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| 1 | Gut microbiota and host metabolism in liver cirrhosis显示文摘The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulatingthe activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probioticstreated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics, synbiotics, and prebiotics, with sufficient nutrition could aid the development of treatments and prevention for liver cirrhosis patients. | Makoto Usami Makoto Miyoshi Hayato Yamashita | 2015 | World Journal of Gastroenterology2015，21，41： | 44 |
| 2 | MR扩散加权成像诊断食管癌的效能显示文摘本研究目的是评价DWI对检出食管癌及评估淋巴结的价值,并与组织病理学对照。对连续24例食管癌病人前瞻性进行背景信号抑制的全身扩散加权成像(DWIBS)。将DWIBS影像与T2WI影像融合,由3名有资质的放射科医师独立盲法分析,内容包括原发肿瘤的检出能力及淋巴结状况,并测量原发肿瘤和淋巴结的表观扩散系数(ADC)。原发肿瘤的平均检出率为49.4%,以病人为目标的淋巴结转移检出的敏感度和特异度分别为77.8%和55.6%, | A. Sakurada T. Takahara T.C. Kwee T. Yamashita S. Nasu T. Horie 王萍(译) 刘筠(校) | 2009 | 国际医学放射学杂志2009，32，4： | 40 |
| 3 | Clinical benefit of radiation therapy and metallic stenting for unresectable hilar cholangiocarcinoma显示文摘AIM:To determine the efficacy of external beam radiotherapy(EBRT),with or without intraluminal brachytherapy(ILBT),in patients with non-resected locally advanced hilar cholangiocarcinoma.METHODS:We analyzed 64 patients with locally advanced hilar cholangiocarcinoma,including 25 who underwent resection(17 curative and 8 non-curative),28 treated with radiotherapy,and 11 who received best supportive care(BSC).The radiotherapy group received EBRT(50 Gy,30 fractions),with 11 receiving an additional 24 Gy(4 fractions) ILBT by iridium-192 with remote after loading.ILBT was performed using percutaneous transhepatic biliary drainage(PTBD) route.Uncovered metallic stents(UMS) were inserted into nonresected patients with obstructive jaundice,with the exception of four patients who received percutaneous transhepatic biliary drainage only.UMS were placed endoscopically or percutaneously,depending on the initial drainage procedure.The primary endpoints were patient death or stent occlusion.Survival time of patients in the radiotherapy group was compared with that of patients in the resection and BSC groups.Stent patency was compared in the radiotherapy and BSC groups.RESULTS:No statistically significant differences in patient characteristics were found among the resection,radiotherapy,and BSC groups.Three patients in the radiotherapy group and one in the BSC group did not receive UMS insertion but received PTBD alone;cholangitis occurred after endoscopic stenting,and patients were treated with PTBD.A total of 16 patients were administered additional systemic chemotherapy(5-fluorouracil-based regimen in 9,S-1 in 6,and gemcitabine in 1).Overall survival varied significantly among groups,with median survival times of 48.7 mo in the surgery group,22.1 mo in the radiotherapy group,and 5.7 mo in the BSC group.Patients who underwent curative resection survived significantly longer than those who were not candidates for surgery(P = 0.0076).Cumulative survival in the radiotherapy group was significantly longer than in the BSC group(P = 0.0031),but did not differ significantly from those in the non-resection group.Furthermore,the median survival time of patients in the radiotherapy group who were considered for possible resection(excluding the seven patients who were not candidates for surgery due to comorbid disease or age) was 25.9 mo.Stent patency was evaluated only in the 24 patients who received a metallic stent.Stent patency was significantly longer in the radiotherapy than in the BSC group(P = 0.0165).Biliary drainage was not eliminated in any patient.To determine the efficacy of ILBT,we compared survival time and stent patency in the EBRT alone and EBRT plus ILBT groups.However,we found no significant difference in survival time between groups or for stent patencies.Hemorrhagic gastroduodenal ulcers were observed in 5 patients(17.9%),three in the EBRT plus ILBT group and two in the EBRT alone group.Ulcers occurred 5 mo,7 mo,8 mo,16 mo,and 29 mo following radiotherapy.All patients required hospitalization,but blood transfusions were unnecessary.All 5 patients recovered following the administration of anti-ulcer medication.CONCLUSION:Radiotherapy improved patient prognosis and the patency of uncovered metallic stents in patients with locally advanced hilar cholangiocarcinoma,but ILBT provided no additional benefits. | Hiroyuki Isayama Takeshi Tsujino Yousuke Nakai Takashi Sasaki Keiichi Nakagawa Hideomi Yamashita Taku Aoki Kazuhiko Koike | 2012 | World Journal of Gastroenterology2012，18，19： | 24 |
