BACKGROUND:Peripheral nerve axon rupture seriously affects patients' physical function and mental health.Microsurgery,nerve autograft,nerve allograft,fibrin glue and catheter technology are the main treatments for peripheral nerve injury,each of which has its own advantages and disadvantages,but the overall treatment effect is not satisfactory.Despite the clinical success of Schwann cells in promoting axonal regeneration,there are still many challenges in the treatment with Schwann cells,such as slow expansion of Schwann cells,immune rejection,and low survival rate of transplanted cells.OBJECTIVE:To summarize the role and mechanism of Schwann cells in promoting the regeneration of peripheral nerve axons,and the difficulties and challenges of Schwann cells in the process of nerve regeneration treatment.METHODS:PubMed,Medline,WanFang,VIP,and CNKI were searched by computer using the search terms of"Schwann cells,synaptic Schwann cell,macrophage,peripheral nerve axon rupture,Wallerian degeneration,Peripheral nerve axon regeneration,Central nervous system repair"in English and Chinese.Literature related to Schwann cell proliferation and differentiation,promotion of peripheral nerve regeneration,and clinical applications was retrieved from database inception to October 2024,and a total of 95 articles were finally included for review.RESULTS AND CONCLUSION:Schwann cells interact with macrophages,T cells and other cells,to initiate the regeneration process through signaling pathways,including Krox20/C-Jun,NRG-1/ErbB,Notch,MAPK,and PI3K/Akt/mTOR,synthesize and release nerve growth factors,and thus promote regeneration of the peripheral nervous system.Schwann cells have been experimentally demonstrated to have great potential in peripheral nerve repair and are expected to become the key target of therapeutic intervention.However,there are still problems such as difficulties in cell harvest and culture,as well as the occurrence of other diseases during the treatment process.

Animal experimentation constitutes a critical link between basic research and clinical application, making its research quality and translational efficiency paramount. Although considerable progress has been made in standardizing operational procedures and ethical guidelines, the standardization of outcome evaluation systems has significantly lagged, creating a key bottleneck that constrains the quality of biomedical research and evidence synthesis. This deficiency is manifested by pronounced heterogeneity in outcome selection across similar studies, incomplete methodological reporting, and disparate criteria for result interpretation, which severely impairs the comparability of findings and the evidence integration. To cope with this challenge, this paper systematically introduces a mature methodological tool from clinical research–the core outcome set (COS)–and explores its construction strategies and application potential in the field of animal experimentation. Given the extensive diversity of animal experiments, a pragmatic strategy of "focusing on key areas, implementing phased pilots, and promoting gradual expansion" should be adopted. This approach prioritizes the development of domain-specific COS for disease areas characterized by high research volume, urgent translational needs, and well-established animal models. A multi-source integration pathway for COS development is detailed, comprising systematic literature searches, methodological appraisals, and expert consensus, with the feasibility of leveraging artificial intelligence (AI) to enhance efficiency also being examined. The development and promotion of such COS are not intended to restrict scientific exploration; rather, they aim to establish a new, tiered evaluation paradigm consisting of "core outcomes" (mandatory), "recommended outcomes" (encouraged), and "exploratory outcomes" (optional). This framework is expected not only to enhance research quality through standardization and to adhere to the "3R" principles but also to accelerate the accumulation of high-quality evidence. This, in turn, provides a solid foundation for higher-level evidence synthesis, ultimately facilitating the effective translation of basic research findings into clinical practice and providing an essential methodological framework for scientific advancement in relevant disciplines.

BACKGROUND:Peripheral nerve axon rupture seriously affects patients' physical function and mental health.Microsurgery,nerve autograft,nerve allograft,fibrin glue and catheter technology are the main treatments for peripheral nerve injury,each of which has its own advantages and disadvantages,but the overall treatment effect is not satisfactory.Despite the clinical success of Schwann cells in promoting axonal regeneration,there are still many challenges in the treatment with Schwann cells,such as slow expansion of Schwann cells,immune rejection,and low survival rate of transplanted cells.OBJECTIVE:To summarize the role and mechanism of Schwann cells in promoting the regeneration of peripheral nerve axons,and the difficulties and challenges of Schwann cells in the process of nerve regeneration treatment.METHODS:PubMed,Medline,WanFang,VIP,and CNKI were searched by computer using the search terms of"Schwann cells,synaptic Schwann cell,macrophage,peripheral nerve axon rupture,Wallerian degeneration,Peripheral nerve axon regeneration,Central nervous system repair"in English and Chinese.Literature related to Schwann cell proliferation and differentiation,promotion of peripheral nerve regeneration,and clinical applications was retrieved from database inception to October 2024,and a total of 95 articles were finally included for review.RESULTS AND CONCLUSION:Schwann cells interact with macrophages,T cells and other cells,to initiate the regeneration process through signaling pathways,including Krox20/C-Jun,NRG-1/ErbB,Notch,MAPK,and PI3K/Akt/mTOR,synthesize and release nerve growth factors,and thus promote regeneration of the peripheral nervous system.Schwann cells have been experimentally demonstrated to have great potential in peripheral nerve repair and are expected to become the key target of therapeutic intervention.However,there are still problems such as difficulties in cell harvest and culture,as well as the occurrence of other diseases during the treatment process.

