ObjectiveTo establish a reliable chronic obstructive pulmonary disease (COPD) mouse model based on a self-developed multichannel automatic control system for long-term continuous cigarette smoke exposure in small animals using a novel continuous cigarette smoke exposure method, and to conduct phenotypic evaluation and analysis, thereby providing an animal experimental basis for investigating COPD pathogenesis and prevention strategies. MethodsTwenty male C57BL/6J mice aged 6 weeks were randomly and equally divided into a control group and a model group. The model group (n=10) underwent 6 h of continuous cigarette smoke exposure daily (6 cigarettes per day for 12 consecutive weeks), while the control group (n=10) received no intervention. Body weight was monitored biweekly. Post-exposure, in vivo micro-CT imaging was performed. After euthanasia, serum and bronchoalveolar lavage fluid (BALF) levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were quantified by ELISA. Lung tissues underwent H&E and Masson's trichrome staining to observe changes in lung morphology and inflammatory cell infiltration, and the mean linear intercept (MLI) was calculated, thereby comprehensively evaluating the clinical features of COPD in the mouse model. ResultsCompared with the control group, the model group showed significantly reduced body weight (P<0.01) from the fourth week. Compared with the control group, IL-6 level in the serum and BALF of the model group increased by 27.2% and 140.0%, respectively (P<0.01). TNF-α level in the serum and bronchoalveolar lavage fluid of the model group increased by 16.7% (P<0.01) and 19.3% (P<0.05), respectively. Histopathological examination revealed alveolar wall thinning, septal rupture, emphysematous bullae formation, reduced alveolar count, bronchial wall thickening with lumen narrowing, and inflammatory cell infiltration. MLI was significantly elevated (P<0.01). Masson's staining confirmed collagen deposition and bronchial remodeling. Micro-CT demonstrated localized high-density shadows exhibiting typical features of chronic bronchitis. Conclusion The self-developed device enables long-term continuous smoke exposure, and the successfully established COPD mouse model exhibits pathological features highly consistent with clinical manifestations, offering an efficient and reliable tool for COPD research.

To analyze the clinical and genetic features of oculopharyngodistal myopathy (OPDM) patients and compare the phenotypic differences among various causative genes.

Neuronal intranuclear inclusion disease(NIID) is a rare, chronic progressive neurodegenerative disease predominantly presenting with adult-onset cases in China. This disease exhibits high clinical phenotypic heterogeneity, with neurological manifestations as the predominant symptoms in most patients and prominent involvement of other systems in a minority of cases. Some patients without characteristic early cranial magnetic resonance imaging(MRI) findings are prone to misdiagnosis and missed diagnosis. Herein, we report an adult female patient with NIID characterized by cyclic vomiting. She initially presented with difficult micturition, followed by the onset of cyclic vomiting several years later, without other neurological involve-ments throughout the disease course. Cranial MRI revealed symmetric progressive periventricular white matter lesions in the lateral ventricles. Genetic testing identified abnormal GGC repeat expansion in the NOTCH2NLC gene.Pathological examination of labial gland biopsy showed intranuclear inclusions positive for p62 and ubiquitin. By summarizing the clinical characteristics of this patient, this article aims to deepen clinicians′ understanding of NIID.

AIM: To investigate the protective effect of β-sitosterol on retinal structure and function and its underlying molecular mechanism in a sodium iodate(NaIO3)-induced mouse model of dry age-related macular degeneration(ARMD).METHODS: A dry ARMD mouse model was established by NaIO3 injection. The therapeutic effect of β-sitosterol intervention was evaluated using fundus photography, histopathology(HE staining), and electroretinography(ERG). Network pharmacology was employed to screen potential targets of β-sitosterol in ARMD, and molecular docking was used to validate the binding ability between β-sitosterol and these targets. The impact of β-sitosterol on ARPE-19 cell viability and apoptosis pathways was analyzed using CCK-8 assay, Hoechst staining, and Western blotting.RESULTS: The β-sitosterol significantly alleviated structural damage in the retinas of model mice(increased retinal and outer nuclear layer thickness, reduced yellowish-white drusen-like deposits)and functional impairment(partial restoration of a-wave and b-wave amplitudes). Network pharmacology identified PON1 as a key target of β-sitosterol; molecular docking demonstrated that β-sitosterol binds to PON1 via hydrophobic interactions and hydrogen bonds. In vitro experiments showed that β-sitosterol(10 μmol/L)significantly increased ARPE-19 cell viability(P<0.01), reduced apoptosis(P<0.01), upregulated PON1 expression(P<0.01), and concurrently suppressed cleaved-Caspase3 expression(P<0.01).CONCLUSION: The β-sitosterol likely protects against oxidative stress-induced retinal damage by modulating PON1 to suppress the Caspase3-dependent apoptotic pathway. These findings provide experimental evidence supporting the development of β-sitosterol as a novel therapeutic agent for dry ARMD.

