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1.
Zhonghua Bing Li Xue Za Zhi ; 53(7): 672-677, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-38955697

RESUMO

Objective: To assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories. Methods: The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory. Results: In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%). Conclusions: A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.


Assuntos
Proteínas de Fusão bcr-abl , Reação em Cadeia da Polimerase em Tempo Real , Humanos , Proteínas de Fusão bcr-abl/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Reprodutibilidade dos Testes
3.
Zhonghua Yi Xue Za Zhi ; 102(45): 3630-3633, 2022 Dec 06.
Artigo em Chinês | MEDLINE | ID: mdl-36480868

RESUMO

From January 1, 2015 to December 31, 2021, 94 patients who were diagnosed with atrial fibrillation (AF) associated anterior circulation large vessel occlusion stroke and underwent mechanical thrombectomy in the First Affiliated Hospital of Dalian Medical University were retrospectively collected, including 52 patients in the direct mechanical thrombectomy (dMT) group and 42 patients in the bridging therapy (BT) group. All patients received stent thrombectomy, and the BT group received intravenous thrombolytic therapy with alteplase within 4.5 hours.There were no significant differences in 7 d National Institute of Health Stroke Scale (NIHSS) score[12.0 (5.2, 42.0) vs 10.0 (6.0, 25.8)], incidence of hemorrhage transformation [44.2%(23/52) vs 45.2%(19/42)], symptomatic intracranial hemorrhage[11.5%(6/52) vs 11.9%(5/42)],90 d mortality[34.6% (18/52) vs 38.1% (16/42)]between the two groups(all P>0.05). The rate of 90 d good prognosis in dMT and BT groups was 36.5% (19/52) and 35.7% (15/42), respectively, and the difference was not statistically significant(OR=1.45, 95%CI: 0.39-3.37, P=0.805). The number of stent passes[2(1,3) vs 1(1,2)] and the vessel recanalization time [(81±41)min vs (57±29)min] in the BT subgroup of middle cerebral artery (MCA) occlusion were longer than those in the dMT group (both P<0.05).Therefore, direct thrombectomy has similar efficacy and safety as bridging therapy in the treatment of AF related anterior circulation large vessel occlusive stroke, which is worthy of further research and verification.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Estudos Retrospectivos
4.
Zhonghua Bing Li Xue Za Zhi ; 51(11): 1135-1140, 2022 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-36323543

RESUMO

Objective: To investigate the mutational features of the immunoglobulin heavy chain variable region (IgHV) gene in patients with chronic lymphocytic leukemia (CLL) using immunophenotypic and molecular genetic methods. Methods: The laboratory results of 266 CLL patients who underwent IgHV gene examination at Sino-US diagnostics laboratory from February 2020 to February 2021 were analyzed for the IgVH mutational status and presence of specific IgVH fragments. In addition, their immunophenotypic, molecular, chromosomal karyotypic, and FISH profiles were investigated and correlated with the IgVH mutational status. Results: Among 266 patients, 172 were male and 94 were female, with a media age of 67 years (20-82 years).There were more patients with mutated IgHV (m-IgHV) than unmutated IgHV (un-IgHV) (69.2%∶30.8%). There was association of VH family and the presence of gene fragments: the overall incidence of VH families including VH3 family (142/266, 53.4%), VH4 family (75/266, 28.2%), and VH1 family (34/266, 12.8%) was about 95%, among which the proportion of VH4-34 (26/266, 9.8%), VH3-23 (25/266, 9.4%), VH3-7 (24/266, 9.0%), and VH4-39 (16/266, 6.0%) was about 35%. VH3-20 and VH3-49 only occurred in un-IgHV (P<0.05). In addition, the expression rates of CD38 (26.3% vs. 3.0%), CD79b (71.1%∶45.5%) and 11q deletion (25.5%∶5.3%) were higher in un-IgHV, and single trisomy 12 (37.9%∶5.6%) were more commonly found in m-IgHV (P<0.05). MYD88 was one of the major mutation genes in m-IgHV, while ATM had the highest mutation rate in un-IgHV. Conclusion: CLL patients have differential expression in terms of IgHV gene mutations, correlating to their immunophenotype and genetics characteristics.


