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| 1 | Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis显示文摘Nonalcoholic fatty liver disease(NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse.Nonalcoholic steatohepatitis(NASH),a severe form of NAFLD,can progress to liver cirrhosis and hepatocellular carcinoma.NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity,type 2 diabetes,and hyperlipemia.Animal models of NAFLD/NASH give crucial information,not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents.An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH.Animal models of NAFLD/NASH are divided into genetic,dietary,and combination models.In this paper,we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages. | Yoshihisa Takahashi Yurie Soejima Toshio Fukusato | 2012 | World Journal of Gastroenterology2012，18，19： | 57 |
| 2 | Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma显示文摘AIM: To assess the clinical features and prognosis of 151 patients with extrahepatic metastases from primary hepatocellular carcinoma (HCC), and describe the treatment strategy for such patients. METHODS: After the diagnosis of HCC, all 995 consecutive HCC patients were followed up at regular intervals and 151 (15.2%) patients were found to have extrahepatic metastases at the initial diagnosis of primary HCC or developed such tumors during the follow-up period. We assessed their clinical features, prognosis, and treatment strategies. RESULTS: The most frequent site of extrahepatic metastases was the lungs (47%), followed by lymph nodes (45%), bones (37%), and adrenal glands (12%). The cumulative survival rates after the initial diagnosis of extrahepatic metastases at 6, 12, 24, and 36 mo were 44.1%, 21.7%, 14.2%, 7.1%, respectively. The median survival time was 4.9 mo (range, 0-37 mo). Fourteen patients (11%) died of extrahepatic HCC, others died of primary HCC or liver failure. CONCLUSION: The prognosis of HCC patients with extrahepatic metastases is poor. With regard to the cause of death, many patients would die of intrahepatic HCC and few of extrahepatic metastases. Although most of HCC patients with extrahepatic metastases should undergo treatment for the primary HCC mainly, treatment of extrahepatic metastases in selected HCC patients who have good hepatic reserve, intrahepatictumor stage (T0-T2), and are free of portal venous invasion may improve survival. | Kiminori Uka Hiroshi Aikata Shintaro Takaki Hiroo Shirakawa Soo Cheol Jeong Keitaro Yamashina Akira Hiramatsu Hideaki Kodama Shoichi Takahashi Kazuaki Chayama | 2007 | World Journal of Gastroenterology2007，13，3： | 44 |
| 3 | Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis显示文摘Nonalcoholic fatty liver disease(NAFLD)/nonalcoholic steatohepatitis(NASH) is considered to be a hepatic manifestation of metabolic syndrome, and its incidence is rapidly increasing worldwide. It is currently the most common chronic liver disease. NASH can progress to liver cirrhosis and hepatocellular carcinoma, and may result in liver-related death. Currently, the principal treatment for NAFLD/NASH is lifestyle modification by diet and exercise. However, pharmacological therapy is indispensable because obese patients with NAFLD often have difficulty maintaining improved lifestyles. The pathogenesis of NAFLD/NASH has not been completely elucidated. However, insulin resistance, inflammatory cytokines, and oxidative stress are thought to be important in the development and/or progression of the disease. Currently, insulin sensitizers(thiazolidinediones) and