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BACKGROUND: To explore the clinical manifestations, diagnosis, and treatment of patients with acquired immunodeficiency syndrome (AIDS) complicated with drug-induced erythroderma. METHODS: The clinical data of 12 AIDS patients with drug-induced erythroderma in our hospital were retrospectively analyzed. The general information, offending medications, complications, modified severity-of-illness score for toxic epidermal necrolysis (SCORTEN) scores, and disease outcome spectrums were analyzed. RESULTS: Drug-induced erythroderma was mostly caused by antiviral drugs, antituberculosis drugs, antibiotics, traditional Chinese medicine, and immune checkpoint inhibitors. The spectrum of sensitizing drugs was broad, the clinical situation was complex, and infections were common. The affected areas were greater than 40% body surface area in all patients. The modified SCOTERN score averaged 3.01±0.99. All patients were treated with glucocorticoids, and nine patients were treated with intravenous immunoglobulin (IVIG) pulse therapy at the same time. The average time to effectiveness was 7.08±2.23 days, and the average hospital stay was 17.92±8.46 days. Eleven patients were cured, and one patient died of secondary multiple infections, who had a modified SCORTEN score of 5 points. The mortality rate in this study was 8.3%. CONCLUSIONS: The clinical situation of AIDS patients with drug-induced erythroderma in hospitalized patients is complex and the co-infection rate is high. The use of modified SCORTEN score may objectively and accurately assess the conditions, and the use of glucocorticoid combined with IVIG therapy may improve the prognosis.
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BACKGROUND: Urticarial vasculitis is a small vessel vasculitis characterized by long-lasting wheals. It was suggested omalizumab is well tolerated and effective in patients with hypocomplementaemic urticarial vasculitis. OBJECTIVE: To evaluate the clinical response and safety of omalizumab for treating patients with normocomplementaemic urticarial vasculitis (NUV) in real-world setting. METHODS: We collected data from a single-center. This study included patients with NUV who was received omalizumab therapy. During a 24-week study period, the clinical efficacy was evaluated by patient's self-assessment instrument urticarial vasculitis activity score and Dermatology Life Quality Index. RESULTS: Five patients with NUV were enrolled. Three patients received 6 doses of 150 or 300 mg omalizumab subcutaneously every 4 weeks. At 24-week follow-up, it was revealed improvement of clinical manifestations and reduction of urticarial vasculitis activity score and Dermatology Life Quality Index. At 24-week visit, mild wheals recurred in one patient who was only administrated with omalizumab for 4 times. One patient did not response to omalizumab therapy. No adverse events were recorded in the 5 patients. CONCLUSION: Omalizumab may be a potential choice in the treatment of patients with NUV in the real-world life.
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Immune-mediated necrotizing myopathy (IMNM) is a type of autoimmune myopathy characterized by severe diffuse proximal myofiber necrosis in the context of inflammatory myopathy. Autoantibodies of anti-signal recognition particle and anti-hydroxy-3-methylglutaryl-CoA reductase are two antibodies specific to IMNM. Erythema nodosum (EN) is often accompanied by various systemic diseases, such as autoimmune diseases. Herein, we report a female patient with signal recognition particle-associated IMNM, with EN as the first presentation. She showed significant clinical improvement after the initiation of glucocorticoids, intravenous immunoglobulin, rituximab, and mycophenolate mofetil. This case indicates that IMNM can initially present as EN. IMNM and EN might have overlapping pathogeneses.
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OBJECTIVE: To analyze the dynamic expression of Wnt family member 5A (Wingless-type MMTV integration Wnt site family, member 5a) in murine hair cycle and its inhibitory effects on follicle in vivo. METHODS: Situ hybridization in full-thickness skin was used to observe the change of mouse protein expression in different growth stages, and Ad-Wnt5a was injected after defeathering to observe the hair follicle growth in vivo. RESULTS: The Wnt5a mRNA was expressed at birth, and was firstly increased then decreased along with the progress of the hair cycle. It reached the peak in advanced stage of growth cycle (P<0.05). Rhoa and ß-catenin expression levels were significantly decreased in three groups. Rac2 expression was significantly up-regulated, and the expression level of Wnt5a, Shh and Frizzled2 was increased, but less significantly than group 2. CONCLUSIONS: The expression of Wnt5a mRNA is consistent with change of murine follicle cycle, and has obvious inhibitory effects on the growth of hair follicle in vivo, indicating that it is antagonistic to Wnts pathway and interferes the growth of follicle together.
