In situ tissue engineering is a powerful strategy for the treatment of bone defects. It could overcome the limitations of traditional bone tissue engineering, which typically involves extensive cell expansion steps, low cell survival rates upon transplantation, and a risk of immuno-rejection. Here, a porous scaffold polycaprolactone (PCL)/decellularized small intestine submucosa (SIS) was fabricated via cryogenic free-form extrusion, followed by surface modification with aptamer and PlGF-2 123-144 *-fused BMP2 (pBMP2). The two bioactive molecules were delivered sequentially. The aptamer Apt19s, which exhibited binding affinity to bone marrow-derived mesenchymal stem cells (BMSCs), was quickly released, facilitating the mobilization and recruitment of host BMSCs. BMP2 fused with a PlGF-2 123-144 peptide, which showed “super-affinity” to the ECM matrix, was released in a slow and sustained manner, inducing BMSC osteogenic differentiation. In vitro results showed that the sequential release of PCL/SIS-pBMP2-Apt19s promoted cell migration, proliferation, alkaline phosphatase activity, and mRNA expression of osteogenesis-related genes. The in vivo results demonstrated that the sequential release system of PCL/SIS-pBMP2-Apt19s evidently increased bone formation in rat calvarial critical-sized defects compared to the sequential release system of PCL/SIS-BMP2-Apt19s. Thus, the novel delivery system shows potential as an ideal alternative for achieving cell-free scaffold-based bone regeneration in situ .

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Objective. To explore the effect of diabetes on short-term (30 days after fracture) and 1-year outcomes for fragility hip fracture patients. Methods. We conducted a retrospective cohort study involving 161 diabetic hip fracture patients (older than 60 years) and 483 nondiabetic hip fracture patients. Patients were followed up on day 30 and 1 year after fracture. The short-term outcome was complications that occurred within 30 days after hip fracture and length of stay. The 1-year outcomes were postfracture functional outcomes and reduced activity level and mortality rate within 1 year after fracture. The clinical characteristics and outcomes of patients were analyzed. Results. Compared with nondiabetic patients, diabetic patients had a longer length of awaiting surgery (6.0 vs. 5.0 days, P=0.031) and a longer length of total hospital stay (17 vs. 15 days, P<0.001). Furthermore, compared with nondiabetic patients, diabetic patients have higher costs (P=0.011), in addition to being more prone to developing urinary tract infections (6.2% vs. 1.7%, P=0.002) and deep vein thrombosis (4.3% vs. 1.4%, P=0.029) complications. However, at one-year follow-up, no differences in recovery of function and mortality were observed between the two groups. Conclusions. Diabetic patients are at an increased risk of urinary tract infections and deep vein thrombosis complications but have similar recovery of function and 1-year mortality compared to nondiabetic patients.

The aim of this study was to describe the characteristics of diabetic foot ulcer (DFU) patients with anemia and assess the relationship between anemia and DFU outcome. A retrospective cohort study was conducted on patients with DFU who attended our hospital from May 2007 to September 2014. All of the variables in the DFU patients with and without anemia were compared. In this study, 353 subjects were included, anemia was present in 236 patients (66.9%). These patients were significantly male, more likely to be a smoker, had a lower level of serum albumin and worse kidney function, more likely to use at least 2 types of antibiotics and had a worse perfusion of the lower limb, a larger and deeper ulcer and a more severe infection. A multivariate analysis showed that male sex, lower serum albumin, and worse kidney function were independent predictors of anemia in DFU patients. Additionally, in multivariate models, anemia was one of the variables that was most significantly associated with adverse outcomes and with similar findings for secondary outcomes. Receiver operating characteristic analysis determined a hemoglobin cutoff of 12.3 g/dL (females) and 12.1 g/dL (males) to identify a high-risk population of DFU patients who would have adverse outcomes. So anemia is common in patients with DFU. Although typically mild or moderate, anemia has been associated with substantial morbidity and mortality in patients with DFU.

