粘液素与哮喘

粘液素分子是一种主要由杯状细胞分泌的大分子糖蛋白 ,其编码基因位于多条染色体上的不同区带 ,分泌产物广泛分布于气道、胃肠道及生殖道 ,主要担任保护和润滑气道 ,吸附吸入的分子、碎屑、衰老细胞及细胞产物的运输和清除功能。在病理条件下 ,多种因素可导致其分泌增高 ,使管腔堵塞 ,可诱发哮喘。粘液素高分泌的调节研究发现 ,刺激性气体、炎症介质、蛋白酶、活性氧、神经肽等多种因素导致粘液素基因表达增高 ,其表达调控涉及多个信号转导级联反应     

TRPV3与皮肤功能障碍的相关研究进展

瞬时感受器电位香草素受体亚家族3 (transient receptor potential vanilloid 3,TRPV3)是存在于细胞膜上的一类非选择性阳离子通道蛋白,其主要在人体皮肤角质细胞表达,在介导钙离子传递、影响表皮角质细胞增殖分化、参与炎症反应以及调节温度觉、痒觉和痛觉等多种生物过程中发挥重要作用.本文综述了TRPV3与遗传角化性皮肤病、皮肤瘙痒、皮肤炎症和疼痛的相关研究进展,为揭示TRPV3基因在皮肤功能障碍中的作用机制提供理论依据.     

CD44与CD62P在原发性肾小球肾炎患者中的表达及其及意义

细胞粘附分子是近几年来发现的一类来自不同基因的配体/受体分子,它们介导了细胞信息传递的关键步骤[1].粘附分子P选择素(CD62P)与细胞表面糖蛋白(CD44)均为粘附分子家族中的重要成员,CD44主要介导细胞与细胞、细胞与基质之间的特异性粘连,与肾小球肾炎时的白细胞浸润、细胞增殖及细胞外基质的增加有关[2].CD62P作为血小板粘附活化与释放反应最特异的标志物,在免疫识别、炎症反应和血栓形成过程中起重要作用.我们采用流式细胞术观察了90例原发性肾小球肾炎患者外周血单核细胞(PBMC)CD62P及CD44分子的表达特征,旨在探讨CD44及CD62P在肾脏疾病中的作用.     

CD44与CD62P在原发性肾小球肾炎患者中的表达及其意义

细胞粘附分子是近几年来发现的一类来自不同基因的配体/受体分子,它们介导了细胞信息传递的关键步骤[1].粘附分子P选择素(CD62P)与细胞表面糖蛋白(CD44)均为粘附分子家族中的重要成员,CD44主要介导细胞与细胞、细胞与基质之间的特异性粘连,与肾小球肾炎时的白细胞浸润、细胞增殖及细胞外基质的增加有关[2].CD62P作为血小板粘附活化与释放反应最特异的标志物,在免疫识别、炎症反应和血栓形成过程中起重要作用.我们采用流式细胞术观察了90例原发性肾小球肾炎患者外周血单核细胞(PBMC)CD62P及CD44分子的表达特征,旨在探讨CD44及CD62P在肾脏疾病中的作用.     

多西环素通过上调自噬调控脂多糖诱导的THP-1细胞炎症因子水平

目的:探讨细胞自噬对多西环素调控脂多糖(LPS)刺激巨噬细胞引发炎症反应的影响及其分子机制。方法:利用LPS刺激人单核/巨噬细胞系THP-1建立炎症反应细胞模型,用多西环素进行干预。通过测定细胞培养上清液中肿瘤坏死因子α(TNF-α)和白细胞介素8(IL-8)等细胞因子评估炎症水平;通过Western blot法检测LC3B、核因子κB(NF-κB)和磷酸化哺乳动物雷帕霉素靶蛋白(p-mTOR)等蛋白水平评估细胞自噬水平及对炎症细胞信号通路的影响。利用3-甲基腺嘌呤(3-MA)和雷帕霉素分别抑制和促进细胞自噬,研究自噬对多西环素调控LPS刺激THP-1细胞炎症因子水平的影响。结果:LPS刺激THP-1细胞诱导细胞因子TNF-α及IL-8快速释放,12 h左右达到峰值;多西环素有效地抑制了LPS诱导的细胞因子产生(P0.05)。多西环素增加了LPS诱导的THP-1细胞自噬水平,且多西环素本身是一种自噬诱导剂。LPS上调p-mTOR蛋白水平,而多西环素抑制p-mTOR的蛋白水平,提示多西环素通过mTOR依赖的途径而LPS通过非mTOR依赖的途径诱导自噬。进一步研究显示,联用LPS、雷帕霉素及多西环素抑制了NF-κB的蛋白水平,雷帕霉素增加了多西环素对细胞因子生成的抑制;反之,自噬抑制剂3-MA减弱了多西环素对NF-κB的抑制效应,同时减弱了多西环素对炎症因子生成的抑制效应。结论:自噬参与多西环素调控LPS刺激单核/巨噬细胞引起的炎症反应。     