Assuntos
Leucemia Linfocítica Crônica de Células B , Masculino , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Região Variável de Imunoglobulina/genética , Genes de Cadeia Pesada de Imunoglobulina , Mutação , Cadeias Pesadas de Imunoglobulinas/genética , Prognóstico
5.
Zhonghua Bing Li Xue Za Zhi ; 51(4): 307-313, 2022 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-35359041

RESUMO

Objective: To analyze the genetic landscape of 52 fusion genes in patients with de novo acute lymphoblastic leukemia (ALL) and to investigate the characteristics of other laboratory results. Methods: The fusion gene expression was retrospectively analyzed in the 1 994 patients with de novo ALL diagnosed from September 2016 to December 2020. In addition, their mutational, immunophenotypical and karyotypical profiles were investigated. Results: In the 1 994 patients with ALL, the median age was 12 years (from 15 days to 89 years). In the panel of targeted genes, 15 different types of fusion genes were detected in 884 patients (44.33%) and demonstrated a Power law distribution. The frequency of detectable fusion genes in B-cell ALL was significantly higher than that in T-cell ALL (48.48% vs 18.71%), and fusion genes were almost exclusively expressed in B-cell ALL or T-cell ALL. The number of fusion genes showed peaks at<1 year, 3-5 years and 35-44 years, respectively. More fusion genes were identified in children than in adults. MLL-FG was most frequently seen in infants and TEL-AML1 was most commonly seen in children, while BCR-ABL1 was dominant in adults. The majority of fusion gene mutations involved signaling pathway and the most frequent mutations were observed in NRAS and KRAS genes. The expression of early-stage B-cell antigens varied in B-cell ALL patients. The complex karyotypes were more common in BCR-ABL1 positive patients than others. Conclusion: The distribution of fusion genes in ALL patients differs by ages and cell lineages. It also corresponds to various gene mutations, immunophenotypes, and karyotypes.


Assuntos
Fusão Oncogênica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Expressão Gênica , Genes ras , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Estudos Retrospectivos , Adulto Jovem
7.
Zhonghua Xue Ye Xue Za Zhi ; 42(6): 480-486, 2021 Jun 14.
Artigo em Chinês | MEDLINE | ID: mdl-34384154

RESUMO

Objective: To analyze the genetic landscape of multiple fusion genes in patients with de novo acute myeloid leukemia (AML) and investigate the characteristics of immunophenotypes and mutations. Methods: The results of multiple fusion genes from 4192 patients with de novo AML were retrospectively analyzed from 2016 to 2020. In addition, the immunophenotypical data and the mutational results from high-through put method were statistically investigated and correlated as well. Results: ①Among the 52 targets, 29 different types of fusion genes were detected in 1948 patients (46.47%) with AML, which demonstrated an "exponential distribution" . ② As the age increased, the number of patients with fusion gene increased first and then decreased gradually. The total incidence rate of fusion genes and MLL rearrangment in children were significantly higher than those in adults (69.18% vs 44.76%, 15.35% vs 8.36%) . ③The mutations involving FLT3 and RAS signaling pathway contributed most in patients with MLL rearrangment. ④No specific immunophenotypic characteristics were found in AML patients with MLL or NUP98 rearrangements. Conclusion: Nearly half of AML patients were accompanied by specific fusion gene expression, the proportions of different fusion genes in pediatric and adults patients were different by multiple PCR. The gene mutations and immunophenotype of these AML patients have certain rules.


Assuntos
Leucemia Mieloide Aguda , Adulto , Criança , Expressão Gênica , Humanos , Imunofenotipagem , Leucemia Mieloide Aguda/genética , Mutação , Proteína de Leucina Linfoide-Mieloide/genética , Estudos Retrospectivos
8.
Compr Child Adolesc Nurs ; 43(1): 48-64, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30640560

RESUMO

In the absence of a mandatory reporting (MR) structure, it is unclear how nurses perceive or exercise their role in child protection. This study examined knowledge and perceptions of child protection and MR among nurses working in Hong Kong. This cross-sectional web-based survey used the Child Abuse Report Intention Scale to measure nurses' child protection knowledge and attitudes, and their perceived norms, control, and intention to report suspected maltreatment. Nurses also indicated if they support MR and to provide an explanation for their preference. Quantitative data were described and analyzed using bivariate and regression analyses. Open-ended responses were analyzed using directed content analysis. A convenient sample of 91 nurses working in Hong Kong completed the survey. The majority (86%) were female with a mean of 9.5 years of nursing experience; their mean knowledge score was 6.64 out of 13 (range 2-10). Compared with other maltreatment types, sexual abuse was perceived to be most severe and most likely to be reported. Perceived severity and attitudes toward child maltreatment was significantly associated with nurses' intention to report. Over half (58%) supported MR; those against MR expressed concerns about lack of support from management. Although nurses working in Hong Kong still hold polarized views about MR, findings point to the importance of creating a supportive reporting culture, and designing training programs that focus on changing perceptions about child protection in order to improve their tendency to report.


