1.Ubiquitination and degradation of RPTPα mediated by MARCH9
Yuqin ZHANG ; AIHEMAITI YILIXIATI ; Yanli WANG ; Zhi YANG ; Jian HUANG
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(8):957-968
Objective·To investigate the molecular mechanisms and biological functions of the E3 ubiquitin ligase membrane-associated RING-CH 9(MARCH9)in regulating the ubiquitination of receptor protein tyrosine phosphatase alpha(RPTPα).Methods·Western blotting was employed to identify the ubiquitination type of RPTPα and to evaluate the regulatory effect of MARCH9 on its ubiquitination level;Comparative analysis of RPTPα protein stability was performed among wild-type MARCH9,catalytically inactive MARCH9 mutants(MARCH9 S198A or MARCH9-HC/CC),and endogenous MARCH9 knockdown via shRNA.Proteasome inhibitor MG132,autophagy inhibitor 3-MA,and lysosomal inhibitor chloroquine(CQ)were used to determine the degradation pathway of MARCH9-mediated RPTPα ubiquitination.The mechanism underlying 43℃heat shock-induced RPTPα degradation was explored.Stable lung cancer cell lines with MARCH9 single-knockdown(H1299-sh MARCH9)and MARCH9/RPTPα double-knockdown(H1299-sh MARCH9-sh RPTPα)were established using lentiviral vectors.CCK-8 proliferation assay,colony formation assay,and soft agar assay were conducted to evaluate the effects of MARCH9 or RPTPα on lung cancer cell proliferation and clonogenicity.Vasculogenic mimicry formation assay and scratch wound healing assay were performed to assess the impacts on tumor cell invasion and migration.Subcutaneous xenograft models in nude mice were established to examine in vivo tumorigenicity.Bioinformatics analysis was used to compare the expression differences and prognostic correlations of MARCH9 and RPTPα in lung cancer patients.Results·RPTPα predominantly underwent K63-linked poly-ubiquitination,which was significantly enhanced by MARCH9 overexpression.Wild-type MARCH9,but not its catalytic mutants,markedly reduced RPTPα protein stability,while endogenous MARCH9 knockdown increased RPTPα levels.CQ,not MG132 or 3-MA,restored RPTPα stability,indicating that MARCH9 mediated lysosomal degradation of RPTPα through ubiquitination.Heat shock at 43℃specifically enhanced MARCH9-RPTPα interaction,promoting RPTPα degradation.Functional assays revealed that,compared to control H1299 cells,MARCH9-knockdown cells exhibited elevated RPTPα levels,accelerated proliferation,enhanced clonogenicity and invasive capacity,and increased tumorigenicity in nude mice.These phenotypes could be reversed by double knockdown of MARCH9/RPTPα.Bioinformatics analysis demonstrated that high RPTPα expression correlated with poor prognosis and tumor metastasis in lung cancer patients,while MARCH9 showed inverse correlations.Conclusion·MARCH9 mediates K63-linked ubiquitination-dependent lysosomal degradation of phosphatase RPTPα,providing new insights into developing RPTPα-targeted cancer therapeutic strategies.
2.Epidemiological characteristics of thyroid cancer in cancer registration areas of Xinjiang Uygur Autonomous Region in 2020 and the trends from 2016 to 2020
Adila Sulidan ; Xiayida Wusimanjiang ; Shawulaxi Rejiafu ; Xiamusiye Muyiduli ; ZHANG Jun ; Danaguli Mala ; Yilixiati Kulaixi ; Abulimiti Muhetaer ; ZHANG Rong
Journal of Preventive Medicine 2025;37(10):1020-10,231,028
Objective:
To investigate the trends in incidence and mortality of thyroid cancer in cancer registration areas of Xinjiang Uygur Autonomous Region from 2016 to 2020 and its epidemiological status in 2020, so as to provide the basis for improving prevention and control measures for thyroid cancer.
