SDF-1/CXCR4在骨髓增生异常综合征患者中的生物学作用

本研究主要探讨骨髓增生异常综合征(MDS)及白血病患者中基质细胞衍生因子-1(SDF-1)在细胞凋亡、迁移和黏附中的作用及相关的信号转导。选取37例初发MDS患者〔低危组(IPSS≤1.0)22例,高危组(IPSS≥1.5)15例〕、10例初发白血病患者及14例良性贫血患者(作为对照组),通过流式细胞术检测骨髓CD34+细胞表面CXCR4的表达水平及CD34+细胞的凋亡情况。选取4例低危MDS患者和5例高危MDS患者,通过微孔细胞迁移实验检测SDF-1对细胞的趋化作用。通过CCK-8法检测SDF-1对细胞之间黏附能力的影响。结果表明,低危MDS组骨髓内CD34+细胞的凋亡率明显高于高危MDS组(21.33%vs 7.27%,p<0.001),同样低危MDS组骨髓内CD34+细胞的凋亡率明显高于白血病组(21.33%vs 7.53%,p<0.001),未发现CD34+细胞的凋亡率与患者年龄性别有相关性。SDF-1能够促进高表达CXCR4患者的细胞黏附于基质细胞并能诱导该细胞的迁移,诱导细胞形态发生极化,上述作用可以被G蛋白抑制剂pertussis toxin、PI3K抑制剂wortmannin及CXCR4拮抗剂AMD3100明显抑制;而对低表达CXCR4的患者细胞则无上述抑制作用。结论:SDF-1/CXCR4通过PI3K信号通路提高细胞的迁移及黏附能力,发挥抗凋亡作用,上述作用可以被PI3K途径抑制剂和G蛋白抑制剂所阻断。     

p57kip2在初发MDS患者的表达及与SDF-1/CXCR4信号的关系

本研究旨在探讨初发骨髓增生异常综合征(MDS)患者抑癌基因p57kip2的表达及其与SDF-1/CXCR4信号的关系在MDS发病中的作用。应用实时荧光定量PCR检测67例初发MDS患者骨髓单个核细胞中p57kip2及CXCR4的表达,流式细胞术检测MDS患者骨髓CD34+细胞百分比,并选择18例正常人骨髓作为对照。在体外实验中探讨SDF-1/CXCR4信号对p57kip2表达的影响,比较其作用在正常及MDS患者中的差异。结果表明,MDS患者p57kip2表达均显著低于正常对照组(P<0.001),且与骨髓CD34+细胞百分比呈负相关(r=-0.458,P<0.001),染色体核型异常MDS患者p57kip2表达低于正常核型者(P=0.045);CXCR4的表达在MDS患者及对照组间无统计学差异,但与p57kip2表达呈正相关(r=0.652,P<0.001)。正常人中,SDF-1剂量依赖性地促进骨髓单个核细胞中p57kip2的表达,该作用能被AMD3100阻断;而在MDS患者BMMNC中,SDF-1不能诱导p57kip2表达增加。结论:抑癌基因p57kip2在初发MDS患者中低表达,可能与MDS发病相关。     

骨髓中CDKN1C的表达在骨髓增生异常综合征和继发性急性髓系白血病患者中检测的临床意义

目的探讨骨髓中蛋白细胞周期激酶抑制剂1C(CDKN1C)的表达在骨髓增生异常综合征(MDS)和继发性急性髓系白血病(AML)患者中检测的临床意义。方法选取125例MDS/AML患者作为研究对象,同时选取20例健康人群作为健康对照组,分析MDS/AML患者骨髓CD34+细胞中CDKN1C mRNA和蛋白表达水平,比较不同CDKN1C的表达水平MDS患者生存率,采用Cox回归分析MDS和AML患者生存率影响因素,并分析治疗方法对不同CDKN1C的表达水平MDS患者生存率的影响。结果 MDS/AML患者骨髓CD34+细胞中CDKN1C mRNA和蛋白表达水平显著高于健康对照组(t=5.324,7.326,P=0.002,0.000),且与BM计数呈正相关(r=2.014,P=0.004);CDKN1C高表达水平组患者的生存率显著低于CDKN1C低表达水平组和CDKN1C中表达水平组(P0.05);Cox回归分析结果显示高龄、高BM计数、细胞遗传学风险差以及CDKN1C阳性显著影响MDS/AML患者生存率(95%CI=1.10～1.32,1.92～4.40,1.18～2.67,1.03～2.32,P=0.034～0.000);MDS/AML化疗的CDKN1C阳性表达组患者生存率显著低于CDKN1C阴性表达组患者(t=5.314,P=0.002)。结论 MDS/AML患者骨髓中CDKN1C的表达显著增高,CDKN1C高表达显著影响化疗MDS/AML患者的生存率。     

