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Psoriasis is a chronic inflammatory disease whose etiology is multifactorial. The contributions of cellular metabolism to psoriasis are unclear. Here, we report that interleukin-17 (IL-17) downregulated Protein Phosphatase 6 (PP6) in psoriatic keratinocytes, causing phosphorylation and activation of the transcription factor C/EBP-ß and subsequent generation of arginase-1. Mice lacking Pp6 in keratinocytes were predisposed to psoriasis-like skin inflammation. Accumulation of arginase-1 in Pp6-deficient keratinocytes drove polyamine production from the urea cycle. Polyamines protected self-RNA released by psoriatic keratinocytes from degradation and facilitated the endocytosis of self-RNA by myeloid dendritic cells to promote toll-like receptor-7 (TLR7)-dependent RNA sensing and IL-6 production. An arginase inhibitor improved skin inflammation in murine and non-human primate models of psoriasis. Our findings suggest that urea cycle hyperreactivity and excessive polyamine generation in psoriatic keratinocytes promote self-RNA sensation and PP6 deregulation in keratinocytes is a pivotal event that amplifies the inflammatory circuits in psoriasis.
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Células Dendríticas/imunologia , Queratinócitos/metabolismo , Fosfoproteínas Fosfatases/deficiência , Poliaminas/metabolismo , Psoríase/patologia , RNA/imunologia , Células 3T3 , Animais , Arginase/antagonistas & inibidores , Arginase/metabolismo , Arginina/metabolismo , Autoantígenos/imunologia , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Células HEK293 , Células HaCaT , Humanos , Interleucina-17/metabolismo , Macaca fascicularis , Glicoproteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Fosfoproteínas Fosfatases/genética , Fosforilação , Pele/patologia , Receptor 7 Toll-Like/imunologiaRESUMO
OBJECTIVE: To identify patients in the subclinical psoriatic arthritis (Sub-PsA) phase by ultrasound (US) and provide a solution to screen them. METHODS: A total of 490 participants with moderate-to-severe psoriasis were evaluated. Among them, 384 participants without arthritis symptoms were enrolled into the silent psoriasis group and 106 participants with arthritis symptoms, called prodromal/active PsA phase, were enrolled into the clinical PsA group. Another 80 non-psoriasis participants were enrolled into the control group. Each participant received clinical assessments and US examinations of 60 joints, 38 tendons, and 40 entheses. We compared the incidences of synovio-enthesitis, synovitis, tenosynovitis, erosion, and dactylitis detected on US among the three groups. Subsequently, on the basis of significant US findings, we distinguished Sub-PsA from psoriasis alone (PsO) in the silent psoriasis group and analyzed the clinical characteristics, mainly including basic clinical characteristics, body surface area (BSA), and Psoriasis Area and Severity Index (PASI) score. RESULTS: Only synovio-enthesitis significantly differed between the control group and the silent psoriasis group (1.3% vs. 16.1%, p < 0.001). The knee was the most commonly involved site of synovio-enthesitis (79.0%). Taking synovio-enthesitis as the standard, 16.1% of silent psoriasis participants and 12.7% of all psoriasis participants were in the Sub-PsA phase. Furthermore, there were no differences in BSA and PASI among the three phases of PsO, Sub-PsA, and prodromal/active PsA. CONCLUSIONS: Since the psoriasis patients in Sub-PsA phase was as high as 12.7% in all patients with moderate-to-severe psoriasis, US-detected synovio-enthesitis was recommended routinely for screening them regardless of arthritis symptoms, especially in the lower limbs. KEY POINTS: ⢠Synovio-enthesitis on ultrasound was significantly associated with subclinical psoriatic arthritis, especially in the lower limbs. ⢠Routine ultrasound evaluation could help screen psoriasis patients in the subclinical psoriatic arthritis phase, which was as high as 12.7% in all psoriasis patients.
