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BACKGROUND: Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials. OBJECTIVE: We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis. METHODS: Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale. RESULTS: In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events. CONCLUSIONS: Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021).
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BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.
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Antifúngicos , Itraconazol , Microsporum , Tinha do Couro Cabeludo , Humanos , Pré-Escolar , Antifúngicos/uso terapêutico , Masculino , Feminino , Tinha do Couro Cabeludo/tratamento farmacológico , Tinha do Couro Cabeludo/epidemiologia , Tinha do Couro Cabeludo/microbiologia , Itraconazol/uso terapêutico , China/epidemiologia , Microsporum/isolamento & purificação , Criança , Lactente , Glucocorticoides/uso terapêutico , Resultado do Tratamento , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/epidemiologia , Dermatite Atópica/microbiologia , Fatores de Risco , Adolescente , Adulto , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection. METHODS: A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2. RESULTS: Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs . 39.8% [92/231] vs . 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685-11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068-2.343), traditional systemic (adjusted OR = 1.887, 95% CI = 1.263-2.818), and nonsystemic treatment (adjusted OR = 1.602, 95% CI = 1.117-2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680-1.274, compared to no treatment), according to multivariable logistic regression analysis. CONCLUSIONS: A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension. TRIAL REGISTRATION: ClinicalTrials.gov (No. NCT05961605).
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COVID-19 , Psoríase , SARS-CoV-2 , Humanos , Psoríase/complicações , Psoríase/tratamento farmacológico , COVID-19/complicações , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , China/epidemiologia , Idoso , Modelos LogísticosRESUMO
Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disease mainly manifested as skin and osteoarticular lesions. Herein, we describe a female patient with SAPHO syndrome exhibited paradoxical psoriasis and primary palmoplantar pustulosis (PPP) worsened during treatment with adalimumab. We then switched to secukinumab and obtained significant improvement in both skin lesions and osteoarticular pain. These findings suggest that secukinumab might be an appropriate option for patients with SAPHO syndrome who present with TNF-α-inhibitor-induced paradoxical psoriasis.
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This study aimed to investigate the molecular mechanism of sporotrichosis and identify possible novel therapeutic targets. Total RNA was extracted from skin lesion samples from sporotrichosis patients and used to construct a long-chain RNA transcriptome library and miRNA transcriptome library for whole transcriptome sequencing. The differentially expressed genes (DEGs) between the groups were identified, and then Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis enrichment analyses were performed based on the DEGs. An lncRNA-miRNA-mRNA ceRNA network was constructed. The expressions of JAK/STAT pathway-related proteins were detected in the patient and control tissues using RT-qPCR and Western blot analysis. Enrichment analysis showed that the DEGs were mainly enriched in various infectious diseases and immune response-related signaling pathways. Competing endogenous RNA network analysis was performed and identified the hub lncRNAs, miRNAs, and mRNAs. Compared with the control group, the mRNA expressions of SOCS3, IL-6, and JAK3 were significantly upregulated, while the expression of STAT3 did not change significantly. Also, the protein expressions of SOCS3, IL-6, JAK3, and STAT3, as well as phosphorylated JAK3 and STAT3, were significantly upregulated. We identified 671 lncRNA DEGs, 3281 mRNA DEGs, and 214 miRNA DEGs to be involved in Sporothrix globosa infection. The study findings suggest that the JAK/STAT pathway may be a therapeutic target for sporotrichosis.
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MicroRNAs , RNA Longo não Codificante , Esporotricose , Humanos , RNA Longo não Codificante/genética , Esporotricose/genética , Sequenciamento do Exoma , Interleucina-6/genética , Janus Quinases/genética , Redes Reguladoras de Genes , Transdução de Sinais/genética , Fatores de Transcrição STAT/genética , MicroRNAs/genética , Transcriptoma , RNA Mensageiro/genéticaRESUMO
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. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05108766.
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Anticorpos Monoclonais Humanizados , Psoríase , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Monoclonais Humanizados/uso terapêutico , Método Duplo-Cego , População do Leste Asiático , Psoríase/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD. METHODS: This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied. RESULTS: At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. CONCLUSION: CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.
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Dermatite Atópica , Adulto , Humanos , Dermatite Atópica/tratamento farmacológico , Resultado do Tratamento , Índice de Gravidade de Doença , Anticorpos Monoclonais Humanizados/uso terapêutico , Injeções Subcutâneas , Método Duplo-CegoRESUMO
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.
