1.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.
2.Analyses of the risk factors of delayed extubation after extended thymectomy in patients with myasthenia gravis
Meiping WANG ; Xueqi SUN ; Li JIANG ; Ran LOU ; Quan SI ; Tingting WANG ; Gaojun LU
Chinese Journal of Internal Medicine 2025;64(1):52-59
Objective:To explore the risk factors of delayed extubation after expanded thymectomy in patients with myasthenia gravis.Methods:Patients with myasthenia gravis who underwent expanded thymectomy from May 2021 to January 2024 and were admitted to Intensive Care Unit (ICU) after surgery were retrospectively analyzed. Patients were divided in to the delayed extubation and successful extubation according to the length of mechanical ventilation whether exceeding than 48 hours. Multivariable logistics regression was used to explore the risk factors for delayed extubation after expanded thymectomy in patients with myasthenia gravis.Results:A total of 95 patients were included.15 (15.8%) of whom were delayed extubation. Compared with the successful extubation patients, the length of mechanical ventilation (94.0 h vs. 15.5 h, P<0.001), ICU station (7.1 days vs. 1.7 days, P<0.001), and hospitalization station (16.0 days vs. 9.1 days, P<0.001) were significantly prolonged in the delayed extubation patients. Adjusted for age,gender, BMI, clinical classification, pathological classification of thymoma, dose of pyridostigmine preoperative, perioperative pneumonia, preoperative pulmonary dysfunction, SBT passing for the first time, neck lift time greater than 20 seconds, the multivariable logistic regression shown, the risk of delayed extubation increased by 29% ( OR=1.290, 95% CI 1.090-1.714), 1% ( OR=1.009, 95% CI 1.002-1.034), 3.9-fold ( OR=4.977, 95% CI 1.486-10.939), and 64% ( OR=1.635, 95% CI 1.396-2.682) for every 60 mg/day increase in preoperative dose of pyridostigmine, pathological classification of thymoma, perioperative pneumonia, and preoperative pulmonary dysfunction, respectively. Neck lift time greater than 20 seconds can reduce the risk of delayed extubation 48% ( OR=0.524, 95% CI 0.322-0.794). Conclusion:Preoperative administration of a large dose of pyridostigmine, pulmonary dysfunction, pathological classification of thymoma, and perioperative pneumonia were risk factors for delayed extubation after thymectomy in these patients. And neck lift time greater than 20 seconds decreased the risk of delayed extubation. In the clinical practice,for high risk of MG patients with delayed extubation, the neck lifting test may be used to assess muscle strength and reduce the occurance of tracheal reintubation and its advise effects.
3.Analyses of the risk factors of delayed extubation after extended thymectomy in patients with myasthenia gravis
Meiping WANG ; Xueqi SUN ; Li JIANG ; Ran LOU ; Quan SI ; Tingting WANG ; Gaojun LU
Chinese Journal of Internal Medicine 2025;64(1):52-59
Objective:To explore the risk factors of delayed extubation after expanded thymectomy in patients with myasthenia gravis.Methods:Patients with myasthenia gravis who underwent expanded thymectomy from May 2021 to January 2024 and were admitted to Intensive Care Unit (ICU) after surgery were retrospectively analyzed. Patients were divided in to the delayed extubation and successful extubation according to the length of mechanical ventilation whether exceeding than 48 hours. Multivariable logistics regression was used to explore the risk factors for delayed extubation after expanded thymectomy in patients with myasthenia gravis.Results:A total of 95 patients were included.15 (15.8%) of whom were delayed extubation. Compared with the successful extubation patients, the length of mechanical ventilation (94.0 h vs. 15.5 h, P<0.001), ICU station (7.1 days vs. 1.7 days, P<0.001), and hospitalization station (16.0 days vs. 9.1 days, P<0.001) were significantly prolonged in the delayed extubation patients. Adjusted for age,gender, BMI, clinical classification, pathological classification of thymoma, dose of pyridostigmine preoperative, perioperative pneumonia, preoperative pulmonary dysfunction, SBT passing for the first time, neck lift time greater than 20 seconds, the multivariable logistic regression shown, the risk of delayed extubation increased by 29% ( OR=1.290, 95% CI 1.090-1.714), 1% ( OR=1.009, 95% CI 1.002-1.034), 3.9-fold ( OR=4.977, 95% CI 1.486-10.939), and 64% ( OR=1.635, 95% CI 1.396-2.682) for every 60 mg/day increase in preoperative dose of pyridostigmine, pathological classification of thymoma, perioperative pneumonia, and preoperative pulmonary dysfunction, respectively. Neck lift time greater than 20 seconds can reduce the risk of delayed extubation 48% ( OR=0.524, 95% CI 0.322-0.794). Conclusion:Preoperative administration of a large dose of pyridostigmine, pulmonary dysfunction, pathological classification of thymoma, and perioperative pneumonia were risk factors for delayed extubation after thymectomy in these patients. And neck lift time greater than 20 seconds decreased the risk of delayed extubation. In the clinical practice,for high risk of MG patients with delayed extubation, the neck lifting test may be used to assess muscle strength and reduce the occurance of tracheal reintubation and its advise effects.
