转录信号传导子和激活子3信号传导通路调控选择性环氧化酶2抑制剂抗结肠癌的机制

目的探究转录信号传导子和激活子3(Stat3)信号传导通路与选择性环氧化酶2(COX-2)抑制剂抗结肠癌细胞株HT-29机制的关系,明确COX-2抑制剂抗结肠癌细胞内信号传导机制。方法将选择性COX-2抑制剂NS-398,作用于结肠癌细胞系HT-29,运用MTT法检测细胞增殖状态;流式细胞仪观察NS-398对细胞凋亡的影响,进一步用RT-PCR检测药物作用前后HT-29中COX-2mRNA的表达;ELISA法测定体系前列腺素E2(PGE2)水平;Westernblot检测药物作用前后Stat3通路相关蛋白JAK2、Stat3的磷酸化活性和cyclinD1、Bcl-2的表达。结果结肠癌细胞系HT-29中COX-2mRNA呈高表达,NS-398呈时间、剂量依赖性方式抑制HT-29细胞增殖,促进其凋亡。NS-398使HT-29细胞COX-2mRNA和PGE2表达水平显著下降。同时p-JAK2、p-Stat3、cyclinD1、Bcl-2表达水平随作用时间延长而下降。结论癌基因Stat3信号传导通路调控了NS-398抗结肠癌的细胞内信号传导机制,最终通过其下游靶基因cyclinD1、Bcl-2影响结肠癌细胞系HT-29的增殖与凋亡。     

溴环己胺醇预先给药对大鼠盐酸吸入性肺损伤的作用

目的 观察溴环己胺醇预先给药对大鼠盐酸吸入性肺损伤是否具有保护作用，并探讨其可能机制。方法30只健康 SD 大鼠，随机分成3组，A 组：生理盐水吸入组；B组：稀盐酸吸入组；C组：稀盐酸吸入 溴环己胺醇处理组，每组10只。C 组腹腔注射溴环己胺醇，1次/d，连续3d，A、B 组以等体积生理盐水代替。第3天注药后30min，B、C 组气管注入pH 值为1.25的稀盐酸1.2ml/kg，制成盐酸吸入性肺损伤模型，A 组气管注入生理盐水1.2ml/kg。观察注药后5h 动脉血气、氧合指数(PaO_2/FiO_2)、肺湿/干重比(W/D)、肺组织及血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)水平。结果 与 A 组比较，B、C 组 PaO_2、PaO_2/FiO_2降低(P<0.01)，B、C 组W/D、B 组肺组织 TNF-α、IL-8含量、血清 IL-8浓度升高(P<0.01)。与 B 组比较，C 组 PaO_2、PaO_2/FiO_2升高(P<0.01)，C 组W/D、肺组织TNF-α、IL-8含量及血清 IL-8浓度降低(P<0.01)。结论 溴环己胺醇可能通过抑制 TNF-α、IL-8炎症因子的产生和释放机制对盐酸吸入性损伤肺产生保护作用。     

转化生长因子在前列腺增生中作用的研究

目的：探讨转化生长因子α(TGF-α)和转化生长因子β(TGF-β)在良性前列腺增生症组织中的表达及意义。方法：利用免疫组织化学方法研究TGF-α和TGF-β在40例BPH组织和5例正常前列腺组织中的表达。结果：TGF-α在BPH组织上皮和间质中的表达强阳性率均高于正常前列腺组织(P＜0．01)。且TGF-α在BPH组织上皮组织的表达明显高于其在间质中的表达(P＜0．01)。TGF-β在BPH组织上皮和间质中的表达明显高于正常前列腺组织(P＜0．01)。且TGF-β在BPH组织间质中的表达明显高于其在上皮组织中的表达(P＜0.01)。结论：TGF-α在前列腺组织中表达增高，尤其在腔上皮细胞的胞浆中高度表达，TGF-β在前列腺包织中表达增高，尤其在间质组织中的过度表达，提示其可能直接或间接参与了前列腺间质细胞的分化和增殖，参与了BPH的病理过程。     