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Doenças da Unha , Onicomicose , Psoríase , Humanos , Masculino , Feminino , Onicomicose/diagnóstico , Estudos Prospectivos , Doenças da Unha/diagnóstico , Psoríase/epidemiologia , Psoríase/terapia , Psoríase/complicações , China/epidemiologiaRESUMO
The development of Immune checkpoint blockade(ICB) therapy and BRAF- and MEK-targeted therapies has reshaped the survival outcomes of the patients with advanced melanoma. PD-1/PD-L1 blockade was an approved strategy in melanoma treatment. Here we design a PD-L1 xCD3 nanobody as a novel bispecific T cell engager (BiTE) in treating PD-L1 overexpression melanoma. BiTE PD-L1×CD3 Nb was predicted to bind near a large acidic surface on CD3-ε similar to UCHT1-scFv antibody based on alpha-fold and molecular docking. BiTE PD-L1×CD3 Nb and anti-CD3 Nb retained the ability to activate T cells to produce TNF-α and IFN-γ in a dose-dependent manner. The IC50 value of BiTE PD-L1×CD3 Nb was 4.208µg/mL. BiTE PD-L1×CD3 Nb showed obvious cytotoxic activity on both A375WT and A375PD-L1 related to PD-L1 expression level.
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Anticorpos Biespecíficos , Melanoma , Humanos , Linfócitos T , Antígeno B7-H1/metabolismo , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Melanoma/tratamento farmacológico , Anticorpos Biespecíficos/farmacologiaRESUMO
The genetic and developmental factors driving the diverse distribution and morphogenesis of feathers and scales on bird feet are yet unclear. Within a single species, Guangxi domestic chickens exhibit dramatic variety in feathered feet, making them an accessible model for research into the molecular basis of variations in skin appendages. In this study, we used H&E staining to observe the morphogenesis of feathered feet, scaled feet and wings skin at different embryonic stages in Longsheng-Feng chickens and Guangxi Partridge chickens. We selected 4 periods (E6, E7, E8, and E12) that play an important role in feather development and performed transcriptome sequencing to screen for candidate genes associated with feathered feet. Through comparison and analysis of transcriptome data, we identified a set of differently expressed genes (DGEs), which were enriched in appendage organ development, hindlimb morphogenesis, activation of transcription factor binding, and binding of sequence-specific DNA in the cis-regulatory region. In addition, we identified some feathered feet-related genes by analyzing the classical signaling pathways that regulate feather development. Finally, we identified candidate genes that regulate feathered feet formation, which include TBX5, PITX1, ZIC1, FGF20, WNT11, WNT7A, WNT16, and SHH. Interestingly, we found that TBX5 was significantly overexpressed in the skin of the feathered feet and had the highest expression at E7 (P < 0.01), whereas PITX1 expression was significantly reduced at E7(P < 0.01). It is hypothesized that TBX5 and PITX1 regulate the development of hair follicles through the Wnt/ß-catenin signaling pathway at E7. Our results provide a theoretical basis for investigating the molecular regulatory mechanisms underlying the formation of chicken feathered feet.
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Galinhas , Plumas , Embrião de Galinha , Animais , Galinhas/genética , China , Pele , Via de Sinalização WntRESUMO
OBJECTIVES: To investigate the current etiological, diagnostic, and therapeutic characteristics of tinea capitis in children in Jilin Province. METHODS: Sixty pediatric patients with tinea capitis were enrolled between August 2020 and December 2021. Data on calcofluor white (CFW) fluorescence microscopy, fungal culture, Wood's lamp examination, dermoscopy, treatment, and follow-up were collected and analyzed. RESULTS: 1. Of all the enrolled patients, 48 had a history of animal contact, mostly with cats and dogs. Fifty-one strains were isolated, of which 46 were Microsporum canis (M. canis). 2. All enrolled patients were examined using fluorescence microscopy, and 59 were positive. Forty-one cases of tinea alba were examined using Wood's lamp, and 38 were positive. Forty-two cases of tinea alba were examined using dermoscopy, and 39 demonstrated specific signs. Effective treatment manifested as a fading bright green fluorescence, decreased mycelial/spore load, reduced specific dermoscopic signs, and hair regrowth. 3. Treatment was terminated in 23 and 37 cases based on mycological and clinical cures, respectively. No recurrence occurred during follow-up. CONCLUSION: 1. M. canis is the predominant pathogen causing tinea capitis in children in Jilin Province. Animal contact is considered the main risk factor. 2. CFW fluorescence microscopy, Wood's lamp, and dermoscopy can be used to diagnose ringworms and follow-up patients. 3. Both mycological and clinical cures can be the endpoint of adequate treatment for tinea capitis.
