Objective: To explore the factors affecting the prognosis of patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT), and to analyze the clinical value of transcatheter arterial chemoembolization (TACE) combined with iodine-125 seed implantation in such patients. Methods: A retrospective analysis of 53 patients with HCC combined with PVTT was performed. In the study group, 32 cases were treated with TACE combined with iodine-125 seed implantation, and 21 cases in the control group were treated with TACE combined with sorafenib. Survival analysis was carried out on eight factors such as gender, age, Child-Pugh classification, alpha fetoprotein level, portal vein tumor thrombosis (PVTT) type, forms of liver tumor, extra-hepatic metastasis and treatment modalities. The efficacy of TACE combined with iodine-125 seed implantation and TACE combined with sorafenib was further compared. The χ ² test was used to evaluate the efficacy of the two groups. A single factor survival analysis was calculated by Kaplan-Meier estimator and multifactor survival analysis by Cox proportional hazards model. Results: All 53 patients were successfully treated. The median tumor progression time (mTTP) and median overall survival (mOS) were 8 months and 11 months, respectively. The disease control rate (DCR) of the study group for PVTT was 93.8%, which was significantly higher than that of the control group (61.9%, χ ² = 6.448, P = 0.011). The difference was statistically significant; the objective remission rate of the study group for PVTT was 75.0%. Significantly higher than 9.5% in the control group, P < 0.05, the difference was statistically significant; the DCR of the primary tumor in the study group was 50.0%, which was lower than the 70.0% of the PVTT in the control group, P = 0.231, the difference was not statistically significant. The progression of primary HCC lesions in patients with multivariate survival analysis: Child-Pugh grade A patients were compared to grade B [Hazard ratio (HR) = 0.236, P = 0.003]; no extra-hepatic metastasis (HR = 0.258, P = 0.002); and TACE combined with iodine-125 seed implantation group compared with TACE combined sorafenib group (HR = 0.372, P = 0.002), the differences were statistically significant. Multivariate survival analysis of patients with overall survival: AFP < 400 ng/mL vs. AFP≥400 ng/mL (HR = 0.389, P = 0.030); Child-Pugh grade A vs. B (HR = 0.263, P = 0.006); and no extra-hepatic metastasis (HR = 0.306, P = 0.006), the differences were statistically significant. Conclusion TACE combined with iodine-125 seed implantation for the treatment of HCC with PVTT can effectively control the progression of PVTT and intrahepatic lesions and improve the prognosis of patients.

Forkhead box protein O1 (FOXO1) has been extensively studied as a tumor suppressor. In oral squamous cell carcinoma, studies have demonstrated that FOXO1 can inhibit tumor cell oxidative stress, stemness and epithelial-mesenchymal transition, and promote tumor cell autophagy and apoptosis. FOXO1 may serve as a potential target for the treatment of oral squamous cell carcinoma.

BACKGROUND:Several studies have found that the total flavonoids of rhizome drynariae can promote neovascularization in the induced membrane,improve the biological properties of the induced membrane,and accelerate bone remodeling in the induced membrane,but the related molecular mechanisms still need to be further explored. OBJECTIVE:To explore the effect of total flavonoids of rhizome drynariae on bone remodeling in rat femoral Masquelet-induced membrane model by regulating H-type blood vessels. METHODS:Thirty-six male Sprague-Dawley rats were stratified by body mass and then randomly divided into blank group,model group and traditional Chinese medicine group,with 12 rats in each group.A 4-mm femoral bone defect model was established in all the rats.Bone defects in the model group and traditional Chinese medicine group were filled with polymethylmethacrylate bone cement.At 6 weeks after modeling,the tail bone of the rats was implanted in the blank group,as well as in the other two groups after removal of bone cement.The traditional Chinese medicine group was given 157.5 mg/kg per day of total flavonoids of rhizome drynariae at 3 days after bone implantation,while the model and blank groups were given the same amount of saline by gavage until the 8th week after bone implantation.Bone graft samples were taken for relevant testing at 8 weeks after implantation. RESULTS AND CONCLUSION:X-ray films showed that in the blank group,the fracture line in the defect area was clear,and only a small amount of bone callus formed;in the model group,the bone defect area still existed,where discontinuous cortical bone was visible;in the traditional Chinese medicine group,the defect area was filled with newborn bone tissues,the bone marrow cavity and part of the cortical bone formed,and the fracture line disappeared.Micro-CT scans showed that the amount of new bone in the defect area was low in the blank group,the number of bone trabeculae in the defect area was significantly increased in the model group,and a large amount of new bone tissue was filled in the bone defect area in the traditional Chinese medicine group.Hematoxylin-eosin staining results showed that in the blank group,only a small amount of new bone formed in the defect area and the quality of osteogenesis was poor;in the model group,there was more new bone tissue in the defect area,but some fibrous connective tissues were interspersed within the bone tissue;and in the traditional Chinese medicine group,a large amount of new bone formed in the defect area and the quality of osteogenesis was the best.CD31/Emcn immunofluorescence double-labeling staining results showed that the number of H-type blood vessels in the newborn bone tissue in the bone defect area of the blank group was sparse and sparsely distributed;compared with the blank group,there were more H-type blood vessels in the bone tissue in the bone defect area of the model group,and the blood vessels were distributed in relatively regular strips;the number of H-type blood vessels in the bone defect area of the traditional Chinese medicine group was the highest and the blood vessels were densely distributed.To conclude,the total flavonoids of rhizoma drynariae can upregulate the expression of H-type blood vessels to enhance the angiogenic-osteogenic effect,improve the osteogenic efficiency of the rat femoral Masquelet induced membrane model,and promote bone remodeling.