antioxidants(vitamin E) seem to be the most promising therapeutic agents for NAFLD/NASH, and lipid-lowering drugs, pentoxifylline, angiotensin receptor blockers, and n-3 polyunsaturated fatty acids also have promise. However, there is a lack of consensus regarding the most effective and appropriate pharmacotherapy for NAFLD/NASH. Animal experiments suggest that herbal medicines and natural products may be promising therapeutic agents for NAFLD/NASH, but their efficacy and safety are yet to be investigated in human studies. In this paper, we review the existing and potential pharmacological therapies for NAFLD/NASH. | Yoshihisa Takahashi Keiichiro Sugimoto Hiroshi Inui Toshio Fukusato | 2015 | World Journal of Gastroenterology2015，21，13： | 41 |
| 4 | 高原鼠兔生境选择的初步研究显示文摘在石渠县西区的高山草甸和高山灌丛草甸分布区采用卫星照片(1∶100000)结合样线法,在草地(雅砻江及其支流两边)每隔150m设置一个样方,其他环境则每隔100m设置一个样方,样方面积为5×5m2,记录样方所在地的海拔高度、坡度、坡向、生境位置、样方内植被的盖度、阔叶植物盖度、阔叶植物高度、灌丛盖度、土壤质地、离水源的距离以及鼠兔洞数量.共设置样方312个,样方内的高原鼠兔洞数量最多为80个,最少为0,平均为13.7±15个.统计结果显示:影响高原鼠兔生境选择的主要因子依次是生境位置、土壤质地、离水源的距离、灌丛植物盖度和阔叶植物高度.分析表明,高原鼠兔选择的最优生境为下坡位、土质松软、离水源的距离小于50m、阔叶植物高度小于等于5cm,没有灌丛的环境. | 王淯 王小明 王正寰 Patrick Giraudoux Kenichi Takahashi Graham Alastair | 2004 | 四川大学学报(自然科学版)2004，41，5： | 37 |
| 5 | 双能CT碘覆盖技术对肾肿块囊实性的鉴别:模型的可行性研究显示文摘本研究的目的是评估双能CT(DECT)区分肾病变模型为囊肿抑或强化肾肿块的能力。将直径为0.5~3.0cm的6个圆筒内注人蒸馏水或滴人碘对比剂溶液,在120kV时其CT值为0HU代表囊肿,10、20、40HU代表增强的肿块。这些圆筒被放在一个直径为12cm肾脏模型里,内含牛肉酱和碘对比剂以模拟CT值为100HU和250HU的强化肾实质。将其浸泡在直径28cm的水浴箱中。这些组合产生48个大小不同、内部和实质强化不同的肾病变模型(12个囊肿和36个强化肿块)。 | C.L. Brown R.P. Hartmau O.P. Dzyubak N. Takahashi A. Kawashima C.H. McCollough 刘洪杰(译) 李威(校) | 2009 | 国际医学放射学杂志2009，32，4： | 39 |
| 6 | 中国北方草原草畜代谢能平衡分析与对策研究显示文摘草畜平衡是天然草地可持续利用和放牧家畜高效生产的前提,草畜平衡评估技术是实现草原保护,提高草地畜牧业可持续发展的基础。本研究建立了以代谢能为指标的草畜平衡评价方法,2008年冬以甘肃肃南草原和典型牧户为研究对象,通过草畜代谢能平衡分析了草畜平衡现状,应用研究试验,验证了实现草畜平衡的优化途径和对策。草畜平衡分析结果表明,在牧草生长期(6月-10月)家畜获得的代谢能高于家畜的维持需要,因此,家畜体重增加,生长速度最快;在枯草期(11月-次年5月)代谢能摄入量低于维持需要量,家畜掉膘,体重下降,夏草场的载畜量最大。冬季暖棚舍饲养殖能够降低家畜的代谢能需要,有助于实现草畜平衡。与对照组相比,暖棚养殖绵羊平均产毛量显著提高(P<0.05),提高了0.73kg/只,冷季体重损失减少14.9%,纯收入增加126.25元/只。产羔时间对草畜平衡具显著的影响,适当推迟产羔时间能够有效的改善草畜平衡状况。分别测定了4月和5月所产羔羊的生长发育情况和母羊体况,5月羔羊平均初生重、1月龄、2月龄体重显著高于4月份羔羊(P<0.05),但由于生长期短,5月羔羊出栏重较4月低4~5kg。草畜代谢能平衡是分析研究草畜平衡的科学、合理和准确的方法和技术,草畜代谢能平衡分析模型的准确度高,适用性强,有利于草原管理,所提出的改善草畜平衡的途径和策略可行性高。 | 杨博 吴建平 杨联 David Kemp 宫旭胤 Taro Takahashi 冯明廷 | 2012 | 草业学报2012，21，2： | 37 |
| 7 | Apoptosis and non-alcoholic fatty liver diseases显示文摘The number of patients with nonalcoholic fatty liver diseases(NAFLD) including nonalcoholic steatohepatitis(NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma(HCC) and is one of the most serious health problems in the world. The mechanism through which NASH progresses is still largely unknown. Activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD/NASH. Apoptotic hepatocytes stimulate immune cells and hepatic stellate cells toward the progression of fibrosis in the liver through the production of inflammasomes and cytokines. Abnormalities in glucose and lipid metabolism as well as microbiota accelerate these processes. The production of reactive oxygen species, oxidative stress, and endoplasmic reticulum stress is also involved. Cell death, including apoptosis, seems very important in the progression of NAFLD and NASH. Recently, inhibitors of apoptosis have been developed as drugs for the treatment of NASH and may prevent cirrhosis and HCC. Increased hepatocyte apoptosis may distinguish NASH from NAFLD, and the improvement of apoptosis could play a role in controlling the development of NASH. In this review, the association between apoptosis and NAFLD/NASH are discussed. This review could provide their knowledge, which plays a role in seeing the patients with NAFLD/NASH in daily clinical practice. | Tatsuo Kanda Shunichi Matsuoka Motomi Yamazaki Toshikatsu Shibata Kazushige Nirei Hiroshi Takahashi Tomohiro Kaneko Mariko Fujisawa Teruhisa Higuchi Hitomi Nakamura Naoki Matsumoto Hiroaki Yamagami Masahiro Ogawa Hiroo Imazu Kazumichi Kuroda Mitsuhiko Moriyama | 2018 | World Journal of Gastroenterology2018，24，25： | 32 |
