OBJECTIVES: To elucidate the underlying mechanisms of macrophage-mediated inflammation and tissue injury in diabetic foot ulcer (DFU). METHODS: Skin tissue samples were collected from patients with DFU and with non-DFU. A total of 79 272 high-quality cell transcriptomes were obtained using single-cell RNA sequencing. An unbiased clustering approach was employed to identify cell subpopulations. Seurat functions were used to identify differentially expressed genes between DFU and non-DFU groups, and gene ontology (GO) enrichment analysis was used to reveal gene function. Furthermore, cell-cell communication network construction and ligand-receptor interaction analysis were performed to reveal the mechanisms underlying cellular interactions and signaling regulation in the DFU microenvironment from multiple perspectives. RESULTS: The results revealed a significant expansion of myeloid cells in DFU tissues, alongside a marked reduction in structural cells such as endothelial cells, epithelial cells, and smooth muscle cells. Major cell types underwent functional reprogramming, characterized by immune activation and impaired tissue remodeling. Specifically, macrophages in DFU skin tissues exhibited a shift toward a pro-inflammatory M1 phenotype, with upregulation of genes associated with inflammation and oxidative stress. Cell communication analysis further demonstrated that M1 macrophages served as both primary signal receivers and influencers in the COMPLEMENT pathway mediated communication network, and as key signal senders and mediators in the secreted phosphoprotein 1 (SPP1) pathway mediated communication network, actively shaping the inflammatory microenvironment. Key ligand-receptor interactions driving macrophage signaling were identified, including C3-(ITGAM+ITGB2) and SPP1-CD44. CONCLUSIONS This study establishes a comprehensive single-cell atlas of DFU, revealing the role of macrophage-driven cellular networks in chronic inflammation and impaired healing. These findings may offer potential novel therapeutic targets for DFU treatment.
Humans ; Macrophages/immunology* ; Diabetic Foot/pathology* ; Single-Cell Analysis ; Transcriptome ; Gene Expression Profiling ; Inflammation ; Skin ; Cell Communication ; Signal Transduction ; Cellular Reprogramming

This study aimed to investigate factors affecting length of hospital stay and mortality of a specific group of patients with infected diabetic foot ulcer who underwent surgical drainage without major amputation, which is frequently encountered by orthopedic surgeons. Data on length of hospital stay, mortality, demographics, and other medical information were collected for 79 consecutive patients (60 men, 19 women; mean age, 66.1 [SD, 12.3] yr) with infected diabetic foot ulcer who underwent surgical drainage while retaining the heel between October 2003 and May 2013. Multiple linear regression analysis was performed to determine factors affecting length of hospital stay, while multiple Cox regression analysis was conducted to assess factors contributing to mortality. Erythrocyte sedimentation rate (ESR, P=0.034), glycated hemoglobin (HbA1c) level (P=0.021), body mass index (BMI, P=0.001), and major vascular disease (cerebrovascular accident or coronary artery disease, P=0.004) were significant factors affecting length of hospital stay, whereas age (P=0.005) and serum blood urea nitrogen (BUN) level (P=0.024) were significant factors contributing to mortality. In conclusion, as prognostic factors, the length of hospital stay was affected by the severity of inflammation, the recent control of blood glucose level, BMI, and major vascular disease, whereas patient mortality was affected by age and renal function in patients with infected diabetic foot ulcer undergoing surgical drainage and antibiotic treatment.
Aged ; Amputation ; Blood Sedimentation ; Blood Urea Nitrogen ; Body Mass Index ; Diabetic Foot/mortality/*pathology/*surgery ; Drainage ; Female ; Hemoglobin A, Glycosylated/analysis ; Humans ; Length of Stay ; Male ; Middle Aged ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Survival Rate ; Vascular Diseases/complications

Gap junctions play a critical role in electrical synchronization and exchange of small molecules between neighboring cells; connexins are a family of structurally related transmembrane proteins that assemble to form vertebrate gap junctions. Hyperglycemia changes the structure gap junction proteins and their expression, resulting in obstruction of neural regeneration, vascular function and wound healing, and also promoting vascular atherosclerosis. These pathogenic factors would cause diabetic foot ulcers. This article reviews the involvement of connexins in pathogenesis of diabetic foot.
Atherosclerosis ; Connexins ; metabolism ; Diabetic Foot ; pathology ; Gap Junctions ; metabolism ; Humans ; Hyperglycemia ; physiopathology ; Regeneration ; Wound Healing

PURPOSE: To determine the 1-year survival rate, 1-year amputation-free survival rate and the risk factors of amputation for patients with diabetic foot ulcers. MATERIALS AND METHODS: One hundred seventy-three patients with diabetic foot ulcers were included in our study. Mean patient age was 67.5 (range, 29 to 87, SD +/-11.4) years. 74% of the patients were male. Time from study entry to amputation and time to death were evaluated separately as censored event times by Kaplan-Meier curves and log-rank tests. A multivariate Cox proportional hazards regression analysis was carried out for determining the risk factors of amputation. RESULTS: The survival rate and amputation-free survival rate were 96.5% (n=167), 65.9% (n=114), respectively, over one year study period. Severity of ulcer was the strongest significant risk factor of amputation [hazard ratio (HR): 7.99; confidence interval (CI): 3.12 to 20.47]. Peripheral artery disease was also independent risk factor of amputation (HR: 2.64; CI: 1.52 to 4.59). CONCLUSION: In assessing the prognosis of diabetic foot ulcers, clinicians should consider the severity of ulcer and presence of peripheral artery disease. Our study provides important insights into clinical practice and supplementary information for both physicians and patients.
Aged ; *Amputation ; Diabetic Foot/*pathology/therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Treatment Outcome

