RESUMO
Inherited deficiency of thymidine phosphorylase (TP), encoded by TYMP, leads to a rare disease with multiple mitochondrial DNA (mtDNA) abnormalities, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). However, the impact of TP deficiency on lysosomes remains unclear, which are important for mitochondrial quality control and nucleic acid metabolism. Muscle biopsy tissue and skin fibroblasts from MNGIE patients, patients with m.3243 A > G mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and healthy controls (HC) were collected to perform mitochondrial and lysosomal functional analyses. In addition to mtDNA abnormalities, compared to controls distinctively reduced expression of LAMP1 and increased mitochondrial content were detected in the muscle tissue of MNGIE patients. Skin fibroblasts from MNGIE patients showed decreased expression of LAMP2, lowered lysosomal acidity, reduced enzyme activity and impaired protein degradation ability. TYMP knockout or TP inhibition in cells can also induce the similar lysosomal dysfunction. Using lysosome immunoprecipitation (Lyso- IP), increased mitochondrial proteins, decreased vesicular proteins and V-ATPase enzymes, and accumulation of various nucleosides were detected in lysosomes with TP deficiency. Treatment of cells with high concentrations of dThd and dUrd also triggers lysosomal dysfunction and disruption of mitochondrial homeostasis. Therefore, the results provided evidence that TP deficiency leads to nucleoside accumulation in lysosomes and lysosomal dysfunction, revealing the widespread disruption of organelles underlying MNGIE.
Assuntos
DNA Mitocondrial , Fibroblastos , Lisossomos , Mitocôndrias , Encefalomiopatias Mitocondriais , Nucleosídeos , Timidina Fosforilase , Humanos , Lisossomos/metabolismo , Timidina Fosforilase/metabolismo , Timidina Fosforilase/deficiência , Timidina Fosforilase/genética , Encefalomiopatias Mitocondriais/metabolismo , Encefalomiopatias Mitocondriais/patologia , Encefalomiopatias Mitocondriais/genética , Fibroblastos/metabolismo , Fibroblastos/patologia , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Mitocôndrias/metabolismo , Nucleosídeos/metabolismo , Pseudo-Obstrução Intestinal/metabolismo , Pseudo-Obstrução Intestinal/patologia , Pseudo-Obstrução Intestinal/enzimologia , Pseudo-Obstrução Intestinal/genética , Oftalmoplegia/metabolismo , Oftalmoplegia/patologia , Oftalmoplegia/congênito , Distrofia Muscular Oculofaríngea/metabolismo , Distrofia Muscular Oculofaríngea/patologia , Masculino , Feminino , Pele/patologia , Pele/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/metabolismoRESUMO
OBJECTIVES: Caveolin family proteins, including caveolin-1 (Cav-1), caveolin-2 (Cav-2), and caveolin-3 (Cav-3), are identified as the principal protein components of caveolae in mammalian cells. Circulating form of caveolin family proteins can be used as a good potential biomarker for predicting disease. METHODS: To investigate the clinical significance of the serological levels of caveolin family proteins in patients with systemic lupus erythematosus (SLE), we evaluated the soluble serum levels of caveolin family proteins in patients with SLE by enzyme-linked immunosorbent assay (ELISA) and assessed their associations with various known clinical variables. RESULTS: The major findings of our study are as follows: Cav-2 was not detected in serum of SLE patients and normal controls (NCs). Serum Cav-1 and Cav-3 levels were higher in SLE patients compared with NCs. There were no significant correlations between serum Cav-1 and Cav-3 levels and SLE disease activity. Further analysis showed that serum Cav-3 may be more valuable as a marker than serum Cav-1 in SLE patients. CONCLUSION: Serum levels of Cav-1 and Cav-3 might have a diagnostic role in patients with SLE. However, their predictive and prognostic value was not determined. Further studies are necessary to determine the potential clinical significance of these assays in SLE.
