OBJECTIVE To investigate the effects of osthole （OST） on skin wound healing and angiogenesis in rats by regulating the sonic hedgehog （SHH） signaling pathway. METHODS Full-layer skin defect wound model rats were established and then randomly separated into Model group， OST low-dose， medium-dose and high-dose groups （OST-L group， OST-M group， OST-H group， 20， 30， 40 mg/kg OST）， high-dose OST+SHH inhibitor cyclopamide group （OST-H+cyclopamide group， 40 mg/kg OST+10 mg/kg cyclopamide）， with 12 rats in each group. Another 12 rats were selected as the control group. The wound healing of rats on 1， 7 and 14 days of administration was observed， and the wound healing rate of rats in each group was measured. The pathological changes and collagen deposition in rat wound tissue were observed； the levels of angiopoietin-1 （Ang-1） and basic fibroblast growth factor （bFGF） in wound tissue of rats were detected； the relative expressions of vascular endothelial growth factor A （VEGFA） and vascular endothelial growth factor receptor-2 （VEGFR-2） mRNA were also detected in wound tissue of rats； the protein expressions of VEGFA， VEGFR-2， SHH and glioma-associated oncogene homolog-1 （GLI1） were determined in wound tissue of rats. RESULTS Compared with Model group， the healing rate of skin wound， relative expression of collagen protein， the levels of Ang-1 and bFGF， the mRNA and protein expressions of VEGFA and VEGFR-2， and the protein expressions of SHH and GLI1 were all significantly increased in OST-M and OST-H groups （P＜0.05）. The wound tissue underwent significant re- epithelialization， with reduced inflammatory cell infiltration and granulation tissue edema， and an increase in the number of new blood vessels. SHH inhibitor cycloparamide weakened the promoting effects of OST on skin wound healing and angiogenesis in rats. CONCLUSIONS OST may promote skin wound healing and angiogenesis in rats by activating the SHH signaling pathway.

Chronic fatigue syndrome (CFS) is a common problem in military maritime navigation, which greatly affects the safety of military missions. The use of animal models to carry out research on the mechanism of CFS and treatment measures is a common method. This paper systematically introduced the construction methods of CFS models such as single-factor and multi-factor models, summarized common evaluation indicators of CFS, including behavioral and biochemical indicators, and summed up key characteristics of CFS animal models in military oceanic navigation combined with common causes of CFS in military contexts, such as prolonged continuous work, high-intensity physical activity, sleep deprivation, psychological stress, and extreme environmental conditions. The key characteristics of the animal models included, but not limited to, chronic fatigue, sleep disorders, impaired cognitive function, psychological stress responses, and abnormal biochemical indicators. Furthermore, this article identified future research directions for CFS animal models in military oceanic navigation to enhance the application value of the models and provide robust support for the health protection and disease prevention of military personnel.

With the main pathological features of glomerulosclerosis and interstitial fibrosis， renal fibrosis is a key pathological process causing chronic kidney disease to progress to end-stage disease. As a cellular autophagic process， mitochondrial autophagy plays a crucial role in maintaining mitochondrial mass and functional stability. Mitochondrial dysfunction is considered to be one of the key factors driving the progression of fibrosis. Phosphatase and tension protein homologue （PTEN） induce various signalling pathways such as putative kinase 1/parkin， Nip3-like protein X/Bcl-2 interacting protein 3， and FUN14 structural domain-containing protein 1 to activate mitochondrial autophagy to participate in the regulation of fibrogenic factors， amelioration of oxidative stress， and inhibition of inflammatory response and apoptosis， which in turn effectively slows down the progression of renal fibrosis. Studies have shown that traditional Chinese medicine monomers and compound preparations， including phenolics， terpenoids， ketones， and alkaloids， can regulate mitochondrial autophagy-related signalling pathways and achieve significant clinical efficacy in intervening in the progression of renal fibrosis for the treatment of chronic kidney disease. This paper summarized the mechanism of mitochondrial autophagy and the research progress of traditional Chinese medicine intervention in renal fibrosis to provide new ideas for the study of the mechanism of traditional Chinese medicine in treating renal fibrosis.

With the main pathological features of glomerulosclerosis and interstitial fibrosis， renal fibrosis is a key pathological process causing chronic kidney disease to progress to end-stage disease. As a cellular autophagic process， mitochondrial autophagy plays a crucial role in maintaining mitochondrial mass and functional stability. Mitochondrial dysfunction is considered to be one of the key factors driving the progression of fibrosis. Phosphatase and tension protein homologue （PTEN） induce various signalling pathways such as putative kinase 1/parkin， Nip3-like protein X/Bcl-2 interacting protein 3， and FUN14 structural domain-containing protein 1 to activate mitochondrial autophagy to participate in the regulation of fibrogenic factors， amelioration of oxidative stress， and inhibition of inflammatory response and apoptosis， which in turn effectively slows down the progression of renal fibrosis. Studies have shown that traditional Chinese medicine monomers and compound preparations， including phenolics， terpenoids， ketones， and alkaloids， can regulate mitochondrial autophagy-related signalling pathways and achieve significant clinical efficacy in intervening in the progression of renal fibrosis for the treatment of chronic kidney disease. This paper summarized the mechanism of mitochondrial autophagy and the research progress of traditional Chinese medicine intervention in renal fibrosis to provide new ideas for the study of the mechanism of traditional Chinese medicine in treating renal fibrosis.

