Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling.     

脑梗死患者颈动脉彩色多普勒超声研究

目的 探讨颈动脉粥样硬化及其危险因素与不同类型的脑梗死间的关系。方法：根据头颅ＣＴ或ＭＲＩ结果将１８８例脑梗死患者分成四个亚组：皮层梗死组（ＣＩ）,皮层下梗死组（ＳＣＩ）,椎－基底动脉支配区梗死组（ＶＢＡＩ）及心源性脑栓塞组（ＣＥＩ）,用彩色多勒超声（彩超）对各型脑梗死患者颅外颈动脉粥样硬化严重程度进行评估,并对可能危险因素进行探讨。结果 ３０％的ＣＩ组患者,１０％ＣＥＩ患者,６．９％ＶＢＡＩ患者     

急性白血病WT1基因的表达及其临床意义

目的　探讨WT 1基因表达水平与急性白血病 (AL)预后的关系及在微小残留病 (MRD )检测中的意义。方法　采用荧光定量RT PCR法 (FQ RT PCR ) ,测定 40例不同类型及处于不同疾病阶段 (2 6例初治、5例复发、9例CR >3年 )的AL患者WT1基因的表达。结果　对照组WT1基因均为阴性。 40例AL患者中有 2 6例WT 1基因表达阳性 ,阳性组与阴性组CR率分别为 3 4.6%和 78.5 % (P <0 .0 5 )。其中初治、复发与CR >3年的患者 ,WT 1阳性基因拷贝数的平均值分别为 4.14× 10 3 拷贝 /ml、8.5 8× 10 3 拷贝 /ml和 7.87× 10 1拷贝 /ml。CR后WT 1基因表达水平明显下降 ,复发后又显著升高。结论　FQ RT PCR实验方法客观准确 ,WT1基因的表达水平与AL患者的化疗效果及预后密切相关 ,可以作为检测MRD的标志     

WT1 peptide‐based immunotherapy for advanced thymic epithelial malignancies

Thymic epithelial tumors are rare malignancies, and no optimal therapeutic regimen has been defined for patients with advanced disease. Patients with advanced thymic epithelial tumors, which were resistant or intolerable to prior therapies, were eligible for this study. Patients received 9 mer‐WT1‐derived peptide emulsified with Montanide ISA51 adjuvant via intradermal administration once a week as a monotherapy. After the 3‐month‐protocol treatment, the treatment was continued mostly at intervals of 2–4 weeks until disease progression or intolerable adverse events occurred. Of the 15 patients enrolled, 11 had thymic carcinoma (TC) and 4 had invasive thymoma (IT). Median period from diagnosis to the start of treatment was 13.3 and 65.5 months for TC and IT, respectively. No patients achieved a complete or partial response. Of the 8 evaluable TC patients, 6 (75.0%) had stable disease (SD) and 2 had progressive disease (PD). Of the 4 evaluable IT patients, 3 (75.0%) had SD and 1 (25.0%) had PD. Median period of monotherapy treatment was 133 and 683 days in TC and IT patients, respectively. No severe adverse events occurred during the 3‐month‐protocol treatment. As adverse events in long responders, thymoma‐related autoimmune complications, pure red cell aplasia and myasthenia gravis occurred in two IT patients. Cerebellar hemorrhage developed in a TC patient complicated with Von Willebrand disease. Induction of WT1‐specific immune responses was observed in the majority of the patients. WT1 peptide vaccine immunotherapy may have antitumor potential against thymic malignancies.     

显微外科条件下鞍区肿瘤入路的选择

目的：评价治疗鞍区肿瘤常用的各种手术入路的治疗效果。方法：应用显微外科手术并采用不同的手术入路治疗４１例鞍区常见肿瘤，从手术显露范围、全切率等不同角度评价呼种手术入路的效果。结果：翼点入路的改良点入路能够取代一些创伤较大的入路，在显微外科条件下已成为最常用的手术入路。结论：结论各类肿瘤的临床特点，尤其是肿瘤与邻近结构、生长方面的关系，选择适当的手术入路并与显微外科技术有机结合是取得最好疗效的关键。     

子宫肌瘤患者的血清性激素及泌乳素水平观察

目的：通过中肌瘤患者的血清性激素和泌乳素水平。了解内分泌因素与子宫 关系。方法：应用放射免疫法检测子宫肌瘤患者的血清雌二醇（Ｅ２），孕酮（Ｐ）、卵泡刺激素（ＦＳＨ）、黄体生成素（ＬＨ）、泌乳素（ＰＲＬ）。结果：３０例子宫肌瘤患者的性激素及泌乳素未见明显异常。结论：子宫肌瘤患者常有正常的卵巢功能，它的发生、发展是多因素作用的结果。     

进展期胃癌术中腹腔温热化疗

目的；探讨腹腔温热化疗与进展期胃癌生存率的关系，方法：通过术中腹腔灌注４３度蒸馏水，１０００ｍｌ－２０００ｍｌ加丝裂霉素１０ｍｇ，约２ｈ后放开引流管引流，统计５年生存率。结果：在１８６例进展期胃癌腹腔温热化疗后５年生存率从１１．８％提高到３８．７％。结论：腹腔温热化疗可提高进展期胃癌５年生存率，且方法简单副作用少。