Assuntos
Biomarcadores , Caveolinas , Lúpus Eritematoso Sistêmico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Caveolina 1/biossíntese , Caveolina 1/sangue , Caveolina 3/biossíntese , Caveolina 3/sangue , Caveolinas/biossíntese , Caveolinas/sangue , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Adulto JovemRESUMO
OBJECTIVE: Human leukocyte antigen (HLA)-B27 plays a crucial role in the pathogenesis of AS. TNF polymorphisms have been reported to be associated with AS susceptibility, but the results of these previous studies have been inconsistent. The aim of this study was to explore whether TNF polymorphism is associated with AS susceptibility in HLA-27-positive population. METHODS: Our search was done in the Pubmed, Embase, and Cochrane databases (up to March 2020). The pooled and individual odds ratios (ORs) with 95% confidence intervals (CIs) of the minor allele of each locus were presented to assess the associations between TNF polymorphisms and AS in HLA-B27-positive population. RESULTS: Ten studies from 8 articles were included in this meta-analysis. In the population of HLA-B27-positive patients and random healthy controls, there were statistical significance in the evaluation of association between the minor allele of TNF-238, -308, -857, -1031 and -863 and AS susceptibility, respectively. In the population of HLA-B27-positive patients and HLA-B27-positive healthy controls, there were no statistical differences in the comparison of minor allele of with their respective major allele in the fixed model. CONCLUSIONS: There was no association of the TNF polymorphisms with AS in the HLA-B27-positive AS group and HLA-B27-positive control group. Polymorphisms of TNF-238, -308, -857, -1031, -863 were associated with AS susceptibility in the HLA-B27-positive AS patients and random control population. Other gene SNPs except TNF may play an important role in AS susceptibility in HLA-B27-positive population.
Assuntos
Antígeno HLA-B27 , Espondilite Anquilosante , Alelos , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença/genética , Antígeno HLA-B27/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Espondilite Anquilosante/genéticaRESUMO
BACKGROUND: Studies investigating the association between the polymorphisms in TNF and ankylosing spondylitis have been reported the conflicting results. Here we performed a meta-analysis based on the evidence available from the literature up-to-date to further clarify this relationship. METHODS: Our systematic search was done in the PubMed, Embase and Cochrane databases (up to March 2020). The pooled and individual odds ratios (ORs) with 95% confidence intervals (CIs) of the minor allele of each locus were presented to assess the associations between TNF polymorphisms and AS in different ethnicities in common population. RESULTS: Seventeen studies, consisting of seven European studies, eight East Asian studies and two Latin-American studies, were included in this meta-analysis. In the total population, the A allele in TNF-238 (OR = 0.702, 95%CI = 0.506-0.973, p = 0.034) and TNF-308 (OR = 0.638, 95%CI = 0.507-0.804, p = 0.000), the C allele in TNF-1031 (OR = 0.594, 95%CI = 0.446-0.791, p = 0.000), the T allele in TNF-850 (OR = 3.462, 95%CI = 1.764-6.798, p = 0.000) and rs769178 (OR = 2.593, 95%CI = 2.175-3.091, p = 0.000) were significantly associated with AS susceptibility. There were no significant association between the minor alleles of TNF-376, TNF-857, TNF-863 and AS susceptibility. There are inconsistent results in the Latin-American population and East Asian population with those in the total population. CONCLUSIONS: Our meta-analysis suggests that TNF-α polymorphisms at positions - 238, - 308, - 850, - 1031 and rs769178 could have an influence on ankylosing spondylitis susceptibility in the total population. But there is no association of the TNF-376, TNF-857, TNF-863 polymorphisms with ankylosing spondylitis. Some results in the subgroups are not consistent with those in the total population.
Assuntos
Espondilite Anquilosante , Alelos , Predisposição Genética para Doença/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Espondilite Anquilosante/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
Uncontrolled activation of NLRP3 inflammasome initiates a series of human inflammatory diseases. Targeting NLRP3 inflammasome has attracted considerable attention in developing potential therapeutic interventions. Here, we reported that dehydrocostus lactone (DCL), a main component of Saussurea lappa from the traditional Chinese medicine, inhibited NLRP3 inflammasome-mediated caspase-1 activation and subsequent interleukin (IL)-1ß production in primary mouse macrophages and human peripheral blood mononuclear cells and exerted an inhibitory effect on NLRP3-driven inflammation. Mechanistically, DCL significantly blocked the ASC oligomerization, which is essential for the assembly of activated inflammasome. Importantly, in vivo experiments showed that DCL reduced IL-1ß secretion and peritoneal neutrophils recruitment in LPS-mediated inflammation mouse model, which is demonstrated to be NLRP3 dependent. These results suggest that DCL is a potent pharmacological inhibitor of NLRP3 inflammasome and may be developed as a therapeutic drug for treating NLRP3-associated diseases.
