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1.
Br J Haematol ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34405393

RESUMO

Despite the high cure probability for acute promyelocytic leukaemia (APL), a minority of patients will relapse and the risk factors for relapse are unclear. We retrospectively analysed 212 patients who were diagnosed with non-high-risk APL and received all-trans retinoic acid (ATRA) plus arsenic as front-line therapy at Peking University Institute of Hematology from February 2014 to December 2018. A total of 176 patients (83%) received oral arsenic (realgar-indigo naturalis formula) plus ATRA, 36 patients (17%) received arsenic trioxide plus ATRA and 203 patients were evaluable for relapse. After a median (range) follow-up of 53·6 (24·3-85·4) months, two patients had molecular relapse and eight had haematological relapse. A promyelocytic leukaemia/retinoic acid receptor alpha (PML-RARA) transcript level of ≥6·5% at the end of induction therapy was associated with relapse (P = 0·031). The 5-year cumulative incidence of relapse, event-free survival and overall survival were 5·5%, 92·3% and 96·3% respectively. In conclusion, the present long-term follow-up study further confirmed the high cure probability of ATRA plus oral arsenic as front-line therapy for non-high-risk APL and showed that the PML-RARA transcript level at the end of induction therapy was associated with relapse.

2.
Am J Pathol ; 191(8): 1431-1441, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34294192

RESUMO

Glomeruli instance segmentation from pathologic images is a fundamental step in the automatic analysis of renal biopsies. Glomerular histologic manifestations vary widely among diseases and cases, and several special staining methods are necessary for pathologic diagnosis. A robust model is needed to segment and classify glomeruli with different staining methods and apply in cases with various glomerular pathologic changes. Herein, pathologic images from renal biopsy slides stained with three basic special staining methods were used to build the data sets. The snapshot group included 1970 glomeruli from 516 patients, and the whole-slide image group included 8665 glomeruli from 148 patients. Cascade Mask region-based convolutional neural net architecture was trained to detect, classify, and segment glomeruli into three categories: i) GN, structural normal; ii) global sclerosis; and iii) glomerular with other lesions. In the snapshot group, total glomeruli, GN, global sclerosis, and glomerular with other lesions achieved an F1 score of 0.914, 0.896, 0.681, and 0.756, respectively, which were comparable with those in the whole-slide image group (0.940, 0.839, 0.806, and 0.753, respectively). Among the three categories, GN achieved the best instance segmentation effect in both groups, as determined by average precision, average recall, F1 score, and Mask mean Intersection over Union. The present model segments and classifies multistained glomeruli with efficiency and robustness. It can be applied as the first step for more detailed glomerular histologic analysis.


Assuntos
Aprendizado Profundo , Interpretação de Imagem Assistida por Computador/métodos , Nefropatias/diagnóstico , Glomérulos Renais/patologia , Biópsia , Humanos , Nefropatias/patologia , Coloração e Rotulagem
3.
Leuk Lymphoma ; : 1-13, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34098836

RESUMO

We explored variables associated with patient-reported outcomes (PROs) including symptom burden, impact on daily life and work, obstacles during therapy, satisfaction level with therapy, and health-related quality of life in 1500 respondents with myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) in a multicenter, cross-sectional study across China, a representative of the developing countries. In multivariate analyses, urban household registration and higher education level were significantly-associated with no symptoms at diagnosis in respondents with ET or MF. CALR mutation was significantly-associated with lower MPN-10 scores in respondents with MF. Higher MPN-10 scores were significantly-associated with negative impact on daily life and work as well as lower satisfaction level in respondents with ET, PV and MF. Receiving ruxolitinib was significantly-associated with high satisfaction and satisfaction in respondents with MF. In addition, other demographics and clinical variables were also impacting PROs.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33835260

