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| 1 | 新疆北部晚古生代埃达克岩、富铌玄武岩组合:古亚洲洋板块南向俯冲的证据显示文摘地球化学研究结果表明 ,新疆北部富蕴县境内的晚古生代下泥盆统托让格库都克组的安山质岩石具有与埃达克岩非常相似的地球化学特征 ,它们具有较高的Al2 O3 ,Na2 O和Sr含量以及Sr/Y比值 ;明显亏损重稀土和Y ,它们的MORB标准化微量元素蛛网图表现为明显的Nb ,Ta负异常和Sr正异常 ,同时强烈亏损高场强元素。与埃达克岩共生的玄武岩的地球化学特征则与富铌玄武岩一致 ,表现为Si过饱和及富Na的特征 ,同时具有较高的Nb ,TiO2 和P2 O5含量 ,并富集高场强元素。由于埃达克岩和富铌玄武岩的形成均与板块俯冲有关 ,因此 ,它们的存在表明 ,古亚洲洋在早 -中泥盆世向南 (哈萨克斯坦 -准噶尔板块 ) | 张海祥 牛贺才 Hiroaki Sato 单强 于学元 Jun’ichi Ito 张旗 | 2004 | 高校地质学报2004，10，1： | 102 |
| 2 | Glypican-3 is a prognostic factor and an immunotherapeutic target in hepatocellular carcinoma显示文摘Glypican-3(GPC3)is a cell surface oncofetal proteoglycan that is anchored by glycosylphosphatidylinositol.Whereas GPC3 is abundant in fetal liver,its expression is hardly detectable in adult liver.Importantly,GPC3is overexpressed in hepatocellular carcinoma(HCC),and several immunohistochemical studies reported that overexpression predicts a poorer prognosis for HCC patients.Therefore,GPC3 would serve as a useful molecular marker for HCC diagnosis and also as a target for therapeutic intervention in HCC.Indeed,some immunotherapy protocols targeting GPC3 are under investigations;those include humanized anti-GPC3cytotoxic antibody,peptide vaccine and immunotoxin therapies.When considering the clinical requirements for GPC3-targeting therapy,companion diagnostics to select the appropriate HCC patients are critical,and both immunohistochemical analysis of tissue sections and measurement of serum GPC3 level have been suggested for this purpose.This review summarizes current knowledge regarding the clinical implication of GPC3detection and targeting in the management of patients with HCC. | Yukihiro Haruyama Hiroaki Kataoka | 2016 | World Journal of Gastroenterology2016，22，1： | 35 |
| 3 | 新疆北部富蕴县沙尔布拉克玻安岩的地球化学特征及构造意义显示文摘详细的地球化学研究表明,新疆北部富蕴县沙尔布拉克中泥盆统北塔山组的辉石安山岩具有中等的SiO2含量(52.13%~60.45%);高MgO(3.91%~9.31%)和相容元素(包括Ni、Cr、Co等)含量,以及高Mg#和Al2O3/TiO2比值;低TiO2含量(0.21%~0.35%);同时具有U型稀土元素分布模式;并强烈亏损高场强元素。这些特征均与玻安岩的地球化学特征一致,应属于玻安岩,形成于前弧环境。沙尔布拉克玻安岩的存在表明,古亚洲洋在早—中泥盆世向南发生了洋壳俯冲作用。 | 张海祥 牛贺才 于学元 Hiroaki Sato Junichi Ito 单强 | 2003 | 地球化学2003，32，2： | 38 |
| 4 | Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy显示文摘瞄准:在部分肝切除术以后在肝新生上学习妨碍的黄疸的效果。方法: Hepatocyte 生长因素( HGF ),它的受体, 遇见c ,脉管的内皮生长因素( VEGF )和转变生长在肝织物和孤立的肝细胞的 factor-beta1 ( TGF-beta1 ) mRNA 表示被量的反向抄写的聚合酶链反应( RT-PCR )用 LightCycler 在胆汁的阻塞( BO )以后调查。为 desmin 和 alpha 光滑的肌肉肌动朊(alpha-SMA ) 染色的 Immunohistochemical 也被学习。标记的原子抗原(PCNA ) 索引的再生肝重量和增殖的房间,和生长因素表示然后与伴随物在 70% 肝切除术以后被评估在 BO 老鼠或假冒操作老鼠的内部胆汁的排水。结果:肝的 TGF-beta1 mRNA 层次显著地在 BO 以后增加了 14 天,并且进一步与胆汁郁积的持续时间增加了。同时, HGF 和 VEGF 趋于增加,但是不是重要的。在房间孤立, TGF-beta1 mRNA 主要在肝的星形的房间(HSC ) 被发现部分。Immunohistochemical 研究揭示了 HSC (desmin 积极的房间) 的一个增加的数字并且在 BO 以后在门区域激活 HSC (alpha-SMA-positive 房间) 。在一个肝切除术模型,肝新生在 BO 老鼠被推迟,作为与假冒操作老鼠相比。在肝切除术,和更早的 HGF mRNA 山峰沉醉于 BO 老鼠以后, TGF-beta1 mRNA 是显著地起来调整的直到 48 h。结论:BO 导致 HSC 增长和激活,导致 TGF-beta1 mRNA 的起来规定和在肝的 HGF mRNA 的抑制。这些改变的表示模式可以强烈与妨碍的黄疸在肝切除术以后涉及推迟的肝新生。 | Hironobu Makino Hiroaki Shimizu Hiroshi Ito Fumio Kimura Satoshi Ambiru Akira Togawa Masayuki Ohtsuka Hiroyuki Yoshidome Atsushi Kato Hideyuki Yoshitomi Shigeaki Sawada Masaru Miyazaki | 2006 | World Journal of Gastroenterology2006，12，13： | 32 |
| 5 | 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 |
| 6 | Zircon SHRIMP U-Pb dating on plagiogranite from Kuerti ophiolite in Altay,North Xinjiang显示文摘Field observation, petrological and geochemical characteristics of plagiogranite from Kuerti ophiolite indicate a similar origin to those in shearing zones. It isderived from partial melting of amphibolite that is developed from gabbro within the ocean layer 3 shear zone by the low-angle shearing deformation during the oceanic crustmigrating process. Zircon SHRIMP age of 372±19 Ma for the plagioganite from Kuerti ophiolite indicates that thisophiolite formed in the Devonian period and it alsorepresented the time of extension of the Kuerti backarc basin that is relevant to the northwards subduction of thePaleo-Asian oceanic crust. Therefore, the northwardssubduction of the Paleo-Asian Ocean beneath the Siberian Plate began in the early stage of the Late Paleozoic era. | ZHANG Haixiang NIU Hecai Kentaro Terada YU Xueyuan Hiroaki Sato Jun抜chi Ito | 2003 | Chinese Science Bulletin2003，48，20： | 28 |
