Background and aims As a ferroptosis inducer, sorafenib, a first-line treatment for hepatocellular carcinoma (HCC), has a significant antitumor effect. Nonetheless, HCC patients frequently develop sorafenib resistance. Here, we investigated the impacts of progestagen-associated endometrial protein (PAEP), which controls sorafenib resistance and tumorigenesis in HCC. Furthermore, we investigated the function of PAEP and the underlying molecular mechanisms that cause HCC ferroptosis when sorafenib is applied. Methods Western blot analysis, cell proliferation, colony formation and animal experiments were performed to investigate the function of PAEP in sorafenib resistance and tumorigenesis in HCC. We detected the levels of reactive oxygen species, iron, and malondialdehyde and preformed transmission electron microscopy to investigate the relationship between PAEP and ferroptosis. Co-immunoprecipitation (co-IP) assay was performed to investigate the underlying molecular mechanisms of PAEP that cause HCC ferroptosis. Results PAEP was significantly overexpressed in HCC tissues, and this was associated with a poor clinical prognosis. PAEP silencing dramatically reduced HCC cells’ malignant phenotype. We found that sorafenib-induced ferroptosis was more sensitive to HCC cells with PAEP knockdown. Furthermore, the orthotopic cell line-derived xenograft mouse model results showed that sorafenib sensitivity can be effectively increased in vivo by PAEP knockdown. We determined that transferrin (TF) was a PAEP target using the String database, and we further supported this finding with Co-IP analysis. Additionally, on sorafenib-induced ferroptosis in HCC cells, TF partially reversed the effects of PAEP knockdown. Conclusions Our research indicates that PAEP may be a potential biomarker for predicting sorafenib resistance in HCC and disruption of PAEP expression may be a potential cancer-directed therapeutic option for HCC.

OBJECTIVE To evaluate the cost-utility of disitamab vedotin （DV） combined with toripalimab versus platinum-containing chemotherapy as first-line therapy for locally advanced or metastatic urothelial carcinoma（UC） with human epidermal growth factor receptor 2 （HER2） expression from the perspective of China’s health-care system.METHODS A cost-utility analysis was performed. A three-state partitioned survival model was constructed based on the RC48-C016 trial with a 1-week cycle length. The long-term health benefits [quality-adjusted life years（QALYs）] and costs of disitamab vedotin combined with toripalimab versus platinum-containing chemotherapy as first-line therapy for locally advanced or metastatic UC with HER2 expression were simulated. The simulation time horizon was set to 15 years， and the discount rate was 4.5%. The willingness-to-pay （WTP） threshold was defined as twice China’s per capita gross domestic product（GDP） in 2025 （199 330 yuan/QALY）. The incremental cost-effectiveness ratio （ICER） between the two groups was compared， and one-way sensitivity analysis and probabilistic sensitivity analysis were conducted.RESULTS Compared with platinum-containing chemotherapy regimen， the DV plus toripalimab regimen yielded an additional 1.01 QALYs with an incremental cost of 183 224.45 yuan， and the ICER was 181 728.15 yuan/QALY， which was below the WTP threshold. At the current threshold， the probability that the DV combination regimen had a cost-utility advantage was 79.9%.CONCLUSIONS Taking twice China’s per capita GDP in 2025 as the WTP threshold， DV combined with toripalimab exhibits a cost-utility advantage over platinum-containing chemotherapy as first-line treatment for HER2-expressing locally advanced or metastatic urothelial carcinoma.