RESUMO

PURPOSE: Define the impact of socio-demographic co-variates on outcomes of persons with newly-diagnosed chronic phase chronic myeloid leukaemia (CML). METHODS: Data of 961 consecutive subjects with newly-diagnosed CML were integrated for these outcomes in multi-variable Cox regression analyses after adjusting for confounders and interactions. RESULTS: Elder age was associated with less use of a 2nd generation TKI as initial therapy. Household registration, comorbidity(ies) and education level were associated with use of a generic rather than branded TKI as initial therapy. Subjects with lower education level were more likely to be diagnosed with CML because of leukaemia-related symptoms. Rural registration and lower education level were also associated with a greater likelihood of switching TKI-therapy. Lower education level was associated with lower likelihood of achieving MMR [HR = 0.8 (0.7, 0.9), p = 0.002], MR4.5 [HR = 0.8 (0.7, 1.0), p = 0.055], and poor FFS [HR = 1.7 (1.3, 2.5); p < 0.001], PFS [HR = 2.0 (1.1, 5.0); p = 0.014], CML-related survival [HR = 2.5 (1.0, 10.0); p = 0.060] and survival [HR = 2.5 (1.0, 10.0); p = 0.043]. Males had lower rates of MMR and MR4.5 and worse FFS, but not survival compared with females. Being married was associated with a higher rate of MR4.5, fewer failures, progressions, and deaths. CONCLUSION: Socio-demographic co-variates have a strong impact on therapy choice and responses in persons with newly-diagnosed CML, including circumstances of diagnosis, risk category and prognosis, use of initial TKI, switching TKIs, response to TKI-therapy, and outcomes.

5.
Ann Hematol ; 100(5): 1203-1212, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33474629

RESUMO

Core binding factor acute myeloid leukemia (CBF-AML), including cases with KIT mutation, is currently defined as a low-risk AML. However, some patients have poor response to treatment, and the prognostic significance of KIT mutation is still controversial. This study aimed to explore the prognostic significance of different KIT mutation subtypes and minimal residual disease (MRD) in CBF-AML. We retrospectively evaluated continuous patients diagnosed with CBF-AML in our center between January 2014 and April 2019. Of the 215 patients, 147 (68.4%) and 68 (31.6%) patients were RUNX1-RUNX1T1- and CBFB-MYH11 positive, respectively. KIT mutations were found in 71 (33.0%) patients; of them, 38 (53.5%) had D816/D820 mutations. After excluding 10 patients who died or were lost to follow-up within a half year, 42.0% (n = 86) of the remaining 205 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). An MRD > 0.1% at the end of two cycles of consolidation predicted relapse (P < 0.001). Multivariate analysis showed that D816 or D820 mutations and MRD > 0.1% at the end of two cycles of consolidation were independent adverse factors affecting relapse-free survival (RFS) and overall survival (OS). Allo-HSCT could improve RFS (74.4% vs. 34.6%, P < 0.001) and OS (78.1% vs. 52.3%, P = 0.002). In conclusion, high-risk CBF-AML patients must be identified before treatment. D816/D820 mutation, MRD > 0.1% at the end of two cycles of consolidation chemotherapy predicted poor survivals, and allo-HSCT can improve the survival of properly identified patients.


Assuntos
Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Proteínas Proto-Oncogênicas c-kit/genética , Adolescente , Adulto , Idoso , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasia Residual , Prognóstico , Estudos Retrospectivos , Adulto Jovem
6.
Br J Haematol ; 192(2): 265-271, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32588434

RESUMO

No consensus has been reached on the relationship between CBFB-MYH11 copies and prognosis. Of 1525 acute myeloid leukemia (AML) patients, 58 with CBFB-MYH11-positive AML (16/58 patients with c-kit mutation) were retrospectively analyzed with a median follow-up duration of 29.8 (range: 4.8-74.4) months. Of these, 25/58 (43.1%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), 10 of whom had the c-kit mutation. Of the 33 patients who did not undergo allo-HSCT, recurrence in patients with CBFB-MYH11/ABL level >0.1% at any time after two consolidation cycles was significantly higher than in patients with CBFB-MYH11/ABL level <0.1% (61.9% vs. 0%, P = 0.001); further, the 3-year relapse-free survival (RFS; 31.4% vs. 100%, P = 0.004) and event-free survival (EFS; 33.1% vs. 100%, P = 0.004) were significantly decreased in patients with CBFB-MYH11/ABL level >0.1% at any time after two consolidation cycles. The 3-year RFS and EFS rates were lower in patients who did not receive allo-HSCT than in those who did (31.4% vs 84.6%, P = 0.000; 31.4% vs. 80.8%, P = 0.001). CBFB-MYH11-positive AML patients with CBFB-MYH11/ABL level >0.1% at any time after two cycles of consolidation had poor prognoses, and allo-HSCT could improve their survival.


