ObjectiveTo explore the relationship between negative life events and depression severity in adolescent patients with depressive disorder， as well as the chain mediating role of insomnia symptoms and quality of life. Methods374 outpatient patients and hospitalized patients with adolescent depressive disorders were enrolled. The Adolescent Life Event Scale （ASLEC）， the Insomnia Severity Index （ISI）， the World Health Organization Quality of Life Questionnaire Short Form （WHOQOL-BREF）， and the Center for Epidemiology Depression Scale （CES-D） were used to evaluate the negative life event situation， insomnia symptoms， quality of life level and depression severity of the subjects， respectively. In addition， the PROCESS 4.0 macroprogram was used to analyze the chain mediating effect of insomnia symptoms and quality of life between negative life events and depression severity in patients with adolescent depressive disorder. ResultsThe results of correlation analysis showed that there was a significant correlation between negative life events and insomnia symptoms， quality of life， and depression severity （all P<0.05）. In addition， the results of chain mediation showed that negative life events had a significant direct effect on depression severity， with an effect size of 0.12 （P<0.001）. Insomnia symptoms and quality of life played a mediating role in the relationship between negative life events and depression severity in patients with adolescent depressive disorders， with indirect effect sizes of 0.062 （95%CI： 0.040-0.087） and 0.091 （95%CI： 0.059-0.123）， respectively. It could also play a chain mediation role， and the effect size was 0.039 （95%CI： 0.024-0.057）. ConclusionNegative life events experienced by patients with adolescent depressive disorder not only directly affect the severity of depressive symptoms， but may also indirectly exacerbate depression through insomnia symptoms and quality of life.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

OBJECTIVE To investigate the efficacy and safety of omadacycline in the treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia （MUMPP） in children. METHODS A retrospective study was conducted on children aged 1-18 years old with MUMPP who were hospitalized in the Department of Pediatrics， the First Affiliated Hospital of Xinjiang Medical University from January 2022 to June 2025. According to the selection of secondary antibiotics after 72 h of initial treatment with macrolides， they were divided into the omadacycline group and the doxycycline group. Based on conventional treatment， children in the omadacycline group were given intravenous infusion of 2.4 mg/kg （once daily） of omadacycline tosylate， while children in the doxycycline group were given oral doxycycline hydrochloride tablets at 2 mg/kg （twice daily）. The efficacy and safety were compared between the two groups of pediatric patients. Univariate analysis and multivariate Logistic regression analysis were performed on clinical efficacy， and subgroup analysis along with multiple sensitivity analyses were conducted to verify the robustness of the conclusions. RESULTS A total of 284 children with MUMPP were included in this study， with 142 in the omadacycline group and 142 in the doxycycline group. In terms of efficacy， although the hospitalization time of children in the omadacycline group was longer than that in the doxycycline group （ P ＜0.05）， the lung lesion absorption rate and clinical efficacy were significantly higher or better than those in the doxycycline group （ P ＜0.05）. The results of multivariate Logistic regression analysis showed that medication （OR＝5.300， 95%CI： 2.526-11.123）， length of hospital stay （OR＝1.348， 95%CI： 1.167-1.556）， and medication duration （OR＝1.422， 95%CI： 1.169-1.729） were influencing factors of clinical efficacy （ P ＜0.05）. The subgroup analysis results showed that the clinical efficacy of omadacycline was significantly better than that of doxycycline in all subgroups （ P ＜0.05）. The results of multiple sensitivity analysis showed that the regression coefficients B of the four models （gradually adjust variables） before and after inverse probability of treatment weighting were significantly greater than 1 （ P ＜0.05）. In terms of safety， there was no statistically significant difference in the inci dence of adverse drug reactions between the two groups of patients （ χ 2 ＝0.447， P ＝0.504）. CONCLUSIONS In the case of hospitalization and prolonged medication， the efficacy of omadacycline in treating childhood MUMPP is superior to that of doxycycline， and its safety is good.

Intravitreal anti-vascular endothelial growth factor(anti-VEGF)therapy has been widely used, but the variability in its therapeutic efficacy limits individualized treatment. In recent years, the application of artificial intelligence(AI)has opened up new avenues for personalized treatment response prediction, and its core branches include machine learning(ML)and deep learning(DL). This review systematically retrieved and analyzed 41 relevant studies published up to April 2025. Comprehensive analysis reveals that AI predictive models are evolving from forecasting single endpoints(such as visual acuity or central retinal thickness)to integrating multi-dimensional endpoints(encompassing anatomical, functional, and treatment demand parameters)and generating predictive imaging outputs. In terms of technical approaches, DL models(28 studies, accounting for 68.3%)dominate this field due to their robust image interpretation capabilities, while ML models(10 studies, 24.4%)retain significant value in the analysis of structured clinical data. Cross-disease comparisons indicate that research efforts are most concentrated on age-related macular degeneration(ARMD)and diabetic macular edema(DME), with shared conceptual frameworks for model construction, yet distinct anatomical and functional indicators are prioritized for each disease. Currently, the field confronts several key challenges, including insufficient prospective clinical validation, limited model interpretability(the “black box problem”), and a scarcity of high-quality multi-center datasets. Moving forward, it is imperative to advance real-world validation and develop explainable AI techniques to expedite the clinical translation of these predictive models.