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Artrite Psoriásica , Entesopatia , Psoríase , Tenossinovite , Humanos , Artrite Psoriásica/complicações , Artrite Psoriásica/diagnóstico por imagem , Psoríase/complicações , Psoríase/diagnóstico por imagem , Ultrassonografia , Entesopatia/complicações , Índice de Gravidade de DoençaRESUMO
The Dangguikushen (DGKS) pill is a proprietary traditional Chinese medicine that has shown superior efficacy in the treatment of acne vulgaris for many years. A network pharmacology-based analysis was performed to explore the potential anti-acne compounds, core therapeutic targets, and the main pathways, involved in the DGKS pill bioactivity. The matching results between the predicted targets of the DGKS pill and the well-known targets of acne vulgaris were collected, followed by network establishment using protein-protein interaction (PPI) data. Cytoscape was utilized to analyze the network and screen the core targets. Furthermore, the Database for Annotation, Visualization and Integrated Discovery (DAVID), and ClueGO were used for the enrichment analysis of the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathways and Gene Ontology biological processes (GO-BP). Finally, the "compound-target-pathway" network was constructed. This approach identified 19 active compounds, 46 therapeutic targets, and 12 core therapeutic targets of the DGKS pill. The biological processes were primarily related to reactive oxygen species (ROS) metabolic process, gland morphogenesis, and female gonad development. The DGKS pill was significantly associated with eight pathways including the PI3K-Akt, TNF, NF-kappa B, and p53 signaling pathways. DGKS pill might have a synergistic effect on the inhibition of excessive sebaceous lipogenesis and sebocyte differentiation, and likewise, anti-inflammatory effects via the different signaling pathways (PI3K-Akt, TNF, NF-kappa B, and p53).
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Acne Vulgar , Medicamentos de Ervas Chinesas , Acne Vulgar/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Humanos , Medicina Tradicional Chinesa , Fosfatidilinositol 3-Quinases , Mapas de Interação de ProteínasRESUMO
BACKGROUND: The typical manifestations of Penicillium marneffei (nowadays Talaromyces marneffei) infection in children without human immunodeficiency virus (HIV) remain unclear. The current work presents the case of a child without an underlying disease who was infected with P. marneffei comorbid with eosinophilia. CASE PRESENTATION: A 2-year-old male was infected with P. marneffei. A physical examination revealed a high-grade fever, ulcerated lesions in the oral mucosa, anemia, pruritic erythematous papules on the sac and thigh and watery diarrhea. A chest enhanced computed tomography scan showed multiple small, nodular, high-density shadows in the lungs, multiple lymphadenectasis in the hilum of the lungs and mediastinum, and liquid in the right pleural cavity. The patient's plasma was negative for HIV. Routine blood tests initially indicated that the patient had leucopenia; however, later tests indicated that he had leukocytosis. This peak was caused by a significant increase in eosinophils. The total IgE and specific allergen levels were normal. The stool was negative for parasite eggs. Aspergillus antigen (galactomannan, GM) levels were significantly increased and were present in the serum for a relatively long period. CONCLUSIONS: Eosinophilia can occur during P. marneffei infection, and this finding might provide additional information on the activity of this intracellular parasite. In addition, GM detection might be useful for monitoring the effect of antifungal treatments; however, this theory requires more data for verification.
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Eosinofilia/complicações , Eosinofilia/diagnóstico , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/patologia , Penicillium/isolamento & purificação , Pré-Escolar , Eosinofilia/patologia , Galactose/análogos & derivados , Humanos , Infecções Fúngicas Invasivas/complicações , Masculino , Mananas/sangueRESUMO
Psoriasis is a chronic recurrent inflammatory skin disorder characterized by the dysregulated cross-talk between epidermal keratinocytes and immune cells, leading to keratinocyte hyperproliferation. Several studies demonstrated that Wnt pathway genes were differentially expressed in psoriatic plaques and likely were involved in the pathophysiology of disease. However, the molecular mechanisms underlying Wnt signaling regulation in epidermal hyperplasia in psoriasis remain largely unknown. We report that the expression of secreted frizzled-related protein (SFRP) 4, a negative regulator of the Wnt signaling pathway, was diminished in lesional skin of mouse models and patients with psoriasis. SFRP4 directly inhibited excessive keratinocyte proliferation evoked by proinflammatory cytokines in vitro. Pharmacological inhibition of Wnt signaling or intradermal injection of SFRP4 decreased the severity of the psoriasiform skin phenotype in vivo, including decreased acanthosis and reduced leukocyte infiltration. Mechanistically, we identified that aberrant promoter methylation resulted in epigenetic downregulation of SFRP4 in inflamed skin of patients with psoriasis and in the IL-23-induced mouse model. Our findings suggest that this epigenetic event is critically involved in the pathogenesis of psoriasis, and the downregulation of SFRP4 by CpG island methylation is one possible mechanism contributing to the hyperplasia of epidermis in the disease.