Assuntos
Subunidade beta de Fator de Ligação ao Core/genética , Leucemia Mieloide Aguda/diagnóstico , Cadeias Pesadas de Miosina/genética , Adolescente , Adulto , Idoso , Quimioterapia de Consolidação , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Neoplasia Residual/terapia , Fusão Oncogênica , Prognóstico , Estudos Retrospectivos , Adulto Jovem
7.
Eur J Haematol ; 105(2): 185-195, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32282962

RESUMO

BACKGROUND: Currently, the prognostic stratification and therapeutic evaluation systems for multiple myeloma (MM) lack specific molecular indicators. OC-STAMP is a new gene and is also highly expressed in MM. METHODS: A total of 160 MM patients have been investigated with both quantitative reverse transcription PCR (RT-qPCR), flow cytometry (FCM) and cytogenetic FISH on the same mononuclear cells isolated from bone marrow specimens. RESULTS: We found that OC-STAMP mRNA levels were significantly higher in newly diagnosed cases of MM than in healthy donors (median, 0.52% vs. 0.02%, P < .001). Moreover, the changes in the OC-STAMP mRNA levels paralleled the disease stages and minimal residual disease, as detected by FCM. Furthermore, we found that patients with high OC-STAMP mRNA levels were more likely to develop ≥3 bone lesions, be diagnosed with Durie-Salmon stages III, and have the P53 (17p13) deletion. In addition, advanced stage patients with high OC-STAMP mRNA levels had a lower 4-year progression-free survival (5.6% vs. 22.9%, P = .0055) and a worse 4-year overall survival (25.8% vs. 48.8%, P = .0137) compared to patients with low mRNA levels of this indicator. CONCLUSIONS: OC-STAMP may be a promising molecular indicator to monitor treatment effects and participate in the prognostic stratification of MM.


Assuntos
Biomarcadores Tumorais , Proteínas de Membrana/genética , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Medula Óssea/patologia , Linhagem Celular Tumoral , Aberrações Cromossômicas , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Humanos , Imunofenotipagem , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Análise de Sobrevida , Translocação Genética , Proteína Supressora de Tumor p53/genética
8.
Clin Lymphoma Myeloma Leuk ; 20(6): e304-e315, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32209331

RESUMO

INTRODUCTION: To compare the efficacy and safety of generic and branded imatinib in adults with newly diagnosed chronic myeloid leukemia in the chronic phase (CML-CP), we retrospectively reviewed data from patients CML-CP who received generic or branded imatinib. PATIENTS AND METHODS: A propensity score matching (PSM) study was performed. A Cox regression model was used to identify factors associated with responses and outcomes. RESULTS: Four hundred forty-two adults receiving generic imatinib (n = 236) or Glivec (Novartis, Basel, Switzerland; n = 206) were included. There were more patients with rural household registration (P < .001), lower education level (P < .001), divorced or widowed status (P = .009), higher white blood cell counts (P = .019), splenomegaly (P < .001), and longer intervals from diagnosis to imatinib initiation (P = .033) in the generic cohort. During the follow-up, there was no significant difference between the 2 cohorts in the 4-year probabilities of achieving a complete cytogenetic response (97.0% vs. 97.3%; P = .736), major molecular response (87.8% vs. 90.1%; P = .113), and molecular response4.5 (32.5% vs. 38.8%; P = .186), as well as failure-free survival (77.3% vs. 81.4%; P = .313), progression-free survival (94.4% vs. 95.8%; P = .489), and overall survival (96.8% vs. 98.3%; P = .088). Multivariate analyses showed that the drug type was not associated with responses and outcomes. After the PSM procedure, 177 pairs of patients with comparable baseline characteristics were reanalyzed. Multivariate analyses confirmed that generic or branded imatinib used as first-line therapy was not associated with either responses or outcomes. CONCLUSION: Sociodemographic characteristics might influence the tyrosine kinase inhibitor that patients chose. Generic and branded imatinib as first-line therapy had comparable efficacy and safety in CML-CP patients.


Assuntos
Medicamentos Genéricos/administração & dosagem , Mesilato de Imatinib/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Medicamentos Genéricos/efeitos adversos , Feminino , Humanos , Mesilato de Imatinib/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Socioeconômicos
9.
Br J Haematol ; 190(4): 533-544, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32090321

