Fuqiu Li

Psoriasis is a recurrent autoimmune disease. No biological factor that is associated with the risk of psoriasis has been definitively identified. The potential role of the immunogen double‐stranded (ds)DNA as a trigger of and biomarker for psoriasis warrants exploration. This multicentre case–control study included 3 069 patients with psoriasis and 7 041 healthy controls from 12 regions in China. The associations of the serum dsDNA level with the psoriasis risk and severity were analysed in the overall population. The serum dsDNA level was significantly higher in patients than in controls. Each 0.1 ng/mL increase in serum dsDNA was significantly associated with increased odds of psoriasis (adjusted odds ratio, 1.45; 95% confidence interval, 1.40–1.48; p < 0.001). The optimal serum dsDNA cutoff value for the diagnosis of psoriasis was 1.11 ng/mL, with 61.6% sensitivity and 74.8% specificity. A significant dose–response relationship was observed between the serum dsDNA level and the risk of psoriasis‐associated morbidity when using the optimal dsDNA cutoff value as the reference. Serum dsDNA levels were positively associated with higher PASI and BSA scores and the severity of psoriasis. These findings suggest that serum dsDNA level is strongly associated with psoriasis morbidity and severity.

Background: Elderly patients with moderate‐to‐severe atopic dermatitis (AD) often exhibit more heterogeneous inflammatory profiles compared with younger adults. To evaluate the efficacy and safety of stapokibart, an anti‐interleukin‐4 receptor α subunit (IL‐4Rα) monoclonal antibody, in different age subgroups. Methods: Eligible adults were randomized to receive subcutaneous stapokibart 300 mg every 2 weeks (Q2W; loading dose 600 mg) or placebo for 16 weeks. All patients subsequently received stapokibart 300 mg Q2W for 36 weeks. In this post hoc analysis, patients were classified as elderly (aged ≥ 60 years, n = 93) and non‐elderly patients (aged 18 and < 60 years, n = 407). Main efficacy outcomes included ≥ 75% improvement from baseline in Eczema Area and Severity Index (EASI‐75), Investigator's Global Assessment (IGA) 0/1, and ≥ 4‐point reduction in weekly average of daily peak pruritus Numerical Rating Scale (PP‐NRS) score. Results: In elderly patients at Week 16, response rates for stapokibart versus placebo were 56.0% vs. 14.0% for EASI‐75 ( p < 0.0001), 40.0% vs. 7.0% for IGA 0/1 ( p = 0.0003), and 32.0% vs. 7.0% for ≥ 4‐point reduction in weekly average of daily PP‐NRS ( p = 0.0023). In non‐elderly patients, corresponding response rates were 69.7% vs. 28.3%, 45.3% vs. 18.0%, and 36.8% vs. 12.7%, respectively (all p < 0.0001). Within both age subgroups, progressive improvements across all efficacy measures were observed during the maintenance treatment period. The incidence of treatment‐emergent adverse events was similar between stapokibart and placebo groups during the 16‐week treatment period, regardless of age. Conclusion: Stapokibart was effective and had a favorable safety profile in elderly patients with moderate‐to‐severe AD.

Sporotrichosis is a chronic subcutaneous infection caused by the Sporothrix complex, a dimorphic fungus that exhibits significant clinical heterogeneity. However, the molecular targets and underlying mechanisms of Sporothrix globosa infection remain unclear. Therefore, in this study, we aimed to integrate whole-transcriptome sequencing analysis of skin lesion tissues from patients with sporotrichosis and healthy controls. In addition, differential gene expression screening, protein-protein interaction network construction, and functional enrichment analysis. We systematically identified the key immune-related genes, Cluster of Differentiation 247 (CD247), Signal Transducer and Activator of Transcription 1 (STAT1), and Lymphocyte-Specific Tyrosine Kinase (LCK), which are majorly upregulated during infections. The high expression of these genes in the disease group was consistently validated by western blot, quantitative polymerase chain reaction, and immunohistochemistry. Mechanistic analysis revealed the contribution of these genes to sporotrichosis-dysregulated immune response. This occurs by causing excessive activation of the interferon signaling pathway, lymphocyte overactivation, and the JAK-STAT signaling pathway, which leads to the host immune imbalance. This suggests their central role in immune evasion and overactivation during sporotrichosis. In this novel study, we revealed the pathological regulatory role of the CD247-STAT1-LCK molecular network in sporotrichosis, which provided novel insights into fungal-host interactions and identified potential therapeutic targets for immune-modulating antifungal treatments.

