CCR7和VEGF-C蛋白与乳腺癌预后之间的关系

目的:探讨趋化因子受体7(CCR7)及血管内皮生长因子C(VEGF-C)蛋白在乳腺癌组织中的表达水平,并分析二者与乳腺癌预后的关系。方法:采用免疫组织化学技术,联合检测CCR7和VEGF-C蛋白分别在乳腺癌组织及正常乳腺组织中的表达差异情况,并分析二者与乳腺癌各相关临床病理特征之间的关系。采用Kaplan-Meier法来评估CCR7及VEGF-C蛋白的异常表达与乳腺癌患者生存期之间的关系。结果:CCR7蛋白在乳腺癌组织(68%)中的阳性表达率高于正常乳腺组织(30%),差异有统计学显著性(P0.01);而VEGF-C蛋白在乳腺癌组织(71%)中的阳性表达率也明显高于正常乳腺组织(24%),差异也有统计学显著性(P0.01)。且在乳腺癌组织中,CCR7与VEGF-C蛋白的表达呈正相关关系(r=0.613,P0.01)。CCR7和VEGF-C蛋白的高表达均与淋巴结转移和TNM分期有关(P0.05),而与年龄、肿瘤大小、雌激素受体和孕激素受体均无关。CCR7及VEGFC蛋白阳性表达者的生存期低于阴性表达者,两组比较差异有统计学显著性(P0.05)。结论:CCR7与VEGF-C的异常高表达可能与乳腺癌预后关系密切,二者可作为判断乳腺癌预后不良的重要指标之一。     

Syk与VEGF-C在乳腺癌中的表达及临床意义

目的:检测Syk与VEGF-C在乳腺癌组织中的表达情况,探讨它们与乳腺癌病理、临床特征间的关系.方法:应用免疫组化Elvsion法检测64例乳腺癌患者手术切除的癌组织和癌周正常组织中Syk和VEGF-C的表达情况.结果:Syk在正常组织中表达的阳性率为90%,在乳腺癌组织中阳性表达率为59.37%;VEGF-C在正常组织中阳性表达率为0.0%,在乳腺癌组织中的阳性表达率为76.56%;二者比较差异均有统计学意义(P＜0.05).Syk与VEGF-C表达水平均与乳腺癌病理分级、临床分期、淋巴结转移有关(P＜0.05).结论:联合检测乳腺癌中Syk和VEGF-C表达水平,对乳腺癌的早期发现及预后判断有一定参考价值.     

乳腺癌中肽转运蛋白1的表达及临床病理意义

目的探讨肽转运蛋白1(peptide transporter 1, PEPT1)在乳腺癌中的表达及临床病理意义。方法利用TIMER 2.0数据库分析PEPT1在乳腺癌不同分子亚型和癌旁正常组织中的表达;通过Kaplan-Meier Plotter数据库分析其与乳腺癌预后的相关性。收集80例乳腺癌及40例癌旁正常组织蜡块及患者临床信息,采用免疫组化MaxVision法检测PEPT1的表达,分析其与临床病理特征及患者无进展生存期(progression free survival, PFS)的相关性。结果 TIMER 2.0数据库分析显示,PEPT1在癌旁正常组织和乳腺癌不同亚型的表达,差异有显著性(P0.001)。Kaplan-Meier Plotter数据库分析显示,Luminal A、Luminal B型及三阴型乳腺癌(triple negative breast cancer, TNBC)中PEPT1高表达,其20年无复发生存期(relapse-free survival, RFS)明显比低表达者长(P0.005)。免疫组化结果显示,PEPT1高表达与乳腺癌的淋巴结转移、远处转移呈负相关(P均0.05);TNBC中PEPT1高表达者(65.7%)明显高于非三阴型乳腺癌者(22.2%),且PEPT1高表达与TNBC患者术后化疗3年PFS呈正相关(P0.05)。结论 PEPT1在乳腺癌不同分子亚型中表达具有明显差异,在TNBC中的表达明显高于非三阴型乳腺癌,且与TNBC患者化疗预后关系密切,有望成为预测TNBC患者疗效的生物学指标。     