| 7 | Narrow-band imaging optical chromocolonoscopy: Advantages and limitations显示文摘Narrow-band imaging (NBI) is an innovative optical technology that modifies the center wavelength and bandwidth of an endoscope’s light into narrow-band illumination of 415 ± 30 nm. NBI markedly improves capillary pattern contrast and is an in vivo method for visualizing microvessel morphological changes in superficial neoplastic lesions. The scientific basis for NBI is that short wavelength light falls within the hemoglobin absorption band, thereby facilitating clearer visualization of vascular structures. Several studies have reported advantages and limitations of NBI colonoscopy in the colorectum. One difficulty in evaluating results, however, has been non-standardization of NBI systems (Sequential and non-sequential). Utilization of NBI technology has been increasing worldwide, but accurate pit pattern analysis and suffi cient skill in magnifying colonoscopy are basic fundamentals required for profi ciency in NBI diagnosis of colorectal lesions. Modern optical technology without proper image interpretation wastes resources, confuses untrained endoscopists and delays inter-institutional validation studies. Training in the principles of 'optical image-enhanced endoscopy' is needed to close the gap between technological advancements and their clinical usefulness. Currently available evidence indicates that NBI constitutes an effective and reliable alternative to chromocolonoscopy forin vivo visualization of vascular structures, but further study assessing reproducibility and effectiveness in the colorectum is ongoing at various medical centers. | Fabian Emura Yutaka Saito Hiroaki Ikematsu | 2008 | World Journal of Gastroenterology2008，14，31： | 25 |
| 8 | Retrospective cohort study Lower incidence of complications in endoscopic nasobiliary drainage for hilar cholangiocarcinoma显示文摘AIM:To identify the most effective endoscopic biliary drainage technique for patients with hilar cholangiocarcinoma.METHODS:In total,118 patients with hilar cholangiocarcinoma underwent endoscopic management[endoscopic nasobiliary drainage(ENBD)or endoscopic biliary stenting]as a temporary drainage in our institution between 2009 and 2014.We retrospectively evaluated all complications from initial endoscopic drainage to surgery or palliative treatment.The risk factors for biliary reintervention,post-endoscopic retrograde cholangiopancreatography(post-ERCP)pancreatitis,and percutaneous transhepatic biliary drainage(PTBD)were also analyzed using patient-and procedure-related characteristics.The risk factors for bilateral drainage were examined in a subgroup analysis of patients who underwent initial unilateral drainage.RESULTS:In total,137 complications were observed in92(78%)patients.Biliary reintervention was required in 83(70%)patients.ENBD was significantly associated with a low risk of biliary reintervention[odds ratio(OR)=0.26,95%CI:0.08-0.76,P=0.012].Post-ERCP pancreatitis was observed in 19(16%)patients.An absence of endoscopic sphincterotomy was significantly associated with post-ERCP pancreatitis(OR=3.46,95%CI:1.19-10.87,P=0.023).PTBD was required in 16(14%)patients,and Bismuth type III or IV cholangiocarcinoma was a significant risk factor(OR=7.88,95%CI:1.33-155.0,P=0.010).Of 102 patients with initial unilateral drainage,49(48%)required bilateral drainage.Endoscopic sphincterotomy(OR=3.24,95%CI:1.27-8.78,P=0.004)and Bismuth II,III,or IV cholangiocarcinoma(OR=34.69,95%CI:4.88-736.7,P<0.001)were significant risk factors for bilateral drainage.CONCLUSION:The endoscopic management of hilar cholangiocarcinoma is challenging.ENBD should be selected as a temporary drainage method because of its low risk of complications. | Kazumichi Kawakubo Hiroshi Kawakami Masaki Kuwatani Shin Haba Taiki Kudo Yoko A Taya Shuhei Kawahata Yoshimasa Kubota Kimitoshi Kubo Kazunori Eto Nobuyuki Ehira Hiroaki Yamato Manabu Onodera Naoya Sakamoto | 2016 | World Journal of Gastrointestinal Endoscopy2016，8，9： | 26 |
