Exploration of a Predictive Model for Keloid and Potential Therapeutic Drugs Based on Immune Infiltration and Cuproptosis-Related Genes.

The aim of this study was to investigate the correlation between cuproptosis-related genes and immunoinfiltration in keloid, develop a predictive model for keloid occurrence, and explore potential therapeutic drugs. The microarray datasets (GSE7890 and GSE145725) were obtained from Gene Expression Omnibus database to identify the differentially expressed genes (DEGs) between keloid and nonkeloid samples. Key genes were identified through immunoinfiltration analysis and DEGs and then analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, followed by the identification of protein-protein interaction networks, transcription factors, and miRNAs associated with key genes. Additionally, a logistic regression analysis was performed to develop a predictive model for keloid occurrence, and potential candidate drugs for keloid treatment were identified. Three key genes (FDX1, PDHB, and DBT) were identified, showing involvement in acetyl-CoA biosynthesis, mitochondrial matrix, oxidoreductase activity, and the tricarboxylic acid cycle. Immune infiltration analysis suggested the involvement of B cells, Th1 cells, dendritic cells, T helper cells, antigen-presenting cell coinhibition, and T cell coinhibition in keloid. These genes were used to develop a logistic regression-based nomogram for predicting keloid occurrence with an area under the curve of 0.859 and good calibration. We identified 32 potential drug molecules and extracted the top 10 compounds based on their P-values, showing promise in targeting key genes and potentially effective against keloid. Our study identified some genes in keloid pathogenesis and potential therapeutic drugs. The predictive model enhances early diagnosis and management. Further research is needed to validate and explore clinical implications.

Machine learning links different gene patterns of viral infection to immunosuppression and immune-related biomarkers in severe burns.

Introduction: Viral infection, typically disregarded, has a significant role in burns. However, there is still a lack of biomarkers and immunotherapy targets related to viral infections in burns. Methods: Virus-related genes (VRGs) that were extracted from Gene Oncology (GO) database were included as hallmarks. Through unsupervised consensus clustering, we divided patients into two VRGs molecular patterns (VRGMPs). Weighted gene co-expression network analysis (WGCNA) was performed to study the relationship between burns and VRGs. Random forest (RF), least absolute shrinkage and selection operator (LASSO) regression, and logistic regression were used to select key genes, which were utilized to construct prognostic signatures by multivariate logistic regression. The risk score of the nomogram defined high- and low-risk groups. We compared immune cells, immune checkpoint-related genes, and prognosis between the two groups. Finally, we used network analysis and molecular docking to predict drugs targeting CD69 and SATB1. Expression of CD69 and SATB1 was validated by qPCR and microarray with the blood sample from the burn patient. Results: We established two VRGMPs, which differed in monocytes, neutrophils, dendritic cells, and T cells. In WGCNA, genes were divided into 14 modules, and the black module was correlated with VRGMPs. A total of 65 genes were selected by WGCNA, STRING, and differential expression analysis. The results of GO enrichment analysis were enriched in Th1 and Th2 cell differentiation, B cell receptor signaling pathway, alpha-beta T cell activation, and alpha-beta T cell differentiation. Then the 2-gene signature was constructed by RF, LASSO, and LOGISTIC regression. The signature was an independent prognostic factor and performed well in ROC, calibration, and decision curves. Further, the expression of immune cells and checkpoint genes differed between high- and low-risk groups. CD69 and SATB1 were differentially expressed in burns. Discussion: This is the first VRG-based signature (including 2 key genes validated by qPCR) for predicting survival, and it could provide vital guidance to achieve optimized immunotherapy for immunosuppression in burns.

Satisfactory Wound Reconstruction with a Local Rotation Flap After Removal of Large Penile Divided Nevi: Original Technique, Early and Mid-Term Results.

Objective: To investigate the application of local rotation flaps for reconstruction of divided nevi of the penises in young male patients. Methods: A group of 8 patients of divided nevi of the penises who underwent wound reconstruction with local rotation flaps after surgical lesion removal was enrolled in a retrospective clinical study. Postoperative complication, sexual function and psychological traits were evaluated during the follow-up. Results: All patients, with ages ranged from 16 to 32 years (mean 23.25 years), were followed up for 6 to 48 months (mean 19.86 months). The patient's average length of hospital stay was 7.85 day (7 to 15 days). The average dimension of the lesions was (2.31±0.44) × (1.46±0.48) cm2 on the glans and (1.38±0.40) × (1.01±0.46) cm2 on the inner prepuce plate. All patients had no postoperative infection and were satisfied with the postoperative outcome upon discharge. Five cases of benign intradermal nevi and 3 cases of compound nevi without malignant transformation were confirmed by pathological evaluation on the removed samples. The sexual function of all patients was unaffected postoperatively by male sexual function scale (BMSFI and IIEF-5) evaluation. The psychological status of depression, anxiety and stress was all improved after the surgical reconstruction confirmed by the psychological traits scale (DASS) evaluation. Conclusion: Reconstruction with the local rotation flap is a simple, safe and appropriate surgical procedure, achieves satisfactory cosmetic outcome, and maintains intact male sexual function when used for the repair of defect after removal of divided nevi of the penises.

Wild-type p53-modulated autophagy and autophagic fibroblast apoptosis inhibit hypertrophic scar formation.