Assuntos
Conhecimento , Notificação de Abuso/ética , Enfermeiras e Enfermeiros/psicologia , Percepção , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hong Kong , Humanos , Masculino , Enfermeiras e Enfermeiros/estatística & dados numéricos , Inquéritos e Questionários
10.
Zhonghua Xue Ye Xue Za Zhi ; 38(3): 192-197, 2017 Mar 14.
Artigo em Chinês | MEDLINE | ID: mdl-28395441

RESUMO

Objective: To investigate the incidence, molecular features and clinical significance of RNA splicing machinery genes mutation in myelodysplastic syndromes (MDS) and related diseases. Methods: Mutational analysis of splicing factor 3B subunit 1 (SF3B1) (K700E) , U2 small nuclear RNA auxiliary factor 1 (U2AF1) (S34, Q157P) and serine/arginine-rich splicing factor 2 (SRSF2) (P95) in 118, de novo MDS and related diseases were separately performed by using polymerase chain reaction (PCR) followed by sequence analysis. Results: Of 118 MDS patients, 76 males and 42 females, the median age was 53.5 (13-84) years old. 19.49% (23/118) had SF3B1 (K700E) mutation. As compared with those with wild type SF3B1, patients with SF3B1 K700E were of older[58 (32-78) years vs 51 (13-84) years, z=-1.981, P=0.048], lower HGB level[63 (40-95) g/L vs 77 (34-144) g/L, z=-3.192, P=0.001], higher platelet counts[121 (22-888) ×10(9)/L vs 59 (6-1 561) ×10(9)/L, z=-3.305, P=0.001], lower bone marrow blast cell counts[0.007 (0-0.122) vs 0.017 (0-0.268) , z=-2.885, P=0.004], higher ring sideroblasts percent [0 (0-64%) vs 0 (0-58%) , z=-4.664, P<0.001]. Of 105 MDS patients, 21.9% had U2AF1 (S34, Q157P) mutations. Of 107 MDS patients, 8 patients (7.48%) had SRSF2 (P95) mutations. Patients with SRSF2 mutations were older at diagnosis, the median age was 63 (50-84) years old, including 4 cases RAEB-1. The ratio of mutation was 14.29% (4/28) , and three patients transformed to AML. SF3B1 K700E and SRSF2 P95H mutations coexisted in 1 patient, and SF3B1 K700E and U2AF1 S34Y mutations were found concomitantly in 2 patients. Conclusion: Only SF3B1 gene mutation was closely related to ring sideroblasts, it was the key to pathogenesis of MDS.


Assuntos
Síndromes Mielodisplásicas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fosfoproteínas , Splicing de RNA , Fatores de Processamento de RNA , Ribonucleoproteína Nuclear Pequena U2 , Fatores de Processamento de Serina-Arginina , Fator de Processamento U2AF , Adulto Jovem
11.
Zhonghua Yi Xue Za Zhi ; 97(3): 193-197, 2017 Jan 17.
Artigo em Chinês | MEDLINE | ID: mdl-28162169

