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1.
Indian Pediatr ; 58(2): 162-168, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33632948

RESUMO

OBJECTIVE: We conducted a systematic review and network meta-analysis to compare the efficacy and safety of nine non-steroidal anti-inflammatory drugs (NSAIDs) in treating patients with juvenile idiopathic arthritis (JIA). METHODS: Randomized controlled trials (RCTs) of NSAIDs for the treatment in children with JIA were searched systematically by using MEDLINE, EMBASE, and the Cochrane Library for available literature up to January 1, 2019. Bayesian network meta-analysis was used to combine direct and indirect evidence on treatment effectiveness and safety. RESULTS: Eight eligible RCTs involving 1112 patients with JIA were identified, addressing 9 interventions. The ranking probability plot based on the surface under the cumulative ranking curve (SUCRA) indicated that celecoxib (6 mg/kg twice-a-day) had the highest probability of being most effective (SUCRA = 76.4%) among four NSAIDs (celecoxib, rofecoxib, meloxicam, and naproxen). Also, rofecoxib (0.3 mg/kg once-a-day) and piroxicam demonstrated a higher probability of safety in treating children with JIA (SUCRA = 33.0% and 35.5%, respectively), compared with other interventions. CONCLUSIONS: The quality of available evidence limits the formation of powerful conclusions regarding the comparative efficacy or safety of NSAIDs used to treat JIA.

2.
Onco Targets Ther ; 13: 11505-11516, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204105

RESUMO

Purpose: Colorectal cancer (CRC) is one of the most common malignancies in the world. The prognosis of advanced CRC is still poor. The purpose of this study was to identify a gene expression profile associated with CRC that may contribute to the early diagnosis of CRC and improve patient prognosis. Patients and Methods: Five pairs of CRC tissues and paracancerous tissues were used to identify causative genes using microarray assays. The prognostic value of Cytochrome C Oxidase Assembly Factor 1 Homolog (COA1) in CRC was assessed in 90 CRC patients. Loss-of-function assays, cell proliferation assays using Celigo and MTT, colony formation assays, a subcutaneous xenograft mouse model, and apoptosis assays were used to define the effects of downregulation of COA1 in CRC cells in vitro and in vivo. The underlying molecular mechanisms of COA1 in CRC were also investigated. Results: The causative gene COA1 was identified through microarray analysis. COA1 expression in CRC was notably associated with pathologic differentiation, tumor size, and tumor depth. COA1 expression may act as an independent prognostic factor for overall survival of CRC. Knockdown of COA1 inhibited the proliferation of CRC cells in vitro and the tumorigenicity of CRC cells in vivo. Decreased COA1 expression induced apoptosis of CRC cells. Based on the microarray assay results comparing HCT116 cells transfected with lentivirus encoding anti-COA1 shRNA or negative control shRNA, ingenuity pathway analysis (IPA) revealed that the PI3K/AKT signaling pathway was significantly enriched. Moreover, CCND1, mTOR, AKT1, and MDM2 were identified as the downstream genes of COA1. Conclusion: These findings demonstrate that COA1 promotes CRC cell proliferation and inhibits apoptosis by regulating the PI3K/AKT signaling pathway. Our results implicate COA1 as a potential oncogene involved in tumor growth and progression of CRC.

3.
Int J Hypertens ; 2020: 6214581, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32953170

RESUMO

Our aim was to investigate factors predicting blood pressure (BP) variability during diagnostic cerebral angiography and associations between BP variability and clinical outcomes in patients with acute and subacute ischemic stroke and intracranial artery stenosis. 114 patients with ischemic stroke and intracranial artery stenosis (stenosis rate >50%) were recruited. Patients who underwent cerebral angiography within 3 days and 3-14 days of disease onset are referred to be Group A and Group S, respectively. BP variability in Group A was defined as the coefficient of variance (CV) of BP. Univariate and multivariate regression analyses were used to identify predictors of CV of BP and associations between CV of BP and clinical outcomes at discharge. In Group A patients, advanced age was associated with increased CV of SBP and diastolic blood pressure (DBP), and antihypertensive use was associated with lower CV of SBP. Male was associated with lower CV of DBP. In Group S, higher CV of SBP was associated with hypertension and antihypertensive use. Males had lower CV of SBP than females. The calcium channel blocker was associated with lower CV of DBP. Higher scores of the Stroke Scale at admission were significantly associated with poor clinical outcomes for both groups, while BP variability was not. Factors associated with BP variability are significantly different between stroke patients undergoing angiography within 3 days vs. 3-14 days after disease onset. BP variability is not significantly associated with clinical outcomes at discharge.

