1.Guidelines for the perioperative diagnosis and treatment of oncogene-driven non-small cell lung cancer (2026)
Weidong WANG ; Yongbin LIN ; Hui TIAN ; Gaofeng LI ; Shun XU ; Yongde LIAO ; Haitao MA ; Junfeng LIU ; Chundong GU ; Xiaolong YAN ; Shumin WANG ; Daqiang SUN ; Jianyang LIU ; Tao XUE ; Shaohua MA ; Zhigang LI ; Shuanghu YUAN ; Gen LIN ; Ling CAI ; Jianping ZHOU ; Wenzhao ZHONG ; Naixin LIANG ; Yi HAN ; Junfeng WANG ; Weidong ZHANG ; Xin WANG ; Lianjuan CHEN ; Lunxu LIU ; Xiuyi ZHI ; Lanjun ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(09):1337-1353
Lung cancer constitutes the most prevalent and lethal malignant tumor in China. Approximately 85% of lung cancer diagnoses correspond to the non-small cell histological subtype [non-small cell lung cancer (NSCLC)]. Despite surgery being the mainstay for early-stage disease, postoperative recurrence remains high and adjuvant chemotherapy offers limited benefit. In recent years, targeted therapy has demonstrated substantial advantages in driver mutation-positive NSCLC. To this end, the Lung Cancer Medical Education Committee of the Chinese Medical Education Association developed guidelines based on a systematic review of evidence through November 2025, using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach and a modified Delphi method. Focusing on epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and addressing ROS proto-oncogene 1 (ROS1), B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E mutation, and mesenchymal-epithelial transition factor (MET) exon 14 (METex14) skipping, the guideline covers molecular testing, neoadjuvant/adjuvant therapy, perioperative strategies, minimal residual disease monitoring, and postoperative surveillance. It defines testing requirements, specifies stage-directed and subtype-specific treatments, and standardizes minimal residual disease monitoring. These recommendations emphasize precision and feasibility to improve survival and quality of life.
2.Effect of NEP1-40/PLGA on facial nerve repair in rats
XUE Bing ; XI Hualei ; YAO Lihong ; XU Wanqiu ; XU Xiaohang ; LIN Song ; PIAO Guiyan ; WANG Xiumei
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(2):110-119
Objective:
To investigate the effect of neurite outgrowth inhibitor extracellular peptide residues 1-40 (NEP1-40) combined with poly (lactic-co-glycolic acid) (PLGA) and gelatin electrospun fiber membrane on facial nerve repair in rats.
Methods:
According to the principle of random grouping, 108 male SD rats were divided into four groups (n = 27 in each group, approved by the ethics committee), namely, the sham group, control group, PLGA group, and NEP1-40 + PLGA group. A facial nerve fracture model was established for all of the groups except for the sham group. The control group received no further treatment, the PLGA group and the NEP1-40+PLGA group were supported by PLGA membrane, and the NEP1-40+PLGA group received one immediate local injection of NEP1-40 (5 μg/μL) at a dose of 10 μL. Facial nerve function analysis, electrophysiological examination, transmission electron microscope observation, HE staining, and immunohistochemical staining of myelin marker S100β and axonal marker β3-tubulin were used to evaluate the recovery of injured facial nerves of rats at 2, 4 and 8 weeks.
Results :
At 8 weeks, the facial nerve function score of the NEP1-40+PLGA group was better than that of the control group and PLGA group (P < 0.001), and facial nerve function was significantly restored. Electrophysiological examination of nerve action potentials at the injured facial nerve showed that the amplitude in the NEP1-40+PLGA group was higher than that of the control group and PLGA group (P < 0.001), but there was no significant difference in latency and conduction velocity results between the groups (P > 0.05). At 2, 4, and 8 weeks, transmission electron microscopy showed that the number of myelinated nerve fibers and myelin sheath thickness in the cross-section of the injured facial nerve in the NEP1-40+PLGA group were greater than those in the other groups (P < 0.05). At 8 weeks, HE staining showed that the facial nerves in the control group had partially recovered, but the overall cell distribution was uneven and the boundary with surrounding tissues was slightly blurred. In contrast, the NEP1-40+PLGA group had a relatively uniform cell distribution and a clearer boundary with surrounding tissues. At 2, 4, and 8 weeks, the immunohistochemical results showed that in the cross-section of the injuried facial nerve, NEP1-40 increased the expression of neural markers S100 β and β3-tubulin, especially β3-tubulin, which was close to normal levels (P > 0.05)
Conclusion
NEP1-40 is beneficial for the generation of new myelin sheaths and axons at the site of injury, and it can promote the repair and regeneration of injured facial nerves to a certain extent, thus accelerating the recovery of injured nerve function.