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Regulação para Baixo/genética , Epiderme/patologia , Epigênese Genética/genética , Hiperplasia/genética , Proteínas Proto-Oncogênicas/genética , Psoríase/genética , Adulto , Animais , Metilação de DNA , Feminino , Humanos , Hiperplasia/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas/genética , Psoríase/patologia , Via de Sinalização WntRESUMO
BACKGROUND: Malignant acanthosis nigricans (MAN), characterized by the presence of a hyperpigmented, velvety cutaneous thickening, is recognized as a cutaneous sign of internal malignancy. Few MAN has been reported in the Asian race ever before. CASE PRESENTATION: Here, we report a rare case of MAN with severe mucosa and soles and extraordinary facial involvement in the Asian race. A 74-year-old man presented with hyperkeratotic eruption for 7 months. Physical examination revealed hyperkeratotic plaques on the face, dorsal skin of fingers and heels, and papillomatosis of buccal mucosa. Biopsy findings from skin lesion revealed hyperkeratosis, papillomatosis, and hyperpigmentation of the basal layer. The endoscopic ultrasound with biopsy of the gastric tissue revealed gastric cardia tubular adenocarcinoma. The patient was diagnosed with MAN associated with gastric adenocarcinoma, immediately following tumor resection and lymphadenectomy. A slight improvement was seen in the skin condition but died of cancer cachexia 3 months later. CONCLUSIONS: We report our typical patient to highlight the importance of MAN, which was an early clue to the discovery of gastric adenocarcinoma.
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Acantose Nigricans/diagnóstico , Adenocarcinoma/diagnóstico , Papiloma/diagnóstico , Neoplasias Gástricas/diagnóstico , Acantose Nigricans/etiologia , Acantose Nigricans/patologia , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Biópsia , Caquexia/etiologia , Endossonografia , Evolução Fatal , Gastrectomia , Humanos , Excisão de Linfonodo , Masculino , Mucosa Bucal/patologia , Papiloma/complicações , Papiloma/patologia , Prognóstico , Pele/patologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND: Photodynamic therapy (PDT) has been widely used in treatment for skin cancer. However, topical 5-aminolevulinic acid (ALA) in PDT demonstrates poor therapeutic effect due to its shallow penetration. And intralesional ALA-PDT can bring great pain. The purpose of this study was to evaluate the efficacy of PDT with needle-free injection of ALA in the treatment of nonmalignant skin tumors. METHODS: 54 non-melanocytic malignant lesions of 54 subjects were treated with needle-free injection of 20% 5-ALA under occlusion for 1.5 hours, and irradiated with light dose of 100 J/cm(2) at 100 mW for 20 minutes. Evaluation of treatment efficacy was conducted at 2 week after treatment. RESULTS: 44 cases showed complete response with six cycles of PDT, three cases with seven cycles, and three cases with nine cycles. The remaining four cases failed to show complete response even with nine cycle of PDT. No case was reported to have recurrence in 6 months posttreatment. Only four cases experienced disease recurrence in 1 year posttreatment. CONCLUSIONS: The treatment with PDT using needle-free injection of 5-ALA appears to be effective and well tolerated with milder therapeutic pain and low recurrence rate. It can be proposed as an effective treatment alternative for non-melanoma skin cancer.
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Ácido Aminolevulínico/administração & dosagem , Fotoquimioterapia/métodos , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-IdadeRESUMO
It is widely believed that non-segmental vitiligo results from the autoimmune destruction of melanocytes. MicroRNAs (miRNAs), a class of small non-coding RNAs that negatively regulate gene expression, are involved in the immune cell development and function and regulate the development of autoimmune diseases. Recent studies demonstrate that functional miRNAs can be detected in the serum and serve as biomarkers of various diseases. In the present study, we used a mouse autoimmune vitiligo model, in which melanocyte autoreactive CD4+ T cells were adoptively transferred into Rag1(-/-) host mice. Serum miRNA expression was profiled in vitiligo developed mice and control mice using TaqMan RT-PCR arrays. We have found that the expressions of 20 serum miRNAs were changed in vitiligo mice compared to control mice. Three increased miRNAs, miR-146a, miR-191, and miR-342-3p, were further confirmed by a single TaqMan RT-PCR. Our findings suggest that miRNAs may be involved in vitiligo development and serum miRNAs could serve as serum biomarkers for vitiligo in mice.