| 8 | 全球气候变化对中国未来地表径流的影响显示文摘本文应用改进的水分平衡模型研究了不同气候变化情景下中国未来地表径流的变化。结果表明 :基于不同的气候变化情景模拟所得的地表径流变化在空间上有差异 ,总体上 ,中国未来的地表径流将增加 ;长江上游地区的地表径流春季下降但在夏季增加 ,而下游地区的则相反 ,夏季径流下降而春季径流剧增 ;气溶胶对地表径流变化方面有影响 ,但在各个气候变化情景下缺乏一致性。 | 游松财 Kiyoshi Takahashi Yuzuru Matsuoka | 2002 | 第四纪研究2002，22，2： | 29 |
| 9 | Earthworm fibrinolytic enzyme:anti-tumor activity on human hepatoma cells in vitro and in vivo显示文摘背景蚯蚓 fibrinolytic 酶(EFE ) 是在蚯蚓的消化的洞是广泛地分布式的复杂蛋白质酶。拥有的强壮的蛋白质水解作用活动, EFE 不仅血纤维蛋白上的直接效果,而且罐头激活 plasminogen。它的治疗学并且血栓相关的疾病上的预防效果临床上被证实了。最近,在那里被增加了对 EFE 的反肿瘤活动的兴趣。在这研究, EFE 的反肿瘤活动,从 Eisenia foetida 孤立,在人的 hepatoma 上,房间在 vitro 并且在包含的 vivo.The 潜力机制被评估也是在 vitro 实验的 studied.Methods 在四根人的 hepatoma 房间线被执行:有在各种各样的集中的 EFE 的 HLE, Huh7, PLC/PRF/5 和 HepG2.After 处理,房间增长的率的抑制被测量。为在里面 vivo 研究,有 Huh7 房间的忍受肿瘤的模特儿 xenografted 在裸体鼠标,然后鼠标被开发一天用 EFE 被喂一次 4 个星期,和接待的控制组仅仅盐。肿瘤生长上的禁止的效果被观察。另外, apoptosis 与流动 cytometric 试金被观察并且荧光灯与氮蒽橘子和 ethidium 溴化物(AO/EB ) 染色的染料。矩阵 metalloproteinase 的表示(MMP-2 ) 2 被西方的弄污的 assay.Results 与 EFE 的各种各样的集中在处理以后检测,所有 hepatoma 房间线的增长被压制到在 vitro 改变度。为 HLE, Huh7, PLC/PCF/5 和 HepG2 的 IC50 分别地是 2.11, 5.87, 25.29 和 17.30 uku/ml。在 EFE 的管理以后口头上地为 4 个星期,在裸体老鼠的 Huh7 房间的肿瘤异种皮移植的生长显著地在 vivo 被禁止。肿瘤在 EFE 500 uku/ 的禁止的率(kg 敨慰潴慭挠汥獬椠 ? 楶牴 ? 湡 ? 湩瘠? | CHEN Hong Shoichi Takahashi Michio Imamura Eiko Okutani ZHANG Zhi-guo Kazuaki Chayama CHEN Bao-an | 2007 | Chinese Medical Journal2007，，10： | 27 |
| 10 | Radiation pneumonitis after stereotactic radiation therapy for lung cancer显示文摘Stereotactic body radiation therapy(SBRT)has a locacontrol rate of 95%at 2 years for non-small cell lungcancer(NSCLC)and should improve the prognosis oinoperable patients,elderly patients,and patients withsignificant comorbidities who have early-stage NSCLCThe safety of SBRT is being confirmed in internationalmulti-institutional PhaseⅡtrials for peripheral lungcancer in both inoperable and operable patients,bureports so far have found that SBRT is a safe and effective treatment for early-stage NSCLC and early metastatic lung cancer.Radiation pneumonitis(RP)is oneof the most common toxicities of SBRT.Although mospost-treatment RP is Grade 1 or 2 and either asymptomatic or manageable,a few cases are severe,symptomatic,and there is a risk for mortality.The reportedrates of symptomatic RP after SBRT range from 9%to28%.Being able to predict the risk of RP after SBRT isextremely useful in treatment planning.A dose-effecrelationship has been demonstrated,but suggesteddose-volume factors like mean lung dose,lung V20and/or lung V2.5 differed among the reports.We foundthat patients who present with an interstitial pneumo-nitis shadow on computed tomography scan and high levels of serum Krebs von den Lungen-6 and surfactant protein D have a high rate of severe radiation pneumo-nitis after SBRT.At our institution,lung cancer patients with these risk factors have not received SBRT since 2006,and our rate of severe RP after SBRT has de-creased significantly since then. | Hideomi Yamashita Wataru Takahashi Akihiro Haga Keiichi Nakagawa | 2014 | World Journal of Radiology2014，6，9： | 22 |
