OBJECTIVE To evaluate the cost-effectiveness of anlotinib combined with penpulimab versus sorafenib as first- line treatment for unresectable hepatocellular carcinoma （uHCC） from the perspective of China’s healthcare system. METHODS Based on data from the APOLLO study， a partitioned survival model was established with a 21-day model cycle to simulate patient survival status over 10 years under anlotinib combined with penpulimab regimen or sorafenib monotherapy. Quality-adjusted life year （QALY） was used as the core evaluation parameter to assess the incremental cost-effectiveness ratio （ICER） of different treatment regimens. Using 3 times China’s per capita gross domestic product （GDP） in 2024 （287 247 yuan/QALY） as the willingness-to-pay （WTP） threshold， cost-utility analysis was performed to evaluate the cost-effectiveness of the treatment regimens. Sensitivity analysis was conducted to validate the robustness of the baseline analysis conclusion. Scenario analysis was performed to consider the impact of anlotinib and penpulimab assistance programs on the results； the price reduction of penpulimab to ensure the cost-effectiveness of the combination regimen was examined under varying WTP thresholds （specifically， 1， 2， and 3 times China’s per capita GDP in 2024）. RESULTS The baseline analysis revealed that the ICER of anlotinib combined with penpulimab regimen relative to the sorafenib regimen was 338 611.20 yuan/QALY， which exceeded the WTP threshold set in this study. Univariate sensitivity analysis indicated that the utility value of progression free survival and penpulimab price significantly influenced the baseline analysis results. Probabilistic sensitivity analysis validated the robustness of the baseline results. The results of scenario analysis indicated that when considering the assistance programs for anlotinib and penpulimab， the obtained ICER values were all below the WTP threshold set at 3 times China’s per capita GDP in 2024. When the price of penpulimab was reduced by 58%， 35%， and 13%， the ICER values were below the WTP threshold， which was 1， 2 and 3 times the per capita GDP of China in 2024， respectively. CONCLUSIONS From the perspective of China’s healthcare system， anlotinib combined with penpulimab regimen for first-line treatment of uHCC lacks cost-effectiveness compared to sorafenib regimen. However， this conclusion would be reversed if the anlotinib and penpulimab assistance programs are taken into account or if the price of penpulimab is reduced by more than 13% and above.

AIM:This study aims to identify how glutamine metabolism affects pulmonary hypertension-in-duced right heart remodeling under chronic hypoxia.METHODS:C57BL/6J mice were randomly divided into control(n=10)and hypoxia(n=10)groups.The hypoxia group was exposed to a hypobaric chamber simulating an altitude of approxi-mately 5,500 m for 28 days.Right ventricular systolic pressure(RVSP)was measured by right heart catheterization.The right ventricle(RV),left ventricle,and interventricular septum(LV+S)were weighed,and the RV/(LV+S)ratio was cal-culated as an index of right ventricular hypertrophy.Metabolomics analysis using UPLC-Orbitrap mass spectrometry was performed on right ventricular tissues.Hematoxylin and eosin staining and immunofluorescence were used to detect YAP and GLS1 co-localization and expression intensity in the myocardium.Expression levels of Yes-associated protein(YAP),phosphorylated YAP(p-YAP),and glutaminase 1(GLS1)from the Hippo pathway were measured by Western blot in mouse right ventricular tissue.RESULTS:The RVSP and RVHI values,along with myocardial fiber sizes and volumes,were significantly increased in the hypoxia group compared to controls(P<0.01).Glutamine metabolism metabolites in right ventricular tissue were significantly decreased(P<0.01).Immunofluorescence revealed decreased GLS1 and in-creased YAP response intensity in the hypoxia group myocardium(P<0.01).Notably,p-YAP protein and GLS1 expres-sion decreased under hypoxic conditions(P<0.05 or P<0.01,respectively).CONCLUSION:Chronic hypoxia exacer-bates pulmonary hypertension-induced right heart remodeling by inhibiting glutaminolysis through glutaminase 1 via the Hippo pathway in mice.

