Risk of incident venous thromboembolism in patients with atopic dermatitis: systematic analysis of the literature and meta-analysis.

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease. While various inflammatory conditions have been linked to venous thromboembolism (VTE), the risk of VTE among patients with AD remains unclear. We sought to systematically review and meta-analyze population-based studies to determine the association between AD and incident VTE. A systematic review was performed of published studies in PubMed, Web of Science, Embase and Cochrane library from their inception to 27 May 2024. At least two reviewers conducted title/abstract, full-text review and data extraction. Cohort studies examining the association of AD with incident VTE were included. Quality of evidence was assessed using the Newcastle-Ottawa Scale. Six cohort studies, encompassing a total of 10,186,861 participants, were included. The meta-analysis revealed a significantly increased risk for incident VTE among AD patients (pooled hazard ratio (HR), 1.10; 95% CI, 1.00-1.21), with an incidence rate of VTE at 3.35 events per 1000 patient-years. Individual outcome analyses suggested that AD was associated with higher risks of deep vein thrombosis (pooled HR, 1.15; 95% CI, 1.04-1.27) but not pulmonary embolism (pooled HR, 0.99; 95% CI, 0.87-1.13). This systematic review and meta-analysis indicated an increased risk of incident VTE among patients with AD. Future studies are necessary to elucidate the underlying pathophysiology of the association between AD and VTE.

Identification of CD19 as a shared biomarker via PPARγ/ß-catenin/Wnt3a pathway linking psoriasis and major depressive disorder.

BACKGROUND: Psoriasis, a chronic inflammatory skin disorder, is frequently linked with metabolic, cardiovascular, and psychological comorbidities. Recent research has highlighted the correlation between psoriasis and major depressive disorder (MDD); however, the underlying mechanism remains unclear. METHODS: Commonly differentially expressed genes (DEGs) in psoriasis and MDD were identified and visualized using data from the GEO database. Subsequently, functional enrichment analysis was conducted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Genemania. The hub gene was selected through LASSO and Random Forest algorithms, validated in clinical tissues using Student's t-test and Receiver Operating Characteristic curve. To investigate the hub gene's function in disease phenotype, we established imiquimod (IMQ)-induced psoriasiform dermatitis and chronic unpredictable mild stress (CUMS) mouse models. Lentiviral shRNA interference was topically applied in mice, and downstream pathways were validated at the mRNA and protein levels. RESULTS: A total of 395 overlapping DEGs were identified from GSE121212 and GSE54568 datasets, and twenty core genes were extracted. Functional enrichment analysis revealed that the core genes were significantly associated with the Wnt signaling pathway, neurodegeneration, and energy metabolism. CD19 was identified as the hub gene through algorithms, and external validation showed remarkable AUC values of 0.69 and 0.74, respectively. The level of CD19 increased significantly in IMQ-treated and CUMS-treated mice. Suppression of CD19 significantly alleviated the phenotypes of IMQ-induced psoriasiform dermatitis and CUMS-induced depressive-like behaviors by regulating the PPARγ/ß-catenin/Wnt3a pathway. CONCLUSION: CD19 may serve as a common biomarker or therapeutic target of psoriasis and MDD via PPARγ/ß-catenin/Wnt3a pathway.

IL-22-Induced Ubiquitin-Specific Protease 15 Promotes Proliferation and Inflammation of Keratinocytes through Stabilization of Squamous Cell Carcinoma Antigen 2.

Ubiquitin-specific protease 15 (USP15) plays a significant role in regulating various biological processes in several autoimmune diseases and cancers. However, its role in psoriatic keratinocytes (KCs) has not been extensively studied. In this study, we described that USP15 promotes proliferation and inflammation in KCs by stabilizing squamous cell carcinoma antigen 2. We discovered that the expression of USP15 and squamous cell carcinoma antigen 2 was elevated in lesions from patients with clinical psoriasis and an imiquimod-induced psoriatic dermatitis mouse model. USP15 was able to bind, deubiquitinate, and stabilize squamous cell carcinoma antigen 2. Knocking down USP15 resulted in reduced KC inflammation and impaired KC viability and clonogenicity. Topically applying USP15 small interfering RNA significantly ameliorated imiquimod-induced psoriatic dermatitis and reduced the infiltration of T cells and neutrophils. In addition, we determined that IL-22 was a key cytokine that upregulated the expression of USP15. These findings provide insights regarding the mechanisms involved in the proliferation and inflammation of KCs mediated by IL-22, suggesting a potential IL-22-USP15-squamous cell carcinoma antigen 2 axis in the pathogenesis of psoriatic KCs.

Identification and characterization of bone/cartilage-associated signatures in common fibrotic skin diseases.

