Sphingosine-1-phosphate (S1P), a key regulator of vascular homeostasis and angiogenesis, is enriched in exosomes derived from platelet-rich plasma (PRP-Exos). However, the potential role of PRP-Exos-S1P in diabetic wound healing remains unclear. In this study, we investigated the underlying mechanism of PRP-Exos-S1P in diabetic angiogenesis and wound repair. Exosomes were isolated from PRP by ultracentrifugation and analysed by transmission electron microscopy, nanoparticle tracking analysis and western blotting. The concentration of S1P derived from PRP-Exos was measured by enzyme-linked immunosorbent assay. The expression level of S1P receptor1–3 (S1PR1–3) in diabetic skin was analysed by Q-PCR. Bioinformatics analysis and proteomic sequencing were conducted to explore the possible signalling pathway mediated by PRP-Exos-S1P. A diabetic mouse model was used to evaluate the effect of PRP-Exos on wound healing. Immunofluorescence for cluster of differentiation 31 (CD31) was used to assess angiogenesis in a diabetic wound model. In vitro, PRP-Exos significantly promoted cell proliferation, migration and tube formation. Furthermore, PRP-Exos accelerated the process of diabetic angiogenesis and wound closure in vivo. S1P derived from PRP-Exos was present at a high level, and S1PR1 expression was significantly elevated compared with S1PR2 and S1PR3 in the skin of diabetic patients and animals. However, cell migration and tube formation were not promoted by PRP-Exos-S1P in human umbilical vein endothelial cells treated with shS1PR1. In the diabetic mouse model, inhibition of S1PR1 expression at wounding sites decreased the formation of new blood vessels and delayed the process of wound closure. Bioinformatics analysis and proteomics indicated that fibronectin 1 (FN1) was closely related to S1PR1 due to its colocalization in the endothelial cells of human skin. Further study supported that FN1 plays an important role in the PRP-Exos-S1P-mediated S1PR1/protein kinase B signalling pathway. PRP-Exos-S1P promotes angiogenesis in diabetic wound healing via the S1PR1/protein kinase B/FN1 signalling pathway. Our findings provide a preliminary theoretical foundation for the treatment of diabetic foot ulcers using PRP-Exos in the future.

Diabetic foot ulcer (DFU) is one of the most serious and alarming diabetic complications, which often leads to high amputation rates in diabetic patients. Machine learning is a part of the field of artificial intelligence, which can automatically learn models from data and better inform clinical decision‐making. We aimed to develop an accurate and explainable prediction model to estimate the risk of in‐hospital amputation in patients with DFU. A total of 618 hospitalised patients with DFU were included in this study. The patients were divided into non‐amputation, minor amputation or major amputation group. Light Gradient Boosting Machine (LightGBM) and 5‐fold cross‐validation tools were used to construct a multi‐class classification model to predict the three outcomes of interest. In addition, we used the SHapley Additive exPlanations (SHAP) algorithm to interpret the predictions of the model. Our area under the receiver‐operating‐characteristic curve (AUC) demonstrated a 0.90, 0.85 and 0.86 predictive ability for non‐amputation, minor amputation and major amputation outcomes, respectively. Taken together, our data demonstrated that the developed explainable machine learning model provided accurate estimates of the amputation rate in patients with DFU during hospitalisation. Besides, the model could inform individualised analyses of the patients' risk factors.

The frequency of chronic cutaneous wounds are sharply increasing in aging populations. Patients with age-related diseases, such as diabetes, tumors, renal failure and stroke are prone to soft tissue and skin injury, compounded by slowed healing in aging. Imbalance of wound inflammation, loss of growth factor secretion, and impairment of tissue repair abilities are all possible reasons for failed healing. Therefore, it is vital to explore novel approaches to accelerate wound healing. Platelet-rich plasma (PRP) as a cell therapy has been widely applied for tissue repair and regeneration. PRP promotes wound healing by releasing antimicrobial peptides, growth factors and micro-RNAs. Medical evidence indicates that autologous platelet-rich plasma (au-PRP) can promote wound healing effectively, safely and rapidly. However, its clinical application is usually restricted to patients with chronic cutaneous wounds, generally because of other severe complications and poor clinical comorbidities. Allogeneic platelet-rich plasma (al-PRP), with abundant sources, has demonstrated its superiority in the field of chronic wound treatment. Al-PRP could overcome the limitations of au-PRP and has promising prospects in clinical applications. The aim of this review is to summarize the current status and future challenges of al-PRP in chronic cutaneous wound management. We also summarized clinical cases to further describe the application of al-PRP for chronic wounds in clinical practice.

This study aimed to explore the clinical characteristic and outcomes of inpatients with diabetic foot ulceration (DFU) in 2019 (prelockdown) and 2020 (postlockdown) due to the COVID‐19 pandemic, at an emergency medical service unit. Prediction models for mortality and amputation were developed to describe the risk factors using a machine learning‐based approach. Hospitalized DFU patients (N = 23) were recruited after the lockdown in 2020 and matched with corresponding inpatients (N = 23) before lockdown in 2019. Six widely used machine learning models were built and internally validated using 3‐fold cross‐validation to predict the risk of amputation and death in DFU inpatients under the COVID‐19 pandemic. Previous DF ulcers, prehospital delay, and mortality were significantly higher in 2020 compared to 2019. Diabetic foot patients in 2020 had higher hs‐CRP levels (P = .037) but lower hemoglobin levels (P = .017). The extreme gradient boosting (XGBoost) performed best in all models for predicting amputation and mortality with the highest area under the curve (0.86 and 0.94), accuracy (0.80 and 0.90), sensitivity (0.67 and 1.00), and negative predictive value (0.86 and 1.00). A long delay in admission and a higher risk of mortality was observed in patients with DFU who attended the emergency center during the COVID‐19 post lockdown. The XGBoost model can provide evidence‐based risk information for patients with DFU regarding their amputation and mortality. The prediction models would benefit DFU patients during the COVID‐19 pandemic.

Vascular disease is the leading cause of death worldwide. Predicting the burden of vascular disease and identifying modifiable key risk factors are critical for developing effective prevention strategies. This study aimed to project the global and regional burden of peripheral artery disease (PAD) from 2021 to 2050, with a specific focus on the impact of modifiable key risk factors and the potential benefits of their management. Compared to the 2021 Global Burden of Disease Study (GBD 2021), the number of PAD cases worldwide is projected to increase by 220% by 2050, reaching a staggering 360 million (95% uncertainty interval, 270 to 450). Age-standardized mortality is expected to double, while disability-adjusted life years (DALYs) are forecasted to rise from 19.7 to 33.1 per 100,000. Among individuals aged ≥65 years, PAD prevalence is projected to surge to 21.7% in women and 14.8% in men. Moreover, over 50% of PAD cases are expected to occur in low- and middle-income countries (LMICs). Metabolic diseases are anticipated to be the primary drivers of the rising PAD burden, with diabetes playing a key role in increasing PAD prevalence and severity. By effectively managing metabolic risk factors, age-standardized prevalence could be reduced by 36%, mortality by 17%, and DALYs by 10%. As metabolic risks, particularly diabetes, continue to rise alongside population aging, the global PAD burden is expected to increase substantially, especially in LMICs. Importantly, proactive metabolic risk management strategies have the potential to markedly alleviate the burden of vascular disease and reduce the growing geographic health disparities.