Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

BACKGROUND: Lupus 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. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This 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. RESULTS: In 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). CONCLUSIONS: These 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.

Identification of active compounds in Vernonia anthelmintica (L.) willd by targeted metabolome MRM and kaempferol promotes HaCaT cell proliferation and reduces oxidative stress.

Introduction: Vernonia anthelmintica (L.) Willd. is a traditional treatment for vitiligo in Xinjiang. However, its therapeutic mechanism remains unclear owing to its complex composition and limited research on its chemical profile. Methods: We employed a targeted metabolome approach, combining selective reaction monitoring/multiple response monitoring (SRM/MRM) with high-performance liquid chromatography and MRM mass spectrometry to quantitatively analyze the flavonoid constituents of Vernonia anthelmintica. We also used network pharmacology and molecular docking to identify potential vitiligo-linked compounds and targets of V. anthelmintica seeds. Additionally, we assessed HaCaT cell proliferation by AAPH-induced, alongside changes in SOD activity and MDA content, following treatment with V. anthelmintica components. Finally, flow cytometry was used to detect apoptosis and ROS levels. Results and Discussion: We identified 36 flavonoid compounds in V. anthelmintica seeds, with 14 compounds exhibiting druggability. AKT1, VEGFA, ESR1, PTGS2, and IL2 have been identified as key therapeutic target genes, with PI3K/AKT signaling being an important pathway. Notably, kaempferol, one of the identified compounds, exhibited high expression in network pharmacology analysis. Kaempferol exhibited a strong binding affinity to important targets. Further, kaempferol enhanced HaCaT cell viability, inhibited apoptosis, reduced MDA levels, suppressed ROS activity, and upregulated SOD activity, increase the expression of cellular antioxidant genes, including HO-1, GCLC, GCLM, Nrf2, NQO1 and Keap1, providing significant protection against oxidative stress damage in vitro. Here, we present the first comprehensive study integrating SRM/MRM approaches and network analysis to identify active flavonoid compounds within V. anthelmintica (L.) Willd. Moreover, we revealed that its active ingredient, kaempferol, offers protection against AAPH-induced damage in keratinocytes, highlighting its potential as a clinical resource.

Identification and validation of RNA-binding protein SLC3A2 regulates melanocyte ferroptosis in vitiligo by integrated analysis of single-cell and bulk RNA-sequencing.

BACKGROUND: The pathogenesis of vitiligo remains unclear. The genes encoding vitiligo-related RNA-binding proteins (RBPs) and their underlying pathogenic mechanism have not been determined. RESULTS: Single-cell transcriptome sequencing (scRNA-seq) data from the CNCB database was obtained to identify distinct cell types and subpopulations and the relative proportion changes in vitiligo and healthy samples. We identified 14 different cell types and 28 cell subpopulations. The proportion of each cell subpopulation significantly differed between the patients with vitiligo and healthy groups. Using RBP genes for unsupervised clustering, we obtained the specific RBP genes of different cell types in vitiligo and healthy groups. The RBP gene expression was highly heterogeneous; there were significant differences in some cell types, such as keratinocytes, Langerhans, and melanocytes, while there were no significant differences in other cells, such as T cells and fibroblasts, in the two groups. The melanocyte-specific RBP genes were enriched in the apoptosis and immune-related pathways in the patients with vitiligo. Combined with the bulk RNA-seq data of melanocytes, key RBP genes related to melanocytes were identified, including eight upregulated RBP genes (CDKN2A, HLA-A, RPL12, RPL29, RPL31, RPS19, RPS21, and RPS28) and one downregulated RBP gene (SLC3A2). Cell experiments were conducted to explore the role of the key RBP gene SLC3A2 in vitiligo. Cell experiments confirmed that melanocyte proliferation decreased, whereas apoptosis increased, after SLC3A2 knockdown. SLC3A2 knockdown in melanocytes also decreased the SOD activity and melanin content; increased the Fe2+, ROS, and MDA content; significantly increased the expression levels of TYR and COX2; and decreased the expression levels of glutathione and GPX4. CONCLUSION: We identified the RBP genes of different cell subsets in patients with vitiligo and confirmed that downregulating SLC3A2 can promote ferroptosis in melanocytes. These findings provide new insights into the pathogenesis of vitiligo.

