OBJECTIVE From the perspective of China’s health system， to evaluate the cost-effectiveness of maintenance therapy with clopidogrel or aspirin monotherapy in percutaneous coronary intervention （PCI） patients after dual antiplatelet therapy （DAPT）. METHODS A Markov model was adopted with a research period of 25 years and a cycle period of 1 year. Cohort simulations were conducted respectively for the clopidogrel group and aspirin group to predict and compare the long-term economic and health outcomes of PCI patients receiving either clopidogrel or aspirin monotherapy maintenance regimens after DAPT， and cost-effectiveness analysis was conducted. The willingness-to-pay （WTP） threshold was set at the level of 1 times China’s per capita gross domestic product （GDP） in 2024[95 749 yuan per quality-adjusted life year （QALY）]， and the incremental cost- effectiveness ratio （ICER） was calculated. The robustness of the basic analysis results was verified by using single-factor sensitivity analysis and probabilistic sensitivity analysis. RESULTS After PCI， patients received DAPT， clopidogrel monotherapy maintenance treatment reduced the occurrence of death events， and aspirin monotherapy maintenance treatment had a lower probability of stroke and myocardial infarction events. The ICER of the clopidogrel group regimen compared with the aspirin group regimen was 34 644.87 yuan/QALY， which was less than the WTP threshold set in this study. The results of univariate sensitivity analysis indicated that notable uncertainties affecting the basic analysis results were the probability of event-free progression to death in the aspirin group， the event-free cost in the clopidogrel group， and the event-free cost in the aspirin group. The results of probabilistic sensitivity analysis indicated that when the WTP threshold was 95 749 yuan /QALY， the economic probabilities of the clopidogrel group and the aspirin group were 83% and 17%， respectively. The economic probability of the clopidogrel group regimens showed an upward trend with the increase of the WTP threshold. CONCLUSIONS Compared to aspirin monotherapy for maintenance therapy， under the WTP threshold of 1 times China’s per capita GDP in 2024， receiving clopidogrel monotherapy for maintenance therapy after DAPT in PCI patients is more cost-effective.

The mandibular condyle is a critical growth center in craniofacial bone development, especially during postnatal stages. Postnatal condyle osteogenesis requires precise spatiotemporal coordination of growth factor signaling cascades and hierarchical gene regulatory networks. Plagl1, which encodes a zinc finger transcription factor, is a paternally expressed gene. We demonstrate that PLAGL1 is highly expressed in cranial neural crest cell (CNCC)-derived lineage cells in mouse condyles. Using the CNCC-derived lineage-specific Plagl1 knockout mouse model, we evaluate the function of PLAGL1 during postnatal mouse condyle development. Our findings show that PLAGL1 contributes significantly to osteoblast differentiation, and its deficiency impairs osteogenic lineage differentiation, which consequently disrupts mandibular condyle development. Mechanistically, insulin-like growth factor 2 (IGF2) in complex with IGF-binding proteins (IGFBPs) has been identified as the principal PLAGL1 effector responsible for osteogenic regulation during postnatal condyle morphogenesis. Plagl1 deficiency significantly downregulates the IGF2/IGFBP pathway, leading to disordered glucose metabolism, defective extracellular matrix organization, and impaired ossification. Exogenous IGF2 treatment rescues impaired osteoblast differentiation caused by Plagl1 deficiency. In conclusion, the PLAGL1-IGF2 axis is a critical regulator of osteogenesis during mandibular condyle development.
