Fetal growth restriction alters hippocampal 17-beta estradiol and estrogen receptor alpha levels in the newborn male rat

Fetal growth restriction (FGR) is associated with impaired neurodevelopmental outcomes in affected newborns. The pathogenesis of FGR-associated neurodevelopmental impairment implicates abnormal hippocampal function. The steroid hormone estrogen and its receptor, estrogen receptor alpha (ERα), are involved in the normal programming of hippocampal development and structure. However, the impact of FGR on hippocampal estrogen and hippocampal ERα is not well characterized. We hypothesized that FGR will reduce hippocampal and serum levels of 17-beta estradiol and its receptor, ERα, in the newborn rat hippocampus. We further hypothesize that FGR will reduce hippocampal ERα levels in a region-specific manner. To test our hypotheses, we used the well characterized rat model of FGR induced by uteroplacental-insufficiency in the pregnant Sprague-Dawley rat. Hippocampi and serum were obtained from FGR and control day 0 rat pups and examined for hippocampal 17-beta estradiol, serum 17-beta estradiol, and ERα mRNA and protein levels. Immunohistochemistry was performed to examine region-specific ERα staining. FGR decreased hippocampal 17-beta estradiol levels in the hippocampi of male newborn rats but not females. Serum 17-beta estradiol levels were not affected by FGR in either gender. FGR decreased hippocampal ERα mRNA levels in males but not females. Hippocampal ERα protein levels by Western blotting were not affected by FGR. However, FGR decreased apparent ERα staining in the cornu ammonis (CA)1, CA3, and dentate gyrus regions in the hippocampi of male newborn rats but not females. We conclude that FGR affects the programming of hippocampal estrogen and hippocampal ERα levels in the newborn rat in a gender-specific manner.     

Diagnostic and Therapeutic Uses of Intestinal Intubation

Intubation of the intestine is widely employed in the clinical management of patients. In this article are discussed some of the more important applications of this procedure in the diagnosis and treatment of intestinal, biliary and pancreatic diseases.     

C‐reactive protein and tumor necrosis factor‐alpha in relation to insulin‐mediated glucose uptake,smoking and atherosclerosis

Objectives. To examine the hypothesis that serum concentration of C‐reactive protein (CRP) is inversely associated with insulin sensitivity and obesity, and that this may by mediated by tumor necrosis factor‐α (TNFα) and interleukin‐6 (IL‐6). Material and methods. Cross‐sectional, one‐center study of a population‐based sample of 58‐year‐old Swedish men (n = 98). Exclusion criteria were cardiovascular disease, clinical diabetes mellitus and/or continuous cardiovascular medication. Glucose infusion‐rate (euglycemic hyperinsulinemic clamp), adjusted for fat‐free mass, which together with total body fat was measured by dual‐energy X‐ray absorptiometry. Serum concentrations of CRP, TNFα, soluble TNFα receptor 2 (sTNFAR2), IL‐6 determined by ELISA. Ultrasound was used to measure intima‐media thickness (IMT) in both common carotid arteries, carotid bulbs and in the right femoral artery. Results. CRP was inversely associated with insulin sensitivity (r = ?0.28, p<0.01) and with total body fat (r = 0.31, p<0.01), but not independently of the TNFα and sTNFAR2 product. Serum CRP, TNFα, sTNFAR2, but not IL‐6, were associated with low insulin sensitivity, total body fat, abdominal obesity, hyperinsulinemia, hypertriglyceridemia, low HDL cholesterol and small LDL particles, i.e. the metabolic syndrome. These associations were independent of smoking and carotid and femoral artery IMT. Conclusions. Serum concentrations of CRP were related to insulin sensitivity and accompanying factors constituting the metabolic syndrome. The results indicate that this association may be mediated by adipose tissue and TNFα effects, the latter measured as the product of TNFα and sTNFAR2. This was a cross‐sectional study and causality cannot be proven.     