骨髓增生异常综合征患者骨髓CD34+细胞 Fas,FasL及Bcl-2的表达和凋亡

为了观察骨髓增生异常综合征 (MDS)患者骨髓CD34+ 细胞Fas ,FasL和Bcl 2的表达和凋亡情况并探讨这些抗原的表达和细胞凋亡的关系。采用流式细胞术测定了 2 6例MDS和 10例急性髓系白血病 (AML)患者及 6例非血液病患者 (对照 )骨髓CD34+ 细胞的Fas,FasL和Bcl 2表达率和细胞凋亡率。结果显示 ,各型MDS患者CD34+ 细胞Fas和FasL表达率较对照组明显增加 (P <0 .0 1) ,Bcl 2的表达率除难治性贫血 /环形铁粒幼细胞性难治性贫血 (RA/RAS)与对照组无显著差异 (P >0 .0 5 )外 ,难治性贫血伴有原始细胞增多 (RAEB)和转变中的难治性贫血伴原始细胞增多 (RAEB t)患者均明显高于对照组 (P <0 .0 1) ;各型MDS间CD34+ 细胞Fas的表达率相近 ,而Bcl 2的表达率却存在非常显著性差异 ,即RA/RAS 相似文献   

骨髓增生异常综合征中基质细胞衍生因子1与血管新生及细胞凋亡的相关性研究

本研究探讨骨髓增生异常综合征(MDS)中骨髓基质细胞衍生因子-1(stromal cell-derived factor-1,SDF-1)的表达,及其与骨髓CD34+细胞的凋亡和骨髓血管新生的关系。搜集40例MDS病例,根据IPSS积分分为低危和高危2组,采集患者的骨髓穿刺物和活检标本。检测骨髓血浆中SDF-1的含量,骨髓CD34+细胞的凋亡率,骨髓活检标本的微血管密度(MVD)。结果显示:SDF-1α在低危组和高危组的表达量分别为(2313±417)pg/ml,(1241±501)pg/ml,前者显著高于后者(p<0.05);且2组的表达率均显著高于健康正常者(710±153)pg/ml(p<0.05);Annexin-Ⅴ/PI双染色显示,低危MDS患者CD34+细胞的凋亡率为(54.75±14.15)%,显著高于对照组的(18.51±8.66)%和高危组的(23.96±12.20)%(p<0.05),后两者相比差异无显著性(p>0.05);相关分析显示:低危组中骨髓SDF-1含量与CD34+细胞凋亡率呈正相关(p<0.05);在高危组中骨髓SDF-1含量与MVD呈现正相关(p<0.05)。结论:骨髓SDF-1含量、CD34+细胞凋亡和MVD在MDS中存在显著异常,在不同风险度的病例中也有明显的不同,且SDF-1水平与骨髓细胞的凋亡和血管新生具有相关性。     

