Neddylation suppression by a macrophage membrane-coated nanoparticle promotes dual immunomodulatory repair of diabetic wounds.

Oxidative stress, infection, and vasculopathy caused by hyperglycemia are the main barriers for the rapid repair of foot ulcers in patients with diabetes mellitus (DM). In recent times, the discovery of neddylation, a new type of post-translational modification, has been found to regulate various crucial biological processes including cell metabolism and the cell cycle. Nevertheless, its capacity to control the healing of wounds in diabetic patients remains unknown. This study shows that MLN49224, a compound that inhibits neddylation at low concentrations, enhances the healing of diabetic wounds by inhibiting the polarization of M1 macrophages and reducing the secretion of inflammatory factors. Moreover, it concurrently stimulates the growth, movement, and formation of blood vessel endothelial cells, leading to expedited healing of wounds in individuals with diabetes. The drug is loaded into biomimetic macrophage-membrane-coated PLGA nanoparticles (M-NPs/MLN4924). The membrane of macrophages shields nanoparticles from being eliminated in the reticuloendothelial system and counteracts the proinflammatory cytokines to alleviate inflammation in the surrounding area. The extended discharge of MLN4924 from M-NPs/MLN4924 stimulates the growth of endothelial cells and the formation of tubes, along with the polarization of macrophages towards the anti-inflammatory M2 phenotype. By loading M-NPs/MLN4924 into a hydrogel, the final formulation is able to meaningfully repair a diabetic wound, suggesting that M-NPs/MLN4924 is a promising engineered nanoplatform for tissue engineering.

3D Inception U-net with Asymmetric Loss for Cancer Detection in Automated Breast Ultrasound.

PURPOSE: Breast cancer is the most common cancer and the leading cause of cancer-related deaths for women all over the world. Recently, automated breast ultrasound (ABUS) has become a new and promising screening modality for whole breast examination. However, reviewing volumetric ABUS is time-consuming and lesions could be missed during the examination. Therefore, computer-aided cancer detection in ABUS volume is extremely expected to help clinician for the breast cancer screening. METHODS: We develop a novel end-to-end 3D convolutional network for automated cancer detection in ABUS volume, in order to accelerate reviewing and meanwhile to provide high detection sensitivity with low false positives (FPs). Specifically, an efficient 3D Inception Unet-style architecture with fusion deep supervision mechanism is proposed to attain decent detection performance. In addition, a novel asymmetric loss is designed to help the network balancing false positive and false negative regions, thus improving detection sensitivity for small cancerous lesions. RESULTS: The efficacy of our network was extensively validated on a dataset including 196 patients with 661 cancer regions. Our network obtained a detection sensitivity of 95.1% with 3.0 FPs per ABUS volume. Furthermore, the average inference time of the network was 0.1 second per volume, which largely shortens the conventional reviewing time. CONCLUSIONS: The proposed network provides efficient and accurate cancer detection scheme using ABUS volume, and may assist clinicians for more efficient breast cancer screening.

Biomechanical Analysis of a Novel Syndesmotic Plate Compared With Traditional Screw and Suture Button Fixation.

Many lateral malleolus fractures have been found to have syndesmosis injuries after anatomic reduction. The main methods for the treatment of syndesmosis injuries are screw fixation and suture-button flexible fixations. In pursuit of innovation, we have designed a novel syndesmotic plate (NSP) for simultaneous fixation of lateral malleolus fractures and distal tibiofibular syndesmosis injuries. The purpose of this study is to compare the biomechanical characteristics of the NSP to syndesmotic screw and suture-button fixations. Twelve adult cadaveric specimens were used in this experiment. Axial loading as well as rotation torque were applied in 3 different ankle positions: neutral, dorsiflexion, and plantarflexion. After the initial specimens were tested, they were made into a pronation-abduction III fracture model as described by Lauge-Hansen. Subsequently, the specimens were fixed sequentially using a distal fibular anatomic locking plate (DFALP) combined with syndesmotic screws, DFALP combined with suture button, and NSP. Then the above tests were repeated. The syndesmotic displacement and the strain of the tibia and fibula were recorded during the experiment. In most cases, the displacements and strains of the NSP group and the screw group were smaller than the suture button groups and the native (SBGAN) (p < .05), and the displacements and strains of the NSP group were also slightly smaller than the screw group in most cases, and there was no significant difference between the 2 groups. The NSP we developed has a fixed strength no less than the traditional syndesmotic screw fixation. This provides us a new idea for the treatment of distal tibiofibular syndesmosis injuries.

