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1.
Front Immunol ; 15: 1412470, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39007153

RESUMO

The etiology of Guillain-Barré syndrome (GBS) may be autoimmune. About two-thirds of patients typically experience their first symptoms within 5 days to 3 weeks after common infectious diseases, surgery, or vaccination. Infection is a triggering factor for over 50% of patients. In recent years, a growing number of studies have indicated that some immune checkpoint inhibitors and COVID-19 may also contribute to the occurrence of GBS. However, drugs are considered a rare cause of GBS. The patient in our case was a 70-year-old man who developed GBS after initiating secukinumab for psoriasis. Upon diagnosis suggesting a potential association between secukinumab and the development of GBS, as per the Naranjo adverse drug reaction (ADR) probability scale, we decided to discontinue the drug. Following this intervention, along with the administration of immunoglobulin, the patient exhibited a significant improvement in extremity weakness. The association of GBS with secukinumab treatment, as observed in this case, appears to be uncommon. The underlying mechanisms that may link secukinumab to the development of GBS are not yet fully understood and warrant further scientific inquiry and rigorous investigation. However, we hope that this report can raise greater awareness and vigilance among medical professionals to enhance the safety of patients' medication.


Assuntos
Anticorpos Monoclonais Humanizados , Síndrome de Guillain-Barré , Psoríase , Humanos , Síndrome de Guillain-Barré/induzido quimicamente , Síndrome de Guillain-Barré/etiologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Idoso , Masculino , Psoríase/tratamento farmacológico , Psoríase/complicações , SARS-CoV-2 , COVID-19/complicações
2.
Front Cell Infect Microbiol ; 14: 1359888, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828265

RESUMO

Toxoplasma, an important intracellular parasite of humans and animals, causes life-threatening toxoplasmosis in immunocompromised individuals. Although Toxoplasma secretory proteins during acute infection (tachyzoite, which divides rapidly and causes inflammation) have been extensively characterized, those involved in chronic infection (bradyzoite, which divides slowly and is surrounded by a cyst wall) remain uncertain. Regulation of the cyst wall is essential to the parasite life cycle, and polysaccharides, such as chitin, in the cyst wall are necessary to sustain latent infection. Toxoplasma secretory proteins during the bradyzoite stage may have important roles in regulating the cyst wall via polysaccharides. Here, we focused on characterizing the hypothetical T. gondii chitinase, chitinase-like protein 1 (TgCLP1). We found that the chitinase-like domain containing TgCLP1 is partially present in the bradyzoite microneme and confirmed, albeit partially, its previous identification in the tachyzoite microneme. Furthermore, although parasites lacking TgCLP1 could convert from tachyzoites to bradyzoites and make an intact cyst wall, they failed to convert from bradyzoites to tachyzoites, indicating that TgCLP1 is necessary for bradyzoite reactivation. Taken together, our findings deepen our understanding of the molecular basis of recrudescence and could contribute to the development of novel strategies for the control of toxoplasmosis.


Assuntos
Quitinases , Proteínas de Protozoários , Toxoplasma , Toxoplasmose , Animais , Humanos , Camundongos , Quitinases/metabolismo , Quitinases/genética , Estágios do Ciclo de Vida , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Toxoplasma/enzimologia , Toxoplasma/genética , Toxoplasma/crescimento & desenvolvimento , Toxoplasma/metabolismo , Toxoplasmose/parasitologia
4.
J Inflamm Res ; 17: 1839-1843, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38523688

