Objective·To investigate the reparative effects of photo-crosslinked gelatin methylacrylated(GelMA)hydrogel scaffolds loaded with tauroursodeoxycholic acid(TUDCA)on cartilage defects in rabbit knee joints.Methods·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA were prepared by the ultraviolet light irradiation method.The physicochemical properties of GelMA hydrogel scaffolds were characterized,and the cumulative release rate of TUDCA was determined.A rabbit knee cartilage defect model was established,and 18 rabbits were randomly assigned into three groups,with six rabbits in each group:the control group(no treatment was applied to the cartilage defect),the GelMA group(the cartilage defect was filled with GelMA hydrogel scaffold),and the GelMA+TUDCA group(the cartilage defect was filled with the GelMA hydrogel scaffold loaded with TUDCA).At 12 weeks postoperatively,the concentrations of two inflammatory factors in synovial fluid,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),were detected by enzyme-linked immunosorbent assay(ELISA).After euthanasia,knee cartilage samples were harvested for gross observation,safranin O-fast green staining,and toluidine blue staining.The repair of the cartilage defects was evaluated according to the International Cartilage Repair Society(ICRS)and Modified O'Driscoll Score(MODS)systems.Immunohistochemical staining was performed to detect type Ⅱ collagen(COL-Ⅱ)protein in the cartilage tissue,and Western blotting was used to assess the protein levels of aggrecan(ACAN)and COL-Ⅱ.Results·GelMA hydrogel scaffolds exhibited a more compact microstructure after ultraviolet light irradiation,along with an suitable mass swelling ratio and compressive modulus.The TUDCA-loaded photo-crosslinked GelMA hydrogel scaffolds demonstrated effective and sustained TUDCA release,achieving a cumulative release rate of 90.2%±2.5%within 28 d.ELISA results showed that compared to the control and GelMA groups,the concentrations of TNF-α and IL-1β in the synovial fluid of the GelMA+TUDCA group were significantly reduced(P<0.001).In the GelMA+TUDCA group,the cartilage defects were nearly fully repaired,with a smooth surface and good integration with the surrounding tissue.The number of newly formed chondrocytes increased,displaying orderly alignment,and the neocartilage exhibited excellent formation.Both ICRS and MODS scores were significantly higher in the GelMA+TUDCA group than those in the control and GelMA groups(P<0.001).Additionally,the expression levels of ACAN and COL-Ⅱ proteins were significantly elevated in the GelMA+TUDCA group compared to the control and GelMA groups(P<0.001).Conclusion·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA can effectively promote the repair of cartilage defects in rabbit knee joints.

Objective·To investigate the reparative effects of photo-crosslinked gelatin methylacrylated(GelMA)hydrogel scaffolds loaded with tauroursodeoxycholic acid(TUDCA)on cartilage defects in rabbit knee joints.Methods·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA were prepared by the ultraviolet light irradiation method.The physicochemical properties of GelMA hydrogel scaffolds were characterized,and the cumulative release rate of TUDCA was determined.A rabbit knee cartilage defect model was established,and 18 rabbits were randomly assigned into three groups,with six rabbits in each group:the control group(no treatment was applied to the cartilage defect),the GelMA group(the cartilage defect was filled with GelMA hydrogel scaffold),and the GelMA+TUDCA group(the cartilage defect was filled with the GelMA hydrogel scaffold loaded with TUDCA).At 12 weeks postoperatively,the concentrations of two inflammatory factors in synovial fluid,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),were detected by enzyme-linked immunosorbent assay(ELISA).After euthanasia,knee cartilage samples were harvested for gross observation,safranin O-fast green staining,and toluidine blue staining.The repair of the cartilage defects was evaluated according to the International Cartilage Repair Society(ICRS)and Modified O'Driscoll Score(MODS)systems.Immunohistochemical staining was performed to detect type Ⅱ collagen(COL-Ⅱ)protein in the cartilage tissue,and Western blotting was used to assess the protein levels of aggrecan(ACAN)and COL-Ⅱ.Results·GelMA hydrogel scaffolds exhibited a more compact microstructure after ultraviolet light irradiation,along with an suitable mass swelling ratio and compressive modulus.The TUDCA-loaded photo-crosslinked GelMA hydrogel scaffolds demonstrated effective and sustained TUDCA release,achieving a cumulative release rate of 90.2%±2.5%within 28 d.ELISA results showed that compared to the control and GelMA groups,the concentrations of TNF-α and IL-1β in the synovial fluid of the GelMA+TUDCA group were significantly reduced(P<0.001).In the GelMA+TUDCA group,the cartilage defects were nearly fully repaired,with a smooth surface and good integration with the surrounding tissue.The number of newly formed chondrocytes increased,displaying orderly alignment,and the neocartilage exhibited excellent formation.Both ICRS and MODS scores were significantly higher in the GelMA+TUDCA group than those in the control and GelMA groups(P<0.001).Additionally,the expression levels of ACAN and COL-Ⅱ proteins were significantly elevated in the GelMA+TUDCA group compared to the control and GelMA groups(P<0.001).Conclusion·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA can effectively promote the repair of cartilage defects in rabbit knee joints.