Zoledronic acid (ZA), a nitrogen-containing bisphosphonate with established clinical utility in osteoporosis management, exhibits emerging antitumor potential in estrogen receptor-positive breast cancer. However, the molecular mechanisms underlying its nonapoptotic anticancer effects remain poorly characterized. This study revealed that ZA induced ferroptosis in ER+ breast cancer cells through dual suppression of cystine-glutamate antiporter SLC7A11 and glutathione peroxidase 4 (GPX4), key repressors of ferroptosis. Pharmacological inhibition of ferroptosis using Ferrostatin-1 significantly attenuated ZA-induced cytotoxicity, while combinatorial treatment with the GPX4 inhibitor RSL3 synergistically enhanced lipid peroxidation and cell death. Mechanistically, ZA activated the Hippo-YAP signaling pathway, promoting YAP phosphorylation, proteasomal degradation, and cytoplasmic retention, thereby silencing SLC7A11 and GPX4. We established a novel metabolic vulnerability in hormone-responsive malignancies.These findings position ZA as a bifunctional ferroptosis inducer in ER+ breast cancer, offering a promising strategy to overcome endocrine resistance.

Radiation-induced lung injury is a prevalent side effect of radiotherapy for chest cancer. The "three phases and three methods "is an innovative theory based on the evolution of the core pathogenesis of radiation-induced lung injury. Its formation also considers the understanding of radiation-induced lung injury by ancient and modern medical practitioners, pathological characteristics, clinical manifestations, and the development patterns of radiation-induced lung injury. The "three phases and three methods" refers to the three phases of the course and the three treatment methods. The core pathogenesis of radiation-induced lung injury from the beginning, middle and late stages is heat toxicity, yin deficiency, and blood stasis. Therefore, the course of radiation-induced lung injury is divided into three phases: blazing heat toxin, yin deficiency and heat accumulation, and static blood obstruction. The method of clearing the lung and resolving toxins, enriching yin and venting heat, invigorating blood and dissolving stasis are used respectively. Traditional Chinese medicines commonly used in each phase include Flos Lonicerae, Atrina Glass, heartleaf houttuynia herb, Radix Ophiopogonis, American Ginseng, Forsythiae Fructus, Radix Salviae Miltiorrhizae, Rhizoma Ligustici chuanxiong, Scorpio, etc. This article presents the theoretical origins of the "three phases and three methods" concept by reviewing of ancient literature, inheriting experience, and summarizing disease pathogenesis, as well as elaborating on the academic connotations of the "three phases and three methods". The scientific validity of the "three phases and three methods" is verified by literature, clinical, and basic research. The "three phases and three methods" interprets the core characteristics of each stage of radiation-induced lung injury, improves the traditional Chinese medicine prevention and treatment system for radiation-induced lung injury, and provides theoretical basis for achieving complete process management.

China is currently in an accelerated stage of population aging, and brain diseases pose a significant threat to the health of the elderly. " Preventing brain aging and maintaining brain health" has become a high-level goal of healthy aging. During the process of aging, the physiological and psychological states of elderly people change, making them prone to nervousness and exhaustion, which can disturb the brain spirit, damage the brain collaterals, and severely endanger brain health. Starting from the holistic view of cultivating both body and spirit in traditional Chinese medicine, based on the physical and mental characteristics of the elderly, this paper applies the concept and method of " relaxation and tranquility" in the protection of elderly brain health, focusing on maintaining relaxation and tranquility in both physical and mental aspects. Specific measures include emphasizing subjective consciousness, relaxing the heart and calming down; utilizing the daoyin method, relaxing the body and calming down, combining relaxation and tranquility, cultivating both body and spirit to prevent diseases and protect the brain, which enables the elderly to have a healthy mind and body, a sense of happiness and fulfillment, and to age gracefully. Simultaneously, advocating for tranquility is also called " respect" for relaxation, following nature to understand constant changes, and improving one′s ability to think positively in old age, in order to expand ideas for the protection of elderly brain health.

