A temperature and pH dual-responsive injectable self-healing hydrogel prepared by chitosan oligosaccharide and aldehyde hyaluronic acid for promoting diabetic foot ulcer healing.

Chronic wound, such as skin defect after burn, pressure ulcer, and diabetic foot ulcer is very difficult to cure. Its pathological process is often accompanied with local temperature rise, pH decrease, and other phenomena. Owing to their outstanding hydrophilic, biocompatibility, and responsive properties, hydrogels could accelerate the healing process. In this study, we chose chitosan oligosaccharide (COS) grafted with Pluronic F127 (F127-COS). Aldehyde hyaluronic acid (A-HA) oxidized by NaIO4. And added boric acid (BA) to prepare a thermosensitive and pH-responsive injectable self-healing F127-COS/A-HA/COS/BA (FCAB) hydrogel, loaded with drug deferoxamine (DFO) in order to have an accurate release and promote angiogenesis of diabetic foot ulcer. In vitro experiments had verified that the FCAB hydrogel system loaded with DFO (FCAB/D) could promote migration and angiogenesis of HUVEC. A diabetes rat back wound model further confirmed its role in promoting angiogenesis in wound repair process. The results showed that the FCAB/D hydrogel exhibited unique physicochemical properties, excellent biocompatibility, and significantly enhanced therapeutic effects for diabetic foot ulcer.

Injectable hydrogel loaded with 4-octyl itaconate enhances cartilage regeneration by regulating macrophage polarization.

Macrophages play a distinctive role in the early stage of inflammation after cartilage defects. Previous studies have shown that macrophages can express different phenotypes, among which M2 polarization is important to maintain the balance of the inflammatory microenvironment and promote cartilage regeneration. In this study, 4-octyl itaconic acid (4-OI), a derivative of the endogenous metabolite itaconic acid, was used to regulate the polarization behavior of macrophages and enhance cartilage repair. Oxidized sodium alginate (OSA) and gelatin (GEL) were selected as materials to form injectable hydrogels with the function of sustained release of 4-OI. In vivo and in vitro experiments have verified that the OSA/GEL hydrogel system loaded with 4-OI could promote M2 macrophage polarization and inhibit the inflammatory reaction. A rat knee joint cartilage defect model further confirmed its role in promoting cartilage regeneration in the later stage. In this study, the OSA/GEL hydrogel was successfully fabricated as a vehicle for delivering 4-OI, which could evidently alleviate the inflammatory reaction and thus accelerate tissue regeneration. The results of this study provide a new method for promoting subsequent tissue regeneration by regulating the early immune response.

Construction of Rapid Extracellular Matrix-Deposited Small-Diameter Vascular Grafts Induced by Hypoxia in a Bioreactor.

Cardiovascular disease has become one of the most globally prevalent diseases, and autologous or vascular graft transplantation has been the main treatment for the end stage of the disease. However, there are no commercialized small-diameter vascular graft (SDVG) products available. The design of SDVGs is promising in the future, and SDVG preparation using an in vitro bioreactor is a favorable method, but it faces the problem of long-term culture of >8 weeks. Herein, we used different oxygen (O2) concentrations and mechanical stimulation to induce greater secretion of extracellular matrix (ECM) from cells in vitro to rapidly prepare SDVGs. Culturing with 2% O2 significantly increased the production of the ECM components and growth factors of human dermal fibroblasts (hDFs). To accelerate the formation of ECM, hDFs were seeded on a polycaprolactone (PCL) scaffold and cultured in a flow culture bioreactor with 2% O2 for only 3 weeks. After orthotopic transplantation in rat abdominal aorta, the cultured SDVGs (PCL-decellularized ECM) showed excellent endothelialization and smooth muscle regeneration. The vascular grafts cultured with hypoxia and mechanical stimulation could accelerate the reconstruction speed and obtain an improved therapeutic effect and thereby provide a new research direction for improving the production and supply of SDVGs.

Combining Raman spectroscopy and machine learning to assist early diagnosis of gastric cancer.

Gastric cancers, with gastric adenocarcinoma (GAC) as the most common histological type, cause quite a few of deaths. In order to improve the survival rate after GAC treatment, it is important to develop a method for early detection and therapy support of GAC. Raman spectroscopy is a potential tool for probing cancer cell due to its real-time and non-destructive measurements without any additional reagents. In this study, we use Raman spectroscopy to examine GAC samples, and distinguish cancerous gastric mucosa from normal gastric mucosa. Average Raman spectra of two groups show differences at 750 cm-1, 1004 cm-1, 1449 cm-1, 1089-1128 cm-1, 1311-1367 cm-1 and 1585-1665 cm-1, These peaks were assigned to cytochrome c, phenylalanine, phospholipid, collagen, lipid, and unsaturated fatty acid respectively. Furthermore, we build a SENet-LSTM model to realize the automatic classification of cancerous gastric mucosa and normal gastric mucosa, with all preprocessed Raman spectra in the range of 400-1800 cm-1 as input. An accuracy 96.20% was achieved. Besides, by using masking method, we found the Raman spectral features which determine the classification and explore the explainability of the classification model. The results are consistent with the conclusions obtained from the average spectrum. All results indicate it is potential for pre-cancerous screening to combine Raman spectroscopy and machine learning.