RESUMO

Acute myeloid leukaemia (AML) patients with biallelic mutations of CEBPA (bi CEBPA) have a 30-50% relapse rate. This study established the value of mutations based on next-generation sequencing (NGS) and multiparameter flow cytometric measurable residual disease (MFC-MRD) detection and compared the outcomes. From 2014 to 2018, 124 newly diagnosed bi CEBPA AML patients were treated. The median age was 37·5 (16-69) years. The 3-year cumulative incidence of relapse (CIR), relapse-free survival (RFS) and overall survival (OS) were 33·0%, 64·7% and 84·3%, respectively. Patients without additional mutations and with GATA2 mutations were defined as 'NGS low risk', which was the only favourable independent factor for CIR and RFS of pretreatment parameters. Patients with sustained positive MRD after two consolidation cycles and MRD negative losses at any time were defined as 'MRD high risk', which was the only poor independent factor for CIR, RFS and OS, including pretreatment and post-treatment parameters. In CR2 and non-remission patients who underwent allo-HSCT, superior OS was achieved. We conclude that NGS low risk was a favourable factor in the analysis of pretreatment parameters. MRD risk stratification was an independent prognostic factor in pretreatment and post-treatment parameters. Relapsed patients still have a favourable outcome followed by allo-HSCT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas Estimuladoras de Ligação a CCAAT/genética , Sequenciamento de Nucleotídeos em Larga Escala , Leucemia Mieloide Aguda/patologia , Proteínas de Neoplasias/genética , Neoplasia Residual/diagnóstico , Adolescente , Adulto , Idoso , Alelos , Aloenxertos , Antraciclinas/administração & dosagem , Terapia Combinada , Citarabina/administração & dosagem , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Idarubicina/administração & dosagem , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Recidiva , Medição de Risco , Adulto Jovem
10.
Cytometry A ; 97(1): 61-69, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31876105

RESUMO

To date, the research on dendritic cells (DCs) and their correlated neoplasms has not been clear. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) and mature plasmacytoid dendritic cell proliferation (MPDCP) are two types of malignancies originating from plasmacytoid dendritic cells (pDCs). Some evidence has indicated the existence of other pDC neoplasms. In addition, cases of myeloid neoplasms (MNs), acute myeloblastic leukemia (AML), and myelodysplastic syndrome (MDS) with increased pDCs (AML/MDS-pDCs) seem to have immature DCs according to the vaguely consistent expression of markers among MNs and pDCs, which appear to fit the developmental pattern of normal DCs. We analyzed 14 AML/MDS-pDC cases mainly for their immunophenotype by flow cytometry and inferred their CD expression pattern. The patients' clinical information and other laboratory data were collected and reviewed. AML/MDS-pDCs show a different pattern of markers from BPDCN and MPDCP. Three maturation-involved stages were found in these AML/MDS-pDCs patients. Stage I was the most immature stage and displayed an expression profile of CD34+/st+ CD117+/st+ BDCA2- BDCA4- CD123+ HLA-DR+/st+ CD4- CD45dim+ ; Stage II was the more immature stage displayed a phenotype of CD34dim+ CD117dim+ BDCA2-/dim+ BDCA4-/dim+ CD123st+ HLA-DR+/st+ CD4- CD45+ ; and Stage III was the mature stage showed CD34- CD117- BDCA2+ /BDCA4+ CD123st+ HLA-DR+/st+ CD4+ CD45+/st+ . Three maturation-involved stages overlapped well with the phenotypes of normal DC progenitors in a continuously developmental process: granulocyte, monocyte, and DC progenitors (GMDPs) and/or monocyte and DC progenitors (MDPs), common DC progenitors (CDPs), pDCs, and/or pre-DCs. In this study, we considered AML/MDS-pDCs as entities that were distinct from BPDCN and MPDCP and correlated the components of this tumor with the normal DC differentiation pathway, which provides new evidence for understanding DC neoplasms. © 2019 International Society for Advancement of Cytometry.


Assuntos
Apresentação do Antígeno/fisiologia , Diferenciação Celular/fisiologia , Células Dendríticas/citologia , Leucemia Mieloide Aguda/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Dendríticas/imunologia , Feminino , Hematopoese/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
11.
Medicine (Baltimore) ; 98(41): e17388, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593089