RESUMO

Cogan's syndrome (CS) is a rare chronic inflammatory disease, characterized by interstitial keratitis and vestibular auditory dysfunction. Hypertrophic pachymeningitis (HP) is a rare chronic aseptic inflammatory disease of the central nervous system. This article reports a patient with CS coexisting with HP. The patient was a 66-year-old male with fever, headache, red eyes, hearing loss, and significantly elevated inflammatory markers. Cerebrospinal fluid examination, blood culture, and tests for autoantibodies such as antinuclear antibodies were negative. Pure tone audiology (PTA) indicated bilateral sensorineural deafness. Both Positron emission tomography-computed tomography (PET/CT) and vascular color Doppler ultrasound suggest the presence of vasculitis. Considering Cogan's syndrome, the patient received 40 mg of methylprednisolone intravenously once daily. The brain's magnetic resonance imaging (MRI) revealed slightly thickened and enhanced dura mater, suggesting HP. The dose of methylprednisolone was increased to 40 mg intravenously every 8 hours, leading to the patient's improved symptoms and decreased inflammatory markers. Both CS and HP are rare chronic inflammatory diseases, and their coexistence is even rarer, with only two reported cases in literature up to date. The coexistence of CS and HP should be considered when the CS patients with headaches do not respond well to treatment.

5.
Int J Rheum Dis ; 27(1): e14762, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37270684

RESUMO

Takayasu arteritis (TAK) is the main type of large vessel arteritis in young adults, which mainly affects the aorta and its main branches, leading to clinical manifestations such as syncope, intermittent limb claudication, hypertension, and abdominal pain. Among them, venous involvement is rarely reported. Here we show a case of TAK presenting as phlebitis. This was a 27-year-old woman, who initially admitted to our hospital with myalgia of the upper and lower extremities and night sweats. She was diagnosed as TAK according to the 1990 American College of Rheumatology TAK criteria. Surprisingly, vascular ultrasonography revealed wall thickening as indicated by macaroni sign of the multiple veins. TAK phlebitis appeared at the active phase, while disappearing rapidly at remission. Phlebitis might have a close relationship with disease activity. By retrospective study in our department, the estimated incidence rate of phlebitis might be 9.1% in TAK. With the literature review, it revealed that phlebitis might be an ignored manifestation in active TAK. However, due to the smaller sample size, it should be noted that a direct cause-effect relationship cannot be established.


Assuntos
Hipertensão , Flebite , Arterite de Takayasu , Feminino , Adulto Jovem , Humanos , Adulto , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/diagnóstico por imagem , Estudos Retrospectivos , Aorta , Flebite/diagnóstico por imagem , Flebite/etiologia
6.
J Int Med Res ; 51(9): 3000605231198742, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37728627

RESUMO

The prognosis of anti-MDA5-positive dermatomyositis (DM)-associated rapidly progressive interstitial lung disease (RPILD) is extremely poor and effective treatment options are limited. In addition, the risk of infection during immunosuppressive treatment is a major challenge. We report here, a case of RPILD in a 31-year-old man with anti-MDA5 antibody-positive DM. Despite treatment with methylprednisolone and human immunoglobulin, his lung condition worsened and his serum ferritin levels increased. Six cycles of plasma exchange (PE) adjuvant treatment significantly mitigated his symptoms and he was discharged from hospital two months later. We suggest that PE may be a promising therapeutic option for patients with anti-MDA5-positive DM-associated RPILD. However, randomized, controlled studies are required to confirm our findings.


Assuntos
Dermatomiosite , Doenças Pulmonares Intersticiais , Masculino , Humanos , Adulto , Troca Plasmática , Dermatomiosite/complicações , Dermatomiosite/terapia , Adjuvantes Imunológicos , Hospitais , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/terapia
7.
Curr Med Imaging ; 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700468

RESUMO

INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is a relatively rare immune-mediated chronic inflammatory disease with fibrosis newly defined in recent years. It can involve multiple systems and organs with complex clinical manifestations. Due to mass-like lesions, it is easily misdiagnosed as tumors. CASE REPORT: Herein, we report a 57-year-old woman treated for submandibular mass and anosmia. The serum IgG4 level was increased. The biopsy of the submandibular gland indicated salivary gland tissue and hyperplasia of fibrous tissue and lymphoid tissue. Immunohistochemical examination showed a large number of IgG4-positive plasma cells. M protein was found in the patient's serum by immunofixation electrophoresis, and plasma cell diseases were excluded by bone marrow puncture. PET/CT examination showed that besides the submandibular glands, the parotid gland, common bile duct, the transitional part of the left renal pelvis and ureter, retroperitoneum in the lower abdomen, and multiple lymph nodes were also involved. The patient was diagnosed with IgG4-RD, and after treatment with glucocorticoid, the enlargement of submandibular glands and decreased olfactory function improved. After 14 weeks of treatment, the serological examinations, PET/CT, and ultrasound re-examination results showed significant improvement. So far, the patient has been followed up for 27 months and is in continuous remission. CONCLUSION: This case report aims to raise awareness of IgG4-RD and explore the value of PET/CT in the diagnosis and efficacy monitoring of the disease.

