1.USP51/GRP78/ABCB1 axis confers chemoresistance through decreasing doxorubicin accumulation in triple-negative breast cancer cells.
Yang OU ; Kun ZHANG ; Qiuying SHUAI ; Chenyang WANG ; Huayu HU ; Lixia CAO ; Chunchun QI ; Min GUO ; Zhaoxian LI ; Jie SHI ; Yuxin LIU ; Siyu ZUO ; Xiao CHEN ; Yanjing WANG ; Mengdan FENG ; Hang WANG ; Peiqing SUN ; Yi SHI ; Guang YANG ; Shuang YANG
Acta Pharmaceutica Sinica B 2025;15(5):2593-2611
Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.
2.Relationship between the geriatric nutritional risk index and cognitive function: a cross-sectional study based on the NHANES database.
Long WANG ; Na WANG ; Weihua LI ; Huanbing LIU ; Lizhong NIE ; Menglian SHI ; Wei XU ; Shuai ZUO ; Xinqun XU
Chinese Critical Care Medicine 2025;37(5):465-471
OBJECTIVE:
To explore the relationship between the geriatric nutritional risk index (GNRI) and cognitive function.
METHODS:
A cross-sectional study method was conducted. People aged ≥ 60 years from the National Health and Nutrition Examination Survey (NHANES) databases from 1999 to 2002 and 2011 to 2014 were included as study subjects. The participants were divided into three groups based on their GNRI scores: a medium-high risk group (82 ≤ GNRI < 92), a low risk group (92 ≤ GNRI < 98), and a no-risk group (GNRI ≥ 98). Demographic characteristics (gender, age, race, education), chronic diseases [chronic bronchitis, emphysema, thyroid problems, coronary heart disease, angina pectoris, stroke, hypertension, diabetes mellitus, and depression score on the patient health questionnaire (PHQ-9)], lifestyle habits (history of smoking, hours of sleep), etc., were collected. Cognitive function was assessed using the consortium to establish a registry for Alzheimer's disease word learning subtest (CERAD-WL), animal fluency test (AFT), and digit symbol substitution test (DSST) for the 2011-2014 data, while only the DSST was used for the 1999-2002 data. Differences in the above information among the GNRI cohorts were compared. Factors affecting cognitive function in the population were analyzed using multifactorial Logistic regression.
RESULTS:
2 653 participants from 2011 to 2014 and 2 380 participants from 1999 to 2002 were enrolled, with a total of 5 033 participants in the study. There were statistically significant differences in age, stroke, diabetes mellitus, DSST score, AFT score, CERAD score test 1 recall (Cst1), and CERAD score test 2 recall (Cst2) among the GNRI groups. Multifactorial Logistic regression analysis of data from 2011 to 2014 showed that in model 3 (DSST score, age, gender, race, marriage, education, hours of sleep, history of smoking, emphysema, thyroid problems, chronic bronchitis, coronary heart disease, angina pectoris, hypertension, diabetes mellitus, depression score on the PHQ-9, and stroke) adjusted for all covariates, GNRI was a protective factor for DSST [odds ratio (OR) = 1.03, 95% confidence interval (95%CI) was 1.00 to 1.05, P = 0.03]; Logistic regression analyse for 1999 to 2002 and 2011 to 2014 showed a significant association even after adjustment for covariates (OR = 1.02, 95%CI was 1.00 to 1.03, P = 0.02). Subgroup Logistic regression analyses of the total population from 2011 to 2014 showed a significant association between GNRI and DSST scores (OR = 1.02, 95%CI was 1.01 to 1.03, P < 0.001), with significant associations in the age subgroups of 60 to 64 years old, across gender, non-Hispanic Whites and Blacks, by education, and by marital status associations were significant (all P < 0.05). Subgroup Logistic regression analyse of the total populations from 1999 to 2002 and 2011 to 2014 showed a significant association between the GNRI and DSST score (OR = 1.01, 95%CI was 1.01 to 1.02, P < 0.001), but did not show a significant year difference (interaction P = 0.503), and the newly found in the smoking population the association was also more significant (P < 0.01).
CONCLUSION
The GNRI correlates with the presence of cognitive functions related to processing speed, sustained attention, and executive function, and may be able to serve as an indicator for the assessment or prediction of related cognitive functions.
