Edible bird's nest (EBN) and its key component, sialic acid (SA), were investigated for their potential to counteract sepsis-induced immunosuppression. In a murine "two-hit" sepsis model, EBN and SA significantly enhanced survival, ameliorated multi-organ damage, and reduced bacterial dissemination. Crucially, they reversed immunosuppression by restoring the TNF-α-secreting capacity of immune cells. Proteomic and KEGG analyses identified T cell proliferation as a central mechanism, which was validated by CFSE assay. Furthermore, we demonstrated that this enhanced T cell proliferation is mediated through the activation of the mTOR signaling pathway. This study reveals that EBN and SA are promising immune-enhancing agents against sepsis-induced immunosuppression, offering a novel therapeutic strategy for secondary infections.

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by epidermal barrier dysfunction and immune dysregulation, yet effective long-term therapies are limited. Although regulated cell death has been linked to AD, the involvement of copper-dependent cell death (cuproptosis) and its therapeutic relevance in AD have not been explored. Herein, we identify aberrant epidermal upregulation of the copper transporter SLC31A1 as a driver of copper overload and cuproptosis in keratinocytes, which in turn promotes GSDMA-dependent pyroptosis through an α-ketoglutarate (α-KG)/H3K9me3 epigenetic mechanism. To target this pathway, we developed a dual-functional microneedle system composed of calcium phosphate nanoparticles delivering Slc31a1 siRNA and embedded within Bletilla striata polysaccharide microneedles (CaP-siSlc31a1@BSP). This platform enables efficient transdermal gene silencing while BSP simultaneously suppresses STAT3/GSDMA signaling and inflammation. In MC903-induced AD-like mice, CaP-siSlc31a1@BSP markedly alleviated skin inflammation, epidermal hyperplasia and pruritus, accompanied by reduced Th2/Th17 responses. Our study reveals a previously unrecognized cuproptosis-pyroptosis axis in AD and establishes SLC31A1 as a promising therapeutic target. The CaP-siSlc31a1@BSP microneedle offers a synergistic drug-gene transdermal strategy with strong potential for AD treatment.

RATIONALE:antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune syndrome characterized by necrotizing inflammation of small-to medium-sized vessels accompanied by the presence of peripheral blood ANCA. Subarachnoid hemorrhage (SAH) is an uncommon complication of AAV. The purpose of this report is to present a rare case of AAV complicated by SAH and to review the existing literature, thereby enhancing awareness of this severe neurological manifestation and its management strategies. PATIENT CONCERNS:We report the case of a 56-year-old male who presented with cough, blood-tinged sputum, proteinuria, elevated serum creatinine levels, and headache. Laboratory examinations confirmed the presence of anti-myeloperoxidaseantibody, imaging revealed SAH, and angiography identified a ruptured anterior communicating artery aneurysm. DIAGNOSES:The final diagnosis was AAV complicated by SAH. INTERVENTIONS:The patient underwent prompt endovascular coiling, with concurrent immunosuppression using methylprednisolone and intravenous cyclophosphamide. OUTCOMES:Following endovascular coiling, the patient's subarachnoid hemorrhage and associated neurological symptoms (headache, dizziness) resolved completely. Immunosuppressive therapy led to the resolution of respiratory symptoms (cough and blood-tinged sputum), the clearance of hematuria, and a significant reduction in inflammatory markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate. However, despite immunosuppressive treatment, with serum creatinine levels fluctuating between 320 and 450 μmol/L, and heavy proteinuria (e.g., 24-hour urine protein of 3360.21mg) persisted. Additionally, the patient developed deep vein thrombosis 1 month after discharge, which was successfully managed with anticoagulation therapy and the placement of an inferior vena cava filter. LESSONS:SAH is a rare but life-threatening complication of AAV. Vigilance for acute neurological symptoms, such as headache, enables early intervention. Combined endovascular repair for SAH and immunosuppressive therapy significantly improve outcomes.

