Mice have been widely used in the study of primary liver cancer owing to the close similarity of its genome to that of humans,its strong reproductive ability,the low cost of model construction,and the ease of genetic manipulation,including molecular mechanisms of pathogenesis and potential drug targets.Traditional animal models are increasingly falling short of meeting the needs of precision medicine research because of their inability to reproduce tumor microenvironment interactions and control the specificity of molecular subtypes.This study systematically compared the technical advantages of tail vein high-pressure injection,combined with transposon system(HTVI-TS),with traditional models in liver cancer research,and focused on the application value of the HTVI-TS model in the mechanism study of tumorigenesis and development,immunotherapy response prediction,and individualized evaluation of targeted drugs.This report presents a new research platform for precise diagnosis and treatment of primary liver cancer by simulating the heterogeneous evolution process of the cancer.The findings provide a theoretical basis for optimizing the selection of preclinical research models for liver cancer;the expansion potential of this technology in liver cancer research is outlined.

With the increasing attention of domestic and foreign scholars to death with dignity, the importance of death with dignity in the field of hospice care is becoming increasingly prominent. This study reviews the fundamental concept of death with dignity, comprehensively analyzes the content, application scenarios, advantages, and limitations of various cognition and practice assessment tools for death with dignity at home and abroad, aiming to provide reference for promoting the development and appropriate use of cognition and practice assessment tools for death with dignity in China.

Objective:To investigate the reliability and validity of different measurement methods under 30° arthroscopy for quantifying the proportion of glenoid bone defect in bony Bankart lesions of the shoulder joint and validate its preliminary application effect.Methods:Eight intact shoulder glenoid specimens were selected, with no existing defects or deformities, from donors of 4 females and 4 males, with their age at death of 43-67 years [(54.4±8.0)years]. Bone defects of 12.5% and 25% were created in the glenoid at 0° and 45° relative to the longitudinal axis, with two specimens per defect category. The defect proportion in each specimen was quantified using direct measurement and CT-based digital reconstruction and these values served as reference standards for subsequent statistical analysis. Using a combined approach of arthroscopic simulation equipment and cadaveric study, five investigators performed simulated examinations through the standard posterior portal (2 cm medial and 1.5 cm inferior to the posterolateral acromial corner) and the modified posteroinferior portal (2 cm medial and 3 cm inferior to the posterolateral acromial corner) separately. Under 30° arthroscopy, the glenoid bone loss percentage was measured using the bare spot method and secant chord method. The reliability was analyzed for these measurements. Furthermore, using direct physical measurements and CT-based three-dimensional reconstruction data from the same specimens as reference standards, the comprehensive validity of four measurement methods was evaluated (standard posterior portal-bare spot method, standard posterior portal-secant chord method, modified posteroinferior portal-bare spot method, and modified posteroinferior portal-secant chord method). The independent validity of each method was assessed according to bone defect morphology classification to determine differences in measurement accuracy across defect types. In an arthroscopic procedure for a patient with Bigliani type IIIB bony Bankart lesion, the standard posterior portal-secant chord method was applied to quantify the proportion of glenoid bone defects.Results:The mean reference values from direct measurement and CT measurement of glenoid bone defect proportion in eight bony Bankart lesion specimens were 12.71%/12.37%, 13.17%/13.10%, 25.71%/24.9%, 26.6%/26.95%, 13.41%/13.10%, 12.90%/12.59%, 26.42%/25.94%, and 26.73%/27.06%, respectively. Measurements obtained by the five investigators showed intraclass correlation coefficients (ICCs) all greater than 0.90, indicating excellent interobserver agreement. In the validity analysis, the standard posterior portal-secant chord method demonstrated the highest overall validity. Using direct measurement and CT-based measurement as reference standards, the overall validity was (0.90±0.38)% and (1.07±0.53)% for the standard posterior portal-bare spot method, (1.33±0.40)% and (1.51±0.54)% for the modified posteroinferior portal-bare spot method, and (0.53±0.17)% and (0.70±0.38)% ( P<0.05) for the modified posteroinferior portal-secant chord method. In contrast, the standard posterior portal-secant chord method showed an overall validity of (0.10±0.10)% and (0.28±0.39)% ( P>0.05). In subsequent independent validity analyses, the standard posterior portal-secant chord method also demonstrated superior validity across all bone defect subtypes over the other three methods. In a patient with a Bigliani type IIIB bony Bankart lesion, we used the standard posterior portal-secant chord method to quantify the glenoid bone loss in 2 minutes, revealing a defect proportion of 26.6%. An arthroscopic autologous iliac bone graft procedure with single-tunnel elastic fixation guided by this measurement achieved favorable outcomes, with stable reduction, secure internal fixation and favorable recovery of shoulder function at 2 months postoperatively. Conclusion:For various types of bony Bankart lesions, the 30° arthroscopic standard posterior portal-secant chord method provides the most accurate quantification of glenoid bone loss and its preliminary clinical application yields satisfactory results.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective To investigate the effects of bis(acetylacetonato)oxovanadium(IV)[VO(acac)?]on human adrenocortical carcinoma cell lines SW-13 and NCI-H295R in vitro,aiming to determine whether VO(acac)?promotes or inhibits the proliferation,migration,and invasion of these cells.Methods SW-13 and NCI-H295R cells in logarithmic growth phase were exposed to VO(acac)? at concentrations of 6.25,12.5,25,50,75,100,and 200 μmol/L for 24 and 48 hours,respectively.Mitotane served as the positive control.Cell viability was assessed using the CCK-8 assay to evaluate the effects of VO(acac)? on SW-13 and NCI-H295R cells.Subsequently,cells were treated with VO(acac)? at concentrations of 0,6.25,12.5,and 25 μmol/L for 48 hours,and flow cytometry was employed to investigate the impact of VO(acac)? on apoptosis.The migratory ability of the cells was evaluated using a wound healing assay,while their invasive capacity was assessed via a Transwell assay.Additionally,the clonogenic assay was used to determine the proliferative potential of SW-13 and NCI-H295R cells following VO(acac)?treatment.Results The CCK-8 results demonstrated that VO(acac)2 inhibited the viability of SW-13 and NCI-H295R cells in a time-and concentration-dependent manner.Specifically,the half-maximal inhibitory concentra-tions(IC50)for VO(acac)2 against SW-13 cells were 62.98±6.67 μmol/L after 24 hours and(14.61±1.66)μmol/L after 48 hours of treatment,while the corresponding IC50 values for NCI-H295R cells were 46.78±7.89 μmol/L and 12.61±2.98 μmol/L,respectively.Flow cytometry analysis revealed that VO(acac)2 induced apoptosis in both SW-13 and NCI-H295R cells in a concentration-dependent manner(P<0.05).The wound healing assay indicated a significant reduction in the migratory rate of SW-13 and NCI-H295R cells with increasing concentrations of VO(acac)2(P<0.05).Transwell assay results showed that VO(acac)2 significantly inhibited the invasive ability of SW-13 and NCI-H295R cells in a concentration-dependent fashion.Finally,the clonogenic assay confirmed that VO(acac)2 suppressed the proliferative capacity of SW-13 and NCI-H295R cells in a concentration-dependent manner.Conclusion VO(acac)2 inhibits the proliferation,migration,and invasion of human adrenocortical carcinoma cells(SW-13 and NCI-H295R),while inducing apoptosis in these cell lines.