Objective: To detect differentially expressed microRNAs in chronic hepatitis B (CHB) before being treated with pegylated interferon (PegIFN) and the relationship between their target genes and HBsAg loss. Methods: Pretreatment differentially expressed microRNAs between different response groups were screened using high throughput microarrays and validated by quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Bioinformatics analysis was performed to determine their target genes potential mechanistic roles. Results: A total of 417 microRNA were differentially expressed between different response groups, among which 342 were up-regulated and 75 were down-regulated. miR-3960, miR-126-3p, miR-23 a-3p and miR-335-5p were verified to be down-regulated by RT-qPCR result in HBsAg loss group. Bioinformatic analysis result show that the relevant pathways of microRNAs include AMPK signal pathway, NOD-like signal pathway, NF-kappa B signal pathway and mTOR signal pathway. Conclusions HBsAg loss is probably achieved as the result of genes expression regulated in association with immune response, further enhance the immune response of HBV elimination and acquire HBsAg loss.

Objective To investigate the influence on patients' coagulation of different anticoagulants during the treatment of severe hepatitis with ALSS (artificial liver support system).Methods According to different means of medication,20 severe hepatitis patients were divided into two groups randomly:heparin group,LMWH (low-molecular-weight heparin) group,and the two groups were provided with ALSS.The coagulation changes were evaluated before and after the treatment in two groups individually.Results There was no significant difference in hemoglobin levels before and after treatment in two groups.Prothrombin time (PT) and activated partial thromboplastin time (APTT) prolonged significantly before treatment,but returned to normal after treatment in heparin group;the two values were significantly lowered after treatment in LMWH group.There were increased fibrinogen level,thrombin time (TT) and decreased factor Ⅷ levels in both heparin and LMWH group.Many complications,such as blood pressure lowering,might occur in heparin group,but not in LMWH group.Conclusion It is effective and safe to use LMWH for severe hepatitis patients when treating with ALSS.

Objective To investigate the influence of vitamin E on type Ⅰ collagen, messenger RNA expression of transforming growth factor ? 1 (TGF? 1) and tissue inhibitor of matrix metalloproteinases-2 (TIMP 2) in hepatic stellate cells (HSC). Methods HSC s were cultured in vitro, the effect of vitamin E on type Ⅰ collagen was observed by mean of immunohistochemistry; mRNA expression of TGF? 1 and TIMP 2 were investigated with in situ hybridization. Results In experiment group, vitamin E markedly inhibited expression of type Ⅰ collagen of HSC as compared with control group, but could not suppress mRNA expression of TGF? 1 and TIMP 2.Conclusions Anti-fibrotic effect of Vitamin E may be implemented through inhibiting the expression of type Ⅰ collagen.