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OBJECTIVES: Takayasu's arteritis (TAK) involves inflammatory vasculitis of large vessels and mainly affects the aorta and its major branches. Abnormal immunity may play a vital role in TAK pathogenesis. Regulatory T cells (Treg cells) are important for peripheral tolerance, but under certain conditions Treg cells can differentiate into Th-like cells that have lost immune suppressive function and promote the development of autoimmune diseases. The role of Th-like Treg cells in TAK is unclear and this study aims to investigate the function of Th-like Treg cell subsets and associated cytokines in TAK. METHODS: A total of 51 patients with TAK and 32 healthy controls were enrolled. The percentage of Th1, Th2, Th17, Tregs and Th-like Treg cells in blood samples was analyzed by flow cytometry. Serum cytokine levels were detected using a cytometric bead array for cytokines. RESULTS: TAK patients had decreased numbers of Th2-like Treg cells in the peripheral blood (p=0.002) relative to healthy controls. The percentage of Treg cells in samples from TAK patients also decreased (p=0.002), but the Th2 cell percentage (p=0.04) increased compared to healthy controls. TAK patients had higher serum levels of IL-4 (p<0.001) and IL-13 (p<0.001) than healthy controls, and levels of both cytokines correlated to IL-6 levels. CONCLUSIONS: We studied changes in T helper-like Treg cell subsets in TAK for the first time and discovered that the number of Th2-like Treg cells in peripheral blood decreased. Results of this study suggested that Th2-like Treg cells could contribute to TAK pathogenesis.
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Linfócitos T Reguladores/imunologia , Arterite de Takayasu/patologia , Estudos de Casos e Controles , Citocinas/sangue , Humanos , Arterite de Takayasu/imunologia , Células Th1 , Células Th17 , Células Th2RESUMO
DHX15 plays a role in leukaemogenesis and leukaemia relapse. However, the mechanism underlying the transcriptional regulation of DHX15 in ALL has not been elucidated. Our present study aimed to explore the functional promoter region of DHX15 and to investigate the transcription factors controlling the transcription of this gene. A luciferase assay performed with several truncated constructs identified a 501-bp region as the core promoter region of DHX15. Site-directed mutagenesis, electrophoretic mobility shift and chromatin immunoprecipitation assays showed that ETS1 and SP1 occupied the DHX15 promoter. Furthermore, knockdown of ETS1 and SP1 resulted in suppression of DHX15, whereas the overexpression of these genes led to up-regulation of DHX15. Interestingly, in samples obtained from patients with ALL at diagnosis, both ETS1 and SP1 correlated positively with DHX15 expression. Additionally, differences in methylation of the DHX15 core promoter region were not observed between the patients and controls. In conclusion, we identified the core promoter region of DHX15 and demonstrated that ETS1 and SP1 regulated DHX15 expression in ALL.
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Regulação Leucêmica da Expressão Gênica , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteína Proto-Oncogênica c-ets-1/metabolismo , RNA Helicases/genética , Fator de Transcrição Sp1/metabolismo , Pareamento de Bases/genética , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Ilhas de CpG/genética , Metilação de DNA/genética , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Regiões Promotoras Genéticas , Ligação Proteica , Proteína Proto-Oncogênica c-ets-1/genética , RNA Helicases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sítio de Iniciação de Transcrição , Transcrição GênicaRESUMO
BACKGROUND: Achilles tendons are the most common sites of tendon xanthomas that are commonly caused by disturbance of lipid metabolism. Achilles tendon thickening is the early characteristic of Achilles tendon xanthomas. The relationship between Achilles tendon thickness (ATT) and LDL-C levels, and risk factors of ATT in patients with hypercholesterolemia, have thus far been poorly documented. METHODS: A total of 205 individuals, aged 18-75 years, were enrolled from March 2014 to March 2015. According to the LDL-C levels and the "Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults", all subjects were divided into 3 groups: normal group (LDL-C < 3.37 mmol/L, n = 51); borderline LDL-C group (3.37 mmol/L ≤ LDL-C ≤ 4.12 mmol/L, n = 50); and hypercholesterolemia group (LDL ≥ 4.14 mmol/L, n = 104). ATT was measured using a standardized digital radiography method and the results were compared among the 3 groups. The correlation between ATT and serum LDL-C levels was analyzed by Pearson's correlation, and the risk factors of ATT were determined by the logistic regression model. RESULTS: ATT in borderline LDL-C group was 8.24 ± 1.73 mm, markedly higher than 6.05 ± 0.28 mm of normal group (P < 0.05). ATT in hypercholesterolemia group was 9.42 ± 3.63 mm which was significantly higher than that of normal group (P < 0.005) and that of borderline LDL-C group (P < 0.05). There was a positive correlation between the serum LDL-C levels and ATT (r = 0.346, P < 0.001). The serum LDL-C level was a risk factor (OR = 1.871, 95% CI: 1.067-3.280) while the levels of HDL-C (OR = 0.099, 95% CI: 0.017-0.573) and Apo AI (OR = 0.035, 95% CI: 0.003-0.412) were protective factors of ATT. CONCLUSIONS: ATT might serve as a valuable auxiliary diagnostic index for hypercholesterolemia and used for the assessment and management of cardiovascular disease.