Shh信号通路在骨髓增生异常综合征和转白血病患者骨髓CD34~+细胞中的表达及临床意义

目的:研究Shh信号通路相关基因Shh、Ptch1、Smo和Gli1在骨髓增生异常综合征(MDS)和MDS转白血病(AML-MRC)患者骨髓CD34~+细胞中的表达及其对预后的影响。方法:对53例MDS和30例AML-MRC患者采用流式细胞术检测骨髓CD34~+细胞数,磁珠分选CD34~+细胞,采用荧光实时定量PCR法检测CD34~+细胞上Shh、Ptch1、Smo和Gli1基因的表达,比较4种基因在MDS和AML-MRC患者中的表达及对预后的影响,并以25例缺铁性贫血患者作为对照。结果:Shh、Smo和Gli1在MDS组和AML-MRC组患者中的表达水平均显著高于对照组(P0.05),且表达水平随疾病进展呈递增趋势(P 0.05); Ptch1表达在3组间差异无统计学意义(P 0.05)。与相对低危组比较,Smo和Gli1在相对高危组和AML-MRC组中的表达水平均明显增高(P 0.05)。MDS组和AMLMRC组患者中位生存时间分别为12(7.5,16.5)和6(3.0,9.0)个月(P=0.000)。生存分析显示,MDS和AMLMRC组中Smo和Gli1高表达患者的中位生存时间明显短于低表达患者(P 0.05)。结论:MDS肿瘤干细胞中存在Shh信号通路的活化,其参与了MDS疾病进展并影响患者预后。     

再生障碍性贫血和骨髓增生异常综合征患者骨髓CD34^＋细胞及其G-CSFR、GM-CSFR的表达和意义

本研究探讨再生障碍性贫血（AA）和骨髓增生异常综合征（MDS）患者骨髓CD34^＋细胞表面粒细胞集落刺激因子受体（G—CSFR）和粒-巨噬细胞集落刺激因子受体（GM—CSFR）的表达。分离27例AA患者、45例MDS患者和20例正常对照者的骨髓单个核细胞（BMMNC），用流式细胞术观察BMMNC中CD34^＋细胞比率和CD34^＋细胞表面G—CSFR、GM—CSFR表达率与外周血中性粒细胞数的关系。结果发现，CD34^＋细胞比率在AA组显著低于对照组，MDS组显著高于对照组，AA组显著低于MDS组，骨髓增生异常综合征-难治性贫血伴原始细胞增多（MDS—RAEB）组显著高于骨髓增生异常综合征-难治性贫血（MDS—RA）组或对照组，MDSr-RA组显著高于AA组（P均〈0．05）；MDS—RA组与对照组无显著性差异（P〉0．05）。各组BMMNC中CD34^＋细胞表面G—CSFR表达率在AA组、对照组、MDS组、MDS—RA组及MDS—RAEB组均无显著性差异（P均〉0．05）。各组BMMNC中CD34^＋细胞表面的GM—CSFR的表达率在AA组与对照组无显著性差异（P〉0．05），MDS组显著高于对照组或AA组（P均〈0．05），MDS—RA组与MDS—RAEB组无显著性差异（P均〉0．05）。SAA患者BMMNC中CD34^＋细胞的比率显著低于CAA患者（P〈0．05），AA患者CD34^＋细胞表面的G—CSFR和GM—CSFR表达率与诊断时外周血中性粒细胞计数均无相关性（r=0．058和r=0．044）；MDS患者BMMNC中的CD34^＋细胞的比率与诊断时外周血中性粒细胞数没有相关性（r=-0．335），其CD34^＋细胞表面的G—CSFR和GM—CSFR表达率与诊断时外周血中性粒细胞数亦无相关性（r=0．064和r=0．051）。结论：AA及MDS患者骨髓CD34^＋细胞占BMMNC的比率及其表面G—CSFR、GM—CSFR的表达率的测定有助于二者的诊断和鉴别诊断。     