BACKGROUND: Currently, lung cancer is one of the malignant tumors with a high morbidity and mortality all over the world. However, the exact mechanisms underlying lung cancer progression remain unclear. The tumor necrosis factor receptor associated factor (TRAF) family members are cytoplasmic adaptor proteins, which function as both adaptor proteins and ubiquitin ligases to regulate diverse receptor signalings, leading to the activation of nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) signaling. The aim of this study was to investigate the expression of TRAFs in different tissues and cancer types, as well as its mRNA expression, protein expression, prognostic significance and functional enrichment analysis in non-small cell lung cancer (NSCLC), in order to provide new strategies for the diagnosis and treatment of NSCLC. METHODS: RNA sequencing data from the The Genotype-Tissue Expression database was used to analyze the expression patterns of TRAF family members in different human tissues. RNA sequencing data from the Cancer Cell Line Encyclopedia database was used to analyze the expression patterns of TRAF family members in different types of cancer cell lines. RNA sequencing data from the The Cancer Genome Atlas (TCGA) database was used to analyze the mRNA levels of TRAF family members across different types of human cancers. Immunohistochemistry (IHC) analyses from HPA database were used to analyze the TRAF protein levels in NSCLC [lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC)]. Overall survival analysis was performed by Log-rank test using original data from Kaplan-Meier Plotter database to evaluate the correlation between TRAF expressions and prognosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on the TRAF family-related genes using RNA sequencing data from the TCGA database for NSCLC. The correlation between the expression levels of TRAF family members and the tumor immune microenvironment was analyzed using the ESTIMATE algorithm based on RNA sequencing data from the TCGA database. RESULTS: The TRAF family members exhibited significant tissue-specific expression heterogeneity. TRAF2, TRAF3, TRAF6 and TRAF7 were widely expressed in most tissues, while the expressions of TRAF1, TRAF4 and TRAF5 were restricted to specific tissues. The expressions of TRAF family members were highly specific among different types of cancer cell lines. In mRNA database of LUAD and LUSC, the expressions of TRAF2, TRAF4, TRAF5 and TRAF7 were significantly upregulated; while TRAF6 did the opposite; moveover, TRAF1 and TRAF3 only displayed a significant upregulation in LUAD and LUSC, respectively. Except for TRAF3, TRAF4 and TRAF7, other TRAF proteins displayed an obviously deeper IHC staining in LUAD and LUSC tissues compared with normal tissues. Additionally, patients with higher expression levels of TRAF2, TRAF4 and TRAF7 had shorter overall survival; while patients with higher expression levels of TRAF3, TRAF5 and TRAF6 had significantly longer overall survival; however, no significant difference had been observed between TRAF1 expression and the overall survival. TRAF family members differentially regulated multiple pathways, including NF-κB, immune response, cell adhesion and RNA splicing. The expression levels of TRAF family members were closely associated with immune cell infiltration and stromal cell content in the tumor immune microenvironment, with varying positive and negative correlations among different members. CONCLUSIONS TRAF family members exhibit highly specific expression differences across different tissues and cancer types. Most TRAF proteins exhibit upregulation at both mRNA and protein levels in NSCLC, whereas, only upregulated expressions of TRAF2, TRAF4 and TRAF7 predict worse prognosis. The TRAF family members regulate processes such as inflammation, immunity, adhesion and splicing, and influence the tumor immune microenvironment.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/mortality* ; Prognosis ; Gene Expression Regulation, Neoplastic ; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism*