RESUMO

Objective: To observe the efficacy and safety of recombinant tissue-type plasminogen activator (rtPA) intravenous thrombolysis (IVT) in the treatment of acute cerebral infarction with hyperdense middle cerebral artery sign (HMCAS). Methods: Acute cerebral infarction patients with HMCAS from July 2010 to November 2015 at the First Affiliated Hospital of Dalian Medical University were collected.These patients were divided into two groups depending on whether they received IVT or not.The Nation Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were used to evaluate early and long-time therapeutic effects.Efficacy and safety were compared between the two groups. Results: A total of 93 patients were eligible for the analysis, with 45 cases in IVT group and 48 cases in non-IVT group.As time went by, NIHSS score in IVT group showed significant downward trend than the non-IVT group.The rate of patients with good outcome in IVT group was higher than that in non-IVT group (P<0.05). The rate of hemorrhage transformation (HT) in IVT group and non-IVT group was 35.6% (16/45) and 10.4% (11/48), respectively, and the difference was statistically significant (P<0.05). While no statistically significant difference was found about the rate of symptomatic intracranial hemorrhage (sICH) (8.9% vs 2.1%, P>0.05) and mortality (33.3% vs 27.1%, P>0.05) between these two groups.Logistic regression analysis identified relativity between IVT treatment and good outcome (P<0.05), hemorrhage transformation (P<0.05), rather than mortality (P>0.05). Conclusions: Intravenous thrombolysis with rt-PA is an effective and safe treatment for most acute ischemic stroke patients with HMCAS and can promote early neurologic improvement and significantly improve long-term functional prognosis.Although Ⅳ thrombolysis can increase the risk of overall HT, it does not add risk in sICH and mortality.


Assuntos
Isquemia Encefálica/terapia , Acidente Vascular Cerebral/terapia , Terapia Trombolítica , Fibrinolíticos , Humanos , Artéria Cerebral Média , Ativador de Plasminogênio Tecidual , Resultado do Tratamento
12.
Zhonghua Er Ke Za Zhi ; 54(10): 761-766, 2016 Oct 02.
Artigo em Chinês | MEDLINE | ID: mdl-27784479

RESUMO

Objective: To report a case of the pulmonary surfactant protein(SP) adenosine triphosphate-binding-cassette-A3 (ABCA3) gene mutations in infant congenital interstitial lung disease(ILD), and review the related literature, to investigate the relationships of ABCA3 gene mutation associated with ILD in infants. Method: A 6-months-old boy was hospitalized in the department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University. The clinical, radiological, histological information from transbronchial lung biopsy (TBLB) and genetic testing in this case was analyzed; 12 reports retrieved on literature search at Pubmed, OVID databases from 2004 to 2015 by using the ABCA3 as keyword were reviewed and analyzed. Result: (1)The patient, a 6-months-old boy, had progressive tachypnea and dyspnea since 4 months old. Physical examination on admission revealed respiratory rate of 78 times/min , heart rate of 187 times/min, SpO2 0.93(mask oxygen-inspiration with 6 L/min), scattered fine moist crackles could be heard over the both lungs, clubbing fingers were found. High-resolution computed tomography(HRCT) revealed diffuse ground-glass opacity, interlobular and intralobular septal thickening. Lung biopsies showed evidences of the alveolar cavity atelectatic changes and interstitial fibrosis. SP-A and SP-B were negative in immunohistochemical stainting. SP-related gene sequence analysis found that there was compound heterozygous missense mutation of ABCA3 gene in c. 1942A>G, c.2701-33G>C and c. 991-105C>A. (2)The review of related literature found that totally 12 cases were reported. The main manifestations were progressive tachypnea and dyspnea, age of onset was between birth and 4 years of age. The imaging characteristics of chest HRCT revealed diffuse infiltration or diffuse ground-glass pattern in the lung. PROGNOSIS: 6 cases died, and 6 cases survived, including 4 cases with pulmonary function disturbance to different degrees; 12 cases had ABCA3 gene mutations, 9 cases had composite ABCA3 gene mutations, in 11 cases the mutation occured in the exon of coding region, in 1 case in the intron, 9 cases had heterozygous mutations, 3 cases had homozygous mutations. Conclusion: The main phenotypes of ABCA3 mutation associated with ILD were full term neonatal respiratory distress syndrome or progressive tachypnea or dyspnea unexplained in infants. The chest HRCT showed two diffuse pulmonary interstitial changes. ABCA3 mutation mainly was multi-site composite mutations and heterozygous mutations in the exon of coding region.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Doenças Pulmonares Intersticiais/genética , Mutação , Trifosfato de Adenosina , Biópsia , Dispneia , Éxons , Heterozigoto , Homozigoto , Humanos , Lactente , Recém-Nascido , Pulmão , Masculino , Fenótipo , Surfactantes Pulmonares , Radiografia , Síndrome do Desconforto Respiratório do Recém-Nascido , Tomografia Computadorizada por Raios X
13.
Zhonghua Bing Li Xue Za Zhi ; 45(9): 626-30, 2016 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-27646892

