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: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: 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 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 describe the distribution of fat-free mass (FFM) and fat-free mass index (FFMI) in children aged 3-17 years in China.Methods:Data were collected from National Nutrition and Health Systematic Survey in 0-18 years old children in China. By using multi-stage stratified randomized cluster sampling method, the project was conducted in 28 survey points in urban and rural areas in 14 provinces (autonomous regions and municipalities) in 7 regions in China from 2019 to 2021. FFM was measured using bioelectrical impedance meter. Finally, the body composition data of 70 853 children were included in the analysis. M ( Q1, Q3) was used to describe the gender and age specific FFM and FFMI of the children in different regions. Kruskal-Wallis H rank sum test was used to compare FFM and FFMI of boys and girls in same age group, boys in different age groups, girls in different age groups, as well as boys in same age group and girls in same age group in different regions. DSCF method was used for pairwise comparisons. Results:After the age of 11 years, the difference of FFMI between boys and girls increased year by year. The FFMI was 14.2 kg/m 2 in boys and 13.8 kg/m 2 in girls at 11 years old, the difference was significant ( χ2=135.86, P<0.001). The difference of FFMI between boys and girls exceed 1.0 kg/m 2 from 12 years old, and FFMI was 15.3 kg/m 2 in boys and 14.2 kg/m 2 in girls at 12 year old, the difference was significant ( χ2=597.27, P<0.001). The FFMI was 17.5 kg/m 2 in boys and 14.7 kg/m 2 in girls at 16 years old, the difference was significant ( χ2=2 543.60, P<0.001). The FFMI was higher in boys in northeast China, while the FFMI was lower in both boys and girls in northwest China. Conclusions:Gender specific difference was observed in the increase of FFMI with age. The FFMI was significantly higher in boys than in girls after 11 years old. It is necessary to pay attention to the problem of FFM in children in northeastern and northwestern China.

Objective:To investigate the distribution characteristics of body height, body weight and body mass index (BMI) in children aged 3-17 years in China.Methods:Data were obtained from the National Nutrition and Health Systematic Survey in 0-18 years old children in China. The study selected 70 853 children aged 3-17 years from 28 urban and rural survey sites in 14 provinces (autonomous regions and municipalities) in 7 regions of China with multi-stage stratified cluster random sampling. M ( Q1, Q3) was used to describe the region, age and gender specific body height, body weight and BMI in the children aged 3-17 years. Wilcoxon rank sum test was used to compare the body height, body weight, and BMI between boys and girls in same age group. Kruskal-Wallis H rank sum test was used to compare the body height, body weight and BMI among boys in different age groups and among girls in different age groups, as well as among boys in same age group and among girls in same age group from different regions, and DSCF method was used for further pairwise comparisons. Results:In this study, the median body height and body weight were 172.0 cm and 62.9 kg in 17-year-old boys and 160.0 cm and 53.7 kg in 17-year-old girls. The median for children's body height, body weight, and BMI in most age groups were higher in northeastern and northern China than in southern China, and the differences could be observed until age 17 years. The differences in body weight and BMI in children in northeastern and northern China were greater in Q3 than in Q1 compared with southern China. Conclusions:The body height of children aged 3-17 years continues to increase in China. Northeastern and northern China have more children with higher bodyweight, showing an obvious body weight increase trend, to which close attention needs to be paid.

Objective:To describe the distribution of fat mass (FM), fat mass percentage (FMP), and fat mass index (FMI) in children aged 3-17 years in China.Methods:Data of this study were from the National Nutrition and Health Systematic Survey in 0-18 years old children in China. A total of 70 853 children aged 3-17 years old selected from seven regions of China were included in this analysis. Body composition were measured by using bioelectrical impedance meter. The region, gender and age specific FM, FMP and FMI of the subjects were described by using M ( Q1, Q3). Kruskal-Wallis H rank sum test was used for the comparison of intergroup differences. DSCF method was used for pairwise comparisons. Results:The medians of FM, FMP and FMI were 3.0 kg, 18.3% and 2.9 kg/m 2 in boys aged 3 years and 2.9 kg, 19.0% and 2.9 kg/m 2 in girls aged 3 years, respectively. The FM increased with age and the FMP and FMI decreased with age in both boys and girls aged 3-5 years. After 11 years old, the FM, FMP and FMI decreased first and then increased in boys. From 6-17 years old, the FM, FMP and FMI increased gradually in girls. The FM, FMP and FMI were higher in girls than in boys after 12 years old (all P<0.05). The FM, FMP and FMI were relatively higher in children at the age of 6-14 in northeastern and northern China than in other regions. Conclusions:The age specific FM, FMP and FMI had different changing characteristics in boys and girls aged 3-17 years in seven regions of China. The FM, FMP and FMI also differed with region.