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OBJECTIVE@#To compare the predictive ability of two extended Cox models in nonlinear survival data analysis.@*METHODS@#Through Monte Carlo simulation and empirical study and with the conventional Cox Proportional Hazards model and Random Survival Forests as the reference models, we compared restricted cubic spline Cox model (Cox_RCS) and DeepSurv neural network Cox model (Cox_DNN) for their prediction ability in nonlinear survival data analysis. Concordance index was used to evaluate the differentiation of the prediction results (a larger concordance index indicates a better prediction ability of the model). Integrated Brier Score was used to evaluate the calibration degree of the prediction (a smaller index indicates a better prediction ability).@*RESULTS@#For data that met requirement of the proportion risk, the Cox_RCS model had the best prediction ability regardless of the sample size or deletion rate. For data that failed to meet the proportion risk, the prediction ability of Cox_DNN was optimal for a large sample size (≥500) with a low deletion (< 40%); the prediction ability of Cox_RCS was superior to those of other models in all other scenarios. For example data, the Cox_RCS model showed the best performance.@*CONCLUSION@#In analysis of nonlinear low maintenance data, Cox_RCS and Cox_DNN have their respective advantages and disadvantages in prediction. The conventional survival analysis methods are not inferior to machine learning or deep learning methods under certain conditions.
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Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Calibración , Simulación por Computador , Análisis de DatosRESUMEN
OBJECTIVE@#To compare different methods for calculating sample size based on confidence interval estimation for a single proportion with different event incidences and precisions.@*METHODS@#We compared 7 methods, namely Wald, AgrestiCoull add z2, Agresti-Coull add 4, Wilson Score, Clopper-Pearson, Mid-p, and Jefferys, for confidence interval estimation for a single proportion. The sample size was calculated using the search method with different parameter settings (proportion of specified events and half width of the confidence interval [ω=0.05, 0.1]). With Monte Carlo simulation, the estimated sample size was used to simulate and compare the width of the confidence interval, the coverage of the confidence interval and the ratio of the noncoverage probability.@*RESULTS@#For a high accuracy requirement (ω =0.05), the Mid-p method and Clopper Pearson method performed better when the incidence of events was low (P < 0.15). In other settings, the performance of the 7 methods did not differ significantly except for a poor symmetry of the Wald method. In the setting of ω=0.1 with a very low p (0.01-0.05), failure of iteration occurred with nearly all the methods except for the Clopper-Pearson method.@*CONCLUSION@#Different sample size determination methods based on confidence interval estimation should be selected for single proportions with different parameter settings.
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Intervalos de Confianza , Tamaño de la Muestra , Simulación por Computador , Método de Montecarlo , ProbabilidadRESUMEN
Medical studies use various methods for assessing agreement among different raters or measurement methods. Many of these coefficients have limitations, and among them the paradoxes of kappa are the best known. To achieve a higher accuracy and reliability, we propose an alternative statistic method based on AC1, known as CEA, which adjusts the chance agreement. We explored the influences of the prevalence rate and chance agreement probability on the total agreement and compared the accuracy and stability of kappa, AC1 and CEA coefficient through simulations and real data analysis. The proposed method offers a stable and reliable option for assessing agreement of binary data.
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<p><b>OBJECTIVE</b>To analyze the effectiveness and safety of controlled-release dinoprostone insert for term labor induction in the Pearl River Delta of Guangdong province.</p><p><b>METHODS</b>Twenty hospitals using controlled-release dinoprostone insert for term labor induction in the Pearl River Delta of Guangdong province were stratified into provincial hospitals and municipal hospitals, and three hospitals of each level were selected as research units. According to the inclusion and exclusion criteria, 1390 pregnant women receiving term labor induction using controlled-release dinoprostone insert were retrospectively analyzed to evaluate the the effectiveness and safety with another 957 pregnant women with induced abortion using oxytocin as the control group.</p><p><b>RESULTS</b>Compared with the control group, the controlled-release dinoprostone insert group showed a significantly longer length of the latent phase of labor (4.06∓2.65 vs 3.20∓2.08 h, P=0.003, 95%CI [0.182, 0.920]) and shorter lengths of the active phase (1.73∓1.32 vs 2.22∓1.75 h, P=0.000, 95%CI [-0.795, -0.363]) and the second stage of labor (0.49∓0.37 vs 0.54∓0.43 h, P=0.003, 95%CI [-0.137, -0.028]). No significant differences were found in the length of the first stage of labor, the vaginal delivery rate, adverse reactions, or fetal outcomes between the two groups.</p><p><b>CONCLUSION</b>Controlled-release dinoprostone insert is effective and safe for labor induction at term.</p>
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<p><b>OBJECTIVE</b>To evaluate the prognosis and complications of expectant therapy and curettage for retained product of conception (RPOC) after second trimester termination of pregnancy (TOP).</p><p><b>METHODS</b>A total of 270 patients with RPOC following second trimester TOP in Nanfang Hospital between January, 2014 and December, 2015 were included in this study. The duration of vaginal bleeding time and menstruation recovery interval were compared between patients receiving expectant therapy and curettage for RPOC, and binary logistic regression was used to assess the risk factors for complications in bivariate and multivariate analyses.</p><p><b>RESULTS</b>The duration of vaginal bleeding time was significantly longer in expectant therapy group than in curettage group (P=0.005), while the menstruation recovery interval did not differ significantly between the two groups. The incidence of vaginal bleeding time for over 42 days was significantly higher in curettage group than in expectant therapy group (P=0.040), and the incidence of a menstruation recovery interval beyond 60 days was comparable between them. The incidence of complications was significantly higher in curettage group than in expectant therapy group either with adjustment of age, gravidity, parity, history of uterine surgery status, gestational age, type of indications, regimens for TOP and induction-abortion interval (OR=18.26 [95% CI: 3.57-93.42], P<0.001) or without adjustment (OR=10.60, [95% CI: 2.36-47.66], P=0.002).</p><p><b>CONCLUSION</b>Expectant therapy and curettage for RPOC after second trimester TOP have comparable prognosis, but curettage is associated with a significantly higher rate of complications.</p>