4.
J Pharm Biomed Anal ; 191: 113609, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32966940

RESUMO

Different therapeutically active ingredients, from plants, animals, and mineral sources, are prescribed as traditional Chinese medicines (TCM). TCMs, from animal sources, are rich in proteins and peptides. Different advanced proteomics technologies, such as two-dimensional gel electrophoresis (2-DE), multi-dimensional liquid chromatography (MDLC), matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS), and isobaric tags for relative and absolute quantitation (iTRAQ), have been applied to analyze TCMs, from animal sources. This paper reviews the common proteomic techniques for analyzing animal - derived TCMs. Various scientific studies have reported the application of proteomics for locating drug targets, identifying active components, and elucidating the mechanisms of action of animal - derived TCMs. However, these researches are still at the preliminary stage. This review has also discussed the existing challenges and future directions in this field of research.

5.
Future Med Chem ; 12(11): 991-1013, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32208864

RESUMO

Aim: Search for a new class of potential antidiabetic agents. Methodology: A series of novel peptidomimetics bearing the p-aminobenzoic acid moiety (TM3-TM6) were designed and synthesized. For all synthetic target molecules, the peroxisome proliferator response element (PPRE) activated activities have been evaluated and the toxicity were computed. Results & discussion: 46 new p-aminobenzoic acid derivatives have been characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS). The results of in vitro PPRE-activated activity, molecular docking study and toxicity prediction revealed that these compounds had potential antidiabetic activities and low toxicity. In particular compound 3b had up to 87% PPRE-activated activity compared with pioglitazone. This discovery may provide new insights for finding novel PPRE lead compound.

6.
World J Pediatr ; 16(1): 68-73, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31612428

RESUMO

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease that includes seven heterogeneous subgroups with different prognoses. In particular, polyarticular JIA (pJIA) has a longer period of active disease and a poorer prognosis. Tumor necrosis factor (TNF)-alpha inhibitors are effective in patients with pJIA, but the therapeutic regimen remains controversial. Here, we performed a single-center study to determine the potential correlation between TNF-alpha inhibitor (infliximab) therapy and outcomes in these patients. METHODS: Clinical data of 40 pJIA patients were collected at our center from January 1, 2010 to January 1, 2018, and patients were grouped according to the timing of infliximab therapy. The erythrocyte sedimentation rate (ESR), the number of joints with active disease, and the 27-point juvenile arthritis disease activity score (JADAS-27) were analyzed. RESULTS: The ESR, the active joint count, and the JADAS-27 decreased significantly in all groups after 3 months (P = 0.041/0.415/0.008, 0.022/0.030/ < 0.001, and 0.05/0.012/ < 0.001, respectively) and 6 months (P = 0.036/0.045/0.041, 0.076/0.037/ < 0.001, and 0.096/0.006/ < 0.001, respectively) of infliximab treatment, although the rates of change of these parameters were similar. However, after 12 months, only patients treated with infliximab within 3 months of disease onset had a stable ESR, active joint count, and JADAS-27, while these parameters increased sharply when infliximab was administered 3 months and especially 1 year after disease onset. CONCLUSIONS: TNF-alpha is a pleiotropic pro-inflammatory cytokine of crucial importance in the pathogenesis of JIA. Infliximab can improve the outcomes of patients with pJIA significantly, and should be introduced early during the clinical course.

7.
Clin Immunol ; 203: 53-58, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31009763

RESUMO

Severe congenital neutropenia caused by ELANE gene mutation is a rare disease. To date, only four families were reported with mosaicism. Here we examined the morphology and function of granulocytes isolated from two patients and their mosaic fathers. Analysis of granulocytes isolated from the fathers revealed no genetic mutations. DNA extracted from fractionated peripheral blood mononuclear cells (PBMCs) and fingernails obtained from both fathers did harbor the mutation, suggesting mosaicism. Granulocytes isolated from the patients displayed significantly weaker ionomycin-induced intracellular reactive oxygen species (ROS) responses than those isolated from the fathers. Both patients showed increased expression of neutrophil elastase, whereas the mosaic fathers showed normal expression. Taken together, the results suggest that granulocytes from these SCN patients are immunocompromised, whereas those from the mosaic fathers are normal. These findings may provide new insight into disease diagnosis, prognosis, therapy and genetic counseling.