Objective:To investigate the reliability and validity of different measurement methods under 30° arthroscopy for quantifying the proportion of glenoid bone defect in bony Bankart lesions of the shoulder joint and validate its preliminary application effect.Methods:Eight intact shoulder glenoid specimens were selected, with no existing defects or deformities, from donors of 4 females and 4 males, with their age at death of 43-67 years [(54.4±8.0)years]. Bone defects of 12.5% and 25% were created in the glenoid at 0° and 45° relative to the longitudinal axis, with two specimens per defect category. The defect proportion in each specimen was quantified using direct measurement and CT-based digital reconstruction and these values served as reference standards for subsequent statistical analysis. Using a combined approach of arthroscopic simulation equipment and cadaveric study, five investigators performed simulated examinations through the standard posterior portal (2 cm medial and 1.5 cm inferior to the posterolateral acromial corner) and the modified posteroinferior portal (2 cm medial and 3 cm inferior to the posterolateral acromial corner) separately. Under 30° arthroscopy, the glenoid bone loss percentage was measured using the bare spot method and secant chord method. The reliability was analyzed for these measurements. Furthermore, using direct physical measurements and CT-based three-dimensional reconstruction data from the same specimens as reference standards, the comprehensive validity of four measurement methods was evaluated (standard posterior portal-bare spot method, standard posterior portal-secant chord method, modified posteroinferior portal-bare spot method, and modified posteroinferior portal-secant chord method). The independent validity of each method was assessed according to bone defect morphology classification to determine differences in measurement accuracy across defect types. In an arthroscopic procedure for a patient with Bigliani type IIIB bony Bankart lesion, the standard posterior portal-secant chord method was applied to quantify the proportion of glenoid bone defects.Results:The mean reference values from direct measurement and CT measurement of glenoid bone defect proportion in eight bony Bankart lesion specimens were 12.71%/12.37%, 13.17%/13.10%, 25.71%/24.9%, 26.6%/26.95%, 13.41%/13.10%, 12.90%/12.59%, 26.42%/25.94%, and 26.73%/27.06%, respectively. Measurements obtained by the five investigators showed intraclass correlation coefficients (ICCs) all greater than 0.90, indicating excellent interobserver agreement. In the validity analysis, the standard posterior portal-secant chord method demonstrated the highest overall validity. Using direct measurement and CT-based measurement as reference standards, the overall validity was (0.90±0.38)% and (1.07±0.53)% for the standard posterior portal-bare spot method, (1.33±0.40)% and (1.51±0.54)% for the modified posteroinferior portal-bare spot method, and (0.53±0.17)% and (0.70±0.38)% ( P<0.05) for the modified posteroinferior portal-secant chord method. In contrast, the standard posterior portal-secant chord method showed an overall validity of (0.10±0.10)% and (0.28±0.39)% ( P>0.05). In subsequent independent validity analyses, the standard posterior portal-secant chord method also demonstrated superior validity across all bone defect subtypes over the other three methods. In a patient with a Bigliani type IIIB bony Bankart lesion, we used the standard posterior portal-secant chord method to quantify the glenoid bone loss in 2 minutes, revealing a defect proportion of 26.6%. An arthroscopic autologous iliac bone graft procedure with single-tunnel elastic fixation guided by this measurement achieved favorable outcomes, with stable reduction, secure internal fixation and favorable recovery of shoulder function at 2 months postoperatively. Conclusion:For various types of bony Bankart lesions, the 30° arthroscopic standard posterior portal-secant chord method provides the most accurate quantification of glenoid bone loss and its preliminary clinical application yields satisfactory results.

Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.

Objective To investigate the effects of bis(acetylacetonato)oxovanadium(IV)[VO(acac)?]on human adrenocortical carcinoma cell lines SW-13 and NCI-H295R in vitro,aiming to determine whether VO(acac)?promotes or inhibits the proliferation,migration,and invasion of these cells.Methods SW-13 and NCI-H295R cells in logarithmic growth phase were exposed to VO(acac)? at concentrations of 6.25,12.5,25,50,75,100,and 200 μmol/L for 24 and 48 hours,respectively.Mitotane served as the positive control.Cell viability was assessed using the CCK-8 assay to evaluate the effects of VO(acac)? on SW-13 and NCI-H295R cells.Subsequently,cells were treated with VO(acac)? at concentrations of 0,6.25,12.5,and 25 μmol/L for 48 hours,and flow cytometry was employed to investigate the impact of VO(acac)? on apoptosis.The migratory ability of the cells was evaluated using a wound healing assay,while their invasive capacity was assessed via a Transwell assay.Additionally,the clonogenic assay was used to determine the proliferative potential of SW-13 and NCI-H295R cells following VO(acac)?treatment.Results The CCK-8 results demonstrated that VO(acac)2 inhibited the viability of SW-13 and NCI-H295R cells in a time-and concentration-dependent manner.Specifically,the half-maximal inhibitory concentra-tions(IC50)for VO(acac)2 against SW-13 cells were 62.98±6.67 μmol/L after 24 hours and(14.61±1.66)μmol/L after 48 hours of treatment,while the corresponding IC50 values for NCI-H295R cells were 46.78±7.89 μmol/L and 12.61±2.98 μmol/L,respectively.Flow cytometry analysis revealed that VO(acac)2 induced apoptosis in both SW-13 and NCI-H295R cells in a concentration-dependent manner(P<0.05).The wound healing assay indicated a significant reduction in the migratory rate of SW-13 and NCI-H295R cells with increasing concentrations of VO(acac)2(P<0.05).Transwell assay results showed that VO(acac)2 significantly inhibited the invasive ability of SW-13 and NCI-H295R cells in a concentration-dependent fashion.Finally,the clonogenic assay confirmed that VO(acac)2 suppressed the proliferative capacity of SW-13 and NCI-H295R cells in a concentration-dependent manner.Conclusion VO(acac)2 inhibits the proliferation,migration,and invasion of human adrenocortical carcinoma cells(SW-13 and NCI-H295R),while inducing apoptosis in these cell lines.

Collaborative diagnosis and treatment between Traditional Chinese Medicine(TCM)and Western Medicine,as an important measure for the modernization and innovation of TCM,faces great challenges such as inadequate medical resource supply and supply-demand imbalance in the context of high-quality development strategy.Supply-demand analysis and the input-output framework of modern economic theory were applied to systematically analyze the operational status of collaborative diagnosis and treatment of TCM and Western Medicine in China,and explore the intrinsic economic mechanism of its development.Furthermore,in line with the concept of the"Three Medical Synergistic Collaborations",it proposes policy recommendations from the dimension of medical care,medical insurance,and medicine.