Background: Fibrotic skin diseases are characterized by excessive accumulation of the extracellular matrix (ECM) and activation of fibroblasts, leading to a global healthcare burden. However, effective treatments of fibrotic skin diseases remain limited, and their pathological mechanisms require further investigation. This study aims to investigate the common biomarkers and therapeutic targets in two major fibrotic skin diseases, namely, keloid and systemic sclerosis (SSc), by bioinformatics analysis. Methods: The keloid (GSE92566) and SSc (GSE95065) datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, followed by functional enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We then constructed a protein-protein interaction (PPI) network for the identification of hub genes. We explored the possibility of further functional enrichment analysis of hub genes on the Metascape, GeneMANIA, and TissueNexus platforms. Transcription factor (TF)-hub gene and miRNA-hub gene networks were established using NetworkAnalyst. We fixed GSE90051 and GSE76855 as the external validation datasets. Student's t-test and receiver operating characteristic (ROC) curve were used for candidate hub gene validation. Hub gene expression was assessed in vitro by quantitative real-time PCR. Results: A total of 157 overlapping DEGs (ODEGs) were retrieved from the GSE92566 and GSE95065 datasets, and five hub genes (COL11A1, COL5A2, ASPN, COL10A1, and COMP) were identified and validated. Functional studies revealed that hub genes were predominantly enriched in bone/cartilage-related and collagen-related processes. FOXC1 and miR-335-5p were predicted to be master regulators at both transcriptional and post-transcriptional levels. Conclusion: COL11A1, COL5A2, ASPN, COL10A1, and COMP may help understand the pathological mechanism of the major fibrotic skin diseases; moreover, FOXC1 and miR-355-5p could build a regulatory network in keloid and SSc.

The expression pattern of pyroptosis-related genes predicts the prognosis and drug response of melanoma.

Cutaneous melanoma (CM, hereafter referred to as melanoma) is a highly malignant tumor that typically undergoes early metastasis. Pyroptosis, as a special programmed cell death process that releases inflammatory factors and has been widely studied in tumors, but its role in melanoma has not been fully elucidated. In this study, we examined the relationship between pyroptosis and the prognosis of melanoma through bioinformatic analysis of RNA-sequencing data. Our results demonstrated that pyroptosis is a protective factor associated with melanoma prognosis. A higher pyroptosis score was associated with a more favorable overall survival. We used weighted gene co-expression networks analysis (WGCNA) to establish an effective prognosis model based on 12 pyroptosis-related genes. We then validated it in two independent cohorts. Furthermore, a nomogram combining clinicopathological characteristics and a pyroptosis-related gene signature (PGS) score was designed to effectively evaluate the prognosis of melanoma. Additionally, we analyzed the potential roles of pyroptosis in the tumor immune microenvironment and drug response. Interestingly, we found that the elevated infiltration of multiple immune cells, such as CD4+ T cells, CD8+ T cells, dendritic cells, and M1 macrophages, may be associated with the occurrence of pyroptosis. Pyroptosis was also related to a better response of melanoma to interferon-α, paclitaxel, cisplatin and imatinib. Through Spearman correlation analysis of the 12 pyroptosis-related genes and 135 chemotherapeutic agents in the Genomics of Drug Sensitivity in Cancer database, we identified solute carrier family 31 member 2 (SLC31A2) and collagen type 4 alpha 5 chain (COL4A5) as being associated with resistance to most of these drugs. In conclusion, this PGS is an effective and novelty prognostic indicator in melanoma, and also has an association with the melanoma immune microenvironment and melanoma treatment decision-making.

Tofacitinib for the treatment of erythematotelangiectatic and papulopustular rosacea: A retrospective case series.

Rosacea is a chronic inflammatory skin disease characterized by facial erythema, papules, pustules, telangiectasia, and flushing. The Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway appears to play a role in the pathogenesis of rosacea. Our study preliminarily explored the efficacy of JAK inhibitor tofacitinib in the treatment of rosacea. We retrospectively reviewed the cases of 21 patients with rosacea who were treated with oral tofacitinib. Patients received oral tofacitinib 5 mg as either monotherapy or adjunctive therapy. We have observed that 15 out of 21 patients (71.4%) patients experienced significant regression of erythema on the face (IGA ≤ 1), and a mean change of -2.24 in the Investigator's Global Assessment (IGA) score was significant improvement from baseline. Treatment with oral tofacitinib might be a potentially effective treatment to ameliorate the symptoms of rosacea.

Pathogen Analysis of Superficial Mucocutaneous Mycosis in a Tertiary A-level Hospital from 2007 to 2018.

