Objective To explore the effective induction scheme for differentiation of adipose-derived mesenchymal stem cell (ADMSC) to insulin producing cell (IPC). Methods Different schemes of small molecule compound were used to induce the differentiation of ADMSC. The purity of cells was analyzed by flow cytometry and the morphological changes of cells were observed under the microscope. The quality, performance and insulin related indicators of cells were detected by hematoxylin-eosin and immunohistochemical staining. The maturity and activity of cells were detected by dithizone (DTZ) and diacetylfluorescein/propidium iodide staining. The induction effect of ADMSC differentiated into IPC was analyzed. Results The purity of ADMSC reached more than 99%, and the sphere forming properties of schemes Ⅰ, Ⅱ and Ⅲ were good. Cell induction mass, the expression effects of pancreatic and duodenal homeobox 1 (PDX1), musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) and insulin and C peptide of schemes Ⅰ were both better than those of other schemes. The DTZ staining depth may be related to IPC maturity, among which the number of apoptotic cells in scheme Ⅰ was significantly less than that of scheme Ⅱ and Ⅲ. Conclusions Induction scheme Ⅰ may improve the differentiation efficiency of ADMSC to IPC and lay a certain foundation for future clinical IPC transplantation applications.

Objective To observe the rehabilitation treatment effect of using a comprehensive quality control model based on ICF concept and PDCA cycle management mode to intervene in stroke recovery patients.Methods The time segmenta-tion method was employed for grouping.A total of 114 stroke patients admitted to the hospital from June 1,2022 to February 28,2023 were selected as the control group,and 109 patients admitted from March 1,2023 to November 1,2023 were chosen as the study group.There was no statistically significant difference in the clinical data of the two groups of patients before treatment.The control group received conventional rehabilitation treatment,while the study group implemented the rehabilitation treatment based on the ICF concept and the PDCA"big loop with small loops"cyclic management mode on the basis of the control group.The basic information of the two groups of patients was compared,and the rehabilitation effects of the patients were comprehensively e-valuated by using the Fugl-Meyer assessment of upper and lower limb functions(with a total of 100 indicators),the Functional Independence Measure(FIM)score of daily activity ability(including 13 motor quality of life indicators and 5 cognitive quality of life indicators),and the satisfaction evaluation.Results After treatment,the scores of upper and lower limb function assess-ment and daily activity ability in both groups were significantly higher than those before treatment.Among them,all the scores of the study group were significantly better than those of the control group(P＜0.01),and the satisfaction of the study group was also significantly improved compared with that of the control group(P＜0.05).Conclusion The comprehensive quality control model based on the ICF concept and the PDCA cycle can significantly improve the rehabilitation effects and patient satisfaction of stroke patients in the recovery period.

Objective To observe the rehabilitation treatment effect of using a comprehensive quality control model based on ICF concept and PDCA cycle management mode to intervene in stroke recovery patients.Methods The time segmenta-tion method was employed for grouping.A total of 114 stroke patients admitted to the hospital from June 1,2022 to February 28,2023 were selected as the control group,and 109 patients admitted from March 1,2023 to November 1,2023 were chosen as the study group.There was no statistically significant difference in the clinical data of the two groups of patients before treatment.The control group received conventional rehabilitation treatment,while the study group implemented the rehabilitation treatment based on the ICF concept and the PDCA"big loop with small loops"cyclic management mode on the basis of the control group.The basic information of the two groups of patients was compared,and the rehabilitation effects of the patients were comprehensively e-valuated by using the Fugl-Meyer assessment of upper and lower limb functions(with a total of 100 indicators),the Functional Independence Measure(FIM)score of daily activity ability(including 13 motor quality of life indicators and 5 cognitive quality of life indicators),and the satisfaction evaluation.Results After treatment,the scores of upper and lower limb function assess-ment and daily activity ability in both groups were significantly higher than those before treatment.Among them,all the scores of the study group were significantly better than those of the control group(P＜0.01),and the satisfaction of the study group was also significantly improved compared with that of the control group(P＜0.05).Conclusion The comprehensive quality control model based on the ICF concept and the PDCA cycle can significantly improve the rehabilitation effects and patient satisfaction of stroke patients in the recovery period.

