OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

Objective:Elucidating causal links between gut microbiota and breast malignancies using mendelian randomization(MR)to Identify specific causal microbial taxa.Methods:Genome-wide association studies(GWAS)summary statistics on gut microbiota and breast malignancies,MiBioGen studied GWAS(N=18473)as exposure samples,and GWAS(N=123579)of breast malignancies in the IEU Open GWAS database as outcome samples.The in-verse variance weighted(IVW),weighted median and MR-Egger methods were used to analyze the MR statistical re-suits.Results:Increased abundance of Pasteurellales increased the risk of breast malignancy(IVW PFDR＜0.05,OR=1.21,95％Cl:1.07～1.36),heterogeneity test and pleiotropy test showed no effect on causality,and the"leave-one-out"method showed that the identified causal association was not driven by any single instrumental variable.The causal relationship is positive.Conclusion:Elevated abundance of pasteurellales in the gut microbiota is associated with an increased risk of breast malignancies

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.

The success of"New Medical Sciences"in higher education requires effective tools in evalua-ting students'performance in courses.Previously,we reported a teamwork(T),critique(C)and ap-preciation(A)(TCA)ideological and political model,a teaching model widely applied in Basic Medical courses.TCA is an abbreviation derived from Tricarboxylic Acid Cycle in Biochemistry as an analogy for nurturing the abilities of thinking and teamwork(T),critique(C)and appreciation(A),which hope-fully could provide students with moral norms for cognition,science and life.This paper further explores the tools to assess the educational outcomes of the TCA model,by which teachers can collect feedback and reflect on teaching quality and effectiveness.Addressing the challenges of individual differences in large classes,fragmented learning feedback,and the difficulty of measuring meta-cognition in educational evaluation,this study employs strategies of value-added assessment,matrix assessment and norm-transfer-able assessment to evaluate the TCA abilities from the aspects of thinking quality,thinking creativity,co-operation ability,iterative thinking,dialectical thinking and job responsibility.By modifying/using 18 e-valuation tools in Education and Psychology,we have established a rubric system composed of 30 primary indicators(with 11 newly designed,10 partly modified and 9 directly adopted),along with 49 secondary indicators and 98 tertiary indicators to enhance the feasibility of the evaluation process.This rubric sys-tem was applied to Biochemistry teaching among the five-year-program undergraduates at Air Force Medi-cal University.Specifically,thinking and teamwork are evaluated by creative works from"the magic bio-chemical-circle",while critiques are assessed in large classes under the guidance of basic and clinical teachers,coupled with appreciation measured by job responsibility in a task-driven virtual reality(VR)project.The results indicate that Biochemistry teaching not only accumulates knowledge in students,but also achieves the goals in nurturing values and cognition.The inclusion of creative performance evalua-tion,cooperative learning and clinical case studies,can enhance students'interpersonal skills,coopera-tion,quality of thinking,creative thinking,iterative thinking and dialectical thinking to varying degrees.TCA-based Biochemistry teaching has a long-lasting impact on character education,and is capable of in-ducing positive long-term changes in students'cognition and lifestyle.Taken together,with the help of this rubric system,teachers can promptly acknowledge the effectiveness of their teaching,thereby facilita-ting their teaching strategies.

Objective:To analyze the association between standardized management of clinical research, initiated by investigators and guided by clinical research management policies in healthcare institutions, and changes in the research behavior of graduate students.Methods:Theses related to cardiovascular health published by graduate students in the Sichuan-Chongqing region of China between January 2019 and June 2024 were retrieved from the China National Knowledge Infrastructure database. Multilevel models were used to analyze changes in ethical compliance awareness, research methodology standardization, and academic collaboration of graduate students before and after policy implementation. Using Shapiro Wilk test and percentage representation.Results:Among the 712 theses included in this study, the proportion of studies with ethical review reports increased from 44.50% to 55.32% following the implementation of standardized management [odds ratio ( OR)=1.80, P=0.017]. Standardized management significantly improved the quality scores of cross-sectional studies and randomized controlled trials ( P<0.001), as well as significantly increased the frequencies of multi-center collaboration ( OR=2.84, P=0.001) and intra-provincial collaboration ( OR=2.80, P=0.001). Conclusions:Standardized clinical research management shows significant association with positive changes in the research behavior of graduate students. Further optimization of management measures is recommended to comprehensively enhance the clinical research capabilities of graduate students.

