OBJECTIVE To construct an evaluation index system for the core competencies of ethics committee members of drug clinical trial institution， providing a basis for optimizing the training system for committee members， improving the quality of ethical review， and fully safeguarding the safety and rights of subjects. METHODS Using methods such as literature research and expert consultation， a preliminary core competency evaluation index system was constructed. The Delphi method was employed to revise and validate it， ultimately forming an evaluation index system for the core competencies of ethics committee members. Based on this system， a questionnaire survey was conducted among 90 ethics committee members from 29 drug clinical trial institutions nationwide， comparing their importance rating and self-assessment scores of the core competency indexes. RESULTS The evaluation system constructed included 4 primary indicators （ethics and professional knowledge， ethics review ability， communication and expression ability， moral integrity and work style） and 39 secondary indicators （familiarity with the content of clinical trial-related laws and regulations， ability to complete project ethics review and identify ethical defects in research protocols within a short period of time， ability to judge the scientific value of clinical research， etc.）. The results of questionnaire survey showed that the interviewed ethics committee members had significant capability gaps in dimensions such as regulatory knowledge， ethical norms， review efficiency， risk judgment， and problem analysis. The differences between the importance rating scores of corresponding secondary indicators and the self-assessment scores were all no less than 0.38. CONCLUSIONS This study has developed a quantifiable and stratified core competency assessment tool for ethics committee members. It can provide a scientific framework for committee member training， qualification certification， and standardized management of ethics committees.

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Objective:To explore the clinical and genetic characteristics of a fetus diagnosed with Congenital myasthenic syndrome type 16 (CMS16).Methods:A couple who had visited Tianjin Medical University General Hospital in February 2018 due to "adverse outcome of two pregnancies" was selected as the study subject. Clinical data was gathered. Peripheral blood and amniotic fluid samples were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Low-depth whole-genome sequencing was carried out to detect copy number variation (CNV) in the fetus.Results:The couple′s first pregnancy had resulted in a miscarriage at 27 + 5 weeks, when ultrasound had revealed pleural effusion and polyhydramnios in the fetus. Their second pregnancy was terminated at 30 + 5 weeks due to fetal hand malformations, polyhydramnios and pleural fluid. Both couple had denied family history of genetic conditions. For their third pregnancy, no CNV abnormality was detected, whilst a compound heterozygous variants, including a maternally derived c. 3172C>T (p.R1058W) and paternal c. 1431delG (p.K477fs*89) in the SCN4A gene were detected. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 3172C>T (p.R1058W) was predicted as a likely pathogenic variant (PM1+ PM2_supporting+ PP3+ PP4), whilst the c. 1431delG (p.K477fs*89) was predicted as a pathogenic variant (PVS1+ PM2_supporting+ PP4). Conclusion:The c. 3172C>T (p.R1058W) and c. 1431delG (p.K477fs*89) compound heterozygous variants of the SCN4A gene probably underlay the CMS16 in the third fetus.

Objective To explore the gene expression profile in paraspinal muscle degeneration(PMD)and identify key ferroptosis genes.Methods RNA sequencing was performed on paraspinal muscle tissue of 3 normal and 3 PMD patients respectively to obtain differentially expressed genes.Through protein-protein interaction(PPI)and gene functional enrichment analysis,the intersection of ferroptosis genes was identified to identify key hub genes associated with ferroptosis.The diagnostic value for PMD disease was analyzed by receiver operating characteristic(ROC)curves.Results A total of 292 differentially expressed genes were identified in PMD.Among them,125 genes were significantly downregulated and 167 genes were significantly upregulated.Bioinformatics analysis revealed that 14 differentially expressed genes were associated with ferroptosis.Among them,ferroptosis genes MUC1,ATF3 and CDKN1A were key hub genes with good specificity and sensitivity for diagnosing PMD.Functional enrichment analysis revealed that they may mediate the occurrence and progression of PMD by regulating cell apoptosis,ferroptosis and skeletal muscle tissue development and differentiation.Conclusion Ferroptosis genes MUC1,ATF3 and CDKN1A can serve as biomarkers for diagnosing PMD,providing theoretical basis for decoding the pathological mechanism of PMD and developing new drugs.