Objective:To investigate the characteristics of fatty acid metabolism in the hepatic steatosis (HS) population and to explore the role of inflammation in the relationship between fatty acid metabolism and HS.Methods:A total of 3 112 subjects from the 2011–2014 National Health and Nutrition Examination Survey (NHANES) database were included in this retrospective study, among whom 1 552 were in the HS group (weighted percentage: 49.87%) and 1 560 in the control group (weighted percentage: 50.13%). The differences in dietary fatty acid and serum free fatty acid (FFA) levels and metabolic characteristics were compared. Logistic and weighted quantile sum (WQS) regression models were used to evaluate the impacts of various FFA indexes on HS. Mediation analysis was conducted to examine whether inflammation served as a mediator in the relationship between FFA and HS.Results:Dietary fatty acid intake did not differ significantly between the HS and control groups. However, serum FFA metabolism characteristics differed between these two groups, with the concentrations of 28 FFAs in the HS group significantly higher than those in the control group. The risk of HS was correlated negatively with serum unsaturated fatty acids/saturated fatty acids ( OR=0.69, 95% CI: 0.64–0.75, P<0.001), polyunsaturated fatty acids/saturated fatty acids ( OR=0.63, 95% CI: 0.99–0.69, P<0.001), and Health Promotion Index ( OR=0.78, 95% CI: 0.74–0.82, P<0.001) but positively with thrombosis index ( OR=2.20, 95% CI: 1.89–2.55, P<0.001). The WQS model showed that behenic acid had the greatest contribution weight to increase the risk of HS among the 30 FFAs. After adjusting for confounding factors, the risk of HS increased by 167% (95% CI: 2.14–3.34, P<0.001) for each unit increase in the WQS index. Further mediation analysis showed that albumin/globulin ratio, white blood cell count, and neutrophil to platelet ratio significantly mediated the relationship between serum FFA and HS ( P<0.05). Conclusion:People with similar dietary fatty acid structures may present different serum FFA metabolism characteristics. Serum FFA level correlates with the risk of HS, and inflammation plays an important role in mediating the relationship between fatty acid metabolism and HS.

Epilepsy is a chronic brain disorder characterized by abnormal synchronous neuronal discharges in the brain, often accompanied by various complications. The pathogenesis of epilepsy has not yet been fully elucidated. Optogenetics, a cutting-edge technique that integrates optics and genetics, enables precise modulation of specific neurons by regulating light-sensitive proteins. Utilizing optogenetic technology has facilitated the dissection of neural circuits involved in epileptic seizures within brain regions such as the hippocampus, thalamus, hypothalamus. It has also helped identify potential therapeutic targets for epilepsy-related complications, including cognitive impairment, sudden unexpected death in epilepsy and mood disorders.However, in the process of advancing from basic research to clinical treatment, its translational path is profoundly influenced by factors such as stimulation modes (the choice between open-loop and closed-loop systems), key parameters (light frequency), and intervention strategies (unilateral or bilateral target selection). The individualized customization of these factors represents the future direction for overcoming current translational bottlenecks and achieving precise treatment.

Objective To investigate the effect of naringenin(NAR)on right ventricular remodeling induced by hypoxic pulmonary hypertension(HPH)and its related mechanism.Methods SD rats were randomly divided into the control group(NC),the NC+NAR group,the HPH group and the HPH+NAR group,with 15 rats in each group.HPH model was established in a low-pressure hypoxic artificial chamber.After the successful construction of the model,rats in the NC+NAR group and the HPH+NAR group were given NAR 100 mg/(kg·d)gavage once a day for 4 weeks,while rats in the NC group and the HPH group were given the same volume of normal saline once a day for 4 weeks.Right ventricular free wall thickness(RVEDWT)and end-diastolic right ventricular diameter(RVEDD)were measured by echocardiography.Right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(mPAP)were measured by cardiac catheter.Right ventricular mass ratio(RV/BW)and right ventricular hypertrophy index(RVHI)were calculated.Masson and Sirius staining of right ventricle was used to calculate the collagen volume fraction(CVF).TUNEL staining was used to evaluate the apoptosis of right ventricular cardiomyocytes.The contents of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in right ventricular myocardium were detected.The expression of Rho associated kinase(ROCK)protein was detected by Western blot assay.Results Compared with the NC group and the NC+NAR group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content and ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were increased in the HPH group.RVEDD and SOD activity in right ventricular myocardium were decreased(P＜0.05).Compared with the HPH group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content,ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were decreased in the HPH+NAR group,and RVEDD and SOD activity in right ventricular myocardium were increased(P＜0.05).Conclusion NAR can reduce HPH-induced right ventricular remodeling,and its mechanism may be related to inhibiting ROCK signaling pathway and further improving apoptosis and oxidative stress in right ventricular myocardium.