A multicenter, randomized, double-blinded, placebo-controlled, phase â ¢ study evaluating the efficacy and safety of Xeligekimab (GR1501) in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Xeligekimab is a fully human monoclonal antibody that selectively neutralizes IL-17A and had shown potential efficacy in preliminary trials. OBJECTIVE: To evaluate the efficacy and safety of Xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200 mg Xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by extending the treatment schedule to GR1501 every 4 weeks for further 40 weeks. Efficacy was assessed by evaluating the Physician's Global Assessment (PGA) 0/1 and Psoriasis Area and Severity Index (PASI) 75/90/100 improvement. The safety profile was also evaluated. RESULTS: At week 12, The PASI 75/90/100 were achieved in 90.7%/74.4%/30.2%% patients in GR1501 group compared with 8.6%/1.4%/0% patients in placebo group, respectively. The PGA 0/1 were achieved in 74.4% patients of GR1501 group and 3.6% patients in placebo group, respectively. The PASI 75 and PGA 0/1 maintained until week 52. No unexpected adverse events were observed. CONCLUSION: Xeligekimab showed high efficacy and is well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.

Tildrakizumab for moderate-to-severe plaque psoriasis in Chinese patients: A 12-week randomized placebo-controlled phase III trial with long-term extension.

BACKGROUND: There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients. METHODS: In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12. RESULTS: At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician's Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks 86.8% [92/106] vs. 82.4% [89/108] and maintained up to 52 weeks 91.3% [95/104] vs. 87.4% [90/103]. Most treatment-emergent adverse events were mild and not related to tildrakizumab. CONCLUSION: Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05108766.

CT-Net: Asymmetric compound branch Transformer for medical image segmentation.

The Transformer architecture has been widely applied in the field of image segmentation due to its powerful ability to capture long-range dependencies. However, its ability to capture local features is relatively weak and it requires a large amount of data for training. Medical image segmentation tasks, on the other hand, demand high requirements for local features and are often applied to small datasets. Therefore, existing Transformer networks show a significant decrease in performance when applied directly to this task. To address these issues, we have designed a new medical image segmentation architecture called CT-Net. It effectively extracts local and global representations using an asymmetric asynchronous branch parallel structure, while reducing unnecessary computational costs. In addition, we propose a high-density information fusion strategy that efficiently fuses the features of two branches using a fusion module of only 0.05M. This strategy ensures high portability and provides conditions for directly applying transfer learning to solve dataset dependency issues. Finally, we have designed a parameter-adjustable multi-perceptive loss function for this architecture to optimize the training process from both pixel-level and global perspectives. We have tested this network on 5 different tasks with 9 datasets, and compared to SwinUNet, CT-Net improves the IoU by 7.3% and 1.8% on Glas and MoNuSeg datasets respectively. Moreover, compared to SwinUNet, the average DSC on the Synapse dataset is improved by 3.5%.

CR-Conformer: a fusion network for clinical skin lesion classification.

Deep convolutional neural network (DCNN) models have been widely used to diagnose skin lesions, and some of them have achieved diagnostic results comparable to or even better than dermatologists. Most publicly available skin lesion datasets used to train DCNN were dermoscopic images. Expensive dermoscopic equipment is rarely available in rural clinics or small hospitals in remote areas. Therefore, it is of great significance to rely on clinical images for computer-aided diagnosis of skin lesions. This paper proposes an improved dual-branch fusion network called CR-Conformer. It integrates a DCNN branch that can effectively extract local features and a Transformer branch that can extract global features to capture more valuable features in clinical skin lesion images. In addition, we improved the DCNN branch to extract enhanced features in four directions through the convolutional rotation operation, further improving the classification performance of clinical skin lesion images. To verify the effectiveness of our proposed method, we conducted comprehensive tests on a private dataset named XJUSL, which contains ten types of clinical skin lesions. The test results indicate that our proposed method reduced the number of parameters by 11.17 M and improved the accuracy of clinical skin lesion image classification by 1.08%. It has the potential to realize automatic diagnosis of skin lesions in mobile devices.