Myiasis is usually caused by flies of the Calliphoridae family, and Cochliomyia hominivorax is the etiological agent most frequently found in myiasis. The first case of myiasis in a diabetic foot of a 54-year-old male patient in Argentina is reported. The patient attended the hospital of the capital city of Tucuman Province for a consultation concerning an ulcer in his right foot, where the larval specimens were found. The identification of the immature larvae was based on their morphological characters, such as the cylindrical, segmented, white yellow-coloured body and tracheas with strong pigmentation. The larvae were removed, and the patient was treated with antibiotics. The larvae were reared until the adults were obtained. The adults were identified by the setose basal vein in the upper surface of the wing, denuded lower surface of the wing, short and reduced palps, and parafrontalia with black hairs outside the front row of setae. The main factor that favoured the development of myiasis is due to diabetes, which caused a loss of sensibility in the limb that resulted in late consultation. Moreover, the poor personal hygiene attracted the flies, and the foul-smelling discharge from the wound favoured the female's oviposition. There is a need to implement a program for prevention of myiasis, in which the population is made aware not only of the importance of good personal hygiene and home sanitation but also of the degree of implication of flies in the occurrence and development of this disease.
Animals ; Argentina ; Diabetic Foot/*complications/parasitology/pathology ; Diptera/anatomy & histology/classification/*growth & development ; Humans ; Male ; Middle Aged ; Myiasis/*diagnosis/*parasitology ; Ulcer/*complications/parasitology/pathology

The classification system of diabetic foot not only helps to assess the wound, but it also can be used to predict the outcome of diabetic foot ulcer in the early stage, dynamically monitor the changes in the wound, and rationally direct the therapeutic schedule. At present, there are diverse systems for classifying the diabetic foot, but none has been internationally recognized. The classification systems can be categorized by time sequence, research objective, or structure type. When one of the classification systems is chosen, it is still very important to take the population, facility, and research type into consideration.
Diabetic Foot ; classification ; pathology ; Humans ; Severity of Illness Index ; Wound Healing

Chronic wounds pose a clinical challenge. Such wounds may present all over the body although the majority appear on the lower extremities. In the main, wounds are caused by hypertension (venous or arterial), diabetes, although infection, trauma, and animal bites can result in non-healing wounds. It is vital to have a reliable diagnosis in order to plan treatment. Despite advances in diagnostics and the development of standard care packages, chronic wounds present a growing burden to all societies. One of the problems faced is the poor understanding of the pathophysiology of wounds; it is commonly accepted that microcirculation is impaired in lower extremity chronic wounds. This paper is focused on the significance and assessment of impaired microcirculation.
Diabetic Foot ; pathology ; Humans ; Microcirculation ; Wound Healing ; physiology

OBJECTIVETo compare the difference between the burn wound and diabetic ulcer wound, and to preliminarily analyze the nonhealing mechanism of diabetic unclear.

METHODSThe tissue of foot ulcer of diabete patients and skin wound tissues from burn patients were harvested. The levels of (FGF)2 and VEGF in the wound tissues were determined after tissue cultivation with enzyme-linked immunosorbent assay (ELISA). The changes in micro-vascular density (MVD) were examined by immunohistochemistry. Human umbilical vein endothelial cells were cultured in medium containing different components, and divided into following groups: A (with treatment of 5 mmol/L glucose for 7 days), B (with treatment of 30 mmol/L glucose for 7 days) and C (with treatment of 30 mmol/L Mannitol for 7 days) groups, then the level of VEGF protein was determined by ELISA.

RESULTSThe levels of FGF2 and VEGF protein in the burn wound were (59 +/- 3) ng/ml and (56 +/- 7) pg/ml, respectively, which were obviously lower than those in diabetic ulcer wound [(89 +/- 6) ng/ml, (108 +/- 5) pg/ml, P < 0.05]. There was also obvious difference in MVD between two kinds of wound (P < 0.05). The level of VEGF protein in both wounds were similar after the addition of FGF2 to the cell culture in vitro, while there were statistically significant difference 2 and 5 days after removal of FGF.

CONCLUSIONThe nonhealing mechanism of diabetic ulcer wound may be related to the inhibition of vacuolation and low expression of factors controlling vessel growth.

Burns ; complications ; metabolism ; pathology ; Cells, Cultured ; Diabetic Foot ; pathology ; Fibroblast Growth Factor 2 ; metabolism ; Foot Ulcer ; etiology ; pathology ; Humans ; Neovascularization, Physiologic ; Vascular Endothelial Growth Factor A ; metabolism ; Wound Healing