AimsAltered expression of epithelial or stromal caveolin-1 (Cav-1) is observed in various types of human cancers. However, the clinical significance of Cav-1 expression in gastric cancer (GC) remains largely unknown. The present study aims to explore the clinicopathological significance and prognostic value of both tumor cells and cancer associated fibroblasts (CAFs) Cav-1 in GC.Methods and ResultsQuantum dots immunofluorescence histochemistry was performed to examine the expression of Cav-1 in 20 cases of gastritis without intestinal metaplasia (IM), 20 cases of gastritis with IM and 286 cases of GC. Positive rates of epithelial Cav-1 in gastritis without IM, gastritis with IM and GC showed a decreasing trend (P = 0.012). Low expression of Cav-1 in CAFs but not in tumor cells was an independent predictor of poor prognosis in GC patients (P = 0.034 and 0.005 respectively in disease free survival and overall survival). Cav-1 level in tumor cells and CAFs showed no significant correlation with classic clinicopathological features.ConclusionsLoss of epithelial Cav-1 may promote malignant progression and low CAFs Cav-1 level herald worse outcome of GC patient, suggesting CAFs Cav-1 may be a candidate therapeutic target and a useful prognostic marker of GC.

Background Patients with diabetes have an increased risk of nonunion and delayed union of fractures. Macrophages have been shown as a key player in diabetic complications. However, it remains obscure how diabetic milieu affects macrophage-derived exosomes and its implications on osteogenic differentiation of BMSCs. In this study, we aim to define the impact of diabetic milieu on macrophage-derived exosomes, role of extracellular vesicles in intercellular communication with BMSCs, and subsequent effects on osteogenic differentiation and fracture repair. Results The osteogenic potential and the ability of fracture repair of exosomes derived from diabetic bone marrow-derived macrophages (dBMDM-exos) were revealed to be lower, as compared with non-diabetic bone marrow-derived macrophages (nBMDM-exos) in vitro and in vivo. Interestingly, miR-144-5p levels were sharply elevated in dBMDM-exos and it could be transferred into BMSCs to regulate bone regeneration by targeting Smad1. In addition, the adverse effects of dBMDM-exos on the osteogenic potential and the ability of fracture repair were reversed through the suppression of miR-144-5p inhibition in vitro and vivo. Conclusions The results demonstrated an important role of exosomal miR-144-5p in bone regeneration, offering insight into developing new strategy for the improvement of fracture healing in patients with diabetes mellitus. Graphic Abstract

Negative pressure wound therapy (NPWT) has been demonstrated to accelerate wound healing by promoting angiogenesis. However, whether blood flow perfusion is regulated by microvessel maturation and pericytes following NPWT remains unclear, as well as the exact association between pericytes and collagen type IV. The aim of this study was to investigate the relevant association between blood flow perfusion and microvessel maturation and pericytes following NPWT, and to further explore the underlying molecular mechanisms. We also aimed to investigate the association between pericytes and collagen type IV. For this purpose, we created a rat model of diabetic wounds and microvascular blood flow perfusion was detected using a laser Doppler blood perfusion imager. The expression levels of angiogenin-1, tyrosine phosphorylation of tyrosine kinase receptor-2 (Tie-2), α-smooth muscle actin (α-SMA) and collagen type IV were detected and analyzed through immunohistochemistry, immunofluorescence, RT-qPCR and western blot analysis. The results revealed that NPWT promoted the overexpression of angiogenin-1, Tie-2, α-SMA and collagen type IV, and significantly increased blood flow perfusion coupled with microvessel maturation in the NPWT group at the later stages (7–10 days) of wound healing. Our results suggested that NPWT can preferentially enhance vessel maturation and increase the number of pericytes, thus regulating blood flow perfusion. On the other hand, pericytes and collagen type IV had a mutual interaction, promoting microvessel maturation.

The use of fibular graft for the reconstruction of bone defects has been demonstrated to be a reliable method. The aim of this study was to assess the clinical outcome of graft union, functional outcome (hypertrophy of the graft bones) and complications of both non-vascularized and vascularized grafts.From 1981 to 2015, 10 patients were treated using non-vascularized fibular graft or free vascularized fibular graft. The outcomes were bony union time, graft hypertrophy and complications based on radiograph and functional outcomes according to the Musculoskeletal Tumor Society (MSTS) score. Mobility of the ankle at the donor site was evaluated using the Kofoed ankle score system.This study included 10 patients with an average follow-up of 6.8 years. The union rate for all patients was 100%. The mean union time was 21.3 weeks for vascularized fibular grafts and 30.5 weeks for non-vascularized fibular grafts (P = .310). There was a significant difference between the upper limbs and the lower limbs regarding hypertrophy of the grafts in 5 patients (P = .003). The mean MSTS score in 10 patients was 84% (range 53%–97%). Stress fracture of the graft occurred in 1 patient. Donor site complications, including valgus deformity and length discrepancy, between 2 legs occurred in 2 patients who were under 18 years of age at the time of operation (P = .114). The mean Kofoed score was 96.8 (range 88–100).A greater increase in hypertrophy of grafts was observed with reconstruction in the lower limbs. There was no difference in MSTS score between these 2 types of grafts. Children were more likely to experience the valgus deformity at the donor site after harvesting the fibula. Keeping at least the distal 1/4 of the fibula intact during the surgery is a valid means of ensuring ankle stability at the donor site, and children should be considered for prophylactic distal tibiofibular synostosis creation to prevent the valgus deformity of the ankle at the donor site.

Angiogenesis is involved in the wound healing process. Increased angiogenesis and blood flow constitute a major mechanism of negative pressure wound therapy (NPWT), which has been shown to facilitate the healing of infected wounds. However, the effect on the expression of angiogensis‑related growth factor remains unknown. The goal of the current study was to investigate the angiogenic factor levels prior to and following NPWT in infected wounds. A total of 20 patients with infected wounds treated with NPWT were included in the study. Patients acted as their own control; the postoperative measurements of patients were considered as the experimental group, while preoperative measurements were considered as the controlled group. Blood flow was recorded prior to and during NPWT. A total of 10 angiogensis‑related growth factors were detected using a protein biochip array to analyze the change in protein levels prior to NPWT, and on the third day during NPWT. All wounds were successfully reconstructed by skin grafting or using local flaps following NPWT. NPWT resulted in significantly increased blood flow in the wound. There was a significant increase in vascular endothelial growth factor (VEGF), EGF, platelet‑derived growth factor and angiotesin‑2 following NPWT, while basic fibroblast growth factor decreased significantly. NPWT affects the local expression of angiogenesis‑associated growth factors, which represents another mechanism to explain how NPWT accelerates wound healing.