Exosomes are vesicles of endocytic origin released from different cell types under both normal and pathological conditions.Proteomics is an emerging discipline for studying composition and mechanics and interac-tion of proteins with regard to disease occurrence、cellular metabolism,etc.Progress of research on exosomes from tumor cell at proteomics technology platforms in aspect of clarifying mechanisms of shaping and sustaining micro-enviroment of tumor growth and survival and metastasis, induce tumor proliferation, Immunosuppressive effects or immune evasion, and discovering biomarker, makes a promising prospect of exsomes in clinical diagnosis and treatment.

Purpose:To evaluate the short-term effect of combination chemotherapy of oxaliplatin plus capecitabine on advanced cancer.Methods:32 patients of advanced gastric cancer were treated with oxaliplatin plus capecitabine for 76 weeks.Results:There were 6 CR, 16 PR, 8 NC, 2 PD, in our group and the overall response rate was 68.75% (22/32). The median alleviative time was 8 months, the median survival time was 12 months and the one-year survival rate was 55%. 30(93.75%) patients benefited from this method. The side effects were all tolerable which were alleviated by active therapy. There was no death and nobody stopped chemotherapy because of side effects.Conclusions:Combination chemotherapy of oxaliplatin plus capecitabine to treat advanced gastric cancers was certainly effective and tolerable to toxicities. This chemotherapy will be used as the first-line in more patients and is worthy of further study.[

Objective Classification of non-small cell lung lymph (NSCLC) node (N) is one of the key factors influencing treatment, however, the cilinical noninvasive and invasive approaches to N classification have their limitations.This study aimed to investigate the risk factors of lymph node metastasis of peripheral lungadenocarcinoma by using CT and PET / CT scans.Methods Retrospective analysis had been done on a total of 248 patients who underwent surgical resection from February 2010 to November 2015 in our hospital.All of them underwent chest CT and 80 patients underwent PET/CT examination.Univariate analysis was applied in the relation of lymph node metastasis to gender, age, smoking situation, CEA, SUV, cancer size, pathological variants, and the degree of differentiation.Multivariable logistic regression analysiss were performed in the prediction of risk factors for lymph node metastasis.ResultsSeventy-four patients (29.8%) had regional lymph node metastases.Univariate analysis showed that lymph node metastasis was related to the serum CEA level, degree of differentiation, SUVmax, tumor size, lobulation/spiculation, pleural retraction, mediastinal or hilar lymphadenopathy (P<0.05).In the multivariable analysis of risk factors, including serum CEA, SUVmax and CT features, for predicting lymph node metastasis, the most important and significantly independent risk factors identified were SUVmax, CEA level, mediastinal or hilar lymphadenopathy, cavitation/bubble-likelucency and pleural retraction (P<0.05).Conclusion The lymph node metastasis is associated with SUVmax of primary tumor, serum CEA level, mediastinal or hilar lymphadenopathy, cavitation/bubble-likelucency and pleural retraction.The combination of radiographic features and serum CEA can help to predict more accurately the risk of lymph node metastasis in patients with peripheral lung adenocarcinoma.

Objective To explore the expression of antiapoptotic gene Aven in childhood acute lymphoblastic leukemia (ALL) and its relationship with clinical features of ALL. Methods Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of Aven mRNA in 55 cases of childhood ALL The control group included 11 childhood patients with no malignant hematological diseases. Results Aven mRNA expression was found to be higher in patients ≥10 years old and was also significantly higher in relapsed patients. Univariate and multivariate analysis indicated that Aven overexpression was an independent poor prognostic factor. Conclusion Aven mRNA expression is abnormal in childhood ALL and is an independent poor prognostic factor.

Aim To study the influence of Si-Wu De-coction (SWD ) and its active components on cyto-chrome P450 activity and mRNA expression in rats in order to provide an experimental basis for compatibility of SWD.Methods SWD and its active components were intragastrically administrated for seven days,the doses of SWD was 10 g · kg -1 · d -1 ,the doses of fructose,ferulic acid,ligustrazine,peoniflorin were 0.334,0.002,0.011 and 0.022 g·kg -1 ·d -1 ,re-spectively.After administration for seven days,rats were executed,and liver microsomes were prepared. The effects of SWD and its active components on cyto-chrome P450 in rats were investigated by hybrid probe and liver microsomes incubation method.The level of mRNA expression in liver was detected by real-time quantitative polymerase chain reaction using specific target primers for CYP450 genes.The level of protein expression of CYP2B1 was detected by Western blot. Results Compared with the control group,fructose significantly decreased the activity of CYP1A2, CYP2B6,CYP2C9,CYP2D6;ferulic acid significantly decreased the activity of CYP2C9,CYP2B6;ligus-trazine significantly decreased the activity of CYP1A2, CYP2C9,CYP2B6;peoniflorin significantly decreased the activity of CYP2D6,CYP2B6;fructose,ferulic acid,peoniflorin inhibited the mRNA expression of CYP2B1;fructose,ferulic acid,ligustrazine and peon-iflorin also inhibit the protein expression of CYP2B1. Conclusion Fructose,ferulic acid,peoniflorin inhib-it the activity of CYP2B1,decrease the expression lev-els of mRNA and protein of CYP2B1.