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Doenças Autoimunes/genética , MicroRNAs/sangue , Vitiligo/genética , Transferência Adotiva , Animais , Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/transplante , Perfilação da Expressão Gênica , Proteínas de Homeodomínio/genética , Melanócitos/imunologia , Camundongos , Camundongos Knockout , MicroRNAs/biossíntese , MicroRNAs/genética , Vitiligo/sangue , Vitiligo/imunologiaRESUMO
Generalized pustular psoriasis (GPP) is a rare, chronic, heterogeneous, and potentially life-threatening disease characterized by primary, sterile, and macroscopically visible pustules with or without systemic symptoms. There are ethnic differences in the genetic mutations associated with GPP that might affect the clinical manifestations and treatment responses. Currently, there is limited evidence from the patient population in the Asia-Pacific (APAC) region, resulting in a general paucity of information on the effective management of patients with GPP in this region. This modified Delphi panel study aimed to identify current evidence and gain advanced insights to facilitate the development of a regionally tailored APAC consensus on the management of GPP. A systematic literature review (SLR) was conducted to identify published literature and develop consensus statements on (i) definition and clinical course, (ii) diagnosis of GPP, (iii) treatment outcomes, goals, and monitoring measures, and (iv) optimal management strategies and clinical practices. Statements were rated by a panel of dermatologists in two rounds, with the threshold for consensus at ≥80% agreement. Twenty experts from the APAC region reached consensus on 106 statements that were developed based on the SLR and experts' collective expertise. The experts agreed that GPP is a rare, severe, and potentially life-threatening condition that is distinct from plaque psoriasis. This consensus emphasized the importance of a tailored treatment strategy taking into account the GPP flare severity and each patient's unique clinical circumstances. The experts reached consensus on the severity classification of GPP flares and recommended first-line and maintenance treatment options for adult GPP, childhood GPP, and GPP in pregnancy. These consensus outcomes have been synthesized into treatment algorithms to guide dermatologists in the APAC region in their clinical decision-making processes.
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Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.
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MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that repress target genes at post-transcriptional level. Langerhans cells (LCs) are skin-residential dendritic cells (DCs) with a life cycle distinct from other types of DCs. miRNA deficiency interrupts the homoeostasis and function of epidermal LCs, suggesting the critical roles of miRNAs in LC development and function. However, the roles of individual miRNAs in regulating LC development and function remain completely unknown. MiRNA miR-150 is highly expressed in mature lymphocytes and regulates T- and B-cell development and function. Here, we reported that miR-150 is also expressed in epidermal LCs, and its expression is significantly down-regulated during in vitro LC maturation. Using a miR-150 knockout mouse model, we found that lack of miR-150 reduces the capacity of LCs to cross-present a soluble antigen to antigen-specific CD8(+) T cells, but does not disturb the development, maturation, migration and phagocytic capacity of LCs. Thus, our data indicate that miR-150 is required for LC cross-presentation.
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Apresentação Cruzada/fisiologia , Epiderme/imunologia , Células de Langerhans/imunologia , MicroRNAs/genética , MicroRNAs/fisiologia , Animais , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Células Epidérmicas , Técnicas de Silenciamento de Genes , Técnicas In Vitro , Células de Langerhans/citologia , Camundongos , Camundongos KnockoutRESUMO
Background: Data pertaining to biologic agents used for treating psoriasis in real-world settings are lacking at present. To compare drug survival at 52 weeks for a range of biologics used to treat psoriasis under real-world conditions. Methods: This was a retrospective, single-center, observational study of a cohort of patients diagnosed with plaque psoriasis treated using ixekizumab, secukinumab, guselkumab, or adalimumab between January 2020 and December 2021. Baseline demographic characteristics, duration of psoriasis, and prior biological treatments for all patients were recorded. Drug survival rates were analyzed in different patient groups using Kaplan-Meier curves and Log rank tests. Results: In total, this study included 386 plaque psoriasis patients, of whom 70, 175, 36, and 105 were, respectively, treated using ixekizumab, secukinumab, guselkumab, and adalimumab. Over a 52-week period, the overall cumulative drug survival rates for ixekizumab, secukinumab, guselkumab, and adalimumab were 67.1%, 63.0%, 72.2%, and 37.1%, respectively. Lack of efficacy was the primary cause of discontinuation for these biologic therapies, followed by economic burden and adverse event incidence. Conclusion: These results suggest that guselkumab exhibited superior drug survival, drug survival outcomes for ixekizumab and secukinumab were comparable, and significantly better than those of adalimumab in China. Preventing a loss of drug efficacy represents a primary approach to improving biologic drug survival in psoriasis patients.