OBJECTIVES: To investigate the regulatory effects of Aurora-A in regulating proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells and the role of actin-related protein 2/3 complex subunit 4 (ARPC4) in mediating its effects. METHODS: The plasmids pCDH-NC, pCDH-Aurora-A, and shRNA-ARPC4 were used for inducing Aurora-A overexpression or ARPC4 knockdown in HeLa cells. The cells were divided into vector group, Aurora-A overexpression group, Aurora-A overexpression+ARPC4 knockdown group, and Aurora-A overexpression+NF‑κBp65 inhibitor group and transfected with the corresponding plasmids. The proliferation, colony-forming ability, migration and invasion of the treated Hela cells was evaluated using EdU immunofluorescence assay, crystal violet staining, scratch assay, Transwell assay, and Matrigel assay. Western blotting was performed to detect the changes in cellular expressions of EMT-related proteins and expression levels of NF-κBp65 and ARPC4. RESULTS: The expression of ARPC4 was significantly decreased in HeLa cells with Aurora-A knockdown and increased in Aurora-A-overexpressing cells. Aurora-A overexpression obviously promoted proliferation, migration, and invasion abilities of HeLa cells, and these effects was significantly antagonized by ARPC4 knockdown. In Aurora-A-overexpressing cells, the phosphorylation level of NF-κBp65 and the expression level of ARPC4 were increased significantly, and application of the NF‑κBp65 inhibitor obviously lowered the expression level of ARPC4. CONCLUSIONS Aurora-A overexpression upregulates the expression of ARPC4 by activating the NF-κBp65 signaling pathway, thereby promoting migration, invasion and EMT of HeLa cells.
Humans ; Uterine Cervical Neoplasms/metabolism* ; Female ; HeLa Cells ; Epithelial-Mesenchymal Transition ; Signal Transduction ; Cell Movement ; Neoplasm Invasiveness ; Cell Proliferation ; Aurora Kinase A/metabolism* ; Transcription Factor RelA/metabolism* ; Neoplasm Metastasis

Objective:To investigate renal impairment and ferroptosis due to severe blast injuries and related mechanism.Methods:The goats were placed 3 meters away from the center of an 8 kg TNT-equivalent explosive to carry out blast injury experiments.The physical parameters of blast waves were measured,and the pathological severity of blast injuries was graded and scored to assess the severity of injuries.Vital signs,blood gas parameters,and renal function markers were measured before injury and at 1,3,6,and 24 hours after injury.Renal tissue samples were collected at 24 hours after injury to prepare tissue sections,which were used to perform HE staining and measure the changes in the content of Fe2+and the expression of the ferroptosis-related marker proteins xCT and GPX4 in renal tissue,and Prussian blue staining was performed for renal tissue sections to investigate the mechanism associated with renal impairment and ferroptosis of renal cells.Results:Severe blast injuries accounted for the highest proportion of 47.2%in experi-mental goats,while mild,moderate,severe,and extremely severe injuries accounted for 2.8%,36.1%,47.2%,and 13.9%,respectively,and the pathologic severity score of blast injury was 2.56±0.15.For the goats after blast injury,there were significant increases in heart rate(F=12.750,P<0.01)and respiratory rate(F=6.500,P<0.01)and significant reductions in anal temperature(F=3.496,P<0.05),partial pressure of blood oxygen(F=24.630,P<0.01),and blood oxygen saturation(F=18.560,P<0.01),as well as significant increases in the levels of blood uric acid(F=22.320,P<0.01),serum creatinine(F=15.350,P<0.01),and blood urea nitrogen(F=22.310,P<0.01).Compared with the control group,swelling of renal tubular epithelial cells and narrowing of tubular lumen were observed at 24 hours after blast injury,with a significant increase in the content of Fe2+in renal tissue(t=5.933,P<0.01),significant reductions in the relative expression protein levels of GPX4(t=7.924,P<0.01)and xCT(t=4.483,P<0.01)in renal tissue,and deposi-tion of a large amount of iron ions in renal tubular epithelial cells.Conclusion:Experimental goats placed 3 meters away from the cen-ter of an 8 kg TNT-equivalent explosive can cause severe blast inju-ries,resulting in the onset of hypoxia,renal impairment,and ferrop-tosis of renal tubular epithelial cells.

