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.

SSGJ-608 is a recombinant, humanized, immunoglobulin G1 monoclonal antibody that targets human interleukin-17A with high specificity and high affinity. We aimed to evaluate the efficacy and safety of SSGJ-608 in patients with moderate-to-severe psoriasis in China. Adult patients aged 18 years or older with moderate-to-severe plaque psoriasis were randomly assigned (2:2:1) to receive subcutaneous injections of placebo (placebo group), 80 mg of SSGJ-608 every 2 weeks after a starting dose of 160 mg at week 0 (608A group), or 160 mg of SSGJ-608 every 4 weeks (608B group). At week 12, patients in the 608A group received SSGJ-608 80 mg every 4 weeks, patients in the 608B group received SSGJ-608 160 mg every 8 weeks, and patients in the placebo group were re-allocated (1:1) to either the 608A or 608B group to receive 608 80 mg every 4 weeks (with an additional 160-mg loading dose of SSGJ-608 at week 12) or 160 mg every 8 weeks. All patients received treatment until week 48. The primary endpoints were a ≥75

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.

Artesunate (ART), a drug renowned for its anti-inflammatory and antiproliferative properties, shows promise in psoriasis treatment by potentially modulating autoimmune responses. This study evaluated the efficacy of ART in an imiquimod (IMQ)-induced mouse psoriatic model via topical application and intraperitoneal injection, alongside in vitro investigations using a HaCaT cell-based model. Our results demonstrated that topical ART application significantly alleviated psoriatic inflammation and hyperkeratinization and reduced Th17 and IL-17A+ γδ T-cell infiltration, proving superior to intraperitoneal administration. Notably, ART markedly suppressed the expression of the pathogenic keratins Krt16 and Krt17, which are crucial in psoriasis pathogenesis. In vitro, ART not only enhanced the anti-inflammatory effect of dexamethasone (DEX) by reducing pro-inflammatory cytokines (IL-1β, IL-6, IL-8) but also effectively counteracted the rebound elevation of CCL-20 exacerbated by DEX in the M4-stimulated model. Importantly, the topical application of ART presents a promising therapeutic strategy, particularly due to its potential to mitigate adverse effects associated with glucocorticoid therapies, such as those linked to CCL-20 rebound. Mechanistically, ART exerted these therapeutic effects primarily by inhibiting the phosphorylation of NF-κB p65 and STAT3 in keratinocytes. The findings underscore that ART ameliorates psoriasis-related inflammation and proliferation through modulating the NF-κB and STAT3 signaling pathways. The inflammatory response centered on IL-17A and the abnormal keratinization state are the most critical pathological processes in psoriasis, with the aberrantly expressed CCL-20 and Keratin17 (Krt17) via NF-κB and STAT3 pathways in keratinocytes serving as key molecular targets within these processes. In complementary and alternative medicine (CAM), ART combined with DEX is an ideal choice for anti-inflammatory treatment. In conclusion, the observed synergy between artesunate and glucocorticoids further highlights its potential in combination therapies.

Background: There remains unmet need for therapies for atopic dermatitis (AD) with favorable symptom control but less frequent dosing.Objective: To evaluate the benefits and safety of MG-K10, a humanized interleukin-4 receptor alpha-targeting antibody, in moderate-to-severe AD.Methods: In this multi-center, double-blind, randomized, phase II trial, 163 moderate-to-severe AD patients were randomized to receive 16-week treatment with MG-K10 150 mg every 4 weeks (Q4W), 300 mg every 2 weeks (Q2W) (n = 41), 300 mg Q4W (n = 41), or placebo (n = 40). Primary endpoint was the change in Eczema Area and Severity Index (EASI) scores from baseline to week 16.Results: The mean differences in EASI score at week 16 for the 300 mg Q4W, 300 mg Q2W, and 150 mg Q4W groups were -38.83% (95% confidence interval [CI]: -56.47% to -21.20%, P < 0.001), -27.06% (95% CI: -44.73% to -9.38%, P = 0.003), and -16.00% (95% CI: -33.66% to 1.67%, P = 0.076) compared with placebo group. The proportion of participants achieving EASI-75 at week 16 was 79.5%, 66.7%, 53.8%, and 28.9% in the 300 mg Q4W, 300 mg Q2W, 150 mg Q4W, and placebo groups. The incidence of adverse events was comparable across groups.Conclusion: MG-K10 demonstrates potential as a long-acting therapeutic option for managing symptoms of moderate-to-severe AD, with favorable safety profile. The preliminary efficacy and safety supported further validation of 300 mg Q4W in phase III trial.

