BACKGROUND:There is still no consensus on the optimal internal fixation for the treatment of Pauwels Ⅲ femoral neck fracture,and most of the related finite element analyses have been performed using a single simplified loading condition,and the biomechanical properties of commonly used internal fixation devices need to be further investigated. OBJECTIVE:To analyze the biomechanical characteristics of Pauwels Ⅲ femoral neck fractures treated with cannulated compression screw,dynamic hip screw,and femoral neck system by finite element method under different loading conditions of single-leg standing loads and sideways fall loads. METHODS:The DICOM data of healthy adult femur were obtained by CT scanning,imported into Mimics 15.0 software to obtain the rough model of bone tissue.The data exported from Mimics were optimized by Geomagics software,and then three internal fixation models were built and assembled with the femur model according to the parameters of the clinical application of the cannulated compression screw,dynamic hip screw,and femoral neck system by using Pro/E software.Finally,the three internal fixation models were imported into Ansys software for loading and calculation to analyze the stress distribution and displacement of the femur and the internal fixation under different working conditions of single-leg standing loads and sideways fall loads,as well as the stress characteristics of the calcar femorale and Ward's triangle. RESULTS AND CONCLUSION:(1)Under the single-leg standing load and the sideways fall load,the proximal femoral stress of the three internal fixation models was mainly distributed above the fracture end of the femoral neck.The peak stress of the proximal femoral end,fracture end,Ward triangle,and calcar femorale of the three internal fixation models were the smallest in the femoral neck system model and the largest in the cannulated compression screw model.(2)Under the single-leg standing load and the sideways fall load,the peak displacement of the proximal femur of the three internal fixation models was all located at the top of the femoral head,and the peak displacement was the smallest in the femoral neck system model and the largest in the cannulated compression screw model.(3)The peak displacement of the three internal fixation models was all located at the top of the internal fixation device under the single-leg standing and sideways fall loading conditions,and the peak displacement values were the smallest in the femoral neck system internal fixation model and the largest in the cannulated compression screw internal fixation model.(4)The internal fixation stress of the three internal fixation models was mainly distributed in the area near the fracture end of the internal fixation device under the single-leg standing and sideways fall loads,and the peak value of internal fixation stress was the smallest in the femoral neck system model and the largest in the cannulated compression screw model.(5)These results suggest that the mechanical stability of the femoral neck system is the best,but there may be a risk of stress shielding of the fracture end and calcar femorale.The stress of the internal fixation device of the femoral neck system is more dispersed,and the risk of internal fixation break is lower.

Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.

Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.

Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.

BACKGROUND: P16 inactivation is frequently accompanied by telomerase reverse transcriptase ( TERT ) amplification in human cancer genomes. P16 inactivation by DNA methylation often occurs automatically during immortalization of normal cells by TERT . However, direct evidence remains to be obtained to support the causal effect of epigenetic changes, such as P16 methylation, on cancer development. This study aimed to provide experimental evidence that P16 methylation directly drives cancer development. METHODS: A zinc finger protein-based P16 -specific DNA methyltransferase (P16-Dnmt) vector containing a "Tet-On" switch was used to induce extensive methylation of P16 CpG islands in normal human fibroblast CCD-18Co cells. Battery assays were used to evaluate cell immortalization and transformation throughout their lifespan. Cell subcloning and DNA barcoding were used to track the diversity of cell evolution. RESULTS: Leaking P16-Dnmt expression (without doxycycline-induction) could specifically inactivate P16 expression by DNA methylation. P16 methylation only promoted proliferation and prolonged lifespan but did not induce immortalization of CCD-18Co cells. Notably, cell immortalization, loss of contact inhibition, and anchorage-independent growth were always prevalent in P16-Dnmt&TERT cells, indicating cell transformation. In contrast, almost all TERT cells died in the replicative crisis. Only a few TERT cells recovered from the crisis, in which spontaneous P16 inactivation by DNA methylation occurred. Furthermore, the subclone formation capacity of P16-Dnmt&TERT cells was two-fold that of TERT cells. DNA barcoding analysis showed that the diversity of the P16-Dnmt&TERT cell population was much greater than that of the TERT cell population. CONCLUSION P16 methylation drives TERT -mediated immortalization and transformation of normal human cells that may contribute to cancer development.
Humans ; Telomerase/genetics* ; DNA Methylation/physiology* ; Fibroblasts/cytology* ; Cyclin-Dependent Kinase Inhibitor p16/metabolism* ; Cell Line ; Cell Transformation, Neoplastic/genetics*

