Psoriasis is a chronic immune-mediated inflammatory skin disorder, with plaque psoriasis being the most common clinical subtype, especially in elderly patients. Conventional therapies often provide suboptimal outcomes, necessitating the exploration of novel treatment approaches. This study evaluates the clinical efficacy of combining Secukinumab with Calcipotriol Cream in elderly patients with moderate to severe psoriasis. A total of 160 elderly patients (≥ 65 years) with plaque psoriasis were retrospectively analyzed between January 2020 and December 2024. All patients received baseline therapy with oral acitretin and topical clobetasol. The observation group (n = 80) additionally received secukinumab and calcipotriol cream. The control group (n = 80) received baseline therapy only. The primary endpoint was overall clinical efficacy based on Psoriasis Area and Severity Index (PASI) improvement. Secondary endpoints included changes in PASI scores, Dermatology Life Quality Index (DLQI), skin barrier parameters (stratum corneum hydration and sebum content), and incidence of adverse events over 12 weeks. The total efficacy rate was significantly higher in the observation group than in the control group (90.0

The clinical efficacy and safety of Dupilumab in the treatment of moderate-to-severe atopic dermatitis (AD) in elderly patients, particularly those over 60 years of age, remains an area requiring further investigation. To address this gap, we conducted a 16-week, single-center, prospective, open-label study at Huashan Hospital affiliated with Fudan University. A total of 110 elderly patients with moderate-to-severe AD were enrolled and received Dupilumab treatment. The primary objective was to evaluate the clinical response and safety profile of Dupilumab in this specific age group under real-world conditions. Patients were systematically assessed at multiple time points: baseline (week 0), week 2, week 4, week 8, week 12, and week 16. Key clinical indicators included the Eczema Area and Severity Index (EASI), the Itching Numerical Rating Scale (NRS), the Dermatology Life Quality Index (DLQI), and the Investigator's Global Assessment (IGA) score. We also calculated the proportion of patients achieving EASI-50, EASI-75, and EASI-90, representing improvements of 50%, 75%, and 90% from baseline, respectively. In addition, laboratory parameters such as serum total IgE levels and blood eosinophil counts were measured at weeks 0, 4, and 16 to evaluate changes in biomarkers associated with AD. All adverse events occurring during the treatment period were documented to assess safety. Among the 110 participants, 78 (70.9%) were male and 32 (29.1%) were female, with a mean age of 72.42 +/- 11.64 years. The results demonstrated that Dupilumab led to early and sustained improvements across all efficacy endpoints. By week 16, a significant majority of patients had achieved meaningful clinical responses: 83.36% attained EASI-50, 71.82% reached EASI-75, and half of the study population (50.91%) achieved EASI-90. Moreover, 69.09% of patients attained an IGA score of 0 or 1, indicating clear or almost clear skin. Laboratory findings further supported the clinical benefits, with statistically significant reductions in both serum total IgE and eosinophil counts by week 16 compared to baseline in patients who had elevated levels initially. Regarding safety, Dupilumab was well-tolerated in the elderly cohort. Adverse events were reported in 13 patients (11.8%), the most common being injection site pain (7 cases, 6.4%) and ocular discomfort, such as conjunctivitis or dry eyes (4 cases, 3.6%). Most adverse events were mild to moderate in severity. In conclusion, this real-world study indicates that Dupilumab offers favorable efficacy and an acceptable safety profile for the treatment of moderate-to-severe atopic dermatitis in elderly Chinese patients. These findings support its use in this growing patient population, although longer-term observational studies are warranted to further confirm its sustained benefits and safety.