Assuntos
Elastase de Leucócito/metabolismo , Leucócitos Mononucleares/fisiologia , Mutação/genética , Neutrófilos/fisiologia , Células Cultivadas , Síndrome Congênita de Insuficiência da Medula Óssea/genética , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Elastase de Leucócito/genética , Masculino , Mosaicismo , Neutropenia/congênito , Neutropenia/genética , Neutrófilos/patologia , Linhagem , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima
8.
Zhongguo Zhong Yao Za Zhi ; 44(24): 5405-5412, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-32237387

RESUMO

Magnolia Officinalis Cortex has been used as a traditional Chinese herb for thousands of years in China. According to Chinese Pharmacopoeia,the processing of Magnolia Officinalis Cortex needs " sweating" or " Fahan",which was a special drying process and considered to be an important symbol for high quality and genuine medicinal materials. In this unique processing mode,Magnolia Officinalis Cortex's microbial community structure may be changed,but little is known about microbial diversity during the " sweating". In this study,to analyze the change and its change rules of microbial community of Magnolia Officinalis Cortex in the whole process of " sweating",and find out the microbial community that affects the quality of Magnolia Officinalis Cortex in the process of its " sweating",and provide a basis for further research on the microbial transformation of Magnolia Officinalis Cortex,MiSeq highthroughput sequencing was used to evaluate the microbial diversity of natural " sweating" of Magnolia Officinalis Cortex. In this research,334 genera fungi and 674 genera bacteria were identified. The dominant species weren' t obvious during the early stage of " sweating". Candida was the dominant fungal species( 45. 01%-71. 93%) during the medium " sweating" stage. Aspergillus is the dominant fungal species( 45. 83%-95. 51%) during the late stage of " sweating". Moreover,Enterobacter and Klebsiella were the primary bacterial genus( ≥56. 05%) during the middle and late stages of " sweating". In addition,the predominant bacteria in the process of " sweating" included Bacillus,Deinococcus,Sphingomonas,Hymenobacter and Jatrophihabitans. In conclusion,the microbial diversities and the main dominant fungi and bacteria in the process of " sweating" of Magnolia Officinalis Cortex were initially determined. It was also found that the metabolism of Aspergillus and Candida may be related to the character formation,which were sweet odor and brown inner surface after " sweating". The results provide a theoretical basis for the study of the influence of different microorganisms on the excellent traits formation of " sweating" Magnolia Officinalis Cortex.


Assuntos
Química Farmacêutica/métodos , Magnolia/microbiologia , Microbiota , China , Sequenciamento de Nucleotídeos em Larga Escala
9.
Neuroradiology ; 59(6): 577-586, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28501949

RESUMO

PURPOSE: The association between intracranial internal carotid artery (IICA) calcification and lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMBs) has been well researched. However, enlarged cerebral perivascular space (PVS) has not yet been reported to correlate with intracranial internal carotid artery calcification. Therefore, the primary aim of this study was to investigate the relationship between IICA calcification and enlarged PVS. METHODS: A total of 189 patients with ischemic stroke in the middle cerebral artery territory who presented within 7 days of ictus from 2012 to 2015 were enrolled respectively. All patients were required to have undergone head computed tomography, magnetic resonance imaging, susceptibility-weighted magnetic resonance imaging, magnetic resonance angiography, or computed tomography angiography. Clinical characteristics were recorded. IICA calcification and enlarged PVS were semi-quantitatively evaluated, and the presence of lacunes, WMH, and CMBs was recorded. RESULTS: Of the 189 patients, 63.5% were male. Mean age of the patients was 68.6 ± 12.2 years. There were 104 patients with IICA calcification. Age, diabetes mellitus, lacunes, and white matter hyperintensity were significantly associated with IICA calcification (P < 0.05). Multivariate logistic regression analysis showed that age, diabetes mellitus, and lacunes were independent predictors of IICA calcification (P < 0.05). A lower risk of IICA calcification was found in patients with a higher enlarged PVS score (P = 0.004). CONCLUSION: Higher enlarged PVS scores were associated with a lesser degree of IICA calcification. There appears to be a relationship between reduced risk of IICA calcification and enlarged PVS.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Neuroimagem/métodos , Calcificação Vascular/diagnóstico por imagem , Idoso , Isquemia Encefálica/patologia , Estenose das Carótidas/patologia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Calcificação Vascular/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
10.
Immunogenetics ; 69(4): 199-209, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28124082

