1.PCSK9 promotes mitochondrial dysfunction to accelerate the process of abdominal aortic aneurysm
Man LI ; Yanyu CHEN ; Mengdie XIA ; Qian XU ; Yating ZHOU ; Huayu ZHANG ; Lushan LIU ; Zhihan TANG ; Juan PENG
Chinese Journal of Arteriosclerosis 2025;33(3):209-218
Aim To explore the impact and mechanism of proprotein convertase subtilisin kexin 9(PCSK9)on the progression of abdominal aortic aneurysm(AAA).Methods 6~8 week old ApoE-/-mice were selected to estab-lish the AAA model.Angiotensin Ⅱ(Ang Ⅱ)was continuously infused through subcutaneous implantation of a micro-os-motic pump.The mice were fed with high-fat diet and killed after 28 days.The expression of PCSK9 in abdominal aor-tic smooth muscle cells was detected by immunohistochemistry and immunofluorescence in normal abdominal aortic blood vessels and AAA samples in human and mice.Primary cultured murine vascular smooth muscle cells(mVSMC)of C57BL/6 mice were treated with different concentrations of AngⅡ for 24 h,and the expression of PCSK9 mRNA and pro-tein was detected.PCSK9 overexpression and knockdown cell models were established,and mitochondrial reactive oxygen species(mtROS),mitochondrial membrane potential(MMP),mitochondrial permeability transition pore(MPTP)open-ing,and Z-DNA binding protein 1(ZBP1)protein expression were detected.Bioinformatics was used to analyze the dif-ferential expression of multiple single-cell sequencing datasets to obtain the key differentially expressed genes,and to study their expression and role in AAA.Results Immunohistochemistry and immunofluorescence results showed that PCSK9 expression in human and mouse AAA increased(P<0.01),and co-localized with smooth muscle.Ang Ⅱ promoted PCSK9 expression in mVSMC in a concentration-dependent manner,the 2.0 μmol/L Ang Ⅱ group showed a 2.9-fold and 1.1-fold increase in the expression of PCSK9 mRNA and protein,respectively(P<0.01),with the most significant effect observed.After successfully constructing PCSK9 overexpression and PCSK9 interference mVSMC models,PCSK9 overex-pression led to an increase in intracellular mtROS,a decrease in MMP,an increase in MPTP opening,and a decrease in cellular activity(P<0.01);PCSK9 knockdown could reduce Ang Ⅱ induced increase in mtROS,decrease in MMP and MPTP opening;compared with the siNC+Ang Ⅱ group,the siPCSK9+Ang Ⅱ group showed a decrease in mtROS and an in-crease in the fluorescence brightness of MMP and MPTP(P<0.05).Bioinformatics analysis revealed that ZBP1 was a core differentially expressed gene in AAA.Immunohistochemistry and immunofluorescence results showed that ZBP1 ex-pression in human and mouse AAA tissues increased,and co-localized with smooth muscle.Western blot results showed that PCSK9 overexpression or treatment with 2.0 μmol/L Ang Ⅱ could increase ZBP1 protein expression(P<0.01),while PCSK9 knockdown could alleviate the increased ZBP1 expression caused by AngⅡ(P<0.05).Conclusion PCSK9 may induce mitochondrial damage in smooth muscle cells,activate downstream molecule ZBP1 to cause cell damage,and promote the development of AAA.
2.PCSK9 promotes mitochondrial dysfunction to accelerate the process of abdominal aortic aneurysm
Man LI ; Yanyu CHEN ; Mengdie XIA ; Qian XU ; Yating ZHOU ; Huayu ZHANG ; Lushan LIU ; Zhihan TANG ; Juan PENG
Chinese Journal of Arteriosclerosis 2025;33(3):209-218
Aim To explore the impact and mechanism of proprotein convertase subtilisin kexin 9(PCSK9)on the progression of abdominal aortic aneurysm(AAA).Methods 6~8 week old ApoE-/-mice were selected to estab-lish the AAA model.Angiotensin Ⅱ(Ang Ⅱ)was continuously infused through subcutaneous implantation of a micro-os-motic pump.The mice were fed with high-fat diet and killed after 28 days.The expression of PCSK9 in abdominal aor-tic smooth muscle cells was detected by immunohistochemistry and immunofluorescence in normal abdominal aortic blood vessels and AAA samples in human and mice.Primary cultured murine vascular smooth muscle cells(mVSMC)of C57BL/6 mice were treated with different concentrations of AngⅡ for 24 h,and the expression of PCSK9 mRNA and pro-tein was detected.PCSK9 overexpression and knockdown cell models were established,and mitochondrial reactive oxygen species(mtROS),mitochondrial membrane potential(MMP),mitochondrial permeability transition pore(MPTP)open-ing,and Z-DNA binding protein 1(ZBP1)protein expression were detected.Bioinformatics was used to analyze the dif-ferential expression of multiple single-cell sequencing datasets to obtain the key differentially expressed genes,and to study their expression and role in AAA.Results Immunohistochemistry and immunofluorescence results showed that PCSK9 expression in human and mouse AAA increased(P<0.01),and co-localized with smooth muscle.Ang Ⅱ promoted PCSK9 expression in mVSMC in a concentration-dependent manner,the 2.0 μmol/L Ang Ⅱ group showed a 2.9-fold and 1.1-fold increase in the expression of PCSK9 mRNA and protein,respectively(P<0.01),with the most significant effect observed.After successfully constructing PCSK9 overexpression and PCSK9 interference mVSMC models,PCSK9 overex-pression led to an increase in intracellular mtROS,a decrease in MMP,an increase in MPTP opening,and a decrease in cellular activity(P<0.01);PCSK9 knockdown could reduce Ang Ⅱ induced increase in