Pathologic scars include keloids and hypertrophic scars due to abnormal wound healing. Both cause symptoms of itching and pain; they also affect one's appearance and may even constrain movement. Such scars place a heavy burden on the individual's physical and mental health; moreover, treatment with surgery alone is highly likely to leave more scarring. Therefore, there is an urgent need for a treatment that is both minimally invasive and convenient. Photodynamic therapy (PDT) is an emerging safe and noninvasive technology wherein photosensitizers and specific light sources are used to treat malignant tumors and skin diseases. Research on PDT from both the laboratory and clinic has been reported. These findings on the treatment of pathologic scars using photosensitizers, light sources, and other mechanisms are reviewed in the present article.

Background: Diabetic foot ulcers (DFUs) represent a significant foot-related concern for patients with multiple co-morbidities, and surgical intervention is often employed. Notably, peripheral nerve block anesthesia (PNB) has emerged as a new approach for the surgical management of DFUs, providing sustained hemodynamic stability and superior postoperative pain control compared to general anesthesia (GEA). Methods: The present study utilized a retrospective analysis of hospitalized patients who met the inclusion criteria for DFUs over a period of 7 years. Patients were categorized into two groups based on the type of anesthesia employed during the procedure: GEA or PNB. Extensive patient information was gathered and analyzed, such as demographics, intraoperative hemodynamic parameters, numeric rating scale (NRS) scores, and healing outcomes. The preliminary results assessed in this study were intraoperative hemodynamic stability and postoperative analgesic efficacy. Results: During the study period, 117 patients received surgical therapy based on GEA, while 145 patients received PNB. Notably, the mean intraoperative blood pressure was significantly lower in the GEA group, and this difference remained statistically significant even after Bonferroni adjustment using linear mixed models. Additionally, the frequency of hypotensive episodes was higher in the GEA group (P < 0.05). Furthermore, the perioperative transfusion volume, overall intraoperative fluid input, and intraoperative bleeding volume were significantly more significant in the GEA group than in the PNB group. The postoperative pain NRS scores differed considerably between the two groups (Bonferroni corrected P < 0.01), with the GEA group exhibiting higher opioid consumption on the day of surgery and the first postoperative day when using patient-controlled intravenous analgesia (PCIA). Supplemental analgesic medication was more significant in the GEA group 24 h postoperatively. However, the two groups had no difference in hospital stay or treatment outcomes. There was no difference between the two groups regarding secondary surgery and amputation procedures. Although the 5-year mortality rate is 30.5%, no significant difference in mortality rates between the two groups was observed. Conclusions: Compared to GEA, PNB is a safe and effective alternative therapy for managing DFUs. Our findings suggest that PNB administration during surgical intervention for this condition results in more stable intraoperative hemodynamics and superior postoperative analgesic effects, despite no significant difference in overall treatment outcomes between the two groups. The two groups did not differ in re-surgery, amputation, or 5-year mortality.

(1) Background: The relationship between lipids, apolipoproteins, and telomere length (TL) has been explored in previous studies; however, the causal relationship between the two remains unclear. This study aims to assess the causal relationship between lipids, apolipoproteins, and TL using the two-sample Mendelian randomization (MR) approach; (2) Methods: This study comprehensively employed both univariate MR (uvMR) and multivariate MR (mvMR) methods to genetically evaluate the associations between 21 exposures related to lipids and apolipoproteins and the outcome of TL. During the analysis process, we utilized various statistical methods, including Inverse Variance Weighting (IVW), Weighted Median, MR-Egger regression, MR-PRESSO, and outlier tests. Furthermore, to confirm the robustness of the results, we conducted several sensitivity analyses to explore potential heterogeneity; (3) Results: The uvMR analysis indicated that an increase in MUFA, MUFA/FA ratio, LDL-C, VLDL-C, total cholesterol, ApoB, and triglycerides (TG) was associated with an increase in TL. However, this relationship did not manifest in the mvMR analysis, suggesting that this association may be based on preliminary evidence; (4) Conclusions: MR analysis results suggest potential suggestive positive causal relationships between genetically predicted MUFA, MUFA/FA ratio, LDL-C, VLDL-C, total cholesterol, ApoB, and TG with TL.

