BACKGROUND:Ivarmacitinib, an oral JAK1 inhibitor, improved efficacy outcomes versus placebo at Week 16 in a phase 3 trial in patients with moderate-to-severe atopic dermatitis (AD). OBJECTIVES:To describe efficacy and safety outcomes through Week 52. METHODS:In this multicentre, double-blind, phase 3 trial (NCT04875169), patients aged 12-75 years were randomized 1:1:1 to receive once-daily oral ivarmacitinib 4 mg, ivarmacitinib 8 mg, or placebo for 16 weeks, followed by a 36-week double-blind extension. At Week 16, placebo-treated patients who continued in the study were re-randomized to ivarmacitinib 4 mg or 8 mg. Key Week 52 endpoints included Investigator's Global Assessment (IGA) 0/1 with at least a 2-grade improvement, Eczema Area and Severity Index 75 (EASI-75), and Worst Itch Numeric Rating Scale (WI-NRS) response. RESULTS:Of 336 randomized patients, 258 completed 52 weeks of treatment. Among patients initially randomized to ivarmacitinib, Week 52 IGA responses were achieved by 42.3% and 40.2% of patients in the 4 mg and 8 mg groups, respectively. EASI-75 responses were achieved by 60.6% and 55.9%, and WI-NRS responses by 59.6% and 45.1%, respectively. During the active-treatment period, treatment-emergent adverse events (TEAEs) occurred in 87.5% and 85.5% of patients in the 4 mg and 8 mg groups, respectively. The most frequent TEAEs were upper respiratory tract infection, COVID-19, SARS-CoV-2 test positive, and increased blood creatine phosphokinase. Serious TEAEs occurred in 5.6% and 4.4% of patients, respectively. CONCLUSION:Ivarmacitinib was associated with generally maintained improvement through Week 52, with a safety profile generally consistent with that observed during the placebo-controlled period. Because the extension phase had no placebo control after Week 16, long-term efficacy findings should be interpreted as descriptive.

ObjectiveElderly patients with moderate-to-severe plaque psoriasis are vulnerable to adverse events (AEs), which raise safety concerns in their management. This post-hoc analysis aimed to evaluate the safety and efficacy of vunakizumab in elderly patients with moderate-to-severe plaque psoriasis, with an emphasis on safety.MethodsData were extracted from a phase III trial (NCT04839016). A total of 70 elderly patients with moderate-to-severe plaque psoriasis were included and assigned to the vunakizumab (n = 49) and placebo (n = 21) groups.ResultsDuring the induction period, the incidence of any AEs (63.3% vs. 76.2%) (p = 0.291) and serious AEs (4.1% vs. 0.0%) (p = 1.000) did not differ between the vunakizumab and placebo groups. During the entire treatment period, the incidence of any AEs (87.8% vs. 90.5%) (p = 1.000) and serious AEs (10.2% vs. 4.8%) (p = 0.661) remained unchanged between the vunakizumab and placebo groups. In the vunakizumab group, the most frequent AEs during the entire treatment period were elevated blood glucose (22.4%), hypertriglyceridemia (12.2%), elevated blood cholesterol (10.2%), eczema (10.2%), hyperuricemia (10.2%), and upper respiratory tract infection (10.2%). The rates of patients achieving psoriasis area and severity index (PASI) 75, 90, 100, and static physician’s global assessment (sPGA) 0/1 responses at week (W) 12 were higher in the vunakizumab group than in the placebo group (all p < 0.001). These trends were sustained for 52 weeks. Patient-reported outcomes (PROs) at certain time points during 52 weeks were better in the vunakizumab group than in the placebo group.ConclusionVunakizumab is safe and effective in elderly patients with moderate-to-severe plaque psoriasis.