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Glucose metabolism is an essential process for energy production and cell survival for both normal and abnormal cellular metabolism. Several glucose transporter/solute carrier 2A (GLUT/SLC2A) superfamily members, including glucose transporter 1 (GLUT1), have been shown to mediate the cellular uptake of glucose in diverse cell types. GLUT1-mediated glucose uptake is a transient and rapid process; thus, the real-time monitoring of GLUT1 trafficking is pivotal for a better understanding of GLUT1 expression and GLUT1-dependent glucose uptake. In the present study, we established a rapid and effective method to visualize the trafficking of GLUT1 between the plasma membrane (PM) and endolysosomal system in live cells using an mCherry-EGFP-GLUT1 tandem fluorescence tracing system. We found that GLUT1 localized at the PM exhibited both red (mCherry) and green (EGFP) fluorescence (yellow when overlapping). However, a significant increase in red punctate fluorescence (mCherry is resistant to acidic pH), but not green fluorescence (EGFP is quenched by acidic pH), was observed upon glucose deprivation, indicating that the mCherry-EGFP-GLUT1 functional protein was trafficked to the acidic endolysosomal system. Besides, we were able to calculate the relative ratio of mCherry to EGFP by quantification of the translocation coefficient, which can be used as a readout for GLUT1 internalization and subsequent lysosomal degradation. Two mutants, mCherry-EGFP-GLUT1-S226D and mCherry-EGFP-GLUT1-ΔC4, were also constructed, which indirectly confirmed the specificity of mCherry-EGFP-GLUT1 for monitoring GLUT1 trafficking. By using a series of endosomal (Rab5, Rab7, and Rab11) and lysosomal markers, we were able to define a model of GLUT1 trafficking in live cells in which upon glucose deprivation, GLUT1 dissociates from the PM and experiences a pH gradient from 6.8-6.1 in the early endosomes to 6.0-4.8 in the late endosomes and finally pH 4.5 in lysosomes, which is appropriate for degradation. In addition, our proof-of-concept study indicated that the pmCherry-EGFP-GLUT1 tracing system can accurately reflect endogenous changes in GLUT1 in response to treatment with the small molecule, andrographolide. Since targeting GLUT1 expression and GLUT1-dependent glucose metabolism is a promising therapeutic strategy for diverse types of cancers and certain other glucose addiction diseases, our study herein indicates that pmCherry-EGFP-GLUT1 can be utilized as a biosensor for GLUT1-dependent functional studies and potential small molecule screening.
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Etanercept biosimilar recombinant human tumour necrosis factor-α receptor II: IgG Fc fusion protein (rhTNFR-Fc, trade name Yisaipu) has shown good efficacy in the treatment of moderate-to-severe plaque psoriasis. To compare the efficacy and safety of rhTNFR-Fc plus methotrexate (MTX) and rhTNFR-Fc plus placebo in Chinese patients with moderate-to-severe plaque psoriasis. In this multicentre, randomized, placebo-controlled trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned in a 1:1 ratio to receive rhTNFR-Fc plus MTX or rhTNFR-Fc plus placebo. The primary endpoint was the proportion of patients achieving Psoriasis Area and Severity Index improvement of at least 75% (PASI 75) from baseline at week 24. Adverse events (AEs) were recorded to evaluate safety. Efficacy analysis was performed using the intent-to-treat principle. A total of 466 patients were enrolled and randomly received rhTNFR-Fc plus MTX (combination group, n = 233) or rhTNFR-Fc plus placebo (monotherapy group, n = 233). PASI 75 at week 24 was significantly higher in the combination group than in the monotherapy group (81.86% vs. 65.50%, p < 0.001). Similar results were observed in other PASI improvement scores at week 12 [PASI 75, 62.39% vs. 44.54% (p < 0.001); PASI 50, 87.17% vs. 75.55% (p = 0.001); and PASI 90, 34.07% vs. 18.78% (p < 0.001)] and week 24 [PASI 50, 92.48% vs. 85.59% (p = 0.019); and PASI 90, 64.16% vs. 42.36% (p < 0.001)]. Significantly more patients had a static Physicians' Global Assessment of clear or almost clear in the combination group than in the monotherapy group at week 12 (26.46% vs. 12.50%, p < 0.001) and week 24 (62.38% vs. 40.83%, p < 0.001). The most common AEs in the two groups were upper respiratory tract infection and abnormal liver function. The combination therapy of rhTNFR-Fc plus MTX was an effective therapy for moderate-to-severe plaque psoriasis with an acceptable safety and tolerability profile, indicating that it was feasible and well tolerated for patients.
