An injectable thermosensitive hydrogel for sustained release of apelin-13 to enhance flap survival in rat random skin flap.

With the advantage of handy process, random pattern skin flaps are generally applied in limb reconstruction and wound repair. Apelin-13 is a discovered endogenous peptide, that has been shown to have potent multiple biological functions. Recently, thermosensitive gel-forming systems have gained increasing attention as wound dressings due to their advantages. In the present study, an apelin-13-loaded chitosan (CH)/ß-sodium glycerophosphate (ß-GP) hydrogel was developed for promoting random skin flap survival. Random skin flaps were created in 60 rats after which the animals were categorized to a control hydrogel group and an apelin-13 hydrogel group. The water content of the flap as well as the survival area were then measured 7 days post-surgery. Hematoxylin and eosin staining was used to evaluate the flap angiogenesis. Cell differentiation 34 (CD34) and vascular endothelial growth factor (VEGF) levels were detected by immunohistochemistry and Western blotting. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were assessed by enzyme linked immunosorbent assays (ELISAs). Oxidative stress was estimated via the activity of tissue malondialdehyde (MDA) and superoxide dismutase (SOD). Our results showed that CH/ß-GP/apelin-13 hydrogel could not only reduce the tissue edema, but also improve the survival area of flap. CH/ß-GP/apelin-13 hydrogel also upregulated levels of VEGF protein and increased mean vessel densities. Furthermore, CH/ß-GP/apelin-13 hydrogel was shown to significantly inhibit the expression of TNF-α and IL-6, along with increasing the activity of SOD and suppressing the MDA content. Taken together, these results indicate that this CH/ß-GP/apelin-13 hydrogel may be a potential therapeutic way for random pattern skin flap.

Mid-term assessment of subtalar arthroereisis with Talar-Fit implant in pediatric patients with flexible flatfoot and comparing the difference between different sizes and exploring the position of the inserted implant.

Background: Subtalar arthroereisis (STA) has gained growing acceptance as a viable approach solution for the management of pediatric flexible flatfoot. However, STA still remains controversial. The purpose of this study is to assess the effect of STA using the Talar-Fit implant for treating pediatric flexible flatfoot. Specifically, the aims of the study are as follows: first, to present the mid-term outcomes of STA using the Talar-Fit implant; second, to compare the radiographic and clinical outcomes associated with varying sizes of Talar-Fit implant; and third, to analyze the optimal position of the inserted implants. Methods: A retrospective analysis was conducted on a cohort of 57 pediatric patients diagnosed with flexible flatfoot (77 feet) who underwent STA utilizing Talar-Fit between January 2014 and December 2021. The participants were categorized into five groups according to the size of the implant: Group 8, Group 9, Group 10, Group 11, and Group 12. The evaluation included the assessment of clinical function using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hind foot score, as well as the assessment of radiographic data such as the calcaneal pitch angle (CPA), lateral Meary angle (LMA), talar declination angle (TDA), and medial longitudinal arch angle (MLAA) were evaluated. Furthermore, the position of the inserted implants was also recorded, including angle, depth, and distance. The comparison of pre- and postoperation was conducted using the paired Student's t-test, whereas the analysis of differences among subgroups was performed using the Wilcoxon rank-sum test. A P-value < 0.05 is considered statistically significant. Results: In total, 57 pediatric patients (77 feet) were successfully followed-up for an average period of 26.8 months. The overall AOFAS score significantly improved from 58.6 ± 10.9 to 85.2 ± 8.6 (P < 0.001). Furthermore, the LMA decreased from 20.3° ± 3.6° to 4.5° ± 1.3°, the CPA increased from 14.8° ± 1.6° to 23.6° ± 2.7°(P < 0.05), the TDA decreased from 40.2° ± 2.3° to 25.5° ± 3.2°(P < 0.05), and the MLAA decreased from 140.1° ± 2.8° to 121.4° ± 3.9°(P < 0.05). No statistically significant differences were observed among subgroups regarding the final outcomes. The improvements of CPA, TDA, and MLAA among different groups were significantly different; however, the adjusted P-values were all greater than 0.05. The implant were inserted at a mean angle of 89.5° ± 2.4°, a mean depth of 0.9 mm ± 2.1 mm, and a mean distance of 9.9 mm ± 0.9 mm. Eight patients experienced complications, including six cases of pain occurrence and two cases of implant dislocation. Conclusion: STA with Talar-Fit has demonstrated satisfactory mid-term outcomes. A Talar-Fit with a larger size may demonstrate a superior effect when compared with that of a smaller size. The implants were inserted in a similar position, indicating that the medial edge of the implant may be possible to transcend the midline of the talus neck.

Intramedullary versus extramedullary fixation for the treatment of subtrochanteric fracture: A systematic review and meta-analysis.