Atopic dermatitis (AD) is a highly heterogeneous chronic inflammatory skin disease, and the exact role and mechanisms of interleukin (IL)-19 in AD remain unclear. This study integrated serum samples from AD patients, transcriptomic data from clinical AD lesions, AD-like mouse models with exogenous IL-19 supplementation or IL-19 gene knockout, and in vitro cellular models to investigate its mechanism of action. Serum IL-19 levels correlated with disease severity after adjustment for clinical covariates and type 2 cytokines in this cohort. In an MC903-induced AD-like mouse model, exogenous IL-19 supplementation exacerbated the dermatitis phenotype, whereas IL-19 gene knockout alleviated it. Mechanistically, keratinocytes constituted the primary source of IL-19 within AD lesions, with house dust mites inducing its upregulation in these cells in vitro. IL-19 acted through the STAT6/STAT3 signaling pathway to suppress loricrin and keratin-10 expression, which may result in epidermal barrier impairment. Simultaneously, it upregulated thymic stromal lymphopoietin and IL-33, potentially facilitating the type 2 inflammatory cascade in AD. Furthermore, IL-19 may additively exacerbate inflammatory responses with IL-13 and IL-4. Collectively, these findings support a role for IL-19 as a pro-inflammatory mediator in AD, suggesting that IL-19 contributes to both epidermal barrier dysfunction and type 2 immune dysregulation in this disease.

Background: Acne vulgaris is a chronic inflammatory skin disease, and photo-based therapies have been adopted as noninvasive alternatives to pharmacological treatment.Objective: To systematically evaluate the therapeutic strategies and biological mechanisms of photo-based therapies in the management of acne vulgaris, focusing on sebum modulation, inflammation control, and the treatment of acne sequelae to inform phenotype-oriented clinical decision-making.Methods: Following PRISMA 2020 guidelines, a systematic search was conducted in PubMed and Web of Science for studies published between 2005 and 2025. From an initial 2,218 records, 64 articles comprising 42 clinical trials and 22 experimental studies were selected for inclusion based on their focus on the efficacy, safety, and molecular mechanisms of light-emitting diodes (LED), intense pulsed light (IPL), laser systems, and photodynamic therapy (PDT).Results: Analysis revealed that photo-based modalities target acne through three primary pathways: 1. Sebum Modulation: Aminolevulinic acid (ALA)-PDT demonstrates superior, durable efficacy in moderate-to-severe acne by inducing sebocyte apoptosis and downregulating lipogenesis via the PI3K/Akt/mTOR and OLR1-Wnt/β-catenin pathways. 2. Inflammation Control: Blue and red light (LED) and IPL provide gradual anti-inflammatory effects suitable for mild-to-moderate acne by reducing C. acnes colonization and modulating cytokines such as TGF-β1, IL-10, and TNF-α. 3. Tissue Remodeling: For acne sequelae, fractional CO2 and picosecond lasers promote collagen remodeling to improve atrophic scars, while vascular-targeted lasers (PDL, Nd:YAG) and IPL effectively reduce post-inflammatory erythema (PAE) and hyperpigmentation (PIH).Conclusions: Photo-based therapies are phenotype-specific rather than interchangeable. Strategies targeting sebaceous activity and inflammation are central to treating active lesions, while tissue-remodeling interventions are most effective for managing sequelae. This review establishes a strategy-oriented framework that supports personalized, evidence-based treatment planning in routine clinical practice.

Melanonychia significantly affects aesthetics and patient well-being, particularly when it advances to subungual melanoma. The causes of melanonychia are multifactorial, encompassing nail matrix melanocyte activation, benign melanocytic proliferation, subungual melanoma, as well as inflammatory, infectious, traumatic, and drug-induced conditions. Among these, subungual melanoma poses a diagnostic challenge due to its nonspecific clinical presentation, leading to delayed or missed diagnoses that adversely affect prognosis. Accurate differentiation between malignant melanonychia and more common benign etiologies-such as onychomycosis, trauma-related pigmentation, drug-induced pigmentation, and subungual warts-is essential to avoid both misdiagnosis and overtreatment. This review summarizes the clinical, dermoscopic, and histopathological characteristics of melanonychia of various origins; highlights key dermoscopic features for distinguishing subungual melanoma from non-melanocytic pigmentation; and outlines diagnostic and therapeutic strategies tailored to both adults and children. Clarifying these distinctions is critical for facilitating earlier recognition of nail melanoma while minimizing unnecessary interventions for benign conditions.