3.Correlation between serum IGF1R and EGFL7 levels and the condition and pregnancy outcome of patients with preeclampsia
Ji MEI ; Qin XUE ; Jiang LIN ; Yujuan XU ; Linhua CHEN ; Meiqin JIANG
International Journal of Laboratory Medicine 2025;46(10):1153-1157,1162
Objective To investigate the correlation between serum insulin like growth factor 1 receptor(IGF1R)and epidermal growth factor-like domain-containing protein 7(EGFL7)levels and the condition and pregnancy outcome of patients with preeclampsia(PE).Methods A total of 120 PE patients admitted to the hospital from January 2021 to January 2024(PE group)and 60 healthy pregnant women during the same peri-od(control group)were selected.The PE patients were divided into severe PE group(68 cases)and mild PE group(52 cases)according to their conditions,and divided into poor group(62 cases)and good group(68 ca-ses)according to the pregnancy outcome.Enzyme-linked immunosorbent assay was used to detect serum IGF1R,EGFL7 levels.Using the pregnancy outcome of PE patients as the dependent variable,multivariate un-conditional Logistic regression was used to determine the influencing factors of their pregnancy outcomes,and receiver operating characteristic curve was used to evaluate the predictive value of serum IGF1R and EGFL7 levels.Results Compared with the control group,serum IGF1R levels were reduced and EGFL7 levels were increased in the PE group(t=-16.908,16.234,P<0.001).Serum IGF1R levels were decreased and EGFL7 levels were increased in the severe PE group compared with the mild PE group(t=-5.317,5.305,P<0.001).The incidence of adverse pregnancy outcomes in PE patients was 51.67%(62/120).The independent risk factors for adverse pregnancy outcomes in patients with PE were severe PE(OR=3.906,95%CI:1.305-11.689),elevated 24-h urinary protein(OR=2.030,95%CI:1.290-3.194),elevated EGFL7(OR=1.116,95%CI:1.040-1.198),and the independent protective factor was elevated IGF1R(OR=0.908,95%CI:0.865-0.954,P<0.05).The area under the curve for serum IGF1R and EGFL7 levels alone and in com-bination to predict adverse pregnancy outcomes in PE patients was 0.791(95%CI:0.707-0.860),0.784(95%CI:0.700-0.854),and 0.866(95%CI:0.781-0.911),and serum IGF1R and EGFL7 levels were grea-ter jointly(Z=2.456,2.244,P<0.05).Conclusion Decreased serum IGF1R levels and increased EGFL7 levels are associated with exacerbation and adverse pregnancy outcomes in patients with PE,and the combina-tion of serum IGF1R and EGFL7 levels is of high value in predicting adverse pregnancy outcomes in patients with PE.
4.Changing antimicrobial resistance profiles of Burkholderia cepacia in hospitals across China:results from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Chunyue GE ; Yunjian HU ; Xiaoman AI ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Hui LI ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(5):557-562
Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1%(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5%,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3%(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1%)were isolated from sputum and respiratory secretions,followed by urine(10.7%)and blood samples(8.1%).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1%.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4%in the patients<18 years old to 20.6%in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.
5.Changing prevalence and antibiotic resistance profiles of carbapenem-resistant Enterobacterales in hospitals across China:data from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Wenxiang JI ; Tong JIANG ; Jilu SHEN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yuanhong XU ; Ying HUANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yingchun XU ; Xiaojiang ZHANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Hong ZHANG ; Chun WANG ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(4):445-454
Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43%(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38%,9.73%,and 8.47%,respectively.The prevalence of CRE strains in Escherichia coli was 1.99%.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)%,followed by blood(20.88±3.40)%and urine(18.40±3.45)%.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)%.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.
6.Changing distribution and antibiotic resistance profiles of the respiratory bacterial isolates in hospitals across China:data from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Ying FU ; Yunsong YU ; Jie LIN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE ; Wenhui HUANG
Chinese Journal of Infection and Chemotherapy 2025;25(4):431-444
Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6%of the isolates were Gram-negative bacteria and 17.4%were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)%and(94.0±0.1)%,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P<0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9%.The prevalence of penicillin-resistant S.pneumoniae was 1.4%.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8%and 41.3%,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7%,20.8%,9.4%,29.8%,and 73.3%,respectively.The prevalence of β-lactamase was 96.1%in Moraxella catarrhalis and 60.0%in Haemophilus influenzae.The H.influenzae isolates from children(<18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P<0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.
