乙酰肝素酶和VEGF在结肠癌组织中的表达及其与肿瘤侵袭及转移的关系

目的:探讨乙酰肝素酶(HPA)和血管内皮生长因子(VEGF)在结肠癌组织中的表达及其与肿瘤侵袭和转移的关系.方法:采用SP免疫组化法,检测60例结肠癌标本和60例癌旁正常组织中HPA和VEGF的表达.结果:结肠癌组HPA和VEGF的平均吸光值明显高于对照组(P<0.05);结肠癌组HPA和VEGF阳性表达率分别为78.3%和71.7%,显著高于对照组(15.0%,18.3%),相比较有统计学差异(P<0.05);有淋巴结转移组HPA和VEGF阳性表达率分别为97.1和94.3%,明显高于无转移组(37.1%,28.6%),相比较有差异(P<0.05).结论:HPA和VEGF在结肠癌组织中呈高表达,HPA和VEGF在结肠癌侵袭、转移的机制中起协同作用.HPA和VEGF可以作为预测结肠癌侵袭、转移的分子生物学指标.     

乳腺良恶性组织中MMP-26表达及其与MMP-9、VEGF和MVD的关系

目的 检测人乳腺良恶性组织中基质金属蛋白酶-26(matrix metalloproteinase-26,MMP-26)、基质金属蛋白酶-9(matrixmetalloproteinase-9,MMP-9)、血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达,计数微血管密度(micro vesseldensity,MVD),探讨4项指标与乳腺浸润性导管癌(infiltrating ductal carcinoma,IDC)临床病理指标的关系,分析MMP-26与MMP-9、VEGF表达的相关性及与MVD的关系.方法 采用免疫组化SP法,检测正常乳腺组织、普通型导管增生(usual ductalhyperplasia,UDH)、导管内原位癌(ductal carcinoma in situ,DCIS)和IDC组织中MMP-26、MMP-9、VEGF的表达并进行评分,以CD34标记肿瘤间质微血管,计数MVD.结果 (1)54例IDC中,MMP-26,MMP-9及VEGF表达的阳性率分别为62.96%、68.52%和75.93%;3种蛋白相关性分析显示:MMP-26与MMP-9表达呈正相关关系(F=0.32,P<0.05),MMP-26与VEGF表达未见相关性(F=0.23,P>0.05),MMP-9与VEGF表达呈正相关关系(F=0.44,P<0.01).(2)3种蛋白表达均与淋巴结转移密切相关(P<0.05),在其他各临床病理参数间差异未见显著性(P>0.05).(3)MMP-26阳性表达率随着MVD的增高而增高,但在高、低MVD组差异未见显著性(P>0.05),高MVD组MMP-9和VEGF阳性表达率明显高于低MVD组(P<0.05).结论 MMP-26在乳腺癌浸润、转移中发挥重要作用;MMP-26可能通过激活MMP-9参与肿瘤血管生成和促进肿瘤的侵袭和转移.     

血清中microRNA-365在结肠癌患者中的表达水平和临床价值

目的 研究血清中microRNA-365表达水平对结肠癌组织中血管生成和癌细胞转移的影响.方法 选择2017年1月至2018年12月我院收治的120例结肠癌患者作为观察组,选择同时期来我院治疗的120例结肠良性肿瘤患者作为对照组.收集并比较两组患者基本资料,RT-PCR法检测患者血清中microRNA-365表达水平,ELISA法检测血清中影响肿瘤血管生成的血管内皮生长因子VEGF、基质金属蛋白酶MMP-2、MMP-9.结果 两组患者的性别、年龄相比均差异无统计学意义,两组具有可比性;观察组microRNA-365水平明显低于对照组(P<0.05),VEGF、MMP-2、MMP-9水平均明显高于对照组(P<0.05);观察组microRNA-365水平在不同年龄、不同性别、不同肿瘤大小的患者之间差异无统计学意义,肿瘤T分期较高、临床分期较高、出现转移的患者microRNA-365水平明显降低(P<0.05);观察组淋巴转移患者的microRNA-365水平明显低于无淋巴转移患者(P<0.05),VEGF、MMP-2、MMP-9水平均明显高于无淋巴转移患者(P<0.05),出现淋巴转移及肝转移患者的microRNA-365水平明显低于淋巴转移患者(P<0.05),VEGF、MMP-2、MMP-9水平均明显高于淋巴转移患者(P<0.05);microRNA-365水平与VEGF、MMP-2、MMP-9呈负相关.结论 结肠癌患者血清中microRNA-365表达水平下降,在结肠癌的诊断及预后中值得进一步研究.     