| 9 | Novel 3-dimensional virtual hepatectomy simulation combined with real-time deformation显示文摘AIM:To develop a novel 3-dimensional(3D) virtual hepatectomy simulation software,Liversim,to visualize the real-time deformation of the liver.METHODS:We developed a novel real-time virtual hepatectomy simulation software program called Liversim. The software provides 4 basic functions:viewing 3D models from arbitrary directions,changing the colors and opacities of the models,deforming the models based on user interaction,and incising the liver parenchyma and intrahepatic vessels based on user operations. From April 2010 through 2013,99 patients underwent virtual hepatectomies that used the conventional software program SYNAPSE VINCENT preoperatively. Between April 2012 and October 2013,11 patients received virtual hepatectomies using the novel software program Liversim; these hepatectomies were performed both preoperatively and at the same that the actual hepatectomy was performed in an operating room. The perioperative outcomes were analyzed between the patients for whom SYNAPSE VINCENT was used and those for whom Liversim wasused. Furthermore,medical students and surgical residents were asked to complete questionnaires regarding the new software.RESULTS:There were no obvious discrepancies(i.e.,the emergence of branches in the portal vein or hepatic vein or the depth and direction of the resection line) between our simulation and the actual surgery during the resection process. The median operating time was 304 min(range,110 to 846) in the VINCENT group and 397 min(range,232 to 497) in the Liversim group(P = 0.30). The median amount of intraoperative bleeding was 510 m L(range,18 to 5120) in the VINCENT group and 470 m L(range,130 to 1600) in the Liversim group(P = 0.44). The median postoperative stay was 12 d(range,6 to 100) in the VINCENT group and 13 d(range,9 to 21) in the Liversim group(P = 0.36). There were no significant differences in the preoperative outcomes between the two groups. Liversim was not found to be clinically inferior to SYNAPSE VINCENT. Both students and surgical residents reported that the Liversim image was almost the same as the actual hepatectomy.CONCLUSION:Virtual hepatectomy with real-time deformation of the liver using Liversim is useful for the safe performance of hepatectomies and for surgical education. | Yukio Oshiro Hiroaki Yano Jun Mitani Sangtae Kim Jaejeong Kim Kiyoshi Fukunaga Nobuhiro Ohkohchi | 2015 | World Journal of Gastroenterology2015，21，34： | 23 |
| 10 | Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma显示文摘AIM:To clarify the association of glypican-3(GPC3)expression with Wnt and other growth signaling molecules in hepatocellular carcinoma(HCC). METHODS:Expression of GPC3,Wnt,matrix metalloproteinases(MMPs),sulfatase(SULF)1,SULF2,and other growth signaling molecules was analyzed in HCC cell lines and tissue samples by real-time reverse transcriptionpolymerase chain reaction,immunoblotting,and/or immunostaining.Expression of various genes in GPC3 siRNA-transfected HCC cells was analyzed. RESULTS:GPC3 was overexpressed in most HCCs at mRNA and protein levels and its serum levels weresignificantly higher in patients with HCC than in non- HCC subjects(P<0.05).Altered expressions of various MMPs and growth signaling molecules,some of which were correlated with GPC3 expression,were observed in HCCs.Down-regulation of GPC3 expression by siRNA in GPC3-overexpressing HCC cell lines resulted in a significant decrease in expressions of MMP2,MMP14,fibroblast growth factor receptor 1,insulin-like growth factor 1 receptor.GPC3 expression was significantly correlated with nuclear/cytoplasmic localization ofβ-catenin. CONCLUSION:These results suggest that GPC3,in conjunction with MMPs and growth signaling molecules, might play an important role in the progression of HCC. | Noriyuki Akutsu Hiroyuki Yamamoto Shigeru Sasaki Hiroaki Taniguchi Yoshiaki Arimura Kohzoh Imai Yasuhisa Shinomura | 2010 | World Journal of Gastroenterology2010，16，28： | 20 |
