Bevacizumab‐enhanced antitumor effect of 5‐fluorouracil via upregulation of thymidine phosphorylase through vascular endothelial growth factor A/vascular endothelial growth factor receptor 2‐specificity protein 1 pathway

Bevacizumab (Bv) can be used synergistically with fluoropyrimidine‐based chemotherapy to treat colorectal cancer. Whether and how it affects the delivery of fluoropyrimidine drugs is unknown. The present study aimed to explore the effect of Bv on the delivery of 5‐fluorouracil (5‐FU) to tumors and the underlying mechanism from metabolic perspective. Bv enhanced the anti‐tumor effects of 5‐FU in LoVo colon cancer xenograft mice and increased the 5‐FU concentration in tumors without affecting hepatic 5‐FU metabolism. Interestingly, Bv remarkably upregulated thymidine phosphorylase (TP) in tumors, which mediated the metabolic activation of 5‐FU. Although TP is reported to promote angiogenesis and resistance, the combination of Bv and 5‐FU resulted in anti‐angiogenesis and vessel normalization in tumors, indicating that the elevated TP mainly contributed to the enhanced response to 5‐FU. Bv also induced TP upregulation in LoVo cancer cells. Treatment with vascular endothelial growth factor receptor 2 (VEGFR2) antagonist apatinib and VEGFR2 silencing further confirmed TP upregulation. Bv and apatinib both enhanced the cytotoxicity of 5‐FU in LoVo cells, but there was no synergism with adriamycin and paclitaxel. We further demonstrated that the effect of Bv was dependent on VEGFR2 blockade and specificity protein 1 activation via MDM2 inhibition. In summary, Bv enhanced the accumulation of 5‐FU in tumors and the cytotoxicity of 5‐FU via TP upregulation. We provide data to better understand how Bv synergizes with 5‐FU from metabolic perspective, and it may give clues to the superiority of Bv in combination with fluoropyrimidine drugs compared to other chemotherapeutic drugs in colon cancer.     

Ordered water and ligand mobility in the HIV-1 integrase-5CITEP complex: a molecular dynamics study.

A 2 ns molecular dynamics simulation has been carried out for the HIV-1 integrase-5CITEP complex in order to understand the role of water in defining the ligand's binding mode and to address issues of binding site flexibility and ligand motion. Although the ligand retains considerable mobility within the active site, a structural water molecule bridging 5CITEP with Asp 64 and Asn 155 is identified in the simulation. Consideration of this water molecule could open a route to new HIV-1 integrase inhibitors.     

肾肿瘤中浸润性树突状细胞的免疫状态变化

目的 通过分析。肾肿瘤中浸润性树突状细胞的免疫状态变化，以探讨其在。肾肿瘤微环境中的功能状态。方法选择未经任何非手术治疗的。肾透明细胞癌患者标本40例作为实验组，10例正常。肾组织作为对照组，通过免疫组织化学技术标记组织中树突状细胞（dendritic cell，DC）的CDla、HLA-DR和CD86抗原，观察正常。肾及。肾透明细胞癌组织中DC的3种抗原的表达，结果进行统计学分析。站果所有。肾透明细胞癌组织中均未见明显CD86＋ DC，但均有CDla＋ DC，其在肾癌组织中的浸润程度明显高于正常。肾组织（P〈O．001），但CDla＋ DC与肾癌临床分期及组织学分级均无相关性；在肾癌组中有34例癌实质内的DC表达HLA-DR抗原，其阳性表达率为85％，与正常肾组织80％的阳性表达率相比无统计学意义（P〉O．05）。站论DC具有趋化性，可以向肿瘤组织聚集，肾癌组织中存在CDIa，肾癌患者CD86表达低下，提示肾癌患者DC存在免疫缺陷，而DC的免疫功能低下则可能是肾癌逃避宿主免疫监视的主要原因。     

膀胱癌患者外周血树突状细胞免疫状态变化及其临床意义

目的探讨膀胱癌患者外周血中树突状细胞（DC）的免疫功能状态变化及其与膀胱癌发生的关系。方法检测15例临床确诊的中晚期膀胱癌患者外周血DC表面CD1a、CD83表达水平及免疫诱导T淋巴细胞增殖的能力，并与10名健康成人比较。结果膀胱癌患者DC表面CDla及CD83表达水平（分别为57．4±1．6，72．1±1．1）明显低于正常对照组（64．9±1．4，80．6±1．2，P〈0．05）；其体外诱导T细胞增殖的能力亦明显低于正常对照组（P〈0．05）。结论膀胱癌患者DC存在免疫功能缺陷可能是膀胱癌逃避宿主免疫监视的重要原因之一。     

Changes in brain function and anatomical structure following treatment of hyperbaric oxygen for visual pathway abnormalities in 16 cases★ Evaluation of functional magnetic resonance imaging combined with diffusion tensor imaging

BACKGROUND： There is a growing research focus on the combination of blood oxygenation level dependent functional magnetic resonance imaging （BOLD-fMRI） and diffusion tensor imaging （DTI） to evaluate visual cortical function and structural changes in the cerebrum, as well as morphological changes to the white matter fiber tracks, after visual pathway lesions. However, the combined application of BOLD-fMRI and DTI in treating of visual pathway abnormalities still requires further studies.
OBJECTIVE： To observe and evaluate the effects of hyperbaric oxygen on visual pathway abnormalities, and to evaluate the characteristics of cerebral function and anatomic structural changes by using BOLD-fMRI combined with DTI technique. DESIGN： Case contrast observation.
SETTING： Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA.
PARTICIPANTS： Sixteen patients （9 males and 7 females, 15-77 years old） with lateral or bilateral visual disorder induced by visual pathway lesions were selected from the Department of Neurology, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA from January 2006 to May 2007. These patients comprised the lesion group. Measures of interventional therapy： hyperbaric oxygen of two normal atmospheres for three courses （10 d/course） and routine internal medicine treatment. In addition, 12 healthy subjects of similar sex and age to the lesion group were regarded as the control group. The control group underwent routine ophthalmological and ocular fundus examinations; diagnostic results were normal. The experiment received confirmed consent from the local ethic committee, and all patients provided informed consent.
METHODS： BOLD-fMRI and DTI manifestations in the lesion group were observed before and after hyperbaric oxygen intervention, and the results were compared with the control group. The subjects were positioned on their back, and BOLD-fMRI images were collected with the following GRE EPI sequence： TR = 2 000 ms, TE = 40     

羊皮覆盖微粒皮肤移植11例体会

目的 探讨异种羊皮作为创面覆盖物行微粒皮肤移植的临床应用。方法 微粒皮肤移植羊皮覆盖１１例。结果 微粒移植Ⅰ类愈合占５７．１％，Ⅱ类愈合占３５．７％。结论 羊皮作为烧伤同的覆盖物必须在保证活力的前提下使用，可以满足临床需要。     

床旁多功能固定器的制作与应用

目前我院使用的病床输液架固定管均位于病床两侧的斜对角固定位置，不能满足病人体位变化的需要。现临床病人留置的引流袋及尿袋常采用大别针、绳子、布袋或铁丝等工具固定，既不美观，又不方便，且操作环节复杂，易致引流袋或尿管滑脱。为了避免上述不足，笔者于2006年3月自行设计制作了床旁多功能固定器，经临床200例应用，效果满意。现介绍如下。