RESUMO

It is not rare to find Immunoglobulin A (IgA) nephropathy (IgAN) combined with other glomerular diseases, which can be called compound IgAN (cIgAN). Till now, clinical-pathological investigation of cIgAN was lacking, especially the severity of "background IgAN lesions." This research aimed to investigate the incidence, clinical and pathological characteristics of cIgAN, and thus improve the understanding of the clinical significance of this combination.Patients with cIgAN diagnosed in Peking University People's Hospital from November 2012 to April 2018 were retrospectively analyzed. Patients with IgAN without compound glomerular diseases (sIgAN) were enrolled as a control group.Among 1407 patients diagnosed with IgAN, 80 (5.69%) were cIgAN patients. Compared with sIgAN, cIgAN patients had a significantly lower prevalence of microscopic hematuria and more urine protein. There were 10 pathological types of glomerular diseases combined with IgAN, led by diabetic nephropathy 37 (46.25%) and membranous nephropathy 14 (17.5%). Histologically, although the mesangial hypercellularity was comparable in 2 groups, cIgAN patients had a lower prevalence of endocapillary proliferation, segmental glomerulosclerosis, and cellular or fibrocellular crescents formation, as well as weaker immunofluorescence intensity for IgA and C3 (all P < .05). Eight out of 27 (29.63%) cIgAN patients with follow-up data (5-48 months) developed irreversible end-stage renal disease requiring dialysis.The order of incidence of concomitant diseases was similar to that of the pure diseases. The "background IgAN associated lesions" except mesangial hypercellularity were relatively mild in cIgAN group. Those might suggest that in some cases, IgAN seems to be a chance finding, and the combined diseases may play a more important role in the clinicopathological features of the patients than the nephritis caused by IgA deposition. While diagnosing IgAN, other combined glomerular diseases need to be carefully considered by nephrologists and pathologists.


Assuntos
Glomerulonefrite por IGA/patologia , Glomerulonefrite/patologia , Adulto , Biópsia , Feminino , Glomerulonefrite/epidemiologia , Glomerulonefrite/imunologia , Glomerulonefrite por IGA/complicações , Humanos , Incidência , Rim/imunologia , Rim/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Acta Haematol ; 142(3): 162-170, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091521

RESUMO

Aplastic anemia (AA) is a hematologic disease characterized by pancytopenia and hypocellular bone marrow, potentially leading to chronic anemia, hemorrhage, and infection. The China Aplastic Anemia Committee and British Committee for Standards in Haematology guidelines recommend hematopoietic stem-cell transplantation (HSCT) or immunosuppressive therapy (IST) comprising antithymocyte globulin (ATG) with cyclosporine (CsA) as initial treatment for AA patients. With limited epidemiological data on the clinical management of AA in Asia, a prospective cohort registry study involving 22 AA treatment centers in China was conducted to describe the disease characteristics of newly diagnosed AA patients and investigate real-world treatment patterns and patient outcomes. Of 340 AA patients, 72.9, 12.6, and 3.5% were receiving IST, traditional Chinese medicine, and HSCT, respectively, at baseline; only 22.2% of IST-treated patients received guideline-recommended ATG with CsA initially. Almost all patients received supportive care (95.6%) as blood transfusion (97.8%), antibiotics (63.7%), and/or hematopoietic growth factors (58.2%). Overall, 64.8% achieved a partial or complete response, and 0.9% experienced relapse. No new safety concerns were identified; serious adverse events were largely unrelated to the treatment regimen. These results demonstrate the need to identify and minimize treatment barriers to standardize and align AA management in China with treatment guideline recommendations and further improve patient outcomes.


Assuntos
Anemia Aplástica , Soro Antilinfocitário/administração & dosagem , Ciclosporina/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Imunossupressão , Medicina Tradicional Chinesa , Sistema de Registros , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Anemia Aplástica/mortalidade , Anemia Aplástica/terapia , Criança , Pré-Escolar , China/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(1): 141-148, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30738461

RESUMO

OBJECTIVE: To study the value of flow cytometric scoring system in the diagnosis of myelodysplastic syndromes (MDS). METHODS: The phenotypes of erythroid and immature cells were analyzed retrospectively in 130 MDS patients, 19 healthy controls and 89 pathological controls, all of them were well clinically immunophenotyped. The 4-parameter scoring system reported in the literature was studied, including myeloblast-related cluster size, B-progenitor-related cluster size, lymphocyte to myeloblast CD45 ratio, and granulocyte to lymphocyte side scatter ratio. The two flow cytomatric parameters of the erythroid scoring system were analyzed, including CD36 coefficient of variation (CV) and CD71CV. According to our previous study, the percentage of CD117+CD105- myeloid progenitor cells and the proportion of CD105+ cells in CD117+ cells were selected to establish a two-parameter scoring system, and compared with the four-parameter scoring system and the erythroid scoring system. RESULTS: The sensitivity of the four-parameter scoring system and the erythroid scoring system for the diagnosis of low-risk MDS was 43.5% and 63.0%, and the specificity was 87.0% and 63.9%, respectively. After combining the two scoring systems, the sensitivity to diagnose low-risk MDS was 73.9% and the specificity was 62.0%. The sensitivity of the two-parameter scoring system for the diagnosis of low-risk MDS was 76.1% with a specificity of 81.5%. Combined with the four-parameter scoring system, the sensitivity was increased to 78.3%, but the specificity was reduced to 71.3%. After combining with the erythroid scoring system, the sensitivity reached 87.0%, but the specificity was reduced to 54.6%. CONCLUSION: Using the two-parameter scoring system alone can achieve great sensitivity and specificity in the diagnosis of low risk MDS.