| 11 | Site effects by generalized inversion technique using strong motion recordings of the 2008 Wenchuan earthquake显示文摘The generalized inversion of S-wave amplitude spectra from the free-field strong motion recordings of the China National Strong Motion Observation Network System (NSMONS) are used to evaluate the site effects in the Wenchuan area. In this regard, a total of 602 recordings from 96 aftershocks of the Wenchuan earthquake with magnitudes of M3.7-M6.5 were selected as a dataset. These recordings were obtained from 28 stations at a hypocenter distance ranging from 30 km to 150 km. The inversion results have been verified as reliable by comparing the site response at station 62WUD using the Generalized Inversion Technique (GIT) and the Standard Spectral Ratio method (SSR). For all 28 stations, the site predominant frequency Fp and the average site amplification in different frequency bands of 1.0-5.0Hz, 5.0-10.0Hz and 1.0-10.0 Hz have been calculated based on the inversion results. Compared with the results from the horizontal-to-vertical spectral ratio (HVSR) method, it shows that the HVSR method can reasonably estimate the site predominant frequency but underestimates the site amplification. The linear fitting between the average site amplification for each frequency band and the Vs20 (the average uppermost-20 m shear wave velocity) shows good correlation. A distance measurement called the asperity distance DAspt is proposed to reasonably characterize the source-to-site distance for large earthquakes. Finally, the inversed site response is used to identify the soil nonlinearity in the main shock and aftershocks of Wenchuan earthquake. In ten of the 28 stations analyzed in the main shock, the soil behaved nonlinearly, where the ground motion level is apparently beyond a threshold of PGA > 300cm/s2 or PGV > 20cm/s, and only one station coded 51SFB has evidence of soil nonlinear behavior in the aftershocks. | Ren Yefei Wen Ruizhi Hiroaki Yamanaka Toshihide Kashima | 2013 | Earthquake Engineering and Engineering Vibration2013，12，2： | 20 |
| 12 | Transcriptional silencing of Dickkopf gene family by CpG island hypermethylation in human gastrointestinal cancer显示文摘AIM: To clarify alterations of Dickkopfs (Dkks) and Kremen2 (Krm2) in gastrointestinal cancer. METHODS: We investigated the expression profiles and epigenetic alterations of Dkks and Krm2 genes in gastrointestinal cancer using RT-PCR, tissue microarray analysis, and methylation specific PCR (MSP). Cancer cells were treated with the demethylating agent and/or histone deacetylase inhibitor. WST-8 assays and in vitro invasion assays after treatment with specific siRNA for those genes were performed. RESULTS: Dkks and Krm2 expression levels were reduced in a certain subset of the gastrointestinal cancer cell lines and cancer tissues. This was correlated with promoter hypermethylation. There were significant correlations between Dkks over-expression levels and beta-catenin over-expression in colorectal cancer. In colorectal cancers with beta-catenin over-expression, Dkk-1 expression levels were significantly lower in those with lymph node metastases than in those without. Down-regulation of Dkks expression by siRNA resulted in a significant increase in cancer cell growth and invasiveness in vitro.CONCLUSION: Down-regulation of the Dkks associated to promoter hypermethylation appears to be frequently involved in gastrointestinal tumorigenesis. | Tadateru Maehata Hiroaki Taniguchi Hiroyuki Yamamoto Katsuhiko Nosho Yasushi Adachi Nobuki Miyamoto Chie Miyamoto Noriyuki Akutsu Satoshi Yamaoka Fumio Itoh | 2008 | World Journal of Gastroenterology2008，14，17： | 19 |