Background and objectiveAtopic dermatitis (AD) is a chronic immune-mediated inflammatory skin disease characterized by persistent pruritus and eczematous lesions. Its core pathophysiology involves Th2-skewed immune responses and epidermal barrier dysfunction. Plasmacytoid dendritic cells (pDCs), known for their potent production of type I interferons, have demonstrated immunomodulatory roles in various diseases, including allergic asthma. However, their specific function and underlying mechanisms in AD remain poorly defined. This study aims to investigate the role of pDCs in AD and elucidate their molecular regulatory pathways.MethodsWe employed an integrative approach combining transcriptomic analysis, flow cytometry, an MC903-induced murine model of AD, in vivo expansion of pDCs using FLT3L, targeted depletion of pDCs with the 120G8 antibody, and IFNAR1-deficient mice. These complementary strategies were used to systematically evaluate the distribution, activation status, and immunological function of pDCs in AD, as well as the mechanisms involved.ResultspDCs were significantly elevated in the peripheral blood of AD patients and were associated with increased expression of Th2 cytokines. In the MC903-induced murine model, pDCs showed dynamic accumulation in skin lesions and draining lymph nodes. Expansion of pDCs by FLT3L markedly alleviated AD-like skin inflammation, suppressed Th2 cytokines (IL-4, IL-13) and IgE production, and enhanced the expression of epidermal barrier proteins. In contrast, depletion of pDCs by 120G8 exacerbated the inflammatory phenotype. Importantly, the anti-inflammatory effects of pDCs were abolished in IFNAR1-deficient mice, indicating that pDCs exert their immunosuppressive function in AD primarily through the IFN-α/IFNAR signaling axis.ConclusionThis study is the first to systematically demonstrate the immunosuppressive role of pDCs in AD. We show that pDCs negatively regulate Th2 inflammation and maintain barrier integrity via the IFN-α/IFNAR1 pathway. These findings provide a theoretical and experimental foundation for targeting pDCs and their downstream signaling as a novel therapeutic strategy in AD.

Skin microbial dysbiosis is a key characteristic of atopic dermatitis (AD). Although Cutibacterium acnes (C. acnes) is the most abundant bacterium in the skin microbiota, its precise functions in AD remain unclear. Here, whole-genome sequencing of C. acnes isolates reveals strain-level genomic and functional heterogeneity between AD patients and healthy individuals. Metabolomic profiling identifies reduced indolelactic acid (ILA), a tryptophan metabolite, in AD skin and in cultures of AD-associated C. acnes strains. In murine models of epidermal-barrier-damaged and AD-like dermatitis, topical ILA application activates the aryl hydrocarbon receptor (AhR) pathway in keratinocytes, upregulating tight junction proteins and suppressing interleukin (IL)-33 to restore barrier integrity and mitigate dermatitis. A proof-of-concept clinical trial confirms ILA’s efficacy in reducing transepidermal water loss and alleviating AD symptoms. Our study establishes C. acnes-derived ILA as a crucial regulator of skin barrier repair via AhR signaling, offering therapeutic potential for AD. Clinical trial registration: ChiCTR2400090988.