Humans
;
Cross-Sectional Studies
;
Aged
;
Middle Aged
;
Nutrition Surveys
;
Cognition
;
Female
;
Male
;
Nutritional Status
;
Risk Factors
;
Geriatric Assessment
3.Analysis of Factors Influencing Decision-Making on the Configuration of Large Medical Equipment in Public Hospitals Based on DEMATEL Method
Shuai JIANG ; Xiaoxue DONG ; Yujie ZHAI ; Jing WANG ; Rui MA ; Yibo ZUO ; Jinjin ZHAO ; Chengzeng WANG
Chinese Hospital Management 2025;45(10):1-5
Objective To identify the key influencing factors and role mechanisms of large-scale medical equip-ment allocation decision-making in public hospitals,and to provide a reference basis for optimizing resource alloca-tion strategies.Methods Through searching the literature related to large-scale medical equipment decision-making in public hospitals and combing the policies,the system of decision-making influencing factors was initially screened.The Delphi method and decision-making trial and evaluation laboratory method were used to obtain the key influencing factors of equipment allocation decision-making and to determine the interaction effects among the factors.Results A total of seven cause factors and nine effect factors were screened.Among them,cost-benefit analysis,equipment technical performance,and evaluation of similar equipment were the top three key drivers;leadership emphasis,equipment market price,and equipment supporting facilities were the top three key con-straints.Conclusion Priority be given to strengthening the management of driving factors,mainly by conducting a full-cycle assessment of cost-effectiveness,paying attention to the clinical value output of equipment technical performance,and monitoring regionally similar equipment.A dynamic response mechanism for constraints should be established,mainly to strengthen leadership decision-making,implement a centralized procurement price nego-tiation model and improve the pre-assessment system for ancillary facilities.
4.Short-term outcomes of using robotic double-flap technique following proximal gastrectomy in patients with carcinoma of esophagogastric junction
Shaorong PAN ; Shuai ZUO ; Yalun LI ; Shanwen CHEN ; Zeyang CHEN ; Pengyuan WANG
Chinese Journal of General Surgery 2025;40(8):619-623
Objective:To evaluate the short-term outcomes of robotic double-flap technique following proximal gastrectomy in patients with carcinoma of esophagogastric junction(AEG).Methods:Clinical data of 5 AEG cases undergoing robotic double-flap technique following proximal gastrectomy were analyzed at the Department of Gastrointestinal Surgery, Peking University First Hospital from Dec 2023 to Aug 2024 .Results:All the 5 patients were of Siewert Ⅱ type AEG. Robot-assisted radical proximal gastrectomy and esophagogastric double-flap anastomosis were successfully completed. The operation time was (361±63) min, the installation time was (21±11) min, the anastomosis time was (90±21) min, and the median intraoperative blood loss was 100 (50,200) ml. The median number of intraoperative lymph nodes resected was 23 (14,32), the first postoperative exhaust time was (4.8±1.1) d, and postoperative hospital stay was (14.6±8.8) d. Postoperative abdominal distension occurred in 1 patient, and no significant anastomotic stenosis or anastomotic leakage was observed by upper gastroenterography. After conservative treatment, the patient recovered. None of them had Clavien-Dindo grade ≥Ⅲ complications. There were no anastomotic complications such as anastomotic leakage, anastomotic hemorrhage and anastomotic stenosis.Conclusion:Robotic double-flap technique following proximal gastrectomy is a safe and effective treatment for AEG.
5.Analysis of Factors Influencing the Technical Labour Value of Teleconsultants Based on the DEMATEL
Yibo ZUO ; Shuai JIANG ; Xiaoxue DONG
Chinese Health Economics 2025;44(9):58-61
Objective:To explore the key influencing factors of the technical and labor value of remote consultation doctors,and to provide references for improving the service pricing and salary mechanism.Methods:The expert consultation method and the Decision-Making Trial and Evaluation Laboratory(DEMATEL)were adopted to identify the key influencing factors of the technical and labor value of remote consultation doctors and the relationships among them.Results:A total of 6 causal factors and 8 outcome factors were screened out.Among them,the subjective feelings of the invited experts were the core causal factor,and work ability was the core outcome factor.Conclusion:Enhancing the subjective sense of acquisition and subjective sense of identity of experts on the invited side of teleconsultation guides doctors to set up correct values and improves doctors' medical knowledge,clinical experience,communication ability and other working abilities to effectively promote the sustainable development of teleconsultation.
6.Analysis of Key Issues and Strategies in Financial Settlement for the Public Hospital under Third-party Payment Methods
Qing HE ; Yibo ZUO ; Shuai JIANG
Chinese Hospital Management 2025;45(1):91-93
Public hospitals have introduced third-party payment methods to improve patients'medical treatment experience,however large public hospitals face challenges in financial reconciliation due to the complexity of income types,multiple accounting units,and delayed cross-hospital reconciliation.Based on the practical experience of the First Affiliated Hospital of Zhengzhou University in financial management,it analyzes the current situation of third-party payment in hospitals and identifies key problems in financial reconciliation,such as increased risk of re-funds,prominent single-sided accounting issues,and low efficiency of manual reconciliation.It proposes strategies for optimizing the hierarchical structure of the reconciliation post,updating accounting subjects rationally,and im-proving the intelligence of the reconciliation system,to provide reference for financial reconciliation work in large pub-lic hospitals under third-party payment methods and improve the operational efficiency of public hospitals.
