神经生长因子对兔脊髓前角运动神经元保护作用的定量研究

钳夹损伤兔右坐骨神经，于损伤处注射蛇毒ＮＧＦ４００Ｂｕ／ｋｇ／日，损伤术后１，３，７天和２，３，４，６，８周动态观察脊髓腰段伤侧第ＩＸ板层外侧的大型运动神经元的ＡＣＰａｓｅ活性改变并应用图像分析仪对其进行定量研究。结果表明术后１，３天实验组和对照组ＡＣＰａｓｅ活性均增加；术后３周实验组ＡＣＰａｓｅ活性达高峰，溶酶体数目及溶酶体、高尔基复合体上的电子密度也明显增加，对照组酶活性不如实验组高，组间差异显著（Ｐ＜００１）。术后６周实验组ＡＣＰａｓｅ活性恢复至正常水平，而对照组ＡＣＰａｓｅ活性才开始回降。本研究显示蛇毒ＮＧＦ对坐骨神经损伤后脊髓前角运动神经元ＡＣＰａｓｅ活性恢复有促进作用，从而对运动神经元可起一定的保护和促进恢复的作用     

GST-π EXPRESSION IN TRANSFORMED CELLS BY TRANSFECTING OF DNA ISOLATED FROM HUMAN FETAL LUNG TISSUES TREATED WITH CARCINOGENS

ＧＳＴπＥＸＰＲＥＳＳＩＯＮＩＮＴＲＡＮＳＦＯＲＭＥＤＣＥＬＬＳＢＹＴＲＡＮＳＦＥＣＴＩＮＧＯＦＤＮＡＩＳＯＬＡＴＥＤＦＲＯＭＨＵＭＡＮＦＥＴＡＬＬＵＮＧＴＩＳＳＵＥＳＴＲＥＡＴＥＤＷＩＴＨＣＡＲＣＩＮＯＧＥＮＳＹａｏＤｅｎｇｇａｏ姚登高ＨｕＧｕ...     

INVESTIGATION OF BLOOD SUPPLY OF BRONCHOGENIC CARCINOMA DERIVING FROM PULMONARY ARTERY

ＩＮＶＥＳＴＩＧＡＴＩＯＮＯＦＢＬＯＯＤＳＵＰＰＬＹＯＦＢＲＯＮＣＨＯＧＥＮＩＣＣＡＲＣＩＮＯＭＡＤＥＲＩＶＩＮＧＦＲＯＭＰＵＬＭＯＮＡＲＹＡＲＴＥＲＹＺｈｅｎｇＲｕｈｅｎｇ郑如恒ＤｏｎｇＹｏｎｇｈｕａ董永华ＺｈｏｕＫａｎｇｒｏｎｇ周康荣（Ｄｅｐａｒ...     

ESTABLISHMENT OF HIGH RISK POPULATION AND PRECANCEROUS LESION OF NASOPHARYNGEAL CARCINOMA(NPC)

ＥＳＴＡＢＬＩＳＨＭＥＮＴＯＦＨＩＧＨＲＩＳＫＰＯＰＵＬＡＴＩＯＮＡＮＤＰＲＥＣＡＮＣＥＲＯＵＳＬＥＳＩＯＮＯＦＮＡＳＯＰＨＡＲＹＮＧＥＡＬＣＡＲＣＩＮＯＭＡ（ＮＰＣ）ＨｕａｎｇＴｅｎｇｂｏ１黄腾波ＷａｎｇＨｕｉｍｉｎ２汪慧民ＬｉＪｉｎｇｌｉａｎ３李...     

APPROACH OF FIVE-YEAR-AVERAGE HAZARD RATES FOR THE BREAST CANCER PATIENTS AND ANALYSES OF PROGNOSTIC FACTORS-AN APPLICATION OF COX REGRESSION MODEL

ＡＰＰＲＯＡＣＨＯＦＦＩＶＥＹＥＡＲＡＶＥＲＡＧＥＨＡＺＡＲＤＲＡＴＥＳＦＯＲＴＨＥＢＲＥＡＳＴＣＡＮＣＥＲＰＡＴＩＥＮＴＳＡＮＤＡＮＡＬＹＳＥＳＯＦＰＲＯＧＮＯＳＴＩＣＦＡＣＴＯＲＳＡＮＡＰＰＬＩＣＡＴＩＯＮＯＦＣＯＸＲＥＧＲＥＳＳＩＯＮＭＯ...     

