BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

Objective:To observe the effects of functional electrical stimulation (FES) controlled by brain-computer interface on upper limb motor dysfunction in stroke patients. Methods:From July, 2019 to November, 2020, 34 stroke patients hospitalized in neurological rehabilitation department were randomly divided into control group (n = 17) and experimental group (n = 17). They were treated with simple FES and FES controlled by brain-computer interface, respectively. The reaction time, joint position error of elbow joint, the scores of Fugl-Meyer Assessment-Upper Extremity (FMA-UE), modified Barthel Index (MBI) and event-related desynchronization (ERD) powers of affected upper limb were evaluated before and after intervention. Results:After intervention, the reaction time, joint position error of the elbow joint, the scores of FMA, MBI and ERD power of the affected elbow joint improved in both groups (F > 10.825, |Z| > 3.624, P < 0.05), and they were better in the experimental group than in the control group (F > 5.853, |Z| > 3.201, P < 0.05). Conclusion:FES controlled by brain-computer interface is positive on the rehabilitation of stroke patients with upper limb dysfunction.