Assuntos
Síndromes Mielodisplásicas , Endoglina , Citometria de Fluxo , Humanos , Imunofenotipagem , Síndromes Mielodisplásicas/diagnóstico , Proteínas Proto-Oncogênicas c-kit , Estudos Retrospectivos
14.
Ecotoxicol Environ Saf ; 168: 9-16, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30384172

RESUMO

Cold exposure aggravates respiratory diseases, which are also influenced by the exposures to particulate matter and endotoxin in the air. The aim of this study was to investigate the potential interactions among cold stress, fine particulate matter (PM2.5, particles with aerodynamic diameter of 2.5 µm or less) and lipopolysaccharide (LPS, pure chemical form of endotoxin) on rat lung and to explore the related possible mechanisms of the interactions. Wistar rats were randomly grouped to be exposed to, 1) normal saline (0.9% NaCl), 2) PM2.5, 3) LPS, and 4) PM2.5 and LPS (PM2.5 + LPS) through intratracheal instillation under cold stress (0 °C) and normal temperature (20 °C). Lung function, lung tissue histology, inflammatory response and oxidative stress levels were measured to examine the lung injury and to investigate the potential mechanisms. Exposure to PM2.5 or LPS substantially changed pulmonary function [indicated by peak inspiratory flow (PIF) and peak expiratory flow (PEF)], inflammatory cytokine levels [indicated by interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)] and lung histology, compared to the non-exposed groups. Exposure to PM2.5 + LPS under cold stress induced the most significant changes, including the increases of IL-6, TNF-α and thiobarbituric acid-reactive substances (TBARS), the decreases of PIF and PEF and more severe lung injury, among all exposure scenarios. Glutathione peroxidase activity and, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were found to be suppressed under cold stress, whereas Nrf2 and HO-1 levels were observed to be upregulated by exposure to PM2.5 or LPS under normal temperature. In conclusion, cold stress may aggravate the lung injury in rats induced by simultaneous exposure to PM2.5 and LPS. The progress may involve the suppressing of Nrf2/HO-1 signal pathway.


Assuntos
Resposta ao Choque Frio/fisiologia , Lipopolissacarídeos/toxicidade , Lesão Pulmonar/etiologia , Material Particulado/toxicidade , Animais , Citocinas/metabolismo , Pulmão/patologia , Lesão Pulmonar/patologia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/fisiologia , Material Particulado/metabolismo , Distribuição Aleatória , Ratos Wistar , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismo
15.
Leuk Res ; 73: 16-20, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30176386

RESUMO

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is 10- to 20-fold less common in Asians (including Han Chinese) compared with persons of predominately European descent. Why is unknown but seems predominately genetic. We observed an increasing frequency of new cases of CLL at our Haematology Centre beginning 2011 and wondered why. OBJECTIVE: Determine the cause(s) for this increased frequency. METHOD: We interrogated the context of CLL diagnosis in 483 consecutive subjects seen at the Institute of Haematology of a large referral hospital in Beijing. 3 cohorts were considered based on why a CBC was done to establish the CLL diagnosis: (1) a CBC-testing situation unrelated to a health condition such as a routine annual health exam or application for employment or medical insurance (termed routine CBC); (2) an unrelated medical condition such as a cold, influenza, heart disease etc. (termed CBC for other disorders); and (3) signs and/or symptoms consistent with CLL such as lymph-adenopathy, hepato- or splenomegaly, fatigue, B-symptoms etc. (termed CBC for possible CLL). RESULTS: Data regarding context of CLL diagnosis were available for 389 subjects (81%). Proportions of subjects in the 3 cohorts were 44% (95% confidence interval [CI]; 39, 49%), 24% (20, 28%) and 32% (28, 37%). The proportion of subjects whose evaluation of CLL was prompted by an abnormal CBC not for possible CLL (cohorts 1 and 2) increased over the surveillance interval (r = 0.164; P = 0.001) as did median age at diagnosis (r = 0.207; P < 0.001). Age at diagnosis was correlated with probability of CLL being suspected because of an abnormal routine CBC (r = 0.249; P < 0.001); 42% (32, 53%) amongst subjects ≤50 years versus 86% (75, 92%; P < 0.001) among those >70 years. Consistent with this, older subjects were diagnosed at Rai stage-0 with asymptomatic disease compared with younger subjects (P < 0.001). CONCLUSION: Our data suggest much of the increased frequency of CLL at our centre and likely elsewhere in China predominately reflects ascertainment bias. Other variables may also operate.