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This study aims to explore the effects of the phosphatase and tension homolog (PTEN) expression level on autophagic status and on the resistance of breast cancer to trastuzumab treatment. PTEN and LC3I/II were knocked down with shRNA expression vectors, which were transfected into estrogen receptor (ER)-positive breast cancer cell lines. After trastuzumab treatment, the changes in the autophagy signal transduction pathways and autophagic proteins (LC3I/II, p62, LAMP, and cathepsin B) in these stably transfected cells were detected using western blot. The cells were also orthotopically implanted into nude mice to explore the influence of PTEN knockdown on tumor size, cell viability, and autophagic proteins after trastuzumab treatment. Similar determinations were performed using the LC3I/II overexpressed shPTEN breast cancer cells (LC3I/II-shPTEN). Downregulation of PTEN and autophagic proteins LC3-I and LC3-II was observed in resistant human breast cancer samples. Knockdown of PTEN and PTEN+ LC3I/II with shRNA in breast cancer cells resulted in increased resistance to trastuzumab. Consistently, trastuzumab treatment could not effectively reduce tumor size. Significant decreases in the levels of autophagic proteins LC3I/II, LAMP, p62, cathepsin B, and PI3K-Akt-mTOR and the signaling pathway protein Akt were found in PTEN knockdown cells, compared to the PTEN normal group, after trastuzumab administration, both in vitro and in vivo. However, these findings were reversed with the LC3I/II-shPTEN treatment. Therefore, the loss of PTEN may promote the development of primary resistance to trastuzumab in breast cancer via autophagy defects.
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Autofagia/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Proteínas Asociadas a Microtúbulos/biosíntesis , Fosfohidrolasa PTEN/genética , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Proteínas Asociadas a Microtúbulos/genética , Proteínas de Unión al ARN/biosíntesis , Receptor ErbB-2/genética , Transducción de Señal , Serina-Treonina Quinasas TOR/biosíntesis , Trastuzumab/administración & dosificación , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Objective To investigate the effect of matrix metalloproteinases(MMPs) in ventilator-induced lung injury inflammatory reaction of newborn rabbits.Methods Seventy-five newborn rabbits aged 1-5 days were randomly arranged to 3 groups:control group(n=3),other 72 rabbits designed by 2?2?3 factorial were divided into high concentration oxygen(100%)and low concentration oxygen(45%) groups,and each group was subdivided into 2 groups:High peak inspiratory pressure(PIP)group and low PIP group.All rabbits were done by mechanical ventilation and killed to obtain lung tissue at 1,3,6 hours after trailing respectively.The concentration of MMP-9 and MMP-2 in lung tissue bomogenate were detected by ELISA,at the same time the ratio of wet to dry was detected and pathological section was analyzed.Results 1.The concentration of MMP-2 in high concentration oxygen group,high PIP group and low PIP group increased compared with that in normal group,and there were significant differences.2.The mean concentration of MMP-9 was lower in high concentration oxygen group than that in normal control group,and there was significant difference between 2 groups.The mean concentration of MMP-9 in low concentration oxygen group was higher than that in normal group,and there was no significant difference between 2 groups.There was no significant difference in effect to mean concentration of MMP-9 by different PIP.3.There were positive correlation between MMP-2 and MMP-9,MMP-2 and the ratio of wet to dry in lung.Conclusions Within 6 hours in newborn rabbits by mechanical ventilation,ventilation with high concentration oxygen up-regulate MMP-2,but down-regulated MMP-9.The lungs stretch by mechanical ventilation increase MMP-9,but decrease MMP-2.Mechanical ventilation can affect the synthesis of MMPs,and MMPs plays an important role in ventilator-induced lung injury of newborn rabbits.
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<p><b>OBJECTIVE</b>To evaluate the effects of Caulis Sinomenii and sinomenine on conditioned place preference (CPP) induced by morphine and brain histamine level in mice.</p><p><b>METHODS</b>Sixty mice were randomized into 6 equal groups and morphine (Mor) was injected subcutaneously (9 mg/kg) for 6 consecutive days to induce CPP using a shuttle box. Since the 4th day of training, the mice in 5 of the groups were treated for 3 consecutive days with Caulis Sinomenii (10 g/kg), sinomenine (60 mg/kg), diphenhydramine (30 mg/kg), CP48/80 (5 mg/kg) and L-histidine (750 mg/kg) in addition to morphine (9 mg/kg) treatment, respectively, leaving the other group with exclusive morphine treatment. Another 10 mice received saline injection to serve as saline control group. The content of histamine (HA) in the mouse brain was measured by fluorospectrophotometry.</p><p><b>RESULTS</b>In morphine group, the mice showed significantly extended stay in morphine-paired compartment whose HA content in the brain was markedly increased (P<0.01). Treatment with Caulis Sinomenii and sinomenine resulted in significantly reduced time of stay in morphine-paired compartment and brain HA level (P<0.01).</p><p><b>CONCLUSION</b>CPP induced by morphine in mice is associated with increased HA level in the brain. Caulis Sinomenii and sinomenine can suppress the acquisition of place preference induced by morphine and modulate HA level in the central nervous system in morphine-dependent mice.</p>