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Quimiotaxia de Leucócito/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Inflamassomos/efeitos dos fármacos , Inflamação/prevenção & controle , Lactonas/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Sesquiterpenos/farmacologia , Adulto , Animais , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/fisiologia , Proteínas Adaptadoras de Sinalização CARD/antagonistas & inibidores , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Proteínas de Ligação ao Cálcio/antagonistas & inibidores , Proteínas de Ligação ao Cálcio/fisiologia , Caspase 1/metabolismo , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/fisiologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Interleucina-1beta/biossíntese , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/efeitos dos fármacos , Nigericina/farmacologia , Poli I-C/farmacologia , Polimerização/efeitos dos fármacos , Organismos Livres de Patógenos Específicos , Ácido Úrico/farmacologiaRESUMO
Objective: To screen the germination and seedling conditions of Trollius chinensis seeds from Chongli county, Zhangjiakou city. To provide the theoretical basis and practical technology for establishing technology system of seedling and cultivation of Trollius chinensis seeds in Zhangjiakou city. Methods: The data were collected and analyzed by the contrast test of greenhouse. Results: The most suitable conditions of Trollius chinensis seedling treatment were as follows, the concentration of GA3 was 800 mg / m L at 4 â,and under this condition in infusing for 4 days, and placed in the artificial climate chamber, the temperature was 20 â,light treatment for 4 days with 12 h light and 12 h darkness, and sprayed PEG 6000( 30 g / L). Trollius chinesis seeds were sowed on the 4th day, peat soil was selected as matrix, and the germination rate reached more than 85%. Conclusion: According to the characteristics of the seedling appearance and the conditions of the seedlings after transplanting, the seedling growth is robust and the survival rate is much higher.
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Germinação , Plântula , Ranunculaceae , Sementes , Solo , TemperaturaRESUMO
A highly luminescent silica film was fabricated using tetraethyl orthosilicate (TEOS) and 3-aminopropyltrimethoxysilane (APS) through a controlled sol-gel reaction. The pre-hydrolysis of TEOS and APS which resulted in the mixture of TEOS and APS in a molecular level is a key for the formation of homogenous films. The aminopropyl groups in APS play an important role for obtaining homogeneous film with high photoluminescence (PL). Red-emitting hybrid SiO2-coated CdTe nano-crystals (NCs) were fabricated by a two-step synthesis including a thin SiO2 coating via a sol-gel process and a subsequent refluxing using green-emitting CdTe NCs. The hybrid SiO2-coated CdTe NCs were embedded in a functional SiO2 film via a two-step process including adding the NCs in SiO2 sol with a high viscosity and almost without ethanol and a subsequent spinning coating. The hybrid SiO2-coated CdTe NCs retained their initial PL efficiency (54%) in the film. Being encapsulated with the hybrid NCs in the film, no change on the absorption and PL spectra of red-emitting CdTe NCs (632 nm) was observed. This indicates the hybrid NCs is stable enough during preparation. This phenomenon is ascribed to the controlled sol-gel process and a hybrid SiO2 shell on CdTe NCs. Because these films exhibited high PL efficiency and stability, they will be utilizable for potential applications in many fields.