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Tendão do Calcâneo/patologia , LDL-Colesterol/sangue , Hipercolesterolemia/patologia , Xantomatose/epidemiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Hipercolesterolemia/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Xantomatose/sangue , Adulto JovemRESUMO
FtmPT1 is a fungal indole prenyltransferase that affords Tryprostatin B from Brevianamide F and dimethylallyl pyrophosphate; however, when a single residue in the active site is mutated (Gly115Thr), a novel five-membered ring compound is obtained as the major product with Tryprostatin B as the minor product. Herein, we describe detailed studies of the catalysis of the Gly115Thr mutant of FtmPT1 with a focus on the observed regioselectivity of the reaction. We employ one- and two-dimensional potential of mean force simulations to explore the catalytic mechanism, along with molecular dynamics simulations exploring the reaction dynamics of the prenyl transfer reaction. Single-point electronic structure calculations were also used to explore the performance of the self-consistent charge density functional tight-binding method to model specific reaction steps. Importantly, we observe that the two reaction pathways have comparable activation parameters and propose that the origin of the novel product is predicated, at least in part, on the topology of the potential energy surface as revealed by reaction dynamics studies.
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Dimetilaliltranstransferase/genética , Dimetilaliltranstransferase/metabolismo , Glicina/genética , Proteínas Mutantes/metabolismo , Mutação , Treonina/genética , Dimetilaliltranstransferase/química , Conformação Molecular , Simulação de Dinâmica Molecular , Proteínas Mutantes/química , Proteínas Mutantes/genética , Teoria QuânticaRESUMO
PURPOSE: Predicting prognosis and treatment outcomes for patients with for nasopharyngeal carcinoma (NPC) has been difficult due to the heterogeneous nature of the disease This study aimed to evaluate pretreatment copy number of plasma Epstein-Barr virus (EBV) DNA as an outcome marker for survival in NPC. METHODS: MEDLINE, CENTRAL and Embase databases were searched until April 7, 2015. Included studies were randomized controlled trials, two-arm prospective studies, or retrospective studies in patients with newly diagnosed NPC. The primary outcome was overall survival and secondary outcomes were progression-free, relapse-free, disease-free and distant metastasis-free survival. Sensitivity, quality and publication bias assessments were performed. RESULTS: Sixteen studies were included in the meta-analysis, with a total of 7698 patients. For overall survival, pooled HR was 3.005 (95% confidence interval [CI] = 2.245-4.022; P < 0.001), indicating that higher levels of EBV DNA were associated with a greater risk of death. Pooled estimates for relapse-free, disease-free, progression-free and distant metastasis-free survival indicated that higher levels of EBV DNA were associated with an increased risk of relapse, disease recurrence, disease progression and distant metastasis in comparison with lower levels of EBV DNA (P values < 0.001). CONCLUSION: This meta-analysis found that high EBV DNA levels indicate poor prognosis and reduced long-term survival in patients with newly diagnosed NPC; hence, EBV DNA levels are highly prognostic of survival in patients with NPC. None of the included studies used the WHO standard for EBV DNA measurement, indicating a greater need for harmonization in future studies.