Assuntos
Etanercepte/uso terapêutico , Fragmentos Fc das Imunoglobulinas/genética , Imunoglobulina G/genética , Metotrexato/uso terapêutico , Psoríase/tratamento farmacológico , Receptores Tipo II do Fator de Necrose Tumoral/genética , Proteínas Recombinantes de Fusão/genética , Adulto , Medicamentos Biossimilares , China , Método Duplo-Cego , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
AIM: To develop a sandwich enzyme-linked immunosorbent assay (ELISA) measuring hepatoma-specific datura stramonium agglutinin-tightly bounding gamma-glutamyltransferase (DSA-GGT) and evaluate its clinical application for hepatocellular carcinoma (HCC) diagnosis. METHODS: Serum DSA-GGT concentrations were measured with the sandwich ELISA system in 96 patients with HCC, 240 patients with chronic liver diseases and 119 healthy subjects. The diagnostic performance of DSA-GGT for HCC was assessed using receiver operating characteristic (ROC) curves. The diagnostic accuracy of DSA-GGT was compared with serum alpha-fetoprotein (AFP). RESULTS: The area under the ROC curve of DSA-GGT in discriminating patients with HCC from non-HCC was 0.865 (95% confidence interval: 0.818-0.915, P < 0.001). Serum DSA-GGT was positive in 67 out of 96 patients with HCC and 23 out of 240 patients with non-HCC diseases. The sensitivity and specificity of DSA-GGT and AFP for the diagnosis of HCC were 69.8% and 90.5%, and 72.9% and 89.1%, respectively. A higher sensitivity (93.8%) in the identification of HCC was observed by combining DSA-GGT and AFP. CONCLUSION: The sandwich ELISA system showed good reliability and reproducibility, and using the measurement, we found that serum DSA-GGT was a valuable marker of HCC, as a usable complementary to AFP. The sensitivity for identifying HCC could be significantly improved by combining DSA-GGT and AFP, and the combination could be used in large-scale screening for HCC in susceptible individuals.
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OBJECTIVE: To test whether nuclear factor kappa B plays an important role in the apoptosis-inhibitory effect of hepatitis B virus (HBV) P22(e) protein. METHODS: HepG2 cells were transfected with recombination plasmid pEGFP-HBVP22(e). The Act-D and TNF alpha were used to induce apoptosis. NF-kappa B inhibitor ALLN were used to inhibit the signaling pathway. The activation of NF-kappa B was EMSA, and the nulear translocation of NF-kappa B was determined by immuno-staining. RESULTS: Laser scanning confocal microscopy and EMSA indicated that HBV P22(e) protein enhanced the nuclear translocation of NF-kappa B after apoptosis induction. ALLN treatment inhibited the nuclear translocation of NF-kappa B, and blocked the apoptosis-inhibiting effect of HBV P22(e) protein. CONCLUSION: This study indicates that HBV P22(e) protein inhibits apoptosis of hepatocyte via the NF-kappa B signaling pathway.