This study systematically examined the effects of atomization as a transdermal permeation enhancer on the transdermal delivery of active ingredients with different physicochemical properties and investigated the underlying mechanisms. Porcine ear skin served as an in vitro model, and skin permeation experiments were conducted using Franz diffusion cells. Receptor fluids were collected at specific time points, and samples of the stratum corneum and viable epidermis–dermis were separated and prepared. Quantitative and visualization methods, including high-performance liquid chromatography, fluorescence derivatization, and confocal laser scanning microscopy, were used to compare skin retention and transdermal permeation of adenosine (AD), tranexamic acid (TXA), calcein (CAL), and tocopheryl acetate (TA) under atomized and non-atomized conditions. Additionally, transepidermal water loss (TEWL) measurements and attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR) were employed to analyze the mechanism behind the penetration enhancement caused by atomization. The findings showed that atomization increased skin retention within the stratum corneum and viable epidermis–dermis, as well as the transdermal permeation of all four active ingredients to varying degrees. The most significant enhancement was observed for TXA, which has a relatively low molecular weight and moderate lipophilicity, while the enhancement effects for highly hydrophilic AD and highly lipophilic TA were comparatively limited; however, atomization significantly increased the skin retention of TA. TEWL results indicated that skin permeability increased within 4 hours after atomization and largely recovered within 8 hours. ATR-FTIR analysis suggested that atomization may facilitate transdermal delivery by disrupting the lipid order and keratin conformation in the stratum corneum.This study provides theoretical support and experimental references for the advancement of atomization transdermal delivery technology, as well as the design and development of related atomization products.

ObjectiveTo investigate the therapeutic mechanism of artemether in diabetic sarcopenia（DS）using network pharmacology and animal experiments. MethodsPotential active components and therapeutic targets were screened using artemisinin as the parent compound. The predicted targets were intersected with DS-related targets， followed by construction of a protein-protein interaction （PPI） network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed to identify the key biological processes and signaling pathways. Molecular docking was further used to evaluate the binding affinity between artemether and core targets. The DS mouse model was established using db/db mice， followed by artemether intervention. Fasting blood glucose， body weight， diabetes-related symptoms， body composition， grip strength， serum and skeletal muscle triglyceride levels， and muscle fiber cross-sectional area （CSA） were assessed. The expression levels of forkhead box O1 （FoxO1）， Atrogin-1， muscle RING finger protein 1 （MuRF1）， acyl-CoA synthetase short-chain family member 2 （ACSS2）， carnitine palmitoyltransferase 2 （CPT2）， and fatty acid-binding protein 3 （FABP3） in skeletal muscle were detected by qRT-PCR， Western blot， immunofluorescence， and immunohistochemistry. In addition， metabolomics was performed to analyze changes in acylcarnitine metabolites in skeletal muscle. ResultsA total of 68 overlapping targets between artemether and diabetic sarcopenia （DS） were identified. The core targets included AKT1， FoxO1， NFKB1， FBXO32， and TRIM63， which were mainly enriched in the phosphoinositide 3-kinase/protein kinase B （PI3K-Akt） signaling pathway， forkhead box O （FoxO） signWaling pathway， tumor necrosis factor （TNF） signaling pathway， and insulin resistance-related pathways. Molecular docking analysis showed that artemether exhibited favorable binding affinity with the core targets. Animal experiments demonstrated that artemether reduced fasting blood glucose， ameliorated metabolic symptoms， increased lean mass and grip strength， decreased serum and skeletal muscle triglyceride levels， and increased muscle fiber cross-sectional area （CSA） in DS mice. In addition， artemether downregulated the mRNA and protein expression levels of FoxO1， FBXO32/Atrogin-1， TRIM63/MuRF1， ACSS2， CPT2， and FABP3， and improved the disturbance of acylcarnitine metabolism in skeletal muscle. ConclusionArtemether improves metabolic and skeletal muscle phenotypes in DS mice. Its effects may be associated with the amelioration of lipid metabolic disorders and the downregulation of FoxO1 and its downstream ubiquitin-proteasome pathway-related factors Atrogin-1 and MuRF1 in skeletal muscle.