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Compostos de Cádmio/química , Medições Luminescentes/métodos , Nanocompostos/química , Pontos Quânticos , Dióxido de Silício/química , Telúrio/química , Adsorção , Transferência de Energia , Teste de Materiais , Nanocompostos/ultraestrutura , Transição de Fase , Propriedades de SuperfícieRESUMO
BACKGROUND: Killer cell immunoglobulin-like receptors (KIR) contribute to the pathogenesis of multiple auto-immune diseases via the modulation of NK-, NKT- and T-cells. Thus, we want to know whether the expression pattern of KIR is associated with systemic lupus erythematosus (SLE) susceptibility. METHODS: Here, real-time quantitative PCR and fluorescence-activated cell sorting (FACS) were used to measure the stimulatory KIR (sKIR) and inhibitory KIR (iKIR) mRAN and protein levels on NK-, NKT- and T-cells in both SLE patients and healthy controls. RESULTS: In SLE patients, CD158a/h (KIR2DL1/S1) was highly expressed while CD158b/i/j (KIR2DL2/L3/S2, iKIR/iKIR/sKIR) was lowly expressed in NK- and NKT-cells in patients. The expression levels of KIR2DL1 and KIR2DL2 (iKIRs) were decreased while the expression levels of KIR2DS1 (sKIR) were increased in NK- and NKT-cells in the patients. CONCLUSIONS: We found that SLE patients represent aberrant expression of stimulatory and inhibitory KIRs in NK- and NKT-cells. Consequently, these different expression levels of KIRs may contribute to the abnormal function of these cells, which lead to the risk of SLE.
Assuntos
Células Matadoras Naturais/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Células T Matadoras Naturais/metabolismo , Receptores KIR2DL2/metabolismo , Receptores KIR/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Células Matadoras Naturais/patologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/patologia , Masculino , Células T Matadoras Naturais/patologia , Receptores KIR/biossíntese , Receptores KIR/genética , Receptores KIR2DL2/biossíntese , Receptores KIR2DL2/genética , Medição de Risco , Adulto JovemRESUMO
OBJECTIVE: To develop and conduct an initial validation of the Damage Index for IgG4-related disease (IgG4-RD DI). METHODS: A draft of index items for assessing organ damages in patients with IgG4-RD was generated by experts from the Chinese IgG4-RD Consortium (CIC). The preliminary DI was refined using the Delphi method, and a final version was generated by consensus. 40 IgG4-RD cases representing four types of clinical scenarios were then selected, each with two time points of assessment for at least 3 years of follow-up. 48 rheumatologists from 35 hospitals nationwide were invited to evaluate organ damage using the CIC IgG4-RD DI. The intraclass correlation coefficient (ICC) and the Kendall-W coefficient of concordance (KW) were used to assess the inter-rater reliability. The criterion validity of IgG4-RD DI was tested by calculating the sensitivity and specificity of raters. RESULTS: IgG4-RD DI is a cumulative index consisting of 14 domains of organ systems, including a total of 39 items. The IgG4-RD DI was capable of distinguishing stable and increased damage across the active disease subgroup and stable disease subgroup. In terms of scores at baseline and later observations by all raters, overall consistency in scores at baseline and later observations by all raters was satisfactory. ICC at the two time points was 0.69 and 0.70, and the KW was 0.74 and 0.73, respectively. In subgroup analysis, ICC and KW in all subgroups were over 0.55 and 0.61, respectively. The analysis of criterion validity showed a good performance with a sensitivity of 0.86 (95% CI 0.82 to 0.88), a specificity of 0.79 (95% CI 0.76 to 0.82) and an area under the curve of 0.88 (95% CI 0.85 to 0.91). CONCLUSION: The IgG4-RD DI is a useful approach to analyse disease outcomes, and it has good operability and credibility. It is anticipated that the DI will become a useful tool for therapeutic trials and studies of prognosis in patients with IgG4-RD.