PURPOSE: This meta-analysis was performed to investigate the outcomes of intramedullary fixation versus extramedullary fixation in the treatment of subtrochanteric fracture from the current literature. METHODS: The electronic literature database of PubMed, Embase, Cochrane library, CNKI and Wanfang were searched in December 2018. The data operation time, intraoperative blood loss, length of incision, length of stay, union time, rate of infection, rate of fixation failure, rate of refracture, rate of reoperation, rate of nonunion and rate of excellent and good results were extracted. Stata 14.0 software was used for our meta-analysis. RESULTS: A total of 11 studies including 8 RCTs and 3 cohort studies met our inclusion criteria. This meta-analysis showed that intramedullary fixation could achieve significantly shorter operation time (P = 0.000), less intraoperative blood loss (P = 0.000), shorter length of incision (P = 0.000) and length of stay (P = 0.001) with evidently lower rate of fixation failure (P = 0.001), rate of reoperation (P = 0.003) and higher rate of excellent and good functional results (P = 0.003) than extramedullary fixation for subtrochanteric fractures. However, no significant difference was found regarding union time (P = 0.17), rate of infection (P = 0.99), rate of refracture (P = 0.98) and rate of nonunion (P = 0.42) between the two groups. CONCLUSION: Our meta-analysis suggested that intramedullary fixation for subtrochanteric fracture might be superior to extramedullary fixation in term of shorter operation time, less intraoperative blood loss, shorter length of incision, length of stay and better functional outcomes. Meanwhile, intramedullary fixation had lower rate of fixation failure and reoperation. Therefore, we recommend intramedullary fixation as the treatment of subtrochanteric fracture. More large multi-center and high-quality RCTs are required for further research.

Inhibiting the PI3K/AKT/NF-κB signal pathway with nobiletin for attenuating the development of osteoarthritis: in vitro and in vivo studies.

Osteoarthritis (OA), an age-related degenerative disease, is characterized by progressive degradation of the articular cartilage. There is increasing evidence that nobiletin (NOB) exerts special biological functions in a variety of diseases. However, whether it protects against OA remains unknown. In this study, we investigated the anti-inflammatory and chondroprotective effects of NOB on IL-1ß-induced human OA chondrocytes and in the surgical DMM mice OA models. In vitro, NOB treatment completely suppressed the overproduction of pro-inflammatory mediators, including PGE2, NO, COX-2, iNOS, TNF-α and IL-6 in IL-1ß-induced human OA chondrocytes. Moreover, NOB exerted a potent inhibitory effect on the expression of MMP-13 and ADAMTS-5 as well as the degradation of aggrecan and collagen-II, which leads to the degradation of the extracellular matrix. Furthermore, NOB dramatically suppressed the IL-1ß-stimulated phosphorylation of PI3K/Akt and activation of NF-κB in human OA chondrocytes. In addition, treatment with NOB not only prevented the destruction of cartilage and the thickening of subchondral bone but also relieved synovitis in mice OA models. In conclusion, our study suggests that NOB holds novel therapeutic potential for the treatment of OA.

With versus without bone grafts for operative treatment of displaced intra-articular calcaneal fractures: A meta-analysis.

PURPOSE: This meta-analysis aimed to investigate the effectiveness of operative treatment of intra-articular calcaneal fractures with bone grafts versus without bone grafts. METHODS: The electronic literature database of Pubmed, Embase, and Cochrane library were searched in April 2018. The data on Böhler angle, Gissane angle, calcaneal width, calcaneal height, AOFAS hindfoot scores and complications (including wound edge necrosis, wound infection, deep infection, hematoma and sural nerve injury) were extracted. The Stata 14.0 software was used for the meta-analysis. RESULTS: Nine studies including 6 RCTs and 3 retrospective cohort studies met our inclusion criteria. This meta-analysis showed that there was no significant difference between the two groups regarding the Böhler angle (P = 0.44), Gissane angle (P = 0.06), calcaneal width (P = 0.09) and calcaneal height (P = 0.44) postoperatively and at the last follow-up. However, the bone graft group had significantly higher AOFAS scores than the non-bone graft group (P < 0.05). No significant difference was found between the two groups in complications (P = 0.63). CONCLUSION: This meta-analysis suggested that operative treatment of intra-articular calcaneal fractures with bone grafts achieved better AOFAS scores than the non-bone graft group. The two groups had similar results in Böhler angle, Gissane angle, calcaneal width and calcaneal height. No increased risk of postoperative complications was identified. More RCTs are required for further research.

Possible therapeutic potential of berberine in the treatment of STZ plus HFD-induced diabetic osteoporosis.