Methods:
The data of thyroid cancer incidence and mortality from 2016 to 2020 in four cancer registration areas of Xinjiang Uygur Autonomous Region were collected through the Tumor Registry. The crude incidence and crude mortality were calculated. The Chinese population-standardized rate and world population-standardized rate were calculated using the age structure of the standard population from the Fifth National Population Census in 2000 and Segi's world standard population. The incidence and mortality characteristics of thyroid cancer in different genders and ages in 2020 were described. The trends in the Chinese population-standardized incidence and mortality of thyroid cancer in Xinjiang Uygur Autonomous from 2016 to 2020 were assessed using the average annual percent change (AAPC).
Results:
In 2020, the crude, Chinese population-standardized and world population-standardized incidences of thyroid cancer in Xinjiang Uygur Autonomous Region were 32.91/100 000, 26.99/100 000, and 25.53/100 000, respectively. The crude, Chinese population-standardized and world population-standardized mortalities of thyroid cancer were 1.25/100 000, 0.96/100 000, and 0.98/100 000, respectively. The Chinese population-standardized incidence and mortality of thyroid cancer in females were 2.44 times and 2.20 times those in males, respectively. The crude incidence of thyroid cancer was increased after age of twenty years, with a peak at age of 55 to 60 years (76.73/100 000) before rapidly declining. In contrast, the crude mortality remained low across all age groups, with the highest rate observed at age of 70 to 75 years (13.70/100 000). From 2016 to 2020, the Chinese population-standardized incidence and mortality of thyroid cancer showed no significant changes (both P>0.05).
Conclusions
From 2016 to 2020, the trends in incidence and mortality of thyroid cancer in cancer registration areas of Xinjiang Uygur Autonomous Region were stable. The disease burden of thyroid cancer was higher in females than in males. The crude incidence first rised and then declined with age, peaks at age of 55-<60 years.
3.Ubiquitination and degradation of RPTPα mediated by MARCH9
Yuqin ZHANG ; AIHEMAITI YILIXIATI ; Yanli WANG ; Zhi YANG ; Jian HUANG
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(8):957-968
Objective·To investigate the molecular mechanisms and biological functions of the E3 ubiquitin ligase membrane-associated RING-CH 9(MARCH9)in regulating the ubiquitination of receptor protein tyrosine phosphatase alpha(RPTPα).Methods·Western blotting was employed to identify the ubiquitination type of RPTPα and to evaluate the regulatory effect of MARCH9 on its ubiquitination level;Comparative analysis of RPTPα protein stability was performed among wild-type MARCH9,catalytically inactive MARCH9 mutants(MARCH9 S198A or MARCH9-HC/CC),and endogenous MARCH9 knockdown via shRNA.Proteasome inhibitor MG132,autophagy inhibitor 3-MA,and lysosomal inhibitor chloroquine(CQ)were used to determine the degradation pathway of MARCH9-mediated RPTPα ubiquitination.The mechanism underlying 43℃heat shock-induced RPTPα degradation was explored.Stable lung cancer cell lines with MARCH9 single-knockdown(H1299-sh MARCH9)and MARCH9/RPTPα double-knockdown(H1299-sh MARCH9-sh RPTPα)were established using lentiviral vectors.CCK-8 proliferation assay,colony formation assay,and soft agar assay were conducted to evaluate the effects of MARCH9 or RPTPα on lung cancer cell proliferation and clonogenicity.Vasculogenic mimicry formation assay and scratch wound healing assay were performed to assess the impacts on tumor cell invasion and migration.Subcutaneous xenograft models in nude mice were established to examine in vivo tumorigenicity.Bioinformatics analysis was used to compare the expression differences and prognostic correlations of MARCH9 and RPTPα in lung cancer patients.Results·RPTPα predominantly underwent K63-linked poly-ubiquitination,which was significantly enhanced by MARCH9 overexpression.Wild-type MARCH9,but not its catalytic mutants,markedly reduced RPTPα protein stability,while endogenous MARCH9 knockdown increased RPTPα levels.CQ,not MG132 or 3-MA,restored RPTPα stability,indicating that MARCH9 mediated lysosomal degradation of RPTPα through ubiquitination.Heat shock at 43℃specifically enhanced MARCH9-RPTPα interaction,promoting RPTPα degradation.Functional assays revealed that,compared to control H1299 cells,MARCH9-knockdown cells exhibited elevated RPTPα levels,accelerated proliferation,enhanced clonogenicity and invasive capacity,and increased tumorigenicity in nude mice.These phenotypes could be reversed by double knockdown of MARCH9/RPTPα.Bioinformatics analysis demonstrated that high RPTPα expression correlated with poor prognosis and tumor metastasis in lung cancer patients,while MARCH9 showed inverse correlations.Conclusion·MARCH9 mediates K63-linked ubiquitination-dependent lysosomal degradation of phosphatase RPTPα,providing new insights into developing RPTPα-targeted cancer therapeutic strategies.
