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.

Objective:To investigate the inpact of thyroid cancer-derived cancer-associated fibroblasts(CAF) autophagy on papillary thyroid cancer(PTC).Methods:CAF and normal fibroblasts were isolated from cancerous and adjacent normal thyroid tissues from four PTC patients. Expressions of fibroblast activation protein(FAP) and α-smooth muscle actin in cells were assessed. Conditioned medium of CAF and normal fibroblasts were prepared and used to culture PTC cells. The effects of CAF and normal fibroblasts on survival, proliferation, migration, invasion and iodine uptake of PTC cells were evaluated through cell proliferation assay, cell scratch assay, cell invasion assay, and cell iodine uptake assay. The autophagy level of CAF was also evaluated. Autophagy inhibition and activation were used to regulate the autophagy of CAF, and then their effects on PTC cell proliferation, migration and invasion were further evaluated. The in vivo effect of CAF autophagy on PTC xenograft tumor growth was evaluated.Results:CAF exhibited higher FAP expression and basal autophagy levels. PTC cells co-cultured with CAF-conditioned media showed enhanced proliferation, migration, invasion, and reduced iodine uptake. Autophagy inhibition reduced these effects, while autophagy activation further promoted them. In vivo, inhibiting CAF autophagy suppressed tumor growth.Conclusions:CAF promotes PTC cell malignancy through autophagy activation, enhancing proliferation, migration, and invasion while reducing iodine uptake.

OBJECTIVE To investigate the effect of salvianolic acid A(SAA)on functions of neutro-phils after activation in vitro.METHODS Rat neutrophils were extracted and activated by lipopolysac-charide(LPS)at 0.3,1,3 mg·L-1,and the number of adherent neutrophils and myeloperoxidase(MPO)activity were detected to determine the concentration of LPS.Neutrophils were divided into the control,model,model+4-aminobenzohydrazide(ABH)20 μmol·L-1,and model+SAA 1,3 and 10 μmol·L-1 groups.LPS was stimulated with 3 mg·L-1 for 30 min,and the neutrophil adhesion rate was detected by immunofluorescence after 1 h of drug incubation.After 2 h of drug incubation,phagocytosis of neutro-phils was detected by immunofluorescence and fluorescein isothiocyanate-immunoglobulin G.After 3 h of drug incubation,the neutrophil adhesion rate to endothelial cells was detected by colorimetric assay.Intracellular MPO activity and hypochlorous acid(HOCl)production were investigated by colorimetric assay in response to the degranulation function.Intracellular reactive oxygen species(ROS)levels were detected by probe assay,and mitochondrial membrane potential by JC-1 assay.The levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)and total antioxidant capacity(T-AOC)were measured to reflect oxidation function of neutrophils.RESULTS LPS increased the number of adherent cells and MPO activity in a concentration-dependent manner,with 3 mg·L-1 of LPS showing the most significant effect,which was used for subsequent experiments.Compared with the control group,LPS-activated neutrophil adhesion and phagocytosis were significantly enhanced.MPO activity and HOCl production significantly increased.The levels of ROS and MDA in LPS-activated neutrophils were significantly increased while the mitochondrial membrane potential and the levels of SOD,GSH,T-AOC were significantly decreased,indicating that the oxidative stress ability was enhanced.Compared with the model group,SAA dose-dependently inhibited LPS-induced adhesion,phagocytosis,degranu-lation,and ROS generation of neutrophils,with significant effects at medium and high doses.CONCLU-SION SAA can inhibit different functions of neutrophils after activation,which may be a potential drug for targeting neutrophil function regulation.

Piezo is a newly discovered mechanosensitive ion channel (MSC) in mammals, characterized by a unique homotrimeric three-leaf propeller-shaped structure that converts mechanical signals into biological and electrical signals, thus participating in the regulation of various physiological and pathological processes. In recent years, an increasing number of studies have demonstrated the crucial role of Piezo channel in renal physiology and pathophysiology. This article aims to provide new perspectives and targets for the prevention and treatment of renal diseases by reviewing the recent research advances in the structure, kinetics and pharmacology of Piezo channel, especially their expression and physiopathologic roles in the kidney.

