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| 1 | FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis显示文摘 | Xu Zhao Ying Yang Bao-Fa Sun Yue Shi Xin Yang Wen Xiao Ya-Juan Hao Xiao-Li Ping Yu-Sheng Chen Wen-Jia Wang Kang-Xuan Jin Xing Wang Chun-Min Huang Yu Fu Xiao-Meng Ge Shu-Hui Song Hyun Seok Jeong Hiroyuki Yanagisawa Yamei Niu Gui-Fang Jia Wei Wu Wei-Min Tong Akimitsu Okamoto Chuan He Jannie M Rendtlew Danielsen Xiu-Jie Wang Yun-Gui Yang | 2014 | Cell Research2014，24，12： | 109 |
| 2 | 肠道病毒71型的RT-PCR诊断及基因特征显示文摘2002~2003年从上海市和重庆市手足口病患儿的疱液标本中分离到10株病毒,其中上海9株,重庆1株。利用两对分别针对EV71和Cox.A16病毒VP1区的特异性引物,用RT PCR方法对病毒进行初步鉴别。根据PCR所用引物及PCR扩增出的产物片段大小不同,可初步判定出EV71和Cox.A16病毒的血清型别。RT PCR结果提示,上海分离到的9株病毒中,有2株为EV71,其余7株病毒为Cox.A16;重庆分离到的1株病毒为EV71。10株病毒的RT PCR产物经序列测定和分析证实,PCR定型结果正确,说明PCR法具有很高的特异性,可作为EV71初步鉴定的首选方法。对所分离的3株EV71病毒进行VP1区编码基因全序列的测定和遗传学分析,通过同源性比较和构建系统发生树发现,此3株EV71病毒和中国大陆已发表的7株EV71病毒(SHZH03、SHZH98、SH F1、SH F2、SH H25、SH H26和CHN 87)全部属于C基因型,与该型代表株比较,同源性为89 3%~94 6%;与A、B基因型代表株比较,同源性为81 3%~84 0%,差异较大。在C基因型中,此3株EV71病毒和中国大陆先前分离的6株病毒(SHZH03、SHZH98、SH F1、SH F2、SH H25、SH H26)的同源性较高,在94 5%~100%范围内。在系统发生树上,这9株病毒形成一个较独立的分支。与CHN 87株的同源性在92 1%~93 6%之间。与已知的C1、C2、C3亚型代表株比较,同源? | 崔爱利 许文波 李秀珠 胡家瑜 凌华 唐伟 杨智宏 张燕 陈立 Hiroyuki Shimizu | 2004 | 病毒学报2004，20，2： | 133 |
| 3 | Association of Fusobacterium nucleatum with immunity andmolecular alterations in colorectal cancer显示文摘The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6%(44/511), which was lower than that in United States cohort studies(13%). Similar to the United States studies, F. nucleatum positivityin Japanese colorectal cancers was significantly associated with microsatellite instability(MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets(i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain micro RNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. Micro RNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may provide insights for strategies to target microbiota, immune cells and tumor molecular alterations for colorectal cancer prevention and treatment. Further investigation is needed to clarify the association of Fusobacterium with T-cells and micro RNA expressions in colorectal cancer. | Katsuhiko Nosho Yasutaka Sukawa Yasushi Adachi Miki Ito Kei Mitsuhashi Hiroyoshi Kurihara Shinichi Kanno Itaru Yamamoto Keisuke Ishigami Hisayoshi Igarashi Reo Maruyama Kohzoh Imai Hiroyuki Yamamoto Yasuhisa Shinomura | 2016 | World Journal of Gastroenterology2016，22，2： | 44 |
| 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 | Randomized controlled trial of pancreatic stenting to prevent pancreatitis after endoscopic retrograde cholangiopancreatography显示文摘AIM:To determine the effectiveness of pancreatic duct(PD) stent placement for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography(ERCP) in high risk patients.METHODS:Authors conducted a single-blind,randomized controlled trial to evaluate the effectiveness of a pancreatic spontaneous dislodgement stent against post-ERCP pancreatitis,including rates of spontaneous dislodgement and complications.Authors defined high risk patients as having any of the following:sphincter of Oddi dysfunction,difficult cannulation,prior history of post-ERCP pancreatitis,pre-cut sphincterotomy,pancreatic ductal biopsy,pancreatic sphincterotomy,intraductal ultrasonography,or a procedure time of more than 30 min.Patients were randomized to a stent group(n = 60) or to a non-stent group(n = 60).An abdominal radiograph was obtained daily to assessspontaneous stent dislodgement.Post-ERCP pancreatitis was diagnosed according to consensus criteria.RESULTS:The mean age(± standard deviation) was 67.4 ± 13.8 years and the male:female ratio was 68:52.In the stent group,the mean age was 66 ± 13 years and the male:female ratio was 33:27,and in the non-stent group,the mean age was 68 ± 14 years and the male:female ratio was 35:25.There were no significant differences between groups with respect to age,gender,final diagnosis,or type of