人乳腺癌组织中VEGF-C和iNOS的表达及意义

目的研究人乳腺癌组织中血管内皮生长因子-C(vascular endothelial growth factor-C,VEGF-C)和诱生型一氧化氮合酶(inducible nitiric oxide synthase,iNOS)的表达并探讨两者的相关性。方法采用免疫组织化学SABC法检测50例乳腺癌组织和癌旁正常乳腺组织中VEGF-C和iNOS的表达,并分析其相互关系。结果 VEGF-C和iNOS在乳腺癌组织中均呈强阳性表达,而在癌旁正常组织则不表达。VEGF-C的表达与患者年龄、肿瘤大小、分化程度及临床分期无关(P>0.05),而与淋巴结转移密切相关(P<0.05)。iNOS的表达与患者年龄及肿瘤大小无关(P>0.05),而与分化程度、临床分期及淋巴结转移密切相关(P<0.05)。VEGF-C和iNOS的表达呈正相关(γ=0.43,P<0.05)。结论 VEGF-C和iNOS蛋白在乳腺癌的发生中具有协同作用,两者可能共同参与肿瘤淋巴管的生成。     

喉鳞状细胞癌中BRAP和VEGF-C的表达及其与淋巴管生成的关系

目的探讨BRAP和VEGF-C在喉鳞状细胞癌(laryngeal squamous cell carcinoma, LSCC)组织中的表达及其与组织内淋巴管生成及淋巴结转移的关系。方法采用免疫组化PV 6000法检测84例LSCC组织及15例癌旁组织中BRAP、VEGF-C的表达,并用D2-40免疫组化染色标记检测微淋巴管生成情况。分析BRAP、VEGF-C蛋白表达与淋巴管生成及淋巴结转移的关系。结果 LSCC中BRAP、VEGF-C的高表达率分别为65.5%和53.6%,均高于癌旁组织(P0.05)。BRAP、VEGF-C在淋巴结转移组的表达均高于无淋巴结转移组(P0.05),两者的表达有相关性(P0.01)。淋巴结转移组的微淋巴管密度(micro-lymphatic vessel density, MLVD)高于无淋巴结转移组(P0.01),BRAP、VEGF-C高表达组的MLVD值比其低表达组均增高(P0.01)。结论 BRAP和VEGF-C在LSCC中呈高表达,BRAP可能通过上调VEGF-C促进肿瘤淋巴管的生成及淋巴结转移。     

MMP-2、MMP-14及VEGF-C在结肠癌组织中的表达及其临床意义

分析基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-14(MMP-14)及血管内皮生长因子-C(VEGF-C)在结肠癌中的表达及其与肿瘤临床特征的关系,探讨三者在结肠癌发生发展中的作用及临床意义。采用免疫组织化学方法检测30例结肠癌患者的癌组织及对应癌旁正常结肠组织中MMP-2、MMP-14及VEGF-C的表达情况,分析三者的表达水平与患者性别、年龄、组织学分级、Dukes分期、肿瘤大小、淋巴结转移等临床病理参数之间的相关性。结果显示:1 30例结肠癌组织中MMP-2、MMP-14及VEGF-C的阳性表达率分别为73.3%、80%和66.7%,而在癌旁正常结肠组织中的阳性表达率分别为10%、13.3%和16.7%,两组比较差异均有统计学意义(P0.05)。2 MMP-2、MMP-14及VEGF-C的表达水平与肿瘤大小、Dukes分期和淋巴结转移有关(P0.05),而与患者性别、年龄及组织学分级无明显相关性(P0.05)。3MMP-2、MMP-14及VEGF-C三者两两间表达均相关(P0.05)。4 30例结肠患者的癌组织中有16例共同高表达MMP-2、MMP-14及VEGF-C,与Dukes分期、病理分级和淋巴结转移有关(P0.05)。     

乳腺癌中INHBA表达及与临床预后的关系

目的检测INHBA(inhibin-βA)在乳腺癌及癌旁乳腺组织中的表达,探讨其与乳腺癌临床病理特征的关系及对乳腺癌患者预后的意义。方法应用免疫组化法检测85例乳腺浸润性导管癌及35例癌旁乳腺组织中INHBA的表达。结果INHBA在乳腺癌和癌旁组织中的表达差异有统计学意义(P0.05)。INHBA高表达和肿瘤较低的分化程度、淋巴结转移及较高的Ki-67增殖指数具有相关性(P0.05)。INHBA高表达乳腺癌患者的生存期明显短于低表达组(P0.05)。多因素Cox比例风险回归模型分析显示,INHBA表达可以作为判断乳腺癌患者的独立危险因素(P0.05)。结论INHBA表达与肿瘤分化程度、淋巴结转移及Ki-67增殖指数密切相关,可能参与乳腺癌的发生发展,可以作为乳腺癌患者预后的判断指标。     

