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1.
目的 研究细胞因子信号抑制物1(SOCS1)在超负荷心室乳头肌中的表达,了解其在心室乳头肌承载负荷后结构重建中的表达特点以及在影响细胞信号转导的立方水母毒素-1(CfTX-1)预处理作用下的生物力学特性。方法 昆明小鼠腹主动脉-静脉穿刺造瘘(n=5),2周后取心室乳头肌匀浆后提取总蛋白,另设正常组(n=5)施假手术作对照。离体培养则采用正常小鼠左心室乳头肌(n=20),负荷培养组心室乳头肌倍比牵拉固定于硅胶板,松弛培养组不予牵拉负荷,两组内均另设一个组添加SOCS1质粒转染。上述各组心室乳头肌均于培养液中37 ℃培养3 d后,匀浆并提取总蛋白,10%十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分离总蛋白,以含SOCS1的23 ku条带为目标条带,计算机图像法测其积分光密度(IOD)值。采用蛋白质印迹法(Western Blot)检测SOCS1蛋白的表达,并测其印迹IOD值。采用微分定位器牵拉造瘘小鼠心室乳头肌至初始负荷为1 g,待稳定后顺序瞬间牵拉15 mm,观察第1次及第5次牵拉时的被动张力特性曲线,计算心室乳头肌在任氏液及CfTX-1预处理后的最大被动张力(PTmax)和最大被动张力下降速度(DV)。结果 造瘘组心室乳头肌总蛋白中23 ku条带及SOCS1印迹IOD值均高于正常组,差异均具有统计学意义(均P<0.01)。松弛转染培养组心室乳头肌总匀浆液中23 ku条带的IOD值显著高于负荷转染及负荷非转染培养组,差异均具有统计学意义(均P<0.01),且后两组间差异无统计学意义(P>0.05)。负荷转染培养组心室乳头肌总匀浆液以及胞核匀浆液中SOCS1印迹IOD平均值均高于负荷非转染培养组和松弛转染培养组,差异均具有统计学意义(均P<0.01)。造瘘组心室乳头肌的PTmax和极限PTmax均低于正常组,DV高于正常组,而极限DV低于正常组,差异均具有统计学意义(均P<0.01)。结论 SOCS1的表达对长度负荷较为敏感,其作为超负荷敏感信号在改善心肌适应性、保护心肌结构及维护舒缩功能方面具有更深层的积极作用。CfTX-1对改善心室乳头肌顺应性也具有积极作用。  相似文献   

2.
目的:探讨氯胺酮相关性膀胱炎(KC)小鼠膀胱平滑肌病理生理改变及其胆碱、嘌呤和整合素β1(ITGB1)信号通路表达的变化。方法:基于氯胺酮腹腔注射诱导小鼠KC模型,通过HE染色、Masson染色及甲苯胺蓝染色检测KC小鼠膀胱平滑肌的病理变化;通过排尿行为模式研究和尿动力学实验检测KC小鼠膀胱功能;利用离体肌条张力实验研究KC小鼠膀胱平滑肌收缩力情况;采用Western blot及免疫荧光明确胆碱、嘌呤和ITGB1信号通路蛋白表达变化。结果:病理实验显示KC小鼠膀胱壁出现明显损伤,上皮细胞脱落,膀胱黏膜屏障变薄,肌肉层间隙增大,结缔组织显著增加,并有明显的炎症细胞和肥大细胞浸润,肌肉层表现出明显病理变化。排尿行为模式研究和尿动力学实验显示KC小鼠排尿频率增加、膀胱容量降低和膀胱顺应性下降,表现出明显的膀胱功能损伤。离体肌条张力实验发现KC小鼠膀胱平滑肌在电场、胆碱信号、嘌呤信号及去极化刺激下收缩力均显著降低。Western blot和免疫荧光检测发现KC小鼠膀胱组织M2和P2X1受体蛋白表达显著减少,而ITGB1及其相关信号蛋白均显著增加。结论:KC小鼠膀胱平滑肌具有明显的病理生理改变和相关信号通路变化。  相似文献   