endoscopic intervention.The frequency of post-ERCP pancreatitis in PD stent and non-stent groups was 1.7%(1/60) and 13.3%(8/60),respectively.The severity of pancreatitis was mild in all cases.The frequency of post-ERCP pancreatitis in the stent group was significantly lower than in the non-stent group(P = 0.032,Fisher's exact test).The rate of hyperamylasemia were 30%(18/60) and 38.3%(23 of 60) in the stent and non-stent groups,respectively(P = 0.05,χ2 test).The placement of a PD stent was successful in all 60 patients.The rate of spontaneous dislodgement by the third day was 96.7%(58/60),and the median(range) time to dislodgement was 2.1(2-3) d.The rates of stent migration,hemorrhage,perforation,infection(cholangitis or cholecystitis) or other complicationss were 0%(0/60),0%(0/60),0%(0/60),0%(0/60),0%(0/60),respectively,in the stent group.Univariate analysis revealed no significant differences in high risk factors between the two groups.The pancreatic spontaneous dislodgement stent safely prevented post-ERCP pancreatitis in high risk patients.CONCLUSION:Pancreatic stent placement is a safe and effective technique to prevent post-ERCP pancreatitis.Therefore authors recommend pancreatic stent placement after ERCP in high risk patients. | Yoshiaki Kawaguchi Masami Ogawa Fumio Omata Hiroyuki Ito Tooru Shimosegawa Tetsuya Mine | 2012 | World Journal of Gastroenterology2012，18，14： | 25 |
| 6 | Cancer-associated fibroblasts in hepatocellular carcinoma显示文摘The hepatic stellate cells in the liver are stimulated sustainably by chronic injury of the hepatocytes, activating myofibroblasts, which produce abundant collagen. Myofibroblasts are the major source of extracellular proteins during fibrogenesis, and may directly, or secreted products, contribute to carcinogenesis and tumor progression. Cancer-associated fibroblasts(CAFs) are one of the components of the tumor microenvironment that promote the proliferation and invasion of cancer cells by secreting various growth factors and cytokines. CAFs crosstalk with cancer cells stimulates tumor progression by creating a favorable microenvironment for progression, invasion, and metastasis through the epithelial-mesenchymal transition. Basic studies on CAFs have advanced, and the role of CAFs in tumors has been elucidated. In particular, for hepatocellular carcinoma, carcinogenesis from cirrhosis is a known fact, and participation of CAFs in carcinogenesis is supported. In this review, we discuss the current literature on the role of CAFs and CAF-related signaling in carcinogenesis, crosstalk with cancer cells, immunosuppressive effects, angiogenesis, therapeutic targets, and resistance to chemotherapy. The role of CAFs is important in cancer initiation and progression. CAF-targeted therapy may be effective for suppression not only of fibrosis but also cancer progression. | Norio Kubo Kenichiro Araki Hiroyuki Kuwano Ken Shirabe | 2016 | World Journal of Gastroenterology2016，22，30： | 25 |
| 7 | 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 |
| 8 | Evolution and Coarsening of Carbides in 2.25Cr-1Mo Steel Weld Metal During High Temperature Tempering显示文摘Transformation and coarsening of carbides in 2.25Cr-1Mo steel weld metal during tempering at 700 ℃ for different time intervals ranging from 1 to 150 h were examined by transmission electron microscopy and scanning electron microscopy. M3C carbides were observed in the as-welded specimens and when tempered, the precipitates were mainly composed of M3C, M7C3, and M23C6 carbides. A sequence for corresponding carbide transformation during tempering with initial precipitation of M3C and the subsequent precipitation of M7C3 and M23C6 was proposed. The precipitation of M7C3 with higher chromium content was the main factor contributing to the decrease in coarsening rate of precipitates after prolonged tempering. The decrease in hardness of the tempered specimens agreed well with the prediction of the weakening of precipitation strengthening owing to the coarsening of carbides. | TAO Peng ZHANG Chi YANG Zhi-gang Takeda Hiroyuki | 2010 | Journal of Iron and Steel Research(International)2010，17，5： | 22 |
