Determination of Flumatinib and Its Two Major Metabolites in Plasma by LC-MS/MS / 医药导报

Objective A simple,specific and rapid LC-MS/MS method was established to determine flumatinib and its two major metabolites in human plasma for clinical therapeutic drug monitoring.Methods The determination was performed on an ACQUITY UPLC HSS T3 column(2.1 mm×50 mm,1.8 μm)with mobile phases consisting of acetonitrile and 10 mmol·L-1 ammonium formate(containing 0.1%formic acid)with gradient elution at the flow rate of 0.5 mL·min-1.The elution time was 6 min.The temperature of the column was 38℃.The ion source was electrospray ion source and the scanning mode was multiple reaction monitoring scanning in positive ion mode.Results The mass concentrations of flumatinib and its metabolites(flumatinib M1 and flumatinib M3)have a good linear relationship within the concentration range investigated.The precision and stability of the method are good.The precision is less than 15%,and the relative deviation is within±15%.The extraction recoveries of flumatinib and its metabolites approach nearly 100%.Conclusion The method is simple and sensitive,and can accurately determine the plasma concentration of flumatinib and its metabolites,providing a basis for clinical rational drug use.

Frequency-Resolved Connectome Hubs and Their Test-Retest Reliability in the Resting Human Brain / 神经科学通报·英文版

Functional hubs with disproportionately extensive connectivities play a crucial role in global information integration in human brain networks. However, most resting-state functional magnetic resonance imaging (R-fMRI) studies have identified functional hubs by examining spontaneous fluctuations of the blood oxygen level-dependent signal within a typical low-frequency band (e.g., 0.01-0.08 Hz or 0.01-0.1 Hz). Little is known about how the spatial distributions of functional hubs depend on frequency bands of interest. Here, we used repeatedly measured R-fMRI data from 53 healthy young adults and a degree centrality analysis to identify voxelwise frequency-resolved functional hubs and further examined their test-retest reliability across two sessions. We showed that a wide-range frequency band (0.01-0.24 Hz) accessible with a typical sampling rate (fsample = 0.5 Hz) could be classified into three frequency bands with distinct patterns, namely, low-frequency (LF, 0.01-0.06 Hz), middle-frequency (MF, 0.06-0.16 Hz), and high-frequency (HF, 0.16-0.24 Hz) bands. The functional hubs were mainly located in the medial and lateral frontal and parietal cortices in the LF band, and in the medial prefrontal cortex, superior temporal gyrus, parahippocampal gyrus, amygdala, and several cerebellar regions in the MF and HF bands. These hub regions exhibited fair to good test-retest reliability, regardless of the frequency band. The presence of the three frequency bands was well replicated using an independent R-fMRI dataset from 45 healthy young adults. Our findings demonstrate reliable frequency-resolved functional connectivity hubs in three categories, thus providing insights into the frequency-specific connectome organization in healthy and disordered brains.

Risk factor analysis of the patients with solitary pulmonary nodules and establishment of a prediction model for the probability of malignancy / 中华肿瘤杂志

Objective@#This study aims to analyze the relationship among the clinical features, radiologic characteristics and pathological diagnosis in patients with solitary pulmonary nodules, and establish a prediction model for the probability of malignancy.@*Methods@#Clinical data of 372 patients with solitary pulmonary nodules who underwent surgical resection with definite postoperative pathological diagnosis were retrospectively analyzed. In these cases, we collected clinical and radiologic features including gender, age, smoking history, history of tumor, family history of cancer, the location of lesion, ground-glass opacity, maximum diameter, calcification, vessel convergence sign, vacuole sign, pleural indentation, speculation and lobulation. The cases were divided to modeling group (268 cases) and validation group (104 cases). A new prediction model was established by logistic regression analying the data from modeling group. Then the data of validation group was planned to validate the efficiency of the new model, and was compared with three classical models(Mayo model, VA model and LiYun model). With the calculated probability values for each model from validation group, SPSS 22.0 was used to draw the receiver operating characteristic curve, to assess the predictive value of this new model.@*Results@#112 benign SPNs and 156 malignant SPNs were included in modeling group. Multivariable logistic regression analysis showed that gender, age, history of tumor, ground -glass opacity, maximum diameter, and speculation were independent predictors of malignancy in patients with SPN(P<0.05). We calculated a prediction model for the probability of malignancy as follow: p=ex/(1+ ex), x=-4.8029-0.743×gender+ 0.057×age+ 1.306×history of tumor+ 1.305×ground-glass opacity+ 0.051×maximum diameter+ 1.043×speculation. When the data of validation group was added to the four-mathematical prediction model, The area under the curve of our mathematical prediction model was 0.742, which is greater than other models (Mayo 0.696, VA 0.634, LiYun 0.681), while the differences between any two of the four models were not significant (P>0.05).@*Conclusions@#Age of patient, gender, history of tumor, ground-glass opacity, maximum diameter and speculation are independent predictors of malignancy in patients with solitary pulmonary nodule. This logistic regression prediction mathematic model is not inferior to those classical models in estimating the prognosis of SPNs.

Metformin improving anxiety-like behaviors through regulation of autophagy following focal cerebral ischemia in rats / 中国生化药物杂志

Objective To investigate probable effect of metformin on anxiety and autophagy pathway in rats with focal cerebral ischemia . Methods The rats were divided into seven groups:shame group, ischemia group, metformin group, compound C group, compound C +ischemia group, metformin+ischemia group, and metformin+compound C+ischemia group.The rats were administered with metformin 14 days and compound C 30 min pretreatment.The blood glucose level, body mass, neurological score and indicators of elevate plus maze test were recorded of two groups after 72h ischemia-perfusion.The autophagy-related protein of Atg-7, Atg-5, beclin-1 were analysed by Western blot.ResuIts Metformin had no significant effect of body mass and blood glucose level.The prior administration of metformin significantly elevated neurological score in ischemia group (P<0.01).The elevate plus maze test results showed that prior administration of metformin significantly elevated percentage of open-arms detention time in ischemia group (P<0.01), but there was no significant difference in open-arms times.Western blot result showed that prior administration of metformin significantly elevated Atg-7, Atg-5, beclin-1 protein expression in ischemia group (P<0.001).Compound C resist the above effects of metformin (P<0.01).ConcIusion The metformin improves psychological disorders and movement disability through regulation of autophagy following focal cerebral ischemia in rats.

Application of immune-enhanced enteral nutrition in preoperative preparation for patients with colorectal carcinoma / 肠外与肠内营养

Objective:The aim of this study was to explore the applicative effects of immune-enhanced enteral nutrition(Supportan) in preoperative preparation for patients with colorectal carcinoma.Methods:56 colorectal carcinoma patients with mid-severe malnutrition were randomly divided into two groups,experiment group and control group,each of 23.Experiment group was administrated with immune-enhanced enteral nutrition(Supportan).Control group was administrated with common enteral nutrition(Nutrison Fibre).Nutritional status,immunological function,inflammatory factor and the satisfaction of colon were observed.Results:After enteral nutrition,the plasma albumin,prealbumin,IgG,IgM,CD4+ T cells and the ratio of CD4+/ CD8+ were higher in experiment group than in control group and TNF-?,IL-6 and PGE2 were lower in experiment group than in control group.Conclusions:Immune-enhanced enteral nutrition(supportan) can improve nutritional status,strengthen immunological function,and decrease inflammatory reaction in the colorectal carcinoma patients with mid-severe malnutrition.