Background:Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition that affects approximately 10% to 20% of children, imposing substantial health and economic burdens. Although education for patients and caregivers is acknowledged as a crucial element in the management of AD, conventional approaches, such as workshops or in-person consultations, are often resource intensive and face challenges related to scalability, personalization, and relapse prevention. Digital tools present promising alternatives; however, empirical evidence supporting their effectiveness in young children is currently limited. Objective:This study aimed to evaluate whether a smartphone-based patient-caregiver educational program could reduce relapse rates in children aged 0 to 6 years with moderate-to-severe AD, compared with conventional outpatient consultation alone. Methods:In this multicenter, randomized, parallel-controlled trial, 615 children were enrolled across 12 tertiary pediatric dermatology centers in China and randomized (1:1) to receive either a smartphone-based digital education program with standard care (intervention group) or conventional face-to-face consultation only (control group). The 12-week digital program, delivered via the WeChat-based Skin Care E-Station platform, included structured multimedia modules, interactive educational materials, and a dynamic electronic action plan tailored to the child's age and disease stage. The primary endpoint was the 12-week relapse rate after the acute treatment phase. The secondary endpoints included changes in disease severity (Scoring Atopic Dermatitis, Peak Pruritus Numerical Rating Scale, and Patient-Oriented Eczema Measure) and quality of life (Children's Dermatology Life Quality Index or Infant's Dermatitis Quality of Life Index and Dermatitis Family Impact) up to 52 weeks. Results:Among 615 randomized participants (mean age 3.3, SD 1.7 y; n=317, 51.5% male), relapse at 12 weeks occurred significantly less frequently in the digital education group than in the control group (16.6% vs 24.0%; relative risk 0.69, 95% CI 0.50-0.96; P=.02). Kaplan-Meier analysis showed superior relapse-free survival over the first 100 days (hazard ratio 0.688, 95% CI 0.490-0.966; P=.03). Differences in relapse rates beyond 12 weeks and in secondary outcomes were not statistically significant. Engagement tracking indicated high adherence to the intervention, with 58.0% of caregivers maintaining regular weekly use of the digital platform. Conclusions:A structured smartphone-based patient-caregiver educational intervention significantly reduced short-term relapse risk among young children with moderate-to-severe AD, likely through improved caregiver recognition and early management of disease flares. Although effects diminished beyond 12 weeks, this approach demonstrates that scalable digital education is a feasible and effective adjunct to standard care in pediatric AD. Future research should focus on sustaining engagement, optimizing long-term reinforcement, and assessing cost-effectiveness in diverse caregiver populations.

Abstract Background: Immune checkpoint inhibitors (ICIs) improve the prognosis of advanced esophageal cancer (ESCA), yet accurate response prediction remains challenging. Traditional biomarkers and imaging often lack timely reflection of disease progression. Circulating tumor DNA (ctDNA) methylation offers novel, non-invasive, real-time monitoring. In this study, we evaluated the early dynamic ctDNA methylation changes in advanced ESCA and predicted ICI response and survival. Methods: This observational exploratory study enrolled advanced ESCA patients on ICI treatment.Peripheral blood samples were collected at baseline and regularly throughout treatment.Plasma ctDNA was subjected to methylation sequencing. Patients were stratified into "decreased" (methylation score reduction from baseline) and "non-decreased" (stable or increased scores) groups based on dynamic changes. Kaplan-Meier and log-rank tests assessed methylation score dynamics' association with progression-free survival (PFS) and overall survival (OS). Consistency between ctDNA dynamics and imaging efficacy (RECIST 1.1) was also evaluated. Results: Baseline ctDNA methylation levels did not significantly correlate with outcomes (p=0.1); however,dynamic changes were strongly prognostic. The "decreased" group demonstrated significantly longer PFS (26.0 vs. 15.85 months; p<0.05) and median OS (35.0 vs. 27.0 months; p=0.01) compared to the "non-decreased" group. CtDNA-defined response occurred significantly earlier than radiological response (1.55 vs. 4.0 months, p<0.05). Median time to ctDNA-defined progression (2.52 vs. 4.0 months) also preceded imaging progression, without statistical significance (p=0.15). Conclusion: Dynamic ctDNA methylation monitoring presents a promising non-invasive approach for assessing ICI efficacy in advanced ESCA. A reduction in post-treatment ctDNA methylation levels significantly correlated with prolonged survival. ctDNA dynamics enabled earlier prediction of treatment response and progression than radiological assessment, highlighting its potential for timely detection. These findings underscore the value of dynamic ctDNA methylation analysis as a novel early efficacy marker. FUNDING: This study was supported by the National Natural Science Foundation of China (Grant No. 81702414), Natural Science Foundation of Fujian Province of China (Grant No. 2020J05306) and Xiamen Medical and Health Guidance Project (Grant No. 3502Z20244ZD1023). Citation Format: Hui Zhang#, Yu Lang#, Yaping Dong#, Wei Li#, Jialin Lin, Lu Yang, Jiapeng Kang, Wenqiang Yu, Changshun Yang, Jingxun Wu, Qiyuan Li, Feng Ye, Weiwei Tang. Dynamic changes in ctDNA methylation predict early response to immunotherapy in advanced esophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5310.