PURPOSE:This study aims to evaluate the clinical efficacy, recurrence rate, and drug retention rate of plaque psoriasis with different severity levels treated with Ixekizumab. MATERIALS AND METHODS:A retrospective, multicenter, real-world study was conducted using the China Cathay database to analyze 354 Chinese patients with mild-to-moderate and severe psoriasis who received ixekizumab therapy. Psoriasis Area and Severity Index (PASI) 75/90/100 response rates, absolute PASI values, 3-year drug retention, and recurrence rates were assessed at 2, 4, 12, 24, and 52 weeks. RESULTS:The baseline PASI scores for the mild-to-moderate group (PASI <10) and severe group (PASI ≥ 10) were 5.6± 2.6 and 20 ± 11, respectively. Except for a difference in the proportion of male patients, there were no differences between the two groups in terms of age,duration of illness, hypertension, hyperlipidemia, cardiovascular diseases, gout and arthropathy. The mild-moderate group showed superior PASI75/90 responses at most timepoints and consistently higher PASI100 rates (all p < 0.05). Absolute PASI values were lower in mild-moderate patients at all timepoints except PASI90 (2/12 weeks) and PASI75 (24 weeks). Severe patients had longer 3-year drug retention (p = 0.007), while recurrence rates were comparable. CONCLUSIONS:Ixekizumab demonstrates superior efficacy in mild-moderate versus severe psoriasis, suggesting greater benefit with early biologic intervention.

Psoriasis is an immuno-inflammatory disease characterized by excessive keratinocyte proliferation, requiring extensive lipids. 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (HMGCS1) is an essential enzyme in the mevalonate pathway, involved in cholesterol synthesis and the inflammatory response. However, the role of HMGCS1 in psoriasis has remained elusive. This study aims to elucidate the mechanism by which HMGCS1 controls psoriasiform inflammation. We discovered an increased abundance of HMGCS1 in psoriatic lesions when analyzing two Gene Expression Omnibus (GEO) datasets and confirmed this in psoriatic animal models and psoriatic patients by immunohistochemistry. In a TNF-α stimulated psoriatic HaCaT cell line, HMGCS1 was found to be overexpressed. Knockdown of HMGCS1 using siRNA suppressed the migration and proliferation of HaCaT cells. Mechanistically, HMGCS1 downregulation also reduced the expression of IL-23 and the STAT3 phosphorylation level. In imiquimod-induced psoriatic mice, intradermal injection of HMGCS1 siRNA significantly decreased the expression of HMGCS1 in the epidermis, which in turn led to an improvement in the Psoriasis Area and Severity Index score, epidermal thickening, and pathological Baker score. Additionally, expression levels of inflammatory cytokines IL-23, IL1-β, chemokine CXCL1, and innate immune mediator S100A7-9 were downregulated in the epidermis. In conclusion, HMGCS1 downregulation improved psoriasis in vitro and in vivo through the STAT3/IL-23 axis.