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Biomarcadores Tumorais/sangue , Carcinoma , DNA Viral/sangue , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4/metabolismo , Neoplasias Nasofaríngeas , Carcinoma/sangue , Carcinoma/mortalidade , Carcinoma/terapia , Carcinoma/virologia , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Feminino , Humanos , Masculino , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/virologiaRESUMO
BACKGROUND: We have previously demonstrated that estrogen could significantly enhance expression of apolipoprotein M (apoM), whereas the molecular basis of its mechanism is not fully elucidated yet. To further investigate the mechanism behind the estrogen induced up-regulation of apoM expression. RESULTS: Our results demonstrated either free 17ß-estradiol (E2) or membrane-impermeable bovine serum albumin-conjugated E2 (E2-BSA) could modulate human apoM gene expression via the estrogen receptor alpha (ER-α) pathway in the HepG2 cells. Moreover, experiments with the luciferase activity analysis of truncated apoM promoters could demonstrate that a regulatory region (from-1580 to -1575 bp (-GGTCA-)) upstream of the transcriptional start site of apoM gene was essential for the basal transcriptional activity that regulated by the ER-α. With the applications of an electrophoresis mobility shift assay and a chromatin immunoprecipitation assay, we could successfully identify a specific ER-α binding element in the apoM promoter region. CONCULSION: In summary, the present study indicates that 17ß-estradiol induced up-regulation of apoM in HepG2 cells is through an ER-α-dependent pathway involving ER-α binding element in the promoter of the apoM gene.
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Apolipoproteínas/genética , Estradiol/fisiologia , Receptor alfa de Estrogênio/fisiologia , Lipocalinas/genética , Ativação Transcricional , Apolipoproteínas/metabolismo , Apolipoproteínas M , Sequência de Bases , Sítios de Ligação , Células Hep G2 , Humanos , Lipocalinas/metabolismo , Células MCF-7 , Regiões Promotoras Genéticas , Ligação Proteica , Análise de Sequência de DNA , Regulação para CimaRESUMO
FtmPT1 is a fungal indole prenyltransferase that catalyzes the reaction of tryptophan derivatives with dimethylallyl pyrophosphate to form various biologically active compounds. Herein, we describe detailed studies of FtmPT1 catalysis involving dimethylallyl pyrophosphate and Brevianamide F following the native pathway (yielding Tryprostatin B) and an alternate pathway observed in the Gly115Thr mutant of FtmPT1 yielding a novel cyclized product. Importantly, these two products arise from the same intermediate state, meaning that a step other than the cleavage of the dimethylallyl pyrophosphate (DMAPP; C-O) bond is differentiating between the two product reaction channels. From detailed potential of mean force (PMF) and two-dimensional PMF analyses, we conclude that the rate-limiting step is the cleavage of the C-O bond in DMAPP, while the deprotonation/cyclization step determines the final product distribution. Hence, in the case of FtmPT1, the optimization of the necessary catalytic machinery guides the generation of the final product after formation of the intermediate carbocation.
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Dimetilaliltranstransferase/metabolismo , Neopreno/metabolismo , Dimetilaliltranstransferase/genética , Regulação Fúngica da Expressão Gênica , Hemiterpenos/química , Hemiterpenos/metabolismo , Alcaloides Indólicos/química , Alcaloides Indólicos/metabolismo , Modelos Moleculares , Compostos Organofosforados/química , Compostos Organofosforados/metabolismo , Piperazinas/química , Piperazinas/metabolismo , Conformação Proteica , Especificidade por SubstratoRESUMO
KYKZL-1, a newly synthesized compound with COX/5-LOX dual inhibition, was subjected to the inhibitory activity test on Hep G2 growth. We found that KYKZL-1 inhibited the growth of Hep G2 cells via inducing apoptosis. Further studies showed that KYKZL-1 activated caspase-3 through cytochrome c release from mitochondria and down regulation of Bcl-2/Bax ratio and reduced the high level of COX-2 and 5-LOX. As shown in its anti-inflammatory effect, KYKZL-1 also exhibited inhibitory effect on the PGE2 and LTB4 production in Hep G2 cells. Accordingly, exogenous addition of PGE2 or LTB4 reversed the decreases in cell viability. In addition, KYKZL-1 caused cell cycle arrest at the S-G2 checkpoint via the activation of p21(CIP1) protein and down-regulation of cyclin A expression. These data indicate that the growth inhibitory effect of KYKZL-1 is associated with inhibition of AA metabolites and caspase-3 pathway and cell cycle arrest. Combined with our previous findings, KYKZL-1 exhibiting COX/5-LOX inhibition may be a promising potential agent not only for inflammation control but also for cancer prevention/therapy with an enhanced gastric safety profile.
