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 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*

【Objective】 To compare the outcomes of robot-assisted laparoscopic transperitoneal and retroperitoneal operation for huge (>6 cm) adrenal tumors. 【Methods】 The clinical data of 45 patients with huge adrenal tumors who underwent robotic surgery during Jan.2017 and Dec.2021 were retrospectively analyzed, including 28 cases via the transperitoneal approach and 17 cases via the retroperitoneal approach. 【Results】 No patients were converted to open operations. There were no significant differences in postoperative drainage time (2.24±0.44 vs. 2.36±0.49) d, operation time (130.88±5.96 vs. 136.61±8.39) min, blood loss (189.41±13.91 vs. 192.5±12.36) mL and postoperative hospital stay (7.06±0.56 vs. 7.46±0.69) d between the retroperitoneal and transperitoneal approaches. Retroperitoneal approach was better than transperitoneal approach in early postoperative feeding [(38.82±6.75 vs. 74.14±6.57) h, P<0.01] . 【Conclusion】 Robotic surgery is safe and effective in the treatment of large adrenal tumors. The choice of surgical approach should be based on patients’ condition, tumor volume and location.

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*

AIM: To explore the improvement effect and mechanism of crocin on cognitive impairmrnt of Alzheimer's disease (AD) rats. METHODS: The hippocampus of SD rats were injected with Aβ 25-35 to establish AD model, then rats were randomly divided into AD group, AD + low, medium, high dose of crocin groups (10, 20, 40 mg/kg) and AD + donepezil group (1 mg/kg), intraperitoneal injection treatment for 4 weeks, set sham group. Dark avoidance test and water maze test were used to evaluate the learning and memory abilities of rats, ELISA was used to detect serum Aβ content, HE staining and Tunel staining were used to determine pathological changes and neuronal apoptosis of hippocampus of rats, immunohistochemistry was used to detect the expression of Brdu, Dcx and NeuN in hippocampus of rats, and Western blot was used to detect the protein expression of Aβ, DKK3, β-catenin, p-GSK-3β/GSK-3β, Caspase-3, Bax, Bcl-2 in hippocampus of rats. RESULTS: Compared to sham group, the learning and memory abilities of AD group rats were decreased, serum Aβ content increased, the pathological change in hippocampus was serious, neuronal apoptosis was increased, the expression of Brdu, Dcx, NeuN were decreased, the protein expression of Aβ, DKK3, p-GSK-3β/GSK-3β, Caspase-3, Bax were increased, protein expression of β-catenin, Bcl-2 were decreased (P<0.01). Compared to AD group, after the treatment of doses of crocin and donepezil, the learning and memory abilities of AD rats were improved, serum Aβ content were increased, and the pathological change in hippocampus were alleviated, neuronal apoptosis were reduced, the expression of Brdu, Dcx, NeuN were decreased, the protein expression of Aβ, DKK3, p-GSK-3β/ GSK-3β, Caspase-3, Bax were decreased, the protein expression of β-catenin, Bcl-2 were increased, notely, dose-dependent effect of crocin was significant. CONCLUSION: Crocin reduced neuronal apoptosis and mediated DKK3 to regulate GSK-3β/ β-catenin pathway to improve the cognitive impairment of AD rats.