Space medicine,as a comprehensive discipline ensuring the safety,health,and efficient performance of astronauts during manned space missions,focuses on elucidating the underlying mechanisms of multi-system physiological effects induced by extreme space environments and developing corresponding protective strategies.With China's space program transitioning into an application and development phase,space medical experiments—a critical domain within space applications—face significant opportunities and challenges.This paper reviews the international development trend in the field of medical experiments and the progress in China from perspectives including platform system construction,utilization of novel technologies,and scientific discoveries.It further outlines the engineering framework,guiding ideology,and key research directions for space medical experiments under China's Space Station Application and Development Project.Deliberations and prospects center on the in-depth analysis of the adaptation law of life in space flight,the application of big data and artificial intelligence technology,the emerging challenges it faces,and the scientific research organization models.This work aims to provide a reference for the development of space medical experiment field in China.

Objective To evaluate the brain injury in children with congenital diaphragmatic hernia(CDH)after surgery through examination methods such as amplitude-integrated electroencephalogram(aEEG),regional cerebral oxygen saturation(rSO2)and neonatal behavioral neurological assessment(NBNA),so as to clarify their diagnostic value.Methods A total of 83 full-term CDH children admitted to our hospital were retrospectively enrolled as the research subjects.According to the brain damage syndrome(BDS)diagnostic criteria,they were divided into brain injury group(n=36)and control group(n=47).We compared the general data of the neonates in the two groups,as well as the modified aEEG scores and rSO2 at admission,14 days after birth,and 28 days after birth.We compared the NBNA scores at 28 days after birth.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of the three tools for brain injury.Results The modified aEEG scores of the children in the brain injury group at each time point were lower than those in the control group.The rSO2 of the children in the brain injury group was lower than that in the control group at 14 days and 28 days after birth and recovered slowly.The NBNA scores also indicated that the neurodevelopment of the children in the brain injury group was significantly lower than that in the control group.The ROC curve showed that the areas under the curve of combined diagnosis exhibited the best diagnostic efficacy compared with rSO2 used alone at 28 days after birth,aEEG at 28 days after birth,and NBNA scores(the area under the curve:0.968 vs.0.701 vs.0.685 vs.0.870;sensitivity:92.0％ vs.53.7％ vs.87.8％ vs.95.1％;specificity:97.0％ vs.86.1％ vs.50.0％ vs.72.2％).Conclusion The combined application of the modified aEEG score,rSO2,and NBNA has high sensitivity and specificity in the diagnosis of brain injury in children with CDH;therefore,it is worthy of clinical promotion and application.

Gene-edited mouse models,as a core tool in modern biomedical research,play an irreplaceable role in fields such as disease mechanism analysis,drug development,and gene function studies.However,universities often face challenges including technical complexity,dispersed resources,and low management efficiency during the preparation,breeding,and data analysis of gene-edited mice.To address these issues,establishing a one-stop service platform for gene-edited mice that integrates full-chain technical services and an intelligent management system has become an inevitable choice for university laboratory animal centers to break through current difficulties.This platform must possess core functions including gene-edited mouse construction,breeding and colony expansion,biological purification,strain preservation,and endangered strain rescue,forming a whole-process technical service system covering"target design-model construction-population expansion-genetic quality control-biological sample preservation",to promote the strategic transformation of university laboratory animal centers from providing"single technical services"to providing"whole-process solutions".Taking the Laboratory Animal Center of Shanghai Jiao Tong University as an example,through technical optimization,the technical defects such as low microoperation success rate and insufficient standardization of genotype identification were solved.Through traceability management and information sharing,problems such as chaotic management of mouse strains in research groups and waste of research funds caused by repeated constructions were solved.Through systematic integration and optimization of technical services,problems such as low efficiency,resource waste,and collaboration difficulties that may be caused by fragmented service systems were solved.This paper systematically discusses the construction path and practical experience of the gene-edited mouse service platform from three perspectives:intensive management,service capacity building,and support system construction,aiming to provide referable management models and implementation paths for the construction of similar platforms in other universities.