Animals ; Osteogenesis/genetics* ; Insulin-Like Growth Factor II/metabolism* ; Mice ; Transcription Factors/metabolism* ; Mice, Knockout ; Cell Differentiation ; DNA-Binding Proteins/genetics* ; Mandibular Condyle/growth & development* ; Osteoblasts/cytology* ; Signal Transduction ; Neural Crest/cytology*

Objective:To compare the efficacy of three-dimensional visualization-assisted intermuscular versus conventional intermuscular cervical expansive open-door laminoplasty (CEOL) in the treatment of cervical spinal cord injury without fracture or dislocation (CSCIWFD).Methods:A retrospective cohort study was conducted to analyze the clinical data of 58 patients with CSCIWFD admitted to Zhengzhou Orthopedic Hospital from October 2021 to January 2024, including 39 males and 19 females, aged 36-77 years [(52.9±8.9)years]. Among them, 26 patients were treated with three-dimensional visualization-assisted intermuscular CEOL (three-dimensional visualization group), while 32 patients were treated with conventional intermuscular CEOL (conventional intermuscular group). All patients were treated with CEOL in 4 segments (C 3-C 6), comprising 104 surgical segments in the three-dimensional visualization group and 128 in the conventional intermuscular group. The following outcomes were compared between the two groups, including the operative duration, intraoperative blood loss, accuracy rate of open-door and hinge placement at the surgical levels, visual analogue scale (VAS) of the neck and shoulder and Japanese Orthopedic Association (JOA) score preoperatively, at 1 week, 1 month, 3 months, 6 months postoperatively and at the last follow-up, American Spinal Injury Association (ASIA) impairment scale preoperatively and at the last follow-up, and postoperative complication rate. Results:All patients were followed up for 12-24 months [(17.5±3.1)months]. The operative duration and intraoperative blood loss were (117.0±12.3)minutes and (151.3±30.9)ml in the three-dimensional visualization group, which were shorter or less than (131.9±15.0)minutes and (184.7±42.9)ml in the conventional intermuscular group ( P<0.01). The accuracy rate of open-door and hinge placement at the surgical levels was 94.2% (98/104) in the three-dimensional visualization group, significantly higher than 83.6% (107/128) in the conventional intermuscular group ( P<0.05). The VAS scores of the neck and shoulder preoperatively, at 1 week, 1 month, 3 months, 6 months postoperatively, and at the last follow-up were 6.0(5.0, 7.0)points, 3.5(3.0, 4.0)points, 3.0(2.0, 3.0)points, 2.0(1.0, 3.0)points, 2.0(1.0, 2.3)points, and 2.0(1.0, 2.0)points in the three-dimensional visualization group, which were not statistically different from 5.0(4.3, 6.8)points, 4.0(3.0, 4.0)points, 3.0(2.0, 3.0)points, 2.0(1.3, 2.0)points, 2.0(1.0, 2.8)points, and 2.0(1.0, 2.0)points in the conventional intermuscular group ( P>0.05). The VAS scores of the neck and shoulder in the two groups were significantly decreased at 1 week, 1 month and 3 months postoperatively from the preoperative values ( P<0.05), while they were stabilized at 6 months postoperatively and at the last follow-up compared with those at 3 months postoperatively, with no significant difference among them ( P>0.05). The JOA scores were (8.1±2.8)points, (10.0±2.6)points, (10.5±2.6)points, (11.6±2.3)points, (12.7±2.3)points, and (13.7±2.4)points in the three-dimensional visualization group, which were not statistically different from (8.8±2.2)points, (10.3±2.1)points, (10.8±2.0)points, (12.0±2.0)points, (12.9±2.0)points, and (13.8±2.1)points in the conventional intermuscular group ( P>0.05). The JOA scores of the two groups showed continuous improvement at 1 week, 1 month, 3 months, 6 months postoperatively and at the last follow-up in comparison with the preoperatively values ( P<0.05). Although no significant difference was observed between the two groups in ASIA grade preoperatively and at the last follow-up ( P>0.05), the ASIA grade at the last follow-up was significantly improved compared with that before surgery in both groups ( P<0.05). The postoperative complication rate was 12% (3/26) in the three-dimensional visualization group, significantly lower than 38% (12/32) in the conventional intermuscular group ( P<0.05). Conclusion:Compared with the conventional intermuscular approach, the three-dimensional visualization-assisted intermuscular CEOL offers advantages in reducing surgical trauma, improving surgical precision, and lowering the postoperative complication rate in the treatment of CSCIWFD.

