Interleukin-33 (IL-33), an alarmin predominantly released by keratinocytes and endothelial cells, plays a pivotal role in type 2 immune responses and has been linked to the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). This study aimed to explore the relationship between plasma IL-33 levels and clinical features in SLE patients. A cross-sectional study was conducted involving 133 SLE patients and 81 normal controls. Plasma IL-33 levels were measured via enzyme-linked immunosorbent assay. Clinical parameters, such as SLEDAI-2K scores, photosensitivity, skin lesion distribution, laboratory indices, immunofluorescence and immunohistochemistry results were collected. SLE patients demonstrated significantly higher circulating IL-33 levels compared to healthy controls (median 342.60 pg/ml vs. 56.77 pg/ml, p < 0.0001). IL-33 levels were positively associated with SLEDAI-2K scores (r = 0.279, p = 0.001), photosensitivity (p = 0.02), and facial skin lesions (p = 0.001). The expression levels of the IL-33 receptor (ST2) in head and face cutaneous tissues were markedly higher than those in other anatomical regions and in normal control subjects (p < 0.001). Multivariate analysis revealed negative correlations with complement C3 (β = - 0.303, p < 0.001) and positive correlations with IgA (β = 0.473, p < 0.001) and hs-CRP (β = 0.310, p < 0.001). Notably, IL-33 levels were higher in male patients (p = 0.002) and treatment-naïve patients (p = 0.03). Our data associate circulating IL-33 with SLE activity, photosensitivity, and specific serological markers. For the association between IL-33 and cutaneous photosensitivity, this study provides further histological evidence. This finding provides a novel perspective on the mechanism of photosensitivity in SLE, demonstrating the potential of IL-33 as a biomarker for patient stratification management.

Background: Objective indicators are urgently needed to evaluate and monitor disease progression in patients with psoriasis. Objective: This study aimed to verify the correlations between blood count-derived inflammatory markers and the Psoriasis Area and Severity Index (PASI) among patients with psoriasis and explore the value of applying the PASI in combination with proinflammatory factors. Methods: This was a cross-sectional observational study that enrolled 719 patients from 2 tertiary hospitals. Receiver operating characteristic curve analysis and binary logistic regression models were applied to assess the evaluative power of blood count-derived inflammatory markers and their consistency with the PASI for stratifying psoriasis severity. The association with the PASI and the combination with proinflammatory factors of the blood count-derived inflammatory markers in 60 patients were analyzed. The exploratory association between blood count-derived markers and proinflammatory factors was analyzed using product terms. To ensure robustness, multivariable combined models were evaluated using receiver operating characteristic curves and decision curve analysis. Model performance was further validated via calibration plots and a predictive nomogram, with the decision curve analysis net benefit axis increased to 1.0 for comprehensive visualization. Results: The area under the curve showed that the systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) were effective in reflecting psoriasis severity and showed advantages in patients with psoriasis complicated by arthritis and cardiovascular metabolic diseases. The comprehensive test showed quite appropriate consistency of the SIRI and PASI in distinguishing severity. The SII, SIRI, and AISI were significantly correlated with interleukin (IL)-6 in lesions (all P<.05), and the combinations of these indices with IL-6, IL-1, and IL-17 were also significantly correlated with the PASI (all P<.05). Conclusions: Blood count-derived inflammatory markers could better reflect the inflammation of patients with psoriasis. The SII, SIRI, and AISI have important clinical significance in evaluating disease severity. The combination with proinflammatory factors showed an advantage.