未破裂颅内动脉瘤患者外周血清microRNA-126、microRNA-125b的表达及其意义

目的:探讨microRNA-126、microRNA-125b在未破裂颅内动脉瘤患者外周血清中的表达及其临床意义。方法:选取2015年9月～2017年12月于我院住院或体检的未破裂颅内动脉瘤患者120例作为动脉瘤组(ICA组),另选取正常健康人群63例作为对照组。采用RT-PCR技术检测两组患者外周血清中microRNA-126、microRNA-125b的表达水平,采用ELISA技术检测两组患者外周血清中血管内皮生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)的表达水平。统计分析microRNA-126、microRNA-125b表达水平与未破裂颅内动脉瘤临床特点的关系以及二者与VEGF、MMP-9表达的相关性。结果:microRNA-126在ICA患者外周血清中表达水平高于正常对照者,而microRNA-125b表达水平低于正常对照者,差异均有显著统计学意义(P 0. 01); microRNA-126、microRNA-125b与瘤体积大小(t值分别为10. 67和-19. 00)、瘤体数目(F值分别为3. 56和-4. 21)显著相关,差异均有显著统计学意义(P 0. 01);相关性分析显示microRNA-126与VEGF、MMP-9的表达呈正相关,而microRNA-125b仅与MMP-9呈负相关,差异均有统计学意义(P 0. 05),microRA-125b与VEGF无相关性(P 0. 05)。结论:microRNA-126、microRNA-125b在ICA中存在差异表达谱,且二者与ICA的临床特点有关。同时,在ICA中microRNA-126与VEGF、MMP-9存在相关性,而microRNA-125b进与MMP-9存在相关性,其具体机制尚需进一步研究。     

血管内皮生长因子、Eph受体酪氨酸激酶A2、基质金属蛋白酶-2和-9在卵巢癌血管生成拟态中的作用

目的 探讨血管内皮生长因子(VEGF)、Eph受体酪氨酸激酶A2 (EphA2)、基质金属蛋白酶(MMP)-2和MMP-9在卵巢癌血管生成拟态中的作用.方法 收集临床和预后资料完整的卵巢癌组织标本84例,切片经明确诊断后进行CD31和过碘酸-雪夫 (PAS) 双重染色,证实肿瘤组织中存在血管生成拟态,行VEGF、EphA2、MMP-2和MMP-9 免疫组织化学染色,根据染色指数统计免疫组织化学染色结果.结果 有血管生成拟态组(36/84)和无血管生成拟态组卵巢癌组织(48/84)的VEGF、EphA2、MMP-9表达差异有统计学意义,有血管生成拟态组的卵巢癌细胞VEGF、EphA2、MMP-9表达明显高于无血管生成拟态组.但有血管生成拟态组和无血管生成拟态组患者的MMP-2表达差异无统计学意义.结论 在卵巢癌中血管生成拟态和内皮依赖性血管并存,VEGF、EphA2和MMP-9等参与了卵巢癌血管生成拟态的形成.检测VEGF、EphA2和MMP-9可作为预测卵巢癌预后的间接指标.     