| 4 | 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 |
| 5 | 地下水硝酸盐污染来源的推断与溯源方法概述显示文摘硝酸盐已经成为中国地下水的一种主要污染物之一,弄清地下水硝酸盐污染物的来源,对于有效控制地下这种物质的污染具有十分重要的意义。不同地区的地下水中硝酸盐污染物的来源可能不同,这些差异可以通过一定的方法分析和追溯,笔者概述了前人在地下水硝酸盐污染来源的推断与溯源几种常用方法,包括六成分法、派珀图法、相关性分析以及稳定同位素方法,希望能够为硝酸盐溯源的研究和污染控制提供参考。 | 赵解春 李玉中 Yamashita Ichiji 徐春英 李巧针 贾晓妨 | 2010 | 中国农学通报2010，26，18： | 22 |
| 6 | 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 |
| 7 | Glucose metabolism in gastric cancer:The cutting-edge显示文摘Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis(Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for early detection, diagnosis, prognosis, and chemosensitivity prediction of gastric cancer. Interfering with the process of glycolysis in cancer cells may provide a new and promising therapeutic strategy for gastric cancer. In this article, we present a brief review of recent studies of glucose metabolism in gastric cancer, with primary focus on the clinical applications of new biomarkers and their potential therapeutic role in gastric cancer. | Lian-Wen Yuan Hiroharu Yamashita Yasuyuki Seto | 2016 | World Journal of Gastroenterology2016，22，6： | 18 |
| 8 | Usefulness of noninvasive transient elastography for assessment of liver fibrosis stage in chronic hepatitis C显示文摘AIM:To evaluate the method of noninvasive transient elastography for assessment of histological stage of liver fibrosis in patients with chronic hepatitis C (CHC). METHODS: Two hundred and thirty-seven patients with CHC were included in this study. Liver biopsy was performed under ultrasonography on 217 of the patients, excluding twenty with clear clinical evidence of liver cirrhosis. Fifty subjects without liver disease were enrolled as a control group (stage 0). Twenty- five patients with sustained virological response (SVR) to interferon (IFN) therapy were also enrolled. These patients underwent liver biopsy before IFN therapy. Examination of liver stiffness (LS) was performed by elastography. RESULTS: Medians (50% levels) of LS were 4.1 (3.5-4.9), 6.3 (4.8-8.5), 8.8 (6.8-12.0), 14.6 (10.5-18.6), and 22.2 (15.4-28.0), respectively, in the fibrosis stages 0-4 (P < 0.001). LS was significantly correlated with four serum fibrosis markers. LS values in patients with SVR were 3.8 (3.5-5.6), 5.2 (4.4-6.8), 6.8 (6.1-7.6), and 6.1 (3.6-7.9), respectively, in the fibrosis stages 1-4. In all stages, LS for patients with SVR was significantly lower than that for patients who did not undergo IFN therapy. LS was significantly correlated with serum concentrations of hyaluronic acid, type Ⅳ collagen, type Ⅳ collagen 7S, and type Ⅲ procollagen N peptide. CONCLUSION: LS correlated well with the histologicalstage of fibrosis. Changes in liver fibrosis stage may thus be estimated noninvasively using transient elastography. | Tadashi Takeda Takahiro Yasuda Yuji Nakayama Mika Nakaya Megumi Kimura Mariko Yamashita Ayumi Sawada Koji Abo Setsuko Takeda Hiroki Sakaguchi Susumu Shiomi Hitoshi Asai Shuichi Seki | 2006 | World Journal of Gastroenterology2006，12，48： | 16 |
| 9 | Dedifferentiated fat cells: an alternative source of adult multipotent cells from the adipose tissues显示文摘When adipose-derived stem cells (ASCs) are retrieved from the stromal vascular portion of adipose tissue, a large amount of mature adipocytes are often discarded. However, by modified ceiling culture technique based on their buoyancy, mature adipocytes can be easily isolated from the adipose cell suspension and dedifferen- tiated into lipid-free fibroblast-like cells, named dedifferentiated fat (DFAT) cells. DFAT cells re-establish active proliferation ability and undertake multipotent capacities. Compared with ASCs and other adult stem cells, DFAT cells showed unique advantages in their abundance, isolation and homogeneity. In this concise review, the establishment and culture methods of DFAT cells are introduced and the current profiles of their cellular nature are summarized. Under proper induction culture in vitro or environment in vivo, DFAT cells could demonstrate adipogenic, osteogenic, chondrogenic and myogenic potentials. In angiogenic conditions, DFAT cells could exhibit perivascular characteristics and elicit neovascularization. Our preliminary findings also suggested the pericyte phenotype underlying such cell lineage, which supported a novel interpretation about the common origin of mesenchymal stem cells and tissue-specific stem cells within blood vessel walls. Current research on DFAT cells indicated that this alternative source of adult multipotent cells has great potential in tissue engineering and regenerative medicine. | Jie-fei Shen Atsunori Sugawara Joe Yamashita Hideo Ogura Soh Sato | 2011 | International Journal of Oral Science2011，3，3： | 16 |