INTRODUCTION:Bone marrow mesenchymal stem cell (BMMSC) transplantation is beneficial in treating Systemic lupus erythematosus (SLE); however, the underlying mechanism remains elusive. This study investigates the role of BMMSCs in regulating lymphocyte proliferation and cell cycle progression during SLE and delves into the contribution of BMMSC-produced galectin-1. METHODS:BMMSCs were co-cultured with T lymphocytes to assess their impact on suppressing CD4+ T cells in SLE patients. Proliferation and cell cycle distribution of CD4+ T cells were analyzed using flow cytometry. The expression of cell cycle-related proteins, including p21, p27, and cyclin-dependent kinase 2 (CDK2), was investigated through western blotting. Extracellular and intracellular galectin-1 levels were determined via ELISA and flow cytometry. The role of galectin-1 in CD4+ T cell proliferation and cell cycle was evaluated through RNAi-mediated galectin-1 expression disruption in BMMSCs. RESULTS AND DISCUSSION:BMMSCs effectively inhibited CD4+ T cell proliferation and impeded their cell cycle progression in SLE patients, concurrently resulting in a reduction in CDK2 levels and an increase in p21 and p27 expression. Moreover, BMMSCs expressed a high level of galectin-1 in the co-culture system. Galectin-1 was found to be critical in maintaining the suppressive activity of BMMSCs and restoring the cell cycle of CD4+ T cells. CONCLUSION:This study demonstrates that BMMSCs suppress the proliferation and influence the cell cycle of CD4+ T cells in SLE patients, an effect mediated by the upregulation of galectin-1 in BMMSCs.

BackgroundLupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE.ObjectivesWe aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes.MethodsThis is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study.ResultsIn the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% +/- 6.94% to 81.25% +/- 4.23% (p = 0.0004).ConclusionsThese results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

Background: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). Objective: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. Methods: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. Results: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. Conclusion: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

The epidemic and outbreaks of influenza B Victoria lineage (Bv) during 2019–2022 led to an analysis of genetic, epitopes, charged amino acids and Bv outbreaks. Based on the National Influenza Surveillance Network (NISN), the Bv 72 strains isolated during 2019–2022 were selected by spatio-temporal sampling, then were sequenced. Using the Compare Means, Correlate and Cluster, the outbreak data were analyzed, including the single nucleotide variant (SNV), amino acid (AA), epitope, evolutionary rate (ER), Shannon entropy value (SV), charged amino acid and outbreak. With the emergence of COVID-19, the non-pharmaceutical interventions (NPIs) made Less distant transmission and only Bv outbreak. The 2021–2022 strains in the HA genes were located in the same subset, but were distinct from the 2019–2020 strains (P < 0.001). The codon G → A transition in nucleotide was in the highest ratio but the transversion of C → A and T → A made the most significant contribution to the outbreaks, while the increase in amino acid mutations characterized by polar, acidic and basic signatures played a key role in the Bv epidemic in 2021–2022. Both ER and SV were positively correlated in HA genes (R = 0.690) and NA genes (R = 0.711), respectively, however, the number of mutations in the HA genes was 1.59 times higher than that of the NA gene (2.15/1.36) from the beginning of 2020 to 2022. The positively selective sites 174, 199, 214 and 563 in HA genes and the sites 73 and 384 in NA genes were evolutionarily selected in the 2021–2022 influenza outbreaks. Overall, the prevalent factors related to 2021–2022 influenza outbreaks included epidemic timing, Tv, Ts, Tv/Ts, P137 (B → P), P148 (B → P), P199 (P → A), P212 (P → A), P214 (H → P) and P563 (B → P). The preference of amino acid mutations for charge/pH could influence the epidemic/outbreak trends of infectious diseases. Here was a good model of the evolution of infectious disease pathogens. This study, on account of further exploration of virology, genetics, bioinformatics and outbreak information, might facilitate further understanding of their deep interaction mechanisms in the spread of infectious diseases.