Objective To investigate the mechanism of benzyl isothiocyanate(BITC)combined with sorafenib(Sor)in the treatment of anaplastic thyroid cancer(ATC).Methods Two ATC cell lines,8505C and CAL-62,were treated with Sor at concentrations of 0,20,30,40,and 50 μmol/L.The cell survival rate was assessed using CCK-8 assay.The combined dose of BITC and Sor was determined by calculating combination index(CI).CAL-62 and 8505C cells were exposed to 10 μmol/L BITC(BITC group),10 μmol/L Sor(Sor group),or a combination of 10 μmol/L BITC and 10 μmol/L Sor(BITC+Sor group)for 24 hours.The control group was not treated.The effects of Sor and BITC on ATC cell viability were evaluated using the CCK-8 method.Apoptosis was analyzed via flow cytometry.Western blot assay was employed to detect the protein expression levels of LC3B Ⅱ,Beclin-1 and nuclear factor(NF)-κB.Real-time fluorescence quantitative PCR was used to quantify the mRNA levels of LC3B.Additionally,CAL-62 cells were subcutaneously injected into mice to establish tumor xenograft model.Mice were treated with BITC(100 mg/kg,intraperitoneal injection),Sor(30 mg/kg,intragastric administration)or a combination of BITC and Sor every other day for 21 days.Finally,the expression levels of LC3B Ⅱ,Beclin-1 and NF-κB in tumor tissue were analyzed by Western blot assay.Results Sor significantly inhibited the viability of CAL-62 and 8505C cells in a concentration-dependent manner.The combination index(CI)was 0.710 at BITC 10 μmol/L and Sor 10 μmol/L,indicating a moderate synergistic effect between the two drugs.In both 8505C and CAL-62 cells,compared with the control group,treatment with BITC or Sor resulted in the decreased cell viability,as well as reduced expression levels of Beclin-1 and NF-κB proteins(P＜0.05),and the apoptosis rate,LC3B mRNA and LC3B Ⅱ protein expression levels were significantly increased(P＜0.05).When BITC and Sor were combined,the cell viability,Beclin-1 and NF-κB protein expressions were further reduced compared to either drug alone,while the apoptosis rate,LC3B mRNA and LC3B Ⅱ protein expression levels were significantly elevated(P＜0.05).In the mouse xenograft tumor model,the BITC+Sor group exhibited increased LC3B Ⅱ expression,along with decreased Beclin-1 and NF-κB expression levels,tumor volume and tumor mass compared to the BITC or Sor groups(P＜0.05).Conclusion The combination of BITC and Sor can inhibit ATC cells through NF-κB pathway,induce autophagy and promote apoptosis in vitro and in vivo.

OBJECTIVE To investigate the effect of salvianolic acid A(SAA)on functions of neutro-phils after activation in vitro.METHODS Rat neutrophils were extracted and activated by lipopolysac-charide(LPS)at 0.3,1,3 mg·L-1,and the number of adherent neutrophils and myeloperoxidase(MPO)activity were detected to determine the concentration of LPS.Neutrophils were divided into the control,model,model+4-aminobenzohydrazide(ABH)20 μmol·L-1,and model+SAA 1,3 and 10 μmol·L-1 groups.LPS was stimulated with 3 mg·L-1 for 30 min,and the neutrophil adhesion rate was detected by immunofluorescence after 1 h of drug incubation.After 2 h of drug incubation,phagocytosis of neutro-phils was detected by immunofluorescence and fluorescein isothiocyanate-immunoglobulin G.After 3 h of drug incubation,the neutrophil adhesion rate to endothelial cells was detected by colorimetric assay.Intracellular MPO activity and hypochlorous acid(HOCl)production were investigated by colorimetric assay in response to the degranulation function.Intracellular reactive oxygen species(ROS)levels were detected by probe assay,and mitochondrial membrane potential by JC-1 assay.The levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)and total antioxidant capacity(T-AOC)were measured to reflect oxidation function of neutrophils.RESULTS LPS increased the number of adherent cells and MPO activity in a concentration-dependent manner,with 3 mg·L-1 of LPS showing the most significant effect,which was used for subsequent experiments.Compared with the control group,LPS-activated neutrophil adhesion and phagocytosis were significantly enhanced.MPO activity and HOCl production significantly increased.The levels of ROS and MDA in LPS-activated neutrophils were significantly increased while the mitochondrial membrane potential and the levels of SOD,GSH,T-AOC were significantly decreased,indicating that the oxidative stress ability was enhanced.Compared with the model group,SAA dose-dependently inhibited LPS-induced adhesion,phagocytosis,degranu-lation,and ROS generation of neutrophils,with significant effects at medium and high doses.CONCLU-SION SAA can inhibit different functions of neutrophils after activation,which may be a potential drug for targeting neutrophil function regulation.