膀胱癌组织中MMP-2、MMP-9、Survivin、Livin和VEGF表达的临床意义分析

目的 探讨膀胱癌组织中MMP-2、MMP-9、Survivin、Livin和VEGF表达的临床意义.方法 应用RT-PCR方法检测51例膀胱癌手术切取标本中的MMP-2、MMP-9、Survivin、Livin和VEGF表达,并分析其临床意义.结果 膀胱癌组织中MMP-2、MMP-9、VEGF、Survivin、Livin表达水平均明显高于正常癌旁组织,组间比较差异有统计学意义,P＜0.05.随着膀胱癌分期及分级的增加,MMP-2、MMP-9、VEGF、Survivin、Livin表达水平均明显提高,且不同分级及分期间表达水平相比较差异有统计学意义(P＜0.05).结论 膀胱癌组织中存在多种基因的表达异常,其发生、发展以及转移与多基因的联合作用有着密切联系.     

VEGF和MMP-7在胆管癌组织中的表达及其与预后的关系

目的:探讨血管内皮生长因子(Vascular endothelial growth factor,VEGF)和基质金属蛋白酶-7(Matrix metalloproteinase-7,MMP-7)在胆管癌组织中的表达及其预后的关系。方法:选取本院2010年5月至2012年8月手术切除胆管癌组织标本35例为观察组,非胆管癌组织标本(癌旁胆管组织)30例为对照组。利用免疫组织化学SP法检测在胆管癌组织及非胆管癌组织中VEGF和MMP-7的表达情况,分析其患者性别、年龄、病理分化、肿瘤大小、淋巴转移等临床特征之间的关系及其与预后的相关性。结果:(1)观察组VEGF和MMP-7的阳性表达率分别为68.57%、71.43%,对照组VEGF和MMP-7的阳性表达率分别为23.33%、36.67%,观察组中VEGF和MMP-7的阳性表达率均明显高于对照组(P0.05);(2)观察组VEGF以及MMP-7的阳性表达均与患者性别、年龄、肿瘤大小无关,而与分化程度及肿瘤的淋巴结转移有关(P0.05);(3)胆管癌患者术后5年总体生存率为22.86%(8/35),VEGF和MMP-7表达均与生存期5年相关(P0.05)。结论:VEGF和MMP-7在胆管癌组织中高表达,与胆管癌的分化程度及淋巴结转移关系密切,对胆管癌预后的评估具有重要的意义。     

胰岛素样生长因子-1受体和血管内皮生长因子在胃癌中的表达

目的: 探讨胰岛素样生长因子1受体(IGF-1R)和血管内皮生长因子受体(VEGF)的表达与胃癌浸润、转移的关系.方法: 选取胃癌患者56例, 以20例癌旁不典型增生组织及28例正常胃黏膜组织作为对照, 应用SABC免疫组化方法检测IGF-1R和VEGF的表达.结果: IGF-1R蛋白在胃癌组织、癌旁不典型增生组织及正常胃黏膜组织中的阳性表达率分别为87.5%、 55.00%和17.86%, 两两比较, 均有统计学差异(P<0.01);IGF-1R蛋白在胃癌转移组和无转移组中的阳性表达率分别为97.06%和72.73%(P<0.05);浸润至黏膜下层、肌层、外膜的胃癌组织中IGF-1R蛋白阳性表达率分别为66.67%、 92.59%、 100%(P<0.05).VEGF蛋白在胃癌组织、癌旁不典型增生组织及正常胃黏膜组织中的阳性表达率分别为69.64%、 45.00%和25.00%, 两两比较, 均有统计学差异(P<0.05);VEGF蛋白在胃癌转移组和无转移组中的阳性表达率分别为85.29%和45.45%(P<0.01);浸润至黏膜下层、肌层、外膜的胃癌组织中VEGF蛋白阳性表达率分别为40.00%、 74.07%、 85.71%(P<0.05).结论: IGF-1R和VEGF与胃癌的发生、浸润、转移有关, 可联合运用, 作为新的胃癌标记物, 对判断预后有一定价值.     

