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.

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 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.

Ureteral stricture is a common urological condition，whose treatment mainly depends on the etiology，location，number，and length of the stricture.For complex long-segment ureteral stricture，the main surgical procedures include endourological treatment，flap pyeloplasty，ureterocalicostomy，buccal mucosal ureteroplasty，lingual mucosal ureteroplasty，bladder mucosal ureteroplasty，appendiceal ureteroplasty，bladder flap ureteroplasty，and ileal ureter substitution ureteroplasty.Although open and laparoscopic surgeries are still prevalent，robotic surgery is gaining popularity due to its minimally invasive nature and precision.Based on the latest clinical advances and diagnostic and therapeutic experience of our team，we will systematically introduce the new surgical techniques and methods for the treatment of long-segment ureteral stricture from a clinical practical perspective.In addition，we will discuss the advantages and disadvantages of different autologous tissue reconstruction techniques，as well as the choices between minimally invasive and open surgery.

Objective:To study the changes in biliary fluid dynamics in patients with hepatolithiasis after cholecystectomy.Methods:The clinical data of 101 patients with hepatolithiasis who underwent percutaneous transhepatic scleroscopic choledochotomy for stone extraction at the First Hospital of Guangzhou Medical University from September 2021 to June 2024 were retrospectively analyzed, among which there were 47 males and 54 females with the age of (51.8±15.7) years. They were divided into two groups based on whether they had undergone previous cholecystectomy or not: cholecystectomy group ( n=53) and non-chole-cystectomy group ( n=48). The pressures in the left hepatic duct, right hepatic duct and lower end of the common bile duct were compared between the two groups, as well as the viscosity of bile at different rates of incision. Results:There were no significant differences in baseline characteristics such as gender, age, and liver function between the two groups (all P>0.05). Compared with the non-cholecystectomy group, the bile viscosity in the cholecystectomy group were significantly lower at shear rates of 1/s, 50/s, and 200/s [1/s: (8.96±1.15) mPa·s vs. (13.13±1.25) mPa·s; 50/s: (2.37±0.18) mPa·s vs. (3.59±0.34) mPa·s; 200/s: (1.82±0.13) mPa·s vs. (2.25±0.15) mPa·s], with statistically significant diffe-rences (all P<0.05). The biliary pressure in the left hepatic duct, right hepatic duct, and lower end of the common bile duct in the cholecystectomy group were significantly higher than that in the non-cholecystectomy group [left hepatic duct: (16.43±7.02) cmH 2O vs. (13.84±5.07) cmH 2O; right hepatic duct: (16.71±7.36) cmH 2O vs. (13.76±5.03) cmH 2O; lower end of the common bile duct: (14.60±6.73) cmH 2O vs. (10.58±4.84) cmH 2O] (1 cmH 2O=0.098 kPa), with statistically significant differences (all P<0.05). Conclusion:Bile viscosity decreases after cholecystectomy in patients with hepatolithiasis, whereas biliary pressure increases at the left and right hepatic ducts and at the lower end of the common bile duct, and these changes may be closely related to the mechanism of hepatolithiasis formation and recurrence.

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 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.

Tumor-associated fibroblasts (CAFs) play a crucial role in promoting the invasion, metastasis, angiogenesis, immune suppression, and drug resistance of pancreatic cancer. The diverse origins, and phenotypic and functional heterogeneity of CAFs poses a significant challenge for targeted anti-tumor therapies against CAFs. However, investigating the interactions between CAFs and pancreatic cancer cells can provide insights for innovative CAFs-targeted therapies for pancreatic cancer. This article reviews the current domestic and international researchs, focusing on the heterogeneity of CAFs and their mechanisms in the progression of pancreatic cancer, with the aim of providing a theoretical basis and research direction for the clinical diagnosis and treatment of pancreatic cancer.

OBJECTIVE To investigate the therapeutic effect of Sanhan Huashi Formula(SHF)on respiratory syncytial virus(RSV)-infected mouse models and explore its potential antiviral and anti-inflammatory mechanisms using lipidomics.METHODS Fifty-four BALB/c mice were randomly divided into six groups(n=9):blank group,model group,Ribavirin group(50 mg·kg-1·d-1),and SHF high(15.46 g·kg-1·d-1),medium(7.73 g·kg-1·d-1),and low-dose(3.87 g·kg-1·d-1)groups.A pneumonia model was established by in-tranasal RSV infection,followed by three consecutive days of oral gavage administration.Lung tissues were collected for histopathologi-cal evaluation using hematoxylin-eosin(HE)staining and inflammation scoring.Real-time quantitative polymerase chain reaction(RT-qPCR)was performed to measure mRNA levels of viral gene fusion protein(F),glycoprotein(G),and inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)to assess lung viral load and inflammation,while immunofluorescence staining was performed to observe the expression of RSV-F protein in lung tissues.Serum lipidomics analysis was conducted using ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q Exactive Or-bitrap MS)to identify lipid metabolism changes and differential lipids.RESULTS Compared with the blank group,mice in the model group exhibited marked pulmonary inflammatory cell infiltration and tissue injury,with significantly elevated pulmonary histopa-thology scores and lung index.The lung viral load and the mRNA expression levels of the inflammatory factors TNF-α and IL-6 were significantly increased,and immunofluorescence likewise indicated high expression of RSV-F protein in lung tissue.Relative to the model group,treatment with SHF at all tested doses clearly ameliorated lung tissue injury,effectively suppressed viral gene expression and inflammatory cytokine levels,and reduced the fluorescence signal intensity of RSV-F protein in the lungs.Lipidomics analysis re-vealed that compared with the blank group,the model group exhibited marked disturbances in lipid metabolism-characterized by dys-regulation of triacylglycerol(TG),phosphatidylcholine(PC),lysophosphatidylcholine(LPC),sphingomyelin(SM),diacylglycerol(DG),lysophosphatidylethanolamine(LPE),and phosphatidylethanolamine(PE).High-dose SHF treatment reversed these RSV-induced lipid abnormalities.CONCLUSION SHF effectively alleviates RSV-induced pulmonary inflammation and pathological injury,re-duces pulmonary RSV viral load,and may exert these effects by modulating dysregulated lipid metabolism in peripheral blood.