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Ácido Araquidônico/antagonistas & inibidores , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Inibidores do Crescimento/farmacologia , Fenilpropionatos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Estilbenos/farmacologia , Ácido Araquidônico/metabolismo , Pontos de Checagem do Ciclo Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Células Hep G2 , Humanos , Transdução de Sinais/fisiologiaRESUMO
The properties of an ideal photosensitizer are water solubility, low cytotoxicity in the dark, high ability to produce reactive oxygen species (ROS). The characteristics of water-soluble fullerene (C60) amino acid nanoparticles as a photosensitizer were evaluated. C60 modified with l-phenylalanine (C60-phe) or glycine (C60-gly) was very efficient to carry out photodynamic activity leading to cleavage of plasmid DNA in vitro. These C60 amino acid nanoparticles were the most active photosensitizer against human Liver cancer cells and induced cancer cells apoptosis after illumination. However, these derivatives exhibited no significant cytotoxicity in dark. It produced diffuse intracellular fluorescence when 2',7'-dichlorfluorescein-diacetate (DCFH-DA) was added as an ROS probe, suggesting phototoxicity of these derivatives related with the generation of intracellular ROS. These findings indicate that these fullerene derivatives may be excellent candidate PDT enhancing agents.
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Fulerenos/uso terapêutico , Glicina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Nanoconjugados/uso terapêutico , Nanopartículas/uso terapêutico , Fenilalanina/uso terapêutico , Fotoquimioterapia/métodos , Linhagem Celular Tumoral , Fulerenos/química , Glicina/química , Humanos , Neoplasias Hepáticas/patologia , Nanoconjugados/química , Nanoconjugados/ultraestrutura , Nanopartículas/química , Nanopartículas/ultraestrutura , Fenilalanina/química , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/uso terapêutico , Resultado do TratamentoRESUMO
Fourier transform infrared (FTIR) microspectroscopy technology is the combination of the FTIR spectrometer and the microscope. This technology is of simple preparation of the samples, can be used in micro-area analysis and micro-samples, and reflect the nature of the samples spectra. Panax ginseng include mountain cultivated ginseng (MCG), garden cultivated ginseng (GCG) and mountain wild ginseng (MWG), but the excavation of MWG is prohibited in China. So, only MCG and GCG were collected and recorded in Chinese pharmacopoeia. In this study, we developed a discriminant analysis (DA) method for recognition of MCG and GCG using FTIR microspectroscopy technology. Twenty MCG samples and twenty four GCG samples were obtained, and their spectra of IR microspectroscopy were collected. Then 33 samples were randomly selected into calibration set and the remaining 11 of the samples were selected into validation set. The authors optimized the pretreatment method, the principal components, the modeling region and the scanning parts when developing the models. The optimized model of discriminant analysis was developed using the pretreatment multiplicative scatter correction (MSC) + Savitzky-Golay filter (SG) smoothing, the region 3 932.14-669.18 cm(-1), 4 principal components and the rhizome part. The accuracy of the optimized model got up to 100%. The result demonstrated that infrared microspectroscopy technology combined with DA is of simple operation, rapid, nondestructive and effective, and can be applied to recognize MCG and GCG.
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Panax/classificação , Espectroscopia de Infravermelho com Transformada de Fourier , China , Análise DiscriminanteRESUMO
Objective: This study aimed to conduct an in-depth investigation of the learning framework used for deriving diagnostic results of temporal bone diseases, including cholesteatoma and Langerhans cell histiocytosis (LCH). In addition, middle ear inflammation (MEI) was diagnosed by CT scanning of the temporal bone in pediatric patients. Design: A total of 119 patients were included in this retrospective study; among them, 40 patients had MEI, 38 patients had histology-proven cholesteatoma, and 41 patients had histology-proven LCH of the temporal bone. Each of the 119 patients was matched with one-third of the disease labels. The study included otologists and radiologists, and the reference criteria were histopathology results (70% of cases for training and 30% of cases for validation). A multilayer perceptron artificial neural network (VGG16_BN) was employed and classified, based on radiometrics. This framework structure was compared and analyzed by clinical experts according to CT images and performance. Results: The deep learning framework results vs. a physician's diagnosis, respectively, in multiclassification tasks, were as follows. Receiver operating characteristic (ROC) (cholesteatoma): (0.98 vs. 0.91), LCH (0.99 vs. 0.98), and MEI (0.99 vs. 0.85). Accuracy (cholesteatoma): (0.99 vs. 0.89), LCH (0.99 vs. 0.97), and MEI (0.99 vs. 0.89). Sensitivity (cholesteatoma): (0.96 vs. 0.97), LCH (0.99 vs. 0.98), and MEI (1 vs. 0.69). Specificity (cholesteatoma): (1 vs. 0.89), LCH (0.99 vs. 0.97), and MEI (0.99 vs. 0.89). Conclusion: This article presents a research and learning framework for the diagnosis of cholesteatoma, MEI, and temporal bone LCH in children, based on CT scans. The research framework performed better than the clinical experts.