Objective To explore gene expression of key cell types in IgA nephropathy(IgAN)and regulatory role of key genes ADI1,BNIP3L and SERPINE2 in occurrence and development of IgAN.Methods The gene expression omnibus(GEO)and eQTLGen consortium database were used to perform Mendelian randomization(MR)and single-cell RNA sequencing(scRNA-seq).Key cell types of IgAN and causal relationship between ADI1,BNIP3L,SERPINE2 and IgAN were investigated.Expression profiles and screened out low expression genes were read through Seurat package,and used differential gene expression analysis to screen TOP100 highly expressed genes.In addition,were used sensitivity analysis and heterogeneity test were used to select significant results.Results ADI1(OR=0.946,95％CI:0.900-0.994,P=0.029),BNIP3L(OR=0.820,95％CI:0.707-0.950,P=0.008),SERPINE2(OR=0.958,95％CI:0.919-0.999,P=0.045)might be associated with a lower risk of IgAN.However,KLF6(OR=1.318,95％CI:1.036-1.678,P=0.025)was associated with high risk of IgAN.Conclusion Genetic characteristics of 18 key cell types including proximal renal tubule cells were revealed.ADI1,BNIP3L and SERPINE2 are closely related to the regulation of IgAN.

Objective To explore gene expression of key cell types in IgA nephropathy(IgAN)and regulatory role of key genes ADI1,BNIP3L and SERPINE2 in occurrence and development of IgAN.Methods The gene expression omnibus(GEO)and eQTLGen consortium database were used to perform Mendelian randomization(MR)and single-cell RNA sequencing(scRNA-seq).Key cell types of IgAN and causal relationship between ADI1,BNIP3L,SERPINE2 and IgAN were investigated.Expression profiles and screened out low expression genes were read through Seurat package,and used differential gene expression analysis to screen TOP100 highly expressed genes.In addition,were used sensitivity analysis and heterogeneity test were used to select significant results.Results ADI1(OR=0.946,95％CI:0.900-0.994,P=0.029),BNIP3L(OR=0.820,95％CI:0.707-0.950,P=0.008),SERPINE2(OR=0.958,95％CI:0.919-0.999,P=0.045)might be associated with a lower risk of IgAN.However,KLF6(OR=1.318,95％CI:1.036-1.678,P=0.025)was associated with high risk of IgAN.Conclusion Genetic characteristics of 18 key cell types including proximal renal tubule cells were revealed.ADI1,BNIP3L and SERPINE2 are closely related to the regulation of IgAN.

Objective To evaluate the effect of mesenchymal stem cell (MSC) coated-islets on instant blood-mediated inflammatory reaction (IBMIR) after islet transplantation. Methods MSC labeled with tracer and human islets were placed into an ultra-low adsorption cell culture dish, shaken and mixed twice at an interval of 0.5 h, and then incubated at 37 ℃ and 5% CO₂ for 24 h to obtain MSC-coated islets. The coating effect of MSC and in vitro function of the islets were assessed. A blood circulation tube-shaped model was established in vitro. In the blank control group, 0.2 mL of islet culture solution was added. In the islet group, 800 islet equivalent quantity (IEQ) of uncoated islets were supplemented. In the MSC-coated islets group, 800 IEQ of MSC-coated islets were added, and circulated for 60 min at 37 ℃. A portion of 0.5 mL blood sample was taken for routine blood test at 0, 30 and 60 min, respectively. After 60 min circulation, the blood sample was filtered with a 70 μm filter to collect plasma, blood clots and islets. Blood clots and islets were subject to hematoxylin-eosin (HE) staining and immunohistochemical staining. Morphological changes and the aggregation of CD11b-positive cells surrounding the islets were observed. The contents of plasma thrombin-antithrombin complex (TAT), tissue factor (TF), C3a, C5b-9, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1 and IL-8 were determined by enzyme-linked immune absorbent assay. Results After 24 h co-incubation, the islets were coated by MSC, with a coating degree of approximately 80%. In the islet and MSC-coated islet group, a large quantity of neutrophils and monocytes were observed surrounding the blood clots and islets, and the quantity of CD11b-positive cells in the MSC-coated islet group was less compared with that in the islet group. After co-incubation with the whole blood for 0, 30 and 60 min, the quantity of platelets, neutrophils and monocytes was declined in the MSC-coated and islet groups, and gradually decreased over time. Compared with the blank control group, the quantity of platelets, monocytes and neutrophils was lower, whereas the TF content was higher in the MSC-coated islet group. Compared with the islet group, the quantity of platelets, monocytes and neutrophils was higher, whereas the TAT and TF contents were less in the MSC-coated islet group, the differences were statistically significant (all P < 0.05). Compared with the blank control group, the expression levels of C3a, C5b-9, IL-6, TNF-α and IL-8 were up-regulated in the MSC-coated islet group. Compared with the islet group, the expression levels of C3a, C5b-9, IL-1β, IL-6, TNF-α, IL-8 and MCP-1 were down-regulated in the MSC-coated islet group, and the differences were statistically significant (all P < 0.05). Conclusions MSC-coated islets may reduce the exposure of islet TF in the blood and prevent the incidence of IBMIR during the coagulation response stage, thereby mitigating the injury and loss of islet allograft in the early stage of islet transplantation.

