Histologically, melanoma tissues had fewer positive cells percentage of pyroptosis-related genes (PRGs), GZMA, GSDMB, NLRP1, IL18, and CHMP4A in epidermal than in normal skin. Pyroptosis, a new frontier in cancer, affects the tumor microenvironment and tumor immunotherapy. Nevertheless, the role of pyroptosis remains controversial, which reason is partly due to the heterogeneity of the cellular composition in melanoma. In this study, we present a comprehensive analysis of the single-cell transcriptome landscape of pyroptosis in melanoma specimens. Our findings reveal dysregulation in the expression of PRGs, particularly in immune cells, such as CD8⁺ cells (representing CD8⁺ T cells) and CD57⁺ cells (representing NK cells). Additionally, the immunohistochemical and multiplex immunofluorescence staining experiments results further confirmed GZMA⁺ cells and GSDMB⁺ cells were predominantly expressed in immune cells, especially in CD8 ⁺ T cells and NK cells. Melanoma specimens secreted a minimal presence of GZMA⁺ merged CD8⁺ T cells (0.11%) and GSDMB⁺ merged CD57⁺ cells (0.08%), compared to the control groups exhibiting proportions of 4.02% and 0.62%, respectively. The aforementioned findings indicate that a reduced presence of immune cells within tumors may play a role in diminishing the ability of pyroptosis, consequently posing a potential risk to the anti-melanoma properties. To quantify clinical relevance, we constructed a prognostic risk model and an individualized nomogram (C-index=0.58, P = 0.002), suggesting a potential role of PRGs in malignant melanoma prevention. In conclusion, our integrated single-cell and bulk RNA-seq analysis identified immune cell clusters and immune gene modules with experiment validation, contributing to our better understanding of pyroptosis in melanoma.

Flat warts are a common and recurrent skin disease that has no specific antiviral treatment. As an alternative or complementary therapy, fire needle therapy has been widely used in the treatment of flat warts. The objective of this study was to systematically evaluate the efficacy and safety of fire needle therapy for flat warts. Using the search terms “flat warts” and “fire needle,” we searched the PubMed, Embase, Cochrane, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, Chinese biomedical (SinoMed) database, and the China Science and Technology Journal databases for studies until March 12, 2020. Randomized controlled trials comparing fire needle therapies with conventional therapies were also included. We calculated the risk ratios (RR) and mean differences with a 95% confidence interval (CI). We analyzed 29 trials involving 2,666 patients. Results showed that the use of fire needle therapy alone may have a higher efficacy rate compared with that of an immunomodulator (RR = 1.11, 95% CI: 1.03 to 1.20, I² = 0%, = 0.006; RR = 1.19, 95% CI: 1.03 to 1.37, I² = 70%, = 0.02, respectively) or tretinoin (RR = 1.39, 95% CI: 1.25 to 1.55, I² = 0%, < 0.00001), with a lower risk of blisters ( = 0.03) or erythema ( = 0.04), but with a higher risk of pigmentation ( = 0.02). We also determined the efficacy rate of fire needle therapy in combination with traditional Chinese medicine (RR = 1.16, 95% CI: 1.10 to 1.23, I² = 21%, < 0.00001), immunomodulators (RR = 1.17, 95% CI: 1.07 to 1.28, I² = 33%, = 0.0005), imiquimod (RR = 1.21, 95% CI: 1.04 to 1.42, = 0.02), or as multidrug therapies (RR = 1.15, 95% CI: 1.07 to 1.24, I² = 0%, = 0.0001) and found that the combination treatments could reduce recurrence rates ( < 0.00001) and provided a lower risk of desquamation ( = 0.006). In conclusion, fire needle therapy seems to be effective for flat warts, with a reduced incidence of adverse events, such as blisters, erythema, and desquamation, but may increase incidence of pigmentation.