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[This retracts the article DOI: 10.1016/j.omtn.2019.10.007.].
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OBJECTIVE: To evaluate the early efficacy and serious adverse events (SAE) related to chemotherapy of different protocols in the treatment of pediatric patients with acute lymphoblastic leukemia (ALL), so as to improve the overall survival rate. METHODS: A comparison of the early efficacy and SAE was performed between pediatric patients treated with Chinese Children Cancer Group-ALL 2015 (CCCG-ALL 2015) protocol from January 2019 to June 2020 and those treated with Chinese Children Leukemia Group-ALL 2008 (CCLG-ALL 2008) protocol from January 2017 to December 2018. RESULTS: The remission rate before consolidation chemotherapy between the two groups was not significantly different (P=0.198), but the negative conversion rate of minimal residual disease (MRD) in CCLG-ALL 2008 group was significantly higher than that in CCCG-ALL 2015 group (P=0.000). The incidence of SAE in CCCG-ALL 2015 group was significantly lower than that in CCLG-ALL 2008 group (P=0.021), and the incidence of infection-related SAE was significantly higher in the latter (P=0.001), while the difference of non-infection-related SAE was not statistically significant (P=0.623). In addition, the treatment-related mortality in CCCG-ALL 2015 group was significantly lower than that in CCLG-ALL 2008 group (P=0.003). CONCLUSION: CCCG-ALL 2015 regimen reduces the intensity of chemotherapy, which can significantly decrease the chemotherapy-related SAE (especially infection-related SAE), as well as treatment-related mortality. However, the MRD negative conversion rate is low before consolidation treatment, and the overall long-term efficacy remains to be further observed.
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Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Intervalo Livre de Doença , Humanos , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Investigation of whole plants of Euphorbia fischeriana afforded three new tigliane-diterpenoid glycosides, fischerosides A-C (1-3), together with 11 known diterpenoids. Fischerosides A-C (1-3) are the first tigliane-type diterpenoid glucosides. Their structures were determined by a combination of 1D and 2D NMR, MS, and acid hydrolysis. Inhibitory activity against HIV-1 was assessed for compounds 1-5. The new compound 3 showed an EC50 value of 0.02 µM and a therapeutic index (TI) of 17.50, while prostratin (4) and 12-deoxyphorbol-13,20-diacetate (5) showed significantly greater anti-HIV-1 activity.
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Fármacos Anti-HIV/isolamento & purificação , Diterpenos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Euphorbia/química , Glucosídeos/isolamento & purificação , HIV-1/efeitos dos fármacos , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
Five new lindenane disesquiterpenoids, chlorajaponilides A-E (1-5), together with 11 known analogues were isolated from whole plants of Chloranthus japonicus. The structure and absolute configuration of 1 was confirmed by X-ray crystallography. Compounds 1 and 2 represent the first examples of lindenane disesquiterpenoids with a C-5 hydroxy group and a C-4-C-15 double bond. Compounds 8, 9, 11, and 12 showed anti-HIV-1 replication activities in both wild-type HIV-1 and two NNRTIs-resistant strains. Shizukaol B (8) exhibited the best activity against HIV(wt), HIV(RT-K103N), and HIV(RT-K103N) with EC50 values of 0.22, 0.47, and 0.50 µM, respectively. Compounds 8, 9, 11, and 12 had significant cytotoxicities against C8166 cells with CC50 values of 0.020, 0.089, 0.047, and 0.022, respectively, and exhibited inhibitory activities against HIV-1 with EC50 values of 0.0014, 0.016, 0.0043, and 0.0033 µM, respectively.