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Tinha do Couro Cabeludo , Tinha , Humanos , Criança , Animais , Gatos , Cães , Tinha do Couro Cabeludo/diagnóstico , Tinha do Couro Cabeludo/epidemiologia , Tinha do Couro Cabeludo/tratamento farmacológico , Microsporum , Cabelo/microbiologiaRESUMO
Although chronic spontaneous urticaria (CSU) is a common disease, GWASs of CSU are lacking. We aimed to identify susceptibility SNPs by performing a GWAS in Chinese Han adults with CSU. The discovery cohort included 430 CSU cases and 482 healthy controls. The GWAS findings were validated in 800 CSU cases and 900 healthy controls. Genetic, functional enrichment, and bioinformatic analyses of genome-wide significant SNPs were performed to assess the association between CSU and autoimmunity or atopy. Five genome-wide significant SNPs were identified: rs434124/LILRA3, rs61986182/IGHG1/2, rs73075571/TDGF1, rs9378141/HLA-G, and rs3789612/PTPN22. The first four SNPs were in linkage disequilibrium with autoimmune-related diseasesâassociated SNPs and were cis-expression quantitative trait loci in immune cells. The five SNPs-annotated genes were significantly enriched in immune processes. Higher polygenic risk scores and allele frequencies of rs3789612∗T, rs9378141∗C, and rs73075571∗G were significantly associated with autoimmune-related CSU phenotypes, including positive antithyroglobulin IgG, positive anti-FcεRIα IgG, total IgE <40 IU/ml, and positive antithyroid peroxidase IgG but not with atopic or allergic sensitized CSU phenotypes. This GWAS of CSU identifies five risk loci and reveals that CSU shares genetic overlap with autoimmune diseases and that genetic factors predisposing to CSU mainly manifest through associations with autoimmune traits.
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Doenças Autoimunes , Urticária Crônica , Urticária , Humanos , Estudo de Associação Genômica Ampla , Urticária/genética , Doença Crônica , Urticária Crônica/genética , Doenças Autoimunes/genética , Imunoglobulina G , Proteína Tirosina Fosfatase não Receptora Tipo 22 , Receptores ImunológicosRESUMO
BACKGROUND: Microcystic adnexal carcinoma (MAC) is a rare malignant cutaneous adnexal neoplasm, often presenting as a flesh-colored and slow-growing indurated plaque or cystic nodule in the mid-facial region. Its characteristic indolent presentation usually leads to initial misdiagnosis, resulting in tumor mismanagement and added morbidity due to increased propensity for local invasion. CASE SUMMARY: A 63-year-old Chinese male patient with a long-term history of excessive ultraviolet irradiation had received two surgeries for an "epidermal cyst" on his glabella and was presented to our hospital's Dermatology Department for further diagnosis and therapy of the lesion on his glabella. One month ago, his two 7 mm × 7 mm subcutaneous nodules were diagnosed as "recurrent epidermal cysts", and he underwent local excision surgery. Additionally, he has post medical history of surgery for right clear cell renal carcinoma. According to his biopsy, the patient was diagnosed as MAC in our hospital, and a tumor remnant was found on his wound. He then underwent wide local excision to achieve negative margins and reconstruction of full-thickness flap transplantation for tissue coverage. He remained tumor-free after six months of follow-up. CONCLUSION: This case highlights the importance of MAC's possible pathogenic factor of excessive ultraviolet exposure, its differential diagnosis to avoid misdiagnosis and mismanagement to adverse prognosis, the patient's particular medical history of clear cell renal carcinoma, the alert for any tumor recurrence in older patients, and his uncommon multiple nodules mess consisting of two 7 mm × 7 mm subcutaneous nodules, that will enrich the existing knowledge of MAC's clinical features.