| 10 | Acute pancreatitis successfully diagnosed by diffusion-weighted imaging: A case report显示文摘Diffusion-weighted imaging (DWI) is an established diagnostic method of acute stroke. The latest advances in magnetic resonance imaging (MRI) technology have greatly expanded the utility of DWI in the examination of various organs. Recent studies have revealed the usefulness of DWI for imaging of the liver, kidney, ovary, and breast. We report a patient with acute pancreatitis detected by DWI and discussed the efficacy of DWI in diagnosing acute pancreatitis. A 50-year old man presented with a primary complaint of abdominal pain. We performed both DWI and computed tomography (CT) for this patient. The signal intensity in a series of DWI was measured and the apparent diffusion coefficient (ADC) values were calculated to differentiate inflammation from normal tissue. Two experienced radiologists evaluated the grade of acute pancreatitis by comparing the CT findings. Initially, the pancreas and multiple ascites around the pancreas produced a bright signal and ADC values were reduced on DWI. As the inflammation decreased, the bright signal faded to an iso-signal and the ADC values returned to their normal level. There was no difference in the abilities of DWI and CT images to detect acute pancreatitis. However, our case indicates that DWI can evaluate the manifestations of acute pancreatitis using no enhancement material andhas the potential to replace CT as a primary diagnostic strategy for acute pancreatitis. | Satoshi Shinya Takamitsu Sasaki Yoshifumi Nakagawa Zhang Guiquing Fumio Yamamoto Yuichi Yamashita | 2008 | World Journal of Gastroenterology2008，14，35： | 16 |
| 11 | Radiation therapy for portal venous invasion by hepatocellular carcinoma显示文摘AIM: To clarify the efficacy and safety of three-dimensional conformal radiotherapy (3-D CRT) for this disease and to specify patient subgroups suitable for this treatment.METHODS: Fifty-two patients with HCC received PVI-targeted radiation therapy from January 1995 through December 2003. Portal venous invasion (PVI) was found in the second or lower order branches of the portal vein in 6 patients, in the first branch in 24 patients and in the main trunk in 22 patients. Child classifications of liver function before radiation therapy were A, B, and C for 19, 24 and 2 patients, respectively. All patients received three-dimensional conformal radiotherapy with a total dose ranging from 39 to 60 Gy (57.0 Gy in average).RESULTS: Overall survival rates at 1, 2, 3, 4, and 5 years were 45.1%, 25.3%, 15.2%, 10.1%, and 5.1%, respectively. Univariate analysis revealed that Child status, the number of tumor foci, tumor type,transcatheter arterial embolization (TAE) after radiation therapy were statistically significant prognostic factors.Multivariate analysis showed that the number of tumor foci and TAE after radiation therapy were statistically significant.CONCLUSION: The results of this study strongly suggest the efficacy of 3-D CRT as treatment for PVI in HCC. 3-D CRT is recommended in combination with postradiation TAE for PVI of HCC with 5 tumor foci or less in the liver and with Child A liver function. | Keiichi Nakagawa Hideomi Yamashita Kenshiro Shiraishi Naoki Nakamura Masao Tago Hiroshi Igaki Yoshio Hosoi Shuichiro Shiina Masao Omata Masatoshi Makuuchi Kuni Ohtomo | 2005 | World Journal of Gastroenterology2005，11，46： | 14 |
| 12 | Recent Advances in Researches on Physiologically Active Substances in Holothurians显示文摘In this report, we reviewed recent literature on physiologically active substances from sea cucumbers (SCs) andtheir activities together with results obtained from our study. Preventive properties against lipid metabolism were reported inrats using a whole SC preparation with no particular constituent specified. Administration of the preparation lowered serumand hepatic cholesterol levels and improved the HDL/LDL ratio. These functions may be attributed to the stimulatory effectof the extract on the secretion of cholesterol in feces. Novel fucosylated chondroitin sulfates (FCSs) from