8.
Placenta ; 137: 38-48, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37068447

RESUMO

INTRODUCTION: Antiphospholipid syndrome is an autoimmune disease characterized by pregnancy-related morbidity, related to persistent positivity of antiphospholipid antibodies (APL). One of the characteristics of pregnancy-related morbidity in patients with antiphospholipid syndrome is recurrent spontaneous abortion (RSA). This study aimed to examine the mechanism through which metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) regulates methyl-CpG-binding domain protein 4 (MBD4) expression in APL-positive RSA. METHODS: Clinical samples were subjected to microarray analysis to filter differentially expressed genes. RSA mice with APL positivity were generated, followed by adenoviral vector injection to artificially upregulate MALAT1. The effects of MALAT1 on the biological behavior of trophoblast cells were assessed. The downstream mechanism of MALAT1 was analyzed using subcellular fractionation and bioinformatics prediction, and the relationship between MALAT1 and CREB binding protein (CREBBP) or MBD4 was investigated in trophoblast cells. RESULTS: MALAT1 was downregulated in APL-positive RSA patients. MALAT1 was predominantly localized in the nucleus and recruited CREBBP to mediate the MBD4 transcription. In the APL-positive RSA mice overexpressing MALAT1, the expression of soluble Fms-related tyrosine kinase 1 and anticardiolipin antibody and the embryonic resorption rate were decreased, indicating that MALAT1 reduced the occurrence of RSA in mice. Moreover, MALAT1 enhanced proliferation, migration, and invasion of trophoblast cells through recruiting CREBBP to promote MBD4 expression. Silencing of CREBBP or MBD4 increased embryonic resorption rate in RSA mice overexpressing MALAT1. DISCUSSION: MALAT1 suppresses APL-positive RSA by promoting MBD4 transcription through recruitment of CREBBP to the MBD4 promoter region.


Assuntos
Aborto Habitual , Aborto Espontâneo , Síndrome Antifosfolipídica , RNA Longo não Codificante , Animais , Feminino , Camundongos , Gravidez , Aborto Habitual/genética , Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica/complicações , Perda do Embrião , RNA Longo não Codificante/genética
9.
J Autoimmun ; 136: 103028, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37001432

RESUMO

Follicular helper T (Tfh) cells are important for generating humoral immune responses by helping B cells form germinal centers (GCs) and the production of high-affinity antibodies. However, aberrant Tfh cell expansion also contributes to the generation of self-reactive autoantibodies and promotes autoantibody-mediated autoimmune diseases such as systemic lupus erythematosus (SLE). Protein phosphatase 2A catalytic subunit alpha isoform (PP2A Cα) expression levels are elevated in peripheral T cells of SLE patients and positively correlate with autoantibody titers and disease activity. Here, we demonstrate a critical role of PP2A in Tfh differentiation by using T cell restricted PP2A Cα deficient mice. We observed impaired Tfh differentiation and GC response in two different classical Tfh induction models. Mechanistic studies revealed that downregulation of protein translation of the Tfh lineage transcription factor BCL6 in PP2A deficient T cells. Importantly, we found that PP2A deficiency by either gene knockout or chemical inhibition alleviated lupus severity in mice. Lastly, we confirmed a positive correlation between PP2A Cα and BCL6 protein levels in human CD4+ T cells from patients with SLE. In summary, our study revealed a critical role of PP2A in regulating Tfh cells and suggests it is a potential therapeutic target for lupus.