Objective:To analyze the key factors,hierarchical structure and internal action paths that affect the ability improvement of medical insurance management personnel in public hospitals,and to provide theoretical basis and practical reference for strengthening the construction of medical insurance management talent teams in hospitals.Methods:Through the mutual verification of literature analysis,policy interpretation and interview results,an index system of influencing factors for the ability improvement of medical insurance management personnel in public hospitals was constructed.A hybrid method combining DEMATEL-ISM-MICMAC was adopted to define the relationships,divide the levels and conduct driving force-dependence analysis of the influencing factors.Results:There are a total of 12 key factors influencing the ability improvement of medical insurance management personnel in public hospitals.Through the ISM model,these influencing factors can be classified into four levels:surface factors,intermediate factors,deep factors,and essential factors.With the help of MICMAC analysis,it can be classified into the spontaneous factor group of"low driving force-low dependence",the independent factor group of"high driving force-low dependence"and the dependent factor group of"low driving force-high dependence".Conclusion:Policy interpretation and knowledge reserve are the fundamental driving factors for ability improvement;Professional ethics and responsibilities are the deep-seated supporting factors of the ability system.The regulatory capacity of medical insurance funds is a key outcome and performance manifestation.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.

Objective:Elucidating causal links between gut microbiota and breast malignancies using mendelian randomization(MR)to Identify specific causal microbial taxa.Methods:Genome-wide association studies(GWAS)summary statistics on gut microbiota and breast malignancies,MiBioGen studied GWAS(N=18473)as exposure samples,and GWAS(N=123579)of breast malignancies in the IEU Open GWAS database as outcome samples.The in-verse variance weighted(IVW),weighted median and MR-Egger methods were used to analyze the MR statistical re-suits.Results:Increased abundance of Pasteurellales increased the risk of breast malignancy(IVW PFDR＜0.05,OR=1.21,95％Cl:1.07～1.36),heterogeneity test and pleiotropy test showed no effect on causality,and the"leave-one-out"method showed that the identified causal association was not driven by any single instrumental variable.The causal relationship is positive.Conclusion:Elevated abundance of pasteurellales in the gut microbiota is associated with an increased risk of breast malignancies

Objective:To analyze the key factors,hierarchical structure and internal action paths that affect the ability improvement of medical insurance management personnel in public hospitals,and to provide theoretical basis and practical reference for strengthening the construction of medical insurance management talent teams in hospitals.Methods:Through the mutual verification of literature analysis,policy interpretation and interview results,an index system of influencing factors for the ability improvement of medical insurance management personnel in public hospitals was constructed.A hybrid method combining DEMATEL-ISM-MICMAC was adopted to define the relationships,divide the levels and conduct driving force-dependence analysis of the influencing factors.Results:There are a total of 12 key factors influencing the ability improvement of medical insurance management personnel in public hospitals.Through the ISM model,these influencing factors can be classified into four levels:surface factors,intermediate factors,deep factors,and essential factors.With the help of MICMAC analysis,it can be classified into the spontaneous factor group of"low driving force-low dependence",the independent factor group of"high driving force-low dependence"and the dependent factor group of"low driving force-high dependence".Conclusion:Policy interpretation and knowledge reserve are the fundamental driving factors for ability improvement;Professional ethics and responsibilities are the deep-seated supporting factors of the ability system.The regulatory capacity of medical insurance funds is a key outcome and performance manifestation.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.