The number of patients with skin diseases visiting hospitals in China has been increasing over the past few decades. Hospital-based analysis of outpatient populations may provide insights into the epidemiology of skin diseases. To explore the epidemiology of skin diseases at the hospital level, this study conducted a cross-sectional analysis by extracting and comparing medical information from 863,466 outpatient visits in 2018 and 1,250,032 in 2023 at the dermatology clinic of Huashan Hospital. Both years of data showed that atopic dermatitis (AD) and acne were the most frequently recorded diseases, followed by vitiligo, infectious skin diseases, psoriasis, urticaria, alopecia, and seborrheic dermatitis. The female-to-male patient ratio was 1.12. The prevalence of dermatological conditions also varied across different age groups. Infectious skin diseases, photosensitivity, and vitiligo were most frequently observed during the summer months, whereas alopecia tended to increase in the fall. Approximately 30.7

Abstract Tumor-infiltrating lymphocyte (TIL) therapy has become a promising immunotherapy for the treatment of solid tumors and has shown substantial therapeutic potential in recent years, offering new options for patients with cancer. Despite its encouraging clinical outcomes, TIL therapy continues to face several research challenges and unresolved issues. Interleukin-2 (IL-2) is a key cytokine in TIL therapy and plays a critical role by promoting TIL proliferation and enhancing their anti-tumor activity. However, the administration of IL-2 may also lead to a range of adverse effects. This study reviews recent clinical research progress in TIL therapy, with particular emphasis on the dual role of IL-2 in this treatment approach. By examining current clinical trial data and recent research findings, this study evaluates both the beneficial effects and potential risks of IL-2 in TIL therapy and aims to provide guidance for future research and clinical practice.

CONTEXT:Skin photoaging induced by chronic ultraviolet B (UVB) exposure is primarily driven by oxidative stress. Emerging evidence suggests that ferroptosis contributes to UVB-induced skin damage. Sauchinone, a phenolic lignan derived from Saururus chinensis, possesses potent antioxidant and anti-inflammatory properties; however, its protective effects and underlying mechanisms against UVB-induced skin damage remain unclear. OBJECTIVE:This study aimed to investigate the potential photoprotective effects and underlying mechanisms of sauchinone against UVB-induced skin damage in dermal fibroblasts. MATERIALS AND METHODS:UVB-induced HFFs were used as an in vitro model of photoaging. Cellular senescence, extracellular matrix (ECM) degradation, oxidative stress, and ferroptosis were evaluated using fluorescence staining, flow cytometry, qPCR, ELISA, and western blot analysis. RESULTS:Sauchinone significantly attenuated cellular senescence and ECM degradation in UVB-induced HFFs, as evidenced by reduced SA-β-gal activity and decreased expression of p16 and p21, increased COL1A1 levels, and decreased MMP1 levels. Sauchinone also alleviated oxidative stress by reducing intracellular ROS and MDA levels while restoring GSH content and antioxidant enzyme activity. In addition, sauchinone attenuated ferroptosis-related features, including reduced lipid ROS and Fe2+ accumulation, and normalized ACSL4, GPX4, FTH1, and SLC7A11 expression. Mechanistically, sauchinone was associated with activation of the Keap1-Nrf2 pathway, as evidenced by decreased Keap1 levels, enhanced nuclear translocation of Nrf2, and upregulation of downstream antioxidant genes. Importantly, pharmacological inhibition of Nrf2 using ML385 partially reversed the protective effects of sauchinone on oxidative stress, ferroptosis, cellular senescence, and ECM degradation. DISCUSSION AND CONCLUSIONS:Our findings revealed that sauchinone protected fibroblasts against UVB-induced photoaging by inhibiting oxidative stress and ferroptosis, potentially through activation of the Keap1-Nrf2 pathway.

