Development of a nomogram to predict surgical site infection after closed comminuted calcaneal fracture.

BACKGROUND: Compared with open comminuted calcaneal fractures, less emphasis is placed on postoperative surgical site infection (SSI) of closed comminuted calcaneal fractures. This study aimed to identify the risk factors associated with SSI and build a nomogram model to visualize the risk factors for postoperative SSI. METHODS: We retrospectively collected patients with closed comminuted calcaneal fractures from the Second Affiliated Hospital of Wenzhou Medical University database from 2017 to 2020. Risk factors were identified by logistics regression analysis, and the predictive value of risk factors was evaluated by ROC (receiver operating characteristic curve). Besides, the final risk factors were incorporated into R4.1.2 software to establish a visual nomogram prediction model. RESULTS: The high-fall injury, operative time, prealbumin, aspartate aminotransferase (AST), and cystatin-C were independent predictors of SSI in calcaneal fracture patients, with OR values of 5.565 (95%CI 2.220-13.951), 1.044 (95%CI 1.023-1.064), 0.988 (95%CI 0.980-0.995), 1.035 (95%CI 1.004-1.067) and 0.010 (95%CI 0.001-0.185) (Ps < 0.05). Furthermore, ROC curve analysis showed that the AUC values of high-fall injury, operation time, prealbumin, AST, cystatin-C, and their composite indicator for predicting SSI were 0.680 (95%CI 0.593-0.766), 0.756 (95%CI 0.672-939), 0.331 (95%CI 0.243-0.419), 0.605 (95%CI 0.512-0.698), 0.319 (95%CI 0.226-0.413) and 0.860 (95%CI 0.794-0.926), respectively (Ps < 0.05). Moreover, the accuracy of the nomogram to predict SSI risk was 0.860. CONCLUSIONS: Our study findings suggest that clinicians should pay more attention to the preoperative prealbumin, AST, cystatin C, high-fall injury, and operative time for patients with closed comminuting calcaneal fractures to avoid the occurrence of postoperative SSI. Furthermore, our established nomogram to assess the risk of SSI in calcaneal fracture patients yielded good accuracy and can assist clinicians in taking appropriate measures to prevent SSI.

Apelin-13 induces mitophagy in bone marrow mesenchymal stem cells to suppress intracellular oxidative stress and ameliorate osteoporosis by activation of AMPK signaling pathway.

Osteoporosis is characterized by impaired bone metabolism. Current estimates show that it affects millions of people worldwide and causes a serious socioeconomic burden. Mitophagy plays key roles in bone marrow mesenchymal stem cells (BMSCs) osteoblastic differentiation, mineralization, and survival. Apelin is an endogenous adipokine that participates in bone homeostasis. This study was performed to determine the role of Apelin in the osteoporosis process and whether it affects mitophagy, survival, and osteogenic capacity of BMSCs in in vitro and in vivo models of osteoporosis. Our results demonstrated that Apelin was down-regulated in ovariectomized-induced osteoporosis rats and Apelin-13 treatment activated mitophagy in BMSCs, ameliorating oxidative stress and thereby reviving osteogenic function via AMPK-α phosphorylation. Besides, Apelin-13 administration restored bone mass and microstructure as well as reinstated mitophagy, enhanced osteogenic function in OVX rats. Collectively, our findings reveal the intrinsic mechanisms underlying Apelin-13 regulation in BMSCs and its potential therapeutic values in the treatment of osteoporosis.

STAT3 activation by catalpol promotes osteogenesis-angiogenesis coupling, thus accelerating osteoporotic bone repair.

BACKGROUND: Bone fracture repair has gained a lot of attention due to the high incidence of delayed union or even nonunion especially in osteoporotic patients, resulting in a dreadful impact on the quality of life. However, current therapies involve the costly expense and hence become unaffordable strategies for fracture recovery. Herein, developing new strategies for better bone repair is essential and urgent. Catalpol treatment has been reported to attenuate bone loss and promote bone formation. However, the mechanisms underlying its effects remain unraveled. METHODS: Rat bone marrow mesenchymal stem cells (BMSCs) were isolated from rat femurs. BMSC osteogenic ability was assessed using ALP and ARS staining, immunofluorescence, and western blot analysis. BMSC-mediated angiogenic potentials were determined using the western blot analysis, ELISA testing, scratch wound assay, transwell migration assay, and tube formation assay. To investigate the molecular mechanism, the lentivirus transfection was used. Ovariectomized and sham-operated rats with calvaria defect were analyzed using micro-CT, H&E staining, Masson's trichrome staining, microfil perfusion, sequential fluorescent labeling, and immunohistochemistry assessment after administrated with/without catalpol. RESULTS: Our results manifested that catalpol enhanced BMSC osteoblastic differentiation and promoted BMSC-mediated angiogenesis in vitro. More importantly, this was conducted via the JAK2/STAT3 pathway, as knockdown of STAT3 partially abolished beneficial effects in BMSCs. Besides, catalpol administration facilitated bone regeneration as well as vessel formation in an OVX-induced osteoporosis calvarial defect rat model. CONCLUSIONS: The data above showed that catalpol could promote osteogenic ability of BMSC and BMSC-dependent angiogenesis through activation of the JAK2/STAT3 axis, suggesting it may be an ideal therapeutic agent for clinical medication of osteoporotic bone fracture.

Therapeutic effect of SIRT3 on glucocorticoid-induced osteonecrosis of the femoral head via intracellular oxidative suppression.

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a serious complication after long-term or excess administration of clinical glucocorticoids intervention, and the pathogenic mechanisms underlying have not been clarified yet. Oxidative stress is considered as a major cause of bone homeostasis disorder. This study is aimed to explore the potential relevance between SIRT3 and GIONFH, as well as the effect of resveratrol, which has been reported for its role in SIRT3 activation, on dexamethasone-induced oxidative stress and mitochondrial compromise in bone marrow stem cells (BMSCs). In this study, our data showed that SIRT3 level was declined in GIONFH rat femoral head, corresponding to a resultant decrease of SIRT3 expression in dexamethasone-treated BMSCs in vitro. We also found that dexamethasone could result in oxidative injury in BMSCs, and resveratrol treatment reduced this deleterious effect via a SIRT3-dependent manner. Moreover, our results demonstrated that rewarding effect of resveratrol on BMSCs osteogenic differentiation was via activation of AMPK/PGC-1α/SIRT3 axis. Meanwhile, resveratrol administration prevented the occurrence of GIONFH, enhanced SIRT3 expression and reduced oxidative level in GIONFH model rats. Therefore, our study provides basic evidence that SIRT3 may be a promising therapeutic target for GIONFH treatment and resveratrol could be an ideal agent for clinical uses.