7.Changes of cardiovascular function and quality of life in patients with chronic heart failure after medi-cal community homogenization management
Yan XU ; Lin XUE ; Yan-chuan WANG ; Yuan-yuan SHU ; Ya-mei WANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(2):241-246
Objective:To investigate the effect of medical community homogenization management(MCHM)on self-care ability,heart function,vascular endothelial function and quality of life in patients with chronic heart failure(CHF).Methods:This randomized controlled study enrolled 110 CHF patients admitted in Panzhihua Central Hos-pital between April 2021 and April 2023.They were divided into intervention group(n=55)and routine group(n=55).The control group received routine management,while intervention group received additional MCHM,both groups were intervened for 3 months.Self-care ability,heart function,vascular endothelial function,quality of life and incidence of adverse events were compared between two groups.Results:Compared with patients in control group,those in intervention group had significant higher total score of self-care of heart failure index(SCHFI)[(82.30±2.98)points vs.(59.46±3.19)points],stroke volume(SV)[(73.30±2.31)ml vs.(54.66±1.96)ml],left ventricular ejection fraction(LVEF)[(58.25±2.90)% vs.(52.41±2.52)%],early diastolic peak flow velocity/late diastolic peak flow velocity(E/A)[(1.95±0.18)vs.(1.30±0.16)]and the level of nitric oxide(NO)[(106.70±4.44)μmol/L vs.(82.36±4.66)μmol/L](P<0.001 all),and significant lower left ventricular end-diastolic diameter(LVEDd)[(49.79±1.58)mm vs.(56.49±2.17)mm],endothelin-1(ET-1)[(36.66±2.65)ng/L vs.(46.88±2.66)ng/L],Minnesota living with heart failure questionnaire(MLHFQ)total score[(36.12±3.23)points vs.(54.67±3.35)points](P<0.001 all).Patients in intervention group had significant lower incidence of adverse events comparing to those in control group(7.27% vs.25.45%,P=0.010).Conclu-sion:Medical community homogenization management could significantly improve self-care ability,heart func-tion,vascular endothelial function and quality of life with good safety in CHF patients.
8.CatLet(Hexu)angiographic scoring system
Xue-cheng SONG ; Yang HE ; Xing-hong LIN ; Cai-yun SONG ; Xiu WANG ; Ming-xing XU ; Yong-ming HE
Chinese Journal of Interventional Cardiology 2025;33(4):231-235
This review has introduced the Coronary Artery Tree description and Lesion EvaluaTion(CatLet or Hexu)angiographic scoring system,which,based solely on coronary angiography results,has characterized 6 types of right coronary artery,3 types of left descending artery,and 3 types of diagonal size,together resulting in 54 types of coronary circulation pattern.This novel angiographic scoring system can be utilized to account for coronary anatomy in its diversity,severity and complexity of diseased coronary arteries,and their subtended myocardial territories in jeopardy.The CatLet angiographic scoring system is unique in that the importance of a coronary artery is weighted according to its subtended myocardial segments,by which the variability of coronary artery has been accounted for and measured.Researchers at home and abroad have increasingly paid attention to its clinical utilities,which warrant further validation in the context of large sample size,prospective,and randomized controlled trials.The CatLet angiographic scoring system is accessible at www.catletscore.com.
9.USP25 ameliorates vascular remodeling by deubiquitinating FOXO3 and promoting autophagic degradation of FOXO3.
Yanghao CHEN ; Bozhi YE ; Diyun XU ; Wante LIN ; Zimin FANG ; Xuefeng QU ; Xue HAN ; Wu LUO ; Chen CHEN ; Weijian HUANG ; Hao ZHOU ; Gaojun WU ; Yi WANG ; Guang LIANG
Acta Pharmaceutica Sinica B 2025;15(3):1643-1658
Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.
10.Deubiquitinase USP13 alleviates doxorubicin-induced cardiotoxicity through promoting the autophagy-mediated degradation of STING.
Liming LIN ; Jibo HAN ; Diyun XU ; Zimin FANG ; Bozhi YE ; Jinfu QIAN ; Xue HAN ; Julian MIN ; Xiaohong LONG ; Gaojun WU ; Guang LIANG
Acta Pharmaceutica Sinica B 2025;15(5):2545-2558
Doxorubicin (Dox) is an anthracycline drug widely applied in various malignancies. However, the fatal cardiotoxicity induced by Dox limits its clinical application. Post-transcriptional protein modification via ubiquitination/deubiquitination in cardiomyocytes mediates the pathophysiological process in Dox-induced cardiotoxicity (DIC). In this study, we aimed to clarify the regulatory role and mechanism of a deubiquitinating enzyme, ubiquitin-specific peptidase 13 (USP13), in DIC. RNA-seq analysis and experimental examinations identified that cardiomyocyte-derived USP13 positively correlated with DIC. Mice with cardiac-specific deletion of USP13 were subjected to Dox modeling. Adeno-associated virus serotype 9 (AAV9) carrying cTNT promoter was constructed to overexpress USP13 in mouse heart tissues. Cardiomyocyte-specific knockout of USP13 exacerbated DIC, while its overexpression mitigated DIC in mice. Mechanistically, USP13 deubiquitinates the stimulator of interferon genes (STING) and promotes the autolysosome-related degradation of STING, subsequently alleviating cardiomyocyte inflammation and death. Our study suggests that USP13 serves a cardioprotective role in DIC and indicates USP13 as a potential therapeutic target for DIC treatment.


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