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.A double-blind randomised controlled clinical trial of Shenling Baizhu Granules in treating low anterior resection syndrome in rectal cancer
Shuo FENG ; Hui YE ; Yingchao WU ; Guowei CHEN ; Tao WU ; Yong JIANG ; Tao LIU ; Shuai ZUO ; Xuezhi ZHANG ; Junling ZHANG ; Xin WANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(7):953-960
Objective This study aimed to assess the clinical efficacy of Shenling Baizhu Granules in treating low anterior resection syndrome(LARS)in rectal cancer.Methods The study employed a randomized,double-blind,placebo-parallel controlled,single-center,validity-tested clinical trial design.December 2019 to June 2022,the Department of Gastrointestinal Surgery and Integrated Traditional Chinese and Western Medicine of Peking University First Hospital recruited 110 patients who had undergone low anterior resection(LAR)for rectal cancer and subsequently developed LARS.These patients,meeting the enrollment criteria,were randomly assigned into the treatment group(55)and the control group(55)using the double-blind method principle.The randomization table was generated by SAS 9.2 software employing the double-blind method.The treatment group received oral Shenling Baizhu Granules,while the control group received oral placebo granules.Both groups commenced treatment on the 10th day after-surgery for 30 consecutive days.Patients were evaluated using LARS score,traditional Chinese medicine(TCM)symptom grading,and XU Zhongfa score before treatment,on the 15th day of treatment,and on the 1st day after treatment cessation.Results Out of 110 patients,107 were included in the full analysis set for efficacy analysis:55 patients in the treatment group and 55 patients in the control group.One case in the treatment group was excluded(against protocol),and two cases in the control group were excluded(one lost to follow-up,one against protocol).Baseline data between the two groups were consistent,with no statistically significant difference.Before treatment,LARS scores for the treatment and control groups were 33.0(31.0,36.0)and 34.0(32.0,37.0)respectively.Patients with TCM symptom scores of grades 2 to 3 accounted for 92.73%and 90.57%in the treatment and control groups,respectively,with no statistically significant difference.After 30 days of treatment,LARS scores for the treatment and control groups were 21.0(19.8,23.0)and 26.0(22.0,28.0)respectively.The percentage of patients with TCM symptom scores of grades 2 to 3 decreased to 33.33%in the treatment group and 66.04%in the control group,with a statistically significant difference.Shenling Baizhu Granules showed rapid improvement in watery or loose stools in post-operative rectal cancer patients.After 30 days of treatment,Shenling Baizhu Granules significantly improved appetite,stool consistency,abdominal distension,abdominal pain,and eructation symptoms in postoperative rectal cancer patients.Before treatment,the XU Zhongfa scores for the treatment and control groups were 3.0(2.0,4.3)and 4.0(2.0,4.0)respectively,with no statistically significant difference.After 30 days of treatment,the XU Zhongfa scores for the treatment and control groups were 7.0(6.0,8.0)and 6.0(5.0,7.0)respectively,with the treatment group significantly higher than the control group(P<0.01).Conclusion Shenling Baizhu Granules can effectively improve LARS symptoms in patients following LAR of rectal cancer within a short period of time.
4.Analysis on Influencing Factors of the Work Performance of Medical Staff in Tertiary Hospitals in Henan Province
Mengyu YANG ; Shuai JIANG ; Mian XIA ; Yibo ZUO ; Hang FU ; Chengzeng WANG
Chinese Health Economics 2024;43(5):9-12
Objective:To understand the current situation of work performance and influencing factors of medical staff in tertiary hospitals in Henan Province,in order to provide references for improving their performance level.Methods:An electronic questionnaire was used to investigate the work engagement and work performance of medical staff in a sample hospital in Henan Province,and multiple regression analysis was used to explore the relationship between work engagement and work performance.Results:The total score of medical staff's job performance was 45.18±5.78;Cronbach's α coefficient of the questionnaire's reliability ranged from 0.870 to 0.964;medical staff's job commitment was positively correlated with their job performance;and the highest level of educational attainment,occupational category,and job commitment were the main influencing factors of job performance(P<0.05).Conclusion:There is still much room for improvement in the work performance of medical staff in tertiary hospitals in Henan Province,and hospitals should focus on improving the work capacity of medical staff and actively improving work engagement in order to enhance the level of medical staff performance.
5.Study on the Influence Mechanism of Salary Satisfaction on Job Performance of Nursing Staff in Henan Province
Yibo ZUO ; Mian XIA ; Shuai JIANG
Chinese Health Economics 2024;43(5):18-22
Objective:To understand the current situation of nursing staff's salary satisfaction and job performance in Henan Province,and to explore the mechanism of salary satisfaction's influence on job performance.Methods:Electronic questionnaire was used to investigate the salary satisfaction,job performance and job involvement of nursing staff in sample public hospitals in Henan Province,and structural equation model was used to analyze the influence path of salary satisfaction on job performance.Results:The scores of nurses'salary satisfaction,job performance and job involvement were(68.59±19.99),(48.95±6.53)and(82.27±18.22)respectively.Nursing salary satisfaction was significantly and positively correlated with job performance(r= 0.594,P<0.01)and work engagement(r= 0.600,P<0.01).The standardized path coefficient of nursing staff's salary satisfaction on job performance was 0.637(P= 0.002).Conclusion:Pay satisfaction for caregivers has a significant positive impact on job outcomes,and job engagement serves as a mediator between reward satisfaction and job outcomes.It is suggested to improve the salary satisfaction and job involvement of nursing staff in order to promote the improvement of job performance.
