高频电场中金属植入物对周围组织影响的实验研究

目的探讨超短波治疗是否会造成动物体内钢板内固定部位周围组织温度的变化,继而造成热损伤,为临床应用提供依据。方法采用同一只兔左右肱骨对照方式,对照组暴露兔左侧上臂肱骨后即时用荧光光纤测温仪记录温热量超短波治疗时肱骨表面的温度变化,采集数据,在肱骨中央位置制造骨折模型,未植入钢板钢钉,术后连续15d温热量超短波治疗;实验组暴露兔右侧上臂肱骨,在肱骨表面植入钢板钢钉后即时用荧光光纤测温仪记录温热量超短波治疗时肱骨表面的温度变化,采集数据,在肱骨中央位置制造骨折模型(已植入钢板钢钉),术后连续15d温热量超短波治疗。15d后取两组骨折周围骨组织、肌肉及神经做病理。结果两组之间温度变化有显著差异(P<0.05)。实验组的温度变化最大为1.25℃,对照组的温度变化最大为1.2℃。病理显示两组骨折周围骨组织均可见未成熟的骨小梁和骨母细胞,纤维修复正在进行,未见明显炎性反应,神经及其周围组织未见异常。结论在本实验条件下,超短波可以安全应用于体内有金属的部位。     

Prognostic significance of defective mismatch repair and BRAF V600E in patients with colon cancer

PURPOSE: Colon tumors with defective DNA mismatch repair (dMMR) have a well-characterized phenotype and accounts for approximately 15% to 20% of sporadic colon cancer as well as those colon cancer patients with Lynch syndrome. Although the presence of dMMR seems to be a favorable prognostic marker, data suggest that these patients do not respond as well to adjuvant chemotherapy. EXPERIMENTAL DESIGN: In this study, we examined the prognostic significance of tumor MMR deficiency and the presence of a specific mutation in BRAF (V600E) in a group of patients (n = 533) who participated in a randomized prospective clinical trial through the North Central Cancer Treatment Group. RESULTS: Tumors with dMMR were found to be associated with higher tumor grade (P = 0.001), proximal location (P < 0.0001), and improved overall and disease-free survival (P = 0.05 and 0.04, respectively). Among all cases examined, evaluation of the BRAF V600E mutation status revealed no statistically significant differences in either disease-free or overall survival. Patients were then grouped into four categories for further analysis: dMMR/BRAF(-), dMMR/BRAF(+), pMMR/BRAF(-), and pMMR/BRAF(+). The dMMR/BRAF(-) group had a significantly improved overall survival (5-year overall survival of 100% versus 73%, P = 0.002) compared with all others. The remaining three groups had very similar survival outcomes. An additional cohort of tumors previously classified as having dMMR were also tested for the BRAF V600E alteration. Results remained significant (P = 0.006) when the two groups were combined for analysis. CONCLUSIONS: Overall, these data suggest that the underlying molecular etiology of those tumors having dMMR may influence the disease outcome in these patients.     

肝细胞癌中PGC-1α基因的表达下调及其意义

目的 探讨PGC-1α在肝细胞癌(HCC)组织中的表达及其在肝细胞癌发生发展中的调节作用.方法 采用定量逆转录聚合酶链反应(RT-PCR)分析HCC组织和正常肝组织中PGC-1α基因的表达,比较癌组织与正常组织的表达差异.采用siRNA干扰技术体外抑制人正常肝细胞株L02中PGC-1α基因的表达,并在光镜下观察细胞形态,电镜下观察细胞超微结构的改变.应用人全基因组Oligo DNA芯片分析比较肝组织和肝细胞基因的表达变化.结果 HCC组织中PGC-1α基因的表达明显下调,仅为正常肝组织的25.0%.抑制PGC-1α基因的表达可使人正常肝细胞株L02呈现出类似肝癌细胞的形态和超微结构变化,即细胞变小、变圆,胞质减少、核增大,细胞数量减少,成簇分布,线粒体膜呈髓鞘样变性等.基因芯片分析显示,抑制PGC-1α基因的表达可使人正常肝细胞株L02呈现出类似肝癌组织的基因变化趋势,即细胞黏附基因(TNFAIP6、ITGAX、ICAM1、FN1、EMR1、ITGA6、PARVA)、成瘤基因(PMAIP1、CRKL、FHIT、IRF1、PLK)和促进细胞增殖基因(STAT1、CCL3L1、IL6、WARS、PCK1、MUC2、PRKR、IFITM1)表达上调,肿瘤抑制基因(FHIT、PRKR、IL24、DLEU1、RCN2)表达下调.结论 PGC-1α表达下调能诱导人正常肝细胞株L02的肿瘤性转化,PGC-1α在肝癌发生发展中具有重要的调节作用.     