Metformin (Met), a first-line therapeutic agent for type 2 diabetes, has been widely recognized for its antifibrotic properties in various pathological conditions. However, its effects on hypertrophic scars (HS) and the underlying mechanisms remain insufficiently explored. The present study aimed to elucidate the role of metformin in HS and to investigate its associated molecular mechanisms. Both in vitro and in vivo experiments demonstrated that metformin markedly inhibited the proliferation, migration, and collagen deposition of hypertrophic scar fibroblasts (HSFs), and alleviated HS formation in a rabbit ear model. Mechanistic investigations further revealed that these effects were closely associated with the downregulation of ribonucleotide reductase regulatory subunit M2 (RRM2). Notably, reduced RRM2 expression suppressed the production of glutathione synthetase (GSS), thereby impairing glutathione (GSH) synthesis. This, in turn, indirectly downregulated glutathione peroxidase 4 (GPX4), leading to the intracellular accumulation of peroxides and triggering ferroptosis in vivo and in vitro. Collectively, these findings suggest that metformin may attenuate HS fibrosis by inducing HSFs ferroptosis through the RRM2/GSS/GPX4 signaling axis. This study not only expands the potential clinical application of metformin in the treatment of skin fibrosis but also provides a theoretical foundation for the development of novel anti-scar therapeutics.

Objective: This study aimed to investigate the causal relationship between diabetes mellitus and pathological scarring, including hypertrophic scars (HS) and keloids, and to elucidate the underlying immune cellular mechanisms and key molecular regulators. Methods: We employed a phenome-wide Mendelian randomization approach (MR-PheWAS) to identify potential causal links between diabetes and pathological scars. Separate Mendelian randomization meta-analyses (MR-Meta) were performed for type 1 diabetes (T1D) and type 2 diabetes (T2D). Integrative analyses incorporating single-cell RNA sequencing (scRNA-seq), cell–cell communication inference, metabolic pathway profiling, and transcriptomic differential expression and enrichment analyses were conducted to delineate scar heterogeneity mediated by diabetes-related cellular subpopulations and molecular drivers. Results: MR-PheWAS revealed significant causal associations between HS and multiple diseases. T2D exhibited a positive causal association with HS (OR: 1.13, 95% CI: 1.09–1.17, P < 0.0001), and a negative association with keloids (OR: 0.95, 95% CI: 0.92–0.99, P = 0.016). T1D showed no significant causal relationship with either scar type. Single-cell analysis identified an upregulation of CD4 ⁺ Naive T cells (CD4 ⁺ NT) in HS and a downregulation in keloids. This subset exhibited strong interactions with endothelial cells in both scar types, primarily enriched in the insulin signaling pathway (INS–INSR) signaling axis. Three pivotal genes (GPR35, TMEM91, and ZBTB32) were identified as overlapping molecular links between T2D and pathological scars, all expressed in CD4 ⁺ NT and showing inverse expression trends across HS and keloids. Pseudotime trajectory analysis further revealed divergent expression kinetics of these genes, characterized by early loss and late-phase upregulation. Metabolic pathway analysis implicated these genes in modulating metabolic reprogramming of the CD4 ⁺ NT population, thereby influencing scar differentiation. Conclusion: Convergent multi-omics evidence supports the hypothesis that T2D exerts opposing causal effects on different forms of pathological scarring, potentially mediated through CD4 ⁺ NT. The transcriptomic features, intercellular communication profiles, key gene signatures, and metabolic landscape of this subset collectively suggest that T2D may contribute to divergent fibrotic pathways in HS and keloids via immune microenvironmental modulation.