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Doença Relacionada a Imunoglobulina G4 , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Consenso , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , China/epidemiologiaRESUMO
It is of vital significance to conduct active post-marketing surveillance of Chinese medicine, as an active response to laws, rules and guidelines issued by the China food and drug administration. The standards for technological specifications based on expert consensus have been drafted. These will provide technological support in evaluating adverse drug reactions (ADRs) or adverse drug events (ADEs). The technological specifications for post-marketing surveillance focus on two surveillance designs; one is a large sample registry study to explore general population ADR/ADE characteristics, the other is a nested case-control study to explore the characteristic and mechanisms of ADRs.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Medicamentos de Ervas Chinesas/normas , Vigilância de Produtos Comercializados/normas , China/epidemiologia , Monitoramento de Medicamentos/efeitos adversos , Monitoramento de Medicamentos/normas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Medicamentos de Ervas Chinesas/efeitos adversos , Sistemas de Informação Hospitalar , Humanos , Vigilância de Produtos Comercializados/métodosRESUMO
BACKGROUND: This study intended to investigate the independent effect of admission heart rate (HR) on the risk of major adverse cardiovascular events (MACEs) in acute myocardial infarction (AMI) patients with different left ventricular ejection fraction (LVEF) levels. METHODS: The study was a secondary analysis of the Acute Coronary Syndrome Quality Improvement in Kerela Trial. The relationship between admission HR and 30-day adverse outcomes in AMI patients with different LVEF levels was detected using a Logistic regression model. Interaction tests were used to compare the effects of different subgroups on HR and MACEs. RESULTS: Our study enrolled 18,819 patients. In both partially and fully adjusted models (Model1 and Model2), the risk of MACEs was highest in patients with HR ≥ 120 (OR: 1.62, 95%CI: (1.16, 2.26), P = 0.004, Model1; OR: 1.46, 95%CI: (1.00, 2.12), P = 0.047, Model2). There was a significant interaction between LVEF and HR (P for interaction = 0.003). Meanwhile, the trend test for this association showed that HR was positively and significantly associated with the MACEs in LVEF≥40% group (OR (95%CI): 1.27 (1.12, 1.45), P < 0.001). However, in LVEF<40% group, the trend test was not statistically significant (OR (95%CI): 1.09 (0.93, 1.29), P = 0.269). CONCLUSION: This study found that elevated admission HR was associated with a significantly higher risk for MACEs in patients admitted with AMI. Elevated admission HR was significantly associated with the risk of MACEs in AMI patients without low LVEF but not those with low LVEF (<40%). LVEF levels should be considered when evaluating the association between admission HR and the prognosis of AMI patients in the future.
Assuntos
Infarto do Miocárdio , Função Ventricular Esquerda , Humanos , Coração , Frequência Cardíaca , Prognóstico , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologiaRESUMO
OBJECTIVE: B-cell activating factor (BAFF) is a key regulator of primary Sjögren's syndrome (pSS), which is characterized by B-lymphocyte hyperactivity. BAFF, also known as tumor necrosis factor ligand superfamily member 13B, is encoded by TNFSF13B. This study aimed to explore the possible relationships between five single-nucleotide polymorphisms (SNPs) of TNFSF13B (rs9514827, rs1041569, rs9514828, rs1224141, and rs12583006) and pSS susceptibility. METHODS: We searched the following databases for articles on TNFSF13B polymorphism and pSS published up to January 2023: PubMed, Cochrane, Elsevier, Web of Science, CNKI, CQVIP, and WanFang. The odds ratios (with 95% confidence intervals) of genotypes and SNP alleles of TNFSF13B were investigated in patients with pSS to determine their relationships with pSS. RESULTS: This meta-analysis employing the fixed-effect model comprised three studies of pSS patients and randomly selected healthy controls (HCs), revealing statistically significant relationships between pSS susceptibility and two SNPs: rs1041569 and rs12583006. Because rs1041569 was not in Hardy-Weinberg equilibrium in the HC group, it was eliminated from the analysis. CONCLUSIONS: Polymorphisms in the BAFF (TNFSF13B) gene were related to vulnerability to pSS among pSS patients and HCs alike. The SNP rs12583006 was significantly related to pSS susceptibility in pSS patients.