Introduction: Omalizumab is an effective treatment for antihistamine-refractory chronic spontaneous urticaria (CSU), although treatment responses vary significantly. While fast and slow responders are well characterized, the profile of super responders (SRs) remains poorly understood. This study aimed to identify clinical and laboratory predictors of super response (SR) and poor/non-response (PR) to omalizumab in refractory CSU. METHODS:This retrospective study analyzed 307 CSU patients treated with omalizumab at a UCARE center between January 2023 and December 2024. SR was defined as achieving Urticaria Activity Score (UAS) = 0 within 1 week and sustained control (UAS7 ≤6, Urticaria Control Test [UCT] >12); PR was defined as UCT <12 after three injections. Demographic, clinical, and laboratory parameters were compared between response groups. RESULTS:SR patients (n = 138) had lower rates of concomitant chronic inducible urticaria (CIndU) (26.8% vs. 48.5%, p < 0.05), higher total immunoglobulin E (IgE) (113.0 IU/mL), and elevated D-dimer. PR patients (n = 35) were older (median 52.0 years) and had higher angioedema rates (65.5%), lower atopy prevalence (47.1%), higher UAS7 scores, lower IgE (53.5 IU/mL), and higher autologous serum skin test (ASST) positivity (61.5%). Multivariate analysis identified male sex as protective for SR (odds ratio [OR] = 0.556, p = 0.025), while concomitant CIndU predicted non-SR (OR = 2.357, p = 0.001). Predictors of PR included body mass index (BMI) ≥28 kg/m2 (OR = 5.147, p = 0.023), angioedema (OR = 3.309, p = 0.042), and ASST positivity (OR = 4.174, p = 0.011); atopy was protective (OR = 0.299, p = 0.025). CONCLUSION:Male sex and absence of CIndU predict super response to omalizumab, while high BMI, angioedema, and ASST positivity predict poor response. Atopy is associated with better omalizumab response. These findings support personalized treatment strategies in refractory CSU, though further multiethnic validation is warranted. .

To investigate the clinical distribution patterns and clinicopathological characteristics of basal cell carcinoma (BCC) in Southwest China. A retrospective analysis was conducted among 2016 patients diagnosed with BCC between April 2003 and May 2025. The study focused on lesion locations, facial distribution patterns, presentations of multiple BCCs, and histopathological features of BCC. A total of 2016 patients with 2138 BCC lesions were included, comprising 881 males (43.70

BACKGROUND:Effective topical therapies for mild-to-moderate atopic dermatitis (AD) should provide rapid itch relief, sustained anti-inflammatory efficacy and minimal local toxicity. Existing options, including corticosteroids and calcineurin inhibitors, are limited by long-term adverse effects, highlighting the need for safer, steroid-sparing alternatives. OBJECTIVES:To evaluate the efficacy and safety of ivarmacitinib ointment, a highly selective topical Janus kinase 1 inhibitor, applied twice daily in adults with mild-to-moderate AD. METHODS:This phase III evaluation was part of a multicentre randomized double-blind vehicle-controlled seamless adaptive phase II/III trial conducted at 27 sites in China. Adults aged 18-75 years with Hanifin-Rajka-defined mild-to-moderate AD were randomized (1 : 1 : 1) to ivarmacitinib ointment 0.5%, ivarmacitinib ointment 1% or vehicle for 8 weeks. Patients who initially received the vehicle were re-randomized to active treatment for a blinded extension through week 52. Co-primary endpoints were Investigator's Global Assessment (IGA) response (score 0/1 with ≥ 2-grade improvement) and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 8. RESULTS:At week 8, significantly more patients achieved an IGA response with ivarmacitinib than with vehicle [ivarmacitinib 0.5%: 21.3% vs. 10.6% (P = 0.02); ivarmacitinib 1%: 26.2% vs. 10.6% (P = 0.001)]. Likewise, EASI 75 responses were higher [ivarmacitinib 0.5%: 42.6% vs. 17.9%; ivarmacitinib 1%: 45.1% vs. 17.9% (both P < 0.001)]. Relief from pruritus was seen within 48 h and maintained through week 52, with sustained improvements in SCORing Atopic Dermatitis (SCORAD), affected body surface area and Dermatology Life Quality Index. During the vehicle-controlled period, treatment-emergent adverse events occurred in 42.6% (n = 52/122), 56.6% (n = 69/122) and 52.0% (n = 64/123) of patients in the ivarmacitinib 0.5%, ivarmacitinib 1% and vehicle groups, respectively; most were mild and infection-related events were infrequent. No treatment-related adverse event occurred in ≥ 2% of patients in the ivarmacitinib 1% or vehicle groups, while in the ivarmacitinib 0.5% group, only folliculitis (n = 5/122; 4.1%) and increased blood uric acid (n = 4/122; 3.3%) were reported in ≥ 2% of patients. No skin atrophy, telangiectasia or application-site irritation was observed. Long-term safety through week 52 remained consistent, with no new safety signals noted. CONCLUSIONS:Twice-daily ivarmacitinib ointment (0.5% or 1%) produced rapid, durable and well-tolerated improvements in the signs, symptoms and itch experienced by adults with mild-to-moderate AD, supporting its potential as a safe, steroid-sparing topical therapy.