| 9 | Review of the diagnosis and management of gastrointestinal bezoars显示文摘The formation of a bezoar is a relatively infrequentdisorder that affects the gastrointestinal system.Bezoars are mainly classified into four types dependingon the material constituting the indigestible mass of thebezoar phytobezoars, trichobezoars, pharmacobezoars,and lactobezoars. Gastric bezoars often cause ulcerativelesions in the stomach and subsequent bleeding,whereas small intestinal bezoars present with smallbowel obstruction and ileus. A number of articles haveemphasized the usefulness of Coca-Cola? administrationfor the dissolution of phytobezoars. However, persimmonphytobezoars may be resistant to such dissolutiontreatment because of their harder consistency comparedto other types of phytobezoars. Better understanding ofthe etiology and epidemiology of each type of bezoarwill facilitate prompt diagnosis and management.Here we provide an overview of the prevalence, classification,predisposing factors, and manifestations ofbezoars. Diagnosis and management strategies arealso discussed, reviewing mainly our own case series.Recent progress in basic research regarding persimmonphytobezoars is also briefly reviewed. | Masaya Iwamuro Hiroyuki Okada Kazuhiro Matsueda Tomoki Inaba Chiaki Kusumoto Atsushi Imagawa Kazuhide Yamamoto | 2015 | World Journal of Gastrointestinal Endoscopy2015，7，4： | 22 |
| 10 | Seed germination and dormancy: The classic story, new puzzles, and evolution显示文摘This review highlights recent progresses in seed germination and dormancy research.Research on the weakening of the endosperm during germination,which is almost a classic theme in seed biology,was resumed byα-xylosidase studies.Strong genetic evidence was presented to suggest that the quality control of xyloglucan biosynthesis in the endosperm(and the embryo)plays a critical role in germination.Further analyses on the endosperm and the adjace nt layers have suggested that the cutin coat in the endosperm-testa interphase negatively affects germination while the en dosperm-embryo in terphase produces a sheath that facilitates germination.These progresses significantly advanced our understanding of seed germination mechanisms.A breakthrough in dormancy research,on the other hand,revealed the unique abscisic acid signaling pathway that is regulated by DELAY OF GERMINATION1(DOG1).The detailed analysis of DOC1 expression uncovered the intriguing story of reciprocal regulation of the sensean tisense pair,which gen erated new questions.Recent studies also suggested that the DOG1 function is not limited to dormancy but extended through general seed maturation,which provokes questions about the evolution of DOG1 family proteins.Seed biology is becoming more exciting with the classic stories being revitalized and new puzzles emerging from the frontier. | Hiroyuki Nonogaki | 2019 | Journal of Integrative Plant Biology2019，61，5： | 22 |
| 11 | Genetic and epigenetic aspects of initiation and progression of hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC) is a primary cancer of the liver that is predominant in developing countries and is responsible for nearly 600000 deaths each year worldwide. Similar to many other tumors, the development of HCC must be understood as a multistep process involving the accumulation of genetic and epigenetic alterations in regulatory genes, leading to the activation of oncogenes and the inactivation or loss of tumor suppressor genes. Extensive research over the past decade has identified a number of molecular biomarkers, including aberrant expression of HCCrelated genes and microRNAs. The challenge facing HCC research and clinical care at this time is to address the heterogeneity and complexity of these genetic and epigenetic alterations and to use this information