RESUMO

In humans, the complete lack of tyrosine kinase ZAP70 function results in combined immunodeficiency (CID), with abnormal thymic development and defective T cell receptor (TCR) signaling of peripheral T cells, characterized by the selective absence of CD8+ T cells. So far, 15 unique ZAP70 mutations have been identified in approximately 20 patients with CID, with variable clinical presentations. Herein, we report the first case from China of novel compound heterozygous mutations in ZAP70 (c.598-599delCT, p.L200fsX28; c.847 C>T, R283H). The patient suffered from early-onset and recurrent infections, but showed normal growth and development without signs of failure to thrive, thus presenting as leaky SCID. The patient also had clinical manifestations of autoimmunity, such as eczematous skin lesion, inflammatory bowel disease (IBD), and intractable diarrhea, suggesting compromised T cell tolerogenic functions. Residual ZAP70 expression was identified. Immunological analysis revealed the selective absence of CD8+ T cells in the periphery and the presence of CD4+ T cells that failed to respond to phytohemagglutinin. Stimulation with lectin from pokeweed mitogen also failed to stimulate B cell proliferation in the patient. The frequency of Tfhs and Tregs in the patient was lower compared with the normal reference. Compared with the age-matched healthy control, the level of IL-17 was higher and the levels of IFN-γ, IL-4, and IL-21 were lower. Infants with selected CD8 deficiency and severe autoimmune disorders or exaggerated inflammation should be screened for ZAP70 deficiency.


Assuntos
Mutação/genética , Receptores de Antígenos de Linfócitos T/genética , Imunodeficiência Combinada Severa/genética , Proteína-Tirosina Quinase ZAP-70/deficiência , China , Citocinas/metabolismo , Heterozigoto , Humanos , Recém-Nascido , Ativação Linfocitária , Masculino , Receptores de Antígenos de Linfócitos T/metabolismo , Imunodeficiência Combinada Severa/metabolismo , Imunodeficiência Combinada Severa/patologia , Proteína-Tirosina Quinase ZAP-70/genética , Proteína-Tirosina Quinase ZAP-70/metabolismo
12.
Hum Immunol ; 76(6): 406-13, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25862925

RESUMO

A spontaneous reversion that restores Wiskott-Aldrich syndrome protein (WASP) expression was reported recently. However, the genetic mechanism underlying the reversion event was unclear. In the present study, a WAS patient with a nonsense mutation (155 C>T, R41X) was followed during a three-year period. No expression of WASP was detected in peripheral blood mononucleated cells (PBMCs) in 2009 and a small population of intracellular WASP positive lymphocytes was detected during the following three years. The increasing trend of the revertant genotype was significant. WASP-expressing cells were present mainly CD56+ NK cells and CD8+ T cells. Sorted WASP+ cells were analyzed, indicating that the population of CD3+ T cells increased from 36.81% to 99.8%. Although the revertant cells in vivo may have a growth advantage, the patient presented a persistent autoimmune disease, thrombocytopenia, and died from extensive pulmonary fibrosis. The results suggest that the clinical consequences of T-cell mosaicism in WAS remain difficult to predict and is not sufficient to fully normalize immune functions in patients with WAS.


Assuntos
Fibrose Pulmonar/genética , Trombocitopenia/genética , Proteína da Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/genética , Adolescente , Grupo com Ancestrais do Continente Asiático , Sequência de Bases , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Evolução Fatal , Expressão Gênica , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Masculino , Dados de Sequência Molecular , Mosaicismo , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/patologia , Trombocitopenia/imunologia , Trombocitopenia/patologia , Síndrome de Wiskott-Aldrich/imunologia , Síndrome de Wiskott-Aldrich/patologia , Proteína da Síndrome de Wiskott-Aldrich/imunologia
13.
Eur J Pediatr ; 174(10): 1311-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25877044