BACKGROUND: Islet transplantation is currently considered the most promising method for treating insulin-dependent diabetes. The two most-studied artificial islets are alginate-encapsulated b cells or b cell spheroids. As three-dimensional (3D) models, both artificial islets have better insulin secretory functions and transplantation efficiencies than cells in twodimensional (2D) monolayer culture. However, the effects of these two methods have not been compared yet. Therefore, in this study, cells from the mouse islet b cell line Min6 were constructed as scaffold-free spheroids or alginate-encapsulated dispersed cells. METHODS: MIN6 cell spheroids were prepared by using Agarose-base microwell arrays. The insulin secretion level was determined by mouse insulin ELISA kit, and the gene and protein expression status of the MIN6 were performed by Quantitative polymerase chain reaction and immunoblot, respectively. RESULTS: Both 3D cultures effectively promoted the proliferation and glucose-stimulated insulin release (GSIS) of MIN6 cells compared to 2D adherent cells. Furthermore, 1% alginate-encapsulated MIN6 cells demonstrated more significant effects than the spheroids. In general, three pancreatic genes were expressed at higher levels in response to the 3D culture than to the 2D culture, and pancreatic/duodenal homeobox-1 (PDX1) expression was higher in the cells encapsulated in 1% alginate than that in the spheroids. A western blot analysis showed that 1% alginate-encapsulated MIN6 cells activated the phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/forkhead transcription factor FKHR (FoxO1) pathway more than the spheroids, 0.5% alginate-, or 2% alginate-encapsulated cells did. The 3D MIN6 culture, therefore, showed improved effects compared to the 2D culture, and the 1% alginate-encapsulated MIN6 cells exhibited better effects than the spheroids. The upregulation of PDX1 expression through the activation of the PI3K/AKT/FoxO1 pathway may mediate the improved cell proliferation and GSIS in 1% alginate-encapsulated MIN6 cells. CONCLUSION This study may contribute to the construction of in vitro culture systems for pancreatic islets to meet clinical requirements.

Objective:To investigate the past continuing medical education (CME) in pediatrics for general practitioners in community health centers in Longhua District, Shenzhen, so as to explore the willingness, needs and suggestions of general practitioners for CME in pediatrics.Methods:A mixed methods research were used in this study. Firstly, the purpose sampling method was used to select general practitioners in community health centers in Longhua District, Shenzhen for personal in-depth interviews. The interview contents were recorded and transcribed. The interview contents were coded by NVivo software. Theme frame analysis method was used for data sorting and theme extraction. Based on the results of qualitative interviews, the questionnaire was developed and distributed through the electronic questionnaire platform, and relevant questionnaire data were analyzed by Excel.Results:The results of qualitative research showed that after personal in-depth interviews with 10 general practitioners, the information reached saturation. Through repeated reading, induction and analysis of the interview data, four themes were extracted: ① previous pediatric training opportunities and satisfaction; ② willingness to participate in pediatric training; ③ the demand of training content, form and duration; ④ measures to encourage participation in training. In terms of quantitative research results, a total of 223 electronic questionnaires were collected, among which there were 219 valid questionnaires. Besides, 150 (68.5%) general practitioners said that they had no or only a few training opportunities in pediatrics CME in the past. There were some problems in the past CME training, such as unsystematic training (39 practitioners, 66.1%), narrow course coverage (30 practitioners, 50.8%), the content divorced from clinical practice (29 practitioners, 49.2%), monotonous teaching method (27 practitioners, 45.8%), etc. And 210 (95.9%) general practitioners were willing to participate in pediatric training, and 161 (73.5%) hoped that the form of training would be a combination of online and offline. In terms of pediatrics specialty content training needs, the general practitioners had higher demand for respiratory (188 practitioners, 85.8%), digestive (160 practitioners, 73.1%), infectious (145 practitioners, 66.2%) and dermatology (136 practitioners, 62.1%) specialty.Conclusion:There are still some problems in pediatrics CME, such as few training opportunities, unsystematic training, etc. In the future, we need to formulate systematic training plans and incentive measures according to the needs of general practitioners, to strengthen the pediatric professional training for general practitioners and improve their ability to receive children, in order to promote the implementation of hierarchical medical system for children.