7.Analysis of Key Issues and Strategies in Financial Settlement for the Public Hospital under Third-party Payment Methods
Qing HE ; Yibo ZUO ; Shuai JIANG
Chinese Hospital Management 2025;45(1):91-93
Public hospitals have introduced third-party payment methods to improve patients'medical treatment experience,however large public hospitals face challenges in financial reconciliation due to the complexity of income types,multiple accounting units,and delayed cross-hospital reconciliation.Based on the practical experience of the First Affiliated Hospital of Zhengzhou University in financial management,it analyzes the current situation of third-party payment in hospitals and identifies key problems in financial reconciliation,such as increased risk of re-funds,prominent single-sided accounting issues,and low efficiency of manual reconciliation.It proposes strategies for optimizing the hierarchical structure of the reconciliation post,updating accounting subjects rationally,and im-proving the intelligence of the reconciliation system,to provide reference for financial reconciliation work in large pub-lic hospitals under third-party payment methods and improve the operational efficiency of public hospitals.
8.Analysis of Factors Influencing the Technical Labour Value of Teleconsultants Based on the DEMATEL
Yibo ZUO ; Shuai JIANG ; Xiaoxue DONG
Chinese Health Economics 2025;44(9):58-61
Objective:To explore the key influencing factors of the technical and labor value of remote consultation doctors,and to provide references for improving the service pricing and salary mechanism.Methods:The expert consultation method and the Decision-Making Trial and Evaluation Laboratory(DEMATEL)were adopted to identify the key influencing factors of the technical and labor value of remote consultation doctors and the relationships among them.Results:A total of 6 causal factors and 8 outcome factors were screened out.Among them,the subjective feelings of the invited experts were the core causal factor,and work ability was the core outcome factor.Conclusion:Enhancing the subjective sense of acquisition and subjective sense of identity of experts on the invited side of teleconsultation guides doctors to set up correct values and improves doctors' medical knowledge,clinical experience,communication ability and other working abilities to effectively promote the sustainable development of teleconsultation.
9.Analysis of Factors Influencing Decision-Making on the Configuration of Large Medical Equipment in Public Hospitals Based on DEMATEL Method
Shuai JIANG ; Xiaoxue DONG ; Yujie ZHAI ; Jing WANG ; Rui MA ; Yibo ZUO ; Jinjin ZHAO ; Chengzeng WANG
Chinese Hospital Management 2025;45(10):1-5
Objective To identify the key influencing factors and role mechanisms of large-scale medical equip-ment allocation decision-making in public hospitals,and to provide a reference basis for optimizing resource alloca-tion strategies.Methods Through searching the literature related to large-scale medical equipment decision-making in public hospitals and combing the policies,the system of decision-making influencing factors was initially screened.The Delphi method and decision-making trial and evaluation laboratory method were used to obtain the key influencing factors of equipment allocation decision-making and to determine the interaction effects among the factors.Results A total of seven cause factors and nine effect factors were screened.Among them,cost-benefit analysis,equipment technical performance,and evaluation of similar equipment were the top three key drivers;leadership emphasis,equipment market price,and equipment supporting facilities were the top three key con-straints.Conclusion Priority be given to strengthening the management of driving factors,mainly by conducting a full-cycle assessment of cost-effectiveness,paying attention to the clinical value output of equipment technical performance,and monitoring regionally similar equipment.A dynamic response mechanism for constraints should be established,mainly to strengthen leadership decision-making,implement a centralized procurement price nego-tiation model and improve the pre-assessment system for ancillary facilities.
10.Short-term outcomes of using robotic double-flap technique following proximal gastrectomy in patients with carcinoma of esophagogastric junction
Shaorong PAN ; Shuai ZUO ; Yalun LI ; Shanwen CHEN ; Zeyang CHEN ; Pengyuan WANG
Chinese Journal of General Surgery 2025;40(8):619-623
Objective:To evaluate the short-term outcomes of robotic double-flap technique following proximal gastrectomy in patients with carcinoma of esophagogastric junction(AEG).Methods:Clinical data of 5 AEG cases undergoing robotic double-flap technique following proximal gastrectomy were analyzed at the Department of Gastrointestinal Surgery, Peking University First Hospital from Dec 2023 to Aug 2024 .Results:All the 5 patients were of Siewert Ⅱ type AEG. Robot-assisted radical proximal gastrectomy and esophagogastric double-flap anastomosis were successfully completed. The operation time was (361±63) min, the installation time was (21±11) min, the anastomosis time was (90±21) min, and the median intraoperative blood loss was 100 (50,200) ml. The median number of intraoperative lymph nodes resected was 23 (14,32), the first postoperative exhaust time was (4.8±1.1) d, and postoperative hospital stay was (14.6±8.8) d. Postoperative abdominal distension occurred in 1 patient, and no significant anastomotic stenosis or anastomotic leakage was observed by upper gastroenterography. After conservative treatment, the patient recovered. None of them had Clavien-Dindo grade ≥Ⅲ complications. There were no anastomotic complications such as anastomotic leakage, anastomotic hemorrhage and anastomotic stenosis.Conclusion:Robotic double-flap technique following proximal gastrectomy is a safe and effective treatment for AEG.

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