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Fator Ativador de Células B , Síndrome de Sjogren , Humanos , Fator Ativador de Células B/genética , Síndrome de Sjogren/genética , Genótipo , Polimorfismo de Nucleotídeo Único , AlelosRESUMO
IMPORTANCE: Digital health applications have been shown to be effective in the management of chronic diseases with simple treatment targets. The potential clinical value of digital health applications in rheumatoid arthritis (RA) has not been well studied. OBJECTIVE: To investigate whether assessing patient-reported outcomes using digital health applications could result in disease control for patients with RA. DESIGN, SETTING, AND PARTICIPANTS: This is a multicenter, open-label randomized clinical trial in 22 tertiary hospitals across China. Eligible participants were adult patients with RA. Participants were enrolled from November 1, 2018, to May 28, 2019, with a 12-month follow-up. The statisticians and rheumatologists who assessed disease activity were blinded. Investigators and participants were not blind to group assignment. Analysis was conducted from October 2020 to May 2022. INTERVENTIONS: Participants were randomly assigned at a 1:1 ratio (block size of 4) to a smart system of disease management group (SSDM) or a conventional care control group. Upon the completion of the 6-month parallel comparison, patients in the conventional care control group were instructed to use the SSDM application for an extension of 6 months. MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of patients with disease activity score in 28 joints using the C-reactive protein (DAS28-CRP) of 3.2 or less at month 6. RESULTS: Of 3374 participants screened, 2204 were randomized, and 2197 patients with RA (mean [SD] age, 50.5 [12.4] years; 1812 [82.5%] female) were enrolled. The study included 1099 participants in the SSDM group and 1098 participants in the control group. At month 6, the rate of patients with DAS28-CRP of 3.2 or less was 71.0% (780 of 1099 patients) in the SSDM group vs 64.5% (708 of 1098 patients) in the control group (difference between groups, 6.6%; 95% CI, 2.7% to 10.4%; P = .001). At month 12, the rate of patients with DAS28-CRP of 3.2 or less in the control group increased to a level (77.7%) that was comparable with that (78,2%) in the SSDM group (difference between groups, -0.2%; 95% CI, -3.9% to 3.4%; P = .90). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of RA, the use of a digital health application with patient-reported outcomes was associated with an increase in disease control rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03715595.
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Antirreumáticos , Artrite Reumatoide , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/induzido quimicamente , Proteína C-Reativa , ChinaRESUMO
Human leukocyte antigen (HLA)-B27 confers a key role in ankylosing spondylitis (AS) susceptibility. Endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphisms are associated with AS susceptibility in common population. In this study we intended to evaluate the possible association between ERAP1 polymorphisms and AS susceptibility in HLA-27 positive population. Data were collected from Pubmed, Embase, and Cochrane databases. The pooled odds ratios and 95% confidence intervals of the minor allele of each locus were calculated to appraise the associations under ERAP1 polymorphisms and AS in HLA-B27 positive population. Bioinformatics analysis was performed to explore the underlying mechanism. Four studies were included in this meta-analysis. There was a significant association between the minor allele of rs2287987 and reducing the risk of developing AS in HLA-B27 positive population. But there was no significant association between the minor allele of rs30187, rs27044, rs10050860 and rs17482078 and AS susceptibility. According to HaploReg, 5 motifs changed for rs2287987 were found. The eQTL analysis demonstrated that rs2287987 may influence ERAP1 expression. Rs2287987 in ERAP1 may have small influence on AS susceptibility in HLA-B27 positive population. Bioinformatics analysis indicated that the altered motifs and the change of EARP1 expression may influence the AS susceptibility.
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Espondilite Anquilosante , Aminopeptidases/genética , Biologia Computacional , Predisposição Genética para Doença , Antígeno HLA-B27/genética , Humanos , Antígenos de Histocompatibilidade Menor/genética , Polimorfismo de Nucleotídeo Único , Espondilite Anquilosante/genéticaRESUMO
The thermal conductivity and thermal diffusivity of both metallic and non-metallic microwires are simultaneously measured by a cross-wire geometry. In this method, the heating wire serves both as a thermometer and a heater. The deflection of the heating wire is in situ modified by using the Ampère force to contact and separate the test wire. By using the quasi-steady-state measurement, the thermal contact resistances under different contact conditions are obtained so that the effect on thermal conductivity can be eliminated. This method is verified by both the metallic wires and carbon fiber to clarify the effect of the surface radiation heat loss of the test wire. The obtained thermal properties are repeatable though the magnitude of the thermal contact resistance under different contact conditions changes significantly. The cross-wire geometry overcomes the obstacle introduced by different thermal interfacial materials, which provides an accurate and convenient way to measure the thermal properties of microwires.
