Proteomic Profiling of Small Extracellular Vesicles Isolated from the Plasma of Vietnamese Patients with Non-Small Cell Lung Cancer Reveals Some Potential Biomarkers

Background: Considering the poor prognosis of non-small cell lung cancer (NSCLC), the objective of this study was to examine the potential of plasma-derived vesicles as a source of lung cancer-specific proteins. Extracellular vesicle (EV) cargos are specific to the source cells, hence they have the potential of being a source of cancer-specific proteins.  Methods: The proteins differently expressed in cancer were determined and derived from EVs isolated from the plasma of NSCLC patients at the National Lung Hospital. To this end, purification was done using gel filtration chromatography and ultracentrifugation. In addition, nano liquid chromatography mass spectrometry (LC–MS/MS) was used for analyzing. Results: Fifty-seven EV-derived proteins related to NSCLC were highlighted in this research. Some of them have not been addressed before, such as EEF1A1 (elongation factor 1-α1), KPNB1 (Importin subunit beta 1), SRC (proto-oncogene tyrosine-protein kinase) and ACTC1 (actin, alpha cardiac muscle 1). This list was further confirmed through a comparison with ExoCarta and Vesiclepedia. Conclusion: This study is the first work to show the involvement of several novel proteins of small EV (EEF1A1, KPNB1, SRC, and ACTC1) in the progression of NSCLC. The results suggested that they could serve as novel biomarkers for non-small cell lung cancer in the future.     

模拟诊疗在留学生心血管内科实习带教中的应用研究

目的　探讨模拟诊疗在留学生心血管内科实习带教中的应用效果。方法　将35名留学生随机编号，分成试验组和对照组。试验组18名学生分成3组（每组6名）进行模拟诊疗教学，对照组17名学生进行常规实习。通过填写评价单和相关的临床能力测试对两组教学效果进行评价。选用SPSS 19.0软件进行t检验。结果　参与模拟诊疗教学的留学生均希望在各科实习中多采用此方法。在临床能力测试方面，试验组学生在病史采集[（22.16±2.17）vs.（20.33±2.03）]、体格检查[（23.05±1.79）vs.（19.78±2.05）]及回答问题[（23.50±1.47）vs.（19.56±1.92）]方面均优于对照组，差异有统计学意义（P<0.05）。但是在病历书写方面，两组差异无统计学意义（P>0.05）。结论　利用高仿真的模拟诊疗教学手段，弥补了留学生在实习期间不能充分接触患者的缺陷，有助于提高其临床操作技能、增强医患沟通能力等医学职业素养。     

Quantile regression and empirical likelihood for the analysis of longitudinal data with monotone missing responses due to dropout,with applications to quality of life measurements from clinical trials

The analysis of quality of life (QoL) data can be challenging due to the skewness of responses and the presence of missing data. In this paper, we propose a new weighted quantile regression method for estimating the conditional quantiles of QoL data with responses missing at random. The proposed method makes use of the correlation information within the same subject from an auxiliary mean regression model to enhance the estimation efficiency and takes into account of missing data mechanism. The asymptotic properties of the proposed estimator have been studied and simulations are also conducted to evaluate the performance of the proposed estimator. The proposed method has also been applied to the analysis of the QoL data from a clinical trial on early breast cancer, which motivated this study.     