Class key feature extraction and fusion for 2D medical image segmentation.

BACKGROUND: The size variation, complex semantic environment and high similarity in medical images often prevent deep learning models from achieving good performance. PURPOSE: To overcome these problems and improve the model segmentation performance and generalizability. METHODS: We propose the key class feature reconstruction module (KCRM), which ranks channel weights and selects key features (KFs) that contribute more to the segmentation results for each class. Meanwhile, KCRM reconstructs all local features to establish the dependence relationship from local features to KFs. In addition, we propose the spatial gating module (SGM), which employs KFs to generate two spatial maps to suppress irrelevant regions, strengthening the ability to locate semantic objects. Finally, we enable the model to adapt to size variations by diversifying the receptive field. RESULTS: We integrate these modules into class key feature extraction and fusion network (CKFFNet) and validate its performance on three public medical datasets: CHAOS, UW-Madison, and ISIC2017. The experimental results show that our method achieves better segmentation results and generalizability than those of mainstream methods. CONCLUSION: Through quantitative and qualitative research, the proposed module improves the segmentation results and enhances the model generalizability, making it suitable for application and expansion.

Nail psoriasis in China: A prospective multicentre study.

BACKGROUND: Data on nail psoriasis (PsO) in China are scarce. OBJECTIVES: To provide nail PsO-related data regarding epidemiologic characteristics, manifestations, fungal infections, arthritic complaints and treatments that may facilitate improved patient management globally. METHODS: From August 2021 to August 2022, patients with nail PsO were enrolled in a prospective multicentre observational study at 25 hospitals in China. We collected and analysed data concerning nail PsO demography, clinical signs, fungal detection, arthritic symptoms and treatment. RESULTS: A total of 817 patients with nail PsO were involved, with a mean body mass index of 24.13 ± 2.93. In addition, 71.41% of the patients were male. The Nail PsO Severity Index score was weakly positively correlated with body surface area. The percentage of nail involvement was 95.29% for fingernails and 57.18% for toenails, with pitting (67.11%) and subungual hyperkeratosis (60.40%) being the most prevalent manifestations, respectively. Toenails showed a significantly higher frequency of nailfold scales, subungual hyperkeratosis and nail plate crumbling and a lower frequency of splinter haemorrhages, pitting and erythema of the lunula. A total of 13.26% of the PsO patients had onychomycosis, and 77.08% were observed in the toenails. Articular symptoms were reported by 12.17% of the patients, with the peripheral type being predominant. Significant associations between articular symptoms and nailfold swelling, subungual hyperkeratosis, nailfold scales, onycholysis and longitudinal ridges were found. Only 2.30% (20 out of 871) of patients with nail PsO received treatment. The most frequently employed therapy for cutaneous PsO with nail involvement was biologic therapy (n = 366). CONCLUSIONS: PsO showed distinct manifestations in the toenails and fingernails. Additionally, toenail PsO combined with onychomycosis requires special attention. Articular symptoms in psoriatic patients are associated with specific nail changes. It is important to research and advocate for more potent treatments for nail PsO.

The Effect of Transplantation of Cultured Autologous Melanocytes on CXCL9, CXCL10 and CXCL11 Expressions in Vitiligo.