Psoriatic arthritis (PsA) and Crohn disease (CD) are chronic immune-mediated illnesses that afflict a growing number of adults and children worldwide. Observational studies have revealed a link between PsA and CD, but the modifiable risk variables that mediate the causal effects remain unknown. We aim to look into the relationship between PsA and CD, and to see if circulating metabolites have a role in the pathophysiology of both disorders. By scanning the whole genome of a large number of people and detecting millions of genetic variation sites in the genome, we take advantage of the random assignment of genotypes in nature and use single nucleotide polymorphisms as instrumental variables to simulate the environment of randomized controlled trials, so as to infer the causal relationship between exposure factors and outcomes. Using summary statistics from genome-wide association studies of predominantly European ancestry, we used two-sample Mendelian randomization (MR) to estimate the effects of PsA on CD (1637 cases/212,242 controls; 1401 cases/461,532 controls), and two-step MR to assess the association with 1400 circulating metabolites. Genetic predisposition to PsA was associated with a higher risk of CD (pooled odds ratio, 1.00051; 95% confidence interval [CI], 1.00023-1.00078; P < .001). The statistical association between PsA and CD was mediated by the concentrations of homocitrulline, 5-hydroxyhexanoate, carnitine C14, gamma-glutamylthreonine, furaneol sulfate, and trans-urocanate, which accounted for 4.23% (95% CI, -0.68% to 9.15%, P = 4.58 × 10-2), 7.85% (95% CI, -1.74% to 17.44%, P = 9.91 × 10-3), 6.09% (95% CI, -1.70% to 13.88%, P = 3.09 × 10-2), 7.45% (95% CI, -1.21% to 16.11%, P = 1.31 × 10-3), 8.88% (95% CI, 0.23% to 17.54%, P = 8.39 × 10-3), and 3.96% (95% CI, -0.48% to 8.40%, P = 2.29 × 10-2) of the total effect, respectively. Our MR analysis identified significant PsA-CD associations mediated through specific metabolites, particularly the gut microbiome-derived furaneol sulfate (showing highest mediation), supporting gut-joint axis involvement. These findings establish a crucial theoretical framework for guiding clinical practice in the management of PsA and CD.

Hidradenitis suppurativa (HS), also known as acne inversa (AI), is a chronic, recurrent inflammatory disease of the pilosebaceous unit that primarily affects intertriginous areas and is characterized by recurrent, painful, deep-seated inflammatory lesions. The pathogenesis of HS/AI is multifactorial, involving genetic susceptibility, immune dysregulation, microbial imbalance, and obesity. HS/AI remains difficult to manage, and current treatment aims to reduce the frequency and duration of flares, decrease disease severity, and improve quality of life. Treatment selection should be guided by disease severity and activity. Pharmacologic therapies include antibiotics, biologics, small-molecule agents, retinoids, and immunosuppressants, while adjunctive approaches include surgical interventions and energy-based therapies. This updated consensus aims to standardize the diagnosis and management of HS/AI in China and to improve clinical practice by providing a stepwise, multidisciplinary treatment framework in which interventions are stratified according to disease severity and recommendation strength. Recommendation strength was determined by expert voting: an agreement rate of ≥85% indicated “Should be recommended,” ≥75% to <85% indicated “Could be recommended,” ≥50% to <75% indicated “May be considered,” and <50% indicated “No consensus reached.” Key recommendations reaching the ≥85% agreement threshold included severity-based treatment selection, topical clindamycin for mild localized disease, systemic tetracyclines for mild-to-moderate HS/AI, and biologics, including adalimumab, secukinumab, and bimekizumab, for moderate-to-severe disease. The consensus has been registered on the International Practice Guidelines Registry Platform (No: PREPARE-2025CN1964).