BACKGROUND:The inconsistency between serum total IgE (tIgE) and allergen-specific IgE (sIgE) results is often encountered in clinical practice, but the distribution and influencing factors of the inconsistent results have not been fully understood. OBJECTIVE:The aim of this study was to analyze the distribution and inconsistency between tIgE and sIgE test results. METHODS:A retrospective study, from the electronic medical records of 2139 patients who underwent both tIgE and sIgE tests, from January to December 2023 was reviewed. The tIgE and sIgE results and their distribution, as well as their inconsistency, were analyzed based on sex, age, and disease subgroups. RESULTS:36.2% of the patients had a positive sIgE, and 43.7% had an elevated tIgE level. sIgE and tIgE results were discordant in nearly 30% of patients, with no difference between genders, while individuals aged over 60 exhibited a significantly higher inconsistency rate than the other age groups, and the inconsistency rate between tIgE and sIgE results was significantly different among different tIgE levels, sIgE grades, positive allergen count and positive allergen types. In addition, patients with chronic urticaria (CU) had a higher inconsistency rate than those with other allergic diseases, but the difference was not statistically significant. CONCLUSION:The overall inconsistency rate between tIgE and sIgE results was about 30%. The elderly group older than 60 years old is more likely to have inconsistent results, and tIgE level, sIgE level, the number and type of positive allergens also affected the consistency of tIgE and sIgE results.

P2X7R (P2X purinoceptor 7) is a ligand-gated ion channel that acts as a specialized sensor of tissue damage and a key regulator of cutaneous immunity via extracellular ATP signaling. This review systematically synthesizes evidence on P2X7R expression, mechanisms, and therapeutic targeting across skin disease models and clinical samples. P2X7R displays remarkable functional plasticity: driving NLRP3/Th17 inflammation in psoriasis, disrupting T-cell homeostasis in lupus, facilitating pathogen clearance in infections, exerting dual effects in melanoma, governing allergic responses, and promoting keratinocyte migration during wound healing. Mechanistically, P2X7R orchestrates inflammasome activation, cytokine release, cell proliferation, apoptosis, and immune regulation. Targeted antagonists demonstrate preclinical efficacy, though optimal delivery strategies remain critical. In conclusion, P2X7R emerges as a pivotal molecular hub in skin pathophysiology. Successful clinical translation requires cell-specific targeting and precise modulation rather than global inhibition.

Systemic lupus erythematosus (SLE) represents a prototypical autoimmune disorder characterized by multi-organ involvement due to loss of immune tolerance. Emerging evidence implicates macrophage polarization dynamics as a pivotal contributor to SLE pathogenesis, with epigenetic regulation by long noncoding RNAs (lncRNAs) emerging as a critical regulatory mechanism. To elucidate the pathogenic role of exosome-derived lncRNAs in this process, we performed comprehensive RNA sequencing analysis on circulating exosomes from SLE patients, identifying lncRNA H19 as a significantly upregulated candidate. Subsequent functional analyses using primary murine macrophages demonstrated that exogenous H19 administration recapitulated the pro-inflammatory phenotype observed in SLE, as evidenced by enhanced M1 macrophage differentiation, transmigration capacity, and renal infiltration patterns in experimental models. Notably, we primarily identified lncRNA H19 as a potential indicator in SLE, the knockdown of which might significantly attenuate these pathological manifestations. Mechanistic investigations revealed that H19 promoted the proliferation and migration of macrophages in vitro and exerted its regulatory function through competitive binding to miR-145-5p, thereby derepressing PAI-1 expression and subsequently activating the JAK2-STAT3 signaling cascade to orchestrate pro-inflammatory cytokine production. Overall, this study reveals novel molecular mechanisms underlying immune dysregulation in SLE, establishing exosomal lncRNA H19 as a key epigenetic modulator of macrophage polarization via the miR-145-5p/PAI-1/STAT3 axis, and proposes a novel potential therapeutic target for restoring immune homeostasis in patients with SLE before clinical practice.