脂氧素在神经系统疾病中的保护作用

脂氧素是花生四烯酸的脂氧酶代谢产物,是机体一类重要的内源性脂质抗炎介质,被称之为炎症反应的"刹车信号".炎症反应是存在于以脑损伤、神经变性疾病等为主的多种神经系统疾病中的重要病理过程.因此,关于脂氧素在相关神经系统疾病中保护性作用的研究近来备受关注.在诸多神经系统疾病中,脂氧素可以通过抑制胶质细胞的激活、降低炎症因子活性等发挥神经保护作用.本文就近年来关于脂氧素及其抗炎效应,以及脂氧素对中枢神经系统保护性作用等方面的研究作一综述.     

白细胞介素17在移植物抗宿主病中的作用

移植物抗宿主病(GVHD)是异基因造血干细胞移植后主要的并发症,是造成移植后非复发死亡的主要原因,限制了异基因造血干细胞移植广泛应用。白细胞介素17(IL-17)及其受体在感染、自身免疫性疾病以及肿瘤的发生发展中起着重要作用,但IL-17及其受体在GVHD的进程中的作用却仍无定论。IL-17在小鼠和移植患者的血清和GVHD损伤组织中均表达增多,募集中性粒细胞和T细胞等炎症细胞,介导炎症反应,从而损伤靶组织和器官。本文综述了GVHD、IL-17及其受体的一般特性及在GVHD中的作用。     

脂氧素A4及其在炎症反应和免疫调节中的研究进展

脂氧素(LXs)是近三十年发现的一类含有三羟四烯结构的花生四烯酸合成产物,其中,脂氧素A4 (LXA4)是LXs家族的一员,近期研究表明其可对多种炎症细胞的功能和炎症相关基因的表达具有广泛调节作用,被称为炎症的“刹车信号”.然而,最新研究显示LXA4还与多种免疫细胞、免疫调节介质之间存在密切联系,且在机体的免疫调节过程中发挥重要作用.     

Ghrelin基因多态性及临床意义

ghrelin是由28个氨基酸组成的肽类激素，为生长激素促分泌受体具生物活性的内源性配体,主要是由胃底内分泌细胞P/D1细胞产生。人的ghrelin基因定位于染色体3p26~p25,整个编码区长5199bp，含4个外显子3个内含子。现已发现ghrelin基因有多种突变类型，其中常见的突变类型主要有下述几种：Arg51Gln9 ，Leu72Met和Gln90Leu 。ghrelin基因多态性与肥胖、糖尿病、高血压、血脂异常等疾病的发生发展有关。     

全身炎症反应综合征中性白细胞基因表达谱的研究

目的:研究全身炎症反应综合征患者外周血中性白细胞和健康人外周血中性白细胞的基因差异表达。方法:应用基因芯片技术对4例SIRS患者外周血中性白细胞和6例正常人外周血中性细胞的mRNA进行检测。结果:在8400条基因中发现差异表达基因382条, 其中SIRS患者中性白细胞基因122条表达增加, 260条表达减少, 差异表达的基因主要是细胞内信号转导通路基因(35％), 细胞受体基因(22％), DNA结合、转录的各种因子基因(23％)以及细胞因子基因(11％)等。结论:SIRS患者体内存在抗炎和促炎两种不同介质作用, 中性白细胞在该环境中基因表达的改变与血液中多种刺激因素作用结果相一致。基因芯片技术可同时大通量研究基因的表达水平, 是一种可应用于检测炎症反应基因改变的新方法。     

Pain and Effusion and Quadriceps Activation and Strength

Context:

Quadriceps dysfunction is a common consequence of knee joint injury and disease, yet its causes remain elusive.

Objective:

To determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion affect the magnitude of quadriceps dysfunction.

Design:

Crossover study.

Setting:

University research laboratory.

Patients or Other Participants:

Fourteen (8 men, 6 women; age = 23.6 ± 4.8 years, height = 170.3 ± 9.16 cm, mass = 72.9 ± 11.84 kg) healthy volunteers.

Intervention(s):

All participants were tested under 4 randomized conditions: normal knee, effused knee, painful knee, and effused and painful knee.

Main Outcome Measure(s):

Quadriceps strength (Nm/kg) and activation (central activation ratio) were assessed after each condition was induced.

Results:

Quadriceps strength and activation were highest under the normal knee condition and differed from the 3 experimental knee conditions (P < .05). No differences were noted among the 3 experimental knee conditions for either variable (P > .05).

Conclusions:

Both pain and effusion led to quadriceps dysfunction, but the interaction of the 2 stimuli did not increase the magnitude of the strength or activation deficits. Therefore, pain and effusion can be considered equally potent in eliciting quadriceps inhibition. Given that pain and effusion accompany numerous knee conditions, the prevalence of quadriceps dysfunction is likely high.Key Words: arthrogenic muscle inhibition, central activation failure, voluntary activation, muscles

Key Points

• Knee pain and effusion resulted in arthrogenic muscle inhibition and weakness of the quadriceps.
• The simultaneous presence of pain and effusion did not increase the magnitude of quadriceps dysfunction.
• To reduce arthrogenic muscle inhibition and improve muscle strength, clinicians should employ interventions that target removing both pain and effusion.