RESUMO

UNLABELLED: Autoimmune disease (AD) is common in patients with Wiskott-Aldrich syndrome (WAS) and patients with WAS who has an AD usually constitute a high-risk group with poor outcome. However, knowledge of AD in WAS is limited in China. In this study, medical records of 53 patients with WAS at Children´s Hospital of Chongqing Medical University from April 2004 to January 2014 were evaluated retrospectively and 14 patients (26%) had at least one AD. Autoimmune hemolytic anemia (AIHA) was the most common and detected in 12 patients (23%), other complications included immune thrombocytopenia (n = 1), immune neutropenia (n = 1), autoimmune arthritis (n = 1), and renal injury (n = 1). No significant differences were found in the level of serum immunoglobulins and lymphocyte subsets between the AD group and non-AD group. Although eight patients with AD received hematopoietic stem cell transplantation (HSCT), three patients died of pulmonary infection after HSCT. CONCLUSIONS: AD is frequent in Chinese patients with WAS and AIHA was the most common. AD is a poor prognosis factor for WAS and should be treated as early as possible by HSCT. WHAT IS KNOWN: • Autoimmune disease is common in patients with WAS. • Manifestations, follow-up finding, and treatment approaches of autoimmune disease in Chinese patients with WAS have received less attention in the literature. What is New: • This study is firstly intended for evaluation of the clinical and immune characteristics of autoimmune disease in a large series Chinese patients with WAS. • AD is frequent in Chinese patients with WAS and AIHA is the most common.


Assuntos
Autoimunidade , Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressores/uso terapêutico , Linfócitos T/imunologia , Síndrome de Wiskott-Aldrich/imunologia , Pré-Escolar , China/epidemiologia , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Síndrome de Wiskott-Aldrich/epidemiologia , Síndrome de Wiskott-Aldrich/terapia
14.
Pediatr Infect Dis J ; 34(2): 203-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25162927

RESUMO

BACKGROUND: Mutations within the ELANE gene, which encodes human neutrophil elastase, are the most common genetic causes of severe congenital neutropenia (SCN). No cases of SCN have been previously described from a Chinese population. Herein, we describe the clinical, hematologic and molecular characteristics of 7 Chinese SCN cases with novel ELANE mutations. METHODS: Seven Chinese pediatric patients (4 males and 3 females) with suspected SCN were enrolled in this study. Clinical data, peripheral blood, bone marrow and immune function were evaluated for SCN. ELANE genomic DNA and cDNA sequences from patients and potential carriers were analyzed using polymerase chain reaction (PCR) and direct sequencing. RESULTS: All the7 patients experienced recurrent infection (soft tissue, lung, oral cavity) during a period of 120 days. Noninfectious conditions such as anemia and osteopenia were found in most patients, and absolute peripheral neutrophil counts varied. DNA and cDNA sequencing demonstrated that the patients harbored a range of heterozygous ELANE gene mutations, including substitution, deletion, insertion and frame shift alterations. All the mutations had not been reported previously; however, no mutation carriers were identified among the parents or siblings, even in a family with 2 affected offspring. CONCLUSION: SCN cases were identified for the first time in China, and all patients carried novel ELANE mutations. Granulocyte-colony stimulating factor (G-CSF) was an effective treatment for most of the SCN patients and prevented life-threatening bacterial infections.


Assuntos
Elastase de Leucócito/genética , Proteínas Mutantes/genética , Mutação , Neutropenia/congênito , Grupo com Ancestrais do Continente Asiático , Pré-Escolar , China , Síndrome Congênita de Insuficiência da Medula Óssea , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Lactente , Elastase de Leucócito/metabolismo , Masculino , Proteínas Mutantes/metabolismo , Neutropenia/tratamento farmacológico , Neutropenia/genética , Neutropenia/patologia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
15.
Zhongguo Zhong Yao Za Zhi ; 39(11): 2000-4, 2014 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-25272830

RESUMO

The paper is aimed to study the dynamic accumulation regulation of curcumin (Cur), demethoxycurcumin (DMC) and bisdemethoxyeurcumin (BDMC) in three strains of Curcuma longa, and provide scientific references for formalized cultivation, timely harvesting, quality control and breeding cultivation of C. longa. The accumulation regulation of the three curcumin derivatives was basically the same in rhizome of three strains. The relative contents decreased along with plant development growing, while the accumulation per hectare increased with plant development growing. The accumulation of curcuminoids per hectare could be taken as the assessment standard for the best harvest time of C. longa. A3 was the best strain in terms of Cur and BDMC content.