4.One-stage revision for reconstructing acetabular defects by trabecular metal acetabular revision system in periprosthetic joint infection
Zhaoxi XUE ; Yilixiati MAIMAITIAIMAITI ; Wentao GUO ; Boyong XU ; Li CAO
Chinese Journal of Surgery 2024;62(9):847-855
Objective:To investigates the clinical efficacy of the trabecular metal acetabular revision system (TMARS) in one-stage reconstruction of acetabular deficiencies associated with periprosthetic joint infection (PJI).Methods:This is a retrospective case series study,including the data of 59 patients with PJI underwent acetabular defect reconstruction by TMARS during one-stage revisions in the Department of Orthopaedics, the First Affiliated Hospital of Xinjiang Medical University from January 2013 to December 2021. There were 32 males and 27 females, aged (59.5±14.6) years (range: 26 to 84 years). Among them, 29 cases used tantalum cups, 13 cases used tantalum cups and tantalum reinforcing blocks, 9 cases used cup-cage, and 8 cases used multi-cup reconstruction techniques. The surgery procedure, Harris Hip score (HHS), recovery of the hip rotation center, implant survival rate, postoperative reinfection rate, and complications were recorded. Data were compared using the Wilcoxon rank-sum test.Results:All of the 59 patients underwent the operations successfully. Operation time was (188.9±48.4) minutes (range: 110 to 340 minutes), and intraoperative bleeding volume was ( M(IQR)) 1 000(400)ml (range: 600 to 1 800 ml). After a postoperative follow-up of 5.1 (2.6) years (range: 2.0 to 10.5 years), the prosthesis survival rate was 94.9% (56/59). Recurrence of infection occurred in 3 cases (5.1%), aseptic loosening in 1case(1.7%), and hip dislocation in 4 cases (6.8%). At the last follow-up, HHS improved significantly(84 (12) vs. 44 (9), Z=-6.671, P<0.01), and the center of rotation of the hips were recovered in all cases. Conclusions:In one-stage revision surgeries aimed at reconstructing acetabular defects, utilizing the TMARS can provide stable initial fixation, restore a more natural center of rotation, significantly enhance early postoperative hip joint function, and reduce the likelihood of infection recurrence. This approach stands as a reliable choice for addressing acetabular defects during revision surgeries for infected hip joints.
5.A Study on the Current Status of Inpatients'Trust in Doctors at Tertiary Public Hospitals in China and Its Influencing Factors
Jiarun MI ; Xinyu DU ; Mingkun LI ; Aili YILIXIATI ; Yuanli LIU
Chinese Hospital Management 2024;44(8):17-22
Objective It aims to investigate the current status of patient trust in physicians among inpatients at tertiary public hospitals in China and to analyze the factors influencing this trust.The goal is to provide insights for enhancing patient trust and improving doctor-patient relationships.Methods Relying on the third"third party evaluation of national action to improve medical services"project,it surveyed inpatients from 136 tertiary public hospitals across 31 provinces(including autonomous regions and municipalities)and the Xinjiang Production and Construction Corps.A total of 21 092 inpatient questionnaires were returned.Data obtained were statistically analyzed using R software version 4.3.2.Results The trust level in attending physicians among inpatients at tertiary public hospitals in China was found to be 98.37%.Influential factors on this trust level included patient occupation,annual family income,type and region of the hospital and so on.Conclusion Overall,the level of trust in physicians among inpatients at tertiary public hospitals in China is high,though regional differences exist.It should pay attention to non-medical factors such as inpatient ward environment and hospital service quality.Improving these aspects can enhance the overall patient experience,further improve doctor-patient relationships.