健脾祛湿方对2型糖尿病并非酒精性脂肪肝患者脂联素、肿瘤坏死因子-α和肝脏脂肪含量的影响

【目的】观察健脾祛湿方对2型糖尿病（type 2 diabetes mellitus, T2DM）并非酒精性脂肪肝（non-alcoholic fatty liver disease, NAFLD）患者脂联素（adiponectin, APN）、肿瘤坏死因子-α（tumor necrosis facto al’pha, TNF-α）及肝脏脂肪含量变化的影响。【方法】将120例T2DM并NAFLD患者随机分为健脾祛湿方组（治疗组）和吡格列酮组（对照组）各60例,在基础降糖治疗的同时,分别给予健脾祛湿方和吡格列酮治疗,观察时间均为24周。利用声触诊组织量化成像技术（virtual touch tissue quantification technique, VTQ）、酶联免疫吸附（ ELISA）法和生化分析仪观察2组治疗前后肝脏脂肪含量、 APN、TNF-α、血糖、血脂和肝功能等指标的变化。【结果】治疗后,2组空腹血糖（FPG）、餐后2 h血糖（2hPG）、糖化血红蛋白（HbA1c）、空腹胰岛素（FINS）、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、 TNF-α含量及肝实质ARFI (acoustic radiation force impulse)值较治疗前均显著下降(P<0．05),高密度脂蛋白胆固醇（HDL-C）、 APN含量较治疗前显著上升(P<0．05);治疗组治疗前后FINS、 TNF-α差值大于对照组(P<0．05)。【结论】健脾祛湿方可能通过升高APN、降低TNF-α,从而达到纠正糖脂代谢紊乱,保护胰岛功能以及减少肝脏脂肪含量的功效。     

肝硬化大鼠部分肝切除后TGF-α和C-met蛋白在肝脏中的表达及其意义

目的：研究转化生长因子－α（TGF－α），C-met蛋白在肝硬化大鼠肝脏中的表达及意义。方法：将成年雄性Wistar大鼠制作为肝硬化大鼠，然后将肝脏部分切除制作肝再生模型。随机分为7组，一组立即处死，计算肝切除率；其他组分别于术后12h,1d,3d,5d,7d,14d处死。用免疫组织化学方法检测TGF－α和C-met蛋白在肝细胞中的表达，以正常大鼠肝再生模型为对照。结果：肝硬化大鼠部分肝脏切除后不同时间肝中TGF－α，C－met蛋白表达的变化均较正常大鼠延迟。结论：TGF－α和C-met在肝脏中的表达显示，硬化肝脏具有再生能力，但较正常肝脏弱。     

坦索罗辛治疗非细菌性慢性前列腺炎临床分析

目的 :评价选择性α1A 肾上腺素能受体阻滞剂坦索罗辛 (tamsulosin)治疗慢性非细菌性前列腺炎 /慢性盆腔痛综合征 (CPPS)的临床疗效。　方法 :4 3例CPPS病人给予坦索罗辛 0 .2mg口服 ,1次 /d ,治疗 4周 ,比较治疗前后慢性前列腺炎症状评分及尿流率的变化。　结果 :治疗后 ,32例 (74 .4 % )病人评分明显降低 ;最大尿流率(MFR)偏低者 ,MFR和平均尿流率 (AFR)分别提高了 30 .4 %和 6 5 .4 % (P <0 .0 5 ) ;无严重副作用发生。　结论 :选择性α1A 肾上腺素能受体阻滞剂坦索罗辛是治疗CPPS的有效药物     

