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.

Objective:To conduct a comprehensive global review of research on toxic leadership behavior among nursing managers and to analyze the current research status.Methods:Literature related to toxic leadership behavior among nursing managers was retrieved from PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP Chinese Science and Technology Journal Database, and China Biomedical Literature Database. The search period extended from the inception of each database to February 15, 2025. The included literature was then organized, analyzed, and summarized.Results:A total of 28 studies were included. There were 23 studies reported the occurrence of toxic leadership behavior among nursing managers, the incidence of toxic leadership behavior was almost at a moderately low level. There were 8 studies reported the influencing factors of toxic leadership behavior, its influencing factors encompassed three primary aspects: the organizational level, the personal characteristics of nursing managers, and characteristics of the nursing staff group. Assessment tools of toxic leadership behavior included the Toxic Leadership Behaviors of Nurse Managers, the Abuse Management Questionnaire, etc. The adverse consequences included increased nurse turnover intention, decreased nursing quality, and reduced organizational trust, etc. Interventions were planned and implemented from three perspectives: the hospital managers, nursing managers, and the nurses.Conclusions:The factors influencing toxic leadership behavior among nursing managers and its adverse consequences require further exploration. Therefore, more intervention studies are warranted to provide new insights and methods for preventing and reducing toxic leadership behavior.

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 analyze pathogens of multiple drug-resistant organism(MDRO)infection and its risk factors during the recovery period of patients with traumatic brain injury,and to construct and validate the predic-tion model for MDRO lung infection.METHODS Patients who were admitted to the Shanxi Second People's Hos-pital for traumatic brain injury(TBI)and developed hospital-acquired pneumonia(HAP)during their hospitaliza-tion between Aug.2019 and Aug.2023 were selected as the study subjects,their clinical data were retrospectively collected,and the patients were randomly divided into a modeling group(n=270)and a verification group(n=90)at a ratio of 3∶1,and they were further categorized into the MDRO infection group(148 cases)and the non-infection group(122 cases)based on whether they developed pneumonia caused by MDRO infections.Clinical data of the patients were collected for analysis,with pathogen identification performed for all patients.The risk factors for MDRO infection in TBI patients with HAP were analyzed by multivariate Logistic regression analysis,a pre-diction model for MDRO infections during the hospitalization and recovery period of TBI patients with HAP was constructed using a formula-based method,the goodness-of-fit of the model was assessed using Hosmer-Leme-show test,and its predictive ability was evaluated using receiver operating characteristic(ROC)curves.RESULTS There was no significant differences in the baseline characteristics of TBI patients with HAP between the modeling group and the verification group.The incidence of MDRO infections among TBI patients with HAP in modeling group was 54.81％(148/270),with Klebsiella pneumoniae(25.27％)being the predominant pathogen.Mechan-ical ventilation duration(OR=5.789,95％CI:2.164-15.486,P=0.001),ICU length of stay(OR=5.441,95％CI:2.153-13.751,P＜0.001),combined kidney diseases(OR=2.770,95％CI:1.321-5.812,P=0.007),duration of antibiotics use(OR=7.486,95％CI:1.928-29.059,P=0.004),occurrence of impaired consciousness(OR=5.720,95％CI:2.586-12.652,P＜0.001)and use of aminoglycoside antibiotics(OR=3.861,95％CI:1.608-9.273,P=0.003)were risk factors for MDRO infections.The Hosmer-Lemeshow for the risk prediction model showed that x2=5.013 and P=0.496.ROC curves analysis showed The area under the curve(AUC)for the modeling group by ROC curve analysis was 0.80(95％CI:0.773-0.877),with a sensitivi-ty of 83.33％and a specificity of 73.60％respectively,and the AUC for the verification group were 0.800(95％CI:0.670-0.895),with a sensitivity of 81.82％and a specificity of 77.27％respectively.CONCLUSION The prediction model constructed in this study,based on the risk factors for MDRO infection pneumonia during the re-covery period in hospitalized patients with traumatic brain injury,demonstrated high goodness-of-fit,as well as satisfactory sensitivity and specificity,and its application in clinical practice may help identify patients at high risk of MDRO infections.

Objective To establish a scheme of immunosuppressant(tacrolimus)tube administration after lung transplantation and evaluate the effect.Methods Utilizing evidence summary and the Delphi method with the Structure-Process-Outcome(SPO)model,a tacrolimus administrating via feeding tubes scheme was established for lung transplantations,incorporating 5 aspects"medication management""risk assessment""enteral feeding implementation""process monitoring"and"evaluation and feedback"from July to September 2023.A convenience sampling method was employed to select patients with lung transplant surgery of a tertiary hospital in Zhejiang Province from November 2023 to June 2024.Among them,18 patients admitted from March to June 2024 were designated as an experimental group,receiving the developed tacrolimus enteral feeding administration plan;18 patients admitted from November 2023 to February 2024 were designated as a control group,receiving standard enteral feeding administration measures.The standard trough concentration of tacrolimus,the coefficient of variation of tacrolimus trough concentration,the daily dosage of tacrolimus and its coefficient of variation,and the rate of achieving the target trough concentration of tacrolimus were compared between the 2 groups.Results Of the initially recruited subjects,15 in the experimental group and 18 in the control group were included in the final analysis.After intervention,the coefficient of variation of trough concentrations and daily doses of tacrolimus in the experimental group were lower than those in the control group,while the rate of achieving target trough concentrations was higher,with all differences being statistically significant(P＜0.05).There was no statistically significant difference in the comparison of standardized blood drug concentrations and the coefficient of variation of daily doses between the 2 groups(P＞0.05).Conclusion The tacrolimus administrating via feeding tubes scheme for lung transplantations based on the SPO model is scientific and practical,providing clinical references for the use of tacrolimus enteral medication after lung transplantation,in order to promote the standardization of tacrolimus enteral administration.

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.

Objective To observe the therapeutic effects and mechanism of Xiezhuo Qutong Formula on gout.Methods(1)Animal experiments:A hyperuricemia(HUA)model was established in SD rats using hypoxanthine combined with potassium oxonate,and an acute gouty arthritis(AGA)model was induced by monosodium urate.The efficacy and safety of Xiezhuo Qutong Formula in reducing serum uric acid levels and exerting anti-inflammatory effects were evaluated.(2)Network pharmacology:The main active components and potential targets of Xiezhuo Qutong Formula were collected,along with gout-related disease targets.The intersection of these targets yielded potential therapeutic targets.A protein-protein interaction(PPI)network was constructed,followed by Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results Xiezhuo Qutong Formula effectively reduced serum uric acid levels in HUA model rats without observed hepatorenal toxicity.It also decreased joint inflammation index,joint swelling degree,and inflammatory cytokine levels in AGA model rats.Network pharmacology analysis identified 156 overlapping targets between the drug and disease,among which TP53,STAT3,PIK3CA,BCL2,PIK3CD,PIK3CB,JUN,HDAC1,ESR1,and RELA may be key targets of Xiezhuo Qutong Formula in treating gout.Combined with GO and KEGG enrichment analyses,the main involved pathways include PI3K/AKT,JAK2/STAT3,and NF-κB signaling pathways.Conclusion Xiezhuo Qutong Formula exerts uric acid-lowering and anti-inflammatory effects in the treatment of gout,and its potential mechanism involves the PI3K/AKT,JAK2/STAT3,and NF-κB signaling pathways.