Assuntos
Lúpus Eritematoso Sistêmico , Linfócitos T Auxiliares-Indutores , Humanos , Camundongos , Animais , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/metabolismo , Autoanticorpos , Linfócitos B , Diferenciação Celular
10.
Front Cardiovasc Med ; 9: 1033297, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505357

RESUMO

Background: The strategy of ablation index (AI)-guided high-power ablation seems to be a novel strategy for performing pulmonary vein isolation (PVI). An AI-guided high-power ablation strategy was used in this study to determine whether superior vena cava isolation (SVCI) after PVI was feasible and safe for patients with AF. Methods: Data from 53 patients with AF were collected. Mapping and ablation of SVC were performed. The applied power was set at 45 W and the procedure was guided by AI. The SVC was divided into six segments in a cranial view. The RF applications and AI values in different segments were compared and analyzed. Using receiver operating characteristic (ROC) analysis, the diagnostic accuracy of AI value for predicting segment block was evaluated. Results: Electrical SVCIs were successfully achieved in all patients. SVCI was performed by segment ablation in most cases, with RF applications in different segments. The mean AI value in non-lateral walls was higher than that of the lateral wall (392 ± 28 vs. 371 ± 37, P < 0.001). Acutely blocked sites had significantly larger AI values compared with no-blocked sites (390 ± 30 vs. 343 ± 23, P < 0.001). The optimal AI cut-off value for non-lateral segments was 379 (sensitivity: 75.9%, specificity: 100%) and for lateral segments was 345 (sensitivity: 82.3%, specificity: 100%). Conclusion: The AI values were predictive of the acute conduction block of SVCI. With AI values of 345 and 379, respectively, conduction block was achieved in the lateral walls at a lower level than in the non-lateral walls.

11.
J Int Med Res ; 50(11): 3000605221131136, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36345172

RESUMO

Cryoglobulinaemia can manifest as fatigue, purpura, and joint pain, and can involve the kidneys and peripheral nervous system. Type II and mixed cryoglobulinemia cases are usually associated with hepatitis C virus infection and autoimmune diseases, and most cases reported outside China have been related to hepatitis C virus. The pathological manifestation of cryoglobulinaemia glomerulonephritis is always membranous proliferative glomerulonephritis or membranous nephropathy; other pathological types are rare. This current case report describes a female patient with hepatitis B virus (HBV)-associated cryoglobulinaemic glomerulonephritis. The patient had hepatitis B complicated with purpura, abnormal urinalysis and renal function. She was positive for rheumatoid factor and had decreased complement, and her blood cryoglobulin level was positive. The pathological findings were consistent with late-stage capillary proliferative glomerulonephritis, which improved after steroid, immunosuppressant and anti-HBV treatment.


Assuntos
Crioglobulinemia , Glomerulonefrite Membranosa , Glomerulonefrite , Hepatite B , Hepatite C , Humanos , Feminino , Crioglobulinemia/complicações , Vírus da Hepatite B , Hepacivirus , Glomerulonefrite/complicações , Glomerulonefrite/tratamento farmacológico , Hepatite B/complicações
12.
J Immunol ; 209(5): 916-925, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35922064

RESUMO

Thymocytes need to proliferate into a significant cell mass to allow a subsequent selection process during the double-positive (DP) stage. However, it is not clear at what stage this massive cell proliferation occurs. Immature CD8 single-positive (ISP) cells are a well-defined thymocyte subpopulation. However, the function of this cell subset has not yet been characterized. In this study, we analyzed the transcription pattern of mouse ISP cells and observed higher expression levels of cell cycling genes. We also found out that ISP cells exhibited the highest cell proliferative capacity among thymocytes in different developmental stages. Nuclear protein ataxia-telangiectasia (NPAT/p220) is one of the highly expressed cell cycling genes in ISP cells, which is known to play a critical role in coordinating histone gene expression necessary for rapid cell proliferation. Selective deletion of NPAT at the ISP stage led to reduced thymus size and significant loss of DP cells, secondary to reduced histone gene expression and impaired ISP cell proliferation capacity. A block of thymocyte development at the ISP stage was also observed, which was due to increased IL-7R expression. Continuous IL-7R signal served as a compensating mechanism for cell proliferation upon NPAT deletion, but in turn inhibited the expression of transcription factors TCF-1 and LEF-1, which is essential for the transition of ISP to DP cells. In summary, our study revealed the proliferation capacity of the ISP subpopulation during thymocyte differentiation as well as a vital role of NPAT in this developmental stage.