Objective:To compare the efficacy of O-arm navigation-assisted and conventional posterior cervical expansive open-door laminoplasty (CEOL) via the intermuscular approach in the treatment of cervical spinal cord injury without fracture-dislocation (CSCIWFD).Methods:A prospective cohort study was conducted to analyze the clinical data of 60 CSCIWFD patients who were admitted to Zhengzhou Orthopedic Hospital from May 2021 to May 2023, with compression at C3-C6. Patients were randomly divided into two groups: 30 patients underwent O-arm navigation-assisted intermuscular approach CEOL (navigation-assisted group) and 30 patients underwent conventional intermuscular approach CEOL (conventional surgery group). Surgical duration, intraoperative blood loss, postoperative drainage volume, and total surgical blood loss were compared between the two groups. At 2 weeks postoperatively, CT scan was performed to evaluate the accuracy of hinge or open-door position preparation of the surgical segments. Visual analogue scale (VAS) for neck and shoulder pain and Japanese Orthopedic Association (JOA) scores were compared between the two groups preoperatively, at 2 weeks, 6 months postoperatively, and at the last follow-up. Complication rates were also evaluated.Results:A total of 60 patients with CSCIWFD were included, comprising 35 males and 25 females, aged 35-77 years [(50.9±8.6)years]. All the patients were followed up for 12-24 months [(16.9±3.1)months]. The surgical duration and intraoperative blood loss were (121.6±17.9)minutes and (144.7±44.2)ml in the navigation-assisted group, shorter or less than (132.3±14.6)minutes and (178.7±48.7)ml in the conventional surgery group ( P<0.05). There were no statistically significant differences in postoperative drainage volume and total surgical blood loss between the two groups ( P>0.05). CT scan reviewed at 2 weeks postoperatively revealed that the accuracy rate of hinge and open-door position preparation of the surgical segments in the navigation-assisted group was 99.2% (119/120), significantly higher than 86.7% (104/120) in the conventional surgery group ( P<0.01). Before operation and at 2 weeks, 6 months postoperatively, and at the last follow-up, the VAS scores for neck and shoulder pain and JOA scores in the navigation-assisted group were 5.0(4.0, 7.0)points and (8.7±2.8)points, 3.0(2.0, 4.0)points and (10.2±2.5)points, 2.0(1.0, 2.0)points and (1 3.0±1.8)points, and 1.0(1.0, 2.0)points and (13.9±1.5)points respectively, while in the conventional surgery group, the VAS scores and JOA scores were 5.5(5.0, 6.3)points and (8.8±2.6)points, 4.0(3.0, 4.0)points and (10.4±2.5)points, 2.0(1.0, 3.0)points and (12.9±2.2)points, and 2.0(1.0, 2.0)points and (13.8±2.0)points ( P>0.05). Both groups showed improvement in neck and shoulder VAS scores and JOA scores at 2 weeks, 6 months postoperatively, and at the last follow-up, compared to preoperative scores ( P<0.05); further improvement was observed at 6 months postoperatively and at the last follow-up compared to that at 2 weeks postoperatively ( P<0.05). There were no significant differences between neck and shoulder VAS scores or JOA scores at 6 months postoperatively and at the last follow-up ( P>0.05). In the navigation-assisted group, 2 patients had axial neck-shoulder pain postoperatively, with a complication rate of 7% (2/30); while in the conventional surgery group, 7 patients had axial neck-shoulder pain and one patient developed cerebrospinal fluid leakage and low-pressure headache, with a complication rate of 27% (8/30) ( P<0.05). Conclusion:Compared to the conventional intermuscular approach, O-arm navigation-assisted intermuscular approach CEOL for CSCIWFD reduces surgical duration and intraoperative blood loss, improves the accuracy of hinge and open-door position preparation, and lowers complication rates.