RESUMO

OBJECTIVE: To characterize the molecular profile in patients with Ph negative myeloproliferative neoplasms (MPN) by exploring 49 gene mutations. METHODS: Targeted gene sequencing were performed to analyze 49 MPN-associated genes in 51 patients with Ph negative MPN, of which CARL (exon 9), NPM1 (exon 12) and CEBPA (TAD, BZIP domains) were investigated by using Sanger sequencing simultaneously, while FLT3-ITD was assessed by PCR method. RESULTS: Mutations were detected in 73.5% (36/49) of genes, and the mutational rates of JAK2-V617F, CALR (exon 9) and MPL were 60.8%(31/51), 7.8%(4/51) and 7.8%(4/51) respectively, whereas the mutational rates of ASXL1, SETBP1, and SF3B1 were around 10%. In addition, 96.1% (49/51) of patients harbored at least one mutation, and more than half of the patients (52.9%, 27/51) possessed 3 or 4 gene mutations. The amount of gene mutations was significantly higher in patients with JAK2-V617F mutation than those without JAK2-V617F or CALR (exon 9) mutation (P<0.05). The last finding was that there was no statistically significant difference in the amount of mutations among four MPN subtypes (PV, ET, PMF, and MPN-U). CONCLUSION: Most patients with Ph negative MPN possesses three or more gene mutations, with various mutational profiles.


Assuntos
Mutação , Transtornos Mieloproliferativos/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas de Transporte/genética , Análise Mutacional de DNA , Éxons , Humanos , Janus Quinase 2/genética , Taxa de Mutação , Proteínas Nucleares/genética , Nucleofosmina , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Reação em Cadeia da Polimerase , Fatores de Transcrição/genética
14.
15.
Zhonghua Yi Xue Za Zhi ; 96(26): 2054-8, 2016 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-27468616

RESUMO

OBJECTIVES: To observe the intravenous thrombolysis effect of rt-PA in different time windows of acute cerebral infarction with atrial fibrillation(AF). METHODS: Acute cerebral infarction patients who accepted the intravenous thrombolysis treatment with AF from January 2012 to December 2015 were included.According to the time from onset to intravenous thrombolysis, patients were divided into two groups: thrombolysis within 3 h and thrombolysis between 3-4.5 h. The Nation Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were used to evaluate early and long-time therapeutic effects. The incidence of hemorrhagic infarction(HI), parenchymal hemorrhage(PH) and symptomatic intracranial hemorrhage(sICH) after thrombolysis within 24 hours were observed in the two groups. RESULTS: A total of 103 patients were included in the study, with 48 cases in thrombolysis within 3 h group and 55 cases in thrombolysis between 3-4.5 h group. After thrombolysis treatment, the 24-hour and 7-day NIHSS score of the two groups were significant lower than before treatment, and the difference was statistically significant(P<0.05). Compared between groups, 24-hour clinical efficacy of thrombolysis within 3 h group was better than that of thrombolysis between 3-4.5 h group, and the difference was statistically significant(P<0.05). There were no statistically significant differences between these two groups about 7-day and 90-day prognosis(P<0.05). The rate of PH in thrombolysis within 3 h group and thrombolysis between 3-4.5 h group is 6.3%(3/48) and 21.8%(12/55) individually, and the difference was statistically significant(P<0.05). While no statistically significant differences was found about the rate of HI(18.8% vs 32.7%, P>0.05) and sICH(8.3% vs 14.5%, P>0.05) between these two groups. CONCLUSIONS: For patients of acute cerebral infarction with AF, intravenous thrombolytic therapy by rt-PA within 3 h may contribute to a greatly improvement in a short time. Thrombolysis between 3-4.5 h increase the incidence of PH, but do not increase the incidence of sICH. There are no statistically significant differences between these two groups about 90-day favorable prognosis, indicating that thrombolysis between 3-4.5 h is safe and effective for acute cerebral infarction patients with AF.


