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.

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.

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.

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.

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.

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.

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.

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.

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.

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.