| 11 | Case of clear-cell hepatocellular carcinoma that developed in the normal liver of a middle-aged woman显示文摘A 36-year-old woman was admitted to our department for close examination of a liver tumor that was found during a medical checkup. Abdominal US, CT and MRI showed a tumor in segment 7 (S7) of the liver. Although imaging suggested hepatocellular carcinoma, laboratory tests showed no abnormality in liver function, hepatitis virus markers were negative, and tumor markers including protein induced by vitamin K absence or antagonist Ⅱ (PIVKA-Ⅱ), α-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) were all within normal ranges. Upon aspiration biopsy of the liver, the histopathological diagnosis was moderately differentiated hepatocellular carcinoma. Therefore, right hepatectomy was performed. Although a part of the tumor was necrotic, about 60% of the viable part showed a clear-cell variant. Consequently, it was diagnosed as clear-cell hepatocellular carcinoma. It was noted that the background liver tissue was normal. This case is worthy of reporting because development of clear-cell hepatocellular carcinoma in the normal liver of a middle-aged woman is rarely seen. | Atsushi Takahashi Hironobu Saito Yukiko Kanno Kazumichi Abe Junko Yokokawa Atsushi Irisawa Akira Kenjo Takuro Saito Mitsukazu Gotoh Hiromasa Ohira | 2008 | World Journal of Gastroenterology2008，14，1： | 20 |
| 12 | Stem cell-derived exosomes as a therapeutic tool for cardiovascular disease显示文摘Mesenchymal stem cells(MSCs) have been used to treat patients suffering from acute myocardial infarction(AMI) and subsequent heart failure. Although it was originally assumed that MSCs differentiated into heart cells such as cardiomyocytes, recent evidence suggests that the differentiation capacity of MSCs is minimal and that injected MSCs restore cardiac function via the secretion of paracrine factors. MSCs secrete paracrine factors in not only naked forms but also membrane vesicles including exosomes containing bioactive substances such as proteins, messenger RNAs, and microR NAs. Although the details remain unclear, these bioactive molecules are selectively sorted in exosomes that are then released from donor cells in a regulated manner. Furthermore, exosomes are specifically internalized by recipient cells via ligand-receptor interactions. Thus, exosomes are promising natural vehicles that stably and specifically transport bioactive molecules to recipient cells. Indeed, stem cell-derived exosomes have been successfully used to treat cardiovascular disease(CVD), such as AMI, stroke, and pulmonary hypertension, in animal models, and their efficacy has been demonstrated. Therefore, exosome administration may be a promising strategy for the treatment of CVD. Furthermore, modifications of exosomal contents may enhance their therapeutic effects. Future clinical studies are required to confirm the efficacy of exosome treatment for CVD. | Etsu Suzuki Daishi Fujita Masao Takahashi Shigeyoshi Oba Hiroaki Nishimatsu | 2016 | World Journal of Stem Cells2016，8，9： | 19 |
| 13 | Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis显示文摘Nonalcoholic fatty liver disease(NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis(NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma(HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC(SH-HCC), showsfeatures that resemble non-neoplastic steatohepatitis,and is thought to be strongly associated with underlying NASH.In this report,we review the histopathological features of NAFLD/NASH. | Yoshihisa Takahashi Toshio Fukusato | 2014 | World Journal of Gastroenterology2014，20，42： | 19 |