Objective This post-hoc analysis used the data from a previous randomized controlled trial (NCT04839016) and aimed to compare patient-reported outcomes (PROs) between patients who achieved complete (PASI 100; N = 178) and near-complete (PASI 90–99; N = 181) skin clearance during 12 weeks of Vunakizumab treatment. Methods PROs included the Dermatology Life Quality Index (DLQI) score, DLQI 0/1 response rate, Itch Numerical Rating Scale (NRS) score, and Short Form-36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS). Results The proportion of patients who achieved a DLQI of 0/1 at week (W)8 (P < 0.010), W12 (P < 0.010), W20 (P < 0.001), W28 (P < 0.050), W36 (P < 0.010), and W52 (P < 0.050) was higher in the PASI 100 group compared to the PASI 90–99 group. The mean DLQI score at W4 (P < 0.010), W8 (P < 0.010), W12 (P < 0.001), W20 (P < 0.001), W28 (P < 0.001), W36 (P < 0.001), W44 (P < 0.001), and W52 (P < 0.001), as well as itch NRS score at W8 (P < 0.001), W12 (P < 0.010), W20 (P < 0.001), W28 (P < 0.010), W36 (P < 0.001), W44 (P < 0.010), and W52 (P < 0.010) were lower in the PASI 100 group than in the PASI 90–99 group. The mean SF-36 MCS at W4 (P < 0.050), W12 (P < 0.001), W20 (P < 0.010), W28 (P < 0.001), W36 (P < 0.050), W44 (P < 0.010), and W52 (P < 0.050), as well as SF-36 PCS at W8 (P < 0.050) and W36 (P < 0.050) were higher in the PASI 100 group than in the PASI 90–99 group. Conclusion Patients with complete skin clearance following Vunakizumab treatment showed improved quality of life, reduced pruritus, and enhanced mental health compared to those with near-complete skin clearance.

: Mycetoma is a granulomatous disease of subcutaneous tissue that is caused by different species of aerobic filamentous bacteria (actinomycetoma) or fungi (eumycetoma). Mycetoma treatment depends on the causative pathogen, and it mainly consists of antimicrobial interventions or surgery. Aspergillus terreus is an etiologic agent of invasive aspergillosis and a rare cause of eumycetoma that is common in central and southern China. The present case report describes a 45-year-old female patient with subcutaneous swelling and multiple active and healed sinuses over the dorsal aspect of the left foot who was diagnosed with eumycetoma caused by A. terreus. This is the first such case reported in China. We applied a combination treatment consisting of itraconazole with topical luliconazole cream and radiofrequency microneedling, and this was followed by significant regression of the lesion. In addition, we reviewed the current literature to summarize the epidemiological characteristics of mycetoma in mainland China and cases of eumycetoma caused by A. terreus worldwide.