BACKGROUND:The problem of intervertebral disc injury and degeneration has been studied in many ways.Many studies have shown that intervertebral disc injury and degeneration is driven by mechanical loading factors.However,the potential relationship between common phenotypes of intervertebral disc injury and degeneration and mechanical loading factors has been rarely summarized. OBJECTIVE:To summarize the types of common structural abnormalities exhibited by intervertebral disc injury and degeneration in the published literature,and sum up the potential links to the types of mechanical loading that lead to these structural abnormalities in in vitro and ex vivo experimental studies. METHODS:Using the terms"intervertebral disc failure,intervertebral disc injury,mechanical load,mechanical factor,load factor,biomechanics"as Chinese and English key words in PubMed,CNKI,and WanFang databases,articles related to intervertebral disc injury degeneration and mechanical load factors were retrieved.Literature screening was performed according to the inclusion and exclusion criteria,and 88 articles were finally included. RESULTS AND CONCLUSION:(1)Common structural abnormalities of intervertebral discs include decreased intervertebral disc height,disc bulge,osteophyte formation,annulus fibrosus tear,intervertebral disc herniation or disc prolapse,endplate damage,Schmorl nodes and intervertebral disc calcification.Intervertebral discs are susceptible to mechanical load types such as compression,bending,axial rotation,and compound loads.(2)The compressive load mainly causes the decrease of the proteoglycan content and the water-binding ability of the intervertebral disc,leading to the decrease or swelling of the intervertebral disc and further damage and degeneration of the intervertebral disc.In addition,the excessive compressive load causes greater damage to the endplate.(3)Bending load and axial rotation load damage the annulus fibrosus more than the endplate,and prolonged or repeated bending loads can cause tearing of the fibrous annulus and herniation or prolapse of the intervertebral disc,while pure axial rotation loads can induce less damage to the intervertebral disc and only cause the tear of the annulus fibrosus.(4)However,when different load types act in combination,it is more likely to result in high stress on the disc and a greater risk of disc injury.(5)Injury and degeneration of the intervertebral disc present progressive structural damage,and early prevention and protection are particularly important in clinical practice.Future tissue engineering research can start with early repair of the intervertebral disc.

BACKGROUND:Exosomes play a role in all stages of wound repair,and there is currently a large body of research on exosomes in skin wound repair,which has been shown to have great potential for clinical applications. OBJECTIVE:To summarize and discuss the main mechanisms and clinical applications of exosomes in the treatment of skin wounds,in order to promote the clinical translation of exosomes. METHODS:PubMed,clinicaltrials.gov,China National Knowledge Infrastructure,Food and Drug Administration database,and Chinese Clinical Trial Register were searched from inception to March 2023.The English search terms were"exosomes,wound healing,stem cells,chronic wound,immunoregulation,inflammation,skin,therapeutic use,isolation,characterization,infections".The Chinese search terms were"exosomes,wound healing,stem cells,immunomodulation,clinical applications".A total of 79 articles were included for the summary. RESULTS AND CONCLUSION:(1)Exosomes can improve and accelerate wound healing through inflammation regulation,immune protection,angiogenesis,cell proliferation and migration,and collagen remodeling.(2)Exosomes derived from stem cells have mature preparation techniques and related mechanism research,which is currently the mainstream research direction.Non-stem cell-derived exosomes have the advantages of convenience,economy,and easy production,and can be used as a supplement for clinical applications.(3)The clinical application of exosomes is still in its infancy,but has great potential for application.Various exosome modification techniques have laid the foundation for the future development of clinically personalized services and require further research.(4)The clinical translation of exosomes faces many challenges,such as low yield,high heterogeneity,lack of unified standards for isolation,purification,and quality control,and difficulties in storage.

BACKGROUND:Vibration environment can cause spinal injury,especially in patients with scoliosis.At present,there is no information about the inherent mode of the whole spine from T1 to the pelvis in scoliosis patients in the free state. OBJECTIVE:To analyze the dynamic characteristics of the whole spine in patients with scoliosis by the finite element method. METHODS:Based on CT scan images,a three-dimensional finite element model of the T1-pelvic total spine of an 11-year-old patient with thoracolumbar biflexion scoliosis was established,and the Cobb angles of thoracolumbar scoliosis were 36° and 24°,respectively.The mode analysis in the free state of the whole spine was carried out by the finite element method. RESULTS AND CONCLUSION:The fifteen-order free modes of the spine were extracted,and the dynamic characteristics of the scolio-curved spine were obtained.The resonance frequency distribution of the spine was concentrated.The thoracic vertebra was the most deformed in the whole spine model,and the amplitude of the thoracic vertebra was larger than that of the lumbar vertebra.Modal analysis was used to analyze the vibration characteristics of scoliosis patients in the vibration environment.It is of great significance to determine the natural frequency,vibration mode,and amplitude of scoliosis patients for analyzing the vibration characteristics of scoliosis.