Studies have shown that an increase in the abundance of triglycerides (TG), oleic acid, and stearic acid can exacerbate the symptoms of psoriasis. Based on this, the present study aimed to employ Mendelian randomization (MR) methods to investigate the causal relationship between fatty acid (FA) and TG levels and the risk of psoriasis. A 2-sample MR analysis was performed using summary statistics from the genome-wide association studies of FA, TG, and psoriasis of European ancestry. Single nucleotide polymorphisms were used as instrumental variables in MR analysis. Inverse variance weighted was used as a primary method to study the causal relationship of FA on psoriasis. Similarly, inverse variance weighted was used to test for the causal effect of TG on psoriasis as well as the causal effect of FA on TG. Finally, sensitivity analysis was used to test the reliability of the MR analysis results. In this study, no significant association was observed between FA and psoriasis, indicating that FA was not a causal factor for psoriasis. TG had a causal relationship with psoriasis, and it was a risk factor for psoriasis. In MR analysis, it was demonstrated that FA did not directly exacerbate psoriasis; TG was a risk factor for psoriasis exacerbation. Our study elucidates the relationship between TG and FAs in psoriasis pathogenesis, thereby refining the understanding of its underlying mechanisms and offering novel theoretical and therapeutic avenues for diagnosis and treatment .

The Indian Journal of Dermatology, Venereology and Leprology (IJDVL) is an open-access peer-reviewed journal committed to publishing high-quality articles in the field of Clinical and Experimental Dermatology, Cutaneous Biology, Dermatological Therapeutics, Cosmetic Dermatology, Dermatopathology, Dermatosurgery, Pediatric Dermatology, Photodermatology, HIV Medicine, Sexually Transmitted Diseases and Leprosy.

BACKGROUND:Clinically, psoriasis (PSO) and ulcerative colitis (UC) coexisted in some patients. However, the molecular pathogenesis of PSO and UC coexistence remains unclear. This study aimed at exploring the risk genes based on bioinformatics analyses, contributing to the pathogenesis of both diseases. METHODS:Gene expression data sets GSE14905 of PSO and GSE87466 of UC were used to screen the differential expression genes (DEGs) shared by these 2 diseases. The potential biological functions and pathways of these DEGs were analyzed to construct protein-protein interaction network, identify hub genes and transcription factor (TF) for the development of a TF-mRNA regulatory network. Finally, the expression of top hub genes was validated in GSE13355 (PSO) and GSE59071 (UC), as well as clinical specimens, using quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry and immunofluorescence. RESULTS:Bioinformatics analyses identified 30 DEGs shared by both PSO and UC (|log fold change|>2.0 and P < .05), primarily enriched in the activation of immune cells and chemokine-chemokine receptor interaction. Furthermore, protein-protein interaction and TF-mRNA regulatory networks pinpointed 9 core genes and 6 TFs. In addition, experimental validation via qRT-PCR confirmed elevated expression of STAT1 (P < .0001), with immunofluorescence showed that concentrated STAT1 expression in CD68 + macrophages in the PSO and UC lesions. Finally, qRT-PCR detected up-regulated CXCL1 (P < .01), CCL20 (P < .01), and matrix metalloproteinase9 (P < .001) expression compared with healthy skin controls, and results of immunohistochemistry of lesional tissue were consistent with the trend. CONCLUSION:PSO and UC share chemokine abnormalities, including elevated levels of CCL20, CXCL1, and matrix metalloproteinase9, potentially linked to STAT1-expressing CD68 + macrophage infiltration. These shared molecular features suggest their potential as biomarkers for co-morbidity risk.