Early medical abortion with methotrexate. Outcome and satisfaction among women aged 15-20 years

Background: We investigated the outcomes of women under age 21 who participated in a multi-center case series of early medical abortion using methotrexate and misoprostol.Methods: We enrolled 1973 women in a case series for medical abortion in the first seven weeks of pregnancy, using a standardized protocol and consent for methotrexate (50 mg/m(2)) and misoprostol (800 mg vaginally, repeated as needed).For this study, women who presented for abortion prior to their 21(st) birthday were compared to older women. Outcomes of abortion were classified as complete medical abortion (CMA) and suction curettage (SC). Secondary outcomes included symptoms. We did an exit interview assessing patient satisfaction during the first year of the study, and have exit interview data for approximately half of the women enrolled.We assessed the relationship of age and outcomes first by bivariate analysis using SAS (SAS Institute, Inc., Cary, NC). A multiple logistic regression model was constructed using age, gestational age, and measures of parity.Results: There were 219 women who were under 21 (18 under the age of 18). Compared to older women, adolescents presented for abortion at the same gestational ages. Compared to older women, younger women were less likely to have finished college (2.8% vs. 38. 7%), and were less likely to have had previous pregnancies (45.4% vs 76.6%) and live births (20.2% vs. 51.3%)The distribution of symptoms during abortion, such as bleeding and cramping, was the same across age groups; the only symptom which was more frequently found in younger women was headache.Overall younger women had a slightly higher rate of CMA as older women (90.2% vs. 86.5%). However, the multiple regression (MR) model did not show an effect of the woman's age on CMA. MR demonstrated an adverse effect of prior live birth, and advancing gestational age on rates of CMA; younger women were less likely to have had prior live births.Younger women were just as likely to report overall satisfaction (86.7% vs. 84.6%) with the abortion procedure and other questions of satisfaction, but were less likely to agree that the bleeding and cramping were acceptable. Conclusions: Younger women having medical abortion with methotrexate and misoprostol have similar outcomes and satisfaction levels as do older women. There is no reason to discourage adolescents who seek abortion from using a medical technique.     

Dexamethasone enhances mallory body formation in drug-primed mouse liver

In a clinical study in which patients with alcoholic hepatitis were treated with prednisone for 1 month, posttreatment liver biopsies showed diminished inflammation, but Mallory bodies were not diminished. This suggested that steroid treatment may reduce inflammation by inhibiting NFkappaB activation. Sparing of Mallory bodies suggests that NFkappaB activation may not be involved mechanistically in Mallory body formation. To test this idea, we induced Mallory body formation in drug-primed mice with or without dexamethasone treatment. As predicted, dexamethasone decreased NFkappaB activation; however, Mallory body formation was increased. Surprisingly, TNFalpha and iNOS, which normally increase as a result of NFkappaB activation, were upregulated by the dexamethasone treatment. It was concluded that NFkappaB activation is not involved in Mallory body formation. Despite this, induced increases in TNFalpha, iNOS, c-jun/API and c-myc expression indicate that oxidative stress is likely involved in Mallory body formation.     

Low-voltage-activated calcium current does not regulate the firing behavior in paired mechanosensory neurons with different adaptation properties

Low-voltage-activated Ca(2+) currents (LVA-I(Ca)) are believed to perform several roles in neurons such as lowering the threshold for action potentials, promoting burst firing and oscillatory behavior, and enhancing synaptic excitation. They also may allow rapid increases in intracellular Ca(2+) concentration. We discovered LVA-I(Ca) in both members of paired mechanoreceptor neurons in a spider, where one neuron adapts rapidly (Type A) and the other slowly (Type B) in response to a step stimulus. To learn if I(Ca) contributed to the difference in adaptation behavior, we studied the kinetics of I(Ca) from isolated somata under single-electrode voltage-clamp and tested its physiological function under current clamp. LVA-I(Ca) was large enough to fire single action potentials when all other voltage-activated currents were blocked, but we found no evidence that it regulated firing behavior. LVA-I(Ca) did not lower the action potential threshold or affect firing frequency. Previous experiments have failed to find Ca(2+)-activated K(+) current (I(K(Ca))) in the somata of these neurons, so it is also unlikely that LVA-I(Ca) interacts with I(K(Ca)) to produce oscillatory behavior. We conclude that LVA-Ca(2+) channels in the somata, and possible in the dendrites, of these neurons open in response to the depolarization caused by receptor current and by the voltage-activated Na(+) current (I(Na)) that produces action potential(s). However, the role of the increased intracellular Ca(2+) concentration in neuronal function remains enigmatic.     