Objective:To investigate the prevalence of Helicobacter pylori infection among family members, and analyze associated risk factors. Methods:The current investigation was a cross-sectional study. The Qinghai region was stratified into urban areas, agricultural areas, and pastoral areas. The urban areas of Xining City, the agricultural areas of Haidong City, and the pastoral areas of Haibei Tibetan Autonomous Prefecture were selected. A total of 396 resident families (1 131 people) who underwent health checkups from 2021 to 2022 in the above areas were included in the survey study. Questionnaires were administered and H. pylori infection was detected using the 13C-urea breath test. Numerical data were expressed as cases and percentages, and the Chi-square test was used to compare differences in H. pylori infection rates in the populations and families in each group. Multifactorial logistic regression was used to analyze risk factors for H. pylori infection, and P<0.05 was considered statistically significant. Results:The prevalence of H. pylori infection in Qinghai province was 52.8% (597/1 131) and the prevalence of H. pylori infection in households was 80.6% (319/396). In H. pylori-positive households with at least 1 infected spouse, 40.4% (36/89) had only 1 infected spouse, and in 59.6% (53/89) both spouses were infected. In analysis of children infected by parents with H. pylori, 20.0% (9/45) of households had fathers and children infected, 48.9% (22/45) had mothers and children infected, and 31.1% (14/45) had both parents and children infected. In univariate analysis there was a statistically significant difference in the overall comparison of H. pylori infection rates among families with different numbers of people living together ( χ2=11.12, P=0.004), and between-group comparisons suggested that H. pylori infection rates were higher in families with 4 or 5 people and more than 5 people living together than in families with 2 or 3 people living together. The H. pylori infection rate was higher in families that did not use serving chopsticks and spoons during family meals than in families that did use serving chopsticks and spoons ( χ2=6.12, P=0.013). In multifactorial logistic regression analyses the number of people living together in a family and whether or not serving chopsticks and spoons were used at family meals were associated with H. pylori infection ( P<0.05). Conclusion:The H. pylori infection rate in families in Qinghai Province is high, and there is a clear association with family aggregation. It is more common for both members of a couple to be infected, and H. pylori infection of a mother has a greater effect on the children′s infection status than H. pylori infection of a father. The infection rate of H. pylori was lower in families that used serving chopsticks and spoons during dinner gatherings, and the fewer the number of people living together in the family, the lower the H. pylori infection rate.

Objective:To investigate the correlation between bronchial wall thickness that was determined by high-resolution computed tomography(HRCT)on lung,and pulmonary function and curative efficacy of patients with chronic obstructive pulmonary disease(COPD).Methods:From January 2020 to December 2022,a total of 154 COPD patients were retrospectively selected as the observation group.According to the indicator of the percentage of forced expiratory volume in the first second(FEV1%),the patients were divided into high-risk group(grade Ⅰ,n=51),mild group(grade Ⅱ,n=45),moderate group(grade Ⅲ,n=35)and severe group(grade Ⅳ,n=23)as the 2023 global initiative for chronic obstructive lung disease(GOLD)scale.At the same time,67 healthy subjects were selected as healthy control group.All of them underwent HRCT scan on their chest,and the thickness of the bronchial wall at the opening of the bronchus of bilateral lung apex was measured.The percentage of forced expiratory volume at the first second(FEV1%),forced expiratory volume at the first second(FEV1)and FEV1/forced vital capacity(FEV1/FVC%)(percentage of forced vital capacity)were measured by the pulmonary function apparatus.Pearson correlation analysis software was used to analyze the correlation between bronchial wall thickening and lung function and curative efficacy.Results:The left bronchial wall thickness(1.49±0.21)mm and the right bronchial wall thickness(1.52±0.24)mm in the observation group were higher than those in the healthy control group(t=18.041,15.504,P<0.05),respectively.In the observation group,the higher GOLD grading of the subgroup has higher thickness at the left and right sides of bronchial walls,and there were also significant differences at the thicknesses of bilateral bronchial walls among different grading groups(F=13.888,25.841,P<0.05),respectively.The FEV1(1.82±0.32),FEV1/FVC%(63.09±5.26)and FEV1%(63.36±6.03)in COPD patients of the each subgroup of observation group were lower than those of healthy control group,and the differences were statistically significant(t=6.693,15.392,7.944,P<0.05),respectively.In the observation group,patients with higher GOLD grade has lower decreasing level of the FEV1,FEV1/FVC%and FEV1%,and there were statistically significant differences in pulmonary function levels among the subgroups of the observation group(F=166.541,141.751,57.120,P<0.05),respectively.The results of Pearson correlation analysis showed that the left and right sides of bronchial wall thickening of HRCT scan on COPD patients were positively correlated with FEV1,FEV1/FVC%and FEV1%levels of pulmonary function in COPD patients(r=0.451,0.503,0.498,0.531,0.488.0.515,P<0.05),respectively.Conclusion:The thickness of bronchial wall of HRCT scan images on lung appears high expression in COPD patients,and its expression level can reflect the severity of patients'disease,and has a strong correlation with pulmonary function.