Ludwigothureagrisea significantly induced fibroblast growth factor 2-dependent angiogenesis in human umbilical vein endothelial cells (HU-VECs). The proangiogenetic activity seemed attributable to the action of the sulfated fucose branches on the polysaccharide.SCs contain mycosporine-like amino acids (MAAs) that are capable of absorbing UV. A biogenetic precursor of MAAs wasfirst reported in SCs. The anti-proliferative effects of a branched chain fatty acid from a sea cucumber on prostate cancercells was reported with the activity of 5-lipoxygenase. Glycosphingolipid constituents in SCs have been systematically ana-lyzed over the past ten years. The results showed that the gangliosides in several SCs differed from those of mammals in thata sialic acid of SC gangliosides directly binded to glucose of cerebroside. Neuritogenic activity of the glycosphingolipids wasdemonstrated in vitro experiments and may lead to the development of therapeutic products for neurological disorders. Ourstudy also showed that sphingoid bases, the hydrolyzed products of glycosphingolipids from SCs, induced significant apoptosisin several tumor cell lines. | Hirata Takashi Zaima Nobuhiro Yamashita Kyoko Noguchi Ryoko XUE Changhu Sugawara Tatsuya | 2005 | Journal of Ocean University of China2005，4，3： | 14 |
| 13 | Gastric cancer arising from the remnant stomach after distal gastrectomy:A review显示文摘Gastric stump carcinoma was initially reported by Balfore in 1922,and many reports of this disease have since been published. We herein review previous reports of gastric stump carcinoma with respect to epidemiology,carcinogenesis,Helicobacter pylori(H. pylori) infection,Epstein-Barr virus infection,clinicopathologic characteristics and endoscopic treatment. In particular,it is noteworthy that no prognostic differences are observed between gastric stump carcinoma and primary upper third gastric cancer. In addition,endoscopic submucosal dissection has recently been used to treat gastric stump carcinoma in the early stage. In contrast,many issues concerning gastric stump carcinoma remain to be clarified,including molecular biological characteristics and the carcinogenesis of H.pylori infection.We herein review the previous pertinent literature and summarize the characteristics of gastric stump carcinoma reported to date. | Shinsuke Takeno Tatsuya Hashimoto Kenji Maki Ryosuke Shibata Hironari Shiwaku Ippei Yamana Risako Yamashita Yuichi Yamashita | 2014 | World Journal of Gastroenterology2014，20，38： | 13 |
| 14 | Arterial steroid injection therapy can inhibit the progression of severe acute hepatic failure toward fulminant liver failure显示文摘AIM: To utilize transcatheter arterial steroid injection therapy (TASIT) via the hepatic artery to reduce hepatic macrophage activity in patients with severe acute hepatic failure.METHODS: Thirty-four patients with severe acute hepatic failure were admitted to our hospital between June 2002 to June 2006 providing for the possibility of liver transplantation (LT). Seventeen patients were treated using traditional liver supportive procedures, and the other 17 patients additionally underwent TASIT with 1000 mg methylprednisolone per day for 3 continuous days. RESULTS: Of the 17 patients who received TASIT, 13 were cured without any complications, 2 died, and 2 underwent LT. Of the 17 patients who did not receive TASIT, 4 were self-limiting, 7 died, and 6 underwent LT. Univariate logistic analysis revealed that ascites, serum albumin, prothrombin time, platelet count, and TASIT were significant variables for predicating the prognosis. Multivariate logistic regression analysis using stepwise variable selection showed that prothrombin time, platelet count, and TASIT were independent predictive factors. CONCLUSION: TASIT might effectively prevent the progression of severe acute hepatic failure to a fatal stage of fulminant liver failure. | Kazuhiro Kotoh Munechika Enjoji Makoto Nakamuta Tsuyoshi Yoshimoto Motoyuki Kohjima Shusuke Morizono Shinsaku Yamashita Yuki Horikawa Kengo Yoshimitsu Tsuyoshi Tajima Yoshiki Asayama Kousei Ishigami Masakazu Hirakawa | 2006 | World Journal of Gastroenterology2006，12，41： | 13 |