Assuntos
Fibrilação Atrial , Infarto Cerebral , Doença Aguda , Administração Intravenosa , Fibrinolíticos , Humanos , Incidência , Infusões Intravenosas , Hemorragias Intracranianas , Prognóstico , Proteínas Recombinantes , Acidente Vascular Cerebral , Terapia Trombolítica , Ativador de Plasminogênio Tecidual , Resultado do Tratamento
16.
J Steroid Biochem Mol Biol ; 154: 85-93, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26134424

RESUMO

Ruscogenin, a natural steroidal sapogenin, presents in both food and medicinal plants. It has been found to exert significant anti-inflammatory activities. Considering that activation of neutrophil is a key feature of inflammatory diseases, this study was performed to investigate the inhibitory effect of ruscogenin and its underlying mechanisms responsible for neutrophil activation. Ruscogenin displayed potent antioxidative effects against Formyl-Met-Leu-Phe (FMLP)-induced extra- and intracellular superoxide generation in mouse bone marrow neutrophils, with IC50 values of 1.07±0.32 µM and 1.77±0.46 µM, respectively. Phorbol myristate acetate (PMA)-elicited extra- and intracellular superoxide generation were also suppressed by ruscogenin, with IC50 values of 1.56±0.46 µM and 1.29±0.49 µM, respectively. However, ruscogenin showed weak inhibition in NaF-induced response. Inhibition of superoxide generation was mediated neither by a superoxide-scavenging ability nor by a cytotoxic effect. Furthermore, ruscogenin inhibited the membrane translocation of p47phox and p67phox. It reduced FMLP-induced phosphorylation of cytosolic phospholipase A2 (cPLA2) and p21-activated kinase (PAK). The cellular cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) expression were increased by ruscogenin. Moreover, ruscogenin inhibited phosphorylation of protein kinase B (Akt), p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and c-Jun N-terminal kinase (JNK). In addition, the inhibitory effects of ruscogenin on superoxide production and the phosphorylation of Akt, p38MAPK, and ERK1/2 were reversed by PKA inhibitor (H89), suggesting a PKA-dependent mechanism. In summary, our data suggest that ruscogenin inhibits activation of neutrophil through cPLA2, PAK, Akt, MAPKs, cAMP, and PKA signaling pathways. Increased PKA activity is associated with suppression of the phosphorylation of Akt, p38MAPK, and ERK1/2 pathways.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Ativação de Neutrófilo/efeitos dos fármacos , Espirostanos/farmacologia , Animais , Ativação Enzimática , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fosfolipases A2 Citosólicas/metabolismo , Superóxidos/metabolismo , Quinases Ativadas por p21/metabolismo
17.
Scand J Rheumatol ; 44(1): 42-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25205256

RESUMO

OBJECTIVES: The aim of this study was to explore the possible association between dermatomyositis/polymyositis (DM/PM) and subsequent acute coronary syndrome (ACS) risk. METHOD: We used data from the National Health Insurance (NHI) system of Taiwan to address the research topic. The exposure cohort contained 2029 patients with new diagnoses of DM/PM. Each patient was randomly frequency-matched according to sex and age with four participants from the general population who did not have a history of ACS at the index date (control group). Cox proportional hazard regression analyses were conducted to estimate the relationship between DM/PM and subsequent ACS risk. RESULTS: Among patients with DM/PM, the overall risk for developing subsequent ACS was significantly higher than that of the control group [adjusted hazard ratio (aHR) 1.98, 95% confidence interval (CI) 1.17-3.35]. Further analysis indicated a higher risk in patients who were male, older, or diagnosed with comorbidities. CONCLUSIONS: The findings from this population-based retrospective cohort study suggest that DM/PM is associated with an increased subsequent ACS risk.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Dermatomiosite/epidemiologia , Adulto , Idoso , Comorbidade , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
18.
Eur J Clin Microbiol Infect Dis ; 34(3): 479-85, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25260789