Objective:To compare the efficacy of O-arm navigation-assisted and conventional posterior cervical expansive open-door laminoplasty (CEOL) via the intermuscular approach in the treatment of cervical spinal cord injury without fracture-dislocation (CSCIWFD).Methods:A prospective cohort study was conducted to analyze the clinical data of 60 CSCIWFD patients who were admitted to Zhengzhou Orthopedic Hospital from May 2021 to May 2023, with compression at C3-C6. Patients were randomly divided into two groups: 30 patients underwent O-arm navigation-assisted intermuscular approach CEOL (navigation-assisted group) and 30 patients underwent conventional intermuscular approach CEOL (conventional surgery group). Surgical duration, intraoperative blood loss, postoperative drainage volume, and total surgical blood loss were compared between the two groups. At 2 weeks postoperatively, CT scan was performed to evaluate the accuracy of hinge or open-door position preparation of the surgical segments. Visual analogue scale (VAS) for neck and shoulder pain and Japanese Orthopedic Association (JOA) scores were compared between the two groups preoperatively, at 2 weeks, 6 months postoperatively, and at the last follow-up. Complication rates were also evaluated.Results:A total of 60 patients with CSCIWFD were included, comprising 35 males and 25 females, aged 35-77 years [(50.9±8.6)years]. All the patients were followed up for 12-24 months [(16.9±3.1)months]. The surgical duration and intraoperative blood loss were (121.6±17.9)minutes and (144.7±44.2)ml in the navigation-assisted group, shorter or less than (132.3±14.6)minutes and (178.7±48.7)ml in the conventional surgery group ( P<0.05). There were no statistically significant differences in postoperative drainage volume and total surgical blood loss between the two groups ( P>0.05). CT scan reviewed at 2 weeks postoperatively revealed that the accuracy rate of hinge and open-door position preparation of the surgical segments in the navigation-assisted group was 99.2% (119/120), significantly higher than 86.7% (104/120) in the conventional surgery group ( P<0.01). Before operation and at 2 weeks, 6 months postoperatively, and at the last follow-up, the VAS scores for neck and shoulder pain and JOA scores in the navigation-assisted group were 5.0(4.0, 7.0)points and (8.7±2.8)points, 3.0(2.0, 4.0)points and (10.2±2.5)points, 2.0(1.0, 2.0)points and (1 3.0±1.8)points, and 1.0(1.0, 2.0)points and (13.9±1.5)points respectively, while in the conventional surgery group, the VAS scores and JOA scores were 5.5(5.0, 6.3)points and (8.8±2.6)points, 4.0(3.0, 4.0)points and (10.4±2.5)points, 2.0(1.0, 3.0)points and (12.9±2.2)points, and 2.0(1.0, 2.0)points and (13.8±2.0)points ( P>0.05). Both groups showed improvement in neck and shoulder VAS scores and JOA scores at 2 weeks, 6 months postoperatively, and at the last follow-up, compared to preoperative scores ( P<0.05); further improvement was observed at 6 months postoperatively and at the last follow-up compared to that at 2 weeks postoperatively ( P<0.05). There were no significant differences between neck and shoulder VAS scores or JOA scores at 6 months postoperatively and at the last follow-up ( P>0.05). In the navigation-assisted group, 2 patients had axial neck-shoulder pain postoperatively, with a complication rate of 7% (2/30); while in the conventional surgery group, 7 patients had axial neck-shoulder pain and one patient developed cerebrospinal fluid leakage and low-pressure headache, with a complication rate of 27% (8/30) ( P<0.05). Conclusion:Compared to the conventional intermuscular approach, O-arm navigation-assisted intermuscular approach CEOL for CSCIWFD reduces surgical duration and intraoperative blood loss, improves the accuracy of hinge and open-door position preparation, and lowers complication rates.

Objective:To compare the efficacy of three-dimensional visualization-assisted intermuscular versus conventional intermuscular cervical expansive open-door laminoplasty (CEOL) in the treatment of cervical spinal cord injury without fracture or dislocation (CSCIWFD).Methods:A retrospective cohort study was conducted to analyze the clinical data of 58 patients with CSCIWFD admitted to Zhengzhou Orthopedic Hospital from October 2021 to January 2024, including 39 males and 19 females, aged 36-77 years [(52.9±8.9)years]. Among them, 26 patients were treated with three-dimensional visualization-assisted intermuscular CEOL (three-dimensional visualization group), while 32 patients were treated with conventional intermuscular CEOL (conventional intermuscular group). All patients were treated with CEOL in 4 segments (C 3-C 6), comprising 104 surgical segments in the three-dimensional visualization group and 128 in the conventional intermuscular group. The following outcomes were compared between the two groups, including the operative duration, intraoperative blood loss, accuracy rate of open-door