宫颈癌与正常宫颈上皮VEGF和MMP-9的表达研究

目的:观察血管内皮生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)在宫颈癌中的表达,分析其对宫颈癌发病的可能影响。方法:免疫组化SP法检测VEGF和MMP-9在宫颈癌和正常宫颈黏膜的表达,探讨其在宫颈癌的作用以及二者之间的相关性并作统计学相关分析。结果:VEGF在宫颈癌及正常宫颈黏膜的上皮细胞、血管内皮细胞、腺上皮细胞和散在分布的炎症细胞均有表达,宫颈癌组表达明显高于正常黏膜对照组(P0.05);MMP-9在对照组正常宫颈黏膜的皮有弱阳性表达,而宫颈癌组在上皮细胞、内皮细胞和腺上皮细胞中有强表达,宫颈癌组表达明显高于对照组(P0.05)。VEGF与MMP-9表达呈正相关(r=0.442,P=0.002)。结论:EGF和MMP-9的表达可能对宫颈癌的发生和发展有重要作用,而且在宫颈癌中VEGF可能对MMP-9的表达也有调控作用。     

胃癌中E-cadherin、MMP-2的表达及侵袭转移机制

目的 通过检测E-cadherin和MMP-2蛋白在胃癌中的表达,探讨它们在肿瘤转移和侵袭过程中的作用.方法 取胃癌组织50例,正常胃黏膜10例;应用SP法免疫组化检测E-cadherin、MMP-2蛋白的表达.结果 (1)胃癌组织中E-cadherin蛋白的阳性表达率为46%(23/50),明显低于正常黏膜100%(10/10,P<0.001).转移组阳性表达率为35.29%(12/34)明显低于非转移组68.75%(11/16),差异有显著性(P<0.05).与临床分期、浸润分级的关系显示,Ⅲ-Ⅳ期和T3-T4级癌组织中E-cadherin蛋白表达分别明显低于Ⅰ-Ⅱ期和T1-T2级(P<0.05).E-cadherin表达还与组织学分级相关:胃癌分化程度低则阳性表达率也低;分化程度高则阳性表达率也高,差异有显著性(P<0.05).(2)MMP-2在胃癌组织中阳性表达率为74%(37/50),而正常胃黏膜上皮细胞中几乎无棕染颗粒,其差异有显著性(P<0.05).转移组MMP-2阳性表达率(82.35%)明显高于非转移组(56.25%,P<0.05).MMP-2的表达与组织学分级明显相关:随着胃癌分化程度降低,MMP-2阳性表达率升高(P<0.05);Ⅲ-Ⅳ期胃癌表达明显高于Ⅰ-Ⅱ期(P<0.05);T3-T4级MMP-2阳性表达率高于T1-T2级(P<0.001).(3)MMP-2与E-cadherin表达之间呈高度负相关(相关系数r=-0.368,P<0.009).结论 MMP-2在胃癌中均呈高表达,而E-cadherin则反之.E-cadherin蛋白表达减弱与胃癌侵袭转移潜能相关,可作为胃癌侵袭转移的生物学标志之一.     

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,     

Opportunities and challenges in the prevention and control of cancer and other chronic diseases: children's diet and nutrition and weight and physical activity

OBJECTIVE: The purpose of this article is to review the role of behavioral research in disease prevention and control, with a particular emphasis on lifestyle- and behavior-related cancer and chronic disease risk factors--specifically, relationships among diet and nutrition and weight and physical activity with adult cancer, and tracking developmental origins of these health-promoting and health-compromising behaviors from childhood into adulthood. METHOD: After reviewing the background of the field of cancer prevention and control and establishing plausibility for the role of child health behavior in adult cancer risk, studies selected from the pediatric published literature are reviewed. Articles were retrieved, selected, and summarized to illustrate that results from separate but related fields of study are combinable to yield insights into the prevention and control of cancer and other chronic diseases in adulthood through the conduct of nonintervention and intervention research with children in clinical, public health, and other contexts. RESULTS: As illustrated by the evidence presented in this review, there are numerous reasons (biological, psychological, and social), opportunities (school and community, health care, and family settings), and approaches (nonintervention and intervention) to understand and impact behavior change in children's diet and nutrition and weight and physical activity. CONCLUSIONS: Further development and evaluation of behavioral science intervention protocols conducted with children are necessary to understand the efficacy of these approaches and their public health impact on proximal and distal cancer, cancer-related, and chronic disease outcomes before diffusion. It is clear that more attention should be paid to early life and early developmental phases in cancer prevention.