6.A Study on the Current Status and Influencing factors of Nurses'Emotional Exhaustion at Tertiary Public Hospitals in China
Xinyu DU ; Jiarun MI ; Aili YILIXIATI ; Yuanyuan SONG ; Mingshen LI ; Yuanli LIU
Chinese Hospital Management 2024;44(8):23-28
Objective It aims to investigate the status quo of nurses'emotional exhaustion in tertiary public hospitals in China and analyze its influencing factors,so as to provide suggestions for formulating targeted policy measures to reduce nurses'emotional exhaustion.Methods Relying on the fifth"The Third-Party Evaluation of the China Healthcare Improvement Initiatives"project,it surveyed nurses from 143 tertiary public hospitals across 31 provinces(including autonomous regions and municipalities)and the Xinjiang Production and Construction Corps.Univariate analyses were performed using the Pearson chi-square test.Multifactorial analyses were performed using ordered multicategorical logistic regression analysis.Results The score of nurses'emotional exhaustion in tertiary public hospitals in China was 8.00(2.00~16.00),of which mild exhaustion accounted for 79.00%,moderate exhaustion accounted for 10.00%,and severe exhaustion accounted for 11.00%.Gender,age,number of children,region,type of hospital,department,employment form,assume scientific research task,excessive workload,salary and hospitals carry out psychological guidance were the influencing factors of nurses'emotional exhaustion.Conclusion Nurses in tertiary public hospitals in China are at a mild level of emotional exhaustion,but in some groups the degree is more serious.Policy makers and hospital managers should focus on special groups,implement the reform of salary system,reduce nurses'workload,reasonably arrange working hours,improve the working environment of hospitals,and strengthen nurses'psychological guidance.
7.A Study on the Current Status of Inpatients'Trust in Doctors at Tertiary Public Hospitals in China and Its Influencing Factors
Jiarun MI ; Xinyu DU ; Mingkun LI ; Aili YILIXIATI ; Yuanli LIU
Chinese Hospital Management 2024;44(8):17-22
Objective It aims to investigate the current status of patient trust in physicians among inpatients at tertiary public hospitals in China and to analyze the factors influencing this trust.The goal is to provide insights for enhancing patient trust and improving doctor-patient relationships.Methods Relying on the third"third party evaluation of national action to improve medical services"project,it surveyed inpatients from 136 tertiary public hospitals across 31 provinces(including autonomous regions and municipalities)and the Xinjiang Production and Construction Corps.A total of 21 092 inpatient questionnaires were returned.Data obtained were statistically analyzed using R software version 4.3.2.Results The trust level in attending physicians among inpatients at tertiary public hospitals in China was found to be 98.37%.Influential factors on this trust level included patient occupation,annual family income,type and region of the hospital and so on.Conclusion Overall,the level of trust in physicians among inpatients at tertiary public hospitals in China is high,though regional differences exist.It should pay attention to non-medical factors such as inpatient ward environment and hospital service quality.Improving these aspects can enhance the overall patient experience,further improve doctor-patient relationships.