Objective: To investigate the annual trend and influencing factors of screening myopia prevalence among children and adolescents in Tianhe District, Guangzhou from 2021 to 2024, so as to provide a scientific basis for optimizing targeted and precise regional myopia prevention and control strategies. Methods: From 2021 to 2024, a stratified cluster random sampling method was adopted to recruit 10 132 students ranging from senior kindergarten to senior high school from fixed monitoring sites for myopia screening. Additionally, a questionnaire survey on myopia related factors was administered to 7 115 students in grade 4 and above. Generalized estimating equation (GEE) models were used to analyze the annual changing trends and interaction effects, and mixed effects models were performed for sensitivity analysis. Results: The screening myopia prevalence among children and adolescents in Tianhe District from 2021 to 2024 was 58.9%, 57.3%, 56.8%, and 54.7%, respectively, and showed a statistically significant difference ( χ 2=9.06, P <0.05). The prevalence rates among senior kindergarten, primary school, junior high school, regular senior high school, and vocational high school students were 8.7%, 40.7%, 74.3%, 86.7%, and 75.6%, respectively （χ 2= 2 493.11， P <0.05). The prevalence was significantly higher in female students (60.9%) than in male students (53.3%) ( χ 2= 59.22 , P <0.05). GEE analysis showed that male students ( OR =0.59), primary school students ( OR =0.45), those who spent less than 6 hours per day sitting indoors ( OR =0.78), and those who used electronic devices for no more than 2 hours per day ( OR = 0.25 ) all had lower risks of screening myopia (all P <0.05). Students in regular high schools ( OR =2.01), those who engaged in activities inside the classroom during breaks ( OR =1.55), those who engaged in activities outside the classroom but within the school building during breaks ( OR = 1.46), those who never or only occasionally maintained proper reading and writing postures ( OR =1.32), those with less than 2 hours of daily outdoor activity ( OR =1.86), those with both parents being myopic ( OR =2.48), those with only the father being myopic ( OR =1.50), and those with only the mother being myopic ( OR =1.63) all had higher risks of screening detected myopia (all P ＜0.05). Interaction effect analysis revealed annual heterogeneity in the effects of daily outdoor activity time ≥2 h and daily electronic device use time >2 h on screening myopia prevalence (all P ＜0.05). Conclusions The screening myopia prevalence among children and adolescents in Tianhe District, Guangzhou, demonstrates a continuous downward trend. The impacts of daily outdoor activity duration and electronic device usage time on screening myopia exhibit annual heterogeneity. Dynamic and targeted myopia prevention and control strategies should be formulated in accordance with regional demographic features and environmental changes.

Objective: To examine the mediating effect of frailty on social isolation and cognitive function among the elderly. Methods: Demographic information, smoking, alcohol consumption and cognitive function of the elderly at ages of 60 years and older were collected from the China Health and Retirement Longitudinal Study 2020. Social isolation and frailty were evaluated using social isolation index and frailty index, respectively. The mediating effect of frailty on social isolation and cognitive function was analyzed using the Process program, and the significance of the mediating role was tested using the Bootstrap test. Results: A total of 2 822 individuals were enrolled, including 1 483 males (52.55%) and 1 339 females (47.45%). There were 2 497 (88.48%) and 325 (11.52%) individuals at ages of 60-<75 years and ≥75 years, respectively. The median cognitive function score was 14 (interquartile range, 16) points. There were 432 cases with social isolation (15.31%), with a median social isolation index of 10 (interquartile range, 5) points. The median frailty index was 0.11 (interquartile range, 0.15). There were 1 111 individuals without frailty, accounting for 39.37%; 1 214 individuals with pre-frailty, accounting for 43.02%; and 497 individuals with frailty, accounting for 17.61%. Mediating effect analysis showed that social isolation affected cognitive function directly and negatively with the effect value of -0.773 (95%CI: -0.899 to -0.647), and also affected cognitive function by frailty indirectly and negatively with the effect value of -0.147 (95%CI: -0.188 to -0.110), with the mediating effect contributed 15.98% of the total effect. Conclusion Frailty can directly or indirectly affect cognitive function among elderly through social isolation.