WT1基因在儿童骨髓增生异常综合征表达的临床意义

目的 探讨儿童骨髓增生异常综合征(MDS)中WT1基因表达规律及其在鉴别MDS与再生障碍性贫血(AA)中的作用.方法 采集2008年9月至2011年12月收治的36例儿童MDS、49例儿童AA及40例儿童急性髓系白血病(AML)患者骨髓细胞,采用实时荧光定量PCR法分析其WT1表达规律.结果 ①重型AA组患儿WT1基因表达阳性率为0,慢性AA组为14.3%,MDS-难治性血细胞减少(RC)组为58.6%,难治性贫血伴原始细胞增多(RAEB)组为100%,AML组为97.5%.MDS-RC组WT1基因表达阳性率高于重型AA组和慢性AA组(P值分别为0.000和0.001).重型AA、慢性AA、MDS-RC、MDS-RAEB、AML组WT1基因相对表达水平平均值分别为0.041%、0.357%、7.037%、12.680%、24.210%.②低增生MDS组WT1基因表达阳性率为66.7%,高于慢性AA组(P=0.001)和重型AA组(P=0.000);低增生MDS患儿WT1相对表达水平为(3.022±5.040)%,高于慢性AA组[(0.357±0.479)%,P=0.002]及重型AA组[(0.041±0.047)%,P=0.000].结论 MDS患儿WT1基因表达水平较AA为高;WT1基因表达水平随着MDS疾病的进展而增高; WT1水平可用于鉴别儿童低增生MDS与AA.     

骨髓增生异常综合征患者外周血NK细胞亚型和功能分子变化的研究

目的:分析骨髓增生异常综合征(MDS)患者外周血自然杀伤(NK)细胞亚型和功能分子的变化及其与骨髓恶性克隆的相关性,并对不同危险度进行分析,探讨NK细胞在MDS发病机制中的作用。方法:用流式细胞术检测2015-2016年间收治的35例MDS患者外周血NK细胞数量及其表面功能分子NKp30、NKp46、NKG2A的表达,并与34名正常对照比较;分析上述变化与骨髓原始细胞百分比、外周血中性粒细胞绝对值、血红蛋白量(Hb)相关性。结果:MDS组NK细胞、CD56~(dim)NK细胞的相对数量和绝对值均显著低于对照组(P0.05),而CD56~(bright) NK细胞数量高于对照组。分析NK细胞的亚型构成发现,MDS组NK细胞杀伤性亚型CD56~(dim) NK比例降低,与对照组相比差异有统计学意义。MDS组NK细胞表面活化性受体NKp30和NKp46的表达明显低于对照组(P0.05)。在MDS组中,高危组NK细胞、CD56~(dim)NK细胞明显低于低危组(P0.05)。MDS患者NK细胞数量与骨髓原始细胞比例(CD34~+%)呈负相关(r=-0.53),与中性粒细胞数(ANC)和血红蛋白含量(Hb)呈正相关(r=0.52);骨髓原始细胞数(CD34~+%)与NKp46的表达与呈负相关(r=-0.584),与NKG2A的表达呈正相关(r=0.523)。结论:MDS患者外周血NK细胞数量不足,亚群失调和功能下降可能导致疾病进展。     

流式细胞仪和免疫组织化学法测定骨髓增生异常综合征、急性髓系白血病患者和正常人骨髓中的CD34阳性细胞的比较

急性髓系白血病(AML)患者骨髓白血病细胞上CD34高表达预示着短生存期和/或对大剂量化疗疗效差,同样骨髓增生异常综合征(MDS)患者骨髓及外周血中CD34阳性细胞增多与短生存期和转化为AML高危险性相关。作者使用流式细胞仪(FC)测定新鲜骨髓细胞悬液中CD34阳性细胞和免疫组织化学法(IH)测定石蜡包埋骨髓样本中CD34阳性细胞,并进行二种方法的比较。 受检患者分为三组:MDS组16例,其中难治性贫血3例,环状铁粒幼细胞性贫血5例,原始细胞过多性难治性贫血3例,转化中原始细胞过多性难治性贫血2例及慢性粒单核细胞白血病3例;AML组12例(M1     

Migraine and genetic and acquired vasculopathies

It is remarkable that migraine is a prominent part of the phenotype of several genetic vasculopathies, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), retinal vasculopathy with cerebral leukodystrophy (RVCL) and hereditary infantile hemiparessis, retinal arteriolar tortuosity and leukoencephalopahty (HIHRATL). The mechanisms by which these genetic vasculopathies give rise to migraine are still unclear. Common genetic susceptibility, increased susceptibility to cortical spreading depression (CSD) and vascular endothelial dysfunction are among the possible explanations. The relation between migraine and acquired vasculopathies such as ischaemic stroke and coronary heart disease has long been established, further supporting a role of the (cerebral) blood vessels in migraine. This review focuses on genetic and acquired vasculopathies associated with migraine. We speculate how genetic and acquired vascular mechanisms might be involved in migraine.     