| 13 | Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer显示文摘AIM:To investigate human epidermal growth factor receptor 2(HER2)-phosphatidylinositol 3-kinase(PI3K)-vAkt murine thymoma viral oncogene homolog signaling pathway.METHODS:We analyzed 231 formalin-fixed,paraffinembedded gastric cancer tissue specimens from Japanese patients who had undergone surgical treatment.The patients' age,sex,tumor location,depth of invasion,pathological type,lymph node metastasis,and pathological stage were determined by a review of the medical records.Expression of HER2 was analyzed by immunohistochemistry(IHC) using the HercepTest TM kit.Standard criteria for HER2 positivity(0,1+,2+,and 3+) were used.Tumors that scored 3+ were considered HER2-positive.Expression of phospho Akt(pAkt) was also analyzed by IHC.Tumors were considered pAkt-positive when the percentage of positive tumor cells was 10% or more.PI3K,catalytic,alpha polypeptide(PIK3CA) mutations in exons 1,9 and 20 were analyzed by pyrosequencing.Epstein-Barr virus(EBV) infection was analyzed by in situ hybridization targeting EBV-encoded small RNA(EBER) with an EBER-RNA probe.Microsatellite instability(MSI) was analyzed by polymerase chain reaction using the mononucleotide markers BAT25 and BAT26.RESULTS:HER2 expression levels of 0,1+,2+ and 3+ were found in 167(72%),32(14%),12(5%) and 20(8.7%) samples,respectively.HER2 overexpression(IHC 3+) significantly correlated with intestinal histological type(15/20 vs 98 /205,P = 0.05).PIK3CA mutations were present in 20 cases(8.7%) and significantly correlated with MSI(10/20 vs 9/211,P < 0.01).The mutation frequency was high(21%) in T4 cancers and very low(6%) in T2 cancers.Mutations in exons 1,9 and 20 were detected in 5(2%),9(4%) and 7(3%) cases,respectively.Two new types of PIK3CA mutation,R88Q and R108H,were found in exon1.All PIK3CA mutations were heterozygous missense singlebase substitutions,the most common being H1047R(6/20,30%) in exon20.Eighteen cancers(8%) were EBV-positive and this positivity significantly correlated with a diffuse histological type(13/18 vs 93/198,P = 0.04).There were 7 cases of lymphoepithelioma-like carcinomas(LELC) and 6 of those cases were EBV-positive(percent/EBV:6/18,33%;percent/all LELC:6/7,86%).pAkt expression was positive in 119(53%) cases but showed no correlation with clinicopathological characteristics.pAkt expression was significantly correlated with HER2 overexpression(16/20 vs 103/211,P < 0.01) but not with PIK3CA mutations(12/20 vs 107/211,P = 0.37) or EBV infection(8/18 vs 103/211,P = 0.69).The frequency of pAkt expression was higher in cancers with exon20 mutations(100%) than in those with exon1(40%) or exon9(56%) mutations.One case showed both HER2 overexpression and EBV infection and 3 cases showed both PIK3CA mutations and EBV infection.However,no cases showed both PIK3CA mutations and HER2 overexpression.One EBVpositive cancer with PIK3CA mutation(H1047R) was MSI-positive.Three of these 4 cases were positive for pAkt expression.In survival analysis,pAkt expression significantly correlated with a poor prognosis(hazard ratio 1.75;95%CI:1.12-2.80,P = 0.02).CONCLUSION:HER2 expression,PIK3CA mutations and EBV infection in gastric cancer were characterized.pAkt expression significantly correlates with HER2 expression and with a poor prognosis. | Yasutaka Sukawa Hiroyuki Yamamoto Katsuhiko Nosho Hiroaki Kunimoto Hiromu Suzuki Yasushi Adachi Mayumi Nakazawa Takayuki Nobuoka Mariko Kawayama Masashi Mikami Takashi Matsuno Tadashi Hasegawa Koichi Hirata Kohzoh Imai Yasuhisa Shinomura | 2012 | World Journal of Gastroenterology2012，18，45： | 19 |
| 14 | 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 |