to direct rational diagnosis and treatment strategies. The multikinase inhibitor sorafenib was the first molecularly targeted drug for HCC to show some extent of survival benefits in patients with advanced tumors. Although the results obtained using sorafenib support the importance of molecular therapies in the treatment of HCC, there is still room for improvement. In addition,no molecular markers for drug sensitivity, recurrence and prognosis are currently clinically available. In this review, we provide an overview of recently published articles addressing HCC-related genes and microRNAs to update what is currently known regarding genetic and epigenetic aspects of the pathogenesis of HCC and propose novel promising candidates for use as diagnostic and therapeutic targets in HCC. | Mitsuro Kanda Hiroyuki Sugimoto Yasuhiro Kodera | 2015 | World Journal of Gastroenterology2015，21，37： | 22 |
| 12 | 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 |
| 13 | Diagnostic and therapeutic single-operator cholangiopancreatoscopy in biliopancreatic diseases:Prospective multicenter study in Japan显示文摘AIM: To assess the utility and safety of single-operator cholangiopancreatoscopy(SOCPS) using the Spy Glass system in widespread clinical application for biliary and pancreatic diseases.METHODS: This study was a prospective case series conducted in 20 referral centers in Japan. There were 148 patients who underwent SOCPS; 124 for biliary diseases and 24 for pancreatic diseases. The attempted interventions were SOCPS examination, SOCPS-directed tissue sampling, and therapy for stone removal, among others. The main outcomes were related to the procedure success rate in terms of visualizing the target lesions, SOCPS-directed adequate tissue sampling, and complete stone removal. RESULTS: A total of 148 patients were enrolled for the diagnosis of indeterminate biliary and pancreatic lesions or treatment of biliary and pancreatic disease. The overall procedure success rate of visualizing the target lesions was 91.2%(135/148). The overall procedural success rates of visualizing the target lesions of diagnostic SOCPS in the bile duct and pancreatic duct were 95.5%(84/89) and 88.2%(15/17), respectively. Diagnosis: the overall adequate tissue for histologic examination was secured in 81.4% of the 86 patients who underwent biopsy under SOCPS(bile duct, 60/75, 80.0%; pancreatic duct, 10/11, 90.9%). The accuracy of histologic diagnosis using SOCPS-directed biopsies in indeterminate bile duct lesions was 70.7%(53/75). In the pancreatic duct, the accuracy of SOCPS visual impression of intraductal papillary mucinous neoplasm was 87.5%(14/16). Stone therapy: complete biliary and pancreatic stone clearance combined with SOCPS-directed stone therapy using electrohydraulic lithotripsy or laser lithotripsy was achieved in 74.2%(23/31) and 42.9%(3/7) of the patients, respectively. Others: SOCPS using the Spy Glass system was used in cannulation of the cystic duct in two patients and for passing across the obstructed self-expandable metallic stent for a malignant biliary stricture in two patients. All procedures were successful in both SOCPS-guided therapies. The incidence of procedure-related adverse events was 5.4%(8/148). CONCLUSION: SOCPS with direct visualization and biopsy for diagnosis and SOCPS-directed therapy for biliary and pancreatic diseases can be safely performed with a high success rate. | Toshio Kurihara Ichiro Yasuda Hiroyuki Isayama Toshio Tsuyuguchi Taketo Yamaguchi Ken Kawabe Yoshinobu Okabe Keiji Hanada Tsuyoshi Hayashi Takao Ohtsuka Syuhei Oana Hiroshi Kawakami Yoshinori Igarashi Kazuya Matsumoto Kiichi Tamada Shomei Ryozawa Hiroki Kawashima Yutaka Okamoto Iruru Maetani Hiroyuki Inoue Takao Itoi | 2016 | World Journal of Gastroenterology2016，22，5： | 20 |