Assuntos
Histonas , Timócitos , Animais , Linfócitos T CD8-Positivos/metabolismo , Proteínas de Ciclo Celular , Diferenciação Celular , Proliferação de Células , Histonas/metabolismo , Camundongos , Proteínas Nucleares/metabolismo , Timócitos/metabolismo , Timo/metabolismo
13.
Rheumatology (Oxford) ; 62(1): 373-383, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-35412608

RESUMO

OBJECTIVES: This study aimed to investigate the high-resolution CT (HRCT) characteristics of anti-melanoma differentiation-associated gene 5 (MDA5) antibody positive dermatomyositis-associated interstitial lung disease (anti-MDA5 DM-ILD), and to clarify the underlying mechanisms of the clinical phenomenon. METHODS: Clinical data and HRCT patterns were compared between anti-MDA5 DM-ILD (n = 32) and antisynthetase syndrome-associated ILD (ASS-ILD) (n = 29). RNA sequencing of whole-blood samples from the two groups, and in vitro experiments using human embryonic lung fibroblasts (HELFs) were conducted to explore the potential mechanisms of the clinical findings. RESULTS: The anti-MDA5 DM-ILD subset had a significantly higher incidence of rapidly progressive ILD (RPILD) than ASS-ILD (65.6% vs 37.9%; P = 0.031). The relative percentage of the lung fibrosis HRCT pattern was significantly lower in the anti-MDA5 DM-ILD group, especially the RPILD subgroup (P = 0.013 and 0.003, respectively). RNA sequencing detected the upregulated genes including interferon-induced helicase C domain 1 (encoding MDA5), and a trend towards downregulated expression of TGF-ß signalling components in anti-MDA5 DM-ILD. In vitro culture of HELFs revealed that upregulated expression of MDA5 in HELFs was correlated with the downregulated expression of alpha smooth muscle actin, connective tissue growth factor, collagen I and collagen III by suppressing the TGF-ß signalling pathway. CONCLUSIONS: Anti-MDA5 DM-ILD patients have significantly less lung fibrosis and elevated MDA5 expression. The upregulated expression of MDA5 has relations with the suppression of the pro-fibrotic function of fibroblasts via the TGF-ß signalling pathway, which may partially explain the mechanism of the clinical phenomenon.


Assuntos
Dermatomiosite , Doenças Pulmonares Intersticiais , Fibrose Pulmonar , Humanos , Autoanticorpos , Progressão da Doença , Helicase IFIH1 Induzida por Interferon/genética , Prognóstico , Fibrose Pulmonar/complicações , Estudos Retrospectivos
14.
Front Pharmacol ; 13: 793394, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35237159

RESUMO

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive bone erosion on diarthrodial joints. RA patients usually experienced three stages before final diagnosis: the health period, the pre-clinical period (immune response exists without clinical symptoms), and the pre-RA period (immune response exists with mild inflammatory manifestation). Presently, there is seldom guidance referring to early intervention which is a benefit for stable disease conditions and low morbidity. Prophylactic treatment is a major feature of traditional Chinese medicine (TCM). In this present study, a multi-center, double-blind, placebo-controlled clinical trial is carried out to evaluate both efficacy and safety in preventing RA progression on Yunpi Qufeng Chushi formula (YQCF). Method: The multi-center, double-blind, placebo-controlled clinical trial is conducted in 13 hospitals nationwide. A total of 390 patients ages between 18 and 70 will be recruited in the trial. They will be randomly assigned to the intervention group (YQCF) and placebo group. The follow-up visit will be taken every 3 months from baseline to 1 year. Diagnosis, disease activity scores, clinical disease activity index (CDAI), simplified disease activity index (SDAI), TCM syndrome scores, and safety assessments will be recorded at every visit. Joint color doppler ultrasound, health assessment questionnaire-disability index (HAQ-DI), and functional assessment of chronic illness therapy-fatigue (FACIT-F) will be recorded at baseline and the last visit. Discussion: This work will provide evidence of YQCF in preventing RA progression. However, whether early intervention would benefit the controlling RA disease still needs a long-term follow-up. Ethics and dissemination: Protocol version 2 (201910-1). This research was approved by the medical ethics committee of Zhejiang Chinese Medical University (2019-045). Results will be published in a peer-reviewed academic journal. Trial registration numbers: http://www.chictr.org.cn/index.aspx, ChiCTR1900024166.