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INTRODUCTION: This phase III trial (NCT04178850) evaluated the efficacy, safety, and immunogenicity of GB242, an infliximab biosimilar, vs. infliximab (Remicade®) reference product in patients with moderate-to-severe active rheumatoid arthritis (RA) combination with methotrexate (MTX) therapy. METHODS: Patients were randomized in a 1:1 ratio to receive either GB242 or INF (3 mg/kg). Therapeutic equivalence of clinical response according to the American College of Rheumatology 20% (ACR20) response rate at week 30 was declared if the two-sided 95% CI for the treatment difference was within ± 14%. The comparison of GB242 with INF also included the proportion of patients achieving a week 30 ACR 50 response, ACR70 response, change in Disease Activity Score 28 (DAS28), as well as safety and immunogenicity. RESULTS: A total of 570 subjects were randomized into GB242 (N = 285) or INF (N = 285) and 283 subjects in each group were analyzed. At week 30, the ACR20 was 62.54% for the GB242 group (95% CI 56.62-68.20%) and 56.89% for the INF group (95% CI 50.90-62.74%). The difference between the two groups was 5.65% with a 95% CI of - 2.48 to 13.74. ACR50 response was 37.12% for GB242 and 32.86% for INF at week 30. ACR70 response was 19.79% for GB242 and 16.96% for INF at week 30, respectively. The incidence of treatment-emergent adverse events was comparable (77.4% in GB242 vs. 80.2% in INF) and detection of antidrug antibodies (ADA) to infliximab up to week 30 (60.8% in GB242 vs. 59.4% in INF) was comparable. CONCLUSIONS: GB242 demonstrated equivalent efficacy to INF at week 30. Moreover, GB242 was well tolerated, with a similar immunogenicity and safety profile comparable to INF.
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BACKGROUND: Coronavirus disease 2019 (COVID-19) infection has caused huge impacts on all of people's lives and health systems. In response to the COVID-19 pandemic, China was the first country to impose lockdown. We aimed to study the influence of COVID-19 on the outpatient visits of rheumatic patients in a non-outbreak area of China. METHODS: We selected three provincial or ministerial hospitals in Jinan, and collected the outpatient appointments data in rheumatology and immunology departments during the Shandong Province first-level public health emergency response period from 25 January 2020 to 8 March 2020. RESULTS: In the early stage, the number of outpatient appointments in the rheumatology and immunology departments of the three provincial or ministerial hospitals were significantly reduced, and gradually restored in the late stage. It showed that in the face of major infectious diseases, strict quarantine measures with the cooperation of the public not only controls the epidemic in a short time, but also lifts the quarantine measures and opens general outpatient clinics in hospitals as soon as possible, thus minimizing the impact on other patients. INTERPRETATION: The impact on the western hospital was greater than that on the Chinese medicine hospital, and the impact on the back-up designated hospitals for COVID-19 was the greatest. Online appointment can reduce the risk of infection in outpatients, but not completely solve the follow-up problem of rheumatic patients. Telemedicine provides a new solution for both management of rheumatic patients and control of COVID-19.
Assuntos
COVID-19 , Pandemias , Controle de Doenças Transmissíveis , Humanos , Pacientes Ambulatoriais , Pandemias/prevenção & controle , SARS-CoV-2RESUMO
Magnetic induction tomography (MIT) is a promising approach in rapid diagnosis and continuous monitoring of cerebral hemorrhage. A new algorithm for the reconstruction of intracerebral hemorrhage with MIT, including the location and volume of hemorrhage, is proposed in this study. First, 2D magnetic resonance imaging and computed tomography images of patients with cerebral hemorrhage were used for the development of simulation models. The Stacked Autoencoder (SAE) network was then used to predict the location and volume of hemorrhage by conductivity reconstruction. Finally, the one-dimensional quantitative monitoring index is proposed as an auxiliary diagnostic indicator for assessment of real-time intracranial electrical characteristics. The 2D simulation results showed that the SAE was able to quickly image the location and volume of the hemorrhages. Compared with the back-projection algorithm, the prediction speed of each frame was improved 15-fold, and the accuracy improved by 90.53%. The extracted one-dimensional quantitative monitoring indicators can describe the bleeding status. The diagnostic accuracy and the imaging speed of cerebral hemorrhage were both improved by constructing a realistic head section model and using the proposed SAE network. This research provides a new alternative for dynamic monitoring of hemorrhages and shows the potential advantages of MIT in noninvasive detection.
