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.     

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.     

慢性心力衰竭护理结局分类评价表的构建研究

目的本研究以护理结局分类(NOC)为基础,筛选符合慢性心力衰竭患者的相关护理结局,由此构建具有专科专病特点的慢性心力衰竭患者护理结局评价表。方法成立研究核心小组,应用文献回顾法、专家函询法确定护理结局分类指标,并进行统计学分析,最终建立慢性心力衰竭护理结局分类评价表。结果通过研究,确定慢性心力衰竭护理结局中包含4个领域、8个一级指标、68个二级指标。4个领域分别是生理健康、功能健康、健康知识和行为、心理社会健康。一级指标中包含心脏泵血功能、活动耐力、社会支持、抑郁水平等。二级指标中包含心脏指数、血压、呼吸困难、情绪波动大、步行距离、步行速度等68个指标。统计学分析中:第一、二轮函询专家的积极系数分别为90%、100%,专家权威系数为0.895,专家意见协调程度(P<0.05)。结论本研究成功建立慢性心力衰竭护理结局分类评价表,有助于临床护士用于评价护理措施的有效性,也使其成为一种标准化语言,便于应用到护理电子信息系统中进行绩效测算等。但是本研究不足之处是未能将该研究进行临床实证,未能进一步确认其有效性。     

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.     

Pick’s disease with Pick bodies combined with progressive supranuclear palsy without tuft‐shaped astrocytes: A clinical,neuroradiologic and pathological study of an autopsied case

We report clinical, neuroradiologic features, and neuropathologic findings of a 76‐year‐old man with coexistent Pick’s disease and progressive supranuclear palsy. The patient presented with loss of recent memory, abnormal behavior and change in personality at the age of 60. The symptoms were progressive. Three years later, repetitive or compulsive behavior became prominent. About 9 years after onset, he had difficulty moving and became bed‐ridden because of a fracture of his left leg. His condition gradually deteriorated and he developed mutism and became vegetative. The patient died from pneumonia 16 years after the onset of symptoms. Serial MRI scans showed progressive cortex atrophy, especially in the bilateral frontal and temporal lobes. Macroscopic inspection showed severe atrophy of the whole brain, including cerebrum, brainstem and cerebellum. Microscopic observations showed extensive superficial spongiosis and severe neuronal loss with gliosis in the second and third cortical layers in the frontal, temporal and parietal cortex. There were Pick cells and argyrophilic Pick bodies, which were tau‐ and ubiquitin‐positive in neurons of layers II–III of the above‐mentioned cortex. Numerous argyrophilic Pick bodies were observed in the hippocampus, especially in the dentate fascia. In addition, moderate to severe loss of neurons was found with gliosis and a lot of Gallyas/tau‐positive globus neurofibrillary tangles in the caudate nucleus, globus pallidus, thalamus, substantia nigra, locus coeruleus and dentate nucleus. Numerous thorned‐astrocytes and coiled bodies but no‐tuft shaped astrocytes were noted in the basal ganglion, brainstem and cerebellar white matter. In conclusion, these histopathological features were compatible with classical Pick’s disease and coexistence with progressive supranuclear palsy without tuft‐shaped astrocytes.     

应用庆大霉素溶液与生理盐水行手外伤清创的效果比较

目的 探讨应用庆大霉素溶液与生理盐水对手外伤清创效果的差异。方法 对102例急诊手外伤患者，随机分为庆大霉素组（45例）和生理盐水组（57例）两组，分别由同一名医师进行常规清创，术后口服头孢氨苄胶囊预防感染5d，每3～4d伤口换药，观察伤口情况，于术后12d拆线，对伤口做出评价。结果 伤口愈合情况：庆大霉素组，甲级愈合20例，乙级愈合17例，丙级愈合8例；生理盐水组，甲级愈合24例，乙级愈合20例，雨级愈合13例。感染率：庆大霉素组17．78％，肥皂水组22．81％，平均为20．9％，两组比较差异无统计学意义（x^2=0．39，P〉0．05）。结论 使用庆大霉素溶液对伤口进行冲洗，并不能降低手外伤清创后的感染率。     

高转换型肾性骨病中骨保护素及其配体的表达和形态计量学观察

目的 观察高转换型肾性骨病中骨保护素及其配体 (OPG，RANKL)的表达，并与骨形态计量学指标进行相关分析。 方法 选择10例慢性肾衰尿毒症患者和3例正常人进行髂骨活检术，获得骨组织标本。采用免疫组化方法检测OPG和RANKL蛋白质的表达。采用全自动图像分析系统进行骨组织形态计量学测定。结果 10例慢性肾衰尿毒症患者经骨病理学检查证实均为高转换型骨病，以破骨细胞活化形成骨吸收陷窝伴或不伴骨矿化不全为特点。免疫组化显示尿毒症患者骨组织中以RANKL阳性表达为主。与正常对照相比，RANKL阳性表达细胞数目显著增加，OPG阳性表达细胞数目显著减少。尿毒症患者RANKL的阳性表达细胞数目与骨吸收面积和破骨细胞数目呈显著正相关。结论 高转换型肾性骨病中，PTH的溶骨作用可能是通过OPG/RANKL/RANK系统介导的。