Objective To investigate the mechanism of benzyl isothiocyanate(BITC)combined with sorafenib(Sor)in the treatment of anaplastic thyroid cancer(ATC).Methods Two ATC cell lines,8505C and CAL-62,were treated with Sor at concentrations of 0,20,30,40,and 50 μmol/L.The cell survival rate was assessed using CCK-8 assay.The combined dose of BITC and Sor was determined by calculating combination index(CI).CAL-62 and 8505C cells were exposed to 10 μmol/L BITC(BITC group),10 μmol/L Sor(Sor group),or a combination of 10 μmol/L BITC and 10 μmol/L Sor(BITC+Sor group)for 24 hours.The control group was not treated.The effects of Sor and BITC on ATC cell viability were evaluated using the CCK-8 method.Apoptosis was analyzed via flow cytometry.Western blot assay was employed to detect the protein expression levels of LC3B Ⅱ,Beclin-1 and nuclear factor(NF)-κB.Real-time fluorescence quantitative PCR was used to quantify the mRNA levels of LC3B.Additionally,CAL-62 cells were subcutaneously injected into mice to establish tumor xenograft model.Mice were treated with BITC(100 mg/kg,intraperitoneal injection),Sor(30 mg/kg,intragastric administration)or a combination of BITC and Sor every other day for 21 days.Finally,the expression levels of LC3B Ⅱ,Beclin-1 and NF-κB in tumor tissue were analyzed by Western blot assay.Results Sor significantly inhibited the viability of CAL-62 and 8505C cells in a concentration-dependent manner.The combination index(CI)was 0.710 at BITC 10 μmol/L and Sor 10 μmol/L,indicating a moderate synergistic effect between the two drugs.In both 8505C and CAL-62 cells,compared with the control group,treatment with BITC or Sor resulted in the decreased cell viability,as well as reduced expression levels of Beclin-1 and NF-κB proteins(P＜0.05),and the apoptosis rate,LC3B mRNA and LC3B Ⅱ protein expression levels were significantly increased(P＜0.05).When BITC and Sor were combined,the cell viability,Beclin-1 and NF-κB protein expressions were further reduced compared to either drug alone,while the apoptosis rate,LC3B mRNA and LC3B Ⅱ protein expression levels were significantly elevated(P＜0.05).In the mouse xenograft tumor model,the BITC+Sor group exhibited increased LC3B Ⅱ expression,along with decreased Beclin-1 and NF-κB expression levels,tumor volume and tumor mass compared to the BITC or Sor groups(P＜0.05).Conclusion The combination of BITC and Sor can inhibit ATC cells through NF-κB pathway,induce autophagy and promote apoptosis in vitro and in vivo.

Objective To explore the potential pathogenesis of SLE and SS based on GEO database with screening differential expression genes common in systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS),analyzing their functions and identifing their expression levels. Methods The gene expression datasets of SLE and SS whole blood samples were retrieved from GEO database. Differential expression genes in peripheral blood cells of SLE and SS were screened using gene expression datasets GSE50772,GSE81622,GSE84844 and GSE48378,respectively,and the shared differential expression genes of SLE and SS were screened. Functional analysis of differentially expressed genes was performed using Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Peripheral blood from SLE and SS patients and healthy controls were collected from March 2024 to April 2024,recruited from the Second Affiliated Hospital of Air Force Medical University. Quantitative fluorescence real-time PCR (qRT-PCR) was used to identify the expression levels of 11 genes with the most significant differences in expression. Results 232 and 110 differentially expressed genes were screened for SLE and SS,respectively,among which 32 genes shared by SLE and SS were up-regulated in expression levels. Functional analysis showed that the 32 differentially expressed genes were mainly enriched in biological processes related to interferon (IFN) signaling pathways,defense response to viruses,response to viruses,negative regulation of viral genome replication,and immune response. KEGG pathway analysis showed that 32 differentialy expressed genes were associated with the process of viral infection. The clinical sample identification results showed that the expression levels of OAS3,IFI44,IFI44L and EPSTI1 were significantly elevated in PBMC of SLE and SS patients. Conclusion This study suggested that changes in biological processes related to IFN signal and viral infection response play important roles in both SLE and SS development,and may be a predisposing factor and potential biomarker for SLE and SS.