This study aims to investigate the causal relationship between Body Mass Index (BMI) and the severity of Psoriasis (PsO) using bidirectional Mendelian Randomization (MR) and regression analyses. We conducted a multicenter study which combined bidirectional MR analyses with regression analyses. The MR analyses included 366,776 individuals from the largest up-to-date published BMI Genome-Wide Association Study (GWAS) data. Regression analyses were performed on 1,979 patients with psoriasis from 12 participating centers (from October 31, 2019, to May 31, 2022). We assessed the impact of BMI on PsO severity using odds ratios (ORs) and regression coefficients for three key measures: the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI). Two independent MR analyses revealed a significant causal association between BMI and PsO development. The first MR1 analysis showed that an increased BMI is significantly associated with a higher risk of psoriasis, with odds ratios of 2.28 (95% CI 1.33-3.92; p = 0.003). A subsequent MR2 analysis yielded consistent results, presenting an odds ratio of 2.37 (95% CI 1.16-4.85; p = 0.018) using the inverse-variance weighted method. Logistic regression showed that for every 1-unit increase in BMI (unadjusted covariates), the risk of severe psoriasis (PASI ≥ 10, BSA ≥ 10%, DLQI ≥ 10) increased by 6%, 6%, and 3%, respectively. Linear regression analysis revealed that each unit increase in BMI (not standardised) was associated with an increase of 0.25 units in the mean PASI score (p < 0.001), 0.34 units in the BSA score (p = 0.001), and 0.14 units in the DLQI score (95% CI 0.05-0.23; p = 0.001). From both the genetic and clinical severity assessment perspectives, it has been verified that abnormal weight gain is correlated with the severity of the condition in psoriasis patients. Clinicians should prioritize weight management and nutritional balance in the management of psoriatic disease. Clinicaltrials.gov: ChiCTR1900024852, date of registration: 2019-07-31.

Severe psoriasis has a long course and poor outcome, and it has long been a problem for patients. Understanding the independent risk factors that contribute to patients with severe psoriasis is critical for the development of effective treatment strategies. This large, multicenter study recruited 2,109 plaque psoriasis patients from 12 hospitals across China (October 31, 2019 - May 31, 2022). The logistic regression model underwent internal validation and external validation using two independent cohorts over future time periods (June 1, 2022 - January 31, 2023). The discriminative power of our model was substantiated by a C-index of 0.863 (95% CI: 0.848-0.879) in internal validation, further affirmed through 1,000 bootstrap validation (C-index: 0.860, 95% CI: 0.836-0.885) and external validation cohorts, where the C-index reached up to 0.910 (95% CI: 0.868-0.953) and 0.951 (95% CI: 0.924-0.977) in 2 external validation cohorts. To enhance accessibility for clinicians, the model has been made available as a dynamic nomogram and QR code. Our study identified 10 risk factors (the "DELPHI" consensus dichotomy, the DLQI index, the extent of skin involvement as measured by body surface area, the age of the patient at the time of clinical visit, sex, body weight in kilograms, career, the presence of scalp involvement, facial involvement, and arthropathy) for the overall severity of psoriasis (PASI >= 10). "Nomogram-10" provides clinicians with a practical tool to develop personalized intervention strategies based on an individual's risk profile.Trial registration: Chinese Clinical Trial Registry: ChiCTR1900024852.

Tobacco-specific nitrosamines (TSNAs) are a group of toxic substances specific to tobacco. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a tobacco-specific nitrosamine measurable in urine with a much longer half-life than cotinine. We aimed to examine the association between urinary tobacco-specific NNAL and HPV infection among American women. We used cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2014 to collect details on their urinary NNAL, HPV infection status, and other essential variables. The association between dietary urinary NNAL and HPV infection status was analyzed by using a weighted multivariate logistic regression model, and stratified subgroup analysis. In total, 5197 participants aged 18-59 years were identified, with overall prevalence of high-risk and low-risk HPV infection of 22.0% and 19.1%, respectively. The highest quartile of NNAL(Q4) was more positively associated with low-risk HPV infection than the lowest quartile of NNAL(Q1) (OR = 1.83 (1.35,2.50), p<0.001). the highest quartile of NNAL(Q4) was more positively associated with high-risk HPV infection than the lowest quartile of NNAL(Q1) (OR = 2.20 (1.57,3.08), p < 0.001). In subgroup analyses, the positive correlation between urinary NNAL levels and low-risk HPV infection status was inconsistent in marital status and BMI (interaction p < 0.05). The positive association of urinary NNAL levels with high-risk HPV infection status was inconsistent in smoking and BMI. (interaction p < 0.05). Tobacco-specific NNAL levels positively correlate with high- and low-risk HPV. Future well-designed longitudinal studies are still needed to validate the effect of tobacco exposure on HPV infection by NNAL.