4.Clinical Advantages of Traditional Chinese Medicine in Treatment of Pediatric Diseases
Yingke LIU ; Hong CUI ; Jian YANG ; Junhong WANG ; Liqun WU ; Xiaohua JI ; Bing AN ; Xiaomei LIU ; Weilin WAN ; Hong WANG ; Gaojun ZHOU ; Wen ZHANG ; Liyi QIU ; Kai GUO ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):224-231
The traditional Chinese medicine (TCM) in pediatric care has a long history,proven efficacy,and distinctive characteristics.The China Association of Chinese Medicine has organized a series of youth salons to discuss the clinical advantages of treating diseases.Experts at this seminar proposed that the superior disease categories in pediatric TCM are significant for showcasing the unique strengths and advantages of TCM in the treatment of pediatric diseases,enhancing diagnostic and treatment levels,inheriting TCM knowledge,promoting the integration of TCM and Western medicine,and meeting patients' needs.The strengths of pediatric TCM are summed up as "having what others do not,excelling at what others have,being special in what others excel at,and ensuring safety in what others specialize in." The scope of superiority in pediatric TCM covers multiple systems,including respiratory,digestive,endocrine,psychological,and dermatological systems.This article summarized the advantages of TCM in treating 13 diseases discussed in the salon,such as upper respiratory tract infections,coughs,pneumonia,allergic rhinitis,bronchial asthma,atopic dermatitis,functional dyspepsia,functional constipation,enuresis,marginal short stature,simple obesity,attention deficit hyperactivity disorder,and tic disorders.The overall advantages were reflected in three aspects:First,the holistic concept and treatment based on syndrome differentiation in TCM highlight the advantage of treating the root causes of diseases,making the treatment methodical and precise.Second,most traditional Chinese herbs are natural and have strong safety profiles.Third,TCM treatment methods are abundant,especially the external treatment methods,which are widely used in pediatrics,highly accepted by parents,and have definite efficacy,as well as good safety and compliance.
5.Extended thymectomy for myasthenia gravis via subxiphoid versus intercostal approaches: A retrospective cohort study in a single center
Gaojun LU ; Ruotian WANG ; Baodong LIU ; Lei SU ; Kun QIAN ; Peilong ZHANG ; Teng ZHAO ; Yi ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(08):1119-1126
Objective To analyze the clinical outcomes of extended thymectomy for myasthenia gravis (MG) patients under different surgical approaches, and to determine the factors affecting the prognosis of MG. Methods The MG patients who underwent extended thymectomy from January 2014 to March 2021 in our hospital were retrospectively collected. According to the surgical approach, they were divided into a subxiphoid group and an intercostal group, and the perioperative results and prognosis were compared between the two groups. A “good outcome” was defined as complete stable remission (CSR), pharmacological remission (PR) or minimal manifestations state (MMS); a “poor outcome” was defined as outcomes worse than MMS. Univariate and multivariate logistic regression analyses were performed to assess the factors associated with the good outcomes. Results A total of 187 MG patients were included in the study, including 82 males and 105 females, with a median age of 50 (36, 60) years. There were 134 patients in the intercostal group and 53 patients in the subxiphoid group. Compared with the intercostal group, although the operation time of the subxiphoid group was longer [200.0 (172.0, 232.0) min vs. 141.0 (118.0, 169.0) min, P<0.001], the intraoperative blood loss was less [10.0 (10.0, 20.0) mL vs. 20.0 (10.0, 50.0) mL, P<0.001], the postoperative hospital stay was shorter [3.0 (2.5, 4.0) d vs. 5.0 (3.0, 7.0) d, P<0.001], and the incidence of complications was lower [1 (1.9%) vs. 26 (19.4%), P=0.001]. A total of 159 (85.0%) patients were followed up for a median period of 46 (13, 99) months, with a good outcome rate of 90.6% and CSR rate of 33.3%. There were no statistical differences in PR, MMS or overall good outcome rates between the two groups (P>0.05). Multivariate logistic analysis showed that age≤50 years was an independent predictor for "good outcome" of MG patients. Conclusion Extended thymectomy via subxiphoid for MG is a safe, feasible and effective surgical approach.