THERAPEUTIC EFFECTS OF rhTNF ALONE AND INCOMBINATION WITH KENGSHENGMYCIN INEXPERIMENTAL HUMAN OVARIAN CANCER

ＴＨＥＲＡＰＥＵＴＩＣＥＦＦＥＣＴＳＯＦｒｈＴＮＦＡＬＯＮＥＡＮＤＩＮＣＯＭＢＩＮＡＴＩＯＮＷＩＴＨ　ＫＥＮＧＳＨＥＮＧＭＹＣＩＮＩＮＥＸＰＥＲＩＭＥＮＴＡＬＨＵＭＡＮＯＶＡＲＩＡＮＣＡＮＣＥＲＺｈａｏＥｎｆｅｎｇ赵恩锋；ＺｈｏｕＭｅｉｑｉｎｇ周美清...     

STUDY ON EXPRESS OF a-HCG AND a-HCGmRNA IN PANCREATIC ENDOCRINE TUMORS

ＳＴＵＤＹＯＮＥＸＰＲＥＳＳＯＦａＨＣＧＡＮＤａＨＣＧｍＲＮＡＩＮＰＡＮＣＲＥＡＴＩＣＥＮＤＯＣＲＩＮＥＴＵＭＯＲＳＹｕＪｉｙａｏ虞积耀ＣｅｓａｒｅＢｏｒｄｉＧｅｎｅｒａｌＨｏｓｐｉｔａｌｏｆｔｈｅＮａｖｙ，Ｂｅｉｊｉｎｇ１０００３７Ｃｈｉｎａ...     

PRELIMINARY STUDY OF RETROVIRAL MEDIATED TRANSFER OF THE HUMAN mdr-1 GENE INTO MURINE AND HUMAN HEMATOPOIETIC STEM/PROGENITOR CELLS

ＰＲＥＬＩＭＩＮＡＲＹＳＴＵＤＹＯＦＲＥＴＲＯＶＩＲＡＬＭＥＤＩＡＴＥＤＴＲＡＮＳＦＥＲＯＦＴＨＥＨＵＭＡＮｍｄｒ１ＧＥＮＥＩＮＴＯＭＵＲＩＮＥＡＮＤＨＵＭＡＮＨＥＭＡＴＯＰＯＩＥＴＩＣＳＴＥＭ／ＰＲＯＧＥＮＩＴＯＲＣＥＬＬＳＦｅｎｇＫａｉ冯凯Ｐｅ...     

乳腺良恶性病变组织中PRL和三种酶的分布及在乳癌中相互关系

本文应用组化方法研究乳腺良恶性病变组织中ＰＲＬ和ＮＡＤＨＤＨ、ＧＤＨ、ＬＤＨ三种酶活性分布及在乳癌中相互关系。乳癌和良性病变ＰＲＬ阳性率分别为８０．５％和８５．７％；乳癌组织ＮＡＤＨＤＨ、ＧＤＨ和ＬＤＨ高酶活性率分别为７３．２％、３９％和８２．９％，良性病变分别为５１．４％、５１．４％和６５．７％，ＮＡＤＨＤＨ和ＬＤＨ高酶活性率乳癌高于良性病变（Ｐ＜０．０５）；ＰＲＬ阳性率及半定量分级均与ＮＡＤＨＤＨ和ＬＤＨ高酶活性率有高度密切关系，ＧＤＨ和ＬＤＨ高酶率均与ＮＡＤＨＤＨ高酶活性率存在密切关系。上述结果提示：大部分乳癌存在ＰＲＬ依赖性，ＰＲＬ可能参与乳癌形成；ＮＡＤＨＤＨ、ＧＤＨ和ＬＤＨ可能是较好的乳癌酶生物学标记物，检测这些酶活性可能对估测乳癌预后及临床治疗方案选择有较重要意义；乳癌组织中ＰＲＬ可能诱导ＮＡＤＨＤＨ和ＬＤＨ酶活性。     