Objective:To investigate the function and mechanism of exosome Linc00665 in modulating CD8+T cell immunoreactivity to promote radiotherapy resistance in OSCC.Methods:HOEC,SCC9 and SCC9-RR exosomes were extracted and identified,and the expression of Linc00665 was detected by qRT-PCR in cell lines and exosomes.The expression of TNF-α,IFN-γ,perforin and granzyme B in each treatment group was detected by ELISA(PBS,SCC9 exo,SCC9-RR exo).The killing ability of CD8+T cells against SCC9 cells in each treatment group was detected by CCK-8 assay.The targets of Linc00665 were further bioinformatically ana-lyzed and verified by qRT-PCR and Western blot.The expression of Linc00665,miR-28-5p and PD-1 in CD8+T cells was exogenous-ly regulated,the expression of immunoreactive factors in the supernatants of each treatment group was detected by ELISA(NC,sh-Linc00665,miR-28-5p inhibitor,sh-PD-1),and the killing ability of cells in each group was detected by CCK-8 method.Results:The concentrations of TNF-α,IFN-γ,perforin and granzyme B in the supernatants of cell culture in the SCC9-RR exo/CD8+T group were significantly decreased compared with those in the PBS/CD8+T group and the SCC9 exo/CD8+T group(P＜0.05),and the kill-ing ability of the cells in the SCC9-RR exo group was significantly decreased compared with those in the PBS group and the SCC9 exo group(P＜0.05),suggesting that SCC9-RR exo could inhibit the tumor killing ability of CD8+T cells.qRT-PCR results suggested that Linc00665 was highly expressed in the SCC9-RR cell line as well as exosome(P＜0.05).It was further verified by bioinformat-ics analysis that Linc00665 could regulate PD-1 expression via miR-28-5p,thereby modulating CD8+T cell immunoreactivity to pro-mote OSCC radiotherapy resistance.Conclusion:Exosome Linc00665 regulates CD8+T cell immunoreactivity through miR-28-5p/PD-1 axis to promote OSCC radiotherapy resistance.

Objective To explore the mechanism of modified Sijunzi Decoction in the intervention of premature ovarian failure(POF)rats through PTEN-mediated PI3K/AKT signaling pathway.Methods Totally 50 SPF-grade healthy female SD rats were divided into normal group(10 rats)and model group(40 rats).The model group was injected with cyclophosphamide to establish a POF model,and then randomly divided into model group and TCM low-,medium-and high-dosage group,with 10 rats in each group,TCM low-,medium-and high-dosage group were given modified Sijunzi Decoction 6.3,12.6,25.2 g/kg by gavage,the normal group and model group were given equal volume of normal saline,once a day for 28 days.The general condition and body mass of rats in each group were observed and recorded daily.After administration,the ovarian index was measured,HE staining was used to observe the morphology of ovarian tissue,ELISA was used to detect the contents of serum estradiol(E2)luteinizing hormone(LH),follicle-stimulating hormone(FSH),anti-Müllerian hormone(AMH),gonadotropin-releasing hormone(GnRH)and β-endorphin(β-EP),RT-PCR was used to detect the mRNA expression of PTEN,PI3K and AKT in ovarian tissue,Western blot was used to detect the protein expression of PTEN,PI3K,AKT,p-PI3K and p-AKT,immunohistochemistry was used to detect the positive expression of PTEN,PI3K and AKT.Results Compared with the normal group,the rats in the model group were depressed,the hair fell off,the diet and drinking water were reduced,the stools became thinner,the body mass was reduced(P<0.05),and the ovarian index was reduced(P<0.05),the ovarian tissue structure was disordered,the number of follicles decreased,and the contents of serum LH,FSH and GnRH increased(P<0.05),the contents of E2,AMH and β-EP decreased(P<0.05),the expression of PTEN mRNA and protein decreased(P<0.05),the expressions of PI3K and AKT mRNA and protein increased(P<0.05),and the expressions of p-PI3K and p-AKT protein increased(P<0.05).Compared with the model group,the general condition of rats in each dosage of TCM groups improved significantly,the body mass increased(P<0.05),ovarian index increased(P<0.05),the number of follicles in rat ovarian tissue increased,the contents of LH,FSH and GnRH decreased(P<0.05),the contents of E2,AMH and β-EP increased(P<0.05),the expression of PTEN mRNA and protein increased(P<0.05),the expression of PI3K and AKT mRNA and protein decreased(P<0.05),and the protein expression of p-PI3K and p-AKT decreased(P<0.05).Conclusion Modified Sijunzi Decoction may regulate the PI3K/AKT signaling pathway mediated by PTEN,repair the excessive consumption of follicles in ovarian tissue of POF rats,improve the ovarian function,so as to intervene the process of POF.