In recent years, with the endless emergence of meibomian gland dysfunction(MGD)diagnostic equipment, rich treatment methods, and in-depth clinical and basic research on MGD at home and abroad, the understanding of MGD has entered a new stage. MGD-related dry eye is considered to be the main cause of lipid abnormal dry eye, and its occurrence and development is a chronic and multi-factorial pathological process. This article reviews the pathogenesis, imaging analysis and clinical treatment progress of MGD-related dry eye, in order to provide scientific evidence and ideas for clinical diagnosis and therapy of MGD-related dry eye.

Objective To discuss the effect of interleukin-17A(IL-17A)and transforming growth factor-β1(TGF-β1)on the benign tracheal stenosis after tracheal injury in experimental dogs.Methods The trachea stenosis model of healthy Beagle dogs was established by burning the middle part of trachea with electric snare under bronchoscopy guidance.A total of 21 dogs were divided into normal group(n=3,receiving normal feeding),molding group(n=12,after airway modeling every 3 dogs were sacrificed each week for 4 weeks),IL-17A suppression group(n=3,receiving Secukinumab after airway modeling),and IL-17A inhibitor+TGF-β1 inhibitor group(n=3,receiving Secukinumab and SB43154 after airway modeling).Bronchoscopy and CT scan were performed once a week,and the stenosis degree was calculated.RT-qPCR,immunohistochemistry,and HE staining of the obtained tracheal tissues were performed.Results Within 1-4 weeks after molding,in module-making dogs the degree of stenosis of the injured trachea gradually increased,and the expressions of ECM-related proteins,TGF-β1 and IL-17A were up-regulated.After treatment with IL-17A inhibitors,the inflammatory infiltration and granulation tissue hyperplasia were reduced and the early tracheal stenosis was improved(P＜0.05).The combination use of IL-17A inhibitor and TGF-β1 inhibitor had a better remission effect(P＜0.05).Conclusion IL-17A and TGF-β1 may synergistically affect the formation of tracheal stenosis.

Objective West Nile virus(WNV)is one of the most common mosquito-borne zoonotic viruses worldwide,with unique transmission dynamics and varied hosts.Lots of ecological and host factors have been reported to influence the host adaptation and transmission of WNVs,however,general genomic features of WNVs are less focused,except for some exact host-specific genotypes at molecular level.Artificial intelligence that analyzes genome composition characteristics currently shows significant advantages in identifying and predicting viral host adaptability.This research aimed to establish a convolutional neural network(CNN)model to predict the host adaptability of WNVs based on general genomic features.Methods Presently available WNV gene sequences were embedded for their genomic features with an embedding approach of dinucleotide composition representation(DCR).And DCR-based distribution difference of WNV samples among various hosts was performed with unsupervised learning methods.Then a classification model was built with a convolutional neural network(CNN)framework based on genomic DCR to evaluate the adaptation of the WNVs from birds,mammals and mosquitos.Additionally,host-specific amino acids in WNV proteins were inferred via Bayes method.Results DCR features could effectively distinguish host-specific WNVs.The trained CNN model predicted accurately mammalian susceptible WNVs from avian susceptible WNVs,however,much less accurately for mosquito/mammalian WNVs.Such predicted host adaptation was interpreted as host specified significance of biased amino acid distribution on the bayes-inferred sites in WNV proteins,implying a possible high significance of these sites for WNV adaptive phenotypes.Conclusions Genomic compositional features of WNVs are host-specific,and such genomic bias facilitates predicting the adaptation of WNVs to avian or mammalian hosts via deep learning methods.DCR-based decomposition is helpful to recognize the high risk of infecting mammals of WNVs.The present study provides a general knowledge of genomic features contributing to host adaptation to WNVs.

