional variations across the country( χ2=17.674 and 148.650,respectively,both P<0.001). No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA( χ2=14.111, P<0.001)and MRCNS( χ2=4.828, P=0.028)in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA( χ2=18.986, P<0.001)and MRCNS( χ2=4.477, P=0.034)in less developed regions(per capita GDP
7.National bloodstream infection bacterial resistance surveillance report (2023) : Gram-negative bacteria
Jinru JI ; Zhiying LIU ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Jiangqin SONG ; Hui DING ; Yanyan LI ; Yuanyuan DAI ; Haifeng MAO ; Pengpeng TIAN ; Lu WANG ; Yongyun LIU ; Yizheng ZHOU ; Jiliang WANG ; Yan JIN ; Donghong HUANG ; Hongyun XU ; Peng ZHANG ; Xinhua QIANG ; Hong HE ; Lin ZHENG ; Junmin CAO ; Zhou LIU ; Ying HUANG ; Yan GENG ; Haiquan KANG ; Dan LIU ; Guolin LIAO ; Lixia ZHANG ; Fenghong CHEN ; Yanhong LI ; Baohua ZHANG ; Haixin DONG ; Xiaoyan LI ; Donghua LIU ; Qiuying ZHANG ; Xuefei HU ; Liang GUO ; Sijin MAN ; Dijing SONG ; Rong XU ; Youdong YIN ; Kunpeng LIANG ; Aiyun LI ; Zhuo LI ; Hongxia HU ; Guoping LU ; Jinhua LIANG ; Qiang LIU ; Yinqiao DONG ; Jilu SHEN ; Shuyan HU ; Liang LUAN ; Jian LI ; Ling MENG ; Dengyan QIAO ; Xiusan XIA ; Bo QUAN ; Dahong WANG ; Chunhua HAN ; Xiaoping YAN ; Fei LI ; Shifu WANG ; Ping SHEN ; Yunbo CHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2025;18(1):47-62
Objective:To report the results of bacterial resistant investigation collaborative system(BRICS)on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023,and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period,11 492 strains of Gram-negative bacteria were collected from 60 hospitals,of which 10 098(87.9%)were Enterobacterales and 1 394(12.1%)were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli(50.0%), Klebsiella pneumoniae(26.1%), Pseudomonas aeruginosa(5.1%), Acinetobacter baumannii complex(5.0%)and Enterobacter cloacae complex(4.1%). The ESBL-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus mirablilis were 46.8%(2 685/5 741),18.3%(549/2 999)and 44.0%(77/175),respectively. The prevalence of carbapenem-resistant Escherichia coli(CREC)and carbapenem-resistant Klebsiella pneumoniae(CRKP)were 1.3%(76/5 741)and 15.0%(450/2 999);32.9%(25/76)and 78.0%(351/450)of CREC and CRKP were sensitive to ceftazidime/avibactam combination,respectively. 94.7%(72/76)and 90.2%(406/450)of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore,57.9%(44/76)and 79.1%(356/450)were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)complex was 64.6%(370/573),while more than 80.0% of CRAB complex was sensitive to tigecycline,eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa(CRPA)was 17.0%(99/581). There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China,with statistically significant differences in the prevalence of CREC,CRKP,CRPA and CRAB complex( χ2=10.6,28.6,10.8 and 19.3, P<0.05). The prevalence of ESBL-producing Escherichia coli, CREC,CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals( χ2=12.5,9.8,12.7 and 57.8,all P<0.01). Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China,and Escherichia coli is ranked in the top,while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend,CREC infecton maintains a low prevalence level,and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.