Quadriceps weakness is a common consequence of traumatic knee joint injury^1,2 and chronic degenerative knee joint conditions.^3,4 Arthrogenic muscle inhibition (AMI), a neurologic decline in muscle activation, results in quadriceps weakness and hinders rehabilitation by preventing gains in strength.⁵ The inability to reverse AMI and restore muscle function can lead to decreased physical abilities,⁶ biomechanical deficits,⁷ and possibly reinjury.⁵ Furthermore, researchers^8,9 have suggested that quadriceps weakness resulting from AMI may place patients at risk for developing osteoarthritis in the knee. In light of the substantial influence of quadriceps AMI on these clinically relevant outcomes, we need to improve our understanding of the factors that contribute to this neurologic decline in muscle activity so efforts to target and reverse it can be implemented and gains in strength can be achieved more easily.Joint injury and disease are accompanied by numerous sequelae (ie, pain, swelling, tissue damage, inflammation), so ascertaining which one ultimately leads to neurologic muscle dysfunction is difficult. Whereas a joint effusion can result in AMI,^10–12 the effects of pain are less understood despite many clinicians attributing AMI to pain. Using techniques that introduce knee pain without accompanying injury may provide insights into the role of pain in eliciting AMI.The degree of knee joint damage may play a role in the quantity of AMI that manifests. Hurley et al^13,14 demonstrated that quadriceps AMI, measured using an interpolated-twitch technique, was greater in patients with extensive traumatic knee injury (eg, fractured tibial plateau, ruptured medial collateral ligament, and medial meniscectomy) than patients with isolated joint trauma (ie, isolated anterior cruciate ligament [ACL] rupture). Similarly, patients with more knee joint symptoms (ie, greater number of symptoms and increased severity of symptoms) may present with greater magnitudes of quadriceps inhibition. Recently, investigators¹⁵ have suggested that patients with more pain display less quadriceps strength, supporting this tenet. Given that effusion and pain often present simultaneously with joint injuries and diseases, such as ACL injury and osteoarthritis, examining both the isolated and cumulative effects of these sequelae appears warranted to determine if they influence the magnitude of muscle inhibition.Experimental joint-effusion and pain models are safe and effective experimental methods that allow for the isolated examination of their effects on muscle function. The effusion model, whereby sterile saline is injected directly into the knee joint capsule,⁷ produces a clinically relevant magnitude of the joint effusion that may be present with traumatic injury. Effusion is thought to activate group II afferents responding to stretch or pressure,^16–18 which in turn may facilitate group Ib interneurons and result in quadriceps AMI.⁵ The pain model involves injecting hypertonic saline into the infrapatellar fat pad to produce anteromedial knee pain similar to that described in patients with patellofemoral pain syndrome.¹⁹ Pain is considered to initiate AMI through activation of group III and IV afferents that act as nocioceptors to signal damage or potential damage to joint structures.^16–18 The firing of these afferents then may lead to facilitation of group Ib interneurons, the flexion reflex, or the gamma loop, ultimately resulting in quadriceps inhibition.²⁰ Thus, these models allow us to create symptoms that are associated with knee injury and have the added benefit of providing a way to examine their effects in isolation.Therefore, the purpose of our study was to determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion would affect the magnitude of quadriceps dysfunction. We hypothesized that pain alone would result in quadriceps inhibition and that the magnitude of inhibition would be greater when effusion and pain were present simultaneously.     

即早基因c-fos与脑血管病及学习记忆

即早基因c-fos是广泛存在于原核细胞和真核细胞的高度保守基因.在正常情况下,c-fos基因参与细胞生长、分化、信息传递、学习和记忆等生理过程,而在病理情况下c-fos基因表达及调控变化与多种疾病的发生和发展有关.C-fos在中枢神经系统的某些部位可有基础水平的表达,但表达很低,当受到如脑缺血、脑出血、痫性发作、应激等刺激后,其在数十分钟内做出反应,在对外界刺激-转录耦联的信忠传递过程中起着核内第三信使的重要作用.     

自主创新学习与问题探究教学改革的探索与实践

<正>人体解剖学与组织学胚胎学是高职护理及助产专业的学生接触最早而又重要的医学基础核心课程。鉴于目前高职护理及助产专业的教学内容多,课时少等难题,教与学的矛盾日益突出。因此,如何在有限的时间内既保证教学体系的完整性,又能解决时间与内容冲突的矛盾,从而使医学生对所学内容真正达到"必须、够用",是授课教师面临的严峻挑战。同时,顺应医学终身教育发展的需求,提高医学生自主学习的能力,