Assuntos
Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
16.
Br J Haematol ; 182(5): 693-700, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29974949

RESUMO

To explore the type, prevalence and outcomes in chronic myeloid leukaemia (CML) patients with uncommon BCR-ABL1 transcripts in the era of tyrosine kinase inhibitors (TKIs), uncommon BCR-ABL1 transcripts were screened in 4750 patients by multiplex polymerase chain reaction (PCR), and type-specific real-time quantitative PCR was regularly performed for molecular monitoring. A total of 19 uncommon transcripts, including e1a2, e1a3, e6a2, e8a2, e12a2, unusual e13a2, e13a3, unusual e14a2, e14a3 and e19a2 were identified in 83 (1·7%) patients. The three most frequent types were e19a2, e13a3/e14a3 and e1a2. Compared with the 571 newly diagnosed CML patients in chronic phase with common e13a2/e14a2 transcripts receiving frontline imatinib therapy, patients with the e19a2 (n = 16) and e1a2 (n = 11) transcripts had significantly reduced probabilities of 1-year complete cytogenetic response (CCyR, P = 0·0004 and 0·016) and major molecular response (MMR, P = 0·0018 and 0·0035), and patients with the e13a3/e14a3 transcript (n = 10) had significantly increased probabilities of 1-year CCyR (P = 0·0072) and MMR (P = 0·0073). Patients with the e19a2 transcript had low probabilities of 2-year event-free survival (EFS, P = 0·0004) and progression-free survival (P = 0·0067), and patients with the e1a2 transcript had low probability of 2-year EFS (P < 0·0001). Therefore, uncommon BCR-ABL1 fusion transcripts are rare and diverse in patients with CML and may be relevant for TKI therapy outcomes.


Assuntos
Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Sequência de Bases , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Prevalência , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , RNA Mensageiro/genética
17.
Nano Lett ; 18(5): 3193-3198, 2018 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-29617142

RESUMO

Tin-based alloys (Sn-M, M = Fe, Co, Ni, and Cu) have been considered as promising alternatives for graphite anode in advanced Li-ion batteries, but their practical application is hindered by huge volume change-induced poor cycle life. We propose here a facile inorganic-organic double-network nanostructured hydrogel-enabled methodology for uniformly immobilizing ultrafine Sn-M alloys in hierarchical carbon frameworks. The double-network nanostructured gel, consisting of three-dimensional (3D) intertwined cyano-bridged Sn(IV)-Fe(II) inorganic gel and chitosan-glutaraldehyde organic polymer gel, can realize 3D space confinement in molecular scale and thus obtain ultrafine Sn-Fe alloy particles (average size ∼2.7 nm) uniformly embedded in hierarchical 1D to 3D carbon framework. These unique structural features enable the Sn-Fe@C framework electrodes to exhibit long cycle life (516 mA h g-1 after 500 cycles at 0.1 A g-1) and high rate capability (491 and 270 mA h g-1 at 1 and 10 A g-1, respectively). This work provides new insight into controlled synthesis of ultrafine alloys in hierarchical 3D carbon frameworks for improving energy storage properties.

18.
Artif Cells Nanomed Biotechnol ; 46(sup1): 806-816, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29513101

RESUMO

Vitamin A deficiency and mitochondrial dysfunction are both associated with neural differentiation-related disorders, such as Alzheimer's disease (AD) and Down syndrome (DS). The mechanism of vitamin A-induced neural differentiation and the notion that vitamin A can regulate the morphology and function of mitochondria in its induction of neural differentiation through the RIP140/PGC-1α axis are unclear. The aim of this study was to investigate the roles and underlying mechanisms of RIP140/PGC-1α axis in vitamin A-induced neural differentiation. Human neuroblastoma cells (SH-SY5Y) were used as a model of neural stem cells, which were incubated with DMSO, 9-cis-retinoic acid (9-cis-RA), 13-cis-retinoic acid (13-cis-RA) and all-trans-retinoic acid (at-RA). Neural differentiation of SH-SY5Y was evaluated by Sandquist calculation, combined with immunofluorescence and real-time polymerase chain reaction (PCR) of neural markers. Mitochondrial function was estimated by ultrastructure assay using transmission electron microscopy (TEM) combined with the expression of PGC-1α and NEMGs using real-time PCR. The participation of the RA signaling pathway was demonstrated by adding RA receptor antagonists. Vitamin A derivatives are able to regulate mitochondrial morphology and function, and furthermore to induce neural differentiation through the RA signaling pathway. The RIP140/PGC-1α axis is involved in the regulation of mitochondrial function in vitamin A derivative-induced neural differentiation.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Neurônios/citologia , Proteína 1 de Interação com Receptor Nuclear/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Vitamina A/farmacologia , Linhagem Celular Tumoral , Humanos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Vitamina A/análogos & derivados
19.
Med Sci Monit ; 24: 758-767, 2018 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-29408852