| 14 | Placenta Previa Accreta and Previous Cesarean Section:Some Clarifications显示文摘 | Shigeki Matsubara Hironori Takahashi | 2018 | Chinese Medical Journal2018，，12： | 18 |
| 15 | Human platelets inhibit liver fibrosis in severe combined immunodeficiency mice显示文摘AIM:To investigate the role of human platelets in liver fibrosis.METHODS:Severe combined immunodeficiency(SCID)mice were administered CCl4and either phosphate-buffered saline(PBS group)or human platelet transfusions(hPLT group).Concentrations of hepatocyte growth factor(HGF),matrix metallopeptidases(MMP)-9,and transforming growth factor-β(TGF-β)in the liver tissue were compared between the PBS and the hPLT groups by enzyme-linked immunosorbent assay(ELISA)and Western blotting.The effects of a human platelet transfusion on liver fibrosis included the fibrotic area,hydroxyproline content,and-smooth muscle actin(α-SMA)expression,which were evaluated by picrosirius red staining,ELISA,and immunohistochemical staining using an anti-mouse-SMA antibody,respectively.Phosphorylations of mesenchymal-epithelial transition factor(Met)and SMAD3,downstream signals of HGF and TGF-β,were compared between the two groups by Western blotting and were quantified using densitometry.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling.Furthermore,the accumulation of human platelets in the liver 2 h after platelet transfusion was compared between normal and fibrotic livers by immunohistochemical staining using an anti-human CD41 antibody.RESULTS:The fibrotic area and hydroxyproline content in the liver were both significantly lower in the hPLT group when compared to the PBS group(fibrotic area,1.7%±0.6%vs 2.5%±0.6%,P=0.03;hydroxyproline content,121±26 ng/g liver vs 156±47 ng/g liver,P=0.04).There was less α-smooth muscle actin staining in the hPLT group than in the PBS group(0.5%±0.1%vs 0.8%±0.3%,P=0.02).Hepatic expression levels of mouse HGF and MMP-9were significantly higher in the hPLT group than in the PBS group(HGF,109±13 ng/g liver vs 88±22 ng/g liver,P=0.03;MMP-9,113%±7%/GAPDH vs 92%±11%/GAPDH,P=0.04).In contrast,the concentration of mouse TGF-β in the liver tissue was significantly lower in the hPLT group than in the PBS group(22±5ng/g liver vs 39±6 ng/g liver,P=0.02).Phosphorylation of Met was more prevalent in the hPLT group than in the PBS group(37%±4%/GAPDH vs 20%±8%/GAPDH,P=0.03).Phosphorylation of SMAD3was weaker in the hPLT group than in the PBS group(60%±12%/GAPDH vs 84%±12%/GAPDH,P=0.1),although this difference was not significant.Furthermore,a lower rate of hepatocyte apoptosis was observed in the hPLT group than in the PBS group(5.9%±1.7%vs 2.9%±2.1%,P=0.02).Significant human platelet accumulation was observed in the fibrotic liver tissues,whereas few platelets accumulated in the normal liver.CONCLUSION:Human platelets inhibit liver fibrosis in SCID mice.Increased concentration of HGF in the liver suppresses hepatic stellate cell activation,induces MMPs,and inhibits hepatocyte apoptosis. | Kazuhiro Takahashi Soichiro Murata Kiyoshi Fukunaga Nobuhiro Ohkohchi | 2013 | World Journal of Gastroenterology2013，19，32： | 17 |