Objective:To analyze the influencing factors of low fall alertness in elderly inpatients,construct a risk prediction model and validate it,providing a reference for clinical medical staff to identify elderly inpatients with low fall alertness in the early stage.Methods:A total of 605 elderly inpatients treated in Yijishan Hospital affiliated to Wannan Medical College from Oct 2023 to Mar 2024 were enrolled and randomly divided into the training group(n=423)and validation group(n=182)at a ratio of 7∶3.The patients were evaluated using a general information questionnaire,the Social Frailty Screening Tool(HALFT),the Tilburg Frailty Indicator(TFI),and the Self-Awareness of Falls in Elderly scale(SAFE).Multivariate logistic analysis was used to determine the influencing factors of low fall alertness in elderly inpatients.RStudio was used to construct a risk prediction model of low fall alertness.The discrimination,calibration,and clinical net benefit of the model were verified using the receiver operating characteristic(ROC)curves,calibration plots,and decision curve analysis(DCA).Results:Multivariate logistic analysis showed that the history of falls,monthly income,previous physical activity time,social frailty score and TFI score were independent risk factors for low fall alertness in elderly inpatients.The Hosmer-Lemeshow χ2 test showed that χ2=8.863,P=0.354,indicating good calibration of the prediction model.The area under the ROC curve of the training group and the validation group were 0.860(95%CI:0.815-0.904)and 0.937(95%CI:0.888-0.986),respectively,and the maximum Youden indices of the model was 0.576 and 0.788,respectively,indicating good discrimination of the model.The DCA decision curve showed that the model had good clinical effectiveness.Conclusion:The constructed model has a good prediction effect and can help clinical medical staff quickly and effectively screen out elderly inpatients at risk of low fall alertness.

Objective To screen the mutations of ABCC8 gene in probands of maturity-onset diabetes of the young pedigrees,and investigate it sgenetic and clinical characteristics.Methods Whole exome sequencing were performed to screen ABCC8 mutations in 56 MODY probands who were admitted to Department of Endocrinology and Metabolism,Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to December 2023.The mutations were verified by Sanger sequencing,and all participants were genotyped.Clinical phenotypes of the mutation carriers were compared with non-DM controls within the families.The identified mutations were evaluated by bioinformatic softwires.Then the pharmacogenomic characteristics of the mutation carriers were analyzed.Results Two heterozygous mutations D655V and R825Q were identified in two MODY probands and their families respectively,and the D655V was a novel mutation.Bioinformatics studies showed that both mutations were deleterious and pathogenic.In comparison with non-DM controls in the two families,mutation carriers with diabetes exhibited significantly lower fasting insulin/fasting plasma glucose,two-hour postprandial insulin/two-hour postprandial insulin plasma glucose,homeostatic model assessment-β(P<0.05).Treatment with oral hypoglycemic agents such as metformin or insulin in these mutation carriers resulted in a moderate reduction in plasma glucose levels.However,switching to targeted Sulfonylurea's(SUs)proved to be more effective.Conclusions In this study,the prevalence of MODY12 is 3.6%in these MODY pedigrees.The remarkable hypoglycemic efficacy of SUs suggests that both D655V and R825Q were activating mutations of ABCC8,and maybe the cause of MODY12 characterized by impaired insulin secretion.

Objective To screen the mutations of ABCC8 gene in probands of maturity-onset diabetes of the young pedigrees,and investigate it sgenetic and clinical characteristics.Methods Whole exome sequencing were performed to screen ABCC8 mutations in 56 MODY probands who were admitted to Department of Endocrinology and Metabolism,Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to December 2023.The mutations were verified by Sanger sequencing,and all participants were genotyped.Clinical phenotypes of the mutation carriers were compared with non-DM controls within the families.The identified mutations were evaluated by bioinformatic softwires.Then the pharmacogenomic characteristics of the mutation carriers were analyzed.Results Two heterozygous mutations D655V and R825Q were identified in two MODY probands and their families respectively,and the D655V was a novel mutation.Bioinformatics studies showed that both mutations were deleterious and pathogenic.In comparison with non-DM controls in the two families,mutation carriers with diabetes exhibited significantly lower fasting insulin/fasting plasma glucose,two-hour postprandial insulin/two-hour postprandial insulin plasma glucose,homeostatic model assessment-β(P<0.05).Treatment with oral hypoglycemic agents such as metformin or insulin in these mutation carriers resulted in a moderate reduction in plasma glucose levels.However,switching to targeted Sulfonylurea's(SUs)proved to be more effective.Conclusions In this study,the prevalence of MODY12 is 3.6%in these MODY pedigrees.The remarkable hypoglycemic efficacy of SUs suggests that both D655V and R825Q were activating mutations of ABCC8,and maybe the cause of MODY12 characterized by impaired insulin secretion.