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Folículo Piloso/metabolismo , Proteínas Wnt/biosíntesis , Animales , Distribución de Chi-Cuadrado , Perfilación de la Expresión Génica , Folículo Piloso/química , Ratones , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Piel/metabolismo , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Proteína Wnt-5aRESUMEN
Ribonucleic acid interference (RNAi) based on microRNA (miRNA) context may provide an efficient and safe therapeutic knockdown effect and can be driven by ribonucleic acid polymerase II (RNAP II). In this study, we designed and synthesized miR155-based artificial miRNAs against heparanase (HPSE) constructed with BLOCK-iT™ Pol II miR RNAi Expression Vector Kit. The expression levels of HPSE declined significantly in both the mRNA and protein levels in HPSE-miRNA transfected melanoma cells that exhibited reduction of adhesion, migration, and invasion ability in vitro and in vivo. We also observed that HPSE miRNA could inhibit the expressions of chemokines of interleukin-8 (IL8) and chemokine (C-X-C motif) ligand 1 (CXCL1), at both the transcriptional and translational levels. Further study on its probable mechanism declared that down-regulation of IL8 and CXCL1 by HPSE-miRNA may be correlated with reduced growth-factor simulated mitogen-activated kinase (MAPK) phosphorylation including p38 MAPK, c-Jun N-terminal kinase (JNK) and extracellular-signal-regulated kinase (ERK) 1 and 2, which could be rescued by miRNA incompatible mutated HPSE cDNA. In conclusion, we demonstrated that artificial miRNAs against HPSE might serve as an alterative mean of therapy to low HPSE expression and to block the adhesion, invasion, and metastasis of melanoma cells. Furthermore, miRNA-based RNAi was also a powerful tool for gene function study.
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Quimiocinas/metabolismo , Regulación hacia Abajo , Glucuronidasa/genética , Melanoma/patología , MicroARNs/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Invasividad Neoplásica/genética , Animales , Secuencia de Bases , Western Blotting , Cartilla de ADN , Ensayo de Inmunoadsorción Enzimática , Expresión Génica , Humanos , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos BALB C , Mutagénesis , Fosforilación , ARN Polimerasa II/metabolismo , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: Matrine is a traditional Chinese medicine with significant inhibitory activity against malignant tumors. Its effects on the invasiveness and metastasis of malignant tumors have rarely been reported. AIM: To investigate whether matrine can inhibit the metastasis-related activities of the human malignant melanoma cell line A375 in vitro. METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and Annexin-V-fluorescein isothiocyanate/propidium iodide (Annexin-V-FITC/PI) affinity assay were used to examine the effects of matrine on the proliferation and apoptosis induction of A375 cells. The morphologic changes of A375 cells were observed by light and electron microscopy. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were performed to evaluate the expression of heparanase mRNA and protein. The effect of matrine on the adhesion ability and invasiveness of treated A375 cells was tested by cell-Matrigel adhesion assay and Matrigel invasion assay, respectively. RESULTS: Matrine showed significant inhibition of the proliferation of A375 cells in a dose- and time-dependent manner. It also induced apoptosis in a dose-dependent manner. Compared with the control group, the levels of heparanase mRNA and protein expression of A375 cells treated with different concentrations of matrine were decreased significantly, as were their adhesion ability and invasiveness. CONCLUSIONS: These findings indicate that matrine inhibits the invasiveness and metastasis of A375 cells in vitro. The mechanisms may be linked to the inhibition of cellular proliferation, induction of apoptosis, and downregulation of heparanase mRNA and protein expression.
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Alcaloides/farmacología , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Melanoma/patología , Quinolizinas/farmacología , Análisis de Varianza , Western Blotting , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Glucuronidasa/genética , Glucuronidasa/metabolismo , Humanos , Medicina Tradicional China , Melanoma/enzimología , Melanoma/fisiopatología , Melanoma/ultraestructura , Microscopía Electrónica de Transmisión , Invasividad Neoplásica/prevención & control , Metástasis de la Neoplasia/prevención & control , Fitoterapia , Plantas Medicinales/química , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sophora/química , MatrinasRESUMEN
OBJECTIVE: To investigate the effect of matrine on the invasiveness and expression of heparanase-mRNA in human malignant melanoma cell line A375. METHODS: The A375 cells were treated by matrine in different concentration. The total RNAs were extracted from the cells 48 hours after treatment and then semi-quantitative RT-PCR were performed to evaluate the heparanase-mRNA expression levels. Effect of matrine on adhesion of treated A375 cells was tested by cell-Matrigel adhesion assay. The invasiveness of treated A375 cells was measured by Matrigel invasion assay. RESULTS: The hepanase-mRNA expression, adhesion and invasiveness of A375 cells treated with matrine of different final concentrations significantly decreased compared with that of the controls (p < 0.01). Besides, the inhibitory effects were signifcantly different when the cells treated with matrine of different concentrations (P < 0.01). CONCLUSION: By down-regulating the expression of heparanase-mRNA, matrine has a significant inhibitory effect on the adhesion and invasiveness of human malignant melanoma cell line in a dose-dependent manner.