Objective The experiment was designed to evaluate whether the tendon healing inside the bone tunnel improved when the periosteal graft was wrapped around the tendon. Methods Sixty normal and healthy New Zealand white rabbits were used in the experiment. These rabbits were randomly divided into three groups. Each group included 20 rabbits. Group Ⅰ, periosteal graft was wrapped around the tendon with the cambium layer facing toward the bone; Group Ⅱ, periosteal graft was wrapped around the tendon with the fibrous layer facing toward the bone; Group Ⅲ, as control group, no periosteal graft was used with the tendon. In control group, the rabbit flexor hallucis longous tendon with calcaneus was designed as tendon-bone model. At 1, 2, 3, 4, 6 weeks after the operation, the specimens in three groups were got respectively and the structural integrity of the tendon bone interface were observed using optical microscope. The histological changes and the biomechanical parameters at varies interval were recorded. Results Three weeks after operation, there was significant osteochondral ossification of the periosteal cambium layer in the group of the cambium layer facing toward the bone, but no new bone appeared in the other two groups. Four weeks after operation, the newborn trabecular in the group of the cambium layer facing toward the bone was more than the other two groups. Six weeks after operation, the amount of the newborn trabecular and the tight interdigitation between the tendon graft and the newly formed bone in the group of the cambium layer facing toward the bone were superior to the group of the fibrous layer toward the bone and the control group. Biomechanical testing, according to a one-factor ANOVA and Student-Newman-Keuls multiple range test, there was significant difference in statistics between the group of the cambium layer facing toward the bone and the other two groups (P0.05). Conclusion Periosteal graft was wrapped around the tendon with the cambium layer facing toward the bone, may shorten the time of osteochondral ossification of the periostum and improve the tendon healing in the bone tunnel.

The obstruction of post-insulin receptor signaling is the main mechanism of insulin-resistant diabetes. Progestin and adipoQ receptor 3 (PAQR3), a key regulator of inflammation and metabolism, can negatively regulate the PI3K/AKT signaling pathway. Here, we report that gentiopicroside (GPS), the main bioactive secoiridoid glycoside of Gentiana manshurica Kitagawa, decreased lipid synthesis and increased glucose utilization in palmitic acid (PA) treated HepG2 cells. Additionally, GPS improved glycolipid metabolism in streptozotocin (STZ) treated high-fat diet (HFD)-induced diabetic mice. Our findings revealed that GPS promoted the activation of the PI3K/AKT axis by facilitating DNA-binding protein 2 (DDB2)-mediated PAQR3 ubiquitinated degradation. Moreover, results of surface plasmon resonance (SPR), microscale thermophoresis (MST) and thermal shift assay (TSA) indicated that GPS directly binds to PAQR3. Results of molecular docking and cellular thermal shift assay (CETSA) revealed that GPS directly bound to the amino acids of the PAQR3 NH₂-terminus including Leu40, Asp42, Glu69, Tyr125 and Ser129, and spatially inhibited the interaction between PAQR3 and the PI3K catalytic subunit (P110α) to restore the PI3K/AKT signaling pathway. In summary, our study identified GPS, which inhibits PAQR3 expression and directly targets PAQR3 to restore insulin signaling pathway, as a potential drug candidate for the treatment of diabetes.