OBJECTIVE：To study the effects of costunolide （COS）on the cell cycle distribution and apoptosis of human breast cancer SK-BR- 3 cells and its mechanism. METHODS ：Human breast cancer SK-BR- 3 cells were divided into blank control group，and COS groups of 10，20，30，40，50 μmol/L. MTT assay was used to detect the effects of COS on cell proliferation. SK-BR-3 cells were divided into blank control group ，COS low ，medium and high concentration groups （10，20，30 μmol/L）. After cultured for 24 h，flow cytometry was used to detect the distribution of cell cycle. Hoechst 33258 fluorescence staining was used to detect cell apoptosis. Western blot assay was used to detect the expression of p 53，caspase-3，Bcl-2，Bax，p21，CDK2 and cyclinE. RESULTS ：Compared with blank control group ，COS could significantly inhibit the proliferation of SK-BR- 3 cells（P＜ 0.05 or P＜0.01），and in a dose and time-dependent manner. Low ，medium and high concentrations of COS could induce cell apoptosis and arrest cell at G 1/S phase （P＜0.05 or P＜0.01），could significantly up-regulate the protein expression of p 53， caspase-3，Bax and p 21（P＜0.05 or P＜0.01），and could significantly down-regulate the protein expression of Bcl- 2，CDK2 and cyclinE（P＜0.01）. CONCLUSIONS ：COS can inhibit the proliferation of human breast cancer SK-BR- 3 cells and induce cell apoptosis and cell cycle arrest. The mechanism may be related to the regulation of p 53/Bax/Bcl-2/caspase-3 apoptosis signal pathway.

Objective To investigate the effects of YAP on the occurrence and progression of acute liver failure by regulating the ferroptosis pathway and its underlying mechanism. Methods A total of 20 8-week-old C57BL/6 mice were randomly divided into four groups: a control group, an acute liver failure model group, a YAP agonist XMU-MP-1 treatment group and a YAP inhibitor verteporfin treatment group, five mice for each group. HE staining was used to observe the pathological changes of hepatic inflammation and necrosis. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected by liver biochemistry. Iron (Fe), malondialdehyde (MDA), glutathione (GSH) determination kits were used to measure their levels in liver tissues of each group. The changes of hepatocyte mitochondrial in each group were observed by electron microscopy. Real time PCR and Western blot analysis were used to detect the mRNA and protein expressions of YAP, glutathione peroxidase 4 (GPX4) and 5-lipoxygenase (5-LOX). Results Compared with the control group, mice in the acute liver failure model group and the YAP inhibitor verteporfin treatment group showed severe liver tissue congestion with inflammatory cell infiltration and structural damage to hepatic lobules. Liver injury was alleviated in the XMU-MP-1 treatment group. With the occurrence of liver failure, plasma ALT and AST levels significantly increased, and liver function was improved in XMU-MP-1 treatment group. Electron microscopy showed that mitochondria in hepatocytes of mice with liver failure became smaller and bilayer membrane density increased, while mitochondria changes in the XMU-MP-1 group were alleviated. In addition, the acute liver failure model group showed an increase in Fe and MDA contents, decreased protein expressions of GPX4, and enhanced expression of 5-LOX, suggesting that ferroptosis was involved in acute liver failure in C57BL/6 mice. Ferroptosis was inhibited by activation of YAP. Conclusion Activation of YAP may ameliorate liver injury by inhibiting ferroptosis.
Animals ; Mice ; Ferroptosis ; Glutathione ; Liver Failure ; Liver Failure, Acute/drug therapy* ; Mice, Inbred C57BL ; Verteporfin ; YAP-Signaling Proteins/metabolism*

OBJECTIVE：To study the effects of costunolide on the proliferation ，migration and apoptosis of breast cancer SK-BR-3 cells and its mechanism. METHODS ：SK-BR-3 cells in logarithmic growth period were collected and cultured with different concentrations （10，20，30，40，50 μmol/L）of costunolide for 24，48，72 h. Inhibitory rate of costunolide on cell proliferation was detected with CCK- 8. The cells were divided into blank control group and costunolide group （10，20，30 μmol/L）. Hoechst 33258 fluorescence was used to observe the morphology and apoptosis of cells ，and apoptotic rate of cells were calculated. Cell scratch test was used to detect the migration ability of cells and calculate the migration rate. Western blotting was used to detect the relative expression level of Bcl- 2，Bax，Caspase-3 and Cleaved Caspase- 3 in cells. RESULTS ：The proliferation of SK-BR-3 cells were significantly inhibited by costunolide （P＜0.05 or P＜0.01），and it shows a trend of concentration and time dependence. In the blank control group ，cells possessed clear contour ，regular shape and good adherence . Compared with blank control group，the number of cells were decreased significantly in 10，20，30 μmol/L costunolide groups，the cell structure was loose，the volume was reduced ，and the gap became larger ，and most of the cell contour disappeared and became round ，the cell adherence was poor ；cell migration rate and Bcl- 2 protein relative expression level were decreased significantly ，while apoptosis rate and the relative expression level of Bax ，Caspase-3 and Cleaved Caspase- 3 protein were significantly increased （P＜0.05 or P＜0.01）. CONCLUSIONS ： Costunolide can inhibit the proliferation and migration ，and induce apoptosis of human breast cancer SK-BR- 3 cells，mechanism of which may be through up-regulating the expression of Bax ，Caspase-3 and Cleaved Caspase- 3 while down-regulating the expression ofBcl-2.