Treatment of Posterior Malleolar Fractures in Elderly Individuals with Kirschner Wire Tension Band Fixation.

BACKGROUND: Generally, posterior malleolar fragments are fixed either with percutaneous anteroposterior screws or through a posterolateral approach using screws and/or a buttress plate. Both surgical methods have some shortcomings, and the use of anteroposterior screws to fix osteoporotic posterior malleolar fractures carries a risk of failure. METHODS: Nine elderly patients (average age, 67 years) with posterior malleolar fractures were treated with transfibular Kirschner wire tension band fixation. According to the Lauge-Hansen classification, all fractures were of the supination-external rotation type. The operative duration, intraoperative blood loss, and wound healing outcome were recorded. During the follow-up period, clinical outcomes were measured using the American Orthopaedic Foot and Ankle Society ankle-hindfoot score, and the occurrence of complications was observed. RESULTS: The patients were followed up for 12 to 18 months (mean, 15 months). The operative duration ranged from approximately 30 to 95 minutes, with an average of 70 minutes. Anatomical reduction was achieved in nine cases, and there were no complications, such as skin necrosis, wound infection, or skin sensory disturbance. There was one case of delayed wound healing caused by fat liquefaction, which was cured by a dressing change. The functional scores were excellent in four cases, good in four cases, fair in one case, and poor in zero cases. The rate of excellent and good results was 88.89% (eight of nine), with an average of 78.78 points. CONCLUSION: Kirschner wire tension band fixation through a transfibular approach for the treatment of posterior malleolar fractures does not require a change in patient posture. It facilitates the reduction and internal fixation of the posterior malleolar fragment; furthermore, it is easier to remove internal fixation after fracture healing, which provides a new surgical method for elderly patients with posterior malleolus fracture. Thus, this has potential as a new surgical method for elderly patients with posterior malleolar fractures.

EZH2 promotes the progression of osteosarcoma through the activation of the AKT/GSK3ß pathway.

Enhancer of zeste homologue 2 (EZH2) is a clarified promoter in a list of tumours, including osteosarcoma (OS). Our research was projected to define the mechanism involved in EZH2-mediated OS progression through the protein kinase B (AKT)/glycogen synthase kinase 3ß (GSK3ß) pathway. EZH2 expression was tested in 66 OS tissues and five osteosarcoma cell lines (143B, SJSA-1, HOS, MG63, and U2OS). In HOS and U2OS cells, cellular malignant characteristics, and the markers of the AKT/GSK3ß signalling pathway were measured when EZH2 was silenced or overexpressed. Meanwhile, rescue assays were implemented to observe whether the AKT/GSK3ß signalling pathway inhibitor (MK-2206) could affect the role of overexpressed EZH2 in OS cells. EZH2 was up-regulated in tumour tissues of OS patients. OS cell lines (HOS and U2OS) showed impairments of proliferative, migratory, invasive and anti-apoptotic properties when EZH2 was silenced. Downregulated EZH2 inhibited the activation of the AKT/GSK3 signalling pathway. However, the situation in HOS and U2OS cells over-expressing EZH2 was opposite. MK-2206 erased EZH2 up-regulation-induced promotion of OS cell growth. It is demonstrated that EZH2 promotes the progression of OS via inducing the activation of the AKT/GSK3ß pathway, offering a therapeutic direction for OS treatment.

PD-L1 Expression and Intra-Tumoral CD8+ T Lymphocytes in Esophageal Carcinosarcoma.

We detected PD-L1 and intra-tumoral CD8+ T lymphocytes (CD8+ TIL) in 19 patients with esophageal carcinosarcoma (ECS). The median follow-up period of these patients was 43 months, and the three- and five-year survival rates were 78.9 and 63.2%, respectively. No statistically significant correlation was observed between PD-L1 and CD8+ TIL in sarcomatous components(SC) (r = -0.262, p = 0.279) and epithelial carcinomatous (EC) (r = 0.055, p = 0.824). This study examined the immunological markers in ECS for the first time. PD-L1 is highly expressed in the SC and is associated with a poorer prognosis.