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Apoptose , Carcinoma Hepatocelular/metabolismo , Antígenos do Núcleo do Vírus da Hepatite B/metabolismo , Neoplasias Hepáticas/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Proteínas do Core Viral/metabolismo , Células Hep G2 , Vírus da Hepatite B/genética , Humanos , Leupeptinas/farmacologia , Plasmídeos , Transdução de Sinais/efeitos dos fármacos , TransfecçãoRESUMO
OBJECTIVE: To prepare oligo microarrays for hepatitis virus detection and genotyping. METHODS: By analyzing the DNA or cDNA of HBV, HDV and 4 different genotypes of HCV with the BLAST program, a group of specific sequences for the candidate probes was specified. Array Designer 3.0 software was applied to analyze the candidates to select probes with high specificity, identical length and similar melting temperature (Tm). Altogether 16, 8 and 68 oligonucleotide probes were designed for diagnosis of HBV, HDV, and genotyping HCV. Following the synthesizing and purification, oligo probes were deposited on oligonucleotide chips as microarrays for hepatitis virus detection and genotyping. The samples were labeled by RD-PCR method. Hybridization results were analyzed to cross out those probes with low specificity and sensitivity, and those with signal to noise ratios (SNR) less than 4.0. RESULTS: Two types of gene chips were successfully developed: microarrays for HBV and HDV simultaneous detection and for HCV genotyping. CONCLUSION: Using oligo probes to construct gene chips for clinical diagnosis of hepatitis virus is a simple and effective method. It may be widely used in detecting hepatitis viruses and their genotyping in clinical settings.
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Genótipo , Vírus da Hepatite B/genética , Análise de Sequência com Séries de Oligonucleotídeos , Sequência de Bases , Impressões Digitais de DNA , DNA Viral/genética , Vírus da Hepatite B/classificação , Dados de Sequência Molecular , Sondas de Oligonucleotídeos , Sensibilidade e EspecificidadeRESUMO
The clinical features of Lophomonas blattarum infection in 26 patients with bacterial pneumonia were analyzed. Common manifestation included fever, cough and breathlessness. Computed tomography (CT) showed interstitial change and alveolar exudation. The parasites were found in sputum smear and from the bronchoalveolar lavage fluid (BALF). Metronidazole was effectively used to cure the pulmonary infection of L. blattarum.
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Eucariotos/isolamento & purificação , Pneumopatias Parasitárias/diagnóstico , Pneumopatias Parasitárias/terapia , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/parasitologia , Adulto JovemRESUMO
Kimura disease (KD) is an uncommon chronic inflammatory disorder of unknown etiology, occurs mainly in Asian young males, presenting as subcutaneous growing masses, with a predilection for head and neck, with or without satellite lymphadenopathy. Herein, we report a case of an atypical manifestation of KD accompanied with NS in a middle-aged man, though the patient was clinically misdiagnosed previously. The diagnosis of KD can be difficult and misleading, so we must explore the main points of KD so as to prevent misdiagnosis.
Assuntos
Hiperplasia Angiolinfoide com Eosinofilia/complicações , Síndrome Nefrótica/etiologia , Hiperplasia Angiolinfoide com Eosinofilia/diagnóstico , Hiperplasia Angiolinfoide com Eosinofilia/terapia , Biópsia , Diagnóstico Diferencial , Erros de Diagnóstico , Glucocorticoides/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/terapia , Valor Preditivo dos Testes , Resultado do TratamentoRESUMO
Psoriasis is a chronic inflammatory skin disease with high rate of recurrence. New anti-interleukin-17 (IL-17) and anti-IL17RA biologics are in Phase 3 clinical trials and may prove to be more effective than existing biologic drugs. Now we perform a meta-analysis on efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis. In this meta-analysis, data analysis was performed with the Cochrane Collaboration's RevMan 5.0 software. Eight randomized controlled trials (RCTs) with a total of 3,213 psoriasis cases were included in the meta-analysis. Co-primary endpoints (week 12) were ≥ 75%/90% improvement in psoriasis area and a score of 0 (clear) or 1 (almost clear) on a 5-point Investigator's Global Assessment scale (IGA mod 2011 0/1) versus placebo [1]. The overall efficacy in the meta-analysis was as follows: PASI 75: for secukinumab 150 mg versus placebo, fixed-effects OR = 49.25, 95% CI: 33.67-72.06, Z = 20.07, P < 0.00001; PASI 90: for secukinumab 150 mg versus placebo, fixed-effects OR = 44.92, 95% CI: 24.72-81.62, Z = 12.49, P < 0.00001; IGA mod 2011 0/1: for secukinumab 150 mg versus placebo, random-effects OR = 22.25, 95% CI: 7.63-64.84, Z = 5.68, P < 0.00001; Compared with placebo, there were no significant adverse effects in the secukinumab groups, demonstrating safety in the treatment of moderate to severe plaque psoriasis. The proportion of patients who achieved 75%, 90% and IGA mod 2011 0/1 reductions respectively was significant in the secukinumab groups, demonstrating a rapid clinical improvement accompanied by a favorable short-term safety profile.