基于多数据库分析RIT1在肝细胞癌中的表达及预后

目的 获取Ras亚家族新分支的创始成员RIT1蛋白(GTP-binding protein Rit1,RIT1)在肝细胞癌(hepa-tocellular carcinoma,HCC)中的表达水平数据,分析RIT1及其共表达基因在HCC发生发展过程中的作用.方法 通过Oncomine数据库和癌症基因图谱(the cancer genome atlas,TCGA)数据库分析RIT1基因在HCC中的表达,及临床特征和预后的关系.利用cBioportal在线分析工具分析RIT1在HCC中的突变情况,并通过GeneMina数据库分析与RIT1相互作用的蛋白.基于LinkedOmics数据库筛选与RIT1在HCC中共表达的蛋白并分析其参与的信号通路.结果 HCC组织中RIT1 mRNA表达和DNA拷贝数变异(copy number variation,CNV)显著高于正常组织(P＜0.01),HCC患者中肿瘤组织的RIT1转录水平显著高于正常组织;随着肿瘤等级和疾病阶段的升高,RIT1的表达量具有升高的趋势.在360例HCC样本中共有62例发生RIT1基因变异,变异率约为17.2％.生存曲线分析显示,RIT1高表达组和RIT1变异组的总体生存期短于RIT1低表达组和无变异组(P＜0.01).RAF原癌基因丝氨酸/苏氨酸蛋白激酶(RAF proto-oncogene serine/threonine-protein kinase,RAF)、神经营养的酪氨酸激酶 1 型受体(neurotrophic receptor tyrosine kinase 1,NTRK1)、Ral 鸟嘌呤核苷酸解离刺激剂样蛋白 1(Ral GDP dissociation stimulator like 1,RGL1)、神经生长因子(nerve growth factor,NGF)、RLF 锌指蛋白、鸟嘌呤核苷酸解离刺激因子(Ral guanine nucleotide-dissociation stimulator,RalGDS)、干扰素相关发育调节因子 1(interferon-related developmental regulator 1,IFRD1)、Ras 相关蛋白 1b(RAS-related protein Rap-1b,RAP1B)、Kelch 样家族成员 12(Kelch like family member 12,KLHL12)、MLLT4、母系DPP 同源物3(mothers against decapentaplegic homolog 3,Smad3)等蛋白与 RIT1 具有明显的相互作用,STX6、MPZL1、PKM2、RNF24和SOAT1等蛋白在HCC中与RIT1共表达,这些蛋白主要涉及小G蛋白信号转导、Ras信号通路和神经营养因子TRK受体信号通路,能够促进DNA构象改变、有丝分裂和细胞周期等.结论 RIT1在HCC组织中呈高表达,具有较高的基因变异频率,并且与患者预后不良相关,为之后深入研究RIT1在HCC发生发展中的作用提供了理论依据.     

HTR2C polymorphisms,olanzapine-induced weight gain and antipsychotic-induced metabolic syndrome in schizophrenia patients: A meta-analysis

Objective. To conduct meta-analyses of all published association studies on the HTR2C -759C/T (rs3813829) polymorphism and olanzapine-induced weight gain in schizophrenia patients and on the HTR2C -759C/T, -697G/C (rs518147) and rs1414334:C> G polymorphisms and olanzapine/clozapine/risperidone-induced metabolic syndrome in schizophrenia patients. Methods. Eligible studies were identified by searching PubMed and Web of Science databases. Meta-analyses were performed using Cochrane Review Manager (RevMan, version 5.2) to calculate the pooled odds ratio (OR) and its corresponding 95% confidence interval (CI). Results. Our meta-analyses revealed both a significant positive association between the rs1414334 C allele and olanzapine/clozapine/risperidone-induced metabolic syndrome and a marginally significant positive association between the -697C allele and the induced metabolic syndrome in schizophrenia patients, but no significant association between the -759C/T polymorphism and the induced metabolic syndrome in schizophrenia patients. Our analysis further revealed a pronounced trend toward a significant negative association between the -759T allele and high olanzapine-induced weight gain and a trend toward a significant positive association between the -759C allele and high olanzapine-induced weight gain in Caucasian schizophrenia patients. Conclusions. Our results support that HTR2C polymorphisms play a role in antipsychotic-induced metabolic disturbance. More association studies are needed to further elucidate association of different HTR2C polymorphisms and antipsychotic-induced metabolic disturbance.     

