Type 1 diabetes mellitus is a chronic autoimmune disease caused by the destruction of pancreatic islet β cells. Pancreatic islet transplantation provides a treatment method for patients with type 1 diabetes mellitus to restore endogenous insulin secretion. However, some problems limit the widespread application of islet transplantation, such as the shortage of donors and post-transplantation rejection damage. Mesenchymal stem cell-derived exosome (MSC-Exo) has become a potential tool for islet transplantation therapy due to their immunomodulatory and tissue repair capabilities. MSC-Exo shows great promise for application, because of low immunogenicity, easily being stored and transported, and the potential as drug delivery vehicles. However, challenges such as preparation, purification, standardization and safety verification need to be overcome before converting MSC-Exo into clinical practice. Therefore, this article reviews the application and potential advantages of MSC-Exo in islet transplantation, aiming to providing more effective and safer treatment options for patients with type 1 diabetes mellitus.

BACKGROUND:The stemness index may be associated with the prognosis and immune infiltration of sarcoma,but the specific regulatory mechanism and characteristic genes have yet to be fully elucidated. OBJECTIVE:To investigate the correlation between stem cells and prognosis as well as immune infiltration in sarcoma employing the gene stemness index model and to identify the ferroptosis signature genes associated with sarcoma stem cells. METHODS:The sarcoma RNA sequencing data and related clinical information were obtained from the Cancer Genome Atlas(TCGA).The sarcoma RNA sequencing data were grouped using the sarcoma stemness index.Survival data were used to analyze prognosis between groups.Differentially expressed genes were obtained for pathway enrichment and immune infiltration analysis.Ferroptosis-related differential genes were used to construct a protein interaction network and analyze prognostic correlation.Rhabdomyosarcoma cell lines were cultured and divided into adherent cell group and stem cell group.The adherent cell group received no intervention,while the stem cell group was treated with serum-free culture to enrich stem cells in rhabdomyosarcoma cells.qRT-PCR was used to evaluate stemness markers,ferroptosis-related genes,and mRNA expression of ferroptosis-related markers in the cells. RESULTS AND CONCLUSION:(1)Patients were divided into high and low stemness index groups based on the median stemness index.The progression-free survival of patients in the high stemness index group was lower than that in the low stemness index group by disease risk prediction,suggesting poor prognosis.(2)According to GO and KEGG analysis,the groups with high and low stemness indices differed from one another.There were differences in immune infiltration between the high and low stemness index groups.Nine of the 23 ferroptosis-related genes in the differential genes have the potential to establish a highly correlated network of protein interactions.Patients with high expression of IDO1,IFNG,and AQP5 have a better prognosis,while those with high expression of CA9 have a poor prognosis.(3)The qRT-PCR results demonstrated a significant upregulation of stem cell-related markers NANOG,SOX2,and OCT4 mRNA expressions in the stem cell group compared to the adherent cell group(P<0.05).Compared to the adherent cell group,the stem cell group exhibited decreased mRNA expression level of ferroptosis-related marker SLC7A11(P<0.05)while showing increased levels of ACSL4,GPX4,FTH1,and COX2(P<0.05).Compared to the adherent cell group,the stem cell group displayed decreased mRNA expression level of differentially expressed gene CA9 alongside elevated levels of IDO1,IFNG,and AQP5(P<0.05).Stem cells were strongly associated with sarcoma survival and ferroptosis by bioinformatics analysis and experimental verification.Sarcoma stem cells have aberrant expression of CA9,IDO1,IFNG,and AQP5,which may serve as new targets for sarcoma therapy as well as diagnostic indicators.

Objective: To investigate the protective effects and underlying mechanisms of sodium pyruvate (SP) on RBC storage lesions using an oxidative damage model. Methods: Six units of leukocyte-depleted suspended RBCs (discarded for non-infectious reasons within three days post-collection) were randomly assigned to four groups: negative control (NS), positive control (PS), experimental group 1 (SP1), and experimental group 2 (SP2). Oxidative stress was induced in the PS group by the addition of hydrogen peroxide (H O ), while SP1 and SP2 received SP supplementation at different concentrations (25 mM and 50 mM, respectively) in the presence of H O . After 1 hour of incubation, RBC morphology was assessed microscopically, and biochemical indicators including glutathione (GSH), malondialdehyde (MDA), methemoglobin (MetHb), adenosine triphosphate (ATP), and Na /K -ATPase activity were measured. Results: RBCs in the PS group exhibited pronounced morphological damage, including cell shrinkage and echinocyte formation, whereas both SP-treated groups showed significantly reduced structural injury. SP treatment led to elevated GSH levels and decreased concentrations of MDA and MetHb, suggesting attenuation of oxidative stress. Additionally, SP enhanced intracellular ATP levels and Na /K -ATPase activity, thereby contributing to membrane stability. Notably, the SP2 group (50 mM) demonstrated superior protective effects compared to SP1 (25 mM). Conclusion: Sodium pyruvate effectively attenuates oxidative storage lesions in RBCs, primarily through its antioxidant properties, energy metabolism supporting ability, and celluar membrane stabilizing function. These findings suggest SP as a promising additive for enhancing the quality and safety of stored RBCs.