AIM:This study aims to identify how glutamine metabolism affects pulmonary hypertension-in-duced right heart remodeling under chronic hypoxia.METHODS:C57BL/6J mice were randomly divided into control(n=10)and hypoxia(n=10)groups.The hypoxia group was exposed to a hypobaric chamber simulating an altitude of approxi-mately 5,500 m for 28 days.Right ventricular systolic pressure(RVSP)was measured by right heart catheterization.The right ventricle(RV),left ventricle,and interventricular septum(LV+S)were weighed,and the RV/(LV+S)ratio was cal-culated as an index of right ventricular hypertrophy.Metabolomics analysis using UPLC-Orbitrap mass spectrometry was performed on right ventricular tissues.Hematoxylin and eosin staining and immunofluorescence were used to detect YAP and GLS1 co-localization and expression intensity in the myocardium.Expression levels of Yes-associated protein(YAP),phosphorylated YAP(p-YAP),and glutaminase 1(GLS1)from the Hippo pathway were measured by Western blot in mouse right ventricular tissue.RESULTS:The RVSP and RVHI values,along with myocardial fiber sizes and volumes,were significantly increased in the hypoxia group compared to controls(P<0.01).Glutamine metabolism metabolites in right ventricular tissue were significantly decreased(P<0.01).Immunofluorescence revealed decreased GLS1 and in-creased YAP response intensity in the hypoxia group myocardium(P<0.01).Notably,p-YAP protein and GLS1 expres-sion decreased under hypoxic conditions(P<0.05 or P<0.01,respectively).CONCLUSION:Chronic hypoxia exacer-bates pulmonary hypertension-induced right heart remodeling by inhibiting glutaminolysis through glutaminase 1 via the Hippo pathway in mice.

Objectives:To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention.Methods:Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted.Results:The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER.Conclusion:In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.

Objective: The association between school bullying and attention deficit hyperactivity disorder (ADHD) symptoms among students in primary schools and the moderating role of gender was explored to provide scientific evidence for the prevention and control of school bullying. Methods: A total of 4 764 students from 2 primary schools in Wuhan were selected using the convenience sampling method in March 2023. The Olweus Bully/Victim Questionnaire and Strengths and Difficulties Questionnaire were used. A Pearson χ 2 test was used to compare differences in school bullying rates among children with and without ADHD symptoms. Pearson correlation analysis and Process 3.3 were used to analyse the association between ADHD symptoms, and school bullying behaviour and the moderating role of gender. Results: The reported rate of bullying victims in primary schools was 24.2% and the rate of bullying perpetration was 3.8%. The rate of ADHD symptom detection among primary school students was 5.9%. ADHD symptoms were positively associated with bullying and bullying victim behaviour ( r =0.16, 0.27, P <0.01). Specifically, the association between ADHD symptoms and bullying behavior tended to be stronger among boys than girls ( β boy =0.17, t =11.13; β girl =0.07, t =4.11, P <0.01). Conclusions ADHD symptoms are an important factor influencing school bullying behaviors in students, and gender moderates the association. In the process of preventing and controlling school bullying, ADHD symptoms and gender differences should be emphasized and comprehensive interventions should be implemented.

Schizophrenia is a chronic psychiatric disorder with complex etiology and diverse clinical manifestations, whose pathogenesis and triggering factors remain incompletely understood. Numerous studies have demonstrated significant gender differences in the age of onset, clinical presentation, disease progression, treatment efficacy, and prognosis among patients with schizophrenia. These differences are largely attributed to variations in sex hormone levels, with estrogen emerging as a key focus of research. Some studies suggest that adjunctive estrogen therapy during schizophrenia treatment not only alleviates symptoms but also reduces the required dosage of antipsychotic medications. A systematic review of research on estrogen as an adjunctive treatment for schizophrenia may provide new perspectives and references for future therapeutic strategies.
Humans ; Schizophrenia/drug therapy* ; Estrogens/therapeutic use* ; Antipsychotic Agents/administration & dosage* ; Male ; Female ; Sex Characteristics ; Clinical Trials as Topic ; Estrogen Replacement Therapy

Objective:To compare the short-term and long-term efficacies and safety of short-term spinal cord stimulation (st-SCS) and pulsed radiofrequency (PRF) in treating zoster-associated pain (ZAP).Methods:A total of 208 ZAP patients who received treatment in Department of Pain Management, Provincial Hospital Affiliated to Shandong University from January 2019 to September 2021 were selected. They were divided into st-SCS group ( n=107) and PRF group ( n=101) according to different treatments. After differences of baseline data being balanced by 1∶1 propensity score matching between the two groups, scores of numerical rating scale (NRS), NRS remission rate, drug dosage, Pittsburgh Sleep Quality Index (PSQI) and complications of 86 patients from each 2 groups were compared and analyzed before surgery, 3 and 7 d after surgery, at discharge, and 1, 3, 6, 12 and 24 months after surgery. Results:NRS scores in st-SCS group and PRF group 3 and 7 d after surgery, at discharge, and 1, 3, 6, 12 and 24 months after surgery were significantly lower than those before surgery ( P<0.05). NRS scores in st-SCS group were significantly lower than those in PRF group at discharge and 1, 3, 6 and 12 months after surgery ( P<0.05). NRS remission rate in st-SCS group was significantly higher than that in PRF group at discharge and 1, 3, 6, 12 and 24 months after surgery, and total effective rate in st-SCS group was significantly higher than that in PRF group 1, 3, 6, and 12 months after surgery ( P<0.05). The pregabalin and gabapentin dosages in st-SCS group and PRF group 1, 3, 6, 12, and 24 months after surgery were significantly lower than those before surgery, and the gabapentin dosage in st-SCS group was significantly lower than that in PRF group 3 months after surgery ( P<0.05). PSQI in st-SCS group and PRF group at discharge and 6, 12 and 24 months after surgery was significantly decreased compared with that before surgery, and PSQI in st-SCS group at discharge and 6, 12 and 24 months after surgery was significantly decreased compared with that in PRF group ( P<0.05). No serious complications as spinal epidural hematoma or spinal nerve root and spinal cord injuries occurred in st-SCS group and PRF group. Conclusion:Both st-SCS and PRF can treat ZAP safely and effectively, but st-SCS has more advantages than PRF.