Of immunodeficiency disorders.The gut microbiota, as a vital ecosystem within the human body, has a significant impact on the host's immune system, metabolism, and nervous system. Recent studies have shown that gut microbiota imbalance is closely associated with the occurrence and progression of various diseases, including skin disorders. Meng et al. used bidirectional Mendelian randomization to analyze data from large-scale genome-wide association studies (GWAS) on gut microbiota and herpes zoster (HZ). They identified a potential bidirectional causal relationship between the gut microbiota and HZ. These findings could pave the way for novel therapeutic approaches to address the global burden of HZ.As one of the most common subcutaneous fungal infections, sporotrichosis is transmitted zoonotically through traumatic inoculation of contaminated soil or plants, or through bites and scratches from infected animals, posing a global threat to both humans and animals. Despite its prevalence, treatment options for sporotrichosis remain limited. Li et al. innovatively investigated the antibacterial peptide In-58 for its in vivo and in vitro antifungal activity against Sporothrix globosa. They discovered that this peptide exhibits significant antifungal properties, highlighting its potential as a novel therapeutic agent for sporotrichosis. This study provides a theoretical foundation for the future clinical translation of antimicrobial peptides.Leprosy is a chronic infectious disease caused by Mycobacterium leprae, characterized by its high disabling potential. Data show that Brazil has the second-highest incidence of leprosy in the world, following India, posing a significant challenge to public health. Brito Gonçalves et al. conducted a retrospective analysis of paucibacillary leprosy in Brazil based on research from the past 20 years. Their analysis revealed significant geographical heterogeneity in Brazilian paucibacillary cases, which has profound implications for subgroup analyses. Addressing these disparities through targeted interventions and localized analyses could enhance the effectiveness of leprosy control efforts in the country. Continuous monitoring of case classification and regional trends is essential for adapting strategies to effectively tackle this public health challenge.In conclusion, the studies in this special issue highlight the need for large-scale interdisciplinary research to fully understand the complexities of various infectious skin diseases and their impact on public health. Further in-depth studies on different pathogens are essential to elucidate their mechanisms of infection and host immune responses, providing a foundation for the development of novel diagnostic and therapeutic approaches.

In-58, a peptide derived from indolicidin, shows extraordinary antibacterial activity and lower toxicity than indolicidin toward mammalian cells. Here, we investigated the antifungal activity of In-58 against the human pathogen Sporothrix globosa in vitro and in vivo. In-58 markedly inhibited the growth of Sporothrix globosa isolates in microdilution assays and showed no antagonism with any tested antifungal agent (itraconazole, terbinafine or amphotericin B). Scanning electron microscopy and propidium iodide staining indicated that In-58 alters the cell wall integrity and interacts with DNA, leading to disruption of S. globosa in a dose-dependent manner. In S. globosa, the mitochondrial membrane potential decreased and reactive oxygen species increased after treatment with In-58. In vivo experiments in the Galleria mellonella (greater wax moth) larval infection model revealed the effectiveness of In-58 against S. globosa infection with low toxicity. Our results indicate that In-58 possesses remarkable antifungal activity against S. globosa in vitro and in vivo. It has potential as a novel drug for the treatment of sporotrichosis.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disease mainly manifested as skin and osteoarticular lesions. Herein, we describe a female patient with SAPHO syndrome exhibited paradoxical psoriasis and primary palmoplantar pustulosis (PPP) worsened during treatment with adalimumab. We then switched to secukinumab and obtained significant improvement in both skin lesions and osteoarticular pain. These findings suggest that secukinumab might be an appropriate option for patients with SAPHO syndrome who present with TNF-α-inhibitor-induced paradoxical psoriasis.

This study aimed to investigate the molecular mechanism of sporotrichosis and identify possible novel therapeutic targets. Total RNA was extracted from skin lesion samples from sporotrichosis patients and used to construct a long-chain RNA transcriptome library and miRNA transcriptome library for whole transcriptome sequencing. The differentially expressed genes (DEGs) between the groups were identified, and then Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis enrichment analyses were performed based on the DEGs. An lncRNA-miRNA-mRNA ceRNA network was constructed. The expressions of JAK/STAT pathway-related proteins were detected in the patient and control tissues using RT-qPCR and Western blot analysis. Enrichment analysis showed that the DEGs were mainly enriched in various infectious diseases and immune response-related signaling pathways. Competing endogenous RNA network analysis was performed and identified the hub lncRNAs, miRNAs, and mRNAs. Compared with the control group, the mRNA expressions of SOCS3, IL-6, and JAK3 were significantly upregulated, while the expression of STAT3 did not change significantly. Also, the protein expressions of SOCS3, IL-6, JAK3, and STAT3, as well as phosphorylated JAK3 and STAT3, were significantly upregulated. We identified 671 lncRNA DEGs, 3281 mRNA DEGs, and 214 miRNA DEGs to be involved in Sporothrix globosa infection. The study findings suggest that the JAK/STAT pathway may be a therapeutic target for sporotrichosis.