| 15 | Perfluorooctane sulfonate(PFOS) and related fluorochemicals in chicken egg in China显示文摘The ubiquitous occurrence of perfluorinated compounds(PFCs) in environmental samples has drawn much attention.Recent human exposure studies found relatively high perfluorooctane sulfonate(PFOS) concentrations in blood samples from several cities in China when compared with other countries.The objectives of the present study were:(1) to measure PFC concentrations and compositions in chicken egg samples from local markets in China;and(2) to conduct a preliminary human health risk assessment of egg consumption.Eight pooled egg samples from eight locations were analyzed for 11 PFCs.The results showed that close to 100% of the PFOS in the egg was distributed in egg yolk and PFOS was not detected in egg white(<0.08 ng/g wet weight,w/w).Of the perfluoroalkylsulfonates,only PFOS was detected in all egg samples,while of the perfluoroalkylcarboxylates,perfluoroundecanoic acid(PFUnDA) was detected in all samples,followed by perfluorooctanoate(PFOA)(75% occurrence) and perfluorodecanoic acid(PFDA)(50% occurrence).PFOS concentrations in egg ranged from 45.0 to 86.9 ng/g w/w.The results suggested that current concentrations of PFOS in domestic chicken eggs are unlikely to cause immediate harm to Chinese populations. | WANG Yuan YEUNG Leo Wai Yin YAMASHITA Nobuyoshi TANIYASU Sachi SO Man Ka Margaret B. MURPHY LAM Paul Kwan Sing | 2008 | Chinese Science Bulletin2008，53，4： | 13 |
| 16 | Treatment and prevention of gastrointestinal bleeding in patients receiving antiplatelet therapy显示文摘Antiplatelet therapy is the standard of care for the secondary prevention of acute coronary syndrome and ischemic stroke, especially after coronary intervention. However, this therapy is associated with bleeding complications such as gastrointestinal bleeding, which is one of the most common life-threatening complications. Early endoscopy is recommended for most patients with acute upper gastrointestinal bleeding. After successful endoscopic hemostasis, immediate resumption of antiplatelet therapy with proton-pump inhibitors(PPIs) is recommended to prevent further ischemic events. PPI prophylaxis during antiplatelet therapy reduces the risk of upper gastrointestinal bleeding. The potential negative metabolic interaction between PPIs and clopidogrel is still unclear. | Hiroshi Yasuda Yasumasa Matsuo Yoshinori Sato Sun-ichiro Ozawa Shinya Ishigooka Masaki Yamashita Hiroyuki Yamamoto Fumio Itoh | 2015 | World Journal of Critical Care Medicine2015，4，1： | 13 |
| 17 | An updated review of gastric cancer in the next-generation sequencing era:Insights from bench to bedside and vice versa显示文摘Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs.Recent studies using nextgeneration sequencing(NGS)have revealed a number of potential cancer-driving genes in GC.Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4,a member of the cadherin gene family.Mutations in chromatin remodeling genes(ARID1A,MLL3 and MLL)have been found in 47%of GCs.Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC.Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery,such as DNA methylation,histone modifications,nucleosome positioning,noncoding RNAs and microRNAs.Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings.The antihuman epidermal growth receptor 2(HER2)antibody trastuzumab has led to an era of personalized therapy in GC.In addition,ramucirumab,a monoclonal antibody targeting vascular endothelial growth factor receptor(VEGFR)-2,is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy.Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets,as well as useful biomarkers.In this review,we will summarize the recent advances in the understanding of the molecular pathogenesis of GC,focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets. | Hiroyuki Yamamoto Yoshiyuki Watanabe Tadateru Maehata Ryo Morita Yoshihito Yoshida Ritsuko Oikawa Shinya Ishigooka Shun-ichiro Ozawa Yasumasa Matsuo Kosuke Hosoya Masaki Yamashita Hiroaki Taniguchi Katsuhiko Nosho Hiromu Suzuki Hiroshi Yasuda Yasuhisa Shinomura Fumio Itoh | 2014 | World Journal of Gastroenterology2014，20，14： | 12 |