OBJECTIVE: This study aimed to analyze the fungal species of pathogens isolated from patients with superficial mucocutaneous mycosis from May 2007 to December 2018. METHODS: A retrospective analysis was carried out to determine the pathogenic fungi isolated from patients with superficial fungal infections in the Medical Mycology Clinical Laboratory, Department of Dermatology and Venereology, Union Hospital, from May 2007 to December 2018. RESULTS: A total of 7639 strains were obtained, belonging to 21 genera and 36 species. They mainly consisted of Candida (3707/7639, 48.53%) and dermatophytes (3594/7639, 47.05%). The specimens were skin scales, nail shavings, secretions on the nail grooves, broken or diseased hair and dandruff, secretions or pseudomembrane of the external genitalia, and the oral mucosa. A total of 7300 patients were enrolled in this study, including 3301 males and 3999 females aged 2 months to 92 years old with a median age of 46.04 years old except for 633 patients whose ages were unknown. Two strains of different species were isolated from each of 339 patients at different body sites. The most frequent species were Trichophyton rubrum complex (2906/7639, 38.04%), Candida albicans (2619/7639, 34.28%), and unclassified Candida spp. Dermatophytes were mostly isolated from glabrous skin (2138/3594, 59.49%), with T. rubrum complex being the predominant species. Candida strains were most commonly isolated from mucosal sites (1979/3707, 53.39%), and C. albicans was the most prevalent causative agent. CONCLUSION: The main distribution of pathogenic fungal species isolated from patients with superficial mycosis from 2007 to 2018 in Wuhan, Hubei province and the surrounding areas was that Candida slightly outnumbered dermatophytes. Among all of the isolated strains, T. rubrum complex was the most abundant.

Identification of Genes Potentially Associated with Melanoma Tumorigenesis Through Co-Expression Network Analysis.

BACKGROUND: Melanoma is one of the most malignant and aggressive skin tumors, and its incidence is increasing worldwide. However, few studies have investigated the process of tumorigenesis from normal skin to melanoma. METHODS: Several bioinformatics analyses, including GEO databases, Oncomine database, TCGA database, STRING, MCODE and cytoHubba plug-ins, GEPIA, TIMER and TRRUST and DGIdb, were performed to disclose the hub genes and immunology implicated in primary melanoma tumorigenesis. Finally, immunohistochemistry (IHC) and quantitative real-time PCR (qPCR) were used to validate the results of bioinformatics analysis in vitro. RESULTS: A total of 295 overlapping DEGs (ODEGs) (157 upregulated and 138 downregulated) and 9 hub genes were identified between primary melanoma and normal skin tissues. Functional analysis of these 9 hub genes indicated that the genes were primarily enriched in cell chemotaxis, the chemokine-mediated signaling pathway, the extracellular region, the extracellular space, chemokine activity and CXCR3 chemokine receptor binding. KEGG pathway enrichment showed that these genes were primarily involved in the chemokine signaling pathway, cytokine-cytokine receptor interaction, the toll-like receptor signaling pathway, the cytosolic DNA-sensing pathway and the TNF signaling pathway. Upregulated CCL5, CCL4, CXCL9 and CXCL10 demonstrated good overall survival (OS), and most of them have a higher expression in stage 0 and 1 of melanoma. Moreover, immune infiltration analysis showed that the above hub genes showed a strong positive correlation between their expression and infiltration of the six immune cell subsets. Transcription factor regulation network suggested that RELA and NFKB1 are the transcription factors of CCL4, CCL5, CXCL10 and CXCL2, while IRF7, IRF3 and IRF1 are the transcription factors of CCL5 and CXCL10. Drug-gene interaction analysis identified 46 drug-gene interactions. In vitro data demonstrated that the level of CCL4, CCL5, CXCL9 and CXCL10 is higher in melanoma than that in normal skin tissues, either at tissue or cell lines level. CONCLUSION: In summary, we identified 4 key chemokine members related to tumorigenesis and progression in primary melanoma, and these results may help to elucidate melanoma tumorigenesis and facilitate its treatment.

Mesenchymal stem cells in cancer progression and anticancer therapeutic resistance.

Increasing evidence indicates that the tumor microenvironment appears to play an increasingly important role in cancer progression and therapeutic resistance. Several types of cells within the tumor stroma had distinct impacts on cancer progression, either promoting or inhibiting cancer cell growth. Mesenchymal stem cells (MSCs) are a distinct type of cells that is linked to tumor development. MSCs are recognized for homing to tumor locations and promoting or inhibiting cancer cell proliferation, angiogenesis and metastasis. Moreover, emerging studies suggests that MSCs are also involved in therapeutic resistance. In this review, we analyzed the existing researches and elaborate on the functions of MSCs in cancer progression and anticancer therapeutic resistance, demonstrating that MSCs may be a viable cancer therapeutic target.