6.Hospital Performance Allocation Strategy Based on Job Classification Evaluation Coefficient Method
Dayong FENG ; Yibo ZUO ; Shuai JIANG
Chinese Health Economics 2024;43(9):75-77
Under the new situation of healthcare reform and high-quality development,public hospitals are committed to explore an efficient and fair strategy for distributing position-based bonuses to all staff.Therefore,the innovative post classification evalua-tion coefficient method can effectively solve this problem.It discusses two kinds of hospital performance distribution management infra-structure:clinical and medical personnel performance management with RBRVS as the core and administrative logistics performance management guided by post evaluation.The general model of basic bonus post coefficient evaluation method is summarized and empiri-cal research is conducted.The results show that the average growth rate of hospital medical income in three years(2021-2023)is more than 35%,during the same period,the hospital achieves profit from loss,the"national examination"score jumps from C to B,and the patient satisfaction steadily increases to more than 97%.Therefore,it puts forward the strategy of hospital performance distribution based on post classification evaluation coefficient method:perfect performance management system provides basic guaran-tee for performance distribution;the establishment of hospital performance management objectives provides strategic support for per-formance distribution;the establishment of performance supervision and feedback mechanism continuously improves hospital perfor-mance distribution.
7.Research on the Problem and Optimization Strategy of Salary Distribution Mechanism in Public Hospitals Based on Grounded Theory
Xiaoru WANG ; Yibo ZUO ; Shuai JIANG ; Shengfang YAN
Chinese Hospital Management 2024;44(9):58-60
Objective To better mobilize the work motivation of the majority of medical staff and to explore the optimization strategy of the remuneration distribution mechanism in public hospitals.Methods A semi-structured interview was conducted on employees of a large public hospital in Henan Province using purposive sampling method in March 2024.Sort out,code,and integrate interview data based on grounded theory.Results Based on 40 interview materials,44 initial concepts,14 basic categories,6 main categories,and 3 core categories were summarized.A model of pay distribution mechanism in public hospitals based on pay distribution principle,pay distribution structure and pay management system was constructed.Conclusion It is recommended that hospitals ensure the fairness and competitiveness of salary distribution,implement diversified salary policies,and continuously improve the salary distribution structure and supervision and management system.
8.Analysis on Influencing Factors of the Work Performance of Medical Staff in Tertiary Hospitals in Henan Province
Mengyu YANG ; Shuai JIANG ; Mian XIA ; Yibo ZUO ; Hang FU ; Chengzeng WANG
Chinese Health Economics 2024;43(5):9-12
Objective:To understand the current situation of work performance and influencing factors of medical staff in tertiary hospitals in Henan Province,in order to provide references for improving their performance level.Methods:An electronic questionnaire was used to investigate the work engagement and work performance of medical staff in a sample hospital in Henan Province,and multiple regression analysis was used to explore the relationship between work engagement and work performance.Results:The total score of medical staff's job performance was 45.18±5.78;Cronbach's α coefficient of the questionnaire's reliability ranged from 0.870 to 0.964;medical staff's job commitment was positively correlated with their job performance;and the highest level of educational attainment,occupational category,and job commitment were the main influencing factors of job performance(P<0.05).Conclusion:There is still much room for improvement in the work performance of medical staff in tertiary hospitals in Henan Province,and hospitals should focus on improving the work capacity of medical staff and actively improving work engagement in order to enhance the level of medical staff performance.
9.Study on the Influence Mechanism of Salary Satisfaction on Job Performance of Nursing Staff in Henan Province
Yibo ZUO ; Mian XIA ; Shuai JIANG
Chinese Health Economics 2024;43(5):18-22
Objective:To understand the current situation of nursing staff's salary satisfaction and job performance in Henan Province,and to explore the mechanism of salary satisfaction's influence on job performance.Methods:Electronic questionnaire was used to investigate the salary satisfaction,job performance and job involvement of nursing staff in sample public hospitals in Henan Province,and structural equation model was used to analyze the influence path of salary satisfaction on job performance.Results:The scores of nurses'salary satisfaction,job performance and job involvement were(68.59±19.99),(48.95±6.53)and(82.27±18.22)respectively.Nursing salary satisfaction was significantly and positively correlated with job performance(r= 0.594,P<0.01)and work engagement(r= 0.600,P<0.01).The standardized path coefficient of nursing staff's salary satisfaction on job performance was 0.637(P= 0.002).Conclusion:Pay satisfaction for caregivers has a significant positive impact on job outcomes,and job engagement serves as a mediator between reward satisfaction and job outcomes.It is suggested to improve the salary satisfaction and job involvement of nursing staff in order to promote the improvement of job performance.
10.Hospital Performance Allocation Strategy Based on Job Classification Evaluation Coefficient Method
Dayong FENG ; Yibo ZUO ; Shuai JIANG
Chinese Health Economics 2024;43(9):75-77
Under the new situation of healthcare reform and high-quality development,public hospitals are committed to explore an efficient and fair strategy for distributing position-based bonuses to all staff.Therefore,the innovative post classification evalua-tion coefficient method can effectively solve this problem.It discusses two kinds of hospital performance distribution management infra-structure:clinical and medical personnel performance management with RBRVS as the core and administrative logistics performance management guided by post evaluation.The general model of basic bonus post coefficient evaluation method is summarized and empiri-cal research is conducted.The results show that the average growth rate of hospital medical income in three years(2021-2023)is more than 35%,during the same period,the hospital achieves profit from loss,the"national examination"score jumps from C to B,and the patient satisfaction steadily increases to more than 97%.Therefore,it puts forward the strategy of hospital performance distribution based on post classification evaluation coefficient method:perfect performance management system provides basic guaran-tee for performance distribution;the establishment of hospital performance management objectives provides strategic support for per-formance distribution;the establishment of performance supervision and feedback mechanism continuously improves hospital perfor-mance distribution.

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