ObjectiveTo establish a rat model of osteoarthritis and study the anti-inflammatory effects and mechanisms of fraxetin. MethodsEighteen 8-week-old male SPF-grade SD rats were randomly divided into three groups: Rats in the blank group received a right articular cavity injection of 50 μL of normal saline for 1 week; the model and intervention groups were injected with monosodium iodoacetate (MIA) into the right joint cavity to induce osteoarthritis, while the intervention group subsequently received fraxetin (5 mg·kg^-1·d^-1) for 1 week. Four weeks after drug intervention, abdominal aortic blood was collected. The animals were then euthanized, and knee joint cartilage were collected. The cartilage samples were stained with hematoxylin-eosin, safranin O-fast green, and toluidine blue for histopathological examination and scoring using the Mankin and OARSI scoring systems. The trabecular bone volume/total volume (Tb.BV/TV), trabecular bone surface density/total volume (Tb.BS/TV), and trabecular number (Tb.N) of each group were compared and analyzed using a micro-CT scanning system. The expression levels of various inflammatory factors [tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6)], and cartilage oligomeric matrix protein (COMP) were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of mitogen-activated protein kinase p38 (p38 MAPK), phosphorylation-p38 MAPK (p-p38 MAPK), c-Jun N-terminal kinase (JNK), and phosphorylation-JNK (p-JNK) were measured by western blotting. ResultsThe staining of cartilage sections of rat knee joints showed that the articular surface defects in the model group were severe, while the cartilage destruction in the intervention group was relatively reduced. Micro-CT results showed that Tb.BV/TV, Tb.BS/TV and Tb.N in the intervention group were significantly higher than those in the model group (P < 0.05); the Mankin score in the model group was significantly higher than that in the blank group (P < 0.05), the Mankin score in the intervention group was significantly lower than that in the model group (P < 0.05); while the OARSI score in the intervention group was significantly lower than that in the model group (P < 0.05). The results of the enzyme-linked immunosorbent assay showed that the serum levels of TNF-α, IL-1β, IL-6, and COMP in the model group were significantly higher than those in the blank group (all P < 0.05), while those in the intervention group were significantly lower than in the model group (P < 0.05). Western blot results showed that the expression levels of p-p38 MAPK and p-JNK in the knee cartilage tissue were significantly lower in the intervention group than in the model group (both P < 0.05), and significantly higher in the model group than in the blank group (both P < 0.05). ConclusionFraxetin may play a therapeutic role in a monosodium iodoacetate-induced rat model of osteoarthritis through the p38 MAPK pathway.

ObjectiveTo establish a rat model of osteoarthritis and study the anti-inflammatory effects and mechanisms of fraxetin. MethodsEighteen 8-week-old male SPF-grade SD rats were randomly divided into three groups: Rats in the blank group received a right articular cavity injection of 50 μL of normal saline for 1 week; the model and intervention groups were injected with monosodium iodoacetate (MIA) into the right joint cavity to induce osteoarthritis, while the intervention group subsequently received fraxetin (5 mg·kg^-1·d^-1) for 1 week. Four weeks after drug intervention, abdominal aortic blood was collected. The animals were then euthanized, and knee joint cartilage were collected. The cartilage samples were stained with hematoxylin-eosin, safranin O-fast green, and toluidine blue for histopathological examination and scoring using the Mankin and OARSI scoring systems. The trabecular bone volume/total volume (Tb.BV/TV), trabecular bone surface density/total volume (Tb.BS/TV), and trabecular number (Tb.N) of each group were compared and analyzed using a micro-CT scanning system. The expression levels of various inflammatory factors [tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6)], and cartilage oligomeric matrix protein (COMP) were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of mitogen-activated protein kinase p38 (p38 MAPK), phosphorylation-p38 MAPK (p-p38 MAPK), c-Jun N-terminal kinase (JNK), and phosphorylation-JNK (p-JNK) were measured by western blotting. ResultsThe staining of cartilage sections of rat knee joints showed that the articular surface defects in the model group were severe, while the cartilage destruction in the intervention group was relatively reduced. Micro-CT results showed that Tb.BV/TV, Tb.BS/TV and Tb.N in the intervention group were significantly higher than those in the model group (P < 0.05); the Mankin score in the model group was significantly higher than that in the blank group (P < 0.05), the Mankin score in the intervention group was significantly lower than that in the model group (P < 0.05); while the OARSI score in the intervention group was significantly lower than that in the model group (P < 0.05). The results of the enzyme-linked immunosorbent assay showed that the serum levels of TNF-α, IL-1β, IL-6, and COMP in the model group were significantly higher than those in the blank group (all P < 0.05), while those in the intervention group were significantly lower than in the model group (P < 0.05). Western blot results showed that the expression levels of p-p38 MAPK and p-JNK in the knee cartilage tissue were significantly lower in the intervention group than in the model group (both P < 0.05), and significantly higher in the model group than in the blank group (both P < 0.05). ConclusionFraxetin may play a therapeutic role in a monosodium iodoacetate-induced rat model of osteoarthritis through the p38 MAPK pathway.