HIV-1慢性感染者CD8＋T淋巴细胞CD127表达与CD8＋T淋巴细胞凋亡的关系

目的 研究HIV-1慢性感染者CD8＋T淋巴细胞表面CD127（白细胞介素-7受体α链,IL-7Rα）分子的表达及临床意义.方法 收集24例HIV-1慢性感染者和12名健康人群的外周血,分离外周血单核细胞（PBMC）,用直接免疫荧光染色法标记并用流式细胞仪检测T淋巴细胞表面CD127表达和CD8＋T淋巴细胞的自发凋亡,并对CD8＋T淋巴细胞CD127的表达与CD4＋T淋巴细胞计数、HIV RNA载量以及CD8＋T淋巴细胞自发凋亡作相关性分析.组间比较采用Mann-Whitney U检验,Spearman评价组间相关性.结果 与健康对照组比较,HIV-1慢性感染组中CD8＋T淋巴细胞CD127的表达显著下降,差异具有统计学意义（Z=-4.796,P＜0.01）.CD8＋T淋巴细胞CD127的表达与患者CD4＋T淋巴细胞计数呈显著正相关（r=0.817,P＜0.01）,与血浆HIV RNA载量和CD8＋T淋巴细胞的自发凋亡呈显著负相关（r=-0.442和-0.688,P＜0.05和＜0.01）.结论 HIV-1慢性感染组CD8＋T淋巴细胞CD127表达进行性下降可能是导致细胞接受存活信号能力降低和发生凋亡的重要原因,提示IL-7可能是治疗HIV感染的新途径.     

Glut1和HIF-1α在原发性肝细胞癌中的表达和意义

目的探讨葡萄糖转运蛋白1（Glut1）和缺氧诱导因子-1α（HIF-1α）在原发性肝细胞癌中的表达,以及在肝细胞癌发生发展过程中相互关系。方法应用免疫组织化学方法（SP法）,检测108例肝细胞癌及其癌旁组织、15例正常肝组织中Glutl,HIF-1α的表达。结果Glutl和HIF-1α在108例肝细胞癌组织中的阳性表达率分别为74.1%和78.7%,明显高于其在癌旁组织（χ^2=15.27,χ^2=8.727）和正常肝组织（χ^2=31.78,χ^2=27.19）中的表达率（P〈0.05）。Glutl的表达强度与HCC的分化程度（χ^2=27.80）,Edmondson分级（χ^2=6.260）,有无转移（χ^2=11.54）等显著相关（P〈0.05）。HIF-1α在原发性肝癌中的表达强度与HCC分化程度（χ^2=13.05）和肿瘤大小（χ^2=11.74）相关（P〈0.05）。统计学分析显示Glutl和HIF-1α在HCC中的表达呈正相关（χ^2=18.81）。结论Glutl和HIF-1α的异常高表达在原发性肝细胞癌的发生发展中起重要作用,可能促进肝细胞癌的增殖和侵袭转移。Glutl和HIF-1α的表达强度对肝癌的诊断具有临床应用价值。     

Tumor necrosis factor‐alpha antagonist administration recovers skeletal muscle dysfunction in ovariectomized rats

Skeletal muscles deteriorate after ovariectomy. Molecular pathway of this deterioration has not been defined. Tumor necrosis factor (TNF)‐alpha activation is assumed to trigger muscle atrophy and administration of its antagonist is hypothesized to recover this atrophy in rats. Slow‐twitch soleus and fast‐twitch extensor digitorum longus muscle functions were investigated in intact, ovariectomized (OVX), and OVX plus 10 µg/g/week TNF‐alpha antagonist administered female rats. Maximum isometric twitch and tetanic contraction responses were lower in the OVX groups. Maximum isometric twitch amplitudes recovered in the extensor digitorum longus but not in the soleus muscles after TNF‐alpha antagonist administration. The decrease in responses to tetanic stimulations recovered in the OVX–TNF group at frequencies higher than 20 Hz in both muscle types. OVX animals body weight was 21% higher than intact animals. Muscle weight to body weight ratios of the OVX groups were higher than the control group which recovered after TNF‐alpha antagonist administration. Findings suggest that the functional loss in OVX rat muscles is TNF‐alpha pathway dependent. Skeletal muscle atrophy and function after OVX recovered by TNF‐alpha antagonist administration. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:275–280, 2011     