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INTRODUCTION: Pulsed dye laser (PDL) is the main treatment for port wine stain (PWS), but a considerable number of patients show low clearances. The reason for the poor efficacy is related to PDL-induced angiogenesis. Vascular endothelial growth factor (VEGF) plays an important role in PDL-induced angiogenesis and can activate the tyrosine kinase activity of VEGF receptor (VEGFR) in endothelial cells. It triggers a full range of responses, and then participates in the regulation of angiogenesis. Tivozanib is an inhibitor of VEGFR tyrosine kinase activity, which can block the pro-angiogenic effect of VEGF and reduce vascular permeability. METHOD: Different energy densities of PDL were used to irradiate the abdominal skin of rats. According to the general and pathological changes of the irradiated area, the energy density of 8 J/cm2 with smaller scab and stronger vascular effect was selected for follow-up experiments. Divided the rat abdomen skin into four areas, irradiated three of them uniformly with an energy density of 8 J/cm2 , and applied different concentrations of Tivozanib coating agent to the laser irradiation area, and grouped them as follows: (1) vacant group, (2) control group, (3) 0.5% Tivozanib group, (4) 1% Tivozanib group. Camera and dermoscopy were used to observe skin changes. Hematoxylin-eosin staining, immunohistochemical staining, and blood vessels were counted to detect dermal vascular regeneration. Transcriptome sequencing and real-time polymerase chain reaction (PCR) were conducted to elucidate the mechanism and validate the reliability. RESULTS: The number of blood vessels in the 0.5% Tivozanib group and 1% Tivozanib group was significantly reduced on the 7, 10, and 14 days compared with the control group. The number of blood vessels in the 1% Tivozanib group was significantly reduced compared with the 0.5% Tivozanib group, indicating that Tivozanib successfully inhibited PDL-induced angiogenesis, and the inhibitory effect of 1% Tivozanib was more significant than that of 0.5% Tivozanib. Transcriptome sequencing results showed a total of 588 significantly differentially expressed genes, including 90 upregulated genes and 498 downregulated genes. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that the significantly differentially expressed genes were mainly enriched in the metabolic pathways which were closely related to angiogenesis. Finally, real-time PCR was used to verify the genes with higher expression differences, the top ranking and closely related to angiogenesis, namely, Cxcl1, Cxcl2, Cxcl3, Cxcl6, Ccl3, Csf3, IL1ß, iNOS, Mmp9, Mmp13, Plau, Ets1, Spp1, Nr4a1. The results were consistent with the trend of transcriptome sequencing results, which proved the reliability of this study. CONCLUSION: This study explored the inhibitory effect of Tivozanib on PDL-induced angiogenesis, and provided a new idea for the treatment of clinical PWS. Transcriptome sequencing explored the mechanism and provided reliable clues for later in-depth research.
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Lasers de Corante , Neovascularização Patológica , Compostos de Fenilureia , Mancha Vinho do Porto , Quinolinas , Animais , Células Endoteliais , Lasers de Corante/efeitos adversos , Neovascularização Patológica/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Mancha Vinho do Porto/patologia , Proteínas Tirosina Quinases , Quinolinas/uso terapêutico , Ratos , Reprodutibilidade dos Testes , Resultado do Tratamento , Fator A de Crescimento do Endotélio VascularRESUMO
Background: The global, regional, and national burden of psoriasis was investigated based on the Global Burden of Disease (GBD) study. Objectives: To report the incidence of psoriasis in 204 countries and territories from 21 regions according to age, sex, region, country, and socialdemographic index (SDI) between 1990 and 2019. Materials & Methods: Estimates from the GBD 2019 study were used to analyse the incidence of psoriasis at the global, regional, and national levels. The estimated annual percentage changes (EAPCs) in the age-standardized incidence rate (ASIR) were calculated to quantify trends between 1990 and 2019. Results: From 1990 to 2019, the global incidence of psoriasis increased by 26.53%, but the ASIR of psoriasis decreased, with an EAPC of -0.77 (95% confidence interval [CI]: -0.78 to -0.76). In 2019, the highest ASIRs of psoriasis (112.58 per 100,000 population; 95% uncertainty interval, 108.89 to 116.07) were observed in high-SDI regions. The male-to-female ratio for psoriasis incidence peaked globally in the 50-54-year-old age group and peaked in the 75-79-year-old age group in high-SDI regions. Regionally, Central Sub-Saharan Africa (EAPC, -0.57; 95% CI: -0.67 to -0.48) and Eastern Sub-Saharan Africa (EAPC, -0.36; 95% CI, -0.38 to -0.34) had the largest decrease in ASIR of psoriasis from 1990 to 2019. Nationally, increases in the ASIR of psoriasis was observed only in Japan (EAPC, 0.04; 95% CI: 0.02 to 0.05). Conclusion: Globally, the incidence of psoriasis showed an increasing trend, but the ASIR of psoriasis decreased significantly from 1990 to 2019. Only Japan showed an unfavourable increasing trend.
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Saúde Global , Psoríase , Idoso , Feminino , Carga Global da Doença , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Psoríase/epidemiologiaRESUMO
We aimed to detect the pathogenic gene mutations in a patient with lamellar ichthyosis (LI). The genomic DNA of the patient was examined using high-throughput whole-exome sequencing to identify the causative mutations. Compound heterozygous mutations of c.1187G>T (p.Arg396Leu) and c.607C>T (p.Gln203*) were found in the transglutaminase-1 gene (TGM1) on chromosome 14 of the proband. The mutations stated above have been reported to impair the function of TGM1 protein and to be pathogenic. Our data suggest that the proband carried compound heterozygous mutations of c.1187G>T(p.Arg396Leu) and c.607C>T(p.Gln203*) in TGM1, which were in the trans position and the cause of his disease. We also found some dermoscopic in this patient which may be specific in LI.