| 16 | Adipose tissue-derived stem cells as a therapeutic tool for cardiovascular disease显示文摘Adipose tissue-deried stem cells( ADSCs) are adult stem cells that can be easily harvested from subcutaneous adipose tissue. Many studies have demonstrated that ADSCs differentiate into vascular endothelial cells(VECs), vascular smooth muscle cells(VSMCs), and cardiomyocytes in vitro and in vivo. However, ADSCs may fuse with tissue-resident cells and obtain the corresponding characteristics of those cells. If fusion occurs, ADSCs may express markers of VECs, VSMCs, and cardiomyocytes without direct differentiation into these cell types. ADSCs also produce a variety of paracrine factors such as vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor-1 that have proangiogenic and/or antiapoptotic activities. Thus, ADSCs have the potential to regenerate the cardiovascular system via direct differentiation into VECs, VSMCs, and cardiomyocytes, fusion with tissueresident cells, and the production of paracrine factors. Numerous animal studies have demonstrated the efficacy of ADSC implantation in the treatment of acute myocardial infarction(AMI), ischemic cardiomyopathy(ICM), dilated cardiomyopathy, hindlimb ischemia, and stroke. Clinical studies regarding the use of autologous ADSCs for treating patients with AMI and ICM have recently been initiated. ADSC implantation has been reported as safe and effective so far. Therefore, ADSCs appear to be useful for the treatment of cardiovascular disease. However, the tumorigenic potential of ADSCs requires careful evaluation before their safe clinical application. | Etsu Suzuki Daishi Fujita Masao Takahashi Shigeyoshi Oba Hiroaki Nishimatsu | 2015 | World Journal of Cardiology2015，7，8： | 17 |
| 17 | Current advances in humanized mouse models显示文摘收到了人的房间或纸巾的人性化的老鼠模型移植在基本、适用的人的疾病研究是极其有用的。高度 immunodeficient 老鼠,不拒绝异种皮移植和支持细胞和织物区别和生长,为产生另外的适当模型是不可缺少的。自从 2000 年代初,为产生人性化的老鼠适当的一系列 immunodeficient 老鼠是连续地由介绍 IL-2Rγ 发展了; 空 基因(例如, NOD/SCID/γ c 空 和 Rag2 空 γc 空 老鼠) 。这些紧张显示出不仅高度人的房间嫁接评价,而且产生区分得好的 multilineage 在人的造血的干细胞(HSC ) 以后的人的造血的房间移植。这些人性化的老鼠在 vivo 便于人的血液学和免疫学的分析。然而,从 HSC 开发的人的造血的房间不与那些 phenotypically 并且机能上地总是相同在人。更最近, immunodeficient 老鼠的一个新系列补偿劣势这些。这些老鼠被遗传上介绍人的 cytokine 基因进 NOD/SCID/γ 产生; c 空 和 Rag2 空 γc 空 老鼠。在这评论,我们描述在这些老鼠开发的人的造血的房间的当前的知识。用这些人性化的老鼠的各种各样的人的疾病老鼠模型被总结。 | Ryoji Ito Takeshi Takahashi Ikumi Katano Mamoru Ito | 2012 | Cellular & Molecular Immunology2012，9，3： | 15 |
| 18 | Sentinel lymph node navigation surgery for early stage gastric cancer显示文摘We attempted to evaluate the history of sentinel node navigation surgery(SNNS),technical aspects,tracers,and clinical applications of SNNS using Infrared Ray Electronic Endoscopes(IREE)combined with Indocyanine Green(ICG).The sentinel lymph node(SLN)is defined as a first lymph node(LN)which receives cancer cells from a primary tumor.Reports on clinical application of SNNS for gastric cancers started to appear since early 2000s.Two prospective multicenter trials of SNNS for gastric cancer have also been accomplished in Japan.Kitagawa et al reported that the endoscopic dual(dye and radioisotope)tracer method for SN biopsy was confirmed acceptable and effective when applied to the early-stage gastric cancer(EGC).We have previously reported the usefulness of SNNS in gastrointestinal cancer using ICG as a tracer,combined with IREE(Olympus Optical,Tokyo,Japan)to detect SLN.LN metastasis rate of EGC is low.Hence,clinical application of SNNS for EGC might lead us to avoid unnecessary LN dissection,which could preserve the patient’s quality of life after operation.The most ideal method of SNNS should allow secure and accurate detection of SLN,and real time observation of lymphatic flow during operation. | Norio Mitsumori Hiroshi Nimura Naoto Takahashi Masahiko Kawamura Hiroaki Aoki Atsuo Shida Nobuo Omura Katsuhiko Yanaga | 2014 | World Journal of Gastroenterology2014，20，19： | 15 |