Abstract Atopic dermatitis (AD) is a chronic inflammatory skin disorder in which keratinocyte (KC)-derived thymic stromal lymphopoietin (TSLP) orchestrates pathogenic crosstalk between epithelial cells and immune cells. Here, we present a boron-doped copper single-atom nanomaterial (Cu/NC-B) designed to achieve a dual functional blockade of the TSLP signaling axis, offering a more comprehensive therapeutic intervention. Therapeutically, Cu/NC-B significantly alleviated MC903-induced AD-like lesions, showing efficacy comparable to that of crisaborole (CB) with a superior safety profile. Single-cell transcriptomics analysis revealed that Cu/NC-B selectively targets a previously uncharacterized, highly inflammatory KC subpopulation (KC_Spinous_Tslp), thereby disrupting a critical cellular node in AD pathology. At the molecular level, Cu/NC-B exerts its effects through two complementary pathways: epigenetic repression of TSLP via nicotinamide adenine dinucleotide (NAD+)-dependent activation of SIRT1/3 and competitive antagonism of the TSLP receptor (TSLPR). Our work establishes Cu/NC-B as a dual-action nanotherapeutic capable of concurrently suppressing TSLP transcription and disrupting its receptor engagement, thereby proposing a targeted intervention for AD treatment.

BACKGROUND:Chronic spontaneous urticaria (CSU) can cause psychosocial and quality of life burden on patients and their family members and caregivers. Despite its recognition as a debilitating disease, limited data exist regarding the impact of CSU on family members, hindering a comprehensive understanding of the disease's broader effects. This study aimed to assess how CSU affects the quality of life of family members who support patients in their daily challenges by applying the Family Dermatology Life Quality Index (FDLQI) questionnaire across multiple countries. METHODS:A cross-sectional, multicentre and international study conducted between January and December 2024 in Urticaria Centres of Reference and Excellence (UCARE) centres located in several countries including Brazil, China, Ecuador, Greece, India, Oman, Poland, Russia, Thailand, Turkey, Peru and North Macedonia. Statistical analyses, including non-parametric tests and multiple regression models, were employed to explore associations between disease severity/control and family burden. RESULTS:Poorly controlled CSU significantly deteriorated family members' quality of life, particularly in emotional, physical and social domains. Higher disease severity and lower disease control scores were associated with increased stress, greater caregiving burden and elevated health expenditures. In opposition to family relations, older age and longer time since diagnosis mitigate negative impacts, while insufficient treatment regimens exacerbated them. CONCLUSIONS:Inadequate control of CSU amplifies the burden on families, underscoring the need for effective and supportive care strategies.

Accurately assessing chemosensitivity to drugs such as cisplatin is crucial for optimizing outcomes of high-grade serous ovarian carcinoma (HGSOC) patients. Developing prediction models and identifying biomarkers can assist differentiate chemotherapy-sensitive from chemotherapy-resistant subtypes. We integrated 908 transcriptome samples from 12 HGSOC datasets of GEO and TCGA across four detection platforms. Differentially ranked genes (DRGs) were identified by applying intra-sample rank transformation and performing T-test. To refine the selection of informative DRGs, a recurrent logistic regression (RLR) model was employed, followed by model optimization using the Pairwise Analysis of Gene Expression (PAGE) algorithm to establish clinically applicable gene pair signature. Kinesin Family Member 20 A (KIF20A) and Chromogranin B (CHGB) were paired to establish a robust gene pair signature, KIF20A::CHGB Pair (KCP), which exhibited remarkable discriminant accuracy (Accuracy = 0.9397; AUROC = 0.9668; AUPRC = 0.9799) in distinguishing HGSOC from controls in eight independent validation cohorts. Further survival and functional analyses revealed that altered rank relationships between KIF20A and CHGB were significantly associated with prognosis and platinum resistance in HGSOC. Following exposure to standard chemotherapy regimens, we conducted RT-qPCR, CCK-8(Cell Counting Kit-8) viability assays, EdU proliferation assays, flow cytometry, and SynergyFinder, which collectively assessed cellular proliferation and cell-cycle responses, demonstrating that both genes contribute comparably to the malignant phenotype. Elevated KIF20A or CHGB expression drives chemoresistance and correlates with poor prognosis in HGSOC. Silencing either gene significantly enhances the growth‑inhibitory effects of cisplatin and other standard chemotherapeutic agents. Our findings establish KCP as a robust diagnostic and prognostic biomarker and highlight KIF20A and CHGB as synergistic targets for overcoming platinum resistance in ovarian cancer. • In silico experiments identified KIF20A::CHGB (KCP) as a cross-platform gene pair signature for distinguishing high-grade serous ovarian carcinoma (HGSOC) from normal tissues, achieving exceptional accuracy (AUROC = 0.9715) across eight independent cohorts. • In vitro experiments demonstrated that KIF20A and CHGB knockdown enhanced the sensitivity of ovarian cancer cells to cisplatin and suppressed tumor cell proliferation. • We developed a novel Recurrent Logistic Regression (RLR) model combined with Pairwise Analysis of Gene Expression (PAGE) to overcome batch effects and improve biomarker generalizability, offering a framework for multi-cohort transcriptomic studies.