| 15 | Prognostic significance of the lymphocyte-to-monocyte ratio in patients with metastatic colorectal cancer显示文摘AIM:To evaluate the prognostic significance of the lymphocyte to monocyte ratio(LMR) in patients with unresectable metastatic colorectal cancer who received palliative chemotherapy.METHODS:A total of 104 patients with unresectable metastatic colorectal cancer who underwent palliative chemotherapy were enrolled. The LMR was calculated from blood samples by dividing the absolute lymphocyte count by the absolute monocyte count. Pretreatment LMR values were measured within one week before the initiation of chemotherapy,while posttreatment LMR values were measured eight weeks after the initiation of chemotherapy.RESULTS:The median pre-treatment LMR was 4.16(range:0.58-14.06). We set 3.38 as the cut-off level based on the receiver operating characteristic curve. Based on the cut-off level of 3.38,66 patients were classified into the high pre-treatment LMR group and 38 patients were classified into the low pretreatment LMR group. The low pre-treatment LMR group had a significantly worse overall survival rate(P = 0.0011). Moreover,patients who demonstrated low pre-treatment LMR and normalization after treatmentexhibited a better overall survival rate than the patients with low pre-treatment and post-treatment LMR values.CONCLUSION:The lymphocyte to monocyte ratio is a useful prognostic marker in patients with unresectable metastatic colorectal cancer who receive palliative chemotherapy. | Masatsune Shibutani Kiyoshi Maeda Hisashi Nagahara Hiroshi Ohtani Katsunobu Sakurai Sadaaki Yamazoe Kenjiro Kimura Takahiro Toyokawa Ryosuke Amano Hiroaki Tanaka Kazuya Muguruma Kosei Hirakawa | 2015 | World Journal of Gastroenterology2015，21，34： | 19 |
| 16 | Optimal treatment for Siewert type Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction: A retrospective cohort study with long-term follow-up显示文摘AIM To determine the optimal treatment strategy for Siewert type Ⅱ and?Ⅲ?adenocarcinoma of the esophagogastric junction.METHODS We retrospectively reviewed the medical records of 83 patients with Siewert type?Ⅱ?and?Ⅲ?adenocarcinoma of the esophagogastric junction and calculated both an index of estimated benefit from lymph node dissection for each lymph node(LN) station and a lymph node ratio(LNR: ratio of number of positive lymph nodes to the total number of dissected lymph nodes). We used Cox proportional hazard models to clarify independent poor prognostic factors. The median duration of observation was 73 mo.RESULTS Indices of estimated benefit from LN dissection were as follows, in descending order: lymph nodes(LN) along the lesser curvature, 26.5; right paracardial LN, 22.8; left paracardial LN, 11.6; LN along the left gastric artery, 10.6. The 5-year overall survival(OS) rate was 58%. Cox regression analysis revealed that vigorous venous invasion(v2, v3)(HR = 5.99; 95%CI: 1.71-24.90) and LNR of > 0.16(HR = 4.29, 95%CI: 1.79-10.89) were independent poor prognostic factors for OS.CONCLUSION LN along the lesser curvature, right and left paracardial LN, and LN along the left gastric artery should be dissected in patients with Siewert type?Ⅱ?or?Ⅲ?adenoca rcinoma of the esophagogastric junction. Patients with vigorous venous invasion and LNR of > 0.16 should be treated with aggressive adjuvant chemotherapy to improve survival outcomes. | Kei Hosoda Keishi Yamashita Hiromitsu Moriya Hiroaki Mieno Masahiko Watanabe | 2017 | World Journal of Gastroenterology2017，23，15： | 19 |