RESUMO

The objective of this study was to evaluate the association between the use of anti-tuberculosis (anti-TB) agents, isoniazid (INH), rifampicin (RIF), and their combination (INH + RIF), and the risk of hepatocellular carcinoma (HCC) in cirrhotic patients. This population-based case-control study was conducted using a research database of Taiwan's National Health Insurance program. Cirrhotic patients first diagnosed with HCC between 1996 and 2011 (n = 50,351), among whom 4,738 were anti-TB medication users, were evaluated. Cirrhotic patients who did not develop HCC within the same period, frequency-matched according to age, sex, and index year, were evaluated as the control group (n = 47,488). The adjusted odds ratio (OR) of HCC was 1.34 [95 % confidence interval (CI), 1.20-1.50] in INH + RIF users compared with non-INH + RIF users. Long-term (>12 months) use of INH, RIF, and INH + RIF was significantly associated with increased risk of HCC, with an adjusted OR of 3.51 (95 % CI, 2.11-5.84), 4.17 (95 % CI, 2.76-4.31), and 7.17 (95 % CI, 4.08-12.6), respectively, after adjusting for age, sex, and comorbidities. An average dose of INH + RIF >16,050 mg/year was associated with increased risk of HCC in cirrhotic patients, with an adjusted OR of 1.48 (95 % CI, 1.27-1.73). Our results indicate that cirrhotic patients with long-term or high-dose INH and RIF treatment, particularly their combination, are associated with increased risk of HCC development.


Assuntos
Antituberculosos/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Cirrose Hepática/complicações , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/efeitos adversos , Estudos de Casos e Controles , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Isoniazida/efeitos adversos , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Rifampina/efeitos adversos , Rifampina/uso terapêutico , Risco , Medição de Risco , Taiwan , Adulto Jovem
19.
Eur J Phys Rehabil Med ; 51(1): 5-13, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25311882

RESUMO

BACKGROUND: Patients with physical disabilities more often have median neuropathies of the wrist and more than 70% of wheelchair users are overweight or obese. AIM: To explore the effects of body composition on the occurrence of distal median neuropathy and to search for the best probabilistic cutoff value of indicators to predict the likelihood of developing distal median neuropathy in patients with physical disabilities. DESIGN: A prospective study. SETTING: A 1-day annual physical checkup program for employees of a social welfare organization. POPULATION: In total, 72 patients with a physical disability (mean age ± SD, 40.0 ± 8.8 years; 40 women). METHODS: Using electrophysiologic testing to assess distal median nerve function and using a dual-energy X-ray absorptiometry examination to assess body composition. The formula for leg exercise burden index (EBI) was: leg EBI = body fat mass of both legs/lean tissue mass of both legs. RESULTS: The risk of developing a low median sensory nerve conduction velocity in the wrist-to-palm segment (< 43 m/s) was greater for patients with a higher leg EBI, yielding an adjusted odds ratio of 6.88 (P < 0.005). The body mass index (BMI) and being a wheelchair user were predictors of developing long median distal motor latency (> 4 ms). Using receiver operating characteristic analyses, we determined that patients with a physical disability were likely to develop distal median sensory neuropathy if they had a leg EBI of ≥ 0.943 and were likely to develop distal median motor neuropathy if they had a BMI of ≥ 24.5 kg/m2. CONCLUSION: The leg EBI is a predictor of having distal median sensory neuropathy among patients with a physical disability. CLINICAL REHABILITATION IMPACT: The value of the leg EBI can be useful information for identifying risk of distal median sensory neuropathy in patients with a physical disability.


Assuntos
Composição Corporal/fisiologia , Pessoas com Deficiência , Neuropatia Mediana/etiologia , Absorciometria de Fóton , Eletrofisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
20.
J Fish Dis ; 38(10): 915-923, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25297376

RESUMO

Cyprinid herpesvirus 3 (CyHV-3) is a highly contagious virus that causes significant morbidity and mortality in common carp Cyprinus carpio L. and considered to be one of the most important pathogens of koi and common carp worldwide. Cyprinid herpesvirus 3 infected consignments imported from East Asian and South-East Asian regions were identified during quarantine period in Singapore, and virus from a 2005 consignment was successfully isolated in koi fin cells. A combination of sequence analyses and duplex PCR were used to characterize 15 CyHV-3 isolates detected in koi consignments between 2005 and 2011. Sequence analyses of the enlarged 9/5, SphI-5 and TK gene regions identified both the Asian 1 (n = 11) and European 4 (n = 4) genotypes. Duplex PCR analysis of two variable marker regions between ORF29 and ORF30 (marker I) as well as ORF133 and its upstream region (marker II) revealed viruses of genotypes J (I++ II+ ), U/I (I-- II- ), an intermediate genotype (I++ II- ) and a novel genotype, I++ II+Δ , which was identified in viruses from seven different consignments. This novel genotype has a 13-bp deletion in marker II, while maintaining the I++ allele of marker I. The I++ II+Δ genotype may have emerged from East Asian and South-East Asian regions in recent years.

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