ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected， 40 female C57BL/6 mice were randomly divided into sham operation group， model group， estrogen group（estradiol valerate， 1.3×10^-4 g·kg^-1）， Erzhiwan low and high dose groups（3.12， 9.36 g·kg^-1）， with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage， and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function， hematoxylin-eosin（HE） staining was used to observe myocardial morphological changes， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of estrogen， N-terminal pro-brain natriuretic peptide（NT-proBNP）， hypersensitive troponin T（hs-TnT）， total cholesterol（TC）， triglyceride（TG）， low density lipoprotein cholesterol（LDL-C）， high density lipoprotein cholesterol（HDL-C）， interleukin（IL）-1β， IL-18 and tumor necrosis factor-α（TNF-α）. The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase（PI3K） and protein kinase B（Akt） in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression levels of PI3K， Akt， phosphorylated（p）-Akt were detected by Western blot. ResultsCompared with the sham operation group， the model group showed abnormal cardiac function， increased myocardial fiber space， cardiomyocyte atrophy， sarcoplasmic aggregation， and occasional dissolution or rupture of muscle fiber， the level of estrogen in the serum was decreased， the levels of NT-proBNP， hs-TnT， IL-1β， IL-18， TNF-α， TG， TC and LDL-C were increased， and the level of HDL-C was decreased（P<0.01）. Compared with the model group， Erzhiwan could increase the level of estrogen， improve the abnormal cardiac function， reduce the pathological injury of myocardial tissue， decrease the levels of myocardial injury markers（NT-proBNP， hs-TnT） and inflammatory factors（IL-1β， IL-18， TNF-α）， decrease the levels of TG， TC， LDL-C， and increased the level of HDL-C（P<0.01）. The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan， which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway， PI3K-Akt pathway， cyclic guanosine monophosphate（cGMP）-protein kinase G（PKG） pathway and other metabolic pathways. Compared with the sham operation group， the levels of phosphatidylcholine（PC， 11 types） and phosphatidylethanolamine（PE， 5 types） in mouse myocardial tissue of the model group were increased（P<0.05， P<0.01）， and the mRNA and protein expressions of PI3K and p-Akt were decreased（P<0.05， P<0.01）. Compared with the model group， the levels of PC（11 types） and PE（5 types） were decreased（P<0.05， P<0.01） in myocardial tissue of Erzhiwan group， the mRNA and protein expressions of PI3K and p-Akt were elevated（P<0.01）. ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice， improve the abnormal cardiac function， improve lipid metabolism disorder， and reduce the levels of myocardial injury markers and inflammatory factors， which involves a number of signaling and metabolic pathways in the heart， among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.