术中 X-线定位在神经内镜切除甲介型蝶窦垂体瘤手术中的应用简

目的探讨术中x-线定位在经神经内镜下甲介型蝶窦垂体瘤手术的应用。方法回顾性分析6例甲介型蝶窦垂体瘤病人的临床资料,均采用神经内镜下垂体瘤切除结合术中X-线定位方法。结果术中X-线定位准确4例;2例发生纵向偏差,均纠正。肿瘤全切除5例,次全切除1例。术后激素水平正常,视力视野改善。出现暂时性尿崩1例,治疗后痊愈。无脑脊液鼻漏、垂体功能低下、蝶窦炎发生,无死亡病例。6例病人随访3年,均无复发。结论神经内镜技术结合术中X-线定位是一种治疗甲介型蝶窦垂体瘤的安全、有效方法。     

Attenuation of Reserpine-Induced Pain/Depression Dyad by Gentiopicroside Through Downregulation of GluN2B Receptors in the Amygdala of Mice

Epidemiological studies demonstrate that pain frequently occurs comorbid with depression. Gentiopicroside (Gent) is a secoiridoid compound isolated from Gentiana lutea that exhibits analgesic properties and inhibits the expression of GluN2B-containing N-methyl-d-aspartate (NMDA) receptors in the anterior cingulate cortex of mice. However, the effects of Gent on the reserpine-induced pain/depression dyad and its underlying mechanisms are unclear. Reserpine administration (1 mg/kg subcutaneous daily for 3 days) caused a significant decrease in the nociceptive threshold as evidenced by the reduced paw withdrawal latency in response to a radiant heat source and mechanical allodynia. Behavioral detection indicated a significant increase in immobility time during a forced swim test, as well as decreased time in the central area and total travel distance in an open field test. Furthermore, reserpinized animals exhibited increased oxidative stress. Systemic Gent administration dose-dependently ameliorated the behavioral deficits associated with reserpine-induced pain/depression dyad. At the same time, the decrease in biogenic amine levels (norepinephrine, dopamine, and serotonin) was integrated with the increase in caspase-3 levels and GluN2B-containing NMDA receptors in the amygdala of the reserpine-injected mice. Gent significantly reversed the changes in the levels of biogenic amines, caspase-3, and GluN2B-containing NMDA receptors in amygdala. However, Gent did not affect the expression of GluN2A-containing NMDA receptors. The inhibitory effects of Gent on oxidative stress were occluded by simultaneous treatment of GluN2B receptors antagonist Ro25-6981. Our study provides strong evidence that Gent inhibits reserpine-induced pain/depression dyad by downregulating GluN2B receptors in the amygdala.     

风电项目光影影响分析方法

风电作为一种清洁能源,是近年来国家鼓励发展的能源项目,以往主要分布在人烟稀少地区,但随着规模的发展,部分风电场区已经涉及到零星居民居住地,随之而来的光影影响不可忽视。     