3.
目的:探讨细胞信号传导抑制因子1/3(SOCS1、SOCS3,SOCS1/3)对Toll样受体3(TLR3)和T细胞分化的调控及其在桥本甲状腺炎(HT)中的作用。方法:收集已确诊的桥本甲状腺炎患者40例(HT组)及正常体检人群30例(对照组);通过Ficoll密度梯度离心法分离外周血单核细胞(PBMCs),流式细胞术检测调节性T细胞(CD4+CD25+Treg,Treg)、辅助性T细胞17(Th17)及滤泡辅助性T细胞(Tfh),免疫组化法(IHC)检测甲状腺组织中SOCS1/3及TLR3蛋白表达,ELISA检测血浆中SOCS1/3、STAT3蛋白水平,qRT-PCR检测PBMCs中TLR3、SOCS1/3、STAT3、RORγt、Bcl6、Foxp3 mRNA的表达水平。结果:HT组PBMCs中Treg细胞数量降低而Th17细胞、Tfh细胞数量升高(P 0. 05),TLR3、SOCS1/3、Bcl6、RORγt mRNA表达升高,Foxp3、STAT3 mRNA表达降低(P 0. 05); HT组甲状腺组织SOCS1/3蛋白、TLR3蛋白浓度升高(P 0. 05),STAT3蛋白表达降低(P 0. 05)。结论:HT患者SOCS1/3表达升高,可能对HT的TLR3表达及T细胞亚群分化起调控作用。  相似文献   

4.
目的:研究脑不对称性对下丘脑中IL -1β、IL -6及细胞因子信号转导抑制因子 3(SOCS -3)表达的影响,从分子水平探讨脑不对称性在神经内分泌免疫调节网络中的作用。方法:运用伸爪取食法将BALB c小鼠区分为左利、右利和双利鼠。小鼠分组一周后断头杀死,迅速分离出下丘脑,一部分标本制备匀浆后采用ELISA法测定下丘脑中IL- 1β、IL- 6的蛋白水平;另一部分标本以RT- PCR法间接测定下丘脑SOCS -3mRNA水平。结果:(1)下丘脑IL 6蛋白水平:左利鼠水平明显高于右利鼠,差异有统计学意义(P <0 . 0 5 )。(2 )下丘脑IL -1β蛋白水平:左利、右利小鼠水平相近,差异无显著性(P >0 . 0 5 )。(3)下丘脑SOCS 3表达:右利鼠下丘脑中SOCS 3的表达显著高于左利鼠(P <0 . 0 5 )。结论:脑不对称BALB c小鼠下丘脑IL -1β、IL- 6及细胞因子信号转导抑制因子SOCS -3的表达存在差异,提示这可能是左、右利人群免疫紊乱性疾病发生率不同原因之一。  相似文献   

5.
目的:探讨干姜吴茱萸水煎液对大鼠结肠平滑肌收缩及平滑肌细胞L型Ca2+通道的影响机制。方法:采用0、0.01、0.1、1、10 g/L干姜吴茱萸(1∶1)水煎液依次作用于正常结肠平滑肌,10 g/L水煎液及L型Ca2+通道激动剂BAY-K-8644依次作用于氯化乙酰胆碱(Ach)诱导后的正常平滑肌,检测平滑肌收缩张力、频率和振幅;全细胞膜片钳记录L型钙电流;Western blot检测各组细胞中L-型电压依赖钙离子通道α1C亚基(α1c)和钙调蛋白(CaM)蛋白表达情况。结果:1、10 g/L水煎液组能显著降低离体结肠平滑肌的收缩张力(P<0.05),对频率及振幅并无显著影响(P>0.05);与0 g/L水煎液组相比,Ach促进平滑肌收缩张力、频率和振幅显著增加(P<0.05);与Ach组相比,10 g/L水煎液显著降低平滑肌的收缩张力、频率和振幅(P<0.05);与10 g/L水煎液组相比,BAY-K-8644显著增加平滑肌的收缩张力、频率和振幅(P<0.05);与0 g/L水煎液组相比,Ach可显著增加ICa...  相似文献   