| 17 | Predictors of kidney tubular dysfunction induced by adefovir treatment for chronic hepatitis B显示文摘AIM:To investigate the predictors of proximal kidney tubular dysfunction(PKTD)induced by adefovir dipivoxil(ADV)treatment for chronic hepatitis B.METHODS:Seventy-nine patients(age at the evaluation of PKTD:56.9±10.7 years)with chronic hepatitis B undergoing long-term oral antiviral nucleos(t)ide analogue treatment were consecutively recruited.PKTD was defined by the presence of at least two of the following five abnormalities:phosphate diabetes,nondiabetic glucosuria,metabolic acidosis,β2-microglobulinuria,or renal hypouricemia.The single-nucleotide polymorphisms(SNPs)in the SLC22A6 gene encoding human organic anion transporter 1(h OAT1)and ABCC2 encoding multidrug resistance protein 2(MRP2)were analyzed using the Taq Man Allelic Discrimination Demonstration Kit.RESULTS:Nine(30.0%)of the 30 ADV-treated patients were diagnosed with PKTD,while no patients without ADV developed PKTD(P<0.001).Three patients with ADV were diagnosed with symptomatic osteomalacia.Among the patients who took ADV,those with PKTD were of higher age at initiation,had significantly longer treatment duration,and had a significantly lower body mass index than those without PKTD.The incidence of PKTD dramatically increased after 96 mo from the start of ADV administration.In contrast,the SNPs were not correlated with PKTD.Logistic regression analysis extracted older age at initiation(OR=5.0,95%CI:1.1-23.4;P=0.040)and longer treatment duration(OR=3.2,95%CI:1.2-8.6;P=0.020)as significant factors associated with PKTD.CONCLUSION:Our results suggest that the tubular function of the kidney of older patients undergoing longterm ADV treatment should be carefully evaluated. | Motohiro Shimizu Norihiro Furusyo Hiroaki Ikezaki Eiichi Ogawa Takeo Hayashi Takeshi Ihara Yuji Harada Kazuhiro Toyoda Masayuki Murata Jun Hayashi | 2015 | World Journal of Gastroenterology2015，21，7： | 18 |
| 18 | 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 |
| 19 | Vascular endothelial growth factor and angiopoietins regulate sinusoidal regeneration and remodeling after partial hepatectomy in rats显示文摘AIM: To study the regulatory mechanisms of sinusoidal regeneration after partial hepatectomy.METHODS: We investigated the expression of angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in regenerating liver tissue by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler (Roche Diagnostics) and also immunohistochemical staining after 70% hepatectomy in rats. In the next step, we isolated liver cells (hepatocytes,sinusoidal endothelial cell (SEC), Kupffer cell, and hepatic stellate cells (HSC)) from regenerating liver tissue by in situ collagenase perfusion and counterflow elutriation,to determine potential cellular sources of these angiogenic factors after hepatectomy. Proliferation and apoptosis of SECs were also evaluated by proliferating cell nuclear antigen (PCNA) staining and the terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling (TUNEL) assay, respectively.RESULTS: VEGF mRNA expression increased with a peak at 72 h after hepatectomy, decreasing thereafter.The expression of Ang-1 mRNA was present at detectable levels before hepatectomy and increased slowly with a peak at 96 h. Meanwhile, Ang-2 mRNA was hardly detected before hepatectomy, but was remarkably induced at 120 and 144 h. In isolated cells, VEGF mRNA expression was found mainly in the hepatocyte fraction.Meanwhile, mRNA for Ang-1 and Ang-2 was foundin the SEC and HSC fractions, but was more prominent in the latter. The PCNA labeling index of SECs increased slowly,reaching a peak at 72 h, whereas apoptotic SECs were detected between 120 h and 144 h.CONCLUSION: Ang-Tie system, together with VEGF,plays a critical role in regulating balance between SEC proliferation and apoptosis during sinusoidal regeneration after hepatectomy. However, the VEGF system plays a more important role in the early phase of sinusoidal regeneration than angiopoietin/Tie system. | Hiroaki Shimizu Noboru Mitsuhashi Masayuki Ohtsuka Hiroshi Ito Fumio Kimura Satoshi Ambiru Akira Togawa Hiroyuki Yoshidome Atsushi Kato Masaru Miyazaki | 2005 | World Journal of Gastroenterology2005，11，46： | 17 |
| 20 | 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 |
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