Objective:To analyze the clinical outcomes of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in the Zista channel assisted by navigation for the treatment of lumbar spinal stenosis.Methods:The medical records of 156 patients who underwent surgery for lumbar spinal stenosis from January 2017 to January 2019 were retrospectively analyzed. The patients were divided into minimally invasive group, navigation open group and open group according to surgical method and navigation usage. 67 cases were treated with MIS-TLIF assisted by navigation in minimally invasive group. In the navigation open group, 31 cases underwent open TLIF surgery assisted by navigation, 58 cases were treated with open TLIF. The database was compared among the three groups including intraoperative blood loss, operative time, postoperative drainage, postoperative hospitalization time and complications. Evaluated the internal fixation and fusion according to CT, assessed the surgical results according to VAS, ODI and SF-36. The clinical effects were evaluated by MacNab scores at the last follow-up.Results:The amount of intraoperative blood loss in the minimally invasive group 116.39±25.88 ml was less than that in the navigation open group 293.94±61.67 ml and the open group 396.97±92.58 ml, and the difference was statistically significant ( F=296.01, P<0.001). The intraoperative blood loss in the navigation open group was less than that in the open group. The postoperative drainage in the minimally invasive group 80.55±27.29 ml, was less than that in the navigation open group 299.94±50.32 ml and the open group 304.86±84.34 ml, and the difference was statistically significant ( F=273.14, P<0.001). The postoperative hospitalization time in the minimally invasive group 3.42±1.00 d was less than that in the navigation open group 7.16±1.39 d and the open group 7.31±1.69 d, and the difference was statistically significant ( F=154.49, P<0.001). There was no significant difference in the operation time ( F=0.15, P=0.859). At 2 weeks and 3 months after operation, the VAS score of low back pain in the open navigation group (3.84±0.82, 1.90±0.91) and the open group (3.67±0.92, 1.91±0.90) and ODI in the navigation open group (34.74%±11.66%, 28.68%±8.19%) and the open group (32.21%±10.66%, 27.17%±9.59%) were lower than those in the minimally invasive group (1.70±0.92, 0.96±0.73), (18.33%±7.43%, 19.15%±7.96%), and the difference were statistically significant [( F=96.63, P<0.001; F=25.12, P<0.001), ( F=45.59, P<0.001; F=18.99, P<0.001)]. The SF-36 score of the minimally invasive group 61.48±9.50 at the last follow-up was higher than that of the navigation open group 52.51±6.99 and the open group 53.48±7.66, and the difference was statistically significant ( F=18.97, P<0.001). In the same group, the VAS score, ODI score and SF-36 score at each follow-up time after surgery were statistical differences compared with those before surgery ( P<0.05). Postoperative follow-up CT showed that the fusion rate of the minimally invasive group was 94.0% (63/67), the navigation open group was 93.5% (29/31), the open group was 93.1% (54/58), and the difference between the three groups was not statistically significant (χ 2=0.05, P=0.978). The success rate and accuracy of one-time nail placement in the minimally invasive group and the navigation open group were higher than those in the open group, the difference was statistically significant (χ 2=17.17, P<0.001; χ 2=15.49, P=0.040). Dural rupture occurred in 1 patient in the minimally invasive group and 2 patients in the open group. The drainage and condition changes were closely observed after surgery. All patients were successfully extubated after surgery without complaining of other discomfort. One patient in the minimally invasive group had endplate destruction and mild intervertebral collapse during postoperative follow-up. There was 1 case of incisional fat liquefaction in each of the navigation open group and the open group. Subgroup analysis of the results of the three groups were roughly the same as the overall results. Conclusion:MIS-TLIF in the Zista channel assisted by navigation is a safe, effective, and worthy of promotion minimally invasive lumbar fusion surgery with the advantages of less trauma and faster recovery in the treatment of different types of lumbar spinal stenosis.

Objective:To analyze the levels of T lymphocyte subsets (CD3, CD4, CD8 and CD4/CD8) in patients with paraquat poisoning, and to explore the relationship between the changes of T lymphocyte subsets and the prognosis of pulmonary fibrosis.Methods:In October 2019, a total of 47 patients with oral 20% paraquat low water solvent poisoning in Guangzhou 12th people's Hospital from June 2018 to June 2019 were selected as the research objects. Patients were divided into early death group (16 cases died within 2 weeks) and non early death group (31 cases survived more than 2 weeks) . The non early death group was divided into pulmonary fibrosis group (23 cases) and normal lung group (8 cases) . 20 healthy people in the same period were randomly selected as the control group. The neutrophils (N) , C reaction protein (CRP) , alanine aminotransferase (ALT) , creatinine (Cr) , amylase (aAMY) , creatine kinase isoenzyme (CKMB) , pH, HCO 3-, blood oxygen saturation (SO 2) and lactic acid (Lac) of patients poisoned within 3 d were examined every day. Independent sample t-test was used for inter group comparison, and paired sample t-test was used for intra group comparison. Results:Compared with non early death group, the levels of N, CRP, ALT, Cr, aAMY, CKMB and Lac in early death group increased ( P<0.05) , while pH and HCO 3- decreased ( P<0.05) . Compared with the control group, the levels of CD3, CD4 and CD4/CD8 were decreased on the first day in the early death group and non early death group ( P<0.05) , and the levels of CD3, CD4 and CD4/CD8 were decreased on the 15th day in the pulmonary fibrosis group ( P<0.05) . Compared with the normal lung group, the levels of CD3, CD4 and CD4/CD8 in the pulmonary fibrosis group decreased on the 15th day ( P<0.05) . Conclusion:The persistent low cellular immune function in patients with paraquat poisoning is related to the progress of pulmonary fibrosis, which is an important factor affecting the prognosis of patients with pulmonary fibrosis.