mtROS,decrease in MMP and MPTP opening;compared with the siNC+Ang Ⅱ group,the siPCSK9+Ang Ⅱ group showed a decrease in mtROS and an in-crease in the fluorescence brightness of MMP and MPTP(P<0.05).Bioinformatics analysis revealed that ZBP1 was a core differentially expressed gene in AAA.Immunohistochemistry and immunofluorescence results showed that ZBP1 ex-pression in human and mouse AAA tissues increased,and co-localized with smooth muscle.Western blot results showed that PCSK9 overexpression or treatment with 2.0 μmol/L Ang Ⅱ could increase ZBP1 protein expression(P<0.01),while PCSK9 knockdown could alleviate the increased ZBP1 expression caused by AngⅡ(P<0.05).Conclusion PCSK9 may induce mitochondrial damage in smooth muscle cells,activate downstream molecule ZBP1 to cause cell damage,and promote the development of AAA.
3.International Comparison of Modern Hospital Operation and Management Mode and Analysis of Typical Cases in China
Zihan MU ; Jian WU ; Li ZHENG ; Di WU ; Yanyu TANG ; Suxian WANG ; Jing WANG ; Yaojun ZHAO
Chinese Hospital Management 2024;44(3):1-4
Optimizing operation management mode is the core task to promote the high-quality development of public hospitals.Drawing on the typical experiences and practices of operation and management of representative in-ternational hospitals in the United States,the United Kingdom,Singapore and West China Hospital of Sichuan Univer-sity,Shanghai Jiao Tong University School of Medicine Affiliated Xinhua Hospital,Jilin University China-Japanese Union Hospital of Jilin University,and carrying out a full range of comparative analyses.Put forward the new situation of China's public hospital operations and management to establish a"big operations management"concept.By iden-tifying the operation management role,rationalizing the operation management organization structure and training operation management compound talents to discuss stablishing a committee system,integrating multi-departmental resources to form a scientific and sound problem identificaiton,feedback,consultation and improvement of working mechanism,and promote the high-quality development of publit hospitals.
4.Research on Access Evaluation System of New Medical Technology Based on HB-HTA
Jing WANG ; Xiaoli FU ; Shuai JIANG ; Yudong MIAO ; Zihan MU ; Yanyu TANG ; Suxian WANG ; Yaojun ZHAO
Chinese Hospital Management 2024;44(3):9-12
The access evaluation of new medical technology is an important part of the preclinical application of medical technology and plays a vital role in ensuring the quality and safety of medical services.However,in the con-crete practice of access evaluation,there are still some problems such as imperfect access theoretical framework,imperfect evaluation index system.With the strategic support of health policies,laws,and regulations,the theory and method of HB-HTA are used for reference,core elements such as assessment subject,assessment object,and assessment content are comprehensively considered,the index system is designed from the dimensions of tech-nical characteristics,safety,effectiveness,economy and applicability,and the access evaluation framework of im-ported medical new technologies is constructed.To offer a theoretical framework and evidence-based basis for medi-cal facility medical technology access management.
5.Evaluation of Operation Effectiveness of Coronary Heart Disease Center in National Cardiovascular Disease Regional Medical Center
Yanyu TANG ; Jian WU ; Leichao WANG ; Zihan MU ; Wenwen LIU ; Lusheng ZHANG ; Zhao CHENG ; Yaojun ZHAO
Chinese Hospital Management 2024;44(3):13-16
Objective To measure and comprehensively analyze the operation efficiency of coronary heart disease Center of National Regional Medical Center for Cardiovascular Disease from the dimensions of department service in-come,department service quality,department service efficiency and department service benefit,and put forward targeted operation management optimization strategies based on the analysis results.Methods The operation effective-ness evaluation index of CHD centers in sample hospitals from 2020 to 2022 was measured by the empirical re-search method from the overall level of the center and the level of clinical departments,and the scores were com-pared and analyzed.Results From 2020 to 2022,the operation effectiveness evaluation index of CHD centers in sam-ple hospitals showed a good trend,increasing from 80.57 points to 82.86 points.The 3-year average score was 81.74;Among them,the score rate of department service benefit dimension is higher,the average is 96.64%;The score rate of department service efficiency was lower,with an average of 68.53%.The departments with the lowest operational efficiency scores from 2020 to 2022 are all A2 departments,with 74.39,72.41 and 75.89 scores respec-tively,mainly due to the relatively low scores of A2 departments in the dimensions of department service revenue and department service efficiency.Conclusion The results of clinical department operation effectiveness evaluation can provide the evidence-based basis for hospital operation management,and hospitals can establish benchmarking management departments according to the evaluation results and take targeted measures to improve the comprehen-sive operation efficiency of departments.