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Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , HIV-1/efeitos dos fármacos , Magnoliopsida/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Fármacos Anti-HIV/química , Cristalografia por Raios X , Humanos , Conformação Molecular , Estrutura Molecular , Sesquiterpenos/química , Relação Estrutura-AtividadeRESUMO
ABSTRACT: To investigate the prognostic value of the circulating peripheral blood cell counts changes in acute myeloid leukemia (AML) at different time points during induction chemotherapy.We retrospectively analyzed the clinical and laboratory data of 237 newly diagnosed AML patients admitted to Fujian Medical University Union Hospital from January 2011 to December 2014.1. When primitive cells were first removed from the circulating peripheral blood, it was called peripheral blood blast clearance (PBBC). These patients were divided into two groups, according to PBBC. Statistical analysis showed that the day 5 of induction chemotherapy was a better cut-off for PBBC. PBBC≤5âdays is defined as early-blast-clearance, while PBBC >6âdays is delayed-blast-clearance. There was significant difference between the two groups on complete remission (CR) rate (Pâ=â.002), recurrence-free survival (RFS) (Pâ=â.026) and overall survival (OS) (Pâ=â.001). 2. Multivariate analysis suggested PBBC is an independent prognostic factor for CR, RFS, and OS in AML. Receiver operating characteristic(ROC) curve analysis showed the CR rate of patients with white blood cell count less than 1.25â×â109/L was significantly higher than that of patients with white blood cell count more than 1.25â×â10â9/L (Pâ<â.001) at day 5 of induction chemotherapy, but the RFS and OS was no significantly different (Pâ>â.05).The dynamics of peripheral blood blast in AML after initiation of induction chemotherapy, especially the time length to achieve PBBC, has important prognostic value for CR rate, RFS, and OS in AML patients. It is a simple and feasible method to evaluate the efficacy of AML.
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Crise Blástica/patologia , Quimioterapia de Indução/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Contagem de Leucócitos/métodos , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Curva ROC , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
Interferon-gamma (IFN-γ) is a cytokine involved in the pathogenesis of Takayasu's arteritis (TAK). However, the source of IFN-γ in TAK patients is not fully clear. We aimed to investigate the source of IFN-γ in TAK. 60 TAK patients and 35 health controls were enrolled. The lymphocyte subsets of peripheral blood were detected by flow cytometry, cytokines were detected by Bio-plex. The correlation among lymphocyte subsets, cytokines and disease activity indexes was analyzed by person correlation. The level of serum IFN-γ in TAK patients was significantly increased (P < 0.05). The percentage of CD3+IFN-γ+ cells in peripheral blood CD3+ cells was significantly higher in TAK patients than that of healthy control group (P = 0.002). A higher proportion of CD3+CD8+IFN-γ+ cells/CD3+IFN-γ+ cells (40.23 ± 11.98% vs 35.12 ± 11.51%, P = 0.049), and a significantly lower CD3+CD4+IFN-γ+/ CD3+CD8+IFN-γ+ ratio (1.34 ± 0.62% vs 1.80 ± 1.33%, P = 0.027) were showed in the TAK group than that of control group. The CD3+CD8+IFN-γ+/CD3+IFN-γ+ ratio was positively correlated with CD3+IFN-γ+cells/ CD3+cells ratio (r = 0.430, P = 0.001), serum IFN-γ level (r = 0.318, P = 0.040) and IL-17 level (r = 0.326, P = 0.031). It was negatively correlated with CD3+CD4+IFN-γ+/CD3+IFN-γ+ ratio (r = - 0.845, P < 0.001). IFN-γ secreted by CD3+CD8 + T cells is an important source of serum IFN-γ in TAK patients.