Objective:To investigate the factors affecting the efficacy of 131I treatment for Graves′ disease (GD) and to construct a predictive model for the treatment outcomes of 131I therapy. Methods:Retrospective analysis of the treatment efficacy was performed on 2 190 patients (547 males, 1 643 females, age (42.9±12.4) years) with GD, who received initial 131I treatment in Tianjin Medical University General Hospital between October 2013 and May 2018. Univariate analysis ( χ2 test, et al) and logistic regression were performed to analyze the possible factors affecting the efficacy of 131I treatment. An efficacy prediction model for 131I treatment of GD was constructed, and decision curve analysis (DCA) was used to evaluate the clinical utility of the prediction model. Results:The overall effectiveness rate of 131I treatment for GD patients was 99.95%(2 189/2 190), with a total cure rate of 83.74%(1 834/2 190), among which 94.11%(1 726/1 834) were cured after a single treatment. Pre-treatment thyroid mass was identified as an independent risk factor affecting the efficacy of initial 131I treatment (odds ratio ( OR)=0.983(95% CI: 0.977-0.989), P<0.001). The clinical cure rate was higher in patients who received an adequate dose of 131I compared with that in patients who didn′t receive an adequate dose (79.97%(1 537/1 922) vs 70.52%(189/268); χ2=12.57, P<0.001), but it did not increase the incidence of hypothyroidism within one year. A predictive model was constructed, and it was found that thyroid mass and disease duration had a relatively high impact on the clinical cure rate. The concordance index (C-index) of the predictive model was 0.623(95% CI: 0.593-0.654). DCA indicated that the predictive model offered substantial net benefits across a wide range of probability thresholds. Conclusions:131I treatment is effective in most patients with GD. The predictive model for efficacy of initial 131I treatment developed in this study can assist in evaluating treatment outcomes and help clinicians select the most suitable 131I treatment dose, enhancing clinical decision-making.

Objective: To explore the safety and feasibility of the disconnection of the left renal artery preferentially during robot-assisted inferior vena cava (IVC) thrombectomy for patients with left renal cell carcinoma and tumor emboli. Methods: Clinical data of 7 patients who underwent robot-assisted IVC thrombectomy and radical nephrectomy in the First Affiliated Hospital of Zhengzhou University during Dec.2021 and Oct.2024 were retrospectively analyzed.Thrombectomy was performed first，followed by nephrectomy. The “IVC-first, kidney-last”robotic technique was developed to minimize chances of IVC thrombus. When patients in left lateral decubitus position, the left renal artery was severed from the right side through the inferior vena cava and abdominal aorta. After removal of thrombus from IVC was completed, patients changed to the right lateral position to complete radical left nephrectomy. Results: Imaging examinations revealed that the median diameter of the renal cell carcinomas was 83(46-99) mm; the median length of the inferior vena cava cancerous emboli was 49(2-91) mm.According to the Mayo classification，the cancerous emboli were gradeⅠ in 2 cases，gradeⅡ in 4 cases，and grade Ⅲ in 1 case.All surgeries were successful.The median operation time was 248(201-331) minutes，blood loss 500(200-1000) mL，and 6 cases required intraoperative blood transfusion.The median time for transition into the intensive care unit was 1(1-4) days，and drainage tube removal 6(5-12) days.Serum creatinine increased significantly in 5 cases，4 of which returned to normal after 1 week，but 1 had renal insufficiency (creatinine 166 μmol/L).Chylous fistula occurred in 1 patient，and lower extremity venous thrombosis developed in 3 patients.Pathological examinations indicated 6 cases of renal cell carcinoma and 1 case of MiT family translocation renal cell carcinoma.During the median follow-up of 17(1-35) months，5 cases were tumor-free，while 2 had lung and retroperitoneal metastases.They received targeted therapy of axitinib combined immunotheraphy and lived with tumors. Conclusion: In the left lateral position for left renal cell carcinoma with cancerous emboli，robot-assisted laparoscopic thrombectomy by crossing the inferior vena cava and abdominal aorta and disconnecting the left renal artery first is safe and feasible.