BACKGROUND:Dental mesenchymal stem cells are considered a promising source for bone tissue repair due to their high proliferation potential,osteogenic differentiation capacity,and immunomodulatory properties.However,some allogeneic applications of stem cells still have potential carcinogenic effects and immune rejection risks.Recently,studies have highlighted the paracrine effects mediated by secretions from dental mesenchymal stem cells in bone tissue repair.These secretions include the soluble factors and extracellular vesicles.OBJECTIVE:To review the research progress of dental mesenchymal stem cells in repairing bone defects through paracrine effects.METHODS:Using search terms"dental mesenchymal stem cell,paracrine,osteogenesis,conditioned medium,extracellular vesicle"in Chinese and English,relevant literature published between 2019 and 2024 was retrieved from databases including CNKI,PubMed,and Elsevier ScienceDirect.A total of 104 studies were ultimately selected for this review.RESULTS AND CONCLUSION:(1)Dental mesenchymal stem cells-conditioned medium contains multiple bioactive factors beneficial for bone repair.These factors directly promote bone formation through regulatory agents such as osteocalcin,osteopontin,bone morphogenetic protein,and dentin sialophosphoprotein.They also play an indirect promoting role in bone tissue repair through neurotrophic factors,vascular endothelial growth factor,and immunomodulatory and anti-inflammatory agents.(2)Dental derived mesenchymal stem cell-derived extracellular vesicles not only contain some cytokines from dental conditioned medium,but also various miRNAs,which promote bone repair by directly promoting osteogenesis,angiogenesis,regulating immune cells,and inflammation control.These extracellular vesicles can be engineered within different scaffold materials to achieve controlled or sustained release,enhancing therapeutic efficacy.

BACKGROUND:Dental mesenchymal stem cells are considered a promising source for bone tissue repair due to their high proliferation potential,osteogenic differentiation capacity,and immunomodulatory properties.However,some allogeneic applications of stem cells still have potential carcinogenic effects and immune rejection risks.Recently,studies have highlighted the paracrine effects mediated by secretions from dental mesenchymal stem cells in bone tissue repair.These secretions include the soluble factors and extracellular vesicles.OBJECTIVE:To review the research progress of dental mesenchymal stem cells in repairing bone defects through paracrine effects.METHODS:Using search terms"dental mesenchymal stem cell,paracrine,osteogenesis,conditioned medium,extracellular vesicle"in Chinese and English,relevant literature published between 2019 and 2024 was retrieved from databases including CNKI,PubMed,and Elsevier ScienceDirect.A total of 104 studies were ultimately selected for this review.RESULTS AND CONCLUSION:(1)Dental mesenchymal stem cells-conditioned medium contains multiple bioactive factors beneficial for bone repair.These factors directly promote bone formation through regulatory agents such as osteocalcin,osteopontin,bone morphogenetic protein,and dentin sialophosphoprotein.They also play an indirect promoting role in bone tissue repair through neurotrophic factors,vascular endothelial growth factor,and immunomodulatory and anti-inflammatory agents.(2)Dental derived mesenchymal stem cell-derived extracellular vesicles not only contain some cytokines from dental conditioned medium,but also various miRNAs,which promote bone repair by directly promoting osteogenesis,angiogenesis,regulating immune cells,and inflammation control.These extracellular vesicles can be engineered within different scaffold materials to achieve controlled or sustained release,enhancing therapeutic efficacy.

Bile-processed Coptidis Rhizoma（B-pCR）， first documented in Shengji Zonglu， is a unique processed products of Coptidis Rhizoma（CR） characterized by "mutual enhancement processing" and "enhancing the cold property of cold-natured herbs". Pig bile can enhance the bitter and cold properties of CR， yielding potent effects in purging excess fire from the liver and gallbladder. The processing increases the dissolution of alkaloids such as berberine， coptisine， and palmatine， while introducing bile acids from pig bile， including taurine-type and glycine-type cholic acids. This enhances its pharmacological effects， such as antipyretic activity， regulation of glucose and lipid metabolism disorders， and intestinal absorption. Traditional processing techniques and quality standards for B-pCR are outlined in the Shanghai Traditional Chinese Medicine（TCM） Decoction Pieces Processing Standard and the Gansu TCM Processing Standard. However， incomplete specifications for critical process parameters and quality criteria significantly impact its production and clinical application. A review of research over the past two decades on the processing history， process optimization， quality evaluation， material basis， and changes in pharmacological effects and properties of B-pCR reveals that the pretreatment method and dosage of pig bile， and processing temperature are key factors influencing its quality. Furthermore， current quality standards lack specific indicators. Additionally， the enhancement of the cold property and medicinal efficacy direction of B-pCR is not only associated with changes in alkaloid groups but also depend on the synergistic effects of bile acids. This review can provide insights for improving the quality evaluation system of B-pCR.