6.
目的 探讨HPV L1衣壳蛋白在HPV阳性的宫颈细胞学标本和活检组织标本中的表达及意义.方法 运用免疫组化SP法检测L1蛋白在宫颈细胞学和组织学标本中表达.结果 52例细胞学标本中,L1蛋白在非典型鳞状细胞(ASCUS)、低级别鳞状上皮内病变(LSIL)、高级别鳞状上皮内病变(HSIL)中阳性表达率分别为43.8%(7/16)、28.5%(10/26)、0(0/10);100例组织学标本中,L1蛋白在炎症、CIN1、CIN2、CIN3中阳性表达率分别为55.6%(15/27)、43.8%(14/32)、15.4%(4/26)、0(0/15);两组资料L1蛋白阳性表达率的差异均具有统计学意义(χ2=9.149,P=0.01;χ2=23.555,P=0.00).结论 早期检测HPV L1蛋白,有助于判断宫颈病变程度及其恶性进展趋势,为宫颈病变患者提供更合理的治疗流程.  相似文献   

7.
目的探讨地塞米松对孕晚期大鼠子宫的收缩是否有影响及可能机制。方法将6只孕20d SD大鼠剖腹,均等切取子宫肌条,每只大鼠取4个肌条,共24个,随机均分放入含有不同药物的4个平皿中,依次分为A空白对照组、B催产素(OXT)组、C地塞米松组、D地塞米松+OXT组,反应30min后检测各组肌条肌张力,然后用Real-time PCR、Western blot和酶联免疫吸附法分别检测各组肌条中OXTR、前列腺素F2α受体(PTGFR)、尿皮素1(UCN1)和缝隙连接蛋白43(CX43)的mRNA及蛋白表达水平,分析比较各组肌条肌张力及蛋白表达水平的关系。结果 4组肌条肌张力(振幅和频率)比较,D组B组A组、D组C组A组(P0.05),B、C组组间肌张力无明显差异(P0.05)。B组、C组OXTR和CX43 mRNA及蛋白表达水平均高于A组(P0.05),D组OXTR、UCN1和CX43 mRNA及蛋白表达水平均高于B组(P0.05),D组UCN1和CX43 mRNA及蛋白表达水平均高于C组(P0.05),而PTGFR在四组间表达均无明显差异(P0.05)。结论 OXT联合地塞米松促子宫收缩作用强于OXT、地塞米松单独使用,二者联合增强子宫收缩可能与增强子宫肌表面OXTR、UCN1和CX43的表达相关。  相似文献   

8.
人早孕母胎界面SOCS1、SOCS2、SOCS3表达   总被引:2,自引:0,他引:2  
目的:研究正常早孕绒毛及蜕膜组织细胞因子信号转导负调控因子(Suppressors of cytoldne signaling,SOCS)基因和蛋白水平表达,以揭示SOCS在母胎界面生理性调节作用。方法:半定量RT-PCR检测早孕绒毛组织、蜕膜组织及原代培养早孕滋养细胞、蜕膜基质细胞SOCS1、SOCS2、SOCS3 mRNA水平;Western blot检测早孕绒毛组织及蜕膜组织SOCS1、SOCS2、SOCS3蛋白表达;免疫组化定位SOCS1、SOCS2、SOCS3在早孕绒毛组织、蜕膜组织表达;ELISA检测滋养细胞、蜕膜基质细胞分泌IL-10、IFN-γ。结果:正常母胎界面见SOCS1、SOCS2、SOCS3基因表达,其中SOCS3绒毛/蜕膜阳性率73.7%/71.1%;SOCS2绒毛/蜕膜阳性率50.0%/39.5%,SOCS1最少,绒毛/蜕膜阳性率34.2%/31.6%;SOCS1、SOCS2、SOCS3蛋白表达与转录水平基本一致;正常母胎界面SOCS1、SOCS2、SOCS3表达主要定位于绒毛滋养细胞和蜕膜间质;体外无血清培养滋养细胞和蜕膜基质细胞SOCS2、SOCS3低表达,SOCS1未见表达,其分泌的IL-10随时间而增高(P〈0.05)。结论:正常早孕母胎界面表达SOCS1、SOCS2、SOCS3,无刺激条件下滋养细胞和蜕膜基质细胞低表达SOCS2、SOCS3,SOCS在正常妊娠Th平衡中具有重要意义。  相似文献   