Diabetic osteoporosis is a complication of diabetes mellitus, and can result in an increased incidence of bone fractures and a delay in fracture healing. Berberine is one of the most widely distributed isoquinoline alkaloid in plants and possesses antioxidant properties. These properties can reduce the high glucose mediated in the dysfunction of human bone marrow stem cells. Therefore, the present study was designed to investigate the apparent beneficial effect of berberine on bone characteristics in streptozotocin plus HFD-induced diabetic rats. Rats were selected at random and divided into four groups: (A) control group (CG) (n = 10); (B) diabetic group (DG) (n = 10); (C) diabetic group with 50 mg kg-1day-1 of berberine (Brb-50) (n = 10); and (D) diabetic group with 100 mg kg-1day-1 of berberine (Brb-100) (n = 10). After 12 weeks of being treated with berberine, the femora from all rats were assessed and other blood biochemistries evaluated. Berberine at 50 mg/kg showed little effect and significance on diabetic osteopenia, while berberine at 100 mg/kg was significantly increased in diabetic rats. The same group also displayed a significantly decreased serum osteocalcin and serum alkaline phosphatase activity in diabetic rats. The impaired micro-architecture of the femurs in diabetic rats could partially be prevented by berberine with 100 mg/kg. In addition, berberine could to an extent restore the decreased bone formation and reabsorption of the femurs in diabetic rats through the histomorphometric analysis. Berberine could not only significantly lower the oxidative level of DNA damage, but also up-regulate the activity of serum antioxidants. According to our investigations and discoveries, we have found, that berberine may be a potential drug for controlling bone loss in diabetic osteoporosis.

Comparison of suture button fixation and syndesmotic screw fixation in the treatment of distal tibiofibular syndesmosis injury: A systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis was performed to investigate the outcomes of syndesmotic screw fixation versus suture button fixation in the treatment of distal tibiofibular syndesmosis injury from the current literature. METHODS: The electronic literature database of PubMed, Embase, and Cochrane library were searched in August 2018. The data on medial clear space, tibiofibular clear space, tibiofibular overlap, American Orthopaedic Foot and Ankle Society (AOFAS) scores and complications (including wound infection, local irritation or discomfort, screw loosening and screw breakage) were extracted. Stata 14.0 software was used for our meta-analysis. RESULTS: A total of 11 studies including 5 randomized controlled trials (RCTs) and 6 cohort studies met our inclusion criteria. This meta-analysis showed that there was no significant difference between the two groups regarding medial clear space (P = 0.54), tibiofibular clear space (P = 0.23) and tibiofibular overlap (P = 0.88) postoperatively. However, the present meta-analysis demonstrated that the suture button fixation group had significantly higher AOFAS scores than the syndesmotic screw fixation group at 3rd, 6th, 12th and 24th months postoperatively (P = 0.001, P = 0.006, P = 0.000 and P = 0.049 respectively). Besides, the time to full weight bearing in the suture button fixation group was significantly earlier than that in the syndesmotic screw fixation group (P = 0.000). As for the complications, the suture button fixation group had a lower rate of post-operative complication (screw loosening and screw breakage) compared with the syndesmotic screw fixation group (P = 0.048 and P = 0.000 respectively). CONCLUSION: Our meta-analysis suggested that suture button fixation could achieve significant higher AOFAS scores with a lower rate of postoperative complications and earlier time to full weight bearing in distal tibiofibular syndesmosis injury. More RCTs are required for further research.

Baicalin suppresses IL-1ß-induced expression of inflammatory cytokines via blocking NF-κB in human osteoarthritis chondrocytes and shows protective effect in mice osteoarthritis models.

Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. Baicalin, a predominant flavonoid isolated from the dry root of Scutellaria baicalensis Georgi, has been reported to have anti-inflammatory effects. However, the anti-inflammatory effects of baicalin on OA have not been reported. Our study aimed to investigate the effect of baicalin on OA both in vitro and in vivo. In vitro, human OA chondrocytes were pretreated with baicalin (10, 50, 100µM) for 2h and subsequently stimulated with IL-1ß for 24h. Production of NO and PGE2 were evaluated by the Griess reaction and ELISAs. The mRNA expression of COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5, aggrecan and collagen-II were measured by real-time PCR. The protein expression of COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5, p65, p-p65, IκBα and p-IκBα was detected by Western blot. The protein expression of collagen-II was evaluated by immunofluorescence. Luciferase activity assay was used to assess the relative activity of NF-kB. In vivo, the severity of OA was determined by histological analysis. We found that baicalin significantly inhibited the IL-1ß-induced production of NO and PGE2, expression of COX-2, iNOS, MMP-3, MMP-13 and ADAMTS-5 and degradation of aggrecan and collagen-II. Furthermore, baicalin dramatically suppressed IL-1ß-stimulated NF-κB activation. In vivo, treatment of baicalin not only prevented the destruction of cartilage but also relieved synovitis in mice OA models. Taken together, these results suggest that baicalin may be a potential agent in the treatment of OA.