Objective:To retrospectively analyze the results of auditory examination,vestibular function examination and laboratory examination of 63 patients diagnosed as vestibular neuritis.Methods:A total of 63 patients diagnosed with vestibular neuritis hospitalized in the Department of Otolaryngology, Head and Neck Surgery of the Third Affiliated Hospital of Sun Yat-sen University, from October 2012 to December 2022 were recruited. All patients met the diagnostic criteria for the 2022 Bárány association vestibular neuritis. Clinical data and the results of pure tone audiometry, electrocochleogram, video electronystagmogram, caloric test, cervical vestibuloevoked myogenic potential（cVEMP）, ocular vestibuloevoked myogenic potential（oVEMP）, video head impulse test（vHIT） was collected.A total of 63 age-and sex-matched healthy subjects in the physical examination center were randomly selected as the control group. The differences of blood indexs and lipid metabolism indexes between the two groups were compared. Results:In patients with vestibular neuritis, 50 out of 63 patients presented normal threshold in pure tone audiometry, 8 out of 63 patients had bilateral high-frequency sensorineural hearing loss and 5 out of 63 patients had unilateral mild high-frequency sensorineural hearing loss, 56 out of 63 cases completed the electrocochleogram, of which 3 cases had a binaural-SP/AP amplitude ratio≥0.4, 5 cases had monaural amplitude ratio ≥0.4. Fifty-five out of 63 patients completed the caloric test with CP values greater than 30% in all. The ratio of patients completed cVEMP, oVEMP and vHIT were 46 cases, 22 cases and 30 cases, respectively. 17 out of 63 cases completed all the four vestibular function tests. According to these tests, 49 patients could determine the extent of injury，including 27 cases with unilateral superior vestibular nerve injury, 21 cases with unilateral superior and inferior vestibular nerve injury and 1 case with unilateral inferior vestibular nerve injury. There were significant differences in neutrophil value（P<0.001）, lymphocyte value（P<0.005）, neutrophil/lymphocyte ratio（P<0.001） and apolipoprotein A1（P<0.001） between patient group and control group. Inflammatory markers were risk factors for patients with vestibular neuritis. The OR values of neutrophil value and blood neutrophil/lymphocyte ratio were 1.81（1.38-2.37, P<0.001） and 2.11（1.41-3.16, P<0.001）, respectively. Apolipoprotein A1 was a protective factor for patients with vestibular neuritis, and the OR value was 0.004（0.001-0.042, P<0.001）. Conclusion:Electrocochleogram could be used in vestibular neuritis patients with normal pure tone threshold to test whether there is hidden hearing loss in these patients. Neutrophil value, lymphocyte value, neutrophil/lymphocyte ratio and apolipoprotein A1 were correlated with vestibular neuritis. The Neutrophil value and neutrophil/lymphocyte ratio were risk factors for morbidity.
Humans ; Vestibular Neuronitis/physiopathology* ; Retrospective Studies ; Female ; Male ; Audiometry, Pure-Tone ; Hearing Loss, Sensorineural/physiopathology* ; Middle Aged ; Adult ; Vestibular Function Tests ; Vestibular Evoked Myogenic Potentials ; Aged

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective To systematically evaluate the effect of speech and language therapies and educational interventions on chil-dren with intellectual and developmental disabilities(IDD). Methods A systematic review was conducted by searching relevant literature in PubMed,PsycINFO,ERIC,Cochrane Library and Web of Science databases,ranging from January,2018 to May,2024. Results A total of eight English articles were included,from six countries including the United States,France,Italy,Nor-way,Poland and New Zealand,involving 610 children with IDD,from journals about speech language pathology,Down syndrome research and speech language hearing research.The publication time was mainly from 2018 to 2023.The age of the subjects was two to twelve years,and the main health conditions included intellectual dis-ability,autism and Down syndrome.The intervention methods included routine speech therapy(individualized therapy and group therapy),augmentative and alternative communication(device-assisted and sign language and picture cards),family-involved language training programs(parent training and family interaction),computer-as-sisted language learning(language learning software and telehealth),and play-based interventions(interactive games and structured games);15 to 150 minutes a time,one to ten times a week,for ten to 144 weeks.The out-comes were reflected in five aspects:increasing the vocabulary in speaking;improving the language comprehen-sion,symbol recognition and vocabulary comprehension;improving both expressive and receptive language skills;improving participation in game diversity and game participation levels,communication,social interaction and interaction skills;and improving overall language and non-verbal communication skills. Conclusion Combining a variety of methods,such as individualized therapy,family participation,technologic assistance and interactive games,speech and language therapies and education are effective on spoken language production,language comprehension,speech production,social interaction and communication skills for children with IDD.

ObjectiveTo investigate the relationship of physical activity (PA) and cognitive function to sleep quality in older adults with cognitive impairment based on resting electroencephalogram (EEG), and to explore the mediating role of specific EEG markers in the relationship between PA and sleep quality. MethodsFrom March to May, 2024, 137 older adults were recruited from Chenfu Jiayuan and Qiangwei Jiuli in Songjiang district, and Luyan communities in Jinshan district, Shanghai. The assessments included Montreal Cognitive Assessment (MoCA), International Physical Activity Questionnaire-Short Form (IPAQ-SF) and Pittsburgh Sleep Quality Index (PSQI), along with a five-minute EEG recording. ResultsThere was significant difference in sleep quality among older adults with different levels of cognitive impairment (t = -7.400, P < 0.001). The PSQI total score was negatively correlated with MoCA scores (r = -0.412, P < 0.001) and total physical activity level (PAL) (r = -0.363, P < 0.001). The θ power in the frontal areas (F3, F4) was significantly correlated with both PSQI scores and PAL (P < 0.01). The θ power in F3 + F4 exhibited a significant partial (effect size = -0.0004, 95%CI -0.0007 to -0.0002) mediating effect between PA and sleep quality in older adults with cognitive impairment. ConclusionOlder adults with more severe cognitive impairment tend to have poorer sleep quality, whereas higher PAL is associated with better sleep quality. PA can indirectly influence sleep quality in older adults with cognitive impairment by affecting θ power (F3 + F4).