IMMUNOLOGICAL CHARACTERISTICS OF THE LEUKEMIA CELLS TRANSFECTED WITH ONCOSTATIN M GENE BY RECOMBINANT ADENOVIRUS

ＩＭＭＵＮＯＬＯＧＩＣＡＬＣＨＡＲＡＣＴＥＲＩＳＴＩＣＳＯＦＴＨＥＬＥＵＫＥＭＩＡＣＥＬＬＳＴＲＡＮＳＦＥＣＴＥＤＷＩＴＨＯＮＣＯＳＴＡＴＩＮＭＧＥＮＥＢＹＲＥＣＯＭＢＩＮＡＮＴＡＤＥＮＯＶＩＲＵＳ１ＷａｎｇＱｕａｎｘｉｎｇ王全兴ＣａｏＸｕｅｔａｏ２...     

人胃癌组织内神经纤维发生可塑性改变的研究

背景与目的：前期研究发现人胃癌组织内存在着较正常组织更多的P物质免疫阳性神经纤维，这些神经与胃癌的关系尚不清楚。本文通过免疫组化技术研究人胃癌组织内P物质免疫阳性神经纤维的分布特点及其功能状态。方法：34例胃癌组织标本进行免疫组织化学染色，检测胃癌组织内磷酸化细胞外信号调节激酶（P-ERK1／2）阳性神经纤维和细胞的分布；免疫细胞化学染色检测胃癌组织和培养的胃癌细胞神经生长因子表达状况。结果：在胃癌组织内可见大量磷酸化ERK1／2免疫阳性反应的神经纤维，呈束状或串珠状走行，片可见呈巢状分布的P-ERK1／2免疫阳性反应细胞。神经纤维主要分布在P—ERK1／2免疫阳性细胞的四周并与这些细胞相毗邻。在胃癌组织有大量表达神经生长因子（NGF）的细胞，体外培养的低分化胃癌细胞系（MNK45）高表达神经生长因子（NGF）。结论：胃癌组织内有大量的呈向心性分布的神经纤维，这些神经发生了可塑性改变：这些神经纤维可能对胃癌细胞的增殖起调控作用。     

奥沙利铂对大鼠后根神经节及神经生长因子表达的影响

目的探讨神经生长因子的表达（nerve growth factor，NGF）在奥沙利铂（草酸铂）应用期间的变化规律以及与其对周围神经系统毒性的靶器官后根神经节（dorsal root ganglia，DRG）的神经元形态改变的相关性。方法采用光镜技术和免疫组化染色法观察DRG在不同时间及不同剂量时的形态改变以及DRG内NGF的表达，并以图像分析仪进行分析。结果DRG内NGF表达下调与神经元的形态改变均在用药后24～48小时最为显著，5周后基本恢复，且均表现为药物剂量依赖性。结论草酸铂应用期间，DRG内NGF表达下调具有药物剂量依赖性及可恢复性的特点，且与DRG内感觉神经元核仁的形态改变呈正相关（r^2=0．9929，P（0．0001），提示NGF表达的变化与草酸铂的周围神经系统毒性有关，为外源性NGF可能缓解其周围神经毒性提供依据。     

Nerve fibers infiltrate the tumor microenvironment and are associated with nerve growth factor production and lymph node invasion in breast cancer

Infiltration of the tumor microenvironment by nerve fibers is an understudied aspect of breast carcinogenesis. In this study, the presence of nerve fibers was investigated in a cohort of 369 primary breast cancers (ductal carcinomas in situ, invasive ductal and lobular carcinomas) by immunohistochemistry for the neuronal marker PGP9.5. Isolated nerve fibers (axons) were detected in 28% of invasive ductal carcinomas as compared to only 12% of invasive lobular carcinomas and 8% of ductal carcinomas in situ (p = 0.0003). In invasive breast cancers, the presence of nerve fibers was observed in 15% of lymph node negative tumors and 28% of lymph node positive tumors (p = 0.0031), indicating a relationship with the metastatic potential. In addition, there was an association between the presence of nerve fibers and the expression of nerve growth factor (NGF) in cancer cells (p = 0.0001). In vitro, breast cancer cells were able to induce neurite outgrowth in PC12 cells, and this neurotrophic activity was partially inhibited by anti‐NGF blocking antibodies. In conclusion, infiltration by nerve fibers is a feature of the tumor microenvironment that is associated with aggressiveness and involves NGF production by cancer cells. The potential participation of nerve fibers in breast cancer progression needs to be further considered.     

