To address the significance of enhancing myelination for functional recovery after white matter injury (WMI) in preterm infants, we characterized hypomyelination associated with chronic hypoxia and identified structural and functional deficits of excitatory cortical synapses with a prolonged motor deficit. We demonstrate that genetically delaying myelination phenocopies the synaptic and functional deficits observed in mice after hypoxia, suggesting that myelination may possibly facilitate excitatory presynaptic innervation. As a gain-of-function experiment, we specifically ablated the muscarinic receptor 1 (M1R), a negative regulator of oligodendrocyte differentiation in oligodendrocyte precursor cells. Genetically enhancing oligodendrocyte differentiation and myelination rescued the synaptic loss after chronic hypoxia and promoted functional recovery. As a proof of concept, drug-based myelination therapies also resulted in accelerated differentiation and myelination with functional recovery after chronic hypoxia. Together, our data indicate that myelination-enhancing strategies in preterm infants may represent a promising therapeutic approach for structural/functional recovery after hypoxic WMI.

Objective: To review postoperative complications reported after closed calcaneus fracture treated by open reduction and internal fixation (ORIF). Methods: Postoperative complications reported in the literature between 1995 and 2012 were identified. Papers were retrieved from publicly available databases and included in this study if they met the following criteria: clinical research of cases of closed calcaneus fracture treated by ORIF; 10 cases; detailed information about complications, treatment and follow up. Results: Twenty-one clinical reports were analysed (2046 cases). Reported complications (and incidence rates) were: infection and skin flap necrosis (13.6%); neurovascular injury (2.8%); posttraumatic arthritis (1.2%); malreduction/implant problems (0.8%); nonunion (0.1%). Conclusions: Postoperative complications after closed calcaneus fracture are common clinical problems that cannot always be avoided. They can even be life altering, due to the requirement for long-term treatment or amputation and their economic impact on the patient. Complications should be diagnosed and treated promptly, to achieve satisfactory outcomes. Nonsurgical treatment (e.g. local wound care, drugs or physical therapy) can be attempted. If such measures fail, surgical treatment (e.g. debridement, skin flap transplantation, implant removal, re-opening of the reduction and internal fixation or subtalar joint arthrodesis) should be considered.

Aloesin is an active constituent of the herb aloe vera and plays a crucial role in anti-inflammatory activity, ultraviolet protection, and antibacterium. We investigated the role and possible mechanisms of aloesin in the cell growth and metastasis of ovarian cancer. It was found that aloesin inhibited cell viability and cell clonality in a dose-dependent manner. It arrests the cell cycle at the S-phase and induced apoptosis in SKOV3 cells. In an in vivo experiment, it was observed that aloesin inhibited tumor growth. Moreover, it inhibited migration and invasion of cancer in SKOV3 cells. Interestingly, members from the mitogen-activated protein kinase (MAPK) signaling family became less phosphorylated as the aloesin dose increased. This suggests that aloesin exerts its anticancer effect through the MAPK signaling pathway. Our data also highlights the possibility of using aloesin as a novel therapeutic drug for ovarian cancer treatment.

Background We aimed to investigate the functions and underlying mechanism of lncRNA SNHG1 in bone differentiation and angiogenesis in the development of osteoporosis. Methods The differential gene or proteins expressions were measured by qPCR or western blot assays, respectively. The targeted relationships among molecular were confirmed through luciferase reporter, RIP and ChIP assays, respectively. Alkaline phosphatase (ALP), alizarin red S (ARS) and TRAP staining were performed to measure the osteoblast/osteoclast differentiation of BMSCs. The viability, migration and angiogenesis in BM-EPCs were validated by CCK-8, clone formation, transwell and tube formation assays, respectively. Western blot and immunofluorescence detected the cytosolic/nuclear localization of β-catenin. Ovariectomized (OVX) mice were established to confirm the findings in vitro. Results SNHG1 was enhanced and miR-181c-5p was decreased in serum and femoral tissue from OVX mice. SNHG1 directly inhibited miR-181c-5p to activate Wnt3a/β-catenin signaling by upregulating SFRP1. In addition, knockdown of SNHG1 promoted the osteogenic differentiation of BMSCs by increasing miR-181c-5p. In contrast, SNHG1 overexpression advanced the osteoclast differentiation of BMSCs and inhibited the angiogenesis of BM-EPCs, whereas these effects were all reversed by miR-181c-5p overexpression. In vivo experiments indicated that SNHG1 silencing alleviated osteoporosis through stimulating osteoblastogenesis and inhibiting osteoclastogenesis by modulating miR-181c-5p. Importantly, SNHG1 could be induced by SP1 in BMSCs. Conclusions Collectively, SP1-induced SNHG1 modulated SFRP1/Wnt/β-catenin signaling pathway via sponging miR-181c-5p, thereby inhibiting osteoblast differentiation and angiogenesis while promoting osteoclast formation. Further, SNHG1 silence might provide a potential treatment for osteoporosis. Graphic abstract

No abstract

Objective:To summarize the clinical results of femoral head fracture-dislocation treated according to Pipkin classification.Methods:Atotal of 19 patients with femoral head fracture-dislocation were retrospectively analyzed from Mar. 2008 to Mar. 2015. According to the classification of Pipkin criteria, there were 4 cases in Type-I, 6 cases in Type-II, 6 cases in Type-IIIand 3 cases in Type-IV. Various procedures were taken according to the different types of the fracture, the time of the fracture, and the age of the patients. X-ray was examined during the follow-up period and functional evaluation was carried out by Harris Hip Score’s criteria. The clinical therapeutic effects were analyzed.Results:All the patientsgot a mean follow-up of 18 months (9-36 months). No patient suffered from infection, skin flap necrosis and X-ray showed no implants loosening or breakage. According to the Harris Hip Score’s criteria, in Type-I, 4 cases were rated as excellent. In Type-II, 2 cases rated as excellent, 3 cases as good and 1 case as fair. In Type-III, 3 cases rated as good, 2 cases as fair and 1 case as poor. In Type-IV, 1 case rated as excellent, 1 case as good and 1 case as fair. The overall rate of excellent and good was 73.7%.Conclusions:Pipkin classification is helpful to make preoperative plan and judging the prognosis in cases of femoral head fracture-dislocation. However, multiple factors such as the time from injury to surgery, the ages of patients, the selection of implants should also be considered, which may affect the clinical results.

No abstract

The connections between energy metabolism and stemness of hematopoietic stem cells (HSCs) at different developmental stages remain largely unknown. We herein generate a transgenic mouse line for the genetically encoded NADH/NAD+ sensor (SoNar) and demonstrate that there exist three distinct fetal liver hematopoietic cell populations according to the ratios of SoNar fluorescence. SoNar-low cells have an enhanced level of mitochondrial respiration, but similar glycolytic level to SoNar-high cells. Interestingly, 10% of SoNar-low cells are enriched for 65% of total immunophenotypical fetal liver HSCs (FL-HSCs) and contain approximately 5-fold greater functional HSCs than that of SoNar-high counterparts. SoNar can monitor sensitively the dynamic changes of energy metabolism in HSCs both in vitro and in vivo. Mechanistically, STAT3 transactivates MDH1 to sustain the malate-aspartate NADH shuttle activity and the HSC self-renewal and differentiation. We reveal an unexpected metabolic program of FL-HSCs and provide a powerful genetic tool for metabolic studies of HSCs or other types of stem cells.