ObjectiveTo investigate the effect of honokiol on proliferation， apoptosis， migration， and invasion of gastric cancer cells and its underlying mechanistic. MethodsHuman gastric cancer cell lines HGC-27 and AGS were treated with Honokiol at concentrations of 0， 15， and 25 μmol/L. CCK-8 assays were conducted to determine the half maximal inhibitory concentration （IC₅₀） for both cell lines. Cell viability， proliferation， migration， and invasion capabilities were assessed using CCK-8， colony formation， wound healing， Transwell migration and Transwell invasion assays. Apoptosis rates were measured via flow cytometry. Western blot analysis examined proteins related to proliferation， apoptosis， migration， invasion， and the endoplasmic reticulum stress pathway ATF4-CHOP-TRIB3. ResultsCompared with the control group， treatment with 15 and 25 μmol/L Honokiol significantly reduced the proliferation， colony formation， migration， and invasion capabilities of the two gastric cancer cell lines， while significantly increasing the apoptosis rate （P<0.05）. Additionally， compared to the control group， the protein expression levels of neural cadherin（N-cadherin）， Vimentin， proliferating cell nuclear antigen（PCNA）， and B-cell lymphoma/leukemia-2 protein（Bcl-2）decreased in the two gastric cancer cell lines after treatment with 15 and 25 μmol/L Honokiol， while the protein expression levels of epithelial cadherin（E-cadherin）， Bcl-2-associated X protein（Bax）， activating transcription factor 4（ATF4）， endoplasmic reticulum stress-related protein（CHOP）， and tribbles homolog 3（TRIB3）increased（P<0.05）. ConclusionHonokiol promotes apoptosis and inhibits proliferation， migration， and invasion of gastric cancer HGC-27 and AGS cells by regulating the ERS signaling pathway ATF4/CHOP/TRIB3.

With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.

Objective: To investigate the association of special family structure and physical activity with psychological sub health among secondary vocational school students, so as to provide reference to inform mental health promotion in the population. Methods: From September to December 2024, a convenience sample was drawn from 16 schools including 5 141 secondary vocational school students across 8 provinces (municipalities) in China (Fujian, Chongqing, Guangdong, Guangxi, Hubei, Jiangxi, Shanghai, Zhejiang). A self developed questionnaire, Multidimensional Sub health Questionnaire of Adolescents and International Physical Activity Questionnaire Short Form were used to investigate and evaluate basic information, family structure, psychological sub health status and physical activity. Descriptive statistics and Logistic regression analysis were performed to explore relationships of special family structures and physical activity with psychological sub health in secondary vocational school students. Results: The detection rate of psychological sub health among secondary vocational school students was 11.0%. The reporting rates for secondary vocational school students who lost their father or lost their mother, whose parents divorced, whose parents remarried, and those from special family structures were 2.8%, 0.8%, 11.8%, 3.9%, and 14.7%, respectively. Moreover, the detection rates of psychological sub health and its sub dimensions significantly differed among secondary vocational school students grouped by family type (divorced parental families, remarried parental families and special family structures)( χ 2=5.90-22.67, all P <0.05). Binary Logistic regression indicated that maternal bereavement was associated with a higher risk of conduct problems [ AOR ( 95% CI )= 2.90(1.15-7.33)], and parental divorce was associated with a higher risk of psychological sub health ( AOR= 2.71 , 95%CI =1.04- 7.06 ) among secondary vocational school students (both P <0.05). Interaction analysis showed that both students with a special family structure and insufficient physical activity [ AOR (95% CI )=1.99(1.44-2.75)] and those with a non-special family structure and insufficient physical activity [ AOR (95% CI )=1.81(1.48-2.22)] were associated with increased risks of psychological sub health among secondary vocational school students (both P <0.01). Conclusion Special family structure and physical activity are associated with psychological sub health among secondary vocational school students; early identification and assessment based interventions for those with a special family structure should be strengthened, while school based physical activity should be implemented to increase physical activity levels,thereby reducing the risk of psychological sub health.

Objective: The efficacy of antidepressants is influenced by a combination of genetic, individual, and environmental factors. This study aimed to investigate the association between the miR-182 rs76481776 polymorphism and the response to antidepressant treatment in major depressive disorder (MDD) patients, and its underlying molecular mechanisms. Methods: This study enrolled 180 MDD patients and 180 healthy controls. The rs76481776 genotype was determined using TaqMan-based qPCR. The severity of depression and treatment response were assessed using the Hamilton Depression Rating Scale (HAMD). The expression of miR-182 and BDNF was measured using RT-qPCR. The regulatory relationship between miR-182 and BDNF was confirmed through a luciferase reporter gene assay. The correlation between miR-182 and BDNF expression was evaluated using the Pearson correlation coefficient. Results: The T allele of rs76481776 was a significant risk factor for MDD (OR = 2.182, 95% CI: 1.424−3.345, p ＜ 0.001) and was significantly associated with higher baseline scores on the HAMD. Moreover, individuals carrying the T allele (CT/TT genotype) exhibited a significantly poorer response to antidepressant treatment and a lower remission rate within 12 months compared to those with the CC genotype (p ＜ 0.05). Mechanistically, miR-182 was highly expressed in patients with MDD (p ＜ 0.05), and its expression was even higher in T allele carriers (p ＜ 0.05). miR-182 could directly target and suppress BDNF, leading to decreased BDNF expression in MDD patients, and its expression was significantly and inversely correlated with BDNF expression. Conclusion The T allele of rs76481776 diminished the therapeutic efficacy of antidepressants by up-regulating miR-182 expression and subsequently suppressing BDNF expression.

