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 compare the safety of laparoscopic live donor nephreetomy(LDN) and open live donor nephrectomy(ODN), evaluate the kidney function and blood pressure of living donors during 1 year follow-up. Methods Thirty cases of LDN and 30 eases of ODN were retrospectively reviewed. The operation time, warm ischemia time, operative blood loss, time to post-operative intake and time to ambulation of the 2 grouups were compared. According to the modified Clavien classifica-tion system procedure-related complications were described and compared. Serum creatinine(SCr) le-vels, blood pressure and 24-h urine protein excretion were measured before nephreetomy and 1 d, 7 d, 3 months, 6 and 12 months after nephrectomy. Glomerular filtration rate (GFR) were measured preo-pratively and at 6 and 12 months postoperatively. These data were statistically analyzed. Results The operation time was (98. 6+13. 6)rain and (96.3+19. 5)rain in the LDN and ODN groups, re- spectively. Warm ischemia time in the LDN group was (90.6±15.1)s, in the ODN group was (86.4±12.3)s. Operative blood loss was (105.2±634.8)ml and (206.3±126.4)ml in the LDN and ODN groups(P<0.01). For the time to post-operative intake and time to ambulation, LDN group was (28.5±2.9)h and (25.8±63.8)h, ODN group was (38.6±63.3)h and (36.5±65.3)h(P<0.01). Perioperative complications rates were 6.6%(2/30) and 23.3%(7/30) for LDN and ODN, respective-ly. SCr was (109.1±7.5), (105.4±69.5), (96.6±10.7), (89.4±11.5), (91.6±69.3)/zmol/L in the LDN group and (107.3±69.6), (103.3±68.4), (95.4±69.1), (90.5±13.6), (90.3±11.7)μmol/L in the ODN group 1 day, 7 days, 3 months, 6 months and 12 months after nephrectomy. The mean GFR of LDN and ODN was 64.7 and 65.8 ml/min at 6 months after nephrectomy, 65.9 and 67.5 ml/min at 12 months postoperatively, which were significantly different comparing with preoperative mean GFR in each group(P<0.05) but no significant difference was found between 6 months and 12 months after nephrectomy and between the 2 groups at the same time point respectively(P>0.05). Mean 24 h protein excretion was elevated after either LDN or ODN during 1 year followup, but was not significantly different either between predonation and 1 year after nephrectomy or between the 2 groups at the same period. Blood pressure increased or decreased slightly with the duration of follow-up,no significant blood presure changes were found before and after nephrectomy or between the two groups at the same period postoperatively. Conclusions LDN has the advantages of minimal trauma, less operative blood loss and quicker convalescence. It is safe and and has no adverse effects regarding kidney function and blood pressure during the first year after living kidney donation comparing to ODN.