Purpose:Optoelectronic advances have boosted interest in noninvasive rosacea treatments. Among them, pulsed dye laser (PDL), intense pulsed light (IPL), and radiofrequency (RF) therapy have been used to treat erythematotelangiectatic rosacea (ETR), and some therapeutic effects have been reported, but comparative studies are lacking. This study aimed to compare the efficacy and safety of PDL, IPL, and RF therapy for the treatment of ETR. Patients and Methods:A retrospective evaluation was conducted of patients with ETR who completed phototherapy between June 2019 and June 2024. The treatment protocol included two sessions of 585 nm PDL therapy (6-week interval), three sessions of IPL (M22 590 filter) therapy (590-1200 nm, 4-week interval), or six sessions of multisource 3DEEP RF therapy (2-week interval), with a follow-up visit at 12 weeks post-final treatment. The clinical efficacy evaluation consisted of the Clinician Erythema Assessment (CEA) scale, patient self-assessment (PSA) scale, the overall efficacy rate, and the Rosacea-Specific Quality of Life instrument (RosaQoL). Safety was evaluated in terms of adverse reactions such as pain, purpura, erythematous edema, blistering, hyperpigmentation, and scarring. Results:This study included 120 patients with ETR treated with PDL, M22 590, or RF therapy. Intragroup analysis revealed significant decreases in the CEA scale, PSA scale, and RosaQoL scores after treatment (p<0.001). The efficacy rates were 57.50%, 45.00%, and 67.50% for PDL, M22 590, and RF therapy, respectively, and no statistically significant intergroup differences were observed. Safety analysis confirmed that all the treatments were well tolerated. Conclusion:PDL, IPL and RF therapy all produced short-term improvements in erythema and quality of life in patients with ETR. RF showed comparable efficacy with better tolerability, suggesting a comfortable, low downtime option, while PDL and IPL are vascular-targeted tools. These exploratory findings require confirmation in longer, dose-standardized prospective studies.

BACKGROUND:Atopic comorbidities are common in chronic spontaneous urticaria (CSU), yet their impact on clinical presentation and omalizumab response remains poorly defined. OBJECTIVE:To compare clinical profiles and omalizumab treatment outcomes in CSU patients with atopic dermatitis (AD) and other atopic comorbidities (OACs). METHODS:This single-center retrospective study included 381 CSU patients treated with ≥3 doses of omalizumab (300 mg/4 weeks) and followed ≥6 months (January 2023-March 2025). Based on the presence or history of atopic comorbidities, patients were stratified into 3 groups: CSU with AD (CSU-AD, n = 76), CSU with OACs (CSU-OACs, n = 93), and CSU with no atopic comorbidities (CSU-NA, n = 212). Clinical features, treatment response (efficacy, speed, and adverse events), and-among 12-month completers-dose reduction/discontinuation and drug survival rates were analyzed. RESULTS:Of all enrolled patients, 44.4% had comorbid allergic diseases. CSU-OACs patients had earlier onset (P = 0.033) and higher angioedema prevalence (P = 0.042); CSU-AD showed higher baseline UAS7 (P = 0.031). Overall omalizumab response rates did not differ significantly among the 3 groups (P = 0.115), but a significantly higher portion of faster-response speed was observed in CSU-OAC (P = 0.019). Adverse events were significantly higher in CSU-OACs (P = 0.004), especially injection-site reactions (P = 0.033) and systemic effects (eg, headache and fatigue; P = 0.025). Drug survival was significantly higher in the CSU-OAC vs. CSU-NA group (P = 0.007). CONCLUSION:CSU-AD differs only in higher baseline activity, otherwise resembling CSU-NA in treatment response and drug survival. CSU-OACs exhibit not only distinct features such as earlier onset, higher angioedema risk, faster response, and higher drug survival but also more adverse events, indicating that CSU-OAC requires individualized management. Larger multicenter studies are needed to further define the impact of AD and OACs in CSU.