OBJECTIVE: To develop a drug-loaded composite microsphere that can simultaneously release the berberine (BBR) and naringin (NG) to repair infectious bone defects. METHODS: The NG was loaded on mesoporous microspheres (MBG) to obtain the drug-loaded microspheres (NG-MBG). Then the dual drug-loaded compound microspheres (NG-MBG@PDA-BBR) were obtained by wrapping NG-MBG with polydopamine (PDA) and modifying the coated PDA with BBR. The composite microspheres were characterized by scanning electron microscopy, X-ray diffraction, specific surface area and pore volume analyzer, and Fourier transform infrared spectroscopy; the drug loading rate and release of NG and BBR were measured; the colony number was counted and the bacterial inhibition rate was calculated after co-culture with Staphylococcus aureus and Escherichia coli for 12 hours to observe the antibacterial effect; the biocompatibility was evaluated by live/dead cell fluorescence staining and cell counting kit 8 assay after co-culture with rat's BMSCs for 24 and 72 hours, respectively, and the osteogenic property was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining after 7 and 14 days, respectively. RESULTS: NG-MBG@PDA-BBR and three control microspheres (MBG, MBG@PDA, and NG-MBG@PDA) were successfully constructed. Scanning electron microscopy showed that NG-MBG@PDA-BBR had a rough lamellar structure, while MBG had a smooth surface, and MBG@PDA and NG-MBG@PDA had a wrapped agglomeration structure. Specific surface area analysis showed that MBG had a mesoporous structure and had drug-loading potential. Low angle X-ray diffraction showed that NG was successfully loaded on MBG. The X-ray diffraction pattern contrast showed that all groups of microspheres were amorphous. Fourier transform infrared spectroscopy showed that NG and BBR peaks existed in NG-MBG@PDA-BBR. NG-MBG@PDA-BBR had good sustained drug release ability, and NG and BBR had early burst release and late sustained release. NG-MBG@PDA-BBR could inhibit the growth of Staphylococcus aureus and Escherichia coli, and the antibacterial ability was significantly higher than that of MBG, MBG@PDA, and NG-MBG@PDA ( P<0.05). But there was a significant difference in biocompatibility at 72 hours among microspheres ( P<0.05). ALP and alizarin red staining showed that the ALP positive area and the number of calcium nodules in NG-MBG@PDA-BBR were significantly higher than those of MBG and NG-MBG ( P<0.05), and there was no significant difference between NG-MBG@PDA and NG-MBG@PDA ( P>0.05). CONCLUSION NG-MBG@PDA-BBR have sustained release effects on NG and BBR, indicating that it has ideal dual performance of osteogenesis and antibacterial property.
Rats ; Animals ; Osteogenesis ; Delayed-Action Preparations/pharmacology* ; Microspheres ; Berberine/pharmacology* ; Anti-Bacterial Agents/pharmacology* ; Escherichia coli