Assuntos
Tomografia Computadorizada por Raios X , Tomografia , Algoritmos , Hemorragia Cerebral/diagnóstico por imagem , Humanos , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is an immune mediated fibro inflammatory condition characterized by abundant IgG4-positive (IgG4+) plasma cell infiltrated lesions and elevated serum IgG4 concentrations. Tubulointerstitial nephritis and glomerular lesions are the most common renal IgG4-RDs. However, solitary mass lesion is rarely observed in renal IgG4-RD. MATERIALS AND METHODS: We reported a 55-year-old male patient with a space-occupying lesion in the right kidney detected during a routine ultrasound medical examination. Computed tomography indicated a 20 mm × 15 mm × 18 mm mass located at the lower pole of the right kidney. Both T1-weighted imaging and T2-weighted imaging magnetic resonance imaging scans showed a hypointense mass. Diffusion-weighted imaging (b value = 800) showed slightly hyperintensity. RESULTS: The lesion was diagnosed as renal cell carcinoma clinically based on the laboratory and radiological findings and treated with laparoscopic resection. However, the postoperative histological examination results indicated the lesion IgG4-RD of the kidney. CONCLUSION: We should consider pseudotumor-like IgG4-RD as a differential diagnosis for solitary renal lesion although the incidence is low.
Assuntos
Carcinoma de Células Renais/diagnóstico , Doença Relacionada a Imunoglobulina G4/diagnóstico , Imunoglobulina G/metabolismo , Neoplasias Renais/diagnóstico , Rim/patologia , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Carcinoma de Células Renais/metabolismo , Diagnóstico Diferencial , Humanos , Doença Relacionada a Imunoglobulina G4/metabolismo , Rim/metabolismo , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: Previous publications indicated that genetic predisposition might play important roles in the onset of osteonecrosis of the femoral head (ONFH) in systemic lupus erythematosus (SLE). Some gene loci such as complement C3d receptor 2 (CR2), nitric oxide synthase 3 (NOS3), collagen type II alpha 1 chain (COL2A1), protein tyrosine phosphatase non-receptor type 22 (PTPN22), and transient receptor potential cation channel subfamily V member 4 (TRPV4) were reported to be involved in this process. AIM: To investigate whether the risk of ONFH in SLE is associated with single nucleotide variations (SNVs) in these five genes. METHODS: SNVs in the CR2, NOS3, COL2A1, PTPN22, and TRPV4 genes were examined by using FastTarget and Illumina Miseq sequencing technologies in 49 cases of SLE with ONFH. Burrows-wheeler aligner was used to align the sequencing reads to hg19, and GATK and Varscan programs were used to perform SNV calling. PolyPhen-2, SIFT, and MutationTaster were used to assess the functional effects of non-synonymous SNVs. RESULTS: Six of the 49 patients were confirmed to have low frequency SNVs, including one patient with SNVs in NOS3 (exon 6: c.814G>A: p.E272K and exon 7: c.814G>A: p.E272K.), four in COL2A1 (rs41263847: exon 29: c.1913C>T: p.T638I, exon 28: c.1706C>T: p.T569I, and rs371445823: exon 8: c.580G>A: p.A194T, exon 7: c.373G>A: p.A125T), and one in CR2 (rs45573035: exon 2: c.200C>G: p.T67S). CONCLUSION: The onset of ONFH in SLE might be associated with the identified SNVs in NOS3, COL2A1, and CR2.