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Linfócitos T CD8-Positivos/imunologia , Interferon gama/metabolismo , Arterite de Takayasu/imunologia , Adulto , Células Cultivadas , Feminino , Humanos , Interferon gama/genética , Masculino , Pessoa de Meia-Idade , Arterite de Takayasu/sangueRESUMO
OBJECTIVE: To investigate the clinical effect and safety of Chinese Children's Leukemia Group (CCLG)-ALL 2008 (high risk group) protocol in the treatment with childhood Mixed phenotype acute leukemia (MPAL). METHODS: The clinical data of 15 new diagnosed patients with MPAL treated in our hospital from January 2013 to December 2017 were retrospectively analyzed, and received CCLG-ALL 2008 (high risk group) protocol chemotherapy. RESULTS: One patient gave up treatment after diagnosed, and 14 children with MPAL after induction remission chemotherapy, 3 patients gave up, and 5 patients received consolidation chemotherapy, and 6 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). The complete remission (CR) rate was 85.7% at d33 of induction remission chemotherapy. The serious adverse event and treatment-related mortality (TRM) rate was 71.4% and 14.3%, respectively. The recurrence rate was 21.4% and the median time of relapse was 12(9.7-18.4) months. Except for 4 patients who gave up treatment, the 5-year event-free survival (EFS) rate in the other 11 patients was (54.5±15.0)%. The 5 years EFS of 4 patients who received consolidation chemotherapy was significantly lower than the 6 patients who received allo-HSCT after CR (25.0%±21.7% vs 83.3%±15.2%, P=0.033). CONCLUSION: The CCLG-ALL2008 (for high-risk group) protocol in treatment of children with MPAL can get a high CR rate, but also with a high incidence of SAE. The patients received allo-HSCT after CR may have a good prognosis.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Criança , Intervalo Livre de Doença , Humanos , Fenótipo , Prognóstico , Indução de Remissão , Estudos RetrospectivosRESUMO
OBJECTIVE: To explore the relationship between polycyclic aromatic hydrocarbon (PAH) exposure and hepatocellular carcinoma (HCC), and the interaction of PAH exposure and other HCC risk factors to HCC. METHODS: Baseline blood samples, collected from 345 HCC cases and 961 controls, were used to determine the level of PAH-albumin adducts by competitive enzyme-linked immunosorbent assay. Conditional logistic regression analysis was used to assess the effect of PAH-albumin adducts on risk of HCC. RESULTS: The mean level of PAH-albumin adducts was significantly higher in cases than in controls ((5.68 +/- 0.72) fmol/mg albumin vs (5.46 +/- 0.63) fmol/mg albumin) (u = 5.98, P < 0.01). When compared to subjects in the lowest quantile (< 1.76 fmol/mg albumin), there was an increase in risk of HCC, with adjusted ORs (95%CI) of 1.03 (0.65 - 1.60), 1.18 (0.76 - 1.78), 2.01 (1.42 - 2.82) for subjects in the second (1.76-fmol/mg albumin), the third (15.28-fmol/mg albumin), and the fourth quantile (> 34.21 fmol/mg albumin), respectively (chi(2)(trend) = 15.06, P < 0.01). There was a significant interaction between PAH-albumin adducts and HBsAg, family history of cancer and diabetes mellitus on HCC after adjusted for other risk factors, and relative excess risks due to the interaction (RERI) were 2.50 (u = 3.60, P < 0.01), 0.52 (u = 2.13, P < 0.05) and 0.88 (u = 2.26, P < 0.05), respectively. CONCLUSION: PAH-albumin adducts was related with HCC, and there is a trend of HCC prevalence increasing with the content of PAH-albumin adducts. There are interactions between PAH-albumin adducts and HBV infection, family history of cancer and diabetes mellitus on HCC.
Assuntos
Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Hidrocarbonetos Policíclicos Aromáticos/sangue , Adulto , Aflatoxinas/sangue , Idoso , Carcinoma Hepatocelular/epidemiologia , Estudos de Casos e Controles , Causalidade , Feminino , Humanos , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
Hepatocellular carcinoma (HCC) accounts for approximately 85%-90% of primary liver cancers. Based on in silico analysis, differentially expressed long non-coding RNA (lncRNA) LINC01224 in HCC, the downstream microRNA (miRNA) miR-330-5p, and its target gene checkpoint kinase 1 (CHEK1) were selected as research subjects. Herein, this study was designed to evaluate their interaction effects on the malignant phenotypes of HCC cells. LINC01224 and CHEK1 were upregulated and miR-330-5p was downregulated in HCC cells. miR-330-5p shared negative correlations with LINC01224 and CHEK1, and LINC01224 shared a positive correlation with CHEK1. Notably, LINC01224 could specifically bind to miR-330-5p, and CHEK1 was identified as a target gene of miR-330-5p. When LINC01224 was silenced or miR-330-5p was elevated, the sphere and colony formation abilities and proliferative, migrative, and invasive potentials of HCC cells were diminished, while cell cycle arrest and apoptosis were enhanced. Moreover, LINC01224 induced HCC progression in vitro and accelerated tumor formation in nude mice by increasing CHEK1 expression. The key findings of the present study demonstrated that silencing LINC01224 could downregulate the expression of CHEK1 by competitively binding to miR-330-5p, thus inhibiting HCC progression. This result highlights the LINC01224/miR-330-5p/CHEK1 axis as a novel molecular mechanism involved in the pathology of HCC.