8.Clinical efficacy of one-stage treatment of bilateral kidney stones under flexible ureteroscopy
Wuhe ZHANG ; Yao JIANG ; Yansheng SU ; Shaoyi QIAO ; Jintao JI ; Shuchang ZHOU
China Journal of Endoscopy 2025;31(10):1-6
Objective To explore the efficacy and safety of one-stage flexible ureteroscopic lithotripsy for bilateral kidney stones.Methods Retrospectively analyzed 112 patients with bilateral kidney stones treated by flexible ureteroscopic lithotripsy from January 2018 to October 2023.Based on the treatment procedure,the participants were divided into an observation group and a control group.The observation group(60 cases)underwent one-stage lithotripsy using flexible ureteroscopy for bilateral kidney stones,the control group(52 cases)received staged lithotripsy for bilateral kidney stones.The operation time,intraoperative blood loss,stone clearance rate one month after operation,postoperative hematuria time,duration of lumbar and abdominal pain,creatinine level one day after operation and incidence of postoperative complications were compared between the two groups of patients.Results Findings indicated that the observation group had a mean operation time of(103.68±27.46)min,which was significantly shorter compared to the control group's mean operation time of(132.51±39.74)min,the difference was statistically significant(P<0.01).Additionally,the stone clearance rate after one month post-operation was 91.67%in the observation group and 90.38%in the control group(P=0.920);The average blood loss of the observation group was(15.29±5.15)mL,and the duration of postoperative lumbar and abdominal pain was(6.18±1.40)d,while the average blood loss of the control group was(12.00±3.62)mL,and the duration of postoperative lumbar and abdominal pain was(4.56±1.12)d,with significant difference(P<0.01);The duration of postoperative hematuria in the observation group was(3.07±0.92)d,the incidence of postoperative irritation sign of bladder was 65.00%,the incidence of postoperative moderate and low fever was 25.00%,and the creatinine level on the first day after surgery was(73.47±17.80)μmol/L,while the duration of postoperative hematuria in the control group was(2.73±1.28)d,the incidence of postoperative irritation sign of bladder was 53.85%,the incidence of postoperative moderate and low fever was 17.31%,and the creatinine level on the first day after surgery was(68.61±17.38)μmol/L,the differences were not statistically significant(P>0.05).Conclusion One stage flexible ureteroscopic lithotripsy for bilateral kidney stones is safe and effective,moreover,the surgical outcome is close to that of staged surgery,but postoperative nursing and pain management should be strengthened in order to improve the effect of comprehensive treatment.
9.Characteristics of changes in HBsAg,HBV DNA and ALT after cessation of nucleos(t)ide analogue therapy in patients with HBeAg-negative chronic hepatitis B
Qiao-Lan LYU ; Li LIU ; Song QING ; Ying-Jie JI ; Yan LIU ; Chao ZHANG ; Fu-Sheng WANG ; Yong-Qian CHEN
Medical Journal of Chinese People's Liberation Army 2025;50(9):1076-1082
Objective To investigate the characteristics of changes in hepatitis B surface antigen(HBsAg),hepatitis B virus(HBV)deoxyribonucleic acid(DNA),and alanine aminotransferase(ALT)levels following the cessation of nucleos(t)ide analogues(NAs)therapy in hepatitis B e antigen(HBeAg)-negative chronic hepatitis B(CHB)patients with baseline HBsAg levels<1000 IU/ml.Methods This retrospective cohort study analyzed 73 HBeAg-negative CHB patients treated at the Fifth Medical Centre of Chinese PLA General Hospital from January 2020 to June 2023.Patients were divided into 3 groups according to baseline HBsAg level and discontinuation strategy:HBsAg-negative discontinuation group(n=14),HBsAg-positive discontinuation group(n=25),and HBsAg-positive continuation group(n=34).All patients were followed for 48 weeks.Baseline clinical characteristics and changes in virological and hepatic biochemical indicators during follow-up were compared among the 3 groups.Univariate logistic regression analysis was performed to assess the correlation between clinical indicators and HBV DNA reappearance in HBsAg-positive discontinuation group,and between clinical indicators and HBsAg decline>0.5 log IU/ml in this group.Results There were no significant differences in the baseline levels of gender,age,albumin,and total bilirubin among the 3 groups(P>0.05).The baseline direct bilirubin level was significantly higher in HBsAg-positive discontinuation group than that in other groups(P<0.05),while the lymphocyte counts were significantly higher in HBsAg-negative discontinuation group(P<0.05).During the 48-week follow-up period,the HBV DNA reappearance rate in HBsAg-positive discontinuation group(72.0%)was significantly higher than that in other groups(P<0.001).There was no significant difference in the incidence of ALT elevation among the three groups(P=0.260).The proportion of patients with HBsAg decline>0.5 log IU/ml in HBsAg-positive discontinuation group(24.0%)was significantly higher than that in HBsAg-positive continuation group(5.9%,P<0.05).The proportion of patients with HBsAg increase>0.5 log IU/ml in HBsAg-positive discontinuation group(12.0%)was also significantly higher than that in HBsAg-positive continuation group(0%,P<0.05).Univariate logistic regression analysis revealed no significant association between the analyzed clinical indicators and HBsAg decline(P>0.05).Conclusions Discontinuation of NAs therapy in HBsAg-negative patients demonstrates high safety,with sustained HBsAg negativity post-cessation and low risks of viral relapse and liver function abnormalities.For HBsAg-positive patients,discontinuation may promote HBsAg decline in some individuals but is associated with risks of HBV DNA reappearance and HBsAg elevation.The decision to discontinue therapy should be comprehensively evaluated based on patients'baseline HBsAg levels and clinical characteristics.
10.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.

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