| 19 | Correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis显示文摘AIM:To elucidate the correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis(AL-LC).METHODS:The subjects included 35 patients with ALLC(34 men,1 woman;mean age,58.9±10.7 years;median age,61 years;range:37-76 years).All patientswere enrolled in this study after obtaining written informed consent.Liver function was measured with tests measuring albumin(Alb),prothrombin time(PT),brain natriuretic peptide(BNP),branched amino acid and tyrosine ratio(BTR),branched chain amino acid(BCAA),tyrosine,ammonia(NH3),cholinesterase(Ch E),immunoreactive insulin(IRI),total bile acid(TBA),and the retention rate of indocyanine green 15 min after administration(ICG R15).Hepatic blood flow,hepatic arterial tissue blood flow(HATBF),portal venous tissue blood flow(PVTBF),and total hepatic tissue blood flow(THTBF)were simultaneously calculated using xenon computed tomography.RESULTS:PVTBF,HATBF and THTBF were 30.2±10.4,20.0±10.7,and 50.3±14.9 m L/100 m L/min,respectively.Alb,PT,BNP,BTR,BCAA,tyrosine,NH3,Ch E,IRI,TBA,and ICG R15 were 3.50±0.50 g/d L,72.0%±11.5%,63.2±56.7 pg/m L,4.06±1.24,437.5±89.4μmol/L,117.7±32.8μmol/L,59.4±22.7μg/d L,161.0±70.8 IU/L,12.8±5.0μg/d L,68.0±51.8μmol/L,and 28.6%±13.5%,respectively.PVTBF showed a significant negative correlation with ICG R15(r=-0.468,P<0.01).No significant correlation was seen between ICG 15R,HATBF and THTBF.There was a significant correlation between PVTBF and Alb(r=0.2499,P<0.05),and NH3 tended to have an inverse correlation with PVTBF(r=-0.2428,P=0.0894).There were also many significant correlations between ICG R15 and liver function parameters,including Alb,NH3,PT,BNP,TBA,BCAA,and tyrosine(r=-0.2156,P<0.05;r=0.4318,P<0.01;r=0.4140,P<0.01;r=0.3610,P<0.05;r=0.5085,P<0.001;r=0.4496,P<0.01;and r=0.4740,P<0.05,respectively).CONCLUSION:Our investigation showed that there is a close correlation between liver function and hepatic blood flow. | Hideaki Takahashi Ryuta Shigefuku Yoshihito Yoshida Hiroki Ikeda Kotaro Matsunaga Nobuyuki Matsumoto Chiaki Okuse Shigeru Sase Fumio Itoh Michihiro Suzuki | 2014 | World Journal of Gastroenterology2014，20，45： | 14 |
| 20 | Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer显示文摘AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability(MSI) status in Japanese colorectal cancer(CRC) population.METHODS: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage Ⅰ-Ⅲ CRC and examined associations of these mutations with disease-free survival(DFS) and overall survival(OS) using uni- and multivariate Cox proportional hazards models.RESULTS: KRAS and BRAF mutations were detected in 312(38%) of 812 and 40(5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males(P = 0.02), while the presence of BRAF mutations was significantly associated with the female gender(P = 0.006), proximal tumor location(P < 0.001), mucinous or poorly differentiated histology(P < 0.001), and MSI-high tumors(P < 0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS(HR = 1.35; 95%CI: 1.03-1.75) and OS(HR = 1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS(HR = 2.20; 95%CI: 1.19-4.06) and OS(HR = 2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS.CONCLUSION: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, inJapanese patients with curatively resected CRC. | Shigenori Kadowaki Miho Kakuta Shuhei Takahashi Akemi Takahashi Yoshiko Arai Yoji Nishimura Toshimasa Yatsuoka Akira Ooki Kensei Yamaguchi Keitaro Matsuo Kei Muro Kiwamu Akagi | 2015 | World Journal of Gastroenterology2015，21，4： | 14 |
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