15.
Int J Gen Med ; 14: 8725-8735, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34849013

RESUMO

BACKGROUND: This study determined the ischaemic J wave pattern associated with ventricular fibrillation (VF). METHODS: A total of 262 patients diagnosed with ST-elevation myocardial infarction (STEMI) were recruited from October 2017 to September 2020. All data were collected and analysed, including baseline characteristics, electrocardiogram (ECG), coronary angiography (CAG), and examination outcomes. RESULTS: There were 193 STEMI patients with J wave elevation but without an ischaemic J wave (NJ group) and 69 patients with an ischaemic J wave; the latter were then subgrouped into early repolarization pattern (ERP; n=62) and Brugada pattern groups (BrP [anteroseptal ERP]; n=7). Univariate and multivariate logistic regression analyses were used to clarify high-risk factors and characteristics of ischaemic J waves. Multivariate logistic regression analysis revealed that an ischaemic J wave (odds ratio [OR], 9.708; 95% CI, 2.570-36.664; P=0.01) independently predicted VF. In the subgroup analysis, BrP (OR, 31.214; 95% CI, 3.949-246.742; P=0.001), slur morphology of the ERP (OR, 8.15; 95% CI, 1.563-42.558; P<0.05), and the number of leads with an ischaemic J wave > 3 (OR, 16.174; 95% CI, 3.064-85.375; P=0.001) were significantly associated with VF occurrence after adjusting for multiple variables. CONCLUSION: An ischaemic J wave is an independent risk factor for VF in STEMI patients. BrP, slur morphology, and > 3 leads with an ischaemic J wave could increase the incidence of VF.

17.
J Interv Card Electrophysiol ; 62(1): 1-7, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33730302

RESUMO

BACKGROUND: Contact force-sensing catheters have been widely used in catheter ablation. During the past few decades, more attention has been paid on the technique of high-power ablation. The purpose of this meta-analysis is to compare the efficacy and safety of conventional power and high power on atrial fibrillation radiofrequency ablation by contact force-sensing catheters. METHODS: We identified studies through searching MEDLINE, Embase, the Web of Science, Scopus, and the Cochrane Library from inception up until July 2020. The primary outcomes were defined as recurrence of atrial tachyarrhythmia and complications. The secondary outcomes were acute reconnections of pulmonary veins (PVs), ablation time, and the total procedural time. RESULTS: Four nonrandomized, observational studies (nROS) were selected involving 231 patients with high-power ablation and 239 patients with conventional power ablation. There were insignificant differences in the recurrence rate of atrial tachyarrhythmia (14.2% versus 20.5%, OR: 0.64, 95%CI: 0.39 to 1.04, Z = 1.82, P = 0.07) and clinical complications (1.7% versus 2.5%, OR: 0.72, 95%CI: 0.21 to 2.47, Z = 0.51, P = 0.61) between high-power and conventional power ablation. However, compared with conventional power group, the high-power group had fewer acute PVs reconnections (P = 0.0001), shorter in ablation time (P < 0.0001), and the total procedural time (P < 0.0001). CONCLUSIONS: High-power ablation could not only ablate safely and efficiently but also reduce focal ablation time and total procedural time significantly.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Fibrilação Atrial/cirurgia , Catéteres , Humanos , Veias Pulmonares/cirurgia , Recidiva , Resultado do Tratamento
18.
Cell Mol Immunol ; 18(8): 1896-1903, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32472023