Islet transplantation is a promising treatment of diabetes mellitus and its complications. Nevertheless, dysfunction post-transplantation, rejection and shortage of donors are the bottleneck issues in the field of islet transplantation. Optimizing the preservation method of pancreas plays a positive role in obtaining a sufficient quantity of effective islets and maintaining their functions. During the culture stage, anti-rejection and anti-apoptosis treatment of islets, including mesenchymal stem cell (MSC), MSC-derived exosomes, anti-apoptosis drugs and gene modification, may become major approaches for islet protection and functional maintenance in clinical islet transplantation. Use of anti-instant blood-mediated inflammatory reaction (IBMIR) drugs after islet transplantation also plays a critical role in protecting islet function. In this article, the whole process from islet preparation to islet transplantation was illustrated, and relevant strategies of islet protection and functional maintenance were reviewed, aiming to provide reference for improving the quality of donors to compensate for the shortage of absolute quantity of donors and elevating the efficiency of islet transplantation.

Objective To identify the key genes and targeted protection methods affecting the survival of human islets. Methods Using bioinformatics method, the gene expression profile (GSE53454) was selected through screening and comparison from Gene Expression Omnibus(GEO) database. GEO2R tool was employed to screen the differentially expressed gene(DEG) between the human islets exposed (exposure group) and non-exposed (non-exposure group) to interleukin (IL)-1β and interferon (IFN)-γ for 24, 48 and 72 h, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID. Protein-protein interaction (PPI) network was constructed by STRING and Cytoscape apps. Results A total of 69 up-regulated DEGs and 2 down-regulated DEGs were identified. GO analysis showed that during the biological process, DEGs were enriched in the aspects of virus defense and inflammatory response. In cellular components, DEGs were significantly enriched in extracellular space, outside plasma membrane and extracellular regions. Regarding molecular functions, DEGs were significantly enriched in chemokine activity and cytokine activity. KEGG analysis revealed that DEGs were mainly enriched in multiple signaling pathways, such as cytokine-cytokine receptor interaction, virus protein-cytokine and cytokine-receptor interaction, etc. Ten key genes (STAT1, CXCL10, IRF1, IL6, CXCL9, CCL5, CXCL11, ISG15, CD274, IFIT3) with high connectivity were selected by STRING analysis, all of which were significantly up-regulated in human islets exposed to IL-1β and IFN-γ. Six genes (STAT1, CXCL10, CXCL9, CXCL11, CCL5, IL6) were screened by KEGG enrichment analysis, mainly in Toll-like receptor signaling pathway. Conclusions STAT1, CXCL10, CXCL9, CXCL11, CCL5 and IL6 are the key genes affecting the survival of human islets, which are mainly enriched in Toll-like receptor signaling pathway and act as important targets for islet protection.

As an effective procedure for type 1 diabetes mellitus and end-stage type 2 diabetes mellitus, islet transplantation could enable those patients to obtain proper control of blood glucose levels. Instant blood-mediated inflammatory reaction (IBMIR) is a nonspecific inflammation during early stage after islet transplantation. After IBMIR occurs, coagulation cascade, complement system activation and inflammatory cell aggregation may be immediately provoked, leading to loss of a large quantity of transplant islets, which severely affects clinical efficacy of islet transplantation. How to alleviate the islet damage caused by IBMIR is a hot topic in islet transplantation. Heparin and etanercept, an inhibitor of tumor necrosis factor-α, are recommended as drugs for treating IBMIR following islet transplantation. Recent studies have demonstrated that multiple approaches and drugs may be adopted to mitigate the damage caused by IBMIR to the islets. In this article, the findings in clinical and preclinical researches were reviewed, aiming to provide reference for the management of IBMIR after islet transplantation.

Islet transplantation is one of the effective therapies for diabetes mellitus. Nevertheless, multiple issues still exist, such as shortage of donors and adverse reactions caused by long-term use of immunosuppressants, which limit the islet survival post-transplantation. Microencapsulated islet transplantation may overcome these difficulties to certain extent, whereas many factors, such as the destruction of immune isolation microenvironment within the microcapsules and insufficient supply of oxygen and nutrients, constrain the application of microencapsulated islet transplantation in clinical practice. In recent years, how to enhance the effect of microencapsulated islet transplantation has been gradually studied. The application of stem cells in microencapsulated islet transplantation has steadily become a research hot spot. Therefore, the optimizing strategies for microencapsulated islet transplantation and the application of stem cells in microencapsulated islet transplantation were reviewed, and the potential improvement techniques of microencapsulated islet transplantation were investigated in this article, aiming to provide reference for further clinical application of microencapsulated islet transplantation.