6.Current status and prospect of bariatric artery embolization
Qingyue CAO ; Zhi WANG ; Gaojun TENG
Journal of Interventional Radiology 2024;33(8):817-820
Over the past 50 years,the global incidence of obesity has dramatically increased,posing a serious threat to human health.Conventional weight loss methods,such as dieting and exercise therapy,are difficult to obtain a stable and rapid weight-loss effect.Besides,most weight-loss drugs available nowadays are not specifically designed for the pure obese population,they are mainly used for diabetes.The prevalence of traditional bariatric surgery is low,and it carries high surgical costs and high risk of developing complications.Therefore,bariatric artery embolization(BAE),regarded as a new weight-loss therapy,has emerged and it has developed rapidly.BAE can not only achieve long-term weight control,but also provide glycemic benefit to patients with pre-diabetes.Compared with traditional bariatric surgery,BAE has the advantages of less trauma,quick recovery and low risk of postoperative complications.However,there is no unified standard for the selection of intraoperative embolization materials and embolization sites so far,and the postoperative changes of gastric function and the specific mechanism of body metabolism improvement need to be further explored.This paper aims to make a detailed review about BAE,focusing on the research background,the technical principles,the latest research progress,and the existing problems.
7.Current status and future of interventional robotic surgical system
Gaojun TENG ; Cheng WANG ; Jian LU
Chinese Journal of Digestive Surgery 2021;20(5):479-486
Interventional medicine plays an important role in the diagnosis and treatment of cardiovascular and cerebrovascular diseases, hepatobiliary tumors and other diseases, which has become the third largest type of treatment technology besides internal and surgical treatment. In recent years, with technological breakthroughs in imaging technology, robotic surgical system, artificial intelligence, Internet of Things and other fields, unprecedented opportunities have been provided for interventional/minimally invasive+robotics. Interventional robotic surgical systems have mushroomed around this field. The authors discuss the current status and future of interventional robotic surgical system with high recognition worldwide, especially the three categories of specialized robotic surgical system for vascular intervention, percutaneous puncture intervention and natural non-vascular luminal intervention.
8.Effect Evaluation of National Drug Centralized Volume-based Procurement in a Public Hospital from the Per- spective of Value-based Healthcare
Jie ZHAO ; Wei LI ; Gaojun WANG
China Pharmacy 2021;32(19):2410-2414
OBJECTIVE:To evaluate the implementation of national drug centralized volume-based procurement (called “VBP”for short)in a public hospital,so as to provide reference for promoting VBP policy guided by value-based healthcare. METHODS:A total of 6 varieties and 12 specifications of antibiotics included in VBP in a public hospital in Chongqing were analyzed. The drug use data of the hospital one year before the implementation of VBP(i.e. April 20,2019- April 19,2020)and one year after the implementation(i.e. April 20,2020-April 19,2021)were collected and analyzed in respects of price change, generic drug substitution rate,average daily cost(DDDc),actual cost savings and other indicators. The problems and suggestions were put forward,and the effects of VBP policy implementation whether reflects the core connotation of value-based healthcare were evaluated. RESULTS:After the implementation of VBP,drug prices fell by an average of 63.44%,the average price drop of original drugs was 27.38% ,and substitution rate of generic drugs was 25.59% . DDDc of selected antibiotics in the hospital decreased in varying degrees,of which the decline of four drugs was 10%-40%,and that of Moxifloxacin hydrochloride tablets was 80.14%. Compared with bef VBP,6 kinds of antibiotics saved about 521 300 yuan,of which the imported Moxifloxacin hydrochloride tablets and Moxifloxacin hydrochloride sodium chloride injection saved 495 300 yuan(accounting for 94.97% of the total cost savings of antibiotics). CONCLUSIONS:The value of VBP based on the perspective of value-based healthcare is mainly reflected in the dual channel management mechanism of drugs,which improves the availability of drugs,effectively controls the unreasonable growth of medical expenses,reduces the expenditure of medical insurance fund,and helps to further reduce the drug burden of patients. At present,the implementation of VBP still faces difficulties,including the need for drug prices to return to a reasonable range,the need for foreign enterprises to change strategies to seek a breakthrough,and different therapeutic efficacy due to the difference in quality between the selected generic drugs and the original drugs. Therefore,the author believes that the pharmaceutical market structure should be transformed positively,value-based healthcare should help the regulation of medical insurance,and the consistency evaluation system should be optimized,so as to further improve the health level of patients.
