Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.Mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver disorders.Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues.It is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC activation.Additionally,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis.This study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis development.The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC.Moreover,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro.MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model.MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells.In conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.

Objective: To investigate the clinical outcomes and second-look arthroscopic findings after high tibial osteotomy (HTO) combined with medial meniscus posterior root (MMPR) repair. Methods: Twenty-five patients who underwent HTO combined with MMPR repair were subjected to second-look arthroscopy and retrospectively analyzed. Biplane HTO combined with MMPR repair was performed on these patients. Arthroscopic transtibial pullout repair was employed to repair the MMPR. The relative degree of the medial meniscus extrusion (MME) were measured. Cartilage regeneration and the healing of MMPR were evaluated at the time of second-look arthroscopy. Clinical outcomes were assessed based on Hospital for Special Surgery (HSS) scores and Lysholm scores. Results: The MMPRs were completely healed in 12 cases (48%), partially healed in 9 cases (36%), healed with scarring in 3 cases (12%), and no healed in 1 case (4%). Follow-up duration was 13.04±1.06 months (12-16 months). There were no statistically significant differences in the Kellgren-Lawrence classifications of the cases before and after surgery (χ²=0.786, P=0.675). The relative position of the mechanical axis of the lower extremity through the tibial plateau was 19.88%±6.44% preoperatively and 58.68%±7.71% after operation with significant difference (t=-18.561, P<0.001). The Lysholm scores was increased significantly from 34.76±3.62 points to 82.08±4.35 points after operation (t=-52.717, P<0.001). The HSS scores was increased significantly from 33.52±6.48 points to 81.52±4.79 points after operation (t=-38.685, P<0.001). The degree of MME was changed from 51.12%±13.55% to 50.48%±15.15% without statistical difference (t=0.550, P=0.588) . The comparison between different degrees of healing groups revealed no statistical differences in all variables (P>0.05). The comparison between different degree of cartilage regeneration groups revealed no statistical differences in all variables (P>0.05). Conclusion HTO combined with MMPR repair can effectively improve the lower limb alignment and patients' symptoms with a satisfactory healing rate of MMPR. The effects of post-root repair after a short period is not obvious. The longer-term clinical effects is worthy of further observation.