Background: Vitiligo is an acquired chronic autoimmune skin disorder with an estimated prevalence of 1% worldwide. The CD8+ T-cell-mediated chemokines such as CXCR3, CXCL9 and CXCL10 are the non-specific action immunomodulators that are responsible for the depigmentation and progression in vitiligo. Aim: This study aimed to explore the expression levels of serum CXCL9-11 in vitiligo patients who received the transplantation of cultured autologous melanocytes (TCAMs) before and after the operation and correlate their expressions with clinical stage, subtype and course of the vitiligo disease. Materials and Methods: The expression levels of serum CXCL9-11 were measured in the peripheral blood of 26 progressive vitiligo patients, 24 stable vitiligo, 13 TCAM patients and 30 healthy control (HC) cases using enzyme-linked immunosorbent assay (ELISA). The potential correlations between their expressions and disease features such as stage, type and surgical treatment were evaluated using Student's t-test. Results: The expression levels of serum CXCL9-11 increased by ~1.4, ~1.6 and ~2.3-fold in vitiligo patients compared with HCs (P < 0.01). The expression levels of all chemokines were significantly higher in progressive vitiligo patients than in stable vitiligo (P < 0.01). The increasing expression levels of serum CXCL9, CXCL10 and CXCL11 were significantly related to the different types of vitiligo patients (P < 0.05). Preoperative expression levels of serum CXCL9-11 were significantly higher than the post-operative expression levels (P < 0.01). Conclusion: Our results demonstrate that increasing expression levels of the CXC family play a key role in the immunopathogenesis of vitiligo. The abnormal expression of the CXC family may be considered an effective and therapeutic target for TCAM treatment.

IgG4-Related Disease Manifested as Cutaneous Plasmacytosis: A Case Report.

Background: IgG4-related disease (IgG4-RD) is a rare fibroinflammatory disease that has a high tendency to misdiagnosis in clinics. Case Presentation: A 48-year-old man developed a rash with progressive itching 3 years ago after hormone therapy for an ocular "inflammatory pseudotumor". The disease condition of this patient involved multiple organs which involved the skin. The patient was misdiagnosed with other diseases during the period of hospitalization, leading to poor therapeutic effects and repeated skin lesions. The dermatopathological report indicated plasma cell proliferative disorder, with IgG4/IgG exceeding 40% and abnormally elevated serum IgG4 levels. After the patient was diagnosed with IgG4-RD, a series of treatments improved skin lesions, relieved other symptoms, and decreased serum IgG4 levels. Conclusion: IgG4-RD is a highly misdiagnosed disease that deserves the attention of physicians. The patient we reported could be considered a representative case of IgG4-RD that presents with skin lesions. For patients with suspected IgG4-RD, serum IgG4 testing should be performed, and further imaging, serological tests, and pathology examinations are needed to exclude malignancy, infection, and autoimmune diseases.

Targeting therapy in pemphigus: Where are we now and where are we going?

Pemphigus is a heterogeneous group of autoimmune skin disorders characterized by blistering of the skin and mucosal membranes, potentially affecting the quality of life if left unchecked. The current mainstay of treatment is systemic corticosteroids and immunosuppressive agents. Nevertheless, long-term use of these drugs can easily cause infections and other life-threatening adverse reactions. Thus, currently, researchers are trying to develop new and safer therapeutic approaches. Specifically, targeted therapies to pathogenic immune pathways have been gradually introduced and used for the treatment of pemphigus or in clinical trials, such as monoclonal anti-CD20 antibody, BAFF inhibitor, BTK inhibitor, CAAR-T therapy, FcRn antagonist, and TNF-α inhibitor. In addition, IL-4Rα antibody, IL-17 blockade, mTOR pathway inhibitor, CTLA-4Ig, and p38 MAPK inhibitors are theoretically promising treatment for pemphigus. Here, we review the research progress on the mechanism of targeted therapies for pemphigus.

The development and transcriptome regulation of the secondary trunk of Ginkgo biloba L.

Secondary trunk Ginkgo biloba is one of the specific germplasms of G. biloba. In this study, paraffin sectioning, high-performance liquid chromatography and transcriptome sequencing technology were used to study the development of the secondary trunk of G. biloba from the morphological, physiological and molecular levels. The results showed that the secondary trunk of G. biloba originated from the latent buds in the stem cortex at the junction of the root and stem of the main trunk. The development process of secondary trunk was divided into 4 periods: the dormancy period of the secondary trunk buds, the differentiation period, the formation period of transport tissue, and the budding period. Transcriptome sequencing was performed by comparing the germination period and elongation growth period of the secondary trunk with the normal parts of the same period where no secondary trunks occurred. Differential genes involved in phytohormone signal transduction, phenylpropane biosynthesis, phenylalanine metabolism, glycolysis and other pathways can regulate not only the inhibition of early dormant buds but also the later development of the secondary trunk. Genes related to IAA synthesis are upregulated and indole-3-acetic acid content is increased, leading to the up-regulated expression of IAA intracellular vector genes. The IAA response gene (SAUR) receives and responds to IAA signals to promote the development of the secondary trunk. Through the enrichment of differential genes and functional annotations, a key regulatory pathway map for the occurrence of the secondary trunk of G. biloba was sorted out.