脑胶质瘤患者长期存活的临床因素分析

目的 探讨胶质瘤患者长期生存相关的临床因素。方法 回顾性调查1980年5月-1995年5月间在本院手术治疗的胶质瘤患者，对收集的资料整理量化，建立Logistic回归模型(stepwise法)进行分析。结果 长期生存的胶质瘤患者102例，长期存活率占随访病例的43．9％(102/232)。病理级别、年龄、KPS、肿瘤部位、复发、复发后再手术、切除程度和手后放疗与胶质瘤患者的长期存活显著相关，其中复发后再手术、切除程度和手术后放疗是提高患者长期存活率的最重要因素。结论 应尽量在显微镜下行胶质瘤全切除，术后及时放疗和化疗；肿瘤复发时如KPS大于70，特别是第一次手术病理级别低者，应予再手术治疗。     

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: I. Effects of primary motor cortex rTMS.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) affects the excitability of the motor cortex and is thought to influence activity in other brain areas as well. We combined the administration of varying intensities of 1-Hz rTMS of the motor cortex with simultaneous positron emission tomography (PET) to delineate local and distant effects on brain activity. METHODS: Ten healthy subjects received 1-Hz rTMS to the optimal position over motor cortex (M1) for producing a twitch in the right hand at 80, 90, 100, 110, and 120% of the twitch threshold, while regional cerebral blood flow (rCBF) was measured using H(2)(15)O and PET. Repetitive transcranial magnetic stimulation (rTMS) was delivered in 75-pulse trains at each intensity every 10 min through a figure-eight coil. The regional relationship of stimulation intensity to normalized rCBF was assessed statistically. RESULTS: Intensity-dependent rCBF increases were produced under the M1 stimulation site in ipsilateral primary auditory cortex, contralateral cerebellum, and bilateral putamen, insula, and red nucleus. Intensity-dependent reductions in rCBF occurred in contralateral frontal and parietal cortices and bilateral anterior cingulate gyrus and occipital cortex. CONCLUSIONS: This study demonstrates that 1-Hz rTMS delivered to the primary motor cortex (M1) produces intensity-dependent increases in brain activity locally and has associated effects in distant sites with known connections to M1.     

移植肾组织TGF-β1和MMP-2表达及IV型胶原沉积与慢性移植肾肾病的关系

目的 探讨移植肾组织中转化生长因子β1(TGF-β1)和基质金属蛋白酶2(MMP-2)的表达及IV型胶原沉积与慢性移植肾肾病(CAN)的关系.方法 对18例CAN患者进行了移植肾切除术.光镜下观察切除的肾组织标本并根据其纤维化的程度进行分期,用免疫组织化学技术和图像分析法检测移植肾组织中TGF-β1和MMP-2表达量及IV型胶原沉积情况,并分析患者血肌酐(Cr)和尿素氮(BUN)的水平与移植肾纤维化程度的关系.结果 随着患者移植肾纤维化程度的加重,血清肌酐、尿素氮及肾组织中TGF-β1、IV型胶原基因表达量均增加,MMP-2表达量于移植肾纤维化早期明显升高,并随移植肾纤维化程度加重而逐渐降低.结论 移植肾组织中TGF-β1表达量增高及IV型胶原沉积可以促进CAN的进程,而MMP-2则可抑制其进展.     

颞叶癫痫大鼠海马CA1区Sema3C、Np1的表达变化研究

目的探讨颞叶癫痫的发病机制。方法取健康雄性SD大鼠制成颞叶癫痫模型，用免疫组织化学和原位杂交技术对匹罗卡品致痫后不同时间点CA1区的Sema3C mRNA、Np1 mRNA和蛋白表达进行分析。结果在匹罗卡品致痫后7d，实验组CA1区Sema3C、Np1的表达明显低于对照组（P〈0．01）。结论CA1区Sema3C、Np1的表达下凋可能参与了海马CA1区内的轴突出芽机制。     

A review of Disrupted-In-Schizophrenia-1 (DISC1): neurodevelopment, cognition, and mental conditions.