Chronic heart failure （CHF）， as the terminal stage of various cardiovascular diseases， is characterized by a prolonged clinical course and recurrent exacerbations. The coexistence of CHF with anxiety and depression falls under the category of psycho-cardiological diseases. Studies have demonstrated that anxiety and depression are closely associated with adverse outcomes including elevated risks of cardiovascular events and increased mortality in CHF patients. The complex pathogenesis poses challenges to modern medical treatments， which often face limited efficacy and concurrent side effects. According to the theory of Shaoyang Pivot in traditional Chinese medicine （TCM）， this paper elucidates that obstructed Shaoyang Pivot—manifested as Qi transformation disorder， dysregulated fluid metabolism， and abnormal distribution of ministerial fire-serves as a critical pathological basis for CHF with anxiety and depression. Bupleuri Radix-based Formulas， such as Xiao Chaihu Tang， Chaihu Guizhi Tang， and Chaihu Jia Longgu Muli Tang， aim to harmonize lesser Yang to restore the Qi transformation， activate Yang to promote water excretion， and redistribute ministerial fire， thus effectively alleviating pathological states such as Qi stagnation， blood stasis， water retention， and phlegm-fire disturbing the heart in CHF patients with anxiety and depression. Consequently， they mitigate symptoms of this psycho-cardiological disease. Mechanism studies have revealed that Bupleuri Radix-based formulas exhibit multi-target effects， including modulation of neurotransmitters， suppression of inflammatory responses， regulation of lipid metabolism， protection of cardiomyocytes， and improvement of the endothelial function. By interpreting the TCM pathogenesis of CHF with anxiety and depression from the theory of Shaoyang Pivot， this paper delves into the therapeutic principles and mechanisms of Bupleuri Radix-based formulas， providing a theoretical foundation for optimizing TCM diagnosis and treatment strategies for psycho-cardiological diseases.

As a widely used anti-tumor drug and anti-rheumatic drug in clinic, methotrexate (MTX) has many toxic and side effects, including gastrointestinal mucosa injury, central nervous system injury, liver and kidney function injury, etc. They often bring great trouble to the follow-up treatment of patients. The clarification of the mechanism of MTX toxicity to various organs has become the key to rescue the toxicity. The purpose of the article is to review the toxicity mechanism of MTX in various organs, so as to save the patients from the adverse reactions in clinical treatment.

BACKGROUND:Some studies have shown that the hounsfield units(HU)value based on lumbar CT can be used to screen osteoporosis.At present,the number of patients with pulmonary infection has increased;the number of patients with pulmonary infection and type 2 diabetes is also increasing,which increases the utilization rate of chest CT. OBJECTIVE:To investigate the role of lumbar 1 vertebral body HU value based on chest CT in the screening of type 2 diabetes mellitus osteoporosis. METHODS:The clinical data of 244 patients with type 2 diabetes mellitus treated in the First Affiliated Hospital of Chengdu Medical College from June 2020 to June 2022 were analyzed retrospectively.The bone mineral density was obtained by dual-energy X-ray absorptiometry.According to WHO's diagnostic criteria for osteoporosis,the subjects were divided into the non-osteoporosis group(n=120)and the osteoporosis group(n=124).The general condition,T value and HU value of lumbar 1 vertebra in chest CT were compared,and the relationship between the HU value and T value of each position was analyzed and the accuracy of type 2 diabetes mellitus osteoporosis was evaluated. RESULTS AND CONCLUSION:(1)There was no significant difference in sex,age,body mass index,glycosylated hemoglobin,mean blood glucose,calcium(Ca),phosphorus(P),time of type 2 diabetes mellitus,history of hypertension and history of hyperlipidemia between the two groups(P>0.05).(2)The HU value was positively correlated with the lowest T value of the hip(r=0.619,P<0.01);the HU value was positively correlated with the hip T value(r=0.584,P<0.01),and the HU value was positively correlated with the femoral neck T value(r=0.641,P<0.01).When the HU value was 98,the prediction of type 2 diabetes mellitus osteoporosis had good accuracy,and the sensitivity was 70.8%.(3)It is concluded that the HU value of the lumbar 1 vertebra based on chest CT examination is of good value for osteoporosis screening in patients with type 2 diabetes mellitus,and may be an opportunistic and cost-free supplementary screening method for type 2 diabetes mellitus osteoporosis.

