Aging has emerged as a cutting edge and hotspot in global life science field， with anti-aging and geriatric disease prevention and treatment becoming critical issues urgently demanding solutions in international medical communities. In the face of the challenge of accelerating global population aging， in-depth exploration of aging mechanisms and the development of effective intervention strategies hold significant scientific and clinical value. This study supported by the national key research and development program of China， employed the essence-Qi-spirit theory of Qiluo doctrine as its guiding framework， focusing on the key scientific issue of the core traditional Chinese pathogenesis of aging， namely "depletion of kidney essence， deficiency of primordial Qi， and impairment of body and spirit". The treatment principle of "tonifying the kidney to replenish essence， harmonizing Yin and Yang， warming and invigorating primordial Qi， and nourishing the body and spirit" was established. Centered on holistic aging， systemic aging， and aging-related diseases， the research integrated multidisciplinary research approaches to construct multi-modal aging models and a multi-dimensional evaluation system， and it utilized multi-omics technologies to deeply analyze aging mechanisms. By systematically reviewing historical kidney-tonifying and anti-aging formulas and combining big data with artificial intelligence technologies， an information database of anti-aging traditional Chinese medicine substance was developed to reveal the differences and synergistic effects of various treatment methods and formulas on anti-aging. Based on this treatment method， the research integrated two millennia of kidney-tonifying medicinal experience to develop the innovative anti-aging traditional Chinese medicine， namely Bazhi Bushen capsules. It was validated that this capsule can delay holistic and systemic aging through multiple targets and mechanisms， thereby elucidating the scientific connotation of the essence-Qi-spirit theory of Qiluo doctrine in guiding anti-aging research from multiple dimensions and providing robust support for leveraging the advantages of traditional Chinese medicine to occupy the commanding heights of international anti-aging research.

The present study aimed to establish an LC-MS/MS method for the quantification of tiamulin in minipig plasma and to further conduct a pharmacokinetic comparison of different formulations. The plasma samples were extracted with acetonitrile (meloxicam as internal standard), separated on a C18 column, and quantified by multiple reaction monitoring mode (ESI+). Sanyuan minipigs were used as experimental animals. Plasma samples were collected after intravenous injection (10 mg/kg) and intragastric administration (20 mg/kg). The method showed good linearity, with intra- and inter-batch RSD of 1.00%–8.13% and RE within ±15%. The extraction recovery, matrix effect and stability of the analytical methods met the relevant requirements. Tiamulin fumarate active pharmaceutical ingredient was intravenously administered, with c0 of about (4383.73±2676.78) ng/mL, AUC0-t of about (4803.50±965.68) h·ng/mL, t1/2 of about (4.66±1.68) h, and CL of about (2.14±0.46) L/(kg·h). Three tiamulin formulations were intragastrically administered, with cmax of (552.00±328.55), (545.00±136.97) and (590.60±237.02) ng/mL, tmax of (1.47±0.68), (0.69±0.75) and (0.72±0.72) h, and F of 24.85%, 15.28% and 16.97%, respectively. The validated method meets the requirements for biological sample analysis and is applicable for the pharmacokinetic evaluation of tiamulin formulations in minipigs.

PURPOSE: We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery. METHODS: A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics. RESULTS: Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%. CONCLUSION Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice.
Humans ; Surgical Wound Infection/epidemiology* ; Male ; Female ; Risk Factors ; Retrospective Studies ; Middle Aged ; Adult ; Case-Control Studies ; Fractures, Bone/surgery* ; Aged ; Drug Resistance, Bacterial ; Logistic Models ; Anti-Bacterial Agents/therapeutic use* ; Incidence ; Bacteria/drug effects*

Objective To explore the expression level,clinical significance of protein disulfide isomerase A3(PDIA3)in endome-trial cancer(EC)tissues,and its effects on Ishikawa cells.Methods Using the TCGA database to analyze the differential expression levels of PDIA3 in different endometrial tissues and explore its relationship with clinical pathological parameters and prognosis of EC pa-tients;Using immunohistochemistry(IHC)to detect the expression level of PDIA3 in clinical endometrial tissue,analyze the clinical pathological parameters,prognosis,and risk factors affecting the prognosis of EC patients with different expression levels;Using Transwell assay,scratch assay,and CCK-8 assay to detect the proliferation,invasion,and migration ability of Ishikawa cells with knockdown PDIA3 expression.Results The expression level of PDIA3 in EC tissue was higher than that in normal endometrial tissue in the TCGA database and clinical specimens(P＜0.05).The expression level of PDIA3 in EC tissue in the G3 grade group was higher than that in the G1 and G2 grade groups in the TCGA database(P＜0.05).The expression level of PDIA3 in EC tissue in FIGO stage Ⅱ-Ⅳ group was higher than that in the stage Ⅰ group,the group with lymph node metastasis was higher than that without lymph node metastasis,and the highly differentiated group was higher than the poorly differentiated group in clinical specimens(P＜0.05);COX regression analysis showed that Federation International of Gynecology and Obstetrics(FIGO)staging and PDIA3 expression level were the independent risk factors of prognosis in EC patients;the survival time of EC patients with high expression of PDIA3 in the TCGA database was shorter than that of the low expression group(P＜0.05),and the survival rate of clinical patients with positive PDIA3 was shorter than that of the neg-ative group(P＜0.05);Transwell assay,scratch assay,and CCK-8 assay showed that the invasion and migration ability of cells in the PDIA3 inhibition group was significantly reduced compared to the normal group and negative control group(P＜0.05).Conclusion PDIA3 is highly expressed in EC tissues and is associated with the malignancy of tumors and poor prognosis of patients;targeted inhibition of PDIA3 expression can reduce the proliferation,invasion,and migration ability of Ishikawa cells.