Interleukin-37 inhibits desmoglein-3 endocytosis and keratinocyte dissociation via upregulation of Caveolin-1 and inhibition of the STAT3 pathway.

BACKGROUND: Pemphigus vulgaris (PV) is a potentially fatal autoimmune bullous disease primarily caused by acantholysis of keratinocytes attributed to pathogenic desmoglein-3 (Dsg3) autoantibodies. Interleukin-37 (IL-37) reportedly plays important roles in a variety of autoimmune diseases, but its role in PV is not clear. OBJECTIVES: To investigate whether IL-37 plays a role in the occurrence and progression of PV. METHODS: HaCaT keratinocytes were stimulated with anti-Dsg3 antibody to establish an in vitro PV model, which was defined as anti-Dsg3 group. Cells incubated with medium without anti-Dsg3 treatment were used as control. IL-37 was cultured with these cells infected with or without lentiviral vector shRNA-Caveolin-1 (sh-Cav-1-LV). Cell dissociation assay and immunocytofluorescence were performed to assess keratinocyte dissociation, keratin retraction and Dsg3 endocytosis. Real-time PCR was used to detect the mRNA level of Cav-1, and western blot was used to determine the protein expression of Cav-1, Dsg3, STAT3 and phosphorylated-STAT3 (p-STAT3). RESULTS: The anti-Dsg3 group showed more cell debris, increased keratin retraction, increased Dsg3 endocytosis, reduced Cav-1 expression and co-localization than the control group, while IL-37 treatment neutralized all of these changes. Interestingly, Cav-1 knockdown supressed the inhibitory effect of IL-37 on keratinocyte dissociation and Dsg3 internalization. The protein expression of p-STAT3 was increased in keratinocytes of the PV model but decreased by IL-37. Re-activation of the STAT3 pathway by colivelin supressed the inhibitory effect of IL-37 on keratinocyte dissociation and Dsg3 internalization, along with upregulation of Cav-1 and Dsg3. CONCLUSIONS: IL-37 inhibited keratinocyte dissociation and Dsg3 endocytosis in an in vitro PV model through the upregulating Cav-1 and inhibiting STAT3 pathway.

Atopic dermatitis is associated with abnormal stool form: a population-based cross-sectional study in college students.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder. Bristol Stool Form Scale (BSFS) is a widely used stool scoring method that could indirectly reflect intestinal function. OBJECTIVES: To evaluate the associations of AD with BSFS. METHODS: This was a population-based cross-sectional study of freshmen in five universities of China. AD diagnosis was performed by dermatologists according to the guideline from the American Academy of Dermatology. BSFS and covariates were collected through an online questionnaire survey. Chronic itch scores were assessed by the numeric rating scales and grouped into quartiles (Q). Mixed logistic regression models were used. Subgroup analysis was conducted by covariates. P value < 0.05 was considered statistically significant. RESULTS: The prevalence of hard stools and loose stools were 8.9% and 7.6%, respectively (20,049 participants). After adjusting covariates, AD was significantly associated with hard stools (OR = 1.38, P < 0.001) and loose stools (OR = 1.24, P = 0.037). In subgroup analysis of hard stool, a stronger effect was observed in intake of milk (> 3 days/week), yogurt (> 3 days/week), pork (< 1 day/week), and higher itch scores (Q4). CONCLUSION: This study found the relationship between AD and abnormal stool forms, and the association with hard stools might be modified by dietary factor.

BALB.NCT-Cpox nct is a unique mouse model of hereditary coproporphyria.

