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.

Root caries is a prevalent chronic oral disease with an average global prevalence of 41.5%, characterized by high incidence, low rate of treatment, and high rate of retreatment. Root caries is primarily caused by core microbiome-induced dysbiosis and has multiple risk factors, including gingival recession, root surface exposure, and salivary dysfunction. The traditional preventive measures and treatments such as fluoride, mineralizing agents, and restorative materials, are unable to restore or maintain oral microecological homeostasis. Recent studies have demonstrated that probiotics, prebiotics, synbiotics, and antimicrobial peptides may prevent and treat root caries by reversing dysbiosis. In addition, these biotherapeutics can reduce acid production by acidiferous bacteria, promote alkali production (hydrogen peroxide and ammonia) by alkali-producing bacteria, inhibit biofilm formation, decrease extracellular polysaccharide production, and suppress microbial adhesion and aggregation. It is expected to play an important role in the prevention and control of root caries. This article aims to review oral probiotics (Streptococcus oligofermentans, Streptococcus oralis subsp. dentisani, and Streptococcus salivarius), prebiotics (arginine, nitrates, and synthetic compounds), synbiotics, and antimicrobial peptides (gallic acid-polyphemusin I and LH12) to provide evidence and guidance for root caries management through microecological modulation.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Objective This study aims to analyze the characteristics of inpatients in the cardiovascular department of a tertiary hospital following the chest-pain-center accreditation,and provide guidance for the prevention and treatment of cardiovas-cular diseases.Methods A retrospective descriptive epidemiological approach was adopted to analyze the data of 2115 inpatients at the department of cardiovascular medicine in a tertiary hospital from 2022 to 2024 following chest pain center accreditation.Re-sults The number of the inpatients in 2022,2023,and 2024 was 582 cases(27.52％),684 cases(32.34％),and 849 cases(40.14％),respectively,with the total rising year by year.The proportion of males was higher than that of females,with a male-to-female sex ratio of 1.45∶1.The group aged 40 to 79 years accounted for the highest percentage(80.90％).The top three diseases categorized by percentage were coronary heart disease(754 cases,35.64％),hypertension(479 cases,22.64％),and arrhythmia(167 cases,7.89％).Epidemiological characterization exhibited a statistically significant difference in the disease composition of hospitalized cardiovascular patients in years,genders,ages,and seasons(x2=155.40,36.591,900.597,856.659,P＜0.05).Specific classification showed significant differences in hypertension and other conditions by age(P＜0.05);coronary heart disease and valvular heart disease by gender(P＜0.05);and significant differences across ages in coronary heart disease,hypertension,heart failure,pericardial disease,peripheral vascular disease,congenital heart disease,and others(all P＜0.05).Seasonal differences in coronary heart disease,hypertension,arrhythmia,cardiomyopathy,valvular heart disease,heart failure,pericardial disease,and others were also statistically significant(P＜0.05).Conclusion Against the backdrop of chest pain center accreditation in our hospital,inpatients in our department now demonstrate extinct demographic profiles and seasonal patterns among hospitalized cardiovascular patients.We should strengthen the prevention and treatment of coronary heart disease and hypertension,and establish a comprehensive prevention and control system based on these epidemio-logical characteristics.

Objective The study aimed to compare the efficacy and safety of tislelizumab combined with chemotherapy versus pembrolizumab combined with chemotherapy as first-line treatments for advanced lung squa-mous cell carcinoma.Methods We retrospectively reviewed and analyzed the medical records of 116 patients with advanced lung squamous cell carcinoma treated with first-line chemotherapy plus tislelizumab or pembrolizumab in Guangzhou Chest Hospital from September 2020 to April 2024.We focused on analysis of time to treatment failure(TTF)and objective response rate(ORR)as well as disease control rate(DCR)and treatment-related adverse events(TRAEs).Results At a median follow up of 19.7 monyhs,the median TTF was 9.7 months in the tislelizumab group and 7.7 months in the pembrolizumab group(P<0.05).In addition,the ORR in the tislelizumab group was significantly higher than that in the pembrolizumab group(77.6%vs.60.3%,P<0.05),with DCRs of 93.1%and 87.9%,respectively(P=0.342).Regarding safety,the proportions of grade 3 or higher TRAEs and any-grade TRAEs were comparable between the two groups:29.3%and 81.0%in the tislelizumab group,and 32.8%and 87.9%in the pembrolizumab group,respectively.The most common TRAEs in both groups were hematological toxicities.Conclusions Tislelizumab plus chemotherapy demonstrated better efficacy and safety compared to pembrolizumab with chemotherapy as first-line treatment for Chinese patients with advanced lung squamous cell carcinoma.