Skin wound healing, a complex biological process that is critical for restoring barrier function, remains a significant clinical challenge. The aim of this study was to investigate the role of meteorin-like (Metrnl) in acute cutaneous wound repair and the underlying mechanisms involved. In a rat full-thickness skin wound model, Metrnl expression was dynamically upregulated, peaking on Day 4 after injury. Topical application of recombinant Metrnl protein (rMet) significantly accelerated wound closure and improved healing quality, as evidenced by increased re-epithelialization, collagen deposition, and epithelial-mesenchymal transition (EMT) marker expression (E-cadherin downregulation; vimentin and N-cadherin upregulation). In vitro, rMet promoted the proliferation and migration of primary rat epidermal keratinocytes (REKs). This finding was further validated by Metrnl overexpression and knockdown. Transcriptomic analysis of wounded rat skin and rMet-stimulated REKs revealed that EMT-related differentially expressed genes (DEGs) were enriched in the PI3K-Akt pathway, among other pathways. Mechanistically, Metrnl activated the c-Kit/Akt/FoxO3a axis in a time-dependent manner; rMet induced the phosphorylation of c-Kit, Akt, and FoxO3a, triggering FoxO3a nuclear export. Inhibitor experiments confirmed that FoxO3a translocation depended on c-Kit/Akt activation. Furthermore, FoxO3a activated Smad7 transcription, whereas Metrnl antagonized this effect, thereby regulating EMT through Smad7 and EMT-related molecules. In conclusion, Metrnl accelerates wound healing by promoting keratinocyte proliferation and migration via the c-Kit/Akt/FoxO3a axis, modulating Smad7 expression and EMT progression. These findings highlight Metrnl as a potential therapeutic target for increasing wound repair.

Alopecia areata (AA) and androgenetic alopecia (AGA) both present with hair loss but require different therapies, and reliable biomarkers to guide treatment remain lacking. We integrated bulk and single-cell RNA-seq to compare JAK–STAT signaling in AA versus AGA. In AA, 257 immune-enriched differentially expressed genes (DEGs) were identified; WGCNA and consensus machine learning (LASSO, SVM-RFE, random forest) yielded six candidate hub genes, and external validation narrowed these to four key genes–granzyme A (GZMA), interleukin-2 receptor β (IL2RB) and γ (IL2RG) chains, and eomesodermin (EOMES). Building on these biology-anchored features, we introduced an interpretable few-shot deep learning classifier as an explainable AI alternative to a nomogram: bulk expression profiles are projected onto pathway/cell-type–aligned MultiPLIER latent variables (a frozen prior), the latent channels are re-weighted via element-wise multiplication with the expression levels of the key hub genes, and a Relation-style set-to-set comparator then aggregates support–query similarities (Hadamard mapping + permutation-invariant aggregation) before a shallow head predicts AA versus control. This prior-informed approach enables robust discrimination under limited sample conditions while retaining mechanistic interpretability, thereby exemplifying a next-generation XAI solution for small-cohort genomic diagnosis. Cross-database functional annotation and wet-lab validation (RT-qPCR and Western blot) in independent AA/AGA/healthy scalp samples confirmed that the IL2RB/IL2RG–EOMES–GZMA axis is selectively activated at both mRNA and protein levels in AA. Single-cell analysis localized GZMA to cytotoxic T cells and IL2RG to proliferating lymphocytes, outlining an EOMES+CD8+ T-cell GZMA–IL2RB/IL2RG cytotoxic loop driving JAK–STAT hyperactivation in AA. Drug–gene network analysis linked these targets to JAK inhibitors and cyclosporine. AGA showed no comparable JAK–STAT perturbation, consistent with its androgen-centric biology. In summary, this four-gene loop provides a non-invasive AA biomarker and a tractable target for precision JAK blockade, while the proposed few-shot framework offers a general, prior-driven alternative to nomograms for transcriptomic diagnosis in small cohorts, illustrating an XAI-driven diagnostic approach for precision medicine.