Disrupted-In-Schizophrenia-1 (DISC1) is a promising candidate gene for schizophrenia (SZ) and bipolar disorder (BP), but its basic biology remains to be elucidated. Accumulating genetic evidence supports that DISC1 is associated with some aspects of cognitive functions relevant to SZ and BP. Here, we provide a summary of the current updates in biological studies of DISC1. Disrupted-In-Schizophrenia-1, preferentially expressed in the forebrain, has multiple isoforms with potential posttranslational modifications. Disrupted-In-Schizophrenia-1 protein occurs in multiple subcellular compartments, which include the centrosome, microtubule fractions, postsynaptic densities, actin cytoskeletal fractions, the mitochondria, and the nucleus. Recent studies have clarified that DISC1 mediates at least centrosome-dynein cascade and cyclic adenosine monophosphate (cAMP) signaling. Furthermore, both cytogenetic and cell biological studies consistently suggest that an overall loss of DISC1 function (either haploinsufficiency or dominant-negative, or both) may be associated with SZ and BP. On the basis of these findings, production of DISC1 genetically engineered mice is proposed as a promising animal model for SZ and BP. Several groups are currently generating DISC1 mice and starting to characterize them. In this review, the advantages and disadvantages of each animal model are discussed.     

脑卒中后遗症老年人易患肺炎及其影响预后的因素

目的分析影响脑卒中后遗症老年人易患肺炎及其影响预后的因素。方法分析117例脑卒中后遗症老年人因肺炎而反复住院的病史资料，对存活与病死不同转归的病人进行比较。结果53例死亡，占45．3％。单因素分析显示性别、卧床不起时间、吞咽反射障碍、血清白蛋白水平是影响脑卒中后遗症老年病人易患肺炎及其影响预后的因素。结论脑卒中后遗症老年人患肺炎及其影响预后有多方面因素，对吞咽反射障碍的病人置入鼻饲管可以改善预后。     

Variation analysis of β3-adrenergic receptor and melanocortin-4 receptor genes in childhood obesity

BACKGROUND: Decreased energy expenditure and increased food intake are principal causes for obesity. In the present study, genotypes of beta(3)-adrenergic receptor (beta(3)AR) and of melanocortin-4 receptor (MC4R), both of which are believed to have a close link to the cause of obesity, were analyzed and compared with phenotypes of childhood obesity. METHODS: Thirty-five obese children with moderate to severe obesity were enrolled. Direct sequencing of the MC4R coding region and pinpoint-polymerase chain reaction were used to detect genomic variation in the beta(3)AR gene using peripheral blood-derived DNA. RESULTS: Allele frequency of Trp64Arg variation in the beta(3)AR gene in the obese subjects was 0.16, which is comparable with that in the healthy general population in eastern Asia. Comparison of phenotypical characteristics did not show a significant difference between Trp/Trp and Trp/Arg subjects. It was notable that body height SD was significantly higher in the Trp/Trp than the Trp/Arg subjects (0.93 +/- 1.0 SD vs 0.07 +/- 1.3 SD, P= 0.03). Annual weight gains were far beyond a hypothetical fat gain in an Arg64 heterozygote with decreased energy consumption, suggesting increased food intake in childhood obesity. There was, however, no variation in the MC4R gene despite thorough sequencing of the entire coding region. CONCLUSIONS: The Trp64Arg variation in the beta(3)AR gene has no relationship to the degree or the incidence of childhood obesity. The majority of childhood obesity can be characterized as tall stature, more rapid weight gain than that expected by decreased energy expenditure. Further investigation is necessary in regard to the increased food intake as a major cause of childhood obesity.