and hinge placement at the surgical levels, visual analogue scale (VAS) of the neck and shoulder and Japanese Orthopedic Association (JOA) score preoperatively, at 1 week, 1 month, 3 months, 6 months postoperatively and at the last follow-up, American Spinal Injury Association (ASIA) impairment scale preoperatively and at the last follow-up, and postoperative complication rate. Results:All patients were followed up for 12-24 months [(17.5±3.1)months]. The operative duration and intraoperative blood loss were (117.0±12.3)minutes and (151.3±30.9)ml in the three-dimensional visualization group, which were shorter or less than (131.9±15.0)minutes and (184.7±42.9)ml in the conventional intermuscular group ( P<0.01). The accuracy rate of open-door and hinge placement at the surgical levels was 94.2% (98/104) in the three-dimensional visualization group, significantly higher than 83.6% (107/128) in the conventional intermuscular group ( P<0.05). The VAS scores of the neck and shoulder preoperatively, at 1 week, 1 month, 3 months, 6 months postoperatively, and at the last follow-up were 6.0(5.0, 7.0)points, 3.5(3.0, 4.0)points, 3.0(2.0, 3.0)points, 2.0(1.0, 3.0)points, 2.0(1.0, 2.3)points, and 2.0(1.0, 2.0)points in the three-dimensional visualization group, which were not statistically different from 5.0(4.3, 6.8)points, 4.0(3.0, 4.0)points, 3.0(2.0, 3.0)points, 2.0(1.3, 2.0)points, 2.0(1.0, 2.8)points, and 2.0(1.0, 2.0)points in the conventional intermuscular group ( P>0.05). The VAS scores of the neck and shoulder in the two groups were significantly decreased at 1 week, 1 month and 3 months postoperatively from the preoperative values ( P<0.05), while they were stabilized at 6 months postoperatively and at the last follow-up compared with those at 3 months postoperatively, with no significant difference among them ( P>0.05). The JOA scores were (8.1±2.8)points, (10.0±2.6)points, (10.5±2.6)points, (11.6±2.3)points, (12.7±2.3)points, and (13.7±2.4)points in the three-dimensional visualization group, which were not statistically different from (8.8±2.2)points, (10.3±2.1)points, (10.8±2.0)points, (12.0±2.0)points, (12.9±2.0)points, and (13.8±2.1)points in the conventional intermuscular group ( P>0.05). The JOA scores of the two groups showed continuous improvement at 1 week, 1 month, 3 months, 6 months postoperatively and at the last follow-up in comparison with the preoperatively values ( P<0.05). Although no significant difference was observed between the two groups in ASIA grade preoperatively and at the last follow-up ( P>0.05), the ASIA grade at the last follow-up was significantly improved compared with that before surgery in both groups ( P<0.05). The postoperative complication rate was 12% (3/26) in the three-dimensional visualization group, significantly lower than 38% (12/32) in the conventional intermuscular group ( P<0.05). Conclusion:Compared with the conventional intermuscular approach, the three-dimensional visualization-assisted intermuscular CEOL offers advantages in reducing surgical trauma, improving surgical precision, and lowering the postoperative complication rate in the treatment of CSCIWFD.

Objective To assess the correlation between the severity of postoperative nausea and vomiting(PONV)with the quality of postoperative recovery and capacity of mobility in patients after video-assisted thoracoscopic surgery.Methods A total of 125 patients,80 males and 45 females,aged 18-64 years,BMI 18-35 kg/m2,ASA physical status Ⅰ-Ⅲ,undergoing video-assisted thoracoscopic surgery were observed.The severity of PONV was assessed using the simplified PONV impact scale day 1 after sur-gery.The patients were divided into three groups according to the severity of PONV:non-PONV group(n = 87),mild PONV group(n = 31),and moderate to severe PONV group(n = 7).The quality of recovery was assessed using the quality of recovery-15(QoR-15)on the first day after surgery,and the capacity of mobility was assessed using the 6-minute walk test(6-MWT)on the second day after surgery.The multiple linear regression model was used to analyze the correlation between the severity of PONV and quality of post-operative recovery and capacity of mobility.Results The results of the corrected multiple linear regression model showed that,compared with the patients without PONV,the QoR-15 scores of the patients with mild and moderate-severe PONV on the first day after surgery were reduced by 4.5 scores(95%CI-8.9 to-0.04 scores,P = 0.048)and 15.8 scores(95%CI-24.8 to-6.8 scores,P = 0.001),respectively.Mild(MD =-27.4 m,95%CI-70.1 to 15.4 m,P = 0.207)and moderate-severe PONV(MD =-57.0 m,95%CI-145.7 to 31.6 m,P = 0.204)were not significantly associated with 6-MWT distance shortening on the second day after surgery.Conclusion Increased PONV severity is associated with poorer recovery quality in patients undergoing pulmonary surgery.Active prevention and treatment of PONV may contribute to early recovery of patients.