Background:Epidermal growth factor receptor inhibitors (EGFRIs) represent a cornerstone in the targeted therapy of malignant tumors. While effective, dermatological adverse events (dAEs) associated with EGFRIs pose a significant challenge, often necessitating treatment discontinuation due to their severity and potential to impede the continuity of cancer therapy. Despite extensive research, the specific mechanisms and predictors of these adverse events remain poorly understood, particularly in diverse populations. This gap in knowledge underscores the need for targeted studies to better predict and manage these events, enhancing patient outcomes and adherence to life-saving therapies. Methods:This observational study was conducted at The First Affiliated Hospital of Guangxi Medical University, covering cancer patients treated with EGFRIs from 2020 to 2022. We analyzed clinical data including patient demographics, treatment specifics, and the development and timing of dAEs. The study employed SPSS 26.0 software for data analysis, focusing on the incidence of dAEs and factors influencing their occurrence. We used Kaplan-Meier and Cox regression methods to establish a predictive model for dAEs, tracking their onset and impact on treatment continuity. Results:In our study of 120 patients treated with EGFR inhibitors at The First Affiliated Hospital of Guangxi Medical University, we found a high prevalence of dAEs, with 84.2% of patients experiencing such effects. The most common manifestations were papulopustular rashes, observed as pustules in 52.5% and papules in 57.4% of cases, followed by nail lesions in 62.4% of patients, oral or other mucosal ulcers in 34.7%, and hair changes in 26.7%. The median incubation time (MIT) for dAEs was 5 weeks. We identified drug type, ethnicity, and occupation as statistically significant risk factors (P<0.05 for all) that influenced the MIT, which the Cox regression model further identified as protective factors. Nomograms were developed to assess the risk of dAEs, although it is important to note that these models have only been internally validated, lacking external validation data at this stage. Conclusions:The study highlights the high incidence of EGFRIs-associated dAEs, with specific dermatological manifestations posing significant challenges in cancer therapy. The identification of drug type, ethnicity, and occupation as influential factors on the MIT for dAEs informs clinical decisions. Our prediction model serves as a practical tool for evaluating the risk of developing dAEs over time, aiming to optimize patient management and mitigate treatment interruptions.

Nocardiosis is a rare opportunistic infection that is classically observed in immunocompromised patients but can also affect immunocompetent individuals. It tends to involve the lung, central nervous system, and skin and is often misdiagnosed.

The management of hair loss is vital in clinical dermatology due to its prevalence and impact on patients' quality of life. Quercetin is recognized for its diverse activities, including anti-inflammatory, anti-cancer, and immune regulation. However, its effects on human hair follicles and mechanisms remain unclear. This study explored quercetin's impact on countering DHT-induced cell damage, emphasizing apoptosis, cell cycle, mitochondria, and autophagy. Quercetin mitigated DHT's harm, restoring dermal papilla cell function and modulating cell cycle proteins. It restrained DHT-induced ROS and ATP loss, preserving mitochondrial integrity. Through network pharmacology analysis, it was discovered that quercetin targets SHP2, thereby regulating AKT signaling. Additionally, in mice, quercetin was found to promote hair growth. These significant insights highlight the potential of quercetin as a promising solution for hair loss and hair regeneration.

系统性红斑狼疮(SLE)是一种由自身抗体介导的慢性自身免疫性疾病,累及皮肤、肾脏、神经系统、血液系统等,其发病机制涉及多个信号通路和免疫细胞的功能异常.研究发现环状RNA(circRNA)可以调节PI3K/Akt/mTOR、JAK/STAT、TLR、Wnt和Notch等信号通路,介导T、B淋巴细胞活化,从而影响SLE的发病.本文针对circRNA在这些通路中所发挥的作用及其与SLE发生发展可能的关联进行综述,以便我们更深入地理解circRNA在SLE中的作用机制,为疾病的诊断和治疗提供新的思路和目标.

