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.

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 the molecular mechanism by which 2',4'-dihydroxychalcone(D2)inhibits proliferation,migration,and epithelial-mesenchymal transition(EMT)in colorectal cancer cells through miR-7-5p-mediated autophagy.Methods:Human colorectal cancer cell lines HCT-15 and SW620 were treated with D2 at concentrations of 0,12.5,25,and 50 μmol/L.Cell proliferation and clonogenic capacity were evaluated using MTT and colony formation assays.Cell migration was assessed by wound healing and Transwell assays.WB assay was used to detect the expression of EMT-related proteins,autophagy-related proteins,and key components of the PI3K/AKT/mTOR pathway.Autophagosome formation was visualized by immunofluorescence staining.TCGA database and KEGG pathway analyses were performed to evaluate miR-7-5p expression and its association with colorectal cancer.RT-qPCR was used to quantify miR-7-5p expression,and lentiviral transduction was employed to establish stable miR-7-5p knockdown or overexpression cell lines.Results:D2 significantly inhibited colorectal cancer cell proliferation,migration,and EMT(P<0.05 or P<0.01).TCGA and KEGG analyses revealed that miR-7-5p expression was downregulated in colorectal cancer and closely associated with disease progression.D2 treatment(12.5,25,and 50 μmol/L)significantly upregulated miR-7-5p expression in HCT-15 and SW620 cells(P<0.01).At 25 μmol/L,D2 increased the expression of autophagy-related proteins(LC3 and p-ULK1)and inhibited the PI3K/AKT/mTOR signaling pathway(P<0.05),accompanied by increased autophagosome formation(P<0.01).In miR-7-5p-knockdown cells treated with D2,the levels of LC3 and p-ULK1 were significantly reduced compared to D2-only treated cells(P<0.05 or P<0.01).Conclusion:D2 upregulates miR-7-5p to induce autophagy,thereby inhibiting colorectal cancer cell proliferation,migration,and EMT,possibly through suppression of the PI3K/AKT/mTOR signaling pathway.

The preferred treatment for adrenal functional tumors is laparoscopic surgical resection. However, in recent years, various ablation techniques have gradually been applied in the treatment of adrenal tumors. This report presents the successful diagnosis and treatment experience of 4 aldosterone-producing adenomas and 1 cortisol-secreting adenoma treated with a combined cold and hot ablation system at Xi’an Daxing Hospital from Dec. 2023 to Dec. 2024, providing a new treatment approach for clinical exploration.

Neuronal intranuclear inclusion disease (NIID) is a genetic degenerative disease characterized by the presence of eosinophilic and p62-positive inclusions in the nucleus. The pathogenic variant is an abnormal CGG repeat expansion in the 5′ untranslated region of the NOTCH2NLC gene, leading to a pathogenesis of RNA toxicity and poly-glycine protein toxicity that impair cellular functions. NIID presents clinically with great heterogeneous phenotypes, comprising five subtypes: cognitive impairment predominance, movement disorder predominance, paroxysmal neurological events predominance, autonomic dysfunction predominance, and neuromuscular disease predominance. The magnetic resonance imaging (MRI) characteristics provide important diagnostic clues, including the "ribbon sign" at the corticomedullary junction on diffusion weighted imaging (DWI), diffuse white matter lesions symmetrically affecting the corona radiata and centrum semiovale, DWI hyperintensities in the splenium of the corpus callosum, and focal cortical edema with linear enhancement on the surface of corresponding cortex. With the applications of skin biopsies and genetic testing, an increasing number of NIID cases have been identified in China, resulting in recent advancements in clinical and basic research. This review highlights the pathogenesis, clinical manifestations, auxiliary examinations, differential diagnosis, and management of this disorder.