BACKGROUND:Bibliometrics and visual analyses based on thematic literature are particularly important for understanding the foundation and frontiers of postmenopausal osteoporosis research. OBJECTIVE:To perform bibliometric,citation,and visualization analyses of highly cited SCI papers in postmenopausal osteoporosis research over the last 20 years. METHODS:The top 100 highly cited papers on postmenopausal osteoporosis published between 2003 and 2022 included in SCI-EXPANDED catalog of the Web of Science database were obtained for bibliometric measure and visual analysis using CiteSpace software. RESULTS AND CONCLUSION:The top 100 highly cited papers have a total of 67 377 citations in the Web of Science Core Collection,with an annual average of 49.17 citations per paper.Postmenopausal osteoporosis research primarily involves medical,engineering,biological,and multidisciplinary fields.The subcategories are dominated by endocrinology and metabolism,and medicine:internal medicine.Stable and close cooperative network relationships have been formed globally.United States,University of California System,Cummings,and Steven R are the country,research institution,and author,respectively,with the most highly-cited publications.The frontiers of postmenopausal osteoporosis research mainly include calcium and vitamin D supplementation and fracture risk,clinical studies of bisphosphonates in the treatment of postmenopausal osteoporosis,atypical femur fracture,clinical studies of new drugs and sequential treatment of postmenopausal osteoporosis,predictors of fracture risk,mid-and long-term follow-up of osteoporotic vertebral compression fractures,genetic polymorphisms and hereditary factors,formulation and updating of clinical practice guidelines for postmenopausal osteoporosis.Large cohort studies,high-quality randomized controlled trials,systematic reviews,meta-analyses,and clinical practice guidelines are the great engines that drive the development of clinical research in postmenopausal osteoporosis.We should make efforts in the above areas to improve China's international influence in the field of osteoporosis.

The purpose of this study is to construct a muscle-specific synthetic promoter library, screen out muscle-specific promoters with high activity, analyze the relationship between element composition and activity of highly active promoters, and provide a theoretical basis for artificial synthesis of promoters. In this study, 19 promoter fragments derived from muscle-specific elements, conserved elements, and viral regulatory sequences were selected and randomLy connected to construct a muscle-specific synthetic promoter library. The luciferase plasmids pCMV-Luc and pSPs-Luc were constructed and transfected into the myoblast cell line C2C12. The activities of the synthesized promoters were evaluated by the luciferase activity assay. Two non-muscle-derived cell lines HeLa and 3T3 were used to verify the muscle specificity of the highly active promoters. The sequences of promoters with high activity, good muscle specificity, and correct sequences were analyzed to explore the relationship between the element composition and activity of promoters. We successfully constructed a muscle-specific promoter library and screened out 321 effective synthetic promoter plasmids. Among them, the activity of SP-301 promoter was 5.63 times that of CMV. The 15 promoters with high activity were muscle-specific. In the promoters with high activity and correct sequences, there was a relationship between their element composition and activity. Muscle-specific elements accounted for a high proportion in the promoters, while they had weak correlations with the promoter activity, being tissue-specific determinants. Viral elements accounted for no less than 20% in highly active promoters, which may be the key elements for the promoter activity. The content of conserved elements was proportional to the promoter activity. This study lays a theoretical foundation for the synthesis of tissue-specific efficient promoters and provides a new idea for the construction and application of in-situ gene delivery systems.
Promoter Regions, Genetic ; Humans ; Animals ; Mice ; Gene Library ; Cell Line ; Transfection ; HeLa Cells ; Luciferases/metabolism* ; Muscle, Skeletal/metabolism* ; Plasmids/genetics* ; Myoblasts/cytology*

Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD⁺/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.
Mice ; Animals ; Butyric Acid/metabolism* ; Ketone Bodies/metabolism* ; Liver/metabolism* ; Hydroxybutyrates/metabolism* ; Down-Regulation ; Sirtuins/metabolism* ; Hydroxymethylglutaryl-CoA Synthase/metabolism*