Background Chronic spontaneous urticaria (CSU) is a relapsing, immune‐mediated skin disease. However, the role of monocytes in its pathogenesis and clinical significance remains unclear. Objective This study aimed to investigate the correlation between peripheral blood monocyte counts and clinical features in CSU patients, as well as to explore their potential predictive value for the therapeutic efficacy of second‐generation H1‐antihistamines (sgAHs) and omalizumab. Methods Two independent patient cohorts were included: Cohort 1 was utilized to evaluate sgAHs treatment efficacy, while Cohort 2 was employed to analyze omalizumab efficacy in CSU patients. Results A total of 656 and 105 CSU patients were enrolled in Cohort 1 and Cohort 2, respectively. Baseline peripheral blood monocyte levels were significantly associated with treatment outcome in both cohorts (OR = 0.005, p < 0.001; OR = 0.07, p = 0.005, respectively). Furthermore, compared to baseline levels, peripheral blood monocyte counts decreased significantly in both cohorts ( p < 0.0001 and p = 0.0205, respectively). In Cohort 2, fast‐responders, but not slow‐responders or non‐responders, exhibited a significantly greater reduction in monocyte counts post‐treatment ( p = 0.0031 for fast‐responders, p = 0.5285 for slow‐responders, and p = 0.7565 for non‐responders, respectively). Conclusion Baseline monocyte counts were significantly correlated with the therapeutic efficacy of both sgAHs and omalizumab in CSU patients. Trial Registration: Chinese Clinical Trial Registry: ChiCTR‐OCH‐14004518

Chronic spontaneous urticaria (CSU) can cause psychosocial and quality of life burden on patients and their family members and caregivers. Despite its recognition as a debilitating disease, limited data exist regarding the impact of CSU on family members, hindering a comprehensive understanding of the disease's broader effects. This study aimed to assess how CSU affects the quality of life of family members who support patients in their daily challenges by applying the Family Dermatology Life Quality Index (FDLQI) questionnaire across multiple countries. A cross-sectional, multicentre and international study conducted between January and December 2024 in Urticaria Centres of Reference and Excellence (UCARE) centres located in several countries including Brazil, China, Ecuador, Greece, India, Oman, Poland, Russia, Thailand, Turkey, Peru and North Macedonia. Statistical analyses, including non-parametric tests and multiple regression models, were employed to explore associations between disease severity/control and family burden. Poorly controlled CSU significantly deteriorated family members' quality of life, particularly in emotional, physical and social domains. Higher disease severity and lower disease control scores were associated with increased stress, greater caregiving burden and elevated health expenditures. In opposition to family relations, older age and longer time since diagnosis mitigate negative impacts, while insufficient treatment regimens exacerbated them. Inadequate control of CSU amplifies the burden on families, underscoring the need for effective and supportive care strategies.