Objective:To explore the phenotypic heterogeneity among patients harboring identical pathogenic variants in the dystrophin ( DMD) gene by analyzing clinical and imaging data from 7 pairs of male twins with dystrophinopathy. Methods:Clinical and laboratory data of 14 (7 pairs) male twins diagnosed with dystrophinopathy through genetic testing among 1 767 patients at Peking University First Hospital from January 2017 to October 2024 were collected. Eleven patients underwent thigh muscle magnetic resonance imaging (MRI), and muscle biopsies were performed in at least 1 case of each pair.Results:Among the 7 pairs of twin patients, 2 pairs had Duchenne muscular dystrophy, and 5 pairs had Becker muscular dystrophy. In terms of variant types, 4 pairs had in-frame deletions, while the remaining 3 pairs had duplication variants, frameshift variants, and nonsense variants, respectively. Clinically, 6 individuals had asymptomatic hypercreatine kinasemia, and 8 had varying degrees of limb weakness. Among the 5 pairs of symptomatic twins, there were differences in the degree of limb weakness. Four individuals showed no significant abnormalities in thigh muscle MRI, 7 showed fat infiltration mainly in the bilateral gluteus maximus and adductor magnus muscles, and 2 pairs of twins had obvious differences in the degree of fat infiltration in muscle MRI. Muscle biopsies revealed dystrophic or mild myopathic pathological changes, with 2 individuals showing severe loss of dystrophin, while the others had partial loss.Conclusions:Dystrophinopathy exhibits significant individual differences. Even among individuals with highly similar genetic background, clinical and imaging manifestations caused by the same pathogenic variant also vary.

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 investigate the influence of a disintegrin and metalloproteinase 12(ADAM12),S100 calcium binding protein A8(S100A8),and serum tumor markers on chemotherapy outcomes and prognosis in patients with triple-negative breast cancer.Methods A totla of 300 patients with breast cancer admitted between January 2020 and January 2021 were included.Based on pathological immunohistochemistry findings,the patients were divided into a triple-negative group(n=98,triple-negative breast cancer)and a non-triple-negative group(n=202,non-triple-negative breast cancer).Serum tumor markers(carcinoembryonic antigen[CEA]and carbohydrate antigen 125[CA125]),the levels of ADAM12 and S100A8,and tissue protein expression levels of ADAM12 and S100A8 were compared between the two groups.The relationship between the protein levels of ADAM12 and S100A8 in the cancer tissues and the clinicopathological characteristics of the triple-negative group was analyzed.Differences in the protein levels of ADAM12 and S100A8 between patients with different chemotherapy outcomes(remission vs.non-remission)and different follow-up outcomes(survival vs.death)were analyzed.Kaplan-Meier survival analysis was used to examine the relationship between the protein levels of ADAM12 and S100A8 in cancer tissues and the prognosis.Results The protein expression levels of ADAM12 and S100A8 in cancer tissues from the triple-negative group were higher than those in the non-triple-negative group(P＜0.05).The protein expression levels of ADAM12 and S100A8 in cancer tissues were correlated with tumor diameter,histological grading,axillary lymph node metastasis,TNM staging,and differentiation degree in the triple-negative group(P＜0.05).The levels of CEA,CA125,ADAM12,and S100A8,as well as the protein expression levels of ADAM12 and S100A8 in cancer tissues in the non-remission group,were higher than those in the remission group(P＜0.05).Similarly,these markers were also significantly elevated in the death group compared to those in the survival group(P＜0.05).After 3 years of follow-up,the overall survival(OS)of patients with low ADAM12 expression was 36.0(8.0,36.0)months,while that of patients with high ADAM12 expression was 32.5(4.0,36.0)months,showing a statistically significant difference(log rank x2=12.913,P＜0.001).The OS of patients with low S100A8 expression was 36.0(7.0,36.0)months,while that of the high-expression group was 31.0(4.9,36.0)months,also showing a statistically significant difference(log rank x2=24.151,P＜0.001).Conclusion ADAM12 and S100A8 protein expression levels in triple-negative breast cancer tissues are higher than those in non-triple-negative breast cancer tissues.Serum tumor markers and ADAM12 and S100A8 protein expression levels(in both serum and tumor tissues)affect the chemotherapy outcomes and prognosis of triple-negative breast cancer patients,among which the expression levels of ADAM12 and S100A8 proteins in tumor tissues can serve as predictors of patient prognosis.