Objective Responding to the imperative to modernize vocational education and establish competency-oriented systems,this study investigates the development of on-campus training bases for speech and hearing rehabilitation(SHR)programs within Chinese higher vocational colleges(HVC).It analyzes their functional role and essential compo-nents,and propose a competency-oriented,modular framework for on-campus training based on World Health Organization(WHO)rehabilitation competency framework(RCF),and professional education standards.Methods This research synthesized theories of higher vocational education and practical pedagogy(e.g.,situated learn-ing,experiential learning and constructivism)with analyses of domestic and international SHR educational poli-cies and standards.It examined the strategic importance and essential components(hardware,software,human re-sources,management)of on-campus training bases in the context of higher vocational education.Synthesizing RCF with standards from ASHA(knowledge and skills acquisition,KASA),International Association of Logope-dics and Phoniatrics(IALP),and Teaching Standards for Higher Vocational Schools from Ministry of Education of the People's Republic of China,a core SHR professional competency model tailored for HVC was developed.This model subsequently guided the design of a modular on-campus training curriculum and associated pedagogi-cal approaches.Results On-campus training bases were pivotal platforms that bridge theory and practice,facilitating'teaching-learning-doing'integration within HVC SHR programs.Effective base construction necessitated synergistic integration across four key domains:hardware facilities(meeting specialized acoustic/equipment needs),software resources(case libraries,standard operating procedure and digital tools),'dual-role'human resources and robust manage-ment systems(operations,evaluation,industry-education linkages).Derived from RCF and related standards,a core SHR competency framework was developed,encompassing dimensions such as foundational knowledge and ethics,assessment(audiological;speech-language),intervention(audiological rehabilitation and technology;speech-language),and communication and collaboration.Consequently,eight core training modules were de-signed,including basic operations of hearing testing,introduction to objective hearing testing,preliminary hear-ing aid fitting,application of standardized speech-language assessment tools,simulation of articulation and voice disorder assessment and intervention,simulation of swallowing disorder screening and basic training,comprehen-sive case analysis and rehabilitation plan development,and practice of professional literacy and communication skills;detailing objectives,activities,and resources,and intended for seamless integration with theoretical cours-es and off-campus practicum,establishing a cohesive'curriculum-training-practicum'continuum.Furthermore,a suite of adaptable pedagogical models,including problem-based learning,case-based learning,simulation-based training,project-based learning and the flipped classroom,were recommended for implementing these modules.Conclusion The effective development of on-campus training bases for SHR programs in HVC necessitates establishing a systematic,competency-oriented practical teaching environment.Grounded in RCF,and essential SHR knowl-edge,skills and abilities,this study proposes a framework incorporating eight core training modules and comple-mentary pedagogical models,providing a theoretically grounded,practically applicable blueprint for enhancing the educational quality and substance of these bases within HVC.Successful realization hinges upon the synergis-tic development of the four key elements(hardware,software,human resources,management),deep integration between training activities,the curriculum,and practicum experiences,and the application of innovative pedago-gy to cultivate student potential.

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel-cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.

Objective:To evaluate the detection rate, anatomical distribution, and influencing factors of bone marrow edema-like signal (BMELS) in the knees of amateur marathon runners.Methods:This was a cross-sectional study. This study publicly recruited amateur marathon runners through the Hangzhou Long-distance Running Association from January 2019 to December 2024. Based on knee magnetic resonance imaging (MRI) results, participants were divided into a BMELS-positive group (BMELS present in at least one knee) and a BMELS-negative group. General clinical information was collected from participants using a questionnaire. All participants underwent a knee MRI scan to screen for the presence of BMELS and to assess its severity. Logistic regression models were used to analyze the associated factors of BMELS in amateur marathon runners, while Spearman′s correlation analysis assessed the correlation between BMELS grade and these factors.Results:A total of 60 subjects (120 knee joints) were enrolled, including 39 males (65%), aged (40.0±8.4) years. Of these, 39 were in the BMELS-positive group, and 21 were in the BMELS-negative group. The BMELS detection rate for the 120 knee joints of these 60 subjects was 53.3% (64/120). BMELS were detected in 43.3%(52/120) of the femur, 34.2% (41/120) of tibia and 17.5% (21/120) of patella. Multivariate logistic regression analysis showed an independent positive correlation between monthly running volume and knee BMELS in amateur marathon runners ( OR=1.007, 95% CI: 1.000-1.013, P=0.035). Spearman′s correlation analysis showed a weak positive correlation between the BMELS grade of the knees and the monthly running volume of amateur marathon runners ( r s=0.360, P=0.005). Conclusions:The detection rate of knee BMELS is high in amateur marathon runners, and they are distributed in a way that is characteristic of the region, with a higher incidence in the medial femoral condyle. In this population, monthly running volume is independently associated with knee BMELS, with a higher grade associated with greater monthly running volume.