延安地区泌尿系结石成分分析的研究

目的利用红外光谱法测定延安大学附属医院泌尿外科手术获得的泌尿系结石成分,探讨延安地区泌尿系结石成分与年龄、性别等关系,比较上、下尿路结石成分特点,分析延安地区泌尿系结石发生的流行病学情况,为临床制定有效的个体化治疗及预防措施提供参考依据。方法收集2013年1月至2017年1月在延安大学附属医院泌尿外科治疗1984例尿路结石患者的年龄、性别、结石部位等临床资料,对比分析延安地区泌尿系结石在不同年龄、不同性别、不同解剖部位的分布特点。结果在1984例泌尿系结石的患者中,按每10岁年龄大小分组排序,统计各年龄阶段泌尿系结石发病情况,男性患者有1346例,女性患者有638例,男性年龄(50.23±14.48)岁,女性年龄(47.87±14.51)岁,男、女患者比例约2.11∶1。在66~75岁年龄段,尿路结石发病率性别差异具有统计学意义(P<0.05)。结石成分以混合性结石为主,以混合性结石为主,共1582例,占79.76%。其中1665例(83.92%)为上尿路结石,上、下尿路结石的比例为5.22∶1,其余为肾结石合并膀胱结石。上尿路结石中男性1062例,女性603例,男女比例为1.76∶1;下尿路结石中男性284例,女性35例,男女比例为8.11∶1。青壮年(年龄≤45岁)泌尿系结石患者草酸钙为主结石、感染性结石多见;中老年(年龄>45岁)泌尿系结石者草酸钙为主结石、尿酸类结石多见。感染性结石患者性别差异具有统计学意义(P<0.05)。结论在延安地区男性较女性更容易患泌尿系结石。同时,不同年龄段结石构成成分具有差异。对于年龄≤45岁患者,主要以草酸钙为主结石、感染性结石多见,这与结石整体发病率基本一致;而对于年龄>45岁患者,主要以草酸钙为主结石、尿酸性结石多见。表明对于不同年龄段的结石患者,可以根据上述结果在结石的预防和治疗上综合考量,给予明确而更加合理的治疗。     

Protein kinase Cδ mediates trimethyltin-induced neurotoxicity in mice in vivo via inhibition of glutathione defense mechanism

We investigated whether protein kinase C (PKC) is involved in trimethyltin (TMT)-induced neurotoxicity. TMT treatment (2.8 mg/kg, i.p.) significantly increased PKCδ expression out of PKC isozymes (i.e., α, βI, βII, δ, and ?) in the hippocampus of wild-type (WT) mice. Consistently, treatment with TMT resulted in significant increases in cleaved PKCδ expression. Genetic or pharmacological inhibition (PKCδ knockout or rottlerin) was less susceptible to TMT-induced seizures than WT mice. TMT treatment increased glutathione oxidation, lipid peroxidation, protein oxidation, and levels of reactive oxygen species. These effects were more pronounced in the WT mice than in PKCδ knockout mice. In addition, the ability of TMT to induce nuclear translocation of Nrf2, Nrf2 DNA-binding activity, and upregulation of γ-glutamylcysteine ligase was significantly increased in the PKCδ knockout mice and rottlerin (10 or 20 mg/kg, p.o. × 6)-treated WT mice. Furthermore, neuronal degeneration (as shown by nuclear chromatin clumping and TUNEL staining) in WT mice was most pronounced 2 days after TMT. At the same time, TMT-induced inhibition of phosphoinositol 3-kinase (PI3K)/Akt signaling was evident, thereby decreasing phospho-Bad, expression of Bcl-xL and Bcl-2, and the interaction between phospho-Bad and 14-3-3 protein, and increasing Bax expression and caspase-3 cleavage were observed. Rottlerin or PKCδ knockout significantly protected these changes in anti- and pro-apoptotic factors. Importantly, treatment of the PI3K inhibitor LY294002 (0.8 or 1.6 µg, i.c.v.) 4 h before TMT counteracted protective effects (i.e., Nrf-2-dependent glutathione induction and pro-survival phenomenon) of rottlerin. Therefore, our results suggest that down-regulation of PKCδ and up-regulations of Nrf2-dependent glutathione defense mechanism and PI3K/Akt signaling are critical for attenuating TMT neurotoxicity.     

Chronic fatigue of the small enterprise workers participating in an occupational health checkup center in southern Taiwan

Purpose  There has been increasing interest in the occupational health of workers in small enterprises, especially in developing countries. This study examines the association between psychosocial job characteristics and fatigue, and attempts to identify risk factors for fatigue among workers of small enterprises in southern Taiwan. Methods  A structured questionnaire was administered to workers receiving regular health examinations between August 2005 and January 2006. The questionnaire collected demographic information and data on working conditions, personal health status and life styles. It also collected information on psychosocial job characteristics, fatigue and psychological distress using three instruments. Results  A total of 647 workers with mean age of 43.7 were completed. Probable fatigue was found in 34.6% of the sample. Fatigue was found by multiple logistic regressions to be associated with the lack of exercise, working in shifts, depression score and lack of social support at workplace. Conclusions  This study found associations between life style, psychosocial job characteristics and fatigue. Because the high prevalence of probable fatigue was found in such small enterprises, the authors suggest that a short interview with some quick questionnaires in health checkup for these small enterprise workers are helpful to early detect psychosocial and fatigue problems.