Low-Rank Based Image Analyses for Pathological MR Image Segmentation and Recovery.

The presence of pathologies in magnetic resonance (MR) brain images causes challenges in various image analysis areas, such as registration, atlas construction and atlas-based segmentation. We propose a novel method for the simultaneous recovery and segmentation of pathological MR brain images. Low-rank and sparse decomposition (LSD) approaches have been widely used in this field, decomposing pathological images into (1) low-rank components as recovered images, and (2) sparse components as pathological segmentation. However, conventional LSD approaches often fail to produce recovered images reliably, due to the lack of constraint between low-rank and sparse components. To tackle this problem, we propose a transformed low-rank and structured sparse decomposition (TLS2D) method. The proposed TLS2D integrates the structured sparse constraint, LSD and image alignment into a unified scheme, which is robust for distinguishing pathological regions. Furthermore, the well recovered images can be obtained using TLS2D with the combined structured sparse and computed image saliency as the adaptive sparsity constraint. The efficacy of the proposed method is verified on synthetic and real MR brain tumor images. Experimental results demonstrate that our method can effectively provide satisfactory image recovery and tumor segmentation.

The improved oval forceps suture-guiding method for minimally invasive Achilles tendon repair.

OBJECTIVE: To discuss the effect and advantage of the improved oval forceps suture-guiding method combined with anchor nail in the treatment of acute Achilles tendon rupture. METHODS: A retrospective research was performed on 35 cases of acute Achilles tendon rupture treated with the improved oval forceps suture-guiding method from January 2013 to October 2016. Instead of the Achillon device, we perform the Achillon technique with the use of simple oval forceps, combined with absorbable anchor nail, percutaneously to repair the acute Achilles tendon rupture. RESULTS: All patients were followed up for at least 12 months (range, 12-19 months), and all the patients underwent successful repair of their acute Achilles tendon rupture using the improved oval forceps suture-guiding method without any major intra- or postoperative complications. All the patients returned to work with pre-injury levels of activity at a mean of 12.51 ±â€¯0.76 weeks. Mean AOFAS ankle-hindfoot scores improved from 63.95 (range, 51-78) preoperatively to 98.59 (range, 91-100) at last follow-up. This was statistically significant difference (P < 0.001). Mean Achilles Tendon Total Rupture Score (ATRS) at final follow-up was 94.87 (range, 90-100). CONCLUSION: The improved oval forceps suture-guiding method could make the advantage of minimally invasive repair with less complications, reduced surgical time and similar functional outcomes compared with the traditional open surgery. In addition, our new technique could save the cost of surgery with the compare of the Achillon device. At the same time for the cases which the remote broken tendon ends were within 2 cm from the calcaneal nodules, because of the less tendon tissue was left in the remote side, traditional percutaneous methods are incapable to ensure the reconstruction strength. By using the anchor nail, the improved technique has better repair capacity and expands the operation indication of oval forceps method.

Comparison of three fixation methods in treatment of tibial fracture in adolescents.

BACKGROUND: Tibial fractures are the most common musculoskeletal injury in adolescents. The optimal management of tibial fractures in adolescents is controversial. In this study, we compared the outcomes including complications of three fixation methods in tibial fractures of adolescents and explored the factors associated with the complications. METHODS: A retrospective cohort study about 83 diaphyseal tibial fractures in 79 children and adolescents, who were treated with plate fixation (PF), elastic stable intramedullary nail fixation (ESINF), or external fixation (EF), was conducted. After adjustment for age, weight, energy of the injury, polytrauma, fracture level and pattern, and extent of comminution, treatment outcomes were compared in accordance with the length of the hospital stay, time to union, and complication rates including many factors. RESULTS: The mean age of the patients was 13.4 years, and their mean weight was 44.2 kg. There was a loss of reduction in two of 33 fractures treated with ESINF and four of 13 treated with EF (P < 0.001). At the time of final follow-up, three patients (two treated with EF and one treated with ESINF) had ≥2.0 cm of shortening. Four of the 32 patients (33 fractures) treated with ESINF underwent a reoperation (two due to loss of reduction and one each because of delayed union and nonunion). Six patients treated with EF required a reoperation (four due to loss of reduction, one for malunion and one for replacement of a pin complicated by infection). Two fracture treated with PF required refixation attributing to nonunion and malunion. A multivariate analysis with adjustment for baseline differences showed that EF was associated with a 7.56-times (95% confidence interval 3.74-29.87) greater risk of loss of reduction and/or malunion than ESINF. CONCLUSIONS: All three treatments had satisfactory outcomes, and EF was correlated with the highest rate of complications in our series of adolescents treated with a tibial fracture. However, we cannot currently recommend that all fractures might be suitable for ESINF. The choice of fixation will remain influenced by surgeon preference in term of expertise and experience, patient and fracture characteristics, and patients and family preferences.