Objective: To analyze the association between each regional fat mass and total body bone mineral density (BMD) in children and adolescents aged 7-17 years in Beijing, so as to provide theoretical basis and practical guidance for implementing interventions. Methods: From September to December 2020, a stratified cluster random sampling method was used to select 1 423 children and adolescents aged 7-17 years in Tongzhou District, Beijing. Dual energy X-ray absorptiometry (DXA) was employed to measure regional body composition and total body BMD. Multiple linear regression was used to analyze the association between regional fat mass and total body BMD. Results: The median (interquartile range) fat mass values for total body, upper limbs, abdomen, hips, and thighs were 13.51(8.84, 19.21), 1.59(1.08, 2.23), 0.73(0.39, 1.29), 2.32(1.46, 3.26), 5.29(3.59, 7.21)kg, respectively. After adjusting for covariates, the results of multiple linear regression analysis showed that total body fat mass (β=0.010), abdominal fat mass (β=-0.100), and hip fat mass (β=0.104) were significant associations with total body BMD (all P<0.01). Sexstratified analysis revealed that in boys, total body fat mass (β=0.008) and hip fat mass (β=0.058) were positively associated with BMD, while thigh fat mass (β=-0.038) showed a negative association with total body BMD (all P<0.05). In girls, total body fat mass (β=0.013), hip fat mass (β=0.163), and thigh fat mass (β=0.023) were positively associated with total body BMD, whereas abdominal fat mass (β=-0.196) showed a negative association with total body BMD (all P<0.05). Among children and adolescents with body fat percentage below the standard range, within the standard range and above the standard range, total body fat masses were positively associated with total body BMD (β=0.021, 0.016, 0.015); among children and adolescents with body fat percentage within the standard range while upper limb (β=-0.042), abdominal (β=-0.067), and thigh fat mass (β=-0.018) showed negative associations with total body BMD, and hip fat mass demonstrated a positive association with total body BMD (β=0.082) (all P<0.05). Conclusion Regional fat distribution is associated with total body BMD in children and adolescents, with the nature of these associations varying by sex and body fat percentage.

Objective:To evaluate the detection rate, anatomical distribution, and influencing factors of bone marrow edema-like signal (BMELS) in the knees of amateur marathon runners.Methods:This was a cross-sectional study. This study publicly recruited amateur marathon runners through the Hangzhou Long-distance Running Association from January 2019 to December 2024. Based on knee magnetic resonance imaging (MRI) results, participants were divided into a BMELS-positive group (BMELS present in at least one knee) and a BMELS-negative group. General clinical information was collected from participants using a questionnaire. All participants underwent a knee MRI scan to screen for the presence of BMELS and to assess its severity. Logistic regression models were used to analyze the associated factors of BMELS in amateur marathon runners, while Spearman′s correlation analysis assessed the correlation between BMELS grade and these factors.Results:A total of 60 subjects (120 knee joints) were enrolled, including 39 males (65%), aged (40.0±8.4) years. Of these, 39 were in the BMELS-positive group, and 21 were in the BMELS-negative group. The BMELS detection rate for the 120 knee joints of these 60 subjects was 53.3% (64/120). BMELS were detected in 43.3%(52/120) of the femur, 34.2% (41/120) of tibia and 17.5% (21/120) of patella. Multivariate logistic regression analysis showed an independent positive correlation between monthly running volume and knee BMELS in amateur marathon runners ( OR=1.007, 95% CI: 1.000-1.013, P=0.035). Spearman′s correlation analysis showed a weak positive correlation between the BMELS grade of the knees and the monthly running volume of amateur marathon runners ( r s=0.360, P=0.005). Conclusions:The detection rate of knee BMELS is high in amateur marathon runners, and they are distributed in a way that is characteristic of the region, with a higher incidence in the medial femoral condyle. In this population, monthly running volume is independently associated with knee BMELS, with a higher grade associated with greater monthly running volume.

