Purpose: Recent studies have confirmed the important role of chronic inflammation in keloid; however, mechanism of chronic inflammation in keloid tissue remains largely unclear, especially the dynamic of infiltrated inflammatory cells. Patients and Methods: Tissue and blood samples collected from keloid patients and healthy subjects were studied by immunohistochemistry and flow cytometry. Fibroblasts from keloid scars and normal skin were isolated by enzymic digestion. Results: We found that CXCL12 expression was elevated which was correlated with decreased dipeptidyl peptidase-4 (DPP4) expression in keloid scars relative to mature scars. In vitro studies suggested that autocrine transforming growth factor β 1 (TGF-β 1) in keloid-derived fibroblasts negatively regulated DPP4 expression which inhibited the reduction of extracellular CXCL12 levels by DPP4. Furthermore, immunofluorescence showed that most fibroblasts in keloid scars were DPP4^lowTGFβ 1^high compared with DPP4^highTGFβ 1^low fibroblasts in normal skin tissue, which facilitated extracellular CXCL12 accumulation in fibroblasts in keloid scars. Furthermore, we found that most circulating leukocytes in peripheral blood and tissue-infiltrated inflammatory cells in keloid scars expressed the C-X-C motif chemokine receptor 4 (CXCR4) instead of CXCR7, indicating that the chemotaxis driven by CXCL12 is likely to be mediated mainly by CXCR4. Conclusion: Our study indicated that the TGF-β/DPP4/CXCL12 axis may contribute to chronic inflammation in keloid scars by recruiting inflammatory cells through the CXCR4 receptor.

Background: Keloids are a fibroproliferative skin disorder with a high recurrence rate. Combined therapies are often used in clinical treatment, but, in addition to the relatively high risk of relapse and complexity of the treatment process, side effects remain unknown for combination therapies. Methods: A total of 99 patients with keloids in 131 positions were included in this retrospective study. Fractional CO₂ laser therapy was first applied with energy ranging from 360 to 1008 mJ; then, 6-Mev, 900-cGy electron beam irradiation was applied twice. The first pass was initiated within 24 hours after the laser therapy, and the second pass was performed on the seventh day after laser therapy. The Patient and Observer Scar Scale evaluated the lesions before the treatment and at 6, 12, and 18 months after treatment. At each follow-up visit, the patients filled out a questionnaire on recurrence, side effects, and satisfaction. Results: The authors found a significant decrease in total Patient and Observer Scar Scale score [29 (23, 39) versus 61.2 ± 13.4; P < 0.001] at the 18-month follow-up compared with the baseline value (before the therapy). A total of 12.1% of the patients had recurrences during the 18-month follow-up period (11.1% partial recurrence and 1.0% complete recurrence). The total satisfaction rate was 97.0%. No severe adverse effects were observed during the follow-up period. Conclusions: Laser combined with radiotherapy is a new comprehensive therapy comprising ablative lasers and radiotherapy for keloids. It had excellent clinical efficacy, low recurrence rate, and no serious adverse effects. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Y-chromosome Haplogroup O2a1c-002611 is one of the dominant lineages of East Asians and Southeast Asians. However, its internal phylogeny remains insufficiently investigated. In this study, we genotyped 89 new highly informative single nucleotide polymorphisms (SNPs) in 305 individuals with Haplogroup O2a1c-002611 identified from 2139 Han Chinese males. Two major branches were identified, O2a1c1-F18 and O2a1c2-L133.2 and the first was further divided into two main subclades, O2a1c1a-F11 and O2a1c1b-F449, accounting for 11.13% and 2.20% of Han Chinese, respectively. In Haplogroup O2a1c1a-F11, we also determined seven sublineages with quite different frequency distributions in Han Chinese ranging from 0.187% to 3.553%, implying they might have different demographic history. The reconstructed haplogroup tree for all the major clades within Haplogroup O2a1c-002611 permits better resolution of male lineages in population studies of East Asia and Southeast Asia. The dataset generated in the present study are also valuable for forensic identification and paternity tests in China.

Keloid disorder is a tumour-like disease with invasive growth and a high recurrence rate. Genetic contribution is well expected due to the presence of autosomal dominant inheritance and various genetic mutations in keloid lesions. However, GWAS failed to reveal functional variants in exon regions but single nucleotide polymorphisms in the non-coding regions, suggesting the necessity of innovative genetic investigation. This study employed combined GWAS, RNA-sequence and Hi-C analyses to dissect keloid disorder genetic mechanisms using paired keloid tissues and normal skins. Differentially expressed genes, miRNAs and lncRNAs mined by RNA-sequence were identified to construct a network. From which, 8 significant pathways involved in keloid disorder pathogenesis were enriched and 6 of them were verified. Furthermore, topologically associated domains at susceptible loci were located via the Hi-C database and ten differentially expressed RNAs were identified. Among them, the functions of six molecules for cell proliferation, cell cycle and apoptosis were particularly examined and confirmed by overexpressing and knocking-down assays. This study firstly revealed unknown key biomarkers and pathways in keloid lesions using RNA-sequence and previously reported mutation loci, indicating a feasible approach to reveal the genetic contribution to keloid disorder and possibly to other diseases that are failed by GWAS analysis alone.