Objective To investigate the expressions of glycolysis-related factors and changes in Notch1 signaling in endometrial tissues of adenomyosis(AM)and Ishikawa cells to explore the pathogenesis of AM.Methods Eutopic endometrial tissues were collected from 8 patients with AM and 8 patients with uterine fibroids matched for clinical characteristics(control group).The expressions of Notch1 signaling proteins and glycolysis-related factors in the collected tissues were detected using qRT-PCR and Western blotting,and the levels of glucose and lactic acid were determined.An Ishikawa cell model with lentivirus-mediated stable Notch1 overexpression was established for assessing cell survival rate with CCK-8 assay,cell migration and invasion abilities with Transwell migration and invasion assays,and glycolytic capacity by determining the extracellular acidification rate.Results Compared with those in the control group,the endometrial tissues in AM group showed significantly increased expression level of carbohydrate antigen 125(CA125),increased mRNA expression levels of Notch1,HK2 and PDHA and protein expressions of Notch1,GLUT1,HK2,PKM and PDHA,lowered glucose level and increased lactate level.The Ishikawa cell models with stable Notch1 overexpression exhibited significantly increased cell survival rate with attenuated cell migration and invasion abilities and decreased glycolysis capacity and reserve.Conclusion The Notch1 signaling pathway participates in the pathogenesis of AM possibly by regulating the proliferation,migration,invasion and glycolysis of endometrial cells.

Objective To explore the lipid-lowering effect of Qige Decoction before and after compatibility through the combination of pharmacodynamics and liver metabolomics,and to provide new research strategies for exploring the scientific notation of traditional Chinese medicine compatibility.Methods According to the pharmacodynamic strategy,three groups of drug administration were set up as Qige Decoction group,Astragali Radix-Puerariae Radix group,and Pericarpium Citri Tangerinae group.Four indices of blood lipids,serum biochemical indicators,and liver morphology and pathology were used to evaluate the intervention effect of Qige Decoction on hyperlipidemic rats.Liver metabolomics technology was used to analyze the effects of Qige Decoction on metabolites before and after compatibility,and multivariate statistical analysis was used to evaluate the differences between groups in terms of differential metabolites and metabolic pathways.Results Compared with the model group,the callback abilities of four indices of blood lipid in the Qige Decoction group were higher than those in Astragali Radix-Puerariae Radix group and Pericarpium Citri Tangerinae group,among which the total cholesterol(TC)and triglyceride(TG)levels in the Qige Decoction group decreased(P＜0.05).A total of 86 potential biomarkers were identified by liver metabolomics,with 23,13,and 7 metabolites being significantly different in the Qige Decoction group,Astragali Radix-Puerariae Radix group,and Pericarpium Citri Tangerinae group,respectively(P＜0.05).Metabolic pathway analysis of 29 specific biomarkers with significant callback effects showed that they were related to glycerophospholipid metabolism,linoleic acid metabolism,α-linolenic acid metabolism,sphingolipid metabolism,arachidonic acid metabolism,and unsaturated fatty acid biosynthesis.Qige Decoction mainly regulates glycerophospholipid and linoleic acid metabolism,and uniquely acts on sphingolipid metabolism.Conclusion Qige Decoction has more lipid-lowering targets after compatibility,with better lipid-lowering effects than the Astragali Radix-Puerariae Radix group and Pericarpium Citri Tangerinae group.This study provides experimental evidence and research strategies for further revealing the scientific notation of traditional Chinese medicine compatibility.

Objective:To explore the value of the classifier model based on CT radiomic characteristics in predicting the activity of pulmonary cystic echinococcosis (CE).Methods:The study was designed as cross-sectional. A retrospective analysis was performed on 81 patients diagnosed with pulmonary CE in the First Affiliated Hospital of Xinjiang Medical University from January 2010 to October 2020. The Python function divided 17 cases into an internal verification group and 64 cases into a training group with a ratio of 2∶8. In addition, 16 patients diagnosed with pulmonary CE from the Fourth Affiliated Hospital of Xinjiang Medical University from October 2020 to 2024 were included in the external validation group. All patients underwent CT examination, and radiomics features were extracted using Radcloud platform of Huimedi Huiying. The intraclass correlation coefficient was performed on the features, then feature screening was performed using the SelectKBest method, variance thresholding method, and least absolute shrinkage and selection operator. Finally, three classifiers (including support vector machine (SVM), K-neighborhood (KNN), and logistic regression (LR)) were used to build the models. The receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the model′s efficiency.Results:Among 81 patients with lung CE, 58 were male, and 23 were female. twenty-eight lesions were active and 53 were inactive. A total of 11 optimal features were selected. Based on the selected features, the SVM classifier model, KNN classifier model, and LR classifier model were established. The KNN classifier model in the training group had the highest AUC value (0.93) and the highest specificity (0.98) in predicting lung CE activity. In the internal validation group, the SVM classifier model had the highest AUC value (0.92) and the highest specificity (0.91) in predicting lung CE activity. The LR classifier model performed best with the highest AUC of 0.85 for predicting lung CE activity in the external validation group, and the specificity of the three models was 0.92.Conclusion:The classifier model established based on CT radiomic features has a certain value in predicting lung CE activity, and may be helpful in clinical decision-making.