CYP3A4在黄曲霉毒素B1诱发大鼠肝癌过程中的表达及意义

探讨CYP3A4在黄曲霉毒素B1（AFB1）实验诱发大鼠肝癌过程中的活性变化及其在肝癌发生过程中的意义。方法:雄性、4周龄、Wistar大鼠随机分为AFB1组和对照组;AFB1组腹腔注射AFB1,对照组则给与溶媒二甲基亚砜。在诱发肝癌过程中,分别于第13、23、33、43、53、63周对大鼠进行肝活检;实验至第73周处死全部动物取肝组织;利用大鼠肝组织微粒体混合酶体外代谢体系,采用荧光分光光度定量法动态检测肝标本中CYP3A4酶活性。结果:AFB1组肝细胞癌发生率为58.8%（10/17）;对照组肝细胞癌发生率为0（0/16）,两组间肝癌发生率比较,AFB1组显著高于对照组（P=0.001）。两组大鼠肝组织代谢酶CYP3A4活性都有不同程度的变化。肝组织CYP3A4活性从13 w开始逐渐升高,至23 w达顶峰,然后逐渐降低,到43 w又升高,出现双波峰变化;从13 w至53 w不同时段AFB1组肝组织CYP3A4活性显著低于对照组（P<0.01）。但是至63 w时AFB1组肝组织CYP3A4活性基本接近对照组（P=0.5086）。结论:CYP3A4活性在AFB1诱癌过程中受到抑制,可能是由于癌变早期的细胞减少对致癌物质的活化有关;CYP3A4活性在AFB1诱癌过程中的表达起伏变化,是由于基因多态性较大程度上影响蛋白表达水平的结果。      

听神经瘤术中面神经监测的临床研究

Objective To determine the method and significance of facial nerve preservation during acoustic neurinoma surgery by intra-operative facial nerve monitoring(IFNM).Methods 62 patients were randomly assigned to the IFNM or the control group.Facial nerve function(FNF)was assessed by a modified House-Brackmann grading(HB)before the operation,10 days and every two months after surgery and com,pared between the two groups. Results Ten days after surgery,26/32 patients in the IFNM group and 15/30 patients in the control group had FNF HB grade,Ⅰ-Ⅲ；FNF HB gradeⅣ-Ⅴ was prestent in 6/32 in the IFNM group and 15/30 in the control group.During follow-up,29/32 patients in the IFNM group and 20/20 patients in the control group had FNF HB gradeⅠ-Ⅲ;FNF HB gradeⅣ-Ⅴ was present in 3/32 in the IFNM group and 10/30 in the control group.All differnces were statistcally significant.Conclusion IFNM significantly improved anatomic and functional facial nerve preservation as well as the quality of life.     

乳腺癌改良根治术保留肋间壁神经的临床观察及意义

目的探讨观察乳腺癌改良根治术中保留肋间臂神经的可行性及临床意义。方法选择拟行乳腺癌改良根治术的乳腺癌患者50例,随机分为两组,实验组26例术时保留肋间臂神经,对照组24例术中切除肋间臂神经。术后对两组患者上臂内侧感觉功能进行随访观察。结果实验组患者术后上臂感觉障碍发生率为11.5%,而对照组高达54.2%,两组比较差异有显著性,两组术后复发率等指标差异无显著性。结论对乳腺癌需行腋淋巴结清扫术的患者,术中保留肋间臂神经可明显减少术后患侧上臂内侧感觉障碍的发生率,不增加手术并发症的发生,不影响手术的根治性,有助于提高患者的生活质量。     

Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: developmental culling and cancer

Germline NF1, c-RET, SDH, and VHL mutations cause familial pheochromocytoma. Pheochromocytomas derive from sympathetic neuronal precursor cells. Many of these cells undergo c-Jun-dependent apoptosis during normal development as NGF becomes limiting. NF1 encodes a GAP for the NGF receptor TrkA, and NF1 mutations promote survival after NGF withdrawal. We found that pheochromocytoma-associated c-RET and VHL mutations lead to increased JunB, which blunts neuronal apoptosis after NGF withdrawal. We also found that the prolyl hydroxylase EglN3 acts downstream of c-Jun and is specifically required among the three EglN family members for apoptosis in this setting. Moreover, EglN3 proapoptotic activity requires SDH activity because EglN3 is feedback inhibited by succinate. These studies suggest that failure of developmental apoptosis plays a role in pheochromocytoma pathogenesis.     

Importance of interaction between nerve growth factor and α9β1 integrin in glial tumor angiogenesis

NGF is a growth factor for which the role in the promotion of angiogenesis is still not completely understood. We found that NGF promotes the pathological neovascularization process in glioma through a direct interaction with α9β1 integrin, which is up-regulated on microvascular endothelial cells in cancer tissue. We propagated gHMVEC primary cells using a new method of immune-selection, and these cells demonstrated α9β1 integrin-dependent binding of NGF in a cell adhesion assay. Moreover, NGF induced gHMVEC proliferation and chemotaxis inhibited by specific blockers of α9β1 integrin, such as MLD-disintegrins and monoclonal antibody Y9A2. A Matrigel tube formation assay revealed that NGF significantly increased capillary-like growth from gHMVEC to a level comparable to treatment with VEGF. The snake venom disintegrin, VLO5, inhibited the agonistic effect of both growth factors, whereas the effect of Y9A2 was not statistically significant. Angiogenesis exogenously induced by NGF was also α9β1-integrin dependent in an embryonic quail CAM system. However, angiogenesis pathologically induced by developing glioma in this system was only sensitive for inhibition with MLD-disintegrin, suggesting a more complex effect of cancer cells on the neovascularization process. The anti-angiogenic effect of MLD-disintegrins is probably related to their pro-apoptotic ability induced in activated tumoral endothelial cells. Therefore, the molecular basis of these disintegrins may be useful for developing new angiostatic pharmaceuticals for application in cancer therapy.     

腮腺良性肿瘤手术保留耳大神经临床价值Meta分析

目的：通过Meta分析评价腮腺良性肿瘤切除术中保留耳大神经（greatauricularnerve,GAN）对术后各并发症发生率影响,探讨其临床价值。方法：以腮腺、耳大神经、并发症等为关键词对1997-04-2013-04期间PubMed、万方数据库等进行中英文文献检索,根据纳入及排除标准对纳入研究采用RevMan5．0软件包进行荟萃分析。结果：12项涉及术后耳廓区暂时性感觉异常的研究中,共有366例出现症状,总发生率为50．76％,实验组（保留耳大神经）113例占27．56％,对照组（切除耳大神经）253例占81．35％,实验组较对照组的发生率降低53．79％,比值比（OR）及其95％置信区间（95％CI）为0．09（0．06～0．13）,z=11．99,P〈0．01;6项关于术后味觉出汗综合征发生率的研究中,共74例出现症状,占总例数18．73％,实验组15例占7．50％,对照组59例占30．26％,前者较后者低22．76％,0R及其95％CI为0．18（0.10～0．35）,z=5．18,P〈0．01;13项涉及影响生活质量并发症的研究中,243例出现不同症状,占总例数的31．93％,实验组62例占14．22％,对照组181例占55．69％,前者显著降低了41．47％,0R值及其95％CI为0．12（0．08～0．18）,z=10．77,P〈0．01。结论：腮腺良性肿瘤手术能够对GAN进行功能保全,其不仅能够降低术后耳廓区暂时性感觉异常和味觉出汗综合征发生率,还能对其他影响生活质量的并发症加以控制,改善患者术后生活质量。