Objective To establish a risk model for lactate metabolism-related genes in soft tissue sarcomas,and to explore their correlation with tumor mutational burden,immune cells,immune related functions and immune checkpoints in the tumor microenvironment.Methods The differentially expressed genes associated with lactate metabolism in soft tissue sarcoma were obtained after intersecting the differentially expressed genes extracted by TCGA and GTEx database with lactate metabolism-related gene sets from the Msigdb database.The pathway enrichment analysis was carried out by gene ontology and Kyoto Encyclopedia of Genes and Genomes.By the univariate Cox regression and least absolute shrinkage and selection operator to construct a risk score model,and divided the soft tissue sarcomas samples into high-risk and low-risk groups.Finally,the differences of the tumor mutational burden and immunity in the tumor microenvironment between the two groups were analyzed.Results A total of 29 differentially expressed genes associated with lactate metabolism were screened,and the results of pathways enrichment analysis showed that they were mainly related to metabolic processes.By constructing a predictive risk score model,soft tissue sarcoma samples were divided into high-risk and low-risk groups.Tumor mutational burden analysis showed that the first mutated gene was tumor protein p53 in all soft tissue sarcoma samples.Missense mutation was the most common type of somatic mutations,and the frequency of mutation was higher in the high-risk group than that in the low-risk group.The analysis of tumor microenvironment indicated that the infiltration of M0 and M2 macrophage was more in the high-risk group,while the low-risk group had a higher percentage of infiltrating CD8+T cells and monocytes.The immune related functional response and immune checkpoints expression was higher in the low-risk group.Conclusion The lactate metabolism scoring model can better evaluate the prognosis of patients with soft tissue sarcoma and reflect the state of tumor microenvironment.

Objective To investigate the molecular mechanism of ferroptosis in glioblastoma(GBM)and to provide insights for identifying new therapeutic targets.Methods GSE108474 was selected from gene expression omnibus(GEO)database and differentially expressed genes(DEGs)in GBM were obtained by using GEO2R,compared with the gene set in the Ferroptosis database(FerrDb)to identify ferroptosis-related gene.GO and KEGG enrich-ment analyses were conducted using DAVID database.A protein-protein interaction network was created using String website.Hub genes with high connectivity were confirmed using Cytoscape software.Prognostic and immune infiltration analyses were performed using TIMER website.RNA expression levels and gene correlation analyses were carried out using GEPIA website.Differential expression of hub gene proteins was analyzed by using the HPA database.Tumor immune characteristic correlations were examined using TISIDB database.Differences in mRNA expression of hub genes between tumor cells A172 and U251MG and normal astrocytes HA1800 were compared u-sing the quantitative real-time PCR.Results Out of 5 331 differentially expressed genes,114 were related to fer-roptosis.GO and KEGG enrichment analysis suggested that these 114 genes might play roles in positive regulation of gene expression,and affect tumor progression through ferroptosis and autophagy pathways.10 hub genes were i-dentified in the protein-protein interaction network,among which cluster of differentiation 44(CD44),murine double minute 2(MDM2)and signal transducer and activator of transcription 3(STAT3)were found to be highly expressed in tumors with lower survival rates.CD44,MDM2 and STAT3 mRNA expression were higher in GBM cells compared to normal cells.Protein expression of CD44,MDM2 and STAT3 was higher in high-grade glioma tis-sues than that in normal tissues.The expression of three genes in the tumor was negatively correlated with ferropto-sis.Immune infiltration analysis revealed that CD44,MDM2 and STAT3 in the tumor were related to the infiltration of neutrophils,CD4+T cells,and dendritic cells,and the expression of three genes was related to various chemo-kines and their receptors.Conclusion CD44,MDM2 and STAT3 may play a role in tumor ferroptosis and immune regulation,which have the potential to become a therapeutic target for GBM.