Assuntos
Curcuma/metabolismo , Curcumina/análogos & derivados , Curcumina/metabolismo , Rizoma/metabolismo , Curcuma/química , Curcuma/crescimento & desenvolvimento , Curcumina/análise , Diarileptanoides , Controle de Qualidade , Rizoma/química , Rizoma/crescimento & desenvolvimento
16.
J Clin Immunol ; 34(6): 633-41, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24943880

RESUMO

PURPOSE: Chronic granulomatous disease (CGD) is an inherited disorder, with phagocytes failing to produce antimicrobial superoxide due to deficient NADPH oxidase activity. Mutations in the gene encoding CYBB are responsible for the majority of the CGD cases. To date, there have been no reports on large samples of children with CGD in China. Therefore, in this study, we described the clinical and molecular features of 38 suspected CGD patients from 36 unrelated Chinese families. METHODS: Clinical diagnosis was performed using dihydrorhodamine assays detected by flow cytometry. Molecular analysis was used to identify underlying CGD-causative genes. RESULTS: The mean age of onset in our 38 patients was 3.4 months, while the mean age at diagnosis was 31.7 months. Apart from recurrent pneumonia and abscesses, tuberculosis (TB) and Bacille Calmette-Guerin (BCG) infections were notable features in our cohort. Overall, 17 cases died and patient 1 did not participate in the follow-up period . In total, we identified 29 different CYBB gene mutations in 31 patients. We found NCF1 and CYBA mutations in 3 and 2 patients, respectively. In addition, we identified 31 carriers and prenatally diagnosed 4 CGD and 4 healthy fetuses. CONCLUSIONS: The results of our study demonstrate that children with BCG infections or recurrent TB infections should have immune function screening tests performed. Moreover, newborns with family histories of primary immunodeficiency diseases should avoid of BCG vaccination. Molecular analysis is an important tool for identifying patients, carriers, and high-risk CGD fetuses.


Assuntos
Doença Granulomatosa Crônica/epidemiologia , Glicoproteínas de Membrana/metabolismo , NADPH Oxidases/metabolismo , Tuberculose Pulmonar/epidemiologia , Idade de Início , Criança , Pré-Escolar , China , Análise Mutacional de DNA , Feminino , Seguimentos , Doença Granulomatosa Crônica/diagnóstico , Humanos , Lactente , Recém-Nascido , Masculino , Glicoproteínas de Membrana/genética , Mutação/genética , NADPH Oxidase 2 , NADPH Oxidases/genética , Gravidez , Risco , Tuberculose Pulmonar/diagnóstico
17.
Hum Immunol ; 75(7): 633-40, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24768948

RESUMO

Type 1 hyper-IgM syndrome (HIGM1) is a rare primary immunodeficiency disease caused by mutations in the CD40L gene. Patients often present with recurrent infections and autoimmune manifestations. We investigated the clinical and molecular characteristics of HIGM1 in thirteen patients from the Chinese mainland and examined the proportion of CD4(+)CD25(+)FoxP3(+)Treg, Th17, and Th1 cells in the peripheral blood. We identified ten distinct CD40L mutations in eleven patients: one missense mutation, one nonsense mutation, one insertion mutation (in frame), and seven deletions. Six of these mutations were novel. We observed the percentage of Tregs in the peripheral blood of HIGM1 patients decreased markedly compared with that in healthy controls, but no statistically significant differences was found in the percentages of Th17 and Th1. The identified mutations reflect the heterogeneity of the CD40L gene in HIGM1. Precise genetic diagnosis of HIGM1 will enable appropriate therapeutic interventions, reliable detection of carriers, and genetic counseling. Skewed Treg, Th17/Treg, and Th1/Treg profiles may be associated with immune responses to autoimmunity or infection, which requires replication in larger studies.


Assuntos
Ligante de CD40/genética , Síndrome de Imunodeficiência com Hiper-IgM/genética , Mutação , Linfócitos T Reguladores/imunologia , Grupo com Ancestrais do Continente Asiático , Sequência de Bases , Antígenos CD4/genética , Antígenos CD4/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Expressão Gênica , Humanos , Síndrome de Imunodeficiência com Hiper-IgM/etnologia , Síndrome de Imunodeficiência com Hiper-IgM/imunologia , Síndrome de Imunodeficiência com Hiper-IgM/patologia , Imunofenotipagem , Lactente , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2/imunologia , Masculino , Dados de Sequência Molecular , Linfócitos T Reguladores/patologia , Células Th1/imunologia , Células Th1/patologia , Células Th17/imunologia , Células Th17/patologia
18.
Zhonghua Er Ke Za Zhi ; 51(6): 472-6, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-24120067