Background:Letibotulinum toxin A has an established efficacy and safety profile for aesthetic treatment of glabellar wrinkles. This study was conducted to demonstrate the noninferiority of letibotulinum toxin A versus onabotulinum toxin A in improving the appearance of moderate-to-severe glabellar wrinkles in Chinese patients.Methods:This phase-III multicenter, randomized, parallel positive control, double-blinded study compared the efficacy and safety of letibotulinum toxin A and onabotulinum toxin A. Eligible participants were randomized 3:1 to receive 20 U of letibotulinum toxin A or onabotulinum toxin A and were observed for 16 weeks postinjection. The primary endpoint was noninferiority in the proportion of study participants receiving a score of 0 or 1 for glabellar wrinkles on a four-point photographic evaluation scale, as assessed by an institution evaluator at maximum frown at week 4. Secondary endpoints included assessments at rest, photographic assessment of efficacy, and subjective self-assessment of the study participants.Results:The proportion of participants (N = 500) receiving a score of 0 or 1 at maximum frown by the institution evaluator at week 4 was 88.49% for letibotulinum toxin A and 87.39% for onabotulinum toxin A (difference, 1.10%; 95% confidence interval, -5.02 to 8.82; P = 0.7469). No significant differences were observed between the treatments for secondary efficacy or safety endpoints. Participants' self-assessment and satisfaction tended to be higher for letibotulinum toxin A than onabotulinum toxin A.Conclusion:Letibotulinum toxin A is noninferior to onabotulinum toxin A in improving the appearance of moderate-to-severe glabellar wrinkles in Chinese patients.

Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01, HLA-C*03:02:02:01, and HLA-DQB1*02:01:01:01 positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies.

该文内容涵盖痤疮临床发病机制到防治等6个部分共100个问题.第一部分主要包括了痤疮概述、痤疮病因及发生机制、痤疮临床表现与分级等共计35个问题,拟以通俗语言诠释痤疮临床诊治中的相关疑问,为广大基层皮肤科医师快速掌握痤疮诊治及规范化诊疗提供依据.

该文内容涵盖痤疮临床发病机制到防治等6个部分共100个问题.第一部分主要包括了痤疮概述、痤疮病因及发生机制、痤疮临床表现与分级等,共计35个问题;第二部分主要包括了痤疮临床的中西医治疗等相关内容,共计30个问题;第三部分主要包括了痤疮患者教育和科学护肤等内容,共计35个问题.拟以通俗语言诠释痤疮临床诊治中的相关疑问,为广大基层皮肤科医师快速掌握痤疮诊治及规范化诊疗提供依据.

Background Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease affecting multiple organs and tissues with high cellular heterogeneity. CD8+ T cell activity is involved in the SLE pathogenesis. However, the cellular heterogeneity and the underlying mechanisms of CD8+ T cells in SLE remain to be identified. Methods Single-cell RNA sequencing (scRNA-seq) of PBMCs from a SLE family pedigree (including 3 HCs and 2 SLE patients) was performed to identify the SLE-associated CD8+ T cell subsets. Flow cytometry analysis of a SLE cohort (including 23 HCs and 33 SLE patients), qPCR analysis of another SLE cohort (including 30 HCs and 25 SLE patients) and public scRNA-seq datasets of autoimmune diseases were employed to validate the finding. Whole-exome sequencing (WES) of this SLE family pedigree was used to investigate the genetic basis in dysregulation of CD8+ T cell subsets identified in this study. Co-culture experiments were performed to analyze the activity of CD8+ T cells. Findings We elucidated the cellular heterogeneity of SLE and identified a new highly cytotoxic CD8+ T cell subset, CD161-CD8+ TEMRA cell subpopulation, which was remarkably increased in SLE patients. Meanwhile, we discovered a close correlation between mutation of DTHD1 and the abnormal accumulation of CD161-CD8+ TEMRA cells in SLE. DTHD1 interacted with MYD88 to suppress its activity in T cells and DTHD1 mutation promoted MYD88-dependent pathway and subsequently increased the proliferation and cytotoxicity of CD161-CD8+ TEMRA cells. Furthermore, the differentially expressed genes in CD161-CD8+ TEMRA cells displayed a strong out-of-sample prediction for case- control status of SLE. Interpretation This study identified DTHD1-associated expansion of CD161-CD8+ TEMRA cell subpopulation is critical for SLE. Our study highlights genetic association and cellular heterogeneity of SLE pathogenesis and provides a mechanistical insight into the diagnosis and treatment of SLE.