BACKGROUND:Osteoporosis vertebral compression fracture is a common fracture secondary to osteoporosis,and there is currently a lack of effective predictive indicators and methods for osteoporosis vertebral compression fracture. OBJECTIVE:To investigate the predictive effects of paravertebral muscle degeneration,functional cross-sectional area,and percentage of fat infiltration on osteoporotic vertebral compression fractures. METHODS:The 224 patients with osteoporosis diagnosed from January 2018 to June 2022 were included.They were followed up for more than 2 years.They were divided into fracture group and non-fracture group according to the presence and absence of vertebral fracture.The detailed information of demographics,body mass index,bone mineral density and so on were collected.The functional cross-sectional area and percentage of fat infiltration of bilateral Psoas major muscle and extensor dorsi(Erector spinae muscles muscle and multifidus muscle)at the level of lower endplate of L2 vertebral body were measured and calculated. RESULTS AND CONCLUSION:(1)224 patients were ultimately included,of which 126 had fractures as the fracture group and 98 had no fractures as the non-fracture group.There was no statistically significant difference in age,gender,height,body mass,body mass index,and fracture segment between the two groups(P>0.05).(2)The bone mineral density of the fracture group was significantly lower than that of the non-fracture group(P<0.05).Functional cross-sectional areas of Psoas major muscle and extensor dorsi in the fracture group were significantly lower than those in the non-fracture group(P<0.05).The percentage of fat infiltration of the extensor dorsi in the fracture group was significantly higher than that in the non-fracture group(P<0.05).There was no significant difference in percentage of fat infiltration of Psoas major muscle between the two groups(P>0.05).(3)Receiver operating characteristic analysis showed that the vertebral bone mineral density,percentage of fat infiltration of extensor dorsi,functional cross-sectional area of extensor dorsi and percentage of fat infiltration of Psoas major muscle were 0.903 g/cm2,35.426%,418.875 mm2,and 6.375%,respectively.The areas under curve were 0.634,0.755,0.876,and 0.585,respectively.(4)These findings indicate that paravertebral muscle degeneration is strongly associated with the occurrence of osteoporotic vertebral compression fractures.The functional cross-sectional area of extensor dorsi muscle can effectively predict the occurrence of osteoporotic vertebral compression fractures,which is helpful for early prevention and treatment of osteoporotic vertebral compression fractures.

Objective:To construct and purify four respiratory syncytial virus (RSV) PreF proteins through gene sequence design and optimization and evaluate their immunogenicity.Methods:Coronin-1A and T4 trimer protein gene sequences were optimized with Human and CHO codons, and then added to RSV F protein sequence. The above plasmids were transfected into Expi293F cells for protein expression. After purification by nickel column, four trimer proteins were prepared. SDS-PAGE and Western blot were performed for protein identification. BALB/c mice were immunized at week 0 and week 3, and blood samples were collected to measure the activities of binding and neutralizing antibodies in serum.Results:SDS-PAGE and Western blot showed that the four proteins had stable trimer structure. Antigen-antibody affinity test showed that the four trimer proteins had strong affinity with RSV-specific monoclonal antibodies 8897, D25, Motavizumab, AM14 and Palivizumab. The titers of antibodies induced by the two T4 trimers were higher after the initial immunization, while there was a substantial increase in the titers of antibodies induced by Human codon-optimized trimer protein after the second immunization.Conclusions:PreF trimer protein can be prepared by adding any of the two different heterotrimer motifs, and induce effective binding and neutralizing antibodies in mice.

This paper mainly discusses the practical significance of the internal quality assurance system of graduate students in a military medical university based on training process management. The integrated internal quality assurance system follows the direction of three core steps—course learning, scientific research practice training, and dissertation writing, and highlights nine key points—learning foundation in admission education and training, knowledge acquisition in course learning, application ability in teaching and scientific research practice, innovation ability in academic activities and innovation competitions, topic selection quality in thesis proposal, training quality in mid-term assessment, paper quality in dissertation writing, output quality in thesis defense, and comprehensive quality in diploma awarding. Our exploration and practical experience is shared in this article.