LRP16反馈增强ERα介导转录激活活性的研究

目的:探讨LRP16对雌激素受体α(ERα)介导转录激活活性的反馈增强作用.方法:ERα模式启动子调控的荧光素酶报告子(3×ERE-Luc)或GC富含的ER反应性LRP16启动子S10(-101bp到-14 bp)调控的荧光素酶报告子(pGL-3-S10)与雌激素受体α(ERα)真核表达载体、LRP16真核表达载体(pcDNA3.1-16)共转染MCF-7细胞,测定3×ERE-Luc和pGL-3-S10的相对荧光素酶活性;3×ERE-Luc或pGL-3-S10与ERα真核表达载体、针对LRP16的小干扰RNA(LRP16-siRNA374、LRP16-siRNA668)或对照小干扰RNA(control-siRNA)共转染MCF-7细胞,测定3×ERE-Luc和pGL-3-S10的相对荧光素酶活性.结果:LRP16增强3×ERE-Luc和pGL-3-S10的相对荧光素活性,抑制LRP16表达显著削弱了3×ERE-Luc和pGL-3-S10的相对荧光素活性,并呈现剂量依赖性,该效应依赖于雌激素对ERα的激活.结论:ERα调控的靶基因LRP16反馈增强ERα介导的转录激活活性,是ERα的一个共激活因子.     

Predictors of weight gain in the Pound of Prevention study

OBJECTIVES: This study examined cross-sectional and prospective relationships between macronutrient intake, behaviors intended to limit fat intake, physical activity and body weight. DESIGN: The overall goal was to identify diet and exercise behaviors that predict and/or accompany weight gain or loss over time. Specific questions addressed included: (a) are habitual levels of diet or exercise predictive of weight change; (b) are habitual diet and exercise levels associated cross-sectionally with body weight; and (c) are changes in diet and exercise associated with changes in body weight over time? PARTICIPANTS: Subjects were a sample of community volunteers (n=826 women, n=218 men) taking part in a weight gain prevention project over a 3-year period. MEASURES: Body weight was measured at baseline and annually over the study period. Self-report measures of diet and exercise behavior were also measured annually. RESULTS: Among both men and women, the most consistent results were the positive association between dietary fat intake and weight gain and an inverse association between frequency of physical activity and weight gain. Individuals who weighed more both ate more and exercised less than those who weighed less. Individuals who increased their physical activity level and decreased their food intake over time were protected from weight gain compared to those who did not. Frequency of high-intensity physical activity was particularly important for both men and women. Additionally, women who consistently engaged in higher levels of moderate physical activity gained weight at a slower rate compared to women who were less active. CONCLUSIONS: Overall results indicated that both cross-sectionally and prospectively, the determinants of weight and weight change are multifactorial. Attention to exercise, fat intake and total energy intake all appear important for successful long term control of body weight.     

心肌显像剂99Tcm N-NOET在健康人体中的安全性、生物学分布及内照射辐射吸收剂量

目的研究心肌显像剂99TcmN-NOET在健康人体中的安全性、生物学分布及内照射辐射吸收剂量。方法10名正常志愿者静脉注射99TcmN-NOET744～792MBq后,观察受试者24h内的生命体征变化及有无不良反应,于给药后1、30min,1、2、4、8和24h进行全身显像以测定生物分布,用感兴趣区技术对重要器官进行放射性计数,用MIR-DOSE3.0剂量估算软件,估算各主要受照器官的内照射辐射吸收剂量。于给药后1和4h进行心肌断层显像。结果试验后24h内受试者的生命体征如心率、血压和心电图无明显变化,无任何不良反应。所有受试者的血清学和生化指标均无改变。心肌对99TcmN-NOET的摄取较高,2h时达2.68%;给药后30min心/肺比值大于1,2h达最大,为1.91±0.53。有效剂量当量为1.28×10-5Sv/MBq,按一次给药740MBq计算,各主要器官的内照射辐射吸收剂量均低于50mGy。结论心肌对99TcmN-NOET的摄取率高,断层图像清晰,99TcmN-NOET的内照射辐射吸收剂量低,安全性好,符合临床用放射性显像剂的要求。