Fracture is a common orthopedic disease in clinical practice,and the resulting nonunion or delayed union of frac-tures is a major challenge in clinical treatment.In the process of fracture healing,there is a complex interaction between angio-genesis and osteogenesis,which is called the"angiogenesis-osteogenesis coupling"mechanism.In recent years,a new capillary subtype characterized by high expression of platelet endothelial cell adhesion molecule-1(PECAM-1/CD31)and salivary glyco-protein(EMCN),namely type H blood vessel,has been identified and found to play an important role in regulation of the angio-genesis-osteogenesis coupling.In this review,the mechanism of type H blood vessels promoting angiogenesis-osteogenesis cou-pling,the related molecules and signal pathways regulating type H blood vessels regeneration were discussed,in order to provide new ideas and methods for promoting fracture healing.

Objective Based on exosomal miRNA and their downstream pathways,we investigated the mechanisms related to the alleviation of cartilage damage in the knee damp-heat type osteoarthritis(KOA)model in rats by Si-Miao-San.Methods Damp-heat type KOA rat model was successfully established and divided into normal control group,model group,positive drug group,and low,medium and high dose groups of Si-Miao-San.The general conditions of the rats were observed daily;behavioural,imaging and histopathological methods were used to assess the effects of Si-Miao-San on pain,swelling,cartilage degeneration,subchondral bone damage and osteophyte formation in rats with damp-heat type KOA.The miRNA high-throughput sequencing technology was used to screen the differentially expressed miRNA after Si-Miao-San intervention in model rats;Western blot was used to test the expression of PI3K/Akt/mTOR pathway(downstream pathway of differentially expressed miRNA)and autophagy-related proteins in the cartilage tissues of rats in each group.Results Compared with the model group,Si-Miao-San could effectively improve the symptoms of damp-heat,mechanical pain threshold and knee joint swelling in rats with damp-heat type KOA model,and at the same time,it could reduce the cartilage damage of the knee joints of the model rats,inhibit the destruction of the subchondral bone and the formation of osteophyte,and the overall efficacy was better in the high-dose group.A total of seven differentially expressed exosomal miRNA were screened after Si-Miao-San intervention in model rats,among which the PI3K/Akt/mTOR pathway might be its key downstream pathway.Si-Miao-San significantly down-regulated the phosphorylation levels of PI3K,AKT,mTOR,and the expression level of P62 protein,and up-regulated the expression level of Beclin-1 protein.Conclusion Si-Miao-San can exert anti-KOA effects by affecting the differential expression of serum exosomal miRNA while inhibiting the PI3K/Akt/mTOR pathway and enhancing chondrocyte autophagy.

Objective Based on exosomal miRNA and their downstream pathways,we investigated the mechanisms related to the alleviation of cartilage damage in the knee damp-heat type osteoarthritis(KOA)model in rats by Si-Miao-San.Methods Damp-heat type KOA rat model was successfully established and divided into normal control group,model group,positive drug group,and low,medium and high dose groups of Si-Miao-San.The general conditions of the rats were observed daily;behavioural,imaging and histopathological methods were used to assess the effects of Si-Miao-San on pain,swelling,cartilage degeneration,subchondral bone damage and osteophyte formation in rats with damp-heat type KOA.The miRNA high-throughput sequencing technology was used to screen the differentially expressed miRNA after Si-Miao-San intervention in model rats;Western blot was used to test the expression of PI3K/Akt/mTOR pathway(downstream pathway of differentially expressed miRNA)and autophagy-related proteins in the cartilage tissues of rats in each group.Results Compared with the model group,Si-Miao-San could effectively improve the symptoms of damp-heat,mechanical pain threshold and knee joint swelling in rats with damp-heat type KOA model,and at the same time,it could reduce the cartilage damage of the knee joints of the model rats,inhibit the destruction of the subchondral bone and the formation of osteophyte,and the overall efficacy was better in the high-dose group.A total of seven differentially expressed exosomal miRNA were screened after Si-Miao-San intervention in model rats,among which the PI3K/Akt/mTOR pathway might be its key downstream pathway.Si-Miao-San significantly down-regulated the phosphorylation levels of PI3K,AKT,mTOR,and the expression level of P62 protein,and up-regulated the expression level of Beclin-1 protein.Conclusion Si-Miao-San can exert anti-KOA effects by affecting the differential expression of serum exosomal miRNA while inhibiting the PI3K/Akt/mTOR pathway and enhancing chondrocyte autophagy.