白癜风是一种获得性色素脱失性皮肤病,其特征为表皮黑素细胞的选择性丢失,临床表现为皮肤和黏膜的色素脱失性白斑.目前白癜风的发病机制主要包括自身免疫、神经内分泌、氧化应激、遗传易感和环境因素等.近年来,研究发现免疫系统调节紊乱在白癜风的发病过程中起着至关重要的作用.本文就目前关于白癜风的免疫发病机制进行综述.

BACKGROUND:Although androgenetic alopecia (AGA) is classified as a non-inflammatory alopecia, histological evidence of microinflammation has long been recognized. However, changes in the immune microenvironment, immune-related pathways and the expression of immune-related genes (IRGs) involved in AGA remain unclear.METHODS:The microarray gene expression data (GSE36169) from patients with male AGA were analyzed. gene set enrichment analysis (GSEA) among statistically changed genes was done. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses among differentially expressed genes were performed. differentially expressed genes were screened to identify IRGs based on the ImmPort database. The cytohubba-MCC plugin of Cytoscape was applied to screen hub immune genes. The infiltration levels of 28 immune cells were quantified adopting single-sample GSEA (ssGSEA) algorithm. The microarray gene expression data (GSE90594) of male AGA was analyzed to validate hub IRGs genes and differential infiltrated immune cells.RESULTS:The ssGSEA revealed γδT cell, central memory CD8+ T cell, mast cell, immature B cell, activated CD8+ T cell, effector memory CD4+ T cell, eosinophil and neutrophil were significantly increased infiltration in the bald scalp. GSEA showed statistically changed genes were most enriched in immune related pathways, including innate immune system, adaptive immune system, cytokine signaling, interferon-γ signaling, interferon signaling and interleukins signaling. The 4 hub IRGs, including matrix metallopeptidase 9, protein tyrosine phosphatase receptor type C, bone morphogenetic protein 2, and thrombospondin 1, were enriched in the pathways of allograft rejection, coagulation and interferon-γ response.CONCLUSION:In summary, we proposed that the increase in γδ T cells, central memory CD8+ T cells, activated CD8+ T cell as well as the infiltration of mast cells contributed to immune microenvironment changes in male AGA. The 4 hub IRGs may be involved in the development and progression of hair loss in male AGA through interferon-γ signal pathways.

目的:探讨降香提取物(DOE)对脂多糖(LPS)诱导的RAW264.7细胞的抗炎及抗氧化作用及其对人毛乳头细胞(hD-PCs)的促毛发生长作用.方法:将RAW264.7细胞分为空白对照组、模型组、4％DOE组和8％DOE组.空白对照组不予处理,模型组使用LPS诱导体外炎症模型,4％DOE组和8％DOE组用LPS处理后分别加入4％和8％的DOE,分别采用Griess法和酶联免疫吸附试验(ELISA)法测定各组细胞培养上清液中一氧化氮(NO)、肿瘤坏死因子α(TNF-α)的含量,DCFH-DA荧光探针检测各组细胞内的活性氧(ROS)含量.体外培养人毛囊分离的hDPCs,设置空白对照组、4％DOE组和8％DOE组,采用CCK-8法检测细胞活力,RT-qPCR法检测毛发生长因子CTNNB1和毛发抑制因子DKK1基因的表达,western blotting法检测β-连环蛋白(β-catenin)蛋白表达水平.结果:与模型组相比,4％DOE组和8％DOE组RAW264.7细胞NO、TNF-α、ROS含量降低(均P＜0.05).与空白对照组相比,4％DOE组和8％DOE组hDPCs细胞活力升高,CTNNB1基因和β-catenin蛋白表达上调,且DKK1基因表达下调(均P＜0.05).结论:DOE对LPS诱导的RAW264.7巨噬细胞具有抗炎和抗氧化作用,并且可以通过增加hDPCs的活力及调节关键基因的表达促进毛发生长.