Hepatic angiomyolipoma is a rare benign tumor that often mimics hepatocellular carcinoma on imaging. Here, we report a rare case of hepatic angiomyolipoma with extensive hemorrhagic degeneration, resulting in a large hemorrhagic component that mimicked a complicated cystic neoplasm. A 43-year-old woman presented with mild abdominal distension, and imaging revealed a 16-cm multiloculated cystic mass in the left hepatic lobe. Computed tomography revealed a thick, enhancing wall and septa with hyperattenuating internal fluid. On gadoxetic acid-enhanced magnetic resonance imaging, arterial enhancement was observed along the thick wall, and a subtle opposedphase signal drop indicated a small fat component that was initially missed. Laparoscopic left lobectomy was performed under suspicion of a malignant cystic neoplasm. Histopathological examination revealed an angiomyolipoma composed of thick-walled vessels, spindle-shaped muscle bundles, and scant adipocytes, with human melanoma black 45 positivity and absence of an epithelial lining, consistent with hemorrhagic degeneration. This case highlights how hemorrhagic degeneration can pose a significant diagnostic challenge by masking the typical features of hepatic angiomyolipoma, leading to diagnostic confusion with complicated cystic tumors.

To summarize the clinical characteristics and genetic mutation spectrum of patients with SELENON-related myopathy(SELENON-RM), in order to improve awareness among physicians.

Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Objective To explore the predictive role of pathological risk score of gastric cancer (PRS_GC) in the prognosis of gastric cancer patients, and to further investigate the correlation between PRS_GC and tumor biological behavior. Methods Clinicopathological data were retrospectively collected from 1 120 patients with gastric cancer who underwent surgical resection at Zhongshan Hospital, Fudan University, between April 2006 and November 2019. PRS_GC was calculated using the previously established DeepRisk model, and patients were divided into high and low PRS_GC groups (560 patients per group) based on the median PRS_GC value. The proportions and spatial distances of immune cell subsets in gastric cancer tissues were assessed between the two groups. Data from stomach adenocarcinoma samples in The Cancer Genome Atlas was integrated to analyze PRS_GC-associated genetic mutations and signaling pathways. Results The survival rate of the high PRS_GC group was lower than that of the low PRS_GC group, and the recurrence rate was higher than that of the low PRS_GC group (P<0.000 1). Compared with the low-PRS_GC group, the high-PRS_GC group exhibited increased infiltration of regulatory T cells (Tregs) and neutrophils within the tumor region (P＜0.05), while the infiltration levels of natural killer T cells and cytotoxic T cells were markedly decreased (P＜0.05). Spatial analysis revealed that a shortened spatial distance between CD4⁺ T cells and Tregs was closely associated with poor prognosis in the high-PRS_GC group (P＝0.03). Furthermore, in the high-PRS_GC group, the number of TIM3⁺ cells showed a positive correlation with the infiltration levels of Tregs (r＝0.69, P＝0.01), CD8⁺ T cells (r＝0.61, P＝0.04), and CD4⁺ T cells (r＝0.67, P＝0.02). Gene set enrichment analysis indicated that a high PRS_GC was associated with the activation of pathways related to actin cytoskeleton regulation, the cGMP-PKG pathway, the Hippo pathway, and tumor proteoglycans. Conclusion A high PRS_GC is associated with an immunosuppressive tumor microenvironment, as well as tumor invasion and metastasis. It effectively predicts the prognosis of patients with gastric cancer and, by doing so, provides a potential theoretical basis for developing individualized strategies that combine targeted therapy with immunotherapy.

Objective To explore the association between serum uric acid levels and the cumulative incidence risk of atrial fibrillation, and to evaluate the predictive value of different uric acid levels for the onset of atrial fibrillation. Methods A retrospective selection of 451 879 participants from the large-scale prospective epidemiological cohort UK Biobank, aged 40-69 years, all completed a median follow-up of 13.6 years. Participants were divided into groups based on the interquartile range of serum uric acid levels (Q1–Q4) related to gender and whether they were diagnosed with hyperuricemia. Cox proportional hazards model, sensitivity analysis, and other methods were used to compare baseline data and atrial fibrillation incidence during follow-up among each group of participants. Results Individuals with higher baseline uric acid levels tended to be older, more obese, and had lower education levels and a history of cancer, along with significantly higher levels of triglyceride, low-density lipoprotein cholesterol, and C-reactive protein, but lower high-density lipoprotein cholesterol levels (P<0.001); the highest uric acid group showed the highest diabetes prevalence (6.49%). Participants with higher serum uric acid levels (log-rank P<0.05) or diagnosed with hyperuricemia had significantly higher incidence of atrial fibrillation (P<0.001). After adjusting for potential confounders, compared to Q1 uric acid level group, the Q4 level was associated with a 20% increased risk of atrial fibrillation (HR=1.20, 95%CI 1.16–1.25). Each 74.7 μmol/L increase in uric acid level was associated with a 9% increased incidence risk of atrial fibrillation (HR=1.09, 95%CI 1.08–1.11). Individuals with hyperuricemia had a 20% increased incidence risk of atrial fibrillation (HR=1.20, 95%CI 1.17–1.24). A nonlinear association was observed between uric acid levels and the incidence risk of atrial fibrillation (P for nonlinearity <0.01). Subgroup analysis indicated significant heterogeneity of the risk effect across subgroups, with a higher risk associated with hyperuricemia in females. Conclusions Elevated blood uric acid levels may increase the cumulative risk of atrial fibrillation, and this pathogenic effect is significantly correlated with age, race, cancer history, body mass index, and sex.