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.

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.

Central positional nystagmus （CPN） is a form of positional nystagmus caused by lesions of the central vestibular system. Since the clinical manifestations and nystagmus features of CPN are highly similar with those of benign paroxysmal positional vertigo， the diagnosis of CPN is highly challenging. The etiology of CPN is complex， involving both structural lesions such as stroke and tumors and non-structural disorders such as vestibular migraine. The primary lesion sites of CPN included the cerebellar nodulus， the uvula， and the tonsil. CPN can be classified into paroxysmal （transient） CPN and persistent CPN. The clinical features of paroxysmal CPN （including latency， duration， direction， intensity， and their correlation with the type and speed of positional maneuvers） suggest that it originates from the semicircular canal， and its pathogenesis involves post-rotatory rebound nystagmus caused by the disinhibition of irregular afferent signals transmitted to the vestibular nuclei due to central damage （often involving the cerebellar nodulus and the uvula）. Persistent CPN may be caused by damage to the velocity storage pathway， resulting in an erroneous assessment of gravity direction and inertia. This article summarizes the latest advances in the etiology， lesion sites， pathogenesis， clinical features， differential diagnosis， and treatment of CPN in China and globally， in order to help clinicians better understand and identify CPN and thus achieve timely diagnosis and effective treatment.
Uvula

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.

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

ObjectiveTo evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) for muscle atrophy in patients with immobilization after surgical fixation of foot and ankle fractures.MethodsThis was a two-arm randomized controlled trial wherein 80 patients were recruited and divided into control (n = 40) and intervention (n = 40) groups. The control group received conventional orthopedic treatment, whereas the intervention group received TEAS and conventional treatment. The intervention group received TEAS 3 times a week for 30 min each time for 8 weeks. The primary outcomes were muscle thickness (MT) and cross-sectional area (CSA) of the rectus femoris and gastrocnemius muscles, whereas the secondary outcome measure was echo intensity (EI). Data were collected before the fixation operations (baseline assessment) and 4 and 8 weeks after intervention.ResultsCompared with baseline, the MT and CSA were reduced in both groups by the end of treatment, whereas EI increased in both groups. At week 4, the reduction in the rectus femoris CSA in the intervention group was significantly lower than that in the control group (P = .02); however, the between-group differences in the MT and EI (all P .05) were not significant. No serious adverse events were observed in either group.ConclusionOur study showed that TEAS can improve muscle atrophy by attenuating the decline in the muscle CSA. Because this was only a pilot trial, subsequent studies will need longer follow-ups and larger sample sizes.