Fibrinogen and fibrin structure and functions

Fibrinogen molecules are comprised of two sets of disulfide-bridged Aalpha-, Bbeta-, and gamma-chains. Each molecule contains two outer D domains connected to a central E domain by a coiled-coil segment. Fibrin is formed after thrombin cleavage of fibrinopeptide A (FPA) from fibrinogen Aalpha-chains, thus initiating fibrin polymerization. Double-stranded fibrils form through end-to-middle domain (D:E) associations, and concomitant lateral fibril associations and branching create a clot network. Fibrin assembly facilitates intermolecular antiparallel C-terminal alignment of gamma-chain pairs, which are then covalently 'cross-linked' by factor XIII ('plasma protransglutaminase') or XIIIa to form 'gamma-dimers'. In addition to its primary role of providing scaffolding for the intravascular thrombus and also accounting for important clot viscoelastic properties, fibrin(ogen) participates in other biologic functions involving unique binding sites, some of which become exposed as a consequence of fibrin formation. This review provides details about fibrinogen and fibrin structure, and correlates this information with biological functions that include: (i) suppression of plasma factor XIII-mediated cross-linking activity in blood by binding the factor XIII A2B2 complex. (ii) Non-substrate thrombin binding to fibrin, termed antithrombin I (AT-I), which down-regulates thrombin generation in clotting blood. (iii) Tissue-type plasminogen activator (tPA)-stimulated plasminogen activation by fibrin that results from formation of a ternary tPA-plasminogen-fibrin complex. Binding of inhibitors such as alpha2-antiplasmin, plasminogen activator inhibitor-2, lipoprotein(a), or histidine-rich glycoprotein, impairs plasminogen activation. (iv) Enhanced interactions with the extracellular matrix by binding of fibronectin to fibrin(ogen). (v) Molecular and cellular interactions of fibrin beta15-42. This sequence binds to heparin and mediates platelet and endothelial cell spreading, fibroblast proliferation, and capillary tube formation. Interactions between beta15-42 and vascular endothelial (VE)-cadherin, an endothelial cell receptor, also promote capillary tube formation and angiogenesis. These activities are enhanced by binding of growth factors like fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), and cytokines like interleukin (IL)-1. (vi) Fibrinogen binding to the platelet alpha(IIb)beta3 receptor, which is important for incorporating platelets into a developing thrombus. (vii) Leukocyte binding to fibrin(ogen) via integrin alpha(M)beta2 (Mac-1), which is a high affinity receptor on stimulated monocytes and neutrophils.     

Telemedicine and teleradiology technologies and applications

Summary. Telemedicine and teleradiology hold the key for improving future health care delivery. In this paper we first review current communication and computer technologies used in telemedicine and teleradiology. Five examples in teleradiology applications are given including hospital-integrated picture archiving and communication systems, tele-neuro-imaging, telemammography, university consortium teleradiology service, and teleradiology for second opinion. Parameters important to teleradiology applications like costs, image quality, system reliability, and turn around time are considered. Data security is discussed, including patient confidentiality and image authenticity-which will be a major issue in future teleradiology applications.     

