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Backgrounds and Aims: Bronchopulmonary dysplasia (BPD) has serious immediate and long-term sequelae as well as morbidity and mortality. The objective of this study is to develop a predictive model of BPD for premature infants using clinical maternal and neonatal parameters. Methods: This single-center retrospective study enrolled 237 cases of premature infants with gestational age less than 32 weeks. The research collected demographic, clinical and laboratory parameters. Univariate logistic regression analysis was carried out to screen the potential risk factors of BPD. Multivariate and LASSO logistic regression analysis was performed to further select variables for the establishment of nomogram models. The discrimination of the model was assessed by C-index. The Hosmer-Lemeshow test was used to assess the calibration of the model. Results: Multivariate analysis identified maternal age, delivery option, neonatal weight and age, invasive ventilation, and hemoglobin as risk predictors. LASSO analysis selected delivery option, neonatal weight and age, invasive ventilation, hemoglobin and albumin as the risk predictors. Both multivariate (AUC = 0.9051; HL P = 0.6920; C-index = 0.910) and LASSO (AUC = 0.8935; HL P = 0.7796; C-index = 0.899) - based nomograms exhibited ideal discrimination and calibration as confirmed by validation dataset. Conclusions: The probability of BPD in a premature infant could be effectively predicted by the nomogram model based on the clinical maternal and neonatal parameters. However, the model required external validation using larger samples from multiple medical centers.
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COTI-2 is a third-generation thiosemicarbazone, which is effective against a diverse group of human cancer cell lines at nanomolar concentrations. COTI-2 also showed superior activity against tumor cells, in vitro and in vivo. As a high efficacy and low toxicity agent, it currently candidates in a phase I clinical study of gynecological malignancies and head and neck squamous cell carcinoma (HNSCC). However, its effect in pediatric T-cell acute lymphoblastic leukemia (T-ALL) is not clear. This study investigates the effect of COTI-2 on T-ALL Jurkat cells in vitro and in vivo. Jurkat cells were exposure to COTI-2 at different concentration and time. Cell apoptosis was detected by flow cytometry to examine the sensitivity of Jurkat cell lines treated with either COTI-2 alone or in combination with MiR-203 mimic or inhibitor in vitro. An orthotopic mouse model was used to examine the sensitivity of Jurkat cells treated with COTI-2 in vivo. Western blotting and RT-qPCR were performed to dissect molecular mechanisms. The results showed that COTI-2 promotes apoptosis of Jurkat cells in dose-and time-dependent way. Enforced expression of miR-203 promotes COTI-2-mediated cell apoptosis, whereas miR-203 silencing attenuates COTI-2-mediated cell apoptosis in Jurkat cells in vitro. COTI-2 is also effective against growth of Jurkat cells in vivo. Mechanistically, COTI-2 induced miR-203 upregulation and inhibited caspase-3/9 activaty leading to inhibition of cell apoptosis. Taken together, COTI-2 inhibits tumor growth in vitro and in vivo in Jurkat cells likely through miR-203-dependent mechanisms. COTI-2 may be a potential approach for T-ALL treatment.
Assuntos
Aminoquinolinas/uso terapêutico , Antineoplásicos/uso terapêutico , MicroRNAs/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Tiossemicarbazonas/uso terapêutico , Aminoquinolinas/farmacologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Western Blotting , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Densitometria , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Células Jurkat/efeitos dos fármacos , Células Jurkat/metabolismo , Camundongos , Camundongos Nus , MicroRNAs/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Tiossemicarbazonas/farmacologiaRESUMO
This study aimed to detect serum miR-203 expression levels in AML and explore its potential clinical significance. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to measure the serum miR-203 levels in 134 patients with AML and 70 healthy controls. The results demonstrated that serum miR-203 expression was significantly reduced in AML patients compared with healthy controls. Receiver operating characteristic curve (ROC) analysis revealed miR-203 could distinguish AML cases from normal controls. Low serum miR-203 levels were associated with worse clinical features, as well as poorer overall survival and relapse free survival of AML patients. Moreover, multivariate analysis confirmed low serum miR-203 expression to be an independent unfavorable prognostic predictor for AML. The bioinformatics analysis showed that the downstream genes and pathways of miR-203 was closely associated with tumorigenesis. Downregulation of miR-203 in AML cell lines upregulated the expression levels of oncogenic promoters such as CREB1, SRC and HDAC1. Thus, these findings demonstrated that serum miR-203 might be a promising biomarker for the diagnosis and prognosis of AML.
Assuntos
Biomarcadores Tumorais/genética , Carcinogênese/genética , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Antagomirs/genética , Antagomirs/metabolismo , Biomarcadores Tumorais/sangue , Carcinogênese/metabolismo , Carcinogênese/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Biologia Computacional/métodos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/sangue , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Perfilação da Expressão Gênica , Ontologia Genética , Histona Desacetilase 1/sangue , Histona Desacetilase 1/genética , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , MicroRNAs/antagonistas & inibidores , MicroRNAs/sangue , Anotação de Sequência Molecular , Análise Multivariada , Proteínas de Neoplasias/sangue , Prognóstico , Curva ROC , Recidiva , Transdução de Sinais , Análise de Sobrevida , Quinases da Família src/sangue , Quinases da Família src/genéticaRESUMO
BACKGROUND The aim of this study was to analyze amplitude-integrated electroencephalography (aEEG) in early diagnosis and prognosis of hypoxic encephalopathy (HE) in premature infants. MATERIAL AND METHODS Thirty-six premature infants with HE who were treated in Linyi Central Hospital were enrolled into the study group, while 40 premature infants without HE were assigned into the control group. aEEG was conducted within 6 h after delivery to compare aEEG continuity, mature sleep-wake cycle, and maximum and minimum voltage in the 2 groups. Correlations between aEEG abnormalities and clinical grading, neurological prognosis, Apgar score, and blood gas were also analyzed among the premature infants with HE. RESULTS Compared with the control group, there were reductions in the continuous rate of aEEG, mature sleep-wake cycle, and the minimum voltage, and an increase in the maximum voltage in the study group (all P<0.05). The study group had a higher abnormal rate of aEEG and a lower normal rate of aEEG than in the control group (both P<0.05). Spearman's rank correlation coefficients for abnormal aEEG and clinical grade and poor neurological prognosis were 0.758 and 0.799, respectively. The sensitivity of abnormal aEEG in predicting severity of clinical grading was 100% with a specificity of 82.5%. The sensitivity of abnormal aEEG in predicting neurological prognosis was 100% with a specificity of 90.3%. The Apgar scores and blood glass pH of the infants with various abnormal rates of aEEG were significantly different at 1 min, 5 min, and 10 min after delivery (all P<0.05). CONCLUSIONS HE in premature infants has specific aEEG characteristics, which can be used to predict the severity and prognosis of HE.