Background: Although ageing could increase the risk of delayed healing in diabetic foot ulcers (DFUs) patients, data from middle-aged patients remains greatly limited. The purpose of this study was to explore the clinical phenotypes, outcomes and predictive factors of DFU in middle-aged patients. Methods: A retrospective cohort study conducted with 422 consecutive inpatients with DFUs who visited our hospital between May 2010 and September 2017; participants were recruited and assigned according to age to either the middle-aged group or the elderly group. The Demographics, ulcer characteristics, comorbidities and diabetes complications, laboratory tests, socioeconomic data and final outcomes were collected. Moreover, predictive factors of adverse outcomes in middle-aged DFUs patients were assessed. Results: Middle-aged patients were more likely to have worse lifestyle and glucose control, were more likely to have microangiopathy as a complication, and tended to have larger and deeper ulcers; however, these patients also had higher rates of healing and lower rates of mortality and major amputaion than elderly patients. Severe infection,living alone,current smoking cigarettes, and having a high white blood cell count were independent risk factors for adverse outcomes in middle-aged patients. Conclusions: DFUs are relatively common in middle-aged patients with diabetes, and these patients have unique clinical phenotypes and risk profiles. Nonetheless, further investigation is needed to clarify whether intervention targeting these easily recognizable risk factors can improve healing and survival rates in middle-aged DFU patients.

Neutrophils constitute abundant cellular components in human gastric cancer (GC) tissues, but their protumorigenic subset in pathogenesis of GC progression is unclear. Here, it is found that patients with GC show significantly higher neutrophil infiltration in tumors that is regulated by CXCL12-CXCR4 chemotaxis. These tumor-infiltrating neutrophils express high level immunosuppressive molecules FasL and PD-L2, and this FasL + PD-L2 + neutrophil subset with a unique phenotype constitutes at least 20% of all neutrophils in advanced GC and predicts poor patient survival. Tumor induces neutrophils to express FasL and PD-L2 proteins with similar phenotype to those in GC tumors in both time-dependent and dose-dependent manners. Mechanistically, Th17 cell-derived IL-17A and tumor cell-derived G-CSF can significantly induce neutrophil FasL and PD-L2 expression via activating ERK-NF-𝜿B and JAK-STAT3 signaling pathway, respectively. Importantly, upon over-expressing FasL and PD-L2, neutrophils acquire immunosuppressive functions on tumor-specific CD8 + T-cells and promote the growth and progression of human GC tumors in vitro and in vivo, which can be reversed by blocking FasL and PD-L2 on these neutrophils. Thus, the work identifies a novel protumorigenic FasL + PD-L2 + neutrophil subset in GC and provides new insights for human cancer immunosuppression and anti-cancer therapies targeting these pathogenic cells.

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Matricellular proteins, a group of extracellular matrix (ECM) proteins, are key regulators of skin repair and their dysregulation impairs wound healing in diabetes. Tubulointerstitial nephritis antigen like 1 (TINAGL1) is a new member of matricellular protein family, and the understanding of its functional role is still relatively limited. In the current study, we detected the expression of TINAGL1 in diabetic skin wound tissues through RT‐PCR, ELISA and Western blot analysis, investigated the contribution of TINAGL1 to wound healing through cutaneous administration of recombinant TINAGL1 protein, and characterized its regulation by hyperglycemia through RNA‐seq and signal pathway inhibition assay. We showed that TINAGL1 expression has dynamic change and reaching a peak on day‐9 after wound during the wound healing process in wild‐type (WT) mice. Interestingly, decreased TINAGL1 expression is detected in skin tissues of diabetic patients and mice after wound. Then, we found that high glucose (HG), an important factor that impairs wound healing, reduces the expression of TINAGL1 in fibroblasts through JNK pathway. Notably, the histology analysis, Masson trichrome assay and IHC assay showed that exogenous TINAGL1 promotes wound healing in diabetic mice by accelerating the formation of granulation tissues. Our study provides evidence that TINAGL1 has an essential role in diabetic wound healing, and meanwhile, indicates that manipulation of TINAGL1 might be a possible therapeutic approach.