RESUMO

Dysregulated B-cell activation plays pivotal roles in systemic lupus erythematosus (SLE), which makes B-cell depletion a potential strategy for SLE treatment. The clinical success of anti-CD19 CAR-T cells in treating B-cell malignancies has attracted the attention of researchers. In this study, we aimed to investigate the feasibility of applying anti-CD19 CAR-T cell therapy to SLE treatment in a mouse disease model. We constructed murine anti-CD19 CARs with either CD28 or 4-1BB as the intracellular costimulatory motif and evaluated the therapeutic function of the corresponding CAR-T cells by infusing them into MRL-lpr mice. Furthermore, anti-CD19 CAR-T cells were transferred to MRL-lpr mice before the onset of disease to determine their role in SLE prevention. According to our observations, compared with antibody treatment, the adoptive transfer of our anti-CD19 CAR-T cells showed a more sustained B-cell-depletion effect in MRL-lpr mice. The transfer of syngeneic anti-CD19 CAR-T cells not only prevented disease pathogenesis before the onset of disease symptoms but also displayed therapeutic benefits at a later stage after disease progression. We also tried to optimize the treatment strategy and found that compared with CAR-T cells with the CD28 costimulatory motif, CAR-T cells with the 4-1BB costimulatory motif showed better therapeutic efficiency without cell enrichment. Taken together, these results show that anti-CD19 CAR-T cell therapy was effective in the prevention and treatment of a murine model of SLE, indicating its potential for clinical use in patients.


Assuntos
Lúpus Eritematoso Sistêmico , Linfócitos T , Animais , Antígenos CD19 , Modelos Animais de Doenças , Humanos , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/terapia , Camundongos , Camundongos Endogâmicos MRL lpr
19.
Clin Rheumatol ; 40(3): 1147-1157, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32676918

RESUMO

The JAK family (JAK1, JAK2, JAK3, and TYK2) have recently emerged as a potential therapeutic management in controlling severe and refractory dermatomyositis. Meanwhile, the progress in the discovery of JAK blockers is significant, with an increasing number of selective JAK inhibitors reported and some are in or prepare for clinical trials. However, the importance of each JAK in dermatomyositis is unclear, which is critical for a comprehensive understanding of dermatomyositis and significant for forming mechanism-based strategy. Here, we presented a case with clinically amyopathic dermatomyositis and essential thrombocytosis with a somatic constitutive active mutation of JAK2(V617F). The coexistence of these two uncommon diseases attracted us to investigate their underlying relationship. To this end, we characterized the clinical course and laboratory findings of this patient. Particularly, we correlated JAK2(V617F) mutation burden in affected peripheral blood subset with clinical activity score of dermatomyositis. Based on our observation, we concluded that these two diseases are independent disorders, and JAK2(V617F) mutation burden is irrelevant to the severity of dermatomyositis. Finally, we reviewed the literature and summarized them with a thorough discussion.


Assuntos
Dermatomiosite , Transtornos Mieloproliferativos , Dermatomiosite/complicações , Dermatomiosite/genética , Humanos , Janus Quinase 2/genética , Janus Quinases , Mutação
20.
DNA Cell Biol ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33181024

RESUMO

Raynaud's phenomenon (RP) is an episodic vasospasm of the peripheral arteries caused by an exaggerated reaction to cold temperature or emotional stress. Restoring the angiogenesis capability of the acral lesional skin is a critical strategy to treat RP. Local injection of botulinum toxin-A (BTX-A) has also been reported for treatment of RP. However, since the exact mechanisms of BTX-A action are still unclear, its administration for treatment of RP is not widely used. In the present study, BTX-A was found to promote angiogenesis and relieve RP in the patient. To elucidate its mechanisms against angiogenesis, BTX-A was used to treat human umbilical vein endothelial cells (HUVECs), one of the most popular in vitro models of angiogenesis, and RNA sequencing was used to investigate differentially expressed genes. A total of 413 genes were upregulated, and 1634 were downregulated, with fold-changes >2.0 in HUVECs treated with BTX-A. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed BTX-A affected expression of angiogenesis-associated, angiogenesis-associated signaling pathway-related, metabolic pathway, and epigenetic regulation-related genes. These results demonstrate potential biomarkers of BTX-A action, thereby providing potential therapeutic mechanism(s) by which BTX-A relieves RP symptoms.

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