6.Research on the Economic Operating Mechanisms of Large Public Hospitals in Henan Province
Rui JIANG ; Jianjun LI ; Jian WU ; Wei NIU ; Li ZHENG ; Chenqi LI ; Yanyu TANG ; Yaojun ZHAO
Chinese Hospital Management 2024;44(3):17-20
The establishment of an economic operating mechanisms for hospitals is a key factor in advancing the growth of public hospitals in the modern age.At present,the due value of key factors such as medical resources and labor value of medical personnel in public hospitals in China has not been fully reflected,which not only restricts the overall operation efficiency of hospitals,but also makes it difficult to realize the marginal value of hospital operation and management.The economic operating mechanisms of public hospitals is in urgent need of reform.Large public hospitals in Henan Province has established an economic operating mechanisms of public hospitals based on intelli-gent finance,comprehensive budget management as the core,and cost control and performance management as the major tools to realize the interconnection of various systems and promote the high-quality development of hospi-tals with the three major supports of industry and finance integration,financial integration and financial integration.
7.Research progress on issues concerning the definition of cognitive frailty
Huiyu TANG ; Qianqian SUN ; Huan ZHU ; Yanyan LIU ; Yanyu CHEN ; Hai QIN ; Shuang WANG
Chinese Journal of Geriatrics 2024;43(1):8-12
Since the first operational definition of cognitive frailty was proposed by the expert consensus group of the International Academy of Nutrition and Aging and the International Association of Gerontology and Geriatrics in 2013, frailty and neurocognitive assessment has become the standard diagnostic tool.Since then, the reported prevalence in the literature for cognitive frailty in community-dwelling elderly people vary by dozens of times, as a result of different scales and diagnostic cut-off points, seriously affecting health decision-making.This article reviewed the current literature with a focus on the re-recognition of the clinical significance of cognitive frailty, the limitations of existing assessment tools for diagnosis, and possible solutions in the future.
8.Research on the High-quality Development Model of the National Regional Medical Center for Cardiovascular Disense Based on the Synergy Theory
Li ZHENG ; Yanyu TANG ; Keke WANG ; Yaojun ZHAO
Chinese Hospital Management 2024;44(10):26-29
The construction of regional medical centers is an important carrier for the country to further promote the reform of the new medical service system during the"14th Five-Year Plan"period.In view of the problems existing in the current construction of national regional medical centers,such as imperfect coordination mechanism,insufficient coordination power and lack of assessment and evaluation system,drawing on collaboration theory and case study method,the construction path of national regional medical centers was analyzed from three dimensions:management system collaboration,operation mechanism collaboration and evaluation mechanism collaboration;It explore and constructs the new management model of"13331"high quality development in National Regional Medical Centers;The results provide experience and case reference for promoting the high-quality development of national regional medical centers under the new situation in terms of party building leadership,medical technology,scientific and technological innovation,medical-education collaboration and brand influence.
9.Research on the High-quality Development Model of the National Regional Medical Center for Cardiovascular Disense Based on the Synergy Theory
Li ZHENG ; Yanyu TANG ; Keke WANG ; Yaojun ZHAO
Chinese Hospital Management 2024;44(10):26-29
The construction of regional medical centers is an important carrier for the country to further promote the reform of the new medical service system during the"14th Five-Year Plan"period.In view of the problems existing in the current construction of national regional medical centers,such as imperfect coordination mechanism,insufficient coordination power and lack of assessment and evaluation system,drawing on collaboration theory and case study method,the construction path of national regional medical centers was analyzed from three dimensions:management system collaboration,operation mechanism collaboration and evaluation mechanism collaboration;It explore and constructs the new management model of"13331"high quality development in National Regional Medical Centers;The results provide experience and case reference for promoting the high-quality development of national regional medical centers under the new situation in terms of party building leadership,medical technology,scientific and technological innovation,medical-education collaboration and brand influence.
10.Research on the High-quality Development Model of the National Regional Medical Center for Cardiovascular Disense Based on the Synergy Theory
Li ZHENG ; Yanyu TANG ; Keke WANG ; Yaojun ZHAO
Chinese Hospital Management 2024;44(10):26-29
The construction of regional medical centers is an important carrier for the country to further promote the reform of the new medical service system during the"14th Five-Year Plan"period.In view of the problems existing in the current construction of national regional medical centers,such as imperfect coordination mechanism,insufficient coordination power and lack of assessment and evaluation system,drawing on collaboration theory and case study method,the construction path of national regional medical centers was analyzed from three dimensions:management system collaboration,operation mechanism collaboration and evaluation mechanism collaboration;It explore and constructs the new management model of"13331"high quality development in National Regional Medical Centers;The results provide experience and case reference for promoting the high-quality development of national regional medical centers under the new situation in terms of party building leadership,medical technology,scientific and technological innovation,medical-education collaboration and brand influence.

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