9. Diagnostic value of folate receptor-positive circulating tumor cell detection in subcentimeter pulmonary nodules
Gaojun LU ; Ruotian WANG ; Xiaoru TIAN ; Xin JIN ; Yi ZHANG
Cancer Research and Clinic 2020;32(1):1-5
Objective:
To investigate the value of the folate receptor (FR)-positive circulating tumor cell (CTC) detection in the diagnosis of benign and malignant subcentimeter pulmonary nodules(the maximum diameter ≤10 mm).
Methods:
Thirty-seven patients with subcentimeter pulmonary nodules (the chest CT showed the maximum diameter was ≤10 mm) in the Xuanwu Hospital of Capital Medical University from July to December 2018 were collected. Among them, 22 cases were diagnosed with early stage lung adenocarcinoma by postoperative pathological diagnosis and another 15 cases were benign lung lesion. Venous blood samples from these patients were collected before surgery and then utilized to detect FR+ CTC level (defined unit as FU/3 ml) by novel ligand-targeted polymerase chain reaction (LT-PCR), and the enzyme-linked immunosorbent assay was used to detect the levels of tumor markers, including carcinoembryonic antigen (CEA), neuron-specific enolase(NSE), cytokeratin 19 fragment CYFRA21-1, carbohydrate antigen 125 (CA125), CA199, pro-gastrin releasing peptide (pro-GRP), etc. The t-test was used to compare the measurement values between the groups. The CTC value 8.70 FU/3 ml described in the detection kit instruction was used as the threshold. The binary logistic regression was used to analyze the risk factors of malignant pulmonary nodules. The kappa consistency test was used to identify the consistency of the diagnosis results obtained by the FR+ CTC level and the pathological results of surgically resected specimens. The receiver operating characteristic curve (ROC) was drawn to evaluate the efficiency of each index for the diagnosis of benign and malignant subcentimeter pulmonary nodules.
Results:
The level of FR+ CTC in patients with early stage lung cancer was higher than that in patients with benign lung lesion, and the difference was statistically significant [(11.0±3.0) FU/3 ml vs. (7.0±3.7) FU/3 ml,
10. Risk factors analysis and prognosis of renal pelvis dilatation in high-risk infants in monocenter
Qian FU ; Lirong FAN ; Ying SHEN ; Gaojun ZHOU ; Huizhen YI ; Ning SUN ; Jiamei WANG ; Liqun JIA ; Xiaoman WANG ; Hui WANG
Chinese Journal of Pediatrics 2018;56(1):53-57
Objective:
To explore the prognosis and risk factors of pyelectasis in high-risk infants.
Methods:
This was a retrospective study. Totally 960 high-risk infants, who accepted type B ultrasonic examination for fetus at 28th week of gestation and for newborns in 48 hours after birth, were included in the study in departments of obstetrics and eonatology, Shunyi Maternal and Children's Hospital of Beijing Children's Hospital during May 2012 to April 2013. The degree of pyelectasis was classified using Grignon grade and the paients were followed up for 3 years. The factors of epidemiology, high risk pregnant women, fetus and high-risk newborns that relate to pyelectasis were summarized. High-risk factors were analyzed by using logistic multivariate regression analysis.
Results:
Of 960 high-risk infants, 103 had abnormal urinary ultrasound results, 87 (9.1% of high-risk infants) were diagnosed with pyelectasis, 16 (1.7% of high-risk infants) were diagnosed with congenital anomalies of the kidney and urinary tract. According to the degree of pyelectasis, 68 infants were Grignon grade Ⅰ, male:female ratio=5.8∶1, left side:right side ratio=1.91∶1; 19 infants were Grignon grade Ⅱ, male:female ratio=5.33∶1, left side:right side ratio=2.12∶1. Postnatal follow-up results showed that pyelectasis disappeared in 48 cases (55% of pyelectasis cae), 40 infants were Grignon grade Ⅰ (59% of all Grignon grade Ⅰ patients), 8 infants were Grignon grade Ⅱ (42% of all Grignon grade Ⅱ patients); The result of risk factors analysis showed that the risk of pyelectasis in males was 4.368 times that of females (95%

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