9.
背景:蛋白质分解是延缓肌萎缩发生的关键环节,在慢性病性、制动性肌萎缩中泛素蛋白连接酶Murf1和核转录因子NF-κB的表达增加,被动运动已被证实可以有效抑制肌萎缩的发生。目的:探讨泛素蛋白连接酶Murf1和核转录因子NF-κB在大鼠失神经肌萎缩中不同时段的表达,以及被动运动对失神经骨骼肌Murf1和NF-κB表达的影响。方法:假手术组大鼠不切断右下肢坐骨神经,失神经组、失神经被动运动组大鼠切断右下肢坐骨神经。术后1d起,将失神经被动运动组大鼠置于自制的网夹内,拉出右后肢,抓住趾部,与脊柱呈45°向后外方牵拉,至右后肢完全伸直,再将右后肢推向身体,使之完全屈曲紧贴身体,每天训练2次,每次屈伸运动300下,3min/次,直至切取标本之日。干预2,14,28d后,采用RT-PCR与WesternBlot技术分别检测Murf1,NF-κBmRNA和蛋白质的表达。结果与结论:与假手术组比较,各时间点失神经组Murf1,NF-κBmRNA及蛋白的表达均明显增加(P0.05);与失神经组比较,各时间点失神经被动运动组Murf1及NF-κBmRNA的表达均显著降低(P0.01)。失神经支配后肌湿质量比明显下降,被动运动14d时肌湿质量比明显高于失神经组(P0.05)。失神经腓肠肌中Murf1,NF-κBmRNA和蛋白的表达与肌湿质量呈负相关(r=-0.795,P0.01;r=-0.834,P0.01),提示被动运动可能通过降低Murf1和NF-κB的表达发挥肌萎缩防治作用。  相似文献   

10.
目的 研究等渗高Ca2+环境对去神经主动脉平滑肌膜电流的影响,以及不同前负荷状态和Ca2+通道阻滞剂干预下去神经主动脉平滑肌的肌源性自主舒缩变化.方法 平滑肌标本取自昆明小鼠主动脉平滑肌层.标本在松弛状态下被两端固定并浸润于任氏液中,待稳定后于显微镜下将玻璃微电极吸附于平滑肌肌膜并高阻封接,观察生理渗透压环境下的膜电流状态.将任氏液中Ca2+浓度由0.9 mol/L提高至1.2 mol/L,观察渗透压改变后的即刻膜电流变化.增加标本前负荷至1 g,观察前负荷增加后标本在同等渗透压环境下膜电位的改变,并记录此时的标本自主舒缩曲线.结果 平滑肌标本处于松弛状态时,在等渗环境下将Ca2+浓度由0.9 mol/L提高至1.2 mol/L后,膜电流改变幅度由(10.25±1.34)pA增至(24.91±3.27)pA,差异具有统计学意义(P<0.05);前负荷增加后标本在等渗高Ca2+及低Ca2+环境下的膜电流改变幅度较松弛状态时均有所增加(低Ca2+浓度时(15.33±4.33) pA比(10.25±1.34) pA,高Ca2+浓度时(33.31±7.25) pA比(24.91±3.27) pA),差异均具有统计学意义(均P<0.05).低Ca2+浓度为0.9 mol/L时,若仅增加前负荷,标本肌源性自主舒缩幅度可增加175%;而Ca2+浓度增至1.2 mol/L时,标本自主舒缩幅度可进一步增长40%.经Ca2+通道阻滞剂(质量浓度为0.5 g/L尼群地平)预处理后,高Ca2+环境下的膜电流及肌源性自主舒缩均明显减弱,结果表明膜电位及自主舒缩均由Ca2+主导.结论 细胞外Ca2+浓度的增加既提高了主动脉平滑肌细胞膜的兴奋性,又使平滑肌产生较明显的自主性舒缩,可在前负荷改变时有效地改善平滑肌组织顺应性.Ca2+通道阻滞剂抑制了Ca2+主导的跨膜电流,降低了肌源性自主舒缩,增加了平滑肌的僵直度,这可能会对改善弹性储器血管的功能产生负面影响.  相似文献   

11.
Renal dysplasia and asplenia in two sibs   总被引:2,自引:0,他引:2  
A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.  相似文献   

12.
Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc2 (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.  相似文献   

13.
About 1900, modern food selection and processing caused widespread epidemics of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a panhypovitaminosis B, i.e., a mixture of substrate beriberi and substrate pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse endemic disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for primates. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.  相似文献   

14.
There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.  相似文献   

15.
16.
Newton H 《Medical history》2011,55(2):153-182
Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.  相似文献   

17.
Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.  相似文献   

18.
HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.  相似文献   

19.
The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.  相似文献   

20.
Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.  相似文献   

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