8.A Study on the Current Status and Influencing factors of Nurses'Emotional Exhaustion at Tertiary Public Hospitals in China
Xinyu DU ; Jiarun MI ; Aili YILIXIATI ; Yuanyuan SONG ; Mingshen LI ; Yuanli LIU
Chinese Hospital Management 2024;44(8):23-28
Objective It aims to investigate the status quo of nurses'emotional exhaustion in tertiary public hospitals in China and analyze its influencing factors,so as to provide suggestions for formulating targeted policy measures to reduce nurses'emotional exhaustion.Methods Relying on the fifth"The Third-Party Evaluation of the China Healthcare Improvement Initiatives"project,it surveyed nurses from 143 tertiary public hospitals across 31 provinces(including autonomous regions and municipalities)and the Xinjiang Production and Construction Corps.Univariate analyses were performed using the Pearson chi-square test.Multifactorial analyses were performed using ordered multicategorical logistic regression analysis.Results The score of nurses'emotional exhaustion in tertiary public hospitals in China was 8.00(2.00~16.00),of which mild exhaustion accounted for 79.00%,moderate exhaustion accounted for 10.00%,and severe exhaustion accounted for 11.00%.Gender,age,number of children,region,type of hospital,department,employment form,assume scientific research task,excessive workload,salary and hospitals carry out psychological guidance were the influencing factors of nurses'emotional exhaustion.Conclusion Nurses in tertiary public hospitals in China are at a mild level of emotional exhaustion,but in some groups the degree is more serious.Policy makers and hospital managers should focus on special groups,implement the reform of salary system,reduce nurses'workload,reasonably arrange working hours,improve the working environment of hospitals,and strengthen nurses'psychological guidance.
9.A Study on the Current Status of Inpatients'Trust in Doctors at Tertiary Public Hospitals in China and Its Influencing Factors
Jiarun MI ; Xinyu DU ; Mingkun LI ; Aili YILIXIATI ; Yuanli LIU
Chinese Hospital Management 2024;44(8):17-22
Objective It aims to investigate the current status of patient trust in physicians among inpatients at tertiary public hospitals in China and to analyze the factors influencing this trust.The goal is to provide insights for enhancing patient trust and improving doctor-patient relationships.Methods Relying on the third"third party evaluation of national action to improve medical services"project,it surveyed inpatients from 136 tertiary public hospitals across 31 provinces(including autonomous regions and municipalities)and the Xinjiang Production and Construction Corps.A total of 21 092 inpatient questionnaires were returned.Data obtained were statistically analyzed using R software version 4.3.2.Results The trust level in attending physicians among inpatients at tertiary public hospitals in China was found to be 98.37%.Influential factors on this trust level included patient occupation,annual family income,type and region of the hospital and so on.Conclusion Overall,the level of trust in physicians among inpatients at tertiary public hospitals in China is high,though regional differences exist.It should pay attention to non-medical factors such as inpatient ward environment and hospital service quality.Improving these aspects can enhance the overall patient experience,further improve doctor-patient relationships.
10.A Study on the Current Status and Influencing factors of Nurses'Emotional Exhaustion at Tertiary Public Hospitals in China
Xinyu DU ; Jiarun MI ; Aili YILIXIATI ; Yuanyuan SONG ; Mingshen LI ; Yuanli LIU
Chinese Hospital Management 2024;44(8):23-28
Objective It aims to investigate the status quo of nurses'emotional exhaustion in tertiary public hospitals in China and analyze its influencing factors,so as to provide suggestions for formulating targeted policy measures to reduce nurses'emotional exhaustion.Methods Relying on the fifth"The Third-Party Evaluation of the China Healthcare Improvement Initiatives"project,it surveyed nurses from 143 tertiary public hospitals across 31 provinces(including autonomous regions and municipalities)and the Xinjiang Production and Construction Corps.Univariate analyses were performed using the Pearson chi-square test.Multifactorial analyses were performed using ordered multicategorical logistic regression analysis.Results The score of nurses'emotional exhaustion in tertiary public hospitals in China was 8.00(2.00~16.00),of which mild exhaustion accounted for 79.00%,moderate exhaustion accounted for 10.00%,and severe exhaustion accounted for 11.00%.Gender,age,number of children,region,type of hospital,department,employment form,assume scientific research task,excessive workload,salary and hospitals carry out psychological guidance were the influencing factors of nurses'emotional exhaustion.Conclusion Nurses in tertiary public hospitals in China are at a mild level of emotional exhaustion,but in some groups the degree is more serious.Policy makers and hospital managers should focus on special groups,implement the reform of salary system,reduce nurses'workload,reasonably arrange working hours,improve the working environment of hospitals,and strengthen nurses'psychological guidance.


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