| 18 | Trend in gastric cancer:35 years of surgical experience in Japan显示文摘AIM:To investigate the trend in gastric cancer surgery in the context of rapid therapeutic advancement in Japan and East Asia.METHODS:A retrospective analysis was performed on 4163 patients who underwent gastric resection for gastric cancer with histological confirmation between 1971 and 2007 at the surgical unit in Kitasato University Hospital,to determine the trend in gastric cancer requiring surgery.RESULTS:Gastric cancer requiring surgical resection increased in our hospital,but the incidence adjusted for population was constant during the observed pe-riod.Interestingly,the ratio of diffuse type/intestinal type gastric cancer was unexpectedly unchanged,and that of advanced/early gastric cancer(EGC)was,however,markedly reduced,while the actual incidence of potentially curative advanced gastric cancer tended to decrease.The incidence of EGC requiring surgery tended to increase as a whole,which is consistent with increased prevalence of endoscopic surveillance.As a result,overall survival and mortality of gastric cancer requiring gastric resection has recently markedly improved.CONCLUSION:In Japan,planned interventions may improve surgical gastric cancer mortality,but an unexpected trend of persistent existence of intestinal type cancer suggests the need for more robust medical intervention. | Keishi Yamashita Shinichi Sakuramoto Masayuki Nemoto Tomotaka Shibata Hiroaki Mieno Natsuya Katada Shiroh Kikuchi Masahiko Watanabe | 2011 | World Journal of Gastroenterology2011，17，29： | 11 |
| 19 | New roles of osteoblasts involved in osteoclast differentiation显示文摘Bone-resorbing osteoclasts are formed from a monocyte/macrophage lineage under the strict control o bone-forming osteoblasts. So far,macrophage colonystimulating factor(M-CSF),receptor activator o nuclear factor-κB ligand(RANKL),and osteoprotegerin(OPG) produced by osteoblasts play major roles in the regulation of osteoclast differentiation. Recent studies have shown that osteoblasts regulate osteoclastogenesis through several mechanisms independent o M-CSF,RANKL,and OPG production. Identification o osteoclast-committed precursors in vivo demonstrated that osteoblasts are involved in the distribution o osteoclast precursors in bone. Interleukin 34(IL-34)a novel ligand for c-Fms,plays a pivotal role in maintaining the splenic reservoir of osteoclast-committed precursors in M-CSF deficient mice. IL-34 is also able to act as a substitute for osteoblast-producing M-CSF in osteoclastogenesis. Wnt5 a,produced by osteoblasts,enhances osteoclast differentiation by upregulating RANK expression through activation of the noncanonical Wnt pathway. Semaphorin 3A produced by osteoblasts inhibits RANKL-induced osteoclast differentiation through the suppression of immunoreceptortyrosine-based activation motif signals. Thus,recent findings show that osteoclast differentiation is tightly regulated by osteoblasts through several different mechanisms. These newly identified molecules are expected to be promising targets of therapeutic agents in bone-related diseases. | Teruhito Yamashita Naoyuki Takahashi Nobuyuki Udagawa | 2012 | World Journal of Orthopedics2012，3，11： | 11 |
| 20 | Hepatitis B virus X protein induces hepatic stem cell-like features in hepatocellular carcinoma by activating KDM5B显示文摘AIM To determine the role of hepatitis B virus X protein(HBx), HBx in regulating hepatic progenitor cell(HPC)-like features in hepatocellular carcinoma(HCC) and the underlying molecular mechanisms.METHODS We used a retrovirus vector to introduce wild type HBx or empty vector into Hep G2 cells. We then used these cells to analyze cell proliferation, senescence, transformation, and stem-like features. Gene expression profiling was carried out on Affymetrix GeneC hip Human U133A2.0 ver.2 arrays according to the manufacturer's protocol. Unsupervised hierarchical clustering analysis and Class Comparison analysis were performed by BRB-Array Tools software Version 4.2.2. A total of 238 hepatitis B virus(HBV)-related HCC patients' array data were used for analyzing clinical features.RESULTS The histone demethylase KDM5 B was significantlyhighly expressed in HBV-related HCC cases(P < 0.01). In HBV proteins, only HBx up-regulated KDM5 B by activating c-myc. Hepatic stem cell(Hp SC) markers(EpC AM, AFP, PROM1, and NANOG) were significantly highly expressed in KDM5B-high HCC cases(P < 0.01). KDM5 B played an important role in maintaining HpS Clike features and was associated with a poor prognosis. Moreover, inhibition of KDM5 B suppressed spheroid formation and cell invasion in vitro.CONCLUSION HBx activates the histone demethylase KDM5 B and induces HPC-like features in HCC. Histone demethylases KDM5 B may be an important therapeutic target against HBV-related HCC cases. | Xuyang Wang Naoki Oishi Tetsuro Shimakami Taro Yamashita Masao Honda Seishi Murakami Shuichi Kaneko | 2017 | World Journal of Gastroenterology2017，23，18： | 10 |
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