Hypertrophic scarring is a serious fibrotic skin disease, and the abnormal activation of hypertrophic scar fibroblasts (HSFs) intensifies its pathogenesis. Our previous studies have demonstrated that the dysregulation of autophagy in HSFs is associated with fibrosis. However, knowledge regarding the regulation of HS fibrosis by p53-modulated autophagy is limited. Here, we investigated the effect of p53-modulated autophagy on HS fibrosis. The overexpression of wtp53 (Adp53) promoted autophagic capacity and inhibited collagen and α-SMA expression in HSFs. In contrast, LC3 (AdLC3) overexpression did not suppress Col 1, Col 3, or α-SMA expression, but LC3 (shLC3) knockdown downregulated collagen expression. Adp53-modulated autophagy altered Bcl-2 and Bcl-xL expression, but AdLC3 affected only Bcl-xL expression. Silencing Bcl-xL suppressed collagen expression, but autophagy was also inhibited. Flow cytometry showed that the silencing of Bcl-2 (sibcl-2), Bcl-xL (sibcl-xL), and Adp53 significantly increased apoptosis in the HSFs. Therefore, wtp53 inhibited fibrosis in the HSFs by modulating autophagic HSF apoptosis; moreover, the inhibition of autophagy by sibcl-xL had antifibrotic effects. In addition, treatment with Adp53, AdLC3, shLC3, sibcl-2, and sibcl-xL reduced scar formation in a rabbit ear scar model. These data confirm that wtp53-modulated autophagy and autophagic HSF apoptosis can serve as potential molecular targets for HS therapy.

MicroRNA-519d inhibits proliferation and induces apoptosis of human hypertrophic scar fibroblasts through targeting Sirtuin 7.

MicroRNAs (miRNAs) play critical roles in various pathological processes, including hypertrophic scar (HS) formation. However, the precise role of miRNAs in HS formation remains largely unknown. In this study, we aimed to investigate the role of miR-519d in HS formation. We found that miR-519d expression was significantly downregulated in HS tissues and fibroblasts. Overexpression of miR-519d inhibited the expression of type I collagen (Col I), type III collagen (Col III) and α-smooth muscle actin (α-SMA) in HS fibroblasts. Moreover, overexpression of miR-519d reduced the proliferation and induced the apoptosis of HS fibroblasts. In contrast, suppression of miR-519d showed the opposite effects. Interestingly, Sirtuin 7 (SIRT7) was identified as a target gene of miR-519d. The results showed that miR-519d directly targeted the 3'-untranslated region of SIRT7 and negatively regulated its expression. Furthermore, miR-519d regulated the expression of TGF-ß type I receptor (TGFBRI) and the phosphorylation of Smad2. Knockdown of SIRT7 by siRNA inhibited the expression of Col I, Col III and α-SMA, and reduced the proliferation and induced the apoptosis of HS fibroblasts. Overexpression of SIRT7 abrogated the effects mediated by miR-519d overexpression in HS fibroblasts. Overall, these results suggest that miR-519d inhibits the expression of extracellular matrix-associated genes, reduces the proliferation and induces the apoptosis of HS fibroblasts by targeting SIRT7, implying a suppressive role of miR-519d in HS formation. This study suggests that miR-519d may serve as a promising therapeutic target for treatment of human HS.

A new method of microskin autografting with a Vaseline-based moisture dressing on granulation tissue.

In the conventional method of microskin autografting, aggressive early excision is adopted, followed by coverage with a microskin-allograft complex to close extensive burn wounds. However, early excision is always associated with a defect of viable tissue, resulting in massive blood loss and causing high risk to aged patients or those with other systemic diseases. We developed a new method in which an eschar thinning operation was first adopted, followed by raising granulation tissue and microskin autografting, which was covered by a Vaseline-based moisture dressing. A total of 52 patients were included in this study and randomly assigned to the control group (n=26) and the experimental group (n=26) for the conventional method and the new method, respectively. The re-epithelisation rate on the 21st day after autografting indicated that there was no significant difference between both groups. There was also no significant difference between the two groups when the re-epithelialisation rate was compared with the type of organisms cultured. However, the Vancouver Burn Skin Score (VBSS) results demonstrated a significant improvement of cosmetic appearance in the experimental group (score=2.1) as compared to the control group (score=3.9). The new method also showed other advantages, including less blood loss, shorter surgical duration and lower cost of surgery. From this prospective study, it can be concluded that the new method can be an alternative to the conventional microskin autografting procedure.

[Clinical application of human tissue engineered skin with full thickness on donor site of split thickness skin graft in burn wounds].

OBJECTIVE: To observe the clinical effect of the human tissue engineered active skin (ActivSkin) with full thickness on the donor site of the split thickness skin graft. METHODS: Nine patients with 18 wounds of the donor sites, and every patient had 2 wounds. The wounds of each patient were randomly assigned to the therapy group and the control group. Auto-control observation was performed. Nine donor sites of the split thickness skin graft were repaired with ActivSkin in the therapy group. Nine donor sites of the split thickness skin graft were repaired with the vash oil gauze in the control group. The wound pain, the time to complete closure, and the ratio of the complete healing in the ActivSkin therapy group was measured and compared with those in the control group. The donor sites of the split thickness skin graft were assessed at 180 days of the follow-up visit. RESULTS: The wound pain was obviously reduced after the harvesting of the skin grafts in the therapy group. The time to complete closure on the donor sites of the split thickness skin graft was significantly shorter in the ActivSkin therapy group than in the control group (9.67 +/- 2.92 d vs. 16. 56 +/- 2.96 d, P < 0.05). Both the ratios of the complete healing in the ActivSkin therapy group and the control group were 100% (P > 0.05). The subsequent results showed that neither the blister nor the residual wound occurred with an alleviated scar after the ActivSkin treatment. CONCLUSION: ActivSkin can promote wound closure, prevent blister and residual wound, and alleviate scarring on the donor sites of the split thickness skin graft after the ActivSkin treatment.