人骨唾液蛋白非融合荧光蛋白载体的构建及在乳腺癌细胞中的表达

背景：人骨唾液蛋白基因在矿化组织以外的易发生骨转移的人乳腺癌中表达。临床观察显示骨转移处的乳腺癌细胞骨唾液蛋白的表达量要高于原发部位的乳腺癌细胞，因此骨唾液蛋白有可能与肿瘤特异性骨转移的关系密切。研究乳腺癌骨转移可为将来临床的预防和治疗提供新的药物靶点。目的：建立骨唾液蛋白的稳定表达乳腺癌细胞系，观察骨唾液蛋白在乳腺癌骨转移的整个过程中的作用。设计：对照实验。单位：华南理工大学生物科学与工程学院，解放军广州军区广州总医院医学实验中心。材料：实验于2003-11／2004-03在解放军广州军区广州总医院医学实验室完成。质粒、菌种和细胞：pIRES2-EGFP载体质粒，E．Coli．Top10、含有人骨唾液蛋白基因全长的克隆载体pB-hBSP和发生特异性骨转移以及脑转移的人乳腺癌细胞株MDA-MB-231BO和MDA-MB-23lBR。方法：将人骨唾液蛋白基因通过聚合酶链式反应的方法从构建好的pB-hBSP载体中亚克隆出来，在其5’和3’端分别引入BglⅡ和PsiⅠ限制性酶切位点，定向克隆至真核表达载体pIRES2-EGFP，构建重组载体pIRES2-hBSP-EGFP。利用脂质体转染的方法将构建好的重组质粒转入特异性脑转移和骨转移的乳腺癌细胞株MDA-MB-231BR和MDA-MB-231BO中。主要观察指标：pIRES2-hBSP-EGFP重组表达载体的构建。重组表达载体pIRES2-hBSP-EGFP转染乳腺癌细胞。结果：①成功构建人骨唾液蛋白和绿色荧光蛋白非融合表达的真核表达载体pIRES2-hBSP-EGFP。②成功转染特异骨转移和脑转移的乳腺癌细胞株，可在荧光显微镜下观察到荧光蛋白标记，人骨唾液蛋白得到相应表达。结论：真核表达载体pIRES2-hBSP-EGFP的构建及转染可为骨唾液蛋白在乳腺癌骨转移中的作用的体内、外研究奠定一定的基础。     

In vitro degradation and controlled release behavior of D,L-PLGA50 and PCL-b-D,L-PLGA50 copolymer microspheres.

Blank and bovine serum albumin (BSA)-loaded microspheres based on poly(lactic-acid-alt-glycolic acid) (D,L-PLGA50) and poly(epsilon-caprolactone)-b-poly(lactic-acid-alt-glycolic acid) (PCL-b-D,L-PLGA50) were successfully fabricated using water-in-oil-in-water (w/o/w) double-emulsion extraction/evaporation technique. In vitro degradation of the blank microspheres was characterized by techniques including nuclear magnetic resonance (1H NMR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The PCL-b-D,L-PLGA50 copolymer (Mn: number-average molecular weight, Mw: weight-average molecular weight, Mn=44800, Mw/Mn=MWD=1.24, epsilon-caprolactone (CL) %=20.4% in molar ratio) had similar rate of molecular weight reduction compared with the D,L-PLGA50 copolymer before 5 weeks of in vitro degradation. The BSA % loading efficiency of microspheres was mainly controlled by both block copolymer composition and macromolecular architecture, while the sequence structure and the molecular weight of copolymer had no apparent effect on it. Significantly, The PCL-b-D,L-PLGA50 copolymer microspheres showed good release profiles with a nearly constant release during 20-110 days.     

Comparison of neck movement smoothness between patients with mechanical neck disorder and healthy volunteers using the spectral entropy method

Purpose

Mechanical neck disorder is one of the most common health issues. No related observations have applied spectral entropy to explore the smoothness of cervical movement. Therefore, the objectives were to ascertain whether the spectral entropy of time-series linear acceleration could extend to estimate the smoothness of cervical movement and compare the characteristics of the smoothness of cervical movement in patients with mechanical neck pain (MND) with healthy volunteers.

Methods

The smoothness of cervical movement during cervical circumduction from 36 subjects (MND: n = 18, asymptomatic: n = 18) was quantified by the spectral entropy of time-series linear acceleration and other speed-dependent parameters, respectively.

Results

Patients with MND showed significantly longer movement time, higher value in the spectral entropy and wider band response in frequency spectrum than healthy volunteers (P = 0.01).

Conclusions

The spectral entropy would be suitable to discriminate the smoothness of cervical movement between patients with MND with healthy volunteers and demonstrated patients with MND had significantly less smooth cervical movement.