Introduction: The Patient Acceptable Symptom State (PASS), a patient-reported outcome measure, has demonstrated correlations with disease severity in various conditions, including psoriasis and scleroderma. However, the clinical relevance of PASS in the context of chronic spontaneous urticaria (CSU) remains to be fully elucidated. Objectives: This study aimed to determine the prevalence of PASS among CSU patients, identify potential predictors, and establish the weekly urticaria activity score (UAS7) threshold for PASS. Methods: Demographic and clinical data from CSU patients were prospectively collected. PASS attainment was assessed using a single-item questionnaire. Logistic regression analysis and interaction effects analysis were employed to identify predictors associated with achieving PASS (PASS-Y) or failing to achieve PASS (PASS-N). The UAS7 threshold corresponding to PASS was determined through receiver operating characteristic (ROC) curve analysis. Results: A total of 161 CSU patients were enrolled in this study. Among them, 70.5% exhibited non-severe disease activity (UAS7<28) and achieved PASS-Y. Logistic regression analysis revealed a significant association between UAS7 scores and PASS status (AOR=1.105, P<0.001). Female patients with severe disease activity (UAS7≥ 28) were significantly less likely to achieve PASS-Y compared to their male counterparts (AOR=3.514, P=0.042). ROC analysis identified a UAS7 threshold of 21.5 for predicting PASS, with an area under the curve (AUC) of 0.821. Conclusions: In patients with CSU, PASS demonstrates a strong correlation with UAS7 scores and is straightforward to implement. It may serve as a valuable complementary tool to UAS7 in clinical settings, facilitating a rapid, patient-centered assessment of disease activity.

Psoriasis is a chronic inflammatory disease characterized by dysregulated interactions between keratinocytes (KCs) and immune cells. However, the details of KCs orchestrating the immune cell infiltration, particularly for natural killer (NK) cells, remain unclear. Here NK cell infiltration is significantly increased in psoriatic skin lesions, and the application of anti-MHC-II treatment or knockout of H2-Ab1 in the epidermis dramatically reduces IMQ-mediated psoriatic dermatitis as well as the infiltration of NK cells through CXCL10 mediated by the ERK-CREB axis. Spatial transcriptomics reveal that NK cells coexist with KCs, driven by enhanced CXCL signaling, and epidermal H2-Ab1 deletion suppresses KC-NK cell communication. NK cells release granzyme B, inducing pyroptosis in adjacent GSDME-expressing KCs, contributing to the inflammatory response. NK cell depletion or Gsdme knockout reduces pyroptosis and alleviates psoriasis-like dermatitis. Multicolor immunohistochemistry confirms that epidermal MHC-II expression in psoriatic lesions correlates positively with NK cell, granzyme B and cleaved-GSDME levels. This study reveals that epidermal MHC-II attracts NK cells, triggering KC pyroptosis and remodeling the immune microenvironment in psoriasis, offering novel insights into its pathogenesis.

Inflammatory skin diseases and skin cancers are usually accompanied by metabolic comorbidities or altered metabolic status. Metabolomic analysis indicates that patients with inflammatory skin diseases and skin cancers exhibit altered metabolites, including glycans, lipids, and amino acids. This suggests that metabolic reprogramming may play a pivotal role in the pathogenesis of these skin diseases. The solute carrier (SLC) superfamily is responsible for the transport of a range of metabolites, which may serve as crucial intermediate links in the metabolic reprogramming of diseases. Nevertheless, research on the SLC superfamily in skin diseases remains limited, and the development of its drug targets is even more scarce. Therefore, this review is devoted to elucidating our current understanding of the role of the SLC family in the pathogenesis of inflammatory skin diseases and skin cancers, with a particular emphasis on its role in metabolic reprogramming. In doing so, we aim to provide a reference point for the subsequent development of drug targets for the SLC family in skin diseases.