NF-κBp65、VEGF-C及受体VEGFR-3在乳腺癌组织中的表达

目的检测乳腺癌组织内NF-κBp65、VEGF-C及受体VEGFR-3的表达水平,并观察它们与临床病理特征的关系,为乳腺癌的早期诊断、治疗提供依据。方法采用免疫组化染色法检测50例乳腺癌组织及10癌旁组织内NF-κBp65、VEGF-C及受体VEGFR-3的表达,并分析与临床病理因素的关系。结果乳腺癌组织内NF-κBp65蛋白表达的阳性率为76.0%,明显高于癌旁对照组织30.0%,二者相比差异显著(P<0.05);乳腺癌组织内VEGF-C蛋白表达的阳性率为84.0%,明显高于癌旁对照组织20.0%,二者相比差异显著(P<0.05);乳腺癌组织内VEGFR-3蛋白表达的阳性率为88.0%,明显高于癌旁对照组VEGFR-3阳性表达率20.0%,两者相比差异显著(P<0.05);乳腺癌组织内NF-κBp65、VEGF-C及受体VEGFR-3三者的表达存在显著相关性(P<0.05),均与肿瘤淋巴转移密切相关(P<0.05),而与病人年龄、肿瘤大小无关(P>0.05)。结论乳腺癌中NF-κBp65的表达可能上调VEGF-C的表达,进而导致肿瘤周围淋巴管增生、扩张,促进肿瘤细胞向区域淋巴结转移。     

乳腺癌中Syk、VEGF-C表达与淋巴结转移的关系

目的研究乳腺癌组织中Syk、VEGF-C的表达与淋巴结转移的关系。方法分别采用免疫组织化学EnVision两步法及SP法检测55例乳腺癌组织中Syk、NFκB(p65)及VEGF-C的表达情况。结果55例乳腺癌组织中,Syk、VEGF-C及p65阳性率分别为50.9%,56.4%,81.8%。Syk在淋巴结转移组的表达低于无淋巴结转移组(P0.05);VEGF-C在淋巴结转移组的表达高于无淋巴结转移组(P0.05);p65在两组之间的表达差异无显著性(P0.75),p65胞核移位率在淋巴结转移组高于无淋巴结转移组(P0.025)。随着Syk表达增强VEGF-C的表达减弱,二者呈负相关(r=-0.620,P=0.000);p65胞核移位与Syk的表达强度降低有关(r=0.448,P=0.002),而与VEGF-C的表达强度增高有关(r=0.310,P=0.036)。结论乳腺癌中,Syk可能通过抑制NFκB的活性而下调VEGF-C的表达,从而抑制乳腺癌的淋巴结转移。     

三阴型乳腺癌中CD151的表达及意义

目的观察CD151在三阴型乳腺癌及非特殊型浸润性乳腺癌中的表达及与乳腺癌临床病理特征的关系。方法采用免疫组化EnVision两步法检测CD151在三阴型乳腺癌及非特殊型浸润性乳腺癌中的表达,运用统计学方法分析CD151表达与乳腺癌临床病理特征、无瘤生存期和预后的关系。结果在三阴型乳腺癌中,CD151表达与淋巴结转移和组织学分级相关(P0.05),CD151表达随着组织学分级的增加而升高,与患者年龄(P=0.081)和肿瘤大小(P=0.170)无明显相关性(P均0.05);三阴型乳腺癌患者肿瘤直径与腋窝淋巴结转移具有相关性(P0.05),CD151高表达患者的腋窝淋巴结转移率较高,无瘤生存期较短。结论 CD151在三阴型乳腺癌患者中高表达,并与淋巴结转移及组织学分级具有相关性,检测CD151有望成为评估三阴型乳腺癌患者预后的重要指标,为临床治疗和研究提供靶标。     

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,