Objective:It aims to examine the effects of the employee medical insurance outpatient mutual assistance on medical insurance costs for patients with diabetes mellitus,offering insights for optimizing outpatient insurance policies and chronic disease management strategies.Methods:Outpatient cost settlement data of urban employees with diabetes mellitus in Lanzhou from 2022 to 2023 was collected.Univariate analysis and interrupted time-series models were used to compare relevant medical insurance cost indicators before and after the reform.Results:The inpatient data of 765 730 diabetes mellitus patients were included in the study,and male patients account for 62.67％.After the reform,average per-visit pooling fund expenditure,average per-visit individual payment expenditures,average per-visit personal account expenditure,average per-visit eligible expense amount,average per-visit total fund payment,and the average per-visit proportion of basic medical pooling payments were decreased(P＜0.05).Moreover,average per-visit pooling fund expenditure,average per-visit individual account expenditure,average per-visit cash payment,average per-visit eligible expense amount,average per-visit total fund payment,and the average per-visit proportion of basic medical pooling payments showed a notable declining trend post-reform(P＜0.05).In contrast,the per-visit fully out-of-pocket expenditure exhibited no significant change before and after the reform(P＞0.05).Conclusion:The reform of the employee medical insurance outpatient mutual assistance system has alleviated the economic burden of disease for diabetic patients and improved the efficiency of medical insurance fund utilization,but it reduced the proportion of basic medical pooling payments.It is recommended to continuously refine the outpatient medical insurance payment system,strengthen supervision of medical expenses and service quality,and balance patient benefits with fund pressure to enhance chronic disease outpatient benefits.

Objective To explore the expression level,clinical significance of protein disulfide isomerase A3(PDIA3)in endome-trial cancer(EC)tissues,and its effects on Ishikawa cells.Methods Using the TCGA database to analyze the differential expression levels of PDIA3 in different endometrial tissues and explore its relationship with clinical pathological parameters and prognosis of EC pa-tients;Using immunohistochemistry(IHC)to detect the expression level of PDIA3 in clinical endometrial tissue,analyze the clinical pathological parameters,prognosis,and risk factors affecting the prognosis of EC patients with different expression levels;Using Transwell assay,scratch assay,and CCK-8 assay to detect the proliferation,invasion,and migration ability of Ishikawa cells with knockdown PDIA3 expression.Results The expression level of PDIA3 in EC tissue was higher than that in normal endometrial tissue in the TCGA database and clinical specimens(P＜0.05).The expression level of PDIA3 in EC tissue in the G3 grade group was higher than that in the G1 and G2 grade groups in the TCGA database(P＜0.05).The expression level of PDIA3 in EC tissue in FIGO stage Ⅱ-Ⅳ group was higher than that in the stage Ⅰ group,the group with lymph node metastasis was higher than that without lymph node metastasis,and the highly differentiated group was higher than the poorly differentiated group in clinical specimens(P＜0.05);COX regression analysis showed that Federation International of Gynecology and Obstetrics(FIGO)staging and PDIA3 expression level were the independent risk factors of prognosis in EC patients;the survival time of EC patients with high expression of PDIA3 in the TCGA database was shorter than that of the low expression group(P＜0.05),and the survival rate of clinical patients with positive PDIA3 was shorter than that of the neg-ative group(P＜0.05);Transwell assay,scratch assay,and CCK-8 assay showed that the invasion and migration ability of cells in the PDIA3 inhibition group was significantly reduced compared to the normal group and negative control group(P＜0.05).Conclusion PDIA3 is highly expressed in EC tissues and is associated with the malignancy of tumors and poor prognosis of patients;targeted inhibition of PDIA3 expression can reduce the proliferation,invasion,and migration ability of Ishikawa cells.

Objective:It aims to examine the effects of the employee medical insurance outpatient mutual assistance on medical insurance costs for patients with diabetes mellitus,offering insights for optimizing outpatient insurance policies and chronic disease management strategies.Methods:Outpatient cost settlement data of urban employees with diabetes mellitus in Lanzhou from 2022 to 2023 was collected.Univariate analysis and interrupted time-series models were used to compare relevant medical insurance cost indicators before and after the reform.Results:The inpatient data of 765 730 diabetes mellitus patients were included in the study,and male patients account for 62.67％.After the reform,average per-visit pooling fund expenditure,average per-visit individual payment expenditures,average per-visit personal account expenditure,average per-visit eligible expense amount,average per-visit total fund payment,and the average per-visit proportion of basic medical pooling payments were decreased(P＜0.05).Moreover,average per-visit pooling fund expenditure,average per-visit individual account expenditure,average per-visit cash payment,average per-visit eligible expense amount,average per-visit total fund payment,and the average per-visit proportion of basic medical pooling payments showed a notable declining trend post-reform(P＜0.05).In contrast,the per-visit fully out-of-pocket expenditure exhibited no significant change before and after the reform(P＞0.05).Conclusion:The reform of the employee medical insurance outpatient mutual assistance system has alleviated the economic burden of disease for diabetic patients and improved the efficiency of medical insurance fund utilization,but it reduced the proportion of basic medical pooling payments.It is recommended to continuously refine the outpatient medical insurance payment system,strengthen supervision of medical expenses and service quality,and balance patient benefits with fund pressure to enhance chronic disease outpatient benefits.

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*