BACKGROUND:Tenosynovial giant cell tumor (TGCT) comprises localized (L-TGCT) and diffuse (D-TGCT) subtypes, but how ferroptosis regulators, tumor-associated immune-cell markers and proliferation indices jointly relate to subtype and recurrence is poorly defined. We explored ACSL4, GPX4, CD8, CD163, CSF1R and Ki-67 as candidate markers for subtype discrimination and recurrence prediction in TGCT. METHODS:This single-center, retrospective cross-sectional study included 49 consecutive patients with histologically confirmed TGCT (25L-TGCT, 24 D-TGCT) treated between 2008 and 2022. Archival FFPE specimens were analyzed. Iron deposition and marker expression were quantified via Prussian blue staining and blinded, standardized immunohistochemistry, with integrated optical density (IOD) measured by digital image analysis. Group comparisons used appropriate statistical tests. Receiver-operating characteristic (ROC) analysis with bootstrap 95% CIs was performed to assess single and combined biomarkers for subtype discrimination and recurrence prediction. RESULTS:D-TGCT specimens showed significantly higher iron deposition, ACSL4, CD163, CSF1R, and Ki-67 expression, along with lower GPX4 and CD8 levels than L-TGCT (all P < 0.05). Recurrent cases (11/49) exhibited similar molecular patterns, with elevated iron, CD163, CSF1R, Ki-67, and reduced GPX4/CD8 (all P < 0.05). The ACSL4+CD8 combination discriminated subtypes with an AUC of 0.992. The Ki-67+CSF1R+tumor diameter model predicted recurrence with an AUC of 0.988. CONCLUSIONS:Ferroptosis, immune, and proliferation markers differ significantly between TGCT subtypes and recurrence status. The ACSL4+CD8 signature shows excellent potential for subtype differentiation, while the Ki-67+CSF1R+tumor diameter index is a strong recurrence predictor. These exploratory findings support targeted biomarker use in TGCT management, though external validation in larger, prospective cohorts is required.

Atopic dermatitis (AD) is a prevalent chronic skin disease worldwide. Emerging evidence suggests that an elevated salt microenvironment is a unique characteristic of skin lesions in AD patients. Emerging data indicate that lesional skin in AD contains abnormally high salt, yet how this microenvironment affects keratinocytes is unknown. We interrogated the impact of elevated NaCl on barrier function and inflammation using HaCaT cells in vitro, and 2,4-dinitrofluorobenzene (DNFB) and ovalbumin (OVA) treatment induced an AD model of mice in vivo. The interaction between SGK-1, mTOR, STAT3, and NFκB was identified with their roles in AD, analyzed through loss-of-function assays and pharmacological inhibitions. Our results showed that the high-salt microenvironment impaired keratinocyte differentiation and promoted inflammatory cytokine production, thereby exacerbating the disease. Mechanistically, NaCl activated STAT3 via the SGK-1-mTOR signaling pathway in keratinocytes, leading to a decrease in the expression of epidermal barrier proteins. In addition, inflammatory cytokines were increased by NaCl-induced SGK-1-mTOR-NFκB activation. We identified the SGK-1 inhibitor GSK 650394, which could rescue the NaCl-induced blockade of keratinocyte differentiation and inflammatory cytokine production. Moreover, in combination with the JAK inhibitor delgocitinib, GSK 650394 exhibits a synergistic effect in ameliorating AD-like symptoms in vivo. Taken together, our findings demonstrate that the high-salt microenvironment promotes the development of AD by activating the SGK-1-mTOR pathway in keratinocytes, suggesting that an SGK-1 inhibitor could potentially serve as a drug to alleviate AD-like symptoms.

BACKGROUND:Evidence regarding the feasibility of Janus kinase inhibitors tapering following adequate response in moderate-to-severe atopic dermatitis (AD) remains limited, and no head-to-head comparisons of tapering regimens have been conducted. OBJECTIVE:To evaluate the feasibility of 24-week abrocitinib tapering in moderate-to-severe AD patients having achieved adequate response and compare 2 tapering methods. METHODS:This retrospective study enrolled moderate-to-severe AD patients who achieved adequate clinical response with abrocitinib and underwent tapering over 24 weeks via dose reduction or interval extension. RESULTS:A total of 78 patients (36 dose reduction, 42 interval extension) were included, and successful tapering was achieved in 76 (97.4%). Nonrelapse rates were 97.4% and 91.0% at weeks 12 and 24, respectively. At week 24, mean cumulative dose was reduced by 9892 mg (6908 mg vs 16,800 mg standard), with cost savings of ¥ 2899.5 (¥ 2016.7 vs ¥ 4916.2 projected). Patients with extended dosing intervals had significantly higher strategy-switch rates due to disease fluctuation [28.6% (12/42) vs 8.3% (3/36), P = .041]. LIMITATIONS:The single-center retrospective design, small sample size, and relatively short follow-up duration. CONCLUSION:Twenty-four-week abrocitinib tapering appears feasible in well-responding moderate-to-severe AD patients, reducing treatment burden while preserving efficacy.