巩固性重复射频消融对甲胎蛋白阴性肝细胞癌射频消融后局部肿瘤进展的疗效

目的 探讨甲胎蛋白(AFP)阴性肝细胞癌(HCC)患者在射频消融(RFA)获得影像学完全消融后,以安全边界(SM)≥1 cm为目标的巩同性重复RFA(CRRFA)对于局部肿瘤进展的影响.方法 课题组在2002年7月至2009年7月间,共收治152例完全消融的AFP阴性HCC.其中,影像学分析显示肿瘤周边部分区域SM＜1 cm者110例,所有区域SM≥1 cm者42例.在SM＜1 cm的110例患者中,59例在首次RFA后6个月内接受了CRRFA,其余51例选择了临床观察随访.然后,据此将符合纳入标准的病例分为窄SM-CRRFA组(n=41)和窄SM-单次RFA组(n=37).此外,还从42例SM≥1.0 cm者,选择符合纳入标准的病例纳入宽SM-单次RFA组(n=30).对三组患者的局部无瘤生存率进行了比较.结果 窄SM-CRRFA组1年、2年、3年、4年和5年局部无瘤生存率分别为97.1%、90.9%、69.6%、47.2%和33.0%;窄SM-单次RFA组分别为85.9%、66.5%、43.5%、15.8%和0.0%;宽SM-单次RFA组分别为92.7%、83.7%、59.3%、36.9%和9.2%.三组间局部无瘤生存率差异有统计学意义(χ2=14.789,P=0.001).两两比较结果 显示,窄SM-CRRFA组和宽SM-单次RFA组的累积局部无瘤生存率均明显高于窄SM-单次RFA组(χ2分别为9.353和5.375,P值分别为0.002和0.020);窄SM-CRRFA组与宽SM-单次RFA组局部无瘤生存率差异无统计学意义(χ2=1.785,P=0.182).结论 对于直径3～5 cm的AFP阴性HCC,RFA治疗后SM≥1 cm是影响局部肿瘤控制效果的重要因素;对于SM＜1 cm者,CRRFA可显著提高局部无瘤生存率.

Abstract：

Objective To retrospectively evaluate the role of consolidative repeat radiofrequency ablation (CRRFA) based on safety margin (SM) analyses in local tumor control for alpha-fetoprotein (AFP) negative hepatocellular carcinoma (HCC) patients who had been shown to have radiological complete ablation (CA) with radiofrequency ablation (RFA). Methods From July 2002 to July 2009,152 AFP negative HCC patients who were shown to have radiological CA with RFA therapy were retrospectively analyzed. Among them, 110 patients had a SM of less than 1 cm and the other 42 patients had a SM of 1cm or more. Among 110 patients with SM less than 1 cm, fifty nine patients accepted CRRFA within 6 months after the first RFA and 51 did not. From these patients, a narrow SM-CRRFA group (n=41) and a narrow SM-single RFA group (n=37) were enrolled respectively. The wide SM-single RFA group (n= 30) was enrolled from the 42 patients with a SM of 1 cm or more.The LTP (local tumor progression)-free survival rate of the 3 groups were compared with a log-rank test. Results One-, two-, three-, four-, and five-year LTP-free survival rates respectively were 97. 1%, 90.9%, 69.6%, 47.2%, and 33. 0% in the narrow SM-CRRFA patients. 85.9%, 66. 5%,43.5%, 15.8%, and 0. 0%, in the narrow SM-single RFA patients, and were 92.7%, 83.7%,59.3%, 36. 9%, and 9.2% in the wide SM-single RFA patients. There were statistically significant differences (χ2 = 14. 789, P= 0. 001) between the groups. Conclusions An ablation zone with an SM of 1 cm or greater was the most important factor for local control of AFP negative HCC ranging from 3 to 5 cm in diameter. For these patients with a SM of less than 1 cm, CRRFA improved the overall local control outcomes.