Objective Responding to the imperative to modernize vocational education and establish competency-oriented systems,this study investigates the development of on-campus training bases for speech and hearing rehabilitation(SHR)programs within Chinese higher vocational colleges(HVC).It analyzes their functional role and essential compo-nents,and propose a competency-oriented,modular framework for on-campus training based on World Health Organization(WHO)rehabilitation competency framework(RCF),and professional education standards.Methods This research synthesized theories of higher vocational education and practical pedagogy(e.g.,situated learn-ing,experiential learning and constructivism)with analyses of domestic and international SHR educational poli-cies and standards.It examined the strategic importance and essential components(hardware,software,human re-sources,management)of on-campus training bases in the context of higher vocational education.Synthesizing RCF with standards from ASHA(knowledge and skills acquisition,KASA),International Association of Logope-dics and Phoniatrics(IALP),and Teaching Standards for Higher Vocational Schools from Ministry of Education of the People's Republic of China,a core SHR professional competency model tailored for HVC was developed.This model subsequently guided the design of a modular on-campus training curriculum and associated pedagogi-cal approaches.Results On-campus training bases were pivotal platforms that bridge theory and practice,facilitating'teaching-learning-doing'integration within HVC SHR programs.Effective base construction necessitated synergistic integration across four key domains:hardware facilities(meeting specialized acoustic/equipment needs),software resources(case libraries,standard operating procedure and digital tools),'dual-role'human resources and robust manage-ment systems(operations,evaluation,industry-education linkages).Derived from RCF and related standards,a core SHR competency framework was developed,encompassing dimensions such as foundational knowledge and ethics,assessment(audiological;speech-language),intervention(audiological rehabilitation and technology;speech-language),and communication and collaboration.Consequently,eight core training modules were de-signed,including basic operations of hearing testing,introduction to objective hearing testing,preliminary hear-ing aid fitting,application of standardized speech-language assessment tools,simulation of articulation and voice disorder assessment and intervention,simulation of swallowing disorder screening and basic training,comprehen-sive case analysis and rehabilitation plan development,and practice of professional literacy and communication skills;detailing objectives,activities,and resources,and intended for seamless integration with theoretical cours-es and off-campus practicum,establishing a cohesive'curriculum-training-practicum'continuum.Furthermore,a suite of adaptable pedagogical models,including problem-based learning,case-based learning,simulation-based training,project-based learning and the flipped classroom,were recommended for implementing these modules.Conclusion The effective development of on-campus training bases for SHR programs in HVC necessitates establishing a systematic,competency-oriented practical teaching environment.Grounded in RCF,and essential SHR knowl-edge,skills and abilities,this study proposes a framework incorporating eight core training modules and comple-mentary pedagogical models,providing a theoretically grounded,practically applicable blueprint for enhancing the educational quality and substance of these bases within HVC.Successful realization hinges upon the synergis-tic development of the four key elements(hardware,software,human resources,management),deep integration between training activities,the curriculum,and practicum experiences,and the application of innovative pedago-gy to cultivate student potential.

Objective To explore the construction of a core competency framework and content for higher vocational speech-lan-guage-hearing rehabilitation technology programs based on World Health Organization rehabilitation competency framework(RCF). Methods Utilizing RCF and integrating the educational objectives for higher vocational speech-language-hearing reha-bilitation programs outlined by the Ministry of Education in 2022,as well as the technical documents from the In-ternational Association of Logopedics and Phoniatrics and the American Speech-Language-Hearing Association,this study analyzed the professional activities in speech-language-hearing rehabilitation technology to construct a competency framework based on RCF and give details in the specific content of each domain. Results The competency for speech-language-hearing rehabilitation technology encompassed seven domains:core val-ues,beliefs,practice,professionalism,learning and development,management and leadership,and research.Each domain was subdivided into specific competency elements and professional activities. Conclusion Establishing a higher vocational education system for speech-language-hearing rehabilitation technology based on RCF will help to set educational objectives,and construct curriculum systems,so that to cultivate practi-tioner who meet social needs and possess comprehensive professional skills and competencies.

Pancreatic ductal adenocarcinoma is a highly malignant gastrointestinal tumour with increasing incidence,and KRAS(KRAS Proto-Oncogene,GTPase)gene mutation is the main driver of its development.Pancreatic ductal adenocarcinomas with different types of KRAS mutations show significant differences in their molecular features and clinical manifestations.Given the critical role of KRAS gene mutations in the progression of pancreatic ductal adenocarcinoma,the development of targeted drugs against KRAS mutations has been a research hot spot.This review has comprehensively summarized the molecular features and clinical characteristics of pancreatic ductal adenocarcinomas with different KRAS mutations,discussed in detail the targeted drugs developed against these mutations and their applications in clinical treatment,outlooked the future perspectives of the development of therapeutic strategies.