Atopic dermatitis (AD) is a chronic, systematic inflammatory dermatosis with a high prevalence worldwide, characterized by multiple heterogeneities. Recent studies have highlighted variations in the incidence and manifestation of AD among different ethnic populations due to genetic and immunological differences. The severity of AD also varies by anatomical sites, influenced by factors such as regional skin microenvironment, microbiome-immune interaction, and environmental exposure. Notably, head and neck dermatitis (HND) is a refractory phenotype of AD, which responds less well to conventional and novel systemic treatment. Furthermore, distinct susceptibility factors exist across age groups, including food allergies in infants and young children, psychological stress in adults, and aging-related AD in the elderly. The heterogeneity of AD requires further exploration of the pathogenesis in different states, which also poses a significant challenge for therapy. This review synthesizes current evidence on AD heterogeneity, elucidating variations across ethnicities, anatomical sites, and age groups to guide the development of precision treatment.

Epithelioid sarcoma (ES) is a rare mesenchymal tumor categorized into proximal (axial) and classical (distal) types. In general, proximal ES come alone with limited treatment options and poor prognosis. Herein, we present the case of a proximal ES treated with a tazemetostat-containing regimen and achieved a favorable response in the third-line setting. A 44-year-old Han woman was noticed a left pelvic floor nodule by computed tomography (CT) scan, and histologically test result confirmed her diagnosis as epithelioid sarcoma (proximal type). Cell staining indicates a negative expression of INI1 but positive expression of PD-L1. Ifosfamide and adriamycin (IA) were introduced as first-line treatment because of multidisciplinary treatment (MDT) of soft-tissue tumor considered tumor invasion is extensive, not eligible to complete surgical resection. Unfortunately, IA was discontinued due to patient intolerance (severe myelosuppression). Anlotinib was used as second-line treatment after rapid disease progression and also discontinued due to vaginal hemorrhage. After the pathology diagnosis, the combination therapy of tislelizumab and tazemetostat was introduced. A significant tumor shrinkage was noticed after 21 months of follow-up, which achieved and continue to maintain a partial response (PR) with further tumor reduction. This case first reported a favorable response of primary proximal epithelioid sarcoma treated with EZH2 inhibitor tazemetostat and PD-1 inhibitor tislelizumab, suggesting a potential and well-tolerated treatment regimen for this rare disease.

ABSTRACT Barrier tissues such as skin, gut, and lung are critical for maintaining homeostasis and preventing pathogen invasion. However, they constantly face microbial, environmental, and mechanical challenges. Fibroblasts, the primary mesenchymal cells within these tissues, are no longer seen as passive structural elements. They show tremendous heterogeneity and plasticity beyond their conventional role, allowing them to act as active immune participants in inflammation. As an immune participant, fibroblasts are capable of undergoing phenotypic alterations in pathological conditions. They are able to release signaling molecules including chemokines and cytokines, remodel extracellular matrix, or even present antigens. The inflammatory landscape is thus shaped. This review integrates recent advances in exploring fibroblast plasticity in barrier inflammation. We summarize their roles in initiating, progressing and resolving inflammatory responses across the skin, gut and respiratory tract. Specific focus is placed on fibroblast–immune cell interactions, key signaling pathways, and the roles of specific subsets in inflammatory conditions. By integrating what has been investigated from single‐cell and multi‐omics analyses, this article highlights fibroblasts as both essential mediators of barrier inflammation and promising targets for targeted treatment.