Despite growing awareness on hand eczema (HE) in Western countries, public attention to HE in China is limited. We aimed to investigate the clinical characteristics of HE and examine its association with atopic dermatitis in the Chinese population. A multicenter cross-sectional study was conducted across 23 tertiary hospitals in China between September 2018 and November 2019. Patients with HE completed a survey covering demographics, allergic diseases, and HE-specific characteristics and underwent patch testing. Clinical severity was assessed using the Hand Eczema Severity Index. Binary logistic and linear regression models were used. In total, 2072 patients with HE were included (mean age = 39.8 years, 60.6% female). The most common HE subtype was allergic contact dermatitis, followed by irritant contact dermatitis. One third had moderate-to-very-severe HE, and at least 64.3% had chronic HE. The positive patch test rate was 50.7%. Approximately one quarter had a physician-confirmed diagnosis of atopic dermatitis that was associated with greater HE severity, longer persistence of HE, higher disease burden, and altered contact sensitization patterns in patients with HE. This study indicates that addressing both HE and atopic dermatitis might improve prognosis and QOL for affected individuals, emphasizing the need for targeted preventions and management strategies for this patient population.

Ivarmacitinib (SHR0302) has demonstrated promising efficacy and safety profiles in patients with moderate-to-severe atopic dermatitis (AD). This study aimed to investigate the effects of ivarmacitinib on the extent and severity of moderate-to-severe AD across anatomical regions. A post-hoc analysis was performed based on the data from a phase III trial of ivarmacitinib (NCT04875169). Patients receiving ivarmacitinib or placebo were included in this study. Eczema Area and Severity Index (EASI) score was assessed in four regions, including the head/neck, upper extremities, trunk, and lower extremities. EASI 75/90/100 response was defined as ≥ 75.0

Chronic spontaneous urticaria (CSU), characterized by recurrent wheals and/or angioedema persisting for more than 6 weeks, represents a substantial clinical challenge. Although international guidelines endorse second-generation H1-antihistamines (sgAHs) as first-line therapy, up to 50% of patients remain refractory even at quadruple doses, significantly compromising quality of life and mental well-being. Notably, standardized guidelines for managing H1 antihistamine-resistant CSU are currently lacking. To address this gap, we aimed to develop an evidence-based clinical practice guideline for the diagnosis, assessment, and step-wise treatment of H1 antihistamine-resistant CSU. A multidisciplinary panel conducted a systematic literature review and through multiple rounds of group discussions, both offline and online, to draft recommendations. Evidence was graded using the Oxford CEBM 2011 system and recommendations assigned GRADE strengths. This guideline provides a standardized, personalized treatment algorithm for H1 antihistamine-resistant CSU, aiming to improve clinical efficacy, reduce socioeconomic burden, and direct future research toward validating novel agents such as JAK inhibitors and optimizing long-term outcomes.

Great advances have been made in malignant melanoma treatments, whereas drug resistance still limits many drug applications. CRKL has been reported to be overexpressed in various tumors and showed poor prognosis. However, its specific function and mechanism in melanoma remain unclear. In the present study, we investigated the expression of CRKL and its clinical association by bioinformatics and clinical analysis, and then performed a series of in vitro and in vivo experiments to demonstrate its function and mechanism. Results showed that CRKL increased during melanoma progression and was strongly associated with poor prognosis. CRKL silencing effectively inhibited melanoma cell growth and invasion via ERK/MMP9 and PI3K/AKT signaling pathways both in vitro and in vivo. Moreover, CRKL silencing induced pyroptosis in melanoma cells by upregulating the levels of pyroptosis-associated proteins, such as NLRP3, cleaved Caspase-1, and GSDMD-N. Importantly, our study demonstrated that interfering with CRKL expression enhanced the chemotherapy sensitivity of melanoma cells to cisplatin by regulating PI3K/AKT and NLRP3/GSDMD signaling pathways. In conclusion, our study uncovers a novel molecular mechanism by which CRKL functions in melanoma and highlights potential therapeutic strategies for improving chemotherapy sensitivity in melanoma patients.