创伤高血糖与感染和MODS早期诊断和干预

本文详细介绍了创伤后血糖应激适度理论,以及高血糖与感染和多器官功能不全综合征的关系;提出涉及胰岛B细胞功能不全的MODS实验诊断新方案和极化液个体化干预新措施,可早期发现创伤MODS、降低感染率及MODS发生率和病死率。     

腹膜后纤维化与肾积水发生关系的临床研究

目的：探讨腹膜后纤维化（RPF）导致肾积水的原因及诊治经验。方法：回顾分析2004年1月—2010年12月24例腹膜后纤维化致肾积水患者的诊治资料。结果：（1）RPF患者常见首发症状为腰背痛或腹痛（69.2%）;（2）红细胞沉降率（ESR）增快和血清IgG4升高最常见。超声检查仅提示上尿路积水。RPF的静脉肾盂造影（IVP）和CT尿路成像（CTU）表现具有特征性。IVP肾盂输尿管显影不良时,CTU能较清晰的显示上尿路影像。CT扫描发现腹膜后软组织肿块9例（37.5%）,优于超声检查;（3）输尿管松解和腹腔化手术治疗22例;行肾切除术1例;行输尿管置双J管术1例。最终确诊为继发性RPF8例,其中4例为术前诊断,3例为术中腹膜后软组织肿块冷冻活检证实,1例为术后病理证实;（4）特发性RPF手术后肾积水均获长期缓解,而继发性RPF的预后取决于原发疾病及其治疗方案。结论：影像学检查是诊断RPF的重要手段,CTU优于超声检查和IVP。输尿管松解和腹腔化手术可以使特发性RPF输尿管梗阻得到长期的缓解,术中对肿块进行冷冻活检有助于鉴别特发性和继发性RPF,及时调整治疗方案。     

探讨儿童慢性顽固性咳嗽与支原体感染的关系及临床治疗观察

目的探讨儿童慢性顽固性咳嗽与肺炎支原体（MP）感染的关系及临床疗效观察。方法采用回顾性研究方法对于现将2005年3月至2008年3月在我院的55例确诊慢性顽固性咳嗽患儿,主要表现为肺炎支原体感染为临床特点进行分析,并进一步临床治疗研究。结果①临床特点：在55例确诊慢性咳嗽的患儿中,以慢性顽固性咳嗽为主要症状。58％（32／55）的病例无肺部体征;②外周血：85％（47／55）的病例外周血变化不大,WBC（4—10）×10 9／L之间,嗜酸性粒细胞增多;③特别检查：47．27％（26／55）肺炎支原体IgM（MP—IgM）抗体阳性,83．64％（46／55）PeR技术检测肺炎支原体特异性DNA;④X光报告为多种形式。结论肺炎支原体（MP）感染是引起儿童慢性顽固性咳嗽的病因之一,对儿童慢性咳嗽,特别是顽固性咳嗽的诊治中应更加重视。     

Acetaminophen and acetylcysteine dose and duration: Past,present and future

Abstract

Acetylcysteine has been utilized successfully in the treatment of acetaminophen overdose since the 1970s. Although prospective trials as to efficacy and safety of acetylcysteine were conducted, there were no randomized controlled trials. This commentary addresses the reasons for this, and the background to choice of dose of acetylcysteine utilized in the oral and IV dosing regimens. Nomograms to predict possible hepatotoxicity based upon time of ingestion of acetaminophen were developed from a relatively arbitrary definition of toxicity as an aspartate aminotransferase/alanine aminotransferase (ALT/AST) greater than 1000 IU/L. While these have proved generally useful, patients still continue to develop hepatic damage after acetaminophen overdose, particularly if they present late after ingestion. The optimum management of these patients remains unclear, and one area of uncertainty is the dose and duration of acetylcysteine in various circumstances. This article discusses the issues that need to be elucidated to better target changes in acetylcysteine dose. The potential for measurements of other markers to improve treatment selection is the subject of further research.     

Physician and Nurse Practitioner Teamwork and Job Satisfaction: Gender and Profession

Designing interprofessional primary care teams composed of physicians and nurse practitioners (NPs) is a national priority. We assessed how profession and gender affect teamwork and job satisfaction among primary care physicians and NPs by using survey data from 186 physicians and 398 NPs practicing in New York State. Our regression models show profession (NP vs physician) moderates the associations of gender with teamwork and job satisfaction. Among NPs, men had higher job satisfaction than women. Among physicians, women had higher job satisfaction than men. Our results can benefit interprofessional primary care teams to optimize their professional and gender mix.