RESUMO

OBJECTIVE: To detect the disparity of three cytokines interleukin-6 (IL-6), interferon-inducible protein 10 (IP-10) and interleukin-17 (IL-17) in peripheral blood (PB) and synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA). METHOD: Serum concentrations of the three cytokines were measured in 27 patients with 13 systemic-onset JIA (sJIA), 14 polyarticular JIA (pJIA) and 28 healthy controls using enzyme-linked immunosorbent assay (ELISA). Nineteen patients with no marked arthritis symptom or only temporary arthralgia were enrolled in probable sJIA group. SF from 18 patients with 7 sJIA, 11 pJIA were examined for cytokine levels. RESULT: (1) The statistically significant difference in serum IL-6 was detected between sJIA and healthy control group [28.0(4.2-59.2) ng/L vs. 12.3 (2.1-13.8) ng/L, P < 0.05], but no significant difference between probable sJIA and healthy control group [11.8(7.7-39.2) ng/L vs. 12.3 (2.1-13.8) ng/L, P > 0.05] was found. There were statistically significant differences between sJIA group and healthy control group in serum concentrations of IL-17 [14.0(9.8-34.3) ng/L vs. 9.8 (7.9-16.2) ng/L, P < 0.05], yet compared to healthy control group, no significant difference in concentration level of IL-17 was found in pJIA Group [14.2(9.9-16.9) ng/L vs. 9.8(7.9-16.2) ng/L, P > 0.05].(2) In sJIA and pJIA SF, the median IP-10 level was significantly higher compared to respective PB levels [619.7 (160.9, 873.1) ng/L vs. 64.8 (27.4-111.9) ng/L;660.9 (401.9, 1349.8) ng/L vs. 97.4 (41.9-222.1) ng/L, P < 0.01, respectively], but there was only significant difference in IL-17 between pJIA SF and PB [22.9 (17.1, 45.8) ng/L vs. 14.2 (9.9-16.9) ng/L, P < 0.01]. CONCLUSION: IL-6 may play more important role in the pathogenesis of sJIA. Moreover, IL-6 may be the biomarker associated with arthritis in early JIA stage. Both autoinflammation and autoimmune response may be involved in the pathogenesis of sJIA. IL-17 enrichment may only occur in local joint, the levels of IL-17 in PB may not be significantly increased. The prominent expression gradient between SF and PB of IP-10 maybe the basis of performing chemotaxis and further causing joint damage.


Assuntos
Artrite Juvenil/metabolismo , Quimiocina CXCL10/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Líquido Sinovial/metabolismo , Adolescente , Artrite Juvenil/sangue , Artrite Juvenil/imunologia , Estudos de Casos e Controles , Quimiocina CXCL10/sangue , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-17/sangue , Interleucina-6/sangue , Articulação do Joelho/metabolismo , Masculino , Líquido Sinovial/imunologia
20.
Pediatr Infect Dis J ; 32(10): 1127-34, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23673420

RESUMO

METHODS: Two hundred three children with genetically proven primary immunodeficiency diseases (PIDs) from 197 unrelated families were enrolled from January 2005 to December 2011. RESULTS: On the basis of criteria developed by the International Union of Immunological Societies, 79 patients were diagnosed as "other well-defined immunodeficiency syndromes" (38.9%), 62 (30.6%) with "predominant antibody deficiencies," 26 (12.8%) with "congenital defects of phagocyte," 25 (12.3%) with "T- and B-cell immunodeficiency" and 11 (5.4%) with "diseases of immune dysregulation." The median time to the diagnosis was 27.9 months and the patients had a wide range of clinical presentations. In addition, a total of 23 pathogenic genes were identified and 213 mutations were detected, including 42 novel mutations. CONCLUSIONS: With the increase in the awareness of PIDs and diagnostic competence, more PID patients will be diagnosed and we will be able to more accurately identify the frequency and the distribution of PIDs in the most populous country in the world.


Assuntos
Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/patologia , Criança , Pré-Escolar , China/epidemiologia , Análise Mutacional de DNA , Feminino , Humanos , Síndromes de Imunodeficiência/terapia , Lactente , Masculino , Estudos Retrospectivos
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