Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

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.

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.