Objective To explore the latent classes and influencing factors of blood glucose trajectories after transplantation in lung transplantation patients,and provide references for identifying high-risk population of post-transplant diabetes mellitus.Methods 122 lung transplantation patients who were hospitalized in a tertiary A general hospital in Hangzhou from January 2022 to March 2023 were selected conveniently as survey subjects.Socio-demographic and disease-related data were collected,and fasting plasma glucose at 1 week before surgery(T0),1 week after surgery(T1),1 month after surgery(T2),3 months after surgery(T3),6 months after surgery(T4),1 year after surgery(T5)were collected.Growth mixture model was used to identify categories of blood glucose trajectories after lung transplantation,and binary Logistic regression analysis was used to explore the influencing factors.Results A total of 109 lung transplantation patients were enrolled in the study,and 2 latent classes of blood glucose trajectories were identified:high risk(23.85％)and low risk(76.15％)of post-transplant diabetes mellitus.BMI,drinking history,afternoon blood glucose and tacrolimus trough concentration were the influencing factors of latent classes of blood glucose trajectories after lung transplantation(all P＜0.05).Conclusion There are 2 latent classes of blood glucose trajectories after lung transplantation,namely high risk and low risk of post-transplant diabetes mellitus.Medical staff should pay attention to diabetes screening and assessment of lung transplantation patients who are overweight or obese,have a drinking history before transplantation,have high afternoon blood glucose in early stage of transplantation and have high tacrolimus trough concentration in stable stage of transplantation,so as to formulate a comprehensive and individualized blood glucose management program.

Purpose To investigate the clinical,imaging,and pathological features of Kikuchi-Fujimoto disease(KFD).Methods A retrospective analysis was conducted on 123 pathologically confirmed KFD cases.Clinical and imaging data were collected,and histopathological features were evaluated using HE staining,immunohistochemistry,in situ hybridization for EBER,and molecular analyses(TCR/Ig gene rearrangements by PCR with capillary electro-phoresis).Results Among the 123 patients,the male-to-female ratio was 1∶2,with a median age of 30 years.All patients presented with lymphadenopathy.Among 30 hospitalized patients,63.3％(19/30)had fever,and 23.3％(7/30)had concurrent autoimmune diseases.Of the 12 patients who underwent PET-CT,91.7％(11/12)were sus-pected of malignancy,prompting biopsy recommendations.Among 47 consultation cases,27.7％(13/47)were ini-tially misdiagnosed as lymphoma.Histopathological examination revealed proliferative,necrotic,and xanthomatous phases,which coexisted or occurred independently.The proliferative phase was characterized by atypical lymphocytes and histiocytes,the necrotic phase by abundant eosinophilic fibrin deposits and nuclear debris,and the xanthomatous phase by clusters of foam-like histiocytes.Immunohistochemically analyses revealed that atypical lymphocytes were neg-ative for CD20,CD4,and CD56 but positive for CD3,CD8,TIA1,Granzyme B,and Perforin.Histiocytes expressed CD68,CD163,and MPO,while CD123-positive plasmacytoid dendritic cells were predominantly located around the le-sions and blood vessels.EBER was positive in individual cells in 4 cases.TCR gene rearrangement was positive in 2 cases and suspected positive in 3 cases,while Ig rearrangement was positive and suspected positive in 1 case each.Conclusion KFD exhibits clinical,imaging,and pathological features that can mimic lymphoma,highlighting the im-portance of accurate diagnosis to avoid misdiagnosis and inappropriate treatment.

This paper summarizes the nursing experience of a pregnant woman with congenital heart disease who developed pulmonary artery hypertension crisis after cesarean section.Nursing key points:monitoring and management of inhaled nitric oxide therapy to reduce pulmonary hypertension;providing sequential respiratory support care and dynamically adjusting oxygen therapy regimen;precise volume regulation and alertness to serious complications;optimizing puerperal supervision strategy to reduce the risk of infection;preventing and controlling stress bleeding and implementing a stepped dietary management strategy;implementing phased rehabilitation training to accelerate the recovery process;carrying out personalized psychological care and health education.With comprehensive nursing care,the patient recovered well and was discharged smoothly after an 18-day hospital stay.