ABSTRACT
PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp(RGDRGD)30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus.The active endostatin fragment of PEPO6 directly targets tumor cells and exerts an antitumoral effect.However,little is known about the kinetics and degradation products of PEP06 in vitro or in vivo.In this study,we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species;we further identified the degradation characteristics of its cleavage products.PEP06 underwent rapid enzymatic degradation in multiple types of living cells,and the liver,kidney,and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06.We identified metabolites of PEP06 using full-scan mass spectrometry(MS)and tandem MS(MS2),wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide,formed by successive losses of amino acids.The metabolites were C and N terminal truncated products of PEP06.The structures of 11 metabolites(M6,M7,M16,M17,M21,M25,M33,M34,M39,M40,and M42)were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites.We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06,which can support further drug research.
ABSTRACT
Objective:To create radiomics models based on abbreviated multimodal magnetic resonance imaging (MRI) for the diagnosis of breast cancer.Methods:All breast MR imaging data between Jun 2014 and Mar 2019 were retrospectively collected. Patients with pathological results of puncture or surgical resection were involved in this study. One thousand three hundred and six patients (416 benign and 890 breast cancer) were divided into training cohort ( n=702), internal validation cohort ( n=302), and external validation cohort ( n=302). All images were reduced to: the joint model group [including T2 weighted imaging (T2WI), DWI (diffusion-weighted imaging) and first contrast-enhanced sequences], non-enhanced group (T2WI and DWI) and single-phase enhanced group (first contrast-enhanced sequences). Analysis of variance (ANOVA) and least absolute shrinkage and selection operator (LASSO) were used to reduce the dimension of texture features. Three supervised machine learning algorithms (Bagging decision tree, Gaussian process, support vector machine) were used to predict benign and malignant breast lesions, and the best classifier was selected to construct breast cancer diagnosis model. Models were validated by internal and external validation cohorts. Results:The Gaussian process algorithm was chosen. The area under the curve (AUC) of the joint model and the non-enhanced model for predicting breast cancer were 0.903 and 0.893 for the training cohort, 0.893 and 0.863 for the internal validation cohort, and 0.878 and 0.864 for the external validation cohort.Conclusions:The radiomics model based on abbreviated multimodal MRI can accurately diagnose breast cancer. And the non-enhanced model can accurately diagnose breast cancer without contrast enhancement, which provides feasibility for simplifying the diagnosis process.
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@#Objective To observe the effect of electroacupuncture at Baihui (DU20) and Shenting (DU24) on brain functional activity and working memory of rats with vascular cognitive impairment (VCI). Methods Eighteen Sprague-Dawley rats were included, in which twelve rats were ligated bilateral common carotid arteries and six rats were not ligated (sham group). The modeled rats were randomly divided into model group (n = 6) and electroacupuncture group (n = 6). The electroacupuncture group received electroacupuncture at Baihui and Shenting for four weeks. They were assessed with Y maze and Morris water maze before and after intervention, and scaned with resting-state functional magnetic resonance imaging after intervention to calculate regional homogeneity (ReHo). Results Compared with the sham group, alternation rate of Y maze decreased (P < 0.001), and escape latency of Morris water maze increased (P < 0.05) in the model group and the electroacupuncture group before intervention. Compared with the model group, alternation rate of Y maze increased (P < 0.05), and escape latency of Morris water maze decreased (P < 0.05) after intervention in the electroacupuncture group. Compared with the sham group, ReHo of bilateral hippocampus, olfactory cortex, sensory cortex and auditory cortex, and left striatum decreased in the model group; compared with the model group, ReHo of bilateral prefrontal lobe, hippocampus and olfactory cortex, and left amygdala increased in the electroacupuncture group. Conclusion Electroacupuncture at Baihui and Shenting can improve the memory function of VCI rats, which may be related to the functional activities of prefrontal lobes, hippocampus and amygdala.
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Objective To study the relationship between umbilical cord leptin levels and fetal growth as well as neonatal birth weight. Methods One hundred and forty - two neonates selected from February 2009 to June 2013 in Shangqiu First People's Hospital according to the different gestational age and birth weight were divided into 3 groups. Group A included 44 cases(small for gestational age,birth weight below the average weight of the 10th percentile at the same gestational age),23 boy cases,21 girl cases;group B included 56 cases(appropriate for gestational age,birth weight at the average weight of the 10th to 90th percentile at the same gestational age),30 boy cases,26 girl cases;group C included 42 cases(large for gestational age,birth weight above the average weight of the 90th percentile at the same gestational age),22 boy cases,20 girl cases. Neonatal body mass index,birth weight,placenta weight and umbilical lep-tin levels of three groups were compared. Results Neonatal birth weight,neonatal body length,body mass index and the placenta weight leptin levels in group A were significantly lower than those of group B,having statistically significant difference(all P ﹤ 0. 001);Neonatal birth weight,neonatal body length,body mass index and the placenta weight leptin levels in group C were significantly higher than those in group B,with statistically significant difference( all P ﹤0. 001). Neonatal birth weight in the boy group was obviously higher than that of the girl group,and the difference was statistically significant(P ﹤ 0. 001). Neonatal leptin levels in the boy group were significantly lower than that of the girl group,and the difference was statistically significant(P ﹤ 0. 001). There were positive correlations between the umbili-cal cord leptin levels and the neonatal birth weight,neonatal length,neonatal weight index and the placenta weight(r =0. 382,0. 276,0. 358,0. 412,all P ﹤ 0. 01). Conclusions The umbilical cord leptin levels are closely associated with neonatal birth weight and intrauterine growth retardation,and it can be used as one of the important indicators for reflec-ting neonatal birth weight and fetal growth.
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Objective To study the value of score for neonatal acute physiology Ⅱ(SNAP]Ⅱ) and its extension version Ⅱ (SNAPPE-Ⅱ) in predicting neonatal necrotizing enterocolitis (NEC) outcome.Methods We explored 73 NEC patients by statistics who were treated in our hospital from January 2002 to January 2012.The patients were divided into two groups:surgery group and non-surgery group,then they were divided into subgroups:alive group and death group.The general information including birth weight,age,clinical manifestations,treatment of patients were collected.Every patient was checked and scored by the methods SNAP-Ⅱ] and SNAPPE-Ⅱ in time.Results The scores (27.0 ± 2.3,26.5 ± 1.8) of surgery group including SNAP-Ⅱ and SNAPPE-Ⅱ were higher than those (14.0 ± 2.1,15.0 ± 2.5) in the non-surgery group(P ＜ 0.01).The scores(31.0 ± 3.2,31.0 ± 3.4) of the death group including SNAP-Ⅱ and SNAPPE-Ⅱ were higher than those(11.0 ± 2.5,10.0 ± 3.6) in the alive group(P ＜ 0.01).According to the area under the curve(AUC) analyzed by the receiver operating characteristic(ROC) curve for measuring the scores of surgery predicting,AUC was 0.726 for SNAP-Ⅱ and 0.732 for SNAPPE-Ⅱ.The value of predicting surgery risk was 20 and 24 respectively.According to the AUC analyzed by the ROC curve for measuring the scores for surgery predicting,AUC was 0.752 for SNAP-Ⅱ and 0.825 for SNAPPE-Ⅱ.The value of predicting mortality risk was 31 and 33 respectively.All P values were less than 0.01 and there were significant differences.Conclusion The two kinds of score for neonatal acute physiology have an important significance in predicting surgery and mortality risk of NEC.