ObjectiveTo evaluate the effects of drinking chlorinated water on the intestinal flora of rats and mice and to explore differences in the intestinal microecological responses of model animals to chlorine stimulation in chlorinated drinking water systems. MethodsSix 8-week-old male SD rats and six 8-week-old male C57BL/6J mice were acclimated for 5 days. Subsequently, the drinking water for both rats and mice was changed from pure water to water containing free chlorine at a concentration of 25.4–32.4 nmol/L. The intervention lasted for 8 weeks, during which all animals were fed the same diet. Fecal samples were collected before the intervention (week 0, as the control group) and on the last day of week 3 and week 8 (as the chlorinated water group), and microbial composition was analyzed by 16S rRNA sequencing, including α diversity (Chao1 and Shannon indices), β diversity [principal component analysis (PCA)], and linear discriminant analysis effect size (LEfSe) analysis. ResultsAfter 3 weeks of intervention, α diversity of the intestinal flora in both rats and mice in the chlorinated water group was significantly lower than that in the control group (P < 0.01). After 8 weeks of intervention, no significant difference in α diversity was observed between rats in the chlorinated water group and those in the control group, whereas α diversity in mice remained significantly lower than that in the control group (P < 0.01). β diversity analysis showed significant alterations in microbial structure in the chlorinated water group. LEfSe analysis indicated that, compared with the control group, the abundances of Bacteroides and Ruminococcus were significantly reduced in the chlorinated water group, and microbial disturbance was more pronounced in mice [linear discriminant analysis (LDA) > 4.0], with a greater decrease in microbial diversity and a larger number of differentially abundant genera. ConclusionConsumption of chlorinated water can alter the diversity and structure of the intestinal flora in both rats and mice, with mice being more sensitive to this exposure. These findings suggest that the potential effects of chlorine on gut microecology should be considered in drinking water management and model selection for animal experiments.

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 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.

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 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 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 explore the therapeutic effect of CD5L targeted therapy on a rat model of collagen-induced arthritis (CIA).Methods:The CIA rat model was established and treated with anti-CD5L antibody. The clinical arthritis score and tissue swelling degree of rats were evaluated. Twenty-four SD rats were randomly divided into the control group, the model group, the isotype control group and the CD5L antibody group. HE staining and safranin fast green staining were used to observe the synovial inflammation and cartilage erosion in the ankle joint of CIA rats. Micro-CT was used to scan the feet of CIA rats to detect bone mineral density and bone destruction. The levels of TNF-α, IL-6 and IL-8 in serum were detected by enzyme-linked immunosorbent assay (ELISA). All experimental data conforming to normal distribution were compared between groups by one-way ANOVA, and Dunnet t test was used to compare the two groups. Results:CD5L antibody improved joint swelling and deformity in CIA rats. The statistics of arthritis scores in rats showed that there was a statistically significant difference in arthritis scores between the CD5L antibody group and the isotype antibody group of rats from Day 23[Day 23 (6.6±0.5) vs. (8.2±0.7), t=-7.07, P<0.05; Day 26 (7.0±0.6) vs. (8.4±0.5), t=-7.59, P<0.05; Day 29 (7.6±0.4) vs. (9.4±0.8), t=-6.96, P<0.05; Day 32 (7.8±0.5) vs.(9.6±1.1), t=-6.50, P<0.05; Day 35 (8.2±0.7) vs. (10.4±0.7), t=-5.88, P<0.05]. The HE staining results showed that there was a statistically significant difference in the HE staining score between the CD5L antibody group and the isotype antibody group of rats [(2.5±0.6) vs. (5.0±0.8), t=-6.73, P<0.05]. The results of safranin fixation green staining showed that there was a statistically significant difference in the safranin fixation green staining score between the CD5L antibody group and the isotype antibody group of rats [(1.8±0.8) vs. (3.5±0.6), t=-5.22, P<0.05]. The Micro-CT imaging results showed that there was a statistically significant difference in bone mineral density between the CD5L antibody group and the isotype antibody group of rats [(5 618±128)g/cm 3vs. (5 202±39)g/cm 3, t=8.06, P<0.01]. The ELISA results showed that there were statistically significant differences in the contents of TNF-α, IL-6 and IL-8 in the serum of rats between the CD5L antibody group and the isotype antibody group [TNF-α: (164±22)pg/ml vs. (213±17)pg/ml, t=5.05, P<0.05; IL-6: (186±17)pg/ml vs. (230.7±25.3)pg/ml, t=4.78, P<0.05; IL-8: (384±21)pg/ml vs. (456±44)pg/ml, t=-5.21, P<0.05]. Conclusion:Targeting CD5L can effectively alleviate synovial inflammation and bone destruction in CIA rats. CD5L may be used as a potential therapeutic target for rheumatoid arthritis.