RESUMO

BACKGROUND Acute myeloid leukemia with intermediate cytogenetic risk (ICR-AML) needs to be stratified. The abnormal gene expression might be prognostic, and its cutoff value for patient grouping is pivotal. MATERIAL AND METHODS Ecotropic viral integration site 1 (EVI1) transcripts were assessed in 191 adult ICR-AML patients at diagnosis who received chemotherapy only. MLL-PTD, WT1 transcript levels, FLT3-ITD, and NPM1 mutations were simultaneously evaluated, and 27 normal bone marrow samples were tested to define normal threshold. RESULTS The normal upper limit of EVI1 transcript levels was 8.0%. Receiver operating characteristic curve analysis showed that 1.0% (a 0.9-log reduction from the normal limit) was the EVI1 optimal cutoff value for significantly differentiating relapse (P=0.049). A total of 23 patients (12%) had EVI1 levels ≥1.0%. EVI1 ≥1.0% had no effect on CR achievement, whereas it was significantly associated with lower 2-year relapse-free survival (RFS), disease-free survival (DFS), and overall survival (OS) rates in the entire cohort (P=0.0003, 0.0017, and 0.0009, respectively), patients with normal karyotypes (P=0.0032, 0.0047, and 0.0007, respectively), and FLT3-ITD (-) patients (all P<0.0001). Multivariate analysis showed that EVI1 ≥1.0% was an independent adverse prognostic factor for RFS, DFS, and OS in the entire cohort. In addition, patients with EVI1 transcript levels between 1.0% and 8.0% had 2-year RFS rates similar to those with EVI1 ≥8.0%, and they both had significantly lower RFS rates than those with EVI1 <1.0% (P=0.0005 and 0.027). CONCLUSIONS High EVI1 expression predicts poor outcome in ICR-AML patients receiving chemotherapy. The optimal cutoff value for patient stratification is different from the normal limit.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Proteína do Locus do Complexo MDS1 e EVI1/genética , Adolescente , Adulto , Idoso , Medula Óssea/patologia , Estudos de Coortes , Citogenética , Intervalo Livre de Doença , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Proteína do Locus do Complexo MDS1 e EVI1/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
20.
Nanoscale ; 10(10): 4962-4968, 2018 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-29485657

RESUMO

The practical application of Sn-M (M = Fe, Ni, Co, and Cu) alloys, a promising anodic category for lithium-ion batteries, is hindered primarily by their huge volume change upon cycling. Immobilization of Sn-M alloys within carbon matrices has proven to be effective to improve their cycling stability, but the traditional pyrolysis of separate Sn, M, and C precursors often leads to uneven distribution of the three components in Sn-M-C ternary anodes. Herein, we report a facile and general aerogel-derived pyrolysis route to realize homogeneous embedding of uniformly-sized Sn-M alloy nanocrystals, within a nanoporous carbon matrix, using cyano-bridged hetero-metallic (Sn-M) aerogels hybridized with carbon sources as precursors. Using the optimized citric acid (CA) as a carbon source, the formations of nanoporous Sn-Fe@C and Sn-Ni@C networks have been illustrated as examples through pyrolyzing CA/Sn-Fe and CA/Sn-Ni aerogels, respectively. By virtue of their compositional/structural superiorities toward lithium storage, the as-prepared Sn-Fe@C and Sn-Ni@C networks manifest higher capacities, enhanced cycling stability, and improved rate capability compared to the Sn-M-C composites and carbon samples derived from bare aerogels and CA precursors, respectively. Specifically, the Sn-Fe@C network manifests a high reversible capacity of 441.6 mA h g-1 after 100 cycles at 100 mA g-1 and an average capacity of 438.6 mA h g-1 at 1 A g-1. This work shows a new guideline for designing highly-uniform Sn-M-C, Sb-M-C, and Bi-M-C ternary anodes for boosting energy storage.

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