Objective:To explore the mediating effect between anxiety, depression and quality of life in adult patients with epilepsy.Methods:A total of 118 adult patients with epilepsy from Affiliated Hospital of Jining Medical University were investigated with the ruminative responses scale (RRS), neurological disorders depression inventory for epilepsy (NDDI-E), generalized anxiety disorder (GAD-7), quality of life scale for adult epilepsy patients (QOLIE-31 Chinese Version) and the self-made general situation questionnaire. Statistical analysis was performed by SPSS 20.0 software.Pearson correlation analysis was employed to assess the relationships between rumination, quality of life, anxiety, and depression scores. Hierarchical regression analysis was employed to examine the mediating effect.Results:Among the 118 participants, 5 (4.24%), 58 (49.15%), and 55 (46.61%) patients exhibited high (RRS=66-88), middle (RRS=44-65), and low (RRS=22-43) level of rumination, respectively. Pearson correlation analysis revealed significantly negative correlations between the scores of rumination and its dimensions and quality of life in patients with epilepsy ( r=-0.411--0.318, all P<0.05). Additionally, there were significantly positive correlations between the scores of rumination and its dimensions and anxiety scores ( r=0.524-0.676, all P<0.05) and depression scores ( r=0.566-0.767, all P<0.05). Hierarchical regression analysis demonstrated that rumination played partially mediating role in the relationship between anxiety and quality of life, as well as the relationship between depression and quality of life, with mediation effect values of -0.201 and -0.215, respectively. Conclusion:Anxiety and depression can affect the quality of life of adult patients with epilepsy through rumination.

Objective: To provide a largescale assessment the prevalence of poor vision in 2020 among children and adolescents in Wuhan City, Hubei province and to provide basis for healthy vision promotion. Methods: This crosssectional epidemiological study was conducted among 156 783 students, who lived in Wuhan during the COVID-19 period participated the vision screening through the online applet designed by Wuhan Center for Adolescent Poor Vision Prevetion and Control under the guidance of their guardians between June 19 and July 6, 2020. The demographic information and daily hours spent on various activities in the past week were investigated. The corresponding visual acuity data of students in 2019 before the COVID-19 outbreak was extracted from school vision monitoring records for each semester, which was measured by the experienced eye care professionals. Results: The detection rate of poor vision (51.04%) in 2020 was significantly higher than that in 2019(43.04%)( χ 2=68 944.95, P <0.01). After adjustment for covariates, the odds ratio and 95% confidence interval for poor vision were 1.17(1.13-1.20), 1.07(1.04-1.10), 0.67 (0.65-0.69) and 0.62(0.60-0.64) in students with online class time, recreational screen time, indoor and outdoor activity time in the highest tertile, compared with the lowest tertile groups. Conclusion Increased rate of poor vision among primary and secondary schoool students deserves further concern. It is necessary to strengthen intervention of eyesight protection. Policies and programs aimed at improving opportunities for physical activities and decreasing multiple screen behaviors should be given priority.

Objective:To understand the true experience and feelings of thestoma therapists on sense of career success, so as to provide a basis for enhancing their sense of career success.Methods:Using the qualitative research method, a semi-structured in-depth interview with 18 stoma therapists from different levels of medical institutions in Henan Province who have been certified for more than one year from August 2 to October 30, 2020. Nvivo12.0 software was used for data analysis, and the Colaizzi 7-step analysis method was used to refine the theme.Results:After repeated reading and analysis of the data, two themes of positive experience and negative experience of stoma therapists' true experience of career success were extracted.Conclusions:The specific policies for the professional development of specialist nurses should be further improved to reduce the negative experience in the career success of stoma therapists and avoid the loss of specialist nursing talents.