No abstract

Abstract In recent years, as living standards have continued to improve, the number of diabetes patients in China, along with the incidence of complications associated with the disease, has been increasing. Among these complications, diabetic foot disease is one of the main causes of disability and death in diabetic patients. Due to the differences in economy, culture, religion and level of medical care available across different regions, preventive and treatment methods and curative results for diabetic foot vary greatly. In multidisciplinary models built around diabetic foot, the timely assessment and diagnosis of wounds and appropriate methods of prevention and treatment with internal and external surgery are key to clinical practice for this pathology. In 2019, under the leadership of the Jiangsu Medical Association and Chinese Diabetes Society, the writing group for the Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition) was established with the participation of scholars from the specialist areas of endocrinology, burn injury, vascular surgery, orthopedics, foot and ankle surgery and cardiology. Drawing lessons from diabetic foot guidelines from other countries, this guide analyses clinical practices for diabetic foot, queries the theoretical basis and grades and gives recommendations based on the characteristics of the pathology in China. This paper begins with assessments and diagnoses of diabetic foot, then describes treatments for diabetic foot in detail, and ends with protections for high-risk feet and the prevention of ulcers. This manuscript covers the disciplines of internal medicine, surgical, nursing and rehabilitation and describes a total of 50 recommendations that we hope will provide procedures and protocols for clinicians dealing with diabetic foot.

Background: Hypertrophic scar (HS) is characterized by the increased proliferation and decreased apoptosis of myofibroblasts. Myofibroblasts, the main effector cells for dermal fibrosis, develop from normal fibroblasts. Thus, the stimulation of myofibroblast apoptosis is a possible treatment for HS. We aimed to explore that whether over-activated myofibroblasts can be targeted for apoptosis by anticancer drug elesclomol. Methods: 4 0 ,6-diamidino-2-phenylindole staining, flow cytometry, western blotting, collagen gel contraction and immunofluorescence assays were applied to demonstrate the proapoptotic effect of elesclomol in scar derived myofibroblasts and TGF-b1 induced myofibroblasts. The therapeutic potential of elesclomol was investigated by establishing rabbit ear hypertrophic scar models. Findings: Both 4 0 ,6-diamidino-2-phenylindole staining and flow cytometry indicated that elesclomol targets myofibroblasts in vitro. Collagen gel contraction assay showed that elesclomol inhibited myofibroblast contractility. Flow cytometry and western blot analysis revealed that elesclomol resulted in excessive intracellular levels of reactive oxygen species(ROS), and caspase-3 and cytochrome c proteins. Moreover, compared with the control group, the elesclomol group had a significantly lower scar elevation index in vivo. Immunofluorescence assays for TUNEL and a-smooth muscle actin indicated that elesclomol treatment increased the number of apoptotic myofibroblasts. Interpretation: The above results indicate that elesclomol exerted a significant inhibitory effect on HS formation via targeted myofibroblast apoptosis associated with increased oxidative stress. Thus, elesclomol is a promising candidate drug for the treatment of myofibroblast-related diseases such as HS.

Hypertrophic scars are pathological scars that result from abnormal responses to trauma, and could cause serious functional and cosmetic disability. To date, no optimal treatment method has been established. A variety of cell types are involved in hypertrophic scar formation after wound healing, but the underlying molecular mechanisms and cellular origins of hypertrophic scars are not fully understood. Macrophages are major effector cells in the immune response after tissue injury that orchestrates the process of wound healing. Depending on the local microenvironment, macrophages undergo marked phenotypic and functional changes at different stages during scar pathogenesis. This review intends to summarize the direct and indirect roles of macrophages during hypertrophic scar formation. The in vivo depletion of macrophages or blocking their signaling reduces scar formation in experimental models, thereby establishing macrophages as positive regulatory cells in the skin scar formation. In the future, a significant amount of attention should be given to molecular and cellular mechanisms that cause the phenotypic switch of wound macrophages, which may provide novel therapeutic targets for hypertrophic scars.

Therapeutic study, level III.

Abnormal wound healing is likely to induce the formation of hypertrophic scars and keloids, which leads to dysfunction, deformity, and mental problem in the patients.Despite the advances in prevention and management of hypertrophic scar and keloids, the mechanism underlying scar and keloid formation has not been fully elucidated. Recent insights into the role of the epithelial-mesenchymal transition (EMT) in development, wound healing, stem cell regulation, fibrosis, and tumorigenesis have increased our understanding of the pathophysiology of hypertrophic scarring and keloids and suggested new therapeutic targets. This review summarizes recent progress in the elucidation of the role of EMT in physiologic wound healing and pathologic scar formation. This knowledge will facilitate an understanding of EMT roles in scar formation and shed new light on the modulation and potential treatment of hypertrophic scars and keloids. K E Y W O R D S epithelial-mesenchymal transition, extracellular matrix, hypertrophic scar, keloid, wound healing

Skin is the largest organ of the human body. Skin wound is one of the most common forms of wound. Mesenchymal stromal cells (MSCs) have been used to aid skin wound healing via their paracrine factors. Because the secretome of MSCs can be greatly enriched and amplified by treatment with IFN-γ and TNF-α (IT), we here tested whether supernatant derived from MSCs pretreated with IT, designated as S-MSCs-IT, possesses improved wound healing effect by using a murine model of cutaneous excision, S-MSCs-IT was found to be more potent in promoting angiogenesis, constricting collagen deposition and accelerating wound closure than control supernatant (S-MSCs) during the healing of skin wound. VEGFC, but not VEGFA, was greatly upregulated by IT and was found to be a key factor in mediating the improved wound healing effect of S-MSCs-IT. Our results indicate that the beneficial paracrine effect of MSCs on wound healing can be enhanced by pretreatment with inflammatory cytokines. IT treatment may represent a new strategy for optimizing the therapeutic effect of MSCs on skin injuries.

Because China is becoming an aging society, the incidence of diabetes and diabetic foot have been increasing. Diabetic foot has become one of the main health-related killers due to its high disability and mortality rates. Negative pressure wound therapy (NPWT) is one of the most effective techniques for the treatment of diabetic foot wounds and great progress, both in terms of research and its clinical application, has been made in the last 20 years of its development. However, due to the complex pathogenesis and management of diabetic foot, irregular application of NPWT often leads to complications, such as infection, bleeding and necrosis, that seriously affect its treatment outcomes. In 2020, under the leadership of Burns, Trauma and Tissue Repair Committee of the Cross-Straits Medicine Exchange Association, the writing group for ‘Consensus on the application of negative pressure wound therapy of diabetic foot wounds’ was established with the participation of scholars from the specialized areas of burns, endocrinology, vascular surgery, orthopedics and wound repair. Drawing on evidence-based practice suggested by the latest clinical research, this consensus proposes the best clinical practice guidelines for the application and prognostic evaluation of NPWT for diabetic foot. The consensus aims to support the formation of standardized treatment schemes that clinicians can refer to when treating cases of diabetic foot.