The role of osteopontin in the development and metastasis of melanoma.

Melanoma is a highly heterogeneous tumor. The incidence of melanoma increases with age and its long-term prognosis is poor. The treatment of melanoma includes surgical removal, chemotherapy and immunotherapy; however, the effect of these treatments is limited on mutated melanoma. Osteopontin is an extracellular protein which is expressed in numerous kinds of cells; it is related to the proliferation and invasion of cancer cells as well as the development of tumor microenvironment. The relationship between osteopontin and metastasis of melanoma has been clarified in recent years. This review focuses on the expression of osteopontin in patients with melanoma and associated signaling pathways involved in development and metastasis of melanoma; the potential role of osteopontin in immune modulation and prognosis prediction is also discussed here.

Discoid lupus erythematosus solely involving the eyelids: case report and literature review.

BACKGROUND AND OBJECTIVE: The involvement of eyelids occurs in only 5-6% of patients with discoid lupus erythematosus (DLE), commonly with mucocutaneous lesions elsewhere. DLE solely involving the eyelids is relatively rare. This study aimed to describe the clinical features and treatments of all the reported cases of DLE with eyelid involvement as the only symptom. METHODS: A systematic review was done of all the related literature published both in English and Chinese from May 1, 1984, to March 1, 2020. Only those cases of DLE solely involving eyelids were selected and summarized in two tables. RESULTS: (i) DLE solely involving the eyelids is five times more likely to affect females than males. (ii) The majority of cases were presenting with unilateral eyelid involvement. Lower lids, especially both lower lids, were the most commonly affected locations. (iii) An erythematous plaque with scales is the most frequent manifestation. (iv) Approximately 22.9% of the cases had a positive antinuclear antibody (ANA) titer, and the speckled pattern was the most seen. For direct immunofluorescence (DIF), 94.4% of the performed cases showed positive results. (v) More than 85% of these cases showed an excellent response to treatment with oral antimalarials. CONCLUSION: Awareness of this atypical presentation is important to avoid underdiagnosis of DLE solely involving the eyelids. A biopsy for both routine histology and DIF is critical for establishing the diagnosis.

Interleukin-22 and connective tissue diseases: emerging role in pathogenesis and therapy.

Interleukin-22 (IL-22), a member of the IL-10 family of cytokines, is produced by a number of immune cells involved in the immune microenvironment of the body. IL-22 plays its pivotal roles by binding to the IL-22 receptor complex (IL-22R) and subsequently activating the IL-22R downstream signalling pathway. It has recently been reported that IL-22 also contributes to the pathogenesis of many connective tissue diseases (CTDs). In this review, we will discuss the role of IL-22 in several CTDs, such as system lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis and dermatomyositis, suggesting that IL-22 may be a potential therapeutic target in CTDs.

Multicentre clinicopathological study of adenoid cystic carcinoma: A report of 296 cases.

AIMS: Adenoid cystic carcinoma (ACC) is a distinctive tumour. Limited studies involving a large population have reported multicentre systematic analyses of the clinical, pathological and immunohistochemical (IHC) features of ACC as well as the potential role of IHC markers in the prognosis of ACC. METHODS AND RESULTS: The clinical, histopathological and IHC data of 296 cases obtained from two tertiary hospitals were analysed. The age at onset ranged from 12 to 87 years with a median age of 52 years. The male-to-female ratio was 1:1.3. Patients with ACC arising from the lacrimal gland were younger than those with tumours arising from other sites. Patients with tumours in the extra auditory canal and nasopharynx were older than those with tumours in other locations. Histopathologically, solid type ACC was the most frequent in the nasal cavity and paranasal sinus (6/51) group. Tumours arising from the oral cavity most commonly showed perineural invasion (10/60) and margin positivity (11/60). IHC analyses showed that CK8/18, CK7, CK14, epithelial membrane antigen and CD117 were expressed in 35/35 (100%), 87/88 (98.8%), 26/27 (96.2%), 42/43 (97.6%) and 113/120 (94.1%) patients, respectively. CK5/6, P63, smooth muscle actin, calponin and S100 were positively expressed in 73/73 (100%), 111/124 (89.5%), 38/43 (88.3%), 41/50 (82.0%) and 61/92 (66.3%) cases, respectively. S100 proteins were expressed in 54 (54/77) primary cases and two (2/9) metastatic cases (p = 0.013). CONCLUSIONS: ACC is a distinctive tumour that mainly affects middle-aged and elderly individuals, with a mild female predominance. Loss of expression of S100 proteins may be a poor prognostic factor associated with metastasis.