In humans, mutations in the coproporphyrinogen oxidase (CPOX) gene can result in hereditary coproporphyria (HCP), characterized by high levels of coproporphyrin excretion in the urine and feces, as well as acute neurovisceral and chronic cutaneous manifestations. Appropriate animal models for comprehending the precise pathogenesis mechanism of HCP have not been reported that show similarities in terms of gene mutation, reduced CPOX activity, excess coproporphyrin accumulation, and clinical symptoms. As previously discovered, the BALB.NCT-Cpox nct mouse carries a hypomorphic mutation in the Cpox gene. Due to the mutation, BALB.NCT-Cpox nct had a drastic increase in coproporphyrin in the blood and liver persistently from a young age. In this study, we found that BALB.NCT-Cpox nct mice manifested HCP symptoms. Similar to HCP patients, BALB.NCT-Cpox nct excreted an excessive amount of coproporphyrin and porphyrin precursors in the urine and displayed neuromuscular symptoms, such as a lack of grip strength and impaired motor coordination. Male BALB.NCT-Cpox nct had nonalcoholic steatohepatitis (NASH)-like liver pathology and sclerodermatous skin pathology. A portion of male mice had liver tumors as well, whereas female BALB.NCT-Cpox nct lacked these hepatic and cutaneous pathologies. In addition, we discovered that BALB.NCT-Cpox nct exhibited microcytic anemia. These results indicate that BALB.NCT-Cpox nct mice serve as the suitable animal model to help gain insight into the pathogenesis and therapy of HCP.

Nine cases of refractory bullous pemphigoid treated with dupilumab and literature review.

BACKGROUND AND AIMS: Bullous pemphigoid is an autoimmune blistering disease that affects the elderly mostly. First-line treatment of systemic corticosteroids may cause significant adverse effects, especially in patients with multiple co-morbidities. Dupilumab shows certain effectiveness in treating BP. We aim to profile our experience with dupilumab in a series of patients with BP and review the articles published to date. METHODS: Medical records of 9 patients with moderate-to-severe BP were retrospectively reviewed. All patients were administered dupilumab. Response to dupilumab was evaluated by NRS scores, number of lesions, and the systemic corticosteroids' dosage. The PubMed, Embase, and Web of Science databases were searched to identify eligible studies. RESULTS: The 9 patients were identified in this case series with a median age of 68 years (range 42-89) and the median duration of disease before being treated with dupilumab was 6 months (range 1-144). Complete remission was achieved in 6 patients while partial response was achieved in one patient. The NRS score had decreased to varying degrees at week 2 in all patients, and skin lesions improved within 2 to 6 weeks. Fifteen publications were included: 3 retrospective studies and 12 case series or reports, with a total of 63 patients. The overall complete response and partial response rates were 74.6 % and 11.1 %, respectively. CONCLUSION: Dupilumab appears to be a safe alternative for the treatment of patients with refractory BP.

Protective effects of isorhamnetin against H2O2-induced oxidative damage in HaCaT cells and comprehensive analysis of key genes.

Isorhamnetin (ISO) is a methylated flavonol present in the leaves, flowers, and fruits of many plants with antitumour, anti-inflammatory, antioxidant, and anti-apoptotic properties. ISO has been suggested as the active substance in Vernonia anthelmintica (L.) to treat vitiligo. However, the mechanisms underlying its effects remain unclear. In this study, human keratinocytes (HaCaT cells) were pre-treated with or without ISO and then stimulated with hydrogen peroxide (H2O2) to generate oxidative damage. Pre-treatment with ISO increased HaCaT cell viability, reduced malondialdehyde content, and enhanced superoxide dismutase activity, resulting in a reduction in the loss of mitochondrial membrane potential, improved cell morphological damage, and apoptosis inhibition. Furthermore, we identified 51 significantly dysregulated differentially expressed genes (DEGs) of HaCaT cells treated with ISO using RNA-sequencing. Enrichment analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases indicated that the protective effect of ISO could be related to its effects on the Wnt signalling pathway. Our study provides novel insights into key gene regulation in the progression of oxidative damage and the mechanisms of action of ISO.