Distal tibial nonunion using a contralateral anterior L-shaped locking compression plate through a posterior-lateral approach: A retrospective case series.

BACKGROUND: Distal tibial nonunion is usually due to severe open distal tibial fractures with high energy injury. The best surgical treatment is not well established because of the poor soft tissue condition. We retrospectively analyzed a series of patients with distal tibial nonunion after severe open distal tibial fractures; our purpose was to introduce a treatment using a contralateral anterior L-shaped locking compression plate through a posterior-lateral approach with Iliac crest bone graft and evaluate the outcomes of patients. METHODS: All patients with distal tibial nonunion who received a contralateral anterior L-shaped locking compression plate fixation through the posterior-lateral approach with Iliac crest bone graft by a single surgeon from 2014 to 2016 were reviewed. 9 patients met the criteria. Five of nine patients had varus deformities (range, 9-40°) and 4 patients had valgus deformities (range, 5-30°). Postoperative radiographs, Postoperative complications, limb alignment and limb functional outcome information of AOFAS ankle-hindfoot score were recorded. RESULTS: All patients were followed up for at least 8 months (range, 8-16 months). Union was achieved in all patients after the index surgery without postoperative wound complications while one patient came up with checkrein deformity. Average time to radiographic union was 16 weeks (range, 12-24 weeks). All patients had correction to neutral alignment in both coronal and sagittal planes. The average AOFAS ankle-hindfoot score was 90 (range, 77-100) at the last follow-up of patients. CONCLUSIONS: Using a contralateral anterior L-shaped locking compression plate fixation through a posterior-lateral approach with Iliac crest bone graft to reconstruct the distal tibial nonunion is a safe and reliable method that can successfully treat patients with poor soft tissue condition of anterior portion of leg because of its adequate exposure, both tibia and fibula rigid fixation and plenty of bone graft. We believe the application of this method resulting in a high union and low complication rate.

Effect of Hypoxia on Self-Renewal Capacity and Differentiation in Human Tendon-Derived Stem Cells.

BACKGROUND Hypoxic conditions play roles in functioning of human tendon-derived stem cells (hTSCs). The goal of this study was to investigate the effect of various hypoxic conditions in self-renewal capacity and differentiation of TSCs. MATERIAL AND METHODS hTSCs was obtain from supraspinatus tendon donors. Colony formation and cell proliferation assay were used to assess the self-renewal of hTSCs. qRT-PCT and Western blot analysis were used to examine stemness and multi-differentiation potential of hTSCs. RESULTS We found that culturing at 5% O2 is more beneficial for the self-renewal of hTSCs than the other 3 culture conditions, with larger colony size and numbers. The proliferation of hTSCs in 5%, 10%, and 20% O2 cultures increased after seeding. The number of cells in the 5% O2 condition was higher than that in other culture; however, self-renewal capacity of hTSCs in 0.5% O2 was inhibited. The expression levels of stem cell markers, including NS, Nanog, Oct-4, and SSEA-4, were highest in 0.5% O2 culture. Furthermore, hTSCs cultured in 20% O2 exhibited significantly higher expression of the 3 markers (PPAR-γ, Sox-9, and Runx-2). CONCLUSIONS Hypoxic condition of culture encouraged self-renewal capacity of hTSCs, but inhibited their multi-differentiation potential, compared to normoxic condition of culture. Moreover, excessively low oxygen concentration impaired the capacity of hTSCs.