Background:The prognosis of gastric cancer (GC) patients with human epidermal growth factor receptor 2 (HER2) positive was poor. To illustrate the underlying effective and distinctive molecular characteristics of programmed cell death protein 1 (PD-1) blockade in the treatment of GC with HER2 positive, we analyzed the survival outcome of PD-1 inhibitors combination regimen as the first-line treatment for GC patients with HER2-positive in China. Methods:This retrospective real-world study compared the prognoses of first-line systemic treatment of PD-1 inhibitors combined with trastuzumab and chemotherapy (PTC group) and trastuzumab and chemotherapy (TC group) in Chinese patients with HER2-positive GC, and then further to identify the specific and molecular characteristics of PD-1 inhibitors treatment by hierarchical analysis. The patients were matched using propensity score matching (PSM). Overall survival (OS) and progression-free survival (PFS) were used as the primary and secondary endpoints of the study. Results:A total of 95 patients with HER2-positive GC receiving first-line treatment at Zhongshan Hospital of Fudan University from January 2019 to September 2022 were included. The median OS (24.67 vs. 16.00 months, P=0.01) and median PFS (15.57 vs. 7.57 months, P=0.008) of patients with HER2-positive GC who received PTC regimen were longer than those treated by TC regimen as first-line systemic treatment after PSM analysis. In hierarchical analysis, we discovered that programmed cell death ligand 1 (PD-L1) positive expression in tumor tissues was not a predictor of PD-1 inhibitors in HER2-positive GC. However, PD-L1 was an indicator of better survival outcomes by combined trastuzumab treatment in all GC patients. Furthermore, in the subgroup analysis, we found that the median OS for the PTC group was longer by nearly 8 months than the TC group in patients with HER2 gene copy number [HER2 fluorescence in situ hybridization (FISH) test] more than six, while the median OS for the PTC group was longer by approximately 12 months than the TC group in patients with HER2-positive GC with TP53 mutations. Conclusions:The results suggested that patients with HER2-positive GC could benefit from PD-1 inhibitors combination with trastuzumab and chemotherapy, especially patients with HER-2 FISH more than six and TP53 mutations.

Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.

HBV integration is considered as the main contributor to hepatocellular carcinoma (HCC). However, whether HBV integrated sequences determine genotype pathogenicity and how to block their function during HCC progression remains unclear. An in vitro HBV-infected PHH model and liver cancer cell lines were established to confirm the pathogenic potential of HBV-SITEs. The roles of HBV-SITE-1 in HCC development were analyzed using cellular phenotypic assays and molecular biology techniques, including the combined analysis of RNA-seq and ChIP-seq. Animal models were also used to evaluate the therapeutic effect of HBV-miR-2 inhibitors. We identified nine fragments of HBV Sequences Integrated To Enhancer, termed as “HBV-SITEs”. Particularly, a single nucleotide variation (T > G) was embedded at seed sequence of HBV-miR-2 in the highest integrated HBV-SITE-1 between genotypes B and H. Unexpectedly, B-HBV-SITE-1, not H-HBV-SITE-1, could abnormally activate oncogenic genes including TERT and accelerate HCC cell proliferation and migration. Meanwhile, HBV-miR-2 was gradually increased in HBV-infected cells and patient plasma with different HCC stages. Importantly, 227 genes upregulated by HBV, were also activated by HBV-miR-2 through triggering HBV-SITE-1 enhancer. Conversely, enhancer activities were particularly decreased by HBV-miR-2 inhibitors, and further downregulated activated oncogenic genes. Finally, HCC growth was dramatically restrained and HBV-induced transcripts were systematically reduced via injection of HBV-miR-2 inhibitors in animal models. HBV-SITEs were identified as novel oncogenic elements for HCC, which provides an insightful perspective for the other cancers caused by oncogenic DNA viruses. We demonstrated that the integrated HBV sequence itself acted as oncogenic enhancers and nucleotide variations of HBV genotypes account for particular pathogenic progression, supporting that the viral nucleotide sequences are vital pathogenic substances beyond viral proteins. And modulation of their enhancer activities could be clinically achievable strategy for blocking DNA viruses-related cancer progression in the future.