Artesunate (ART), an antimalarial drug with a multifunctional immunomodulatory effect, reduces psoriasis disease. ART can alleviate psoriasis-like dermatitis in mice but has no effect on proinflammatory cytokines in the blood. Thus, we hypothesized that the skin might be the target tissue of ART during the treatment of psoriasis. The interleukin (IL)-23/IL-17 axis has a key role in the pathogenesis of psoriasis. However, whether and how ART manipulates the IL-23 signal during psoriasis is unknown. This study found that IL-23 is highly expressed in the epidermis of psoriasis lesions and positively correlated with histological neutrophil infiltration and clinical psoriasis area and severity index (PASI) scores. Furthermore, ART inhibits the migration and cell cycle, as well as tumor necrosis factor-alpha (TNF-α)-induced IL-23 expression in HaCaT cells in a dose-dependent manner, probably through interference with the nuclear factor kappa B (NF-κB) signalling pathway. Animal experiments in imiquimod (IMQ)-induced psoriasis-like mice model also suggested that ART dose-dependently reduces IL-23 in the epidermis and ameliorates neutrophil infiltration. These findings thus provide further molecular evidence supporting ART as a promising drug for psoriasis in clinic.

Overlapping syndrome is a syndrome that meets the criteria for at least two connective tissue diseases. When systemic lupus erythematosus (SLE) overlaps with systemic sclerosis (SSc), dermatomyositis/polymyositis, Sjogren's syndrome (SS), rheumatoid arthritis (RA), and other diseases, the lack of specific serological indicators and clinical manifestations can result in missed diagnosis and/or misdiagnosis, leading to life-threatening in severe cases. Early diagnosis and treatment of overlap syndrome can help alleviate the impact on patients′ quality of life and improve the prognosis. This article reviews the research progress in this disorder and its management strategies. Although there is currently limited research on SLE related overlap syndrome, its clinical manifestations and immunological characteristics are strongly related to the overlapping diseases. Specific tests and examinations in time can facilitate the diagnosis and treatment of overlap syndrome.

Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that associates with aberrant activation of B lymphocytes and excessive autoantibodies. Interleukin 10 (IL-10)/interleukin 35 (IL-35) and IL-10/IL-35-producing regulatory B cells have been demonstrated to possess immunosuppressive functions during systemic lupus erythematosus. Here, we detected the proportion of CD19 + CD24 high CD27 + B cells as well as IL-10 and IL-35 levels in peripheral blood of SLE patients and healthy individuals, and investigated their relations with clinical features of SLE. Methods 41 SLE patients and 25 healthy controls were recruited. The patients were divided into groups based on SLEDAI score, anti-dsDNA antibody, rash, nephritis and hematological disorder. Flow cytometry was used to detect the proportion of CD24 hi CD27 + B cells. ELISA was used to detect serum levels of IL-10 and IL-35. Results Our results showed that the CD19 + CD24 high CD27 + B population was decreased in active SLE patients, and anti-correlated with the disease activity. Of note, we found significant increase of IL-10 and decrease of IL-35 in SLE patients with disease activity score > 4, lupus nephritis or hematological disorders compared to those without related clinical features. Conclusions Reduced CD19 + CD24 high CD27 + B cells expression may be involved in the pathogenesis of SLE. Moreover, we supposed that IL-35 instead of IL-10 played a crucial role in immune regulation during SLE disease.

硬斑病是一种以皮肤及皮肤周围组织纤维化为特点的疾病,其发病机制尚未完全明确,目前缺乏针对病因的特效治疗方法.近年来国内外在硬斑病的治疗研究方面取得一定进展,主要包括局部治疗、系统治疗、紫外线光疗、激光治疗和手术治疗.不同的治疗方法适用于不同类型的硬斑病,如局限型硬斑病可以选择局部治疗、紫外线光疗、激光治疗和手术治疗,而纤维化较广较深的其他类型硬斑病则需要系统治疗.本文将对这些进展进行全面系统的梳理和总结,为硬斑病的相关研究提供参考.