| 14 | Clinicopathological features of alpha-fetoprotein producing early gastric cancer with enteroblastic differentiation显示文摘AIM To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation(GCED).METHODS We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer(CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital.GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection rate.RESULTS Six cases(5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases(139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC(66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED(positivity, 83.3%), immunohistochemically.CONCLUSION Even in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological features of this highly malignant type of cancer. | Kohei Matsumoto Hiroya Ueyama Kenshi Matsumoto Yoichi Akazawa Hiroyuki Komori Tsutomu Takeda Takashi Murakami Daisuke Asaoka Mariko Hojo Natsumi Tomita Akihito Nagahara Yoshiaki Kajiyama Takashi Yao Sumio Watanabe | 2016 | World Journal of Gastroenterology2016，22，36： | 20 |
| 15 | Importance of adequate immunosuppressive therapy for the recovery of patients with 'life-threatening' severe exacerbation of chronic hepatitis B显示文摘AIM: Hepatitis B virus (HBV) re-activation often occurs spontaneously or after withdrawal of immunosuppressive therapy in patients with chronic hepatitis B. Severe exacerbation, sometimes developing into fulminant hepatic failure, is at high risk of mortality. The efficacy of corticosteroid therapy in 'clinically severe' exacerbation of chronic hepatitis B has not been well demonstrated. In this study we evaluated the efficacy of early introduction of high-dose corticosteroid therapy in patients with lifethreatening severe exacerbation of chronic hepatitis B.METHODS: Twenty-two patients, 14 men and 8 women,were defined as 'severe' exacerbation of chronic hepatitis B using uniform criteria and enrolled in this study. Eleven patients were treated with corticosteroids at 60 mg or more daily with or without anti-viral drugs within 10 d after the diagnosis of severe disease ('early high-dose'group) and 11 patients were either treated more than 10 d or untreated with corticosteroids ('non-early high-dose'group).RESULTS: Mean age, male-to-female ratio, mean prothrombin time (PT) activity, alanine transaminase (ALT)level, total bilirubin level, positivity of HBeAg, mean IgMHBc titer, and mean HBV DNA polymerase activity did not differ between the two groups. Ten of 11 patients of the 'early high-dose' group survived, while only 2 of 11 patients of the 'non-early high-dose' group survived (P<0.001). During the first 2 wk after the introduction of corticosteroids, improvements in PT activities and total bilirubin levels were observed in the 'early high-dose'group. Both ALT levels and HBV DNA polymerase levels fell in both groups.CONCLUSION: The introduction of high-dose corticosteroid can reverse deterioration in patients with 'clinically lifethreatening' severe exacerbation of chronic hepatitis B,when used in the early stage of illness. | Keiichi Fujiwara Osamu Yokosuka Hiroshige Kojima Tatsuo Kanda Hiromitsu Saisho Hiroyuki Hirasawa Hiroshi Suzuki | 2005 | World Journal of Gastroenterology2005，11，8： | 20 |
| 16 | Leaching of phosphorus from incinerated sewage sludge ash by means of acid extraction followed by adsorption on orange waste gel显示文摘Ashes from sewage sludge incineration have a high phosphorus content, approximately 8% (W/W), which indicates a potential resource of the limiting nutrient. Incineration of sewage sludge with subsequent recovery of phosphorus is a relatively new sludge treatment technique. In this article, the leaching of phosphorus by using sulfuric acid as well as hydrochloric acid by means of several batch experiments was presented. At the same time a selective recovery of phosphorus by adsorption was also discussed. The effects of acid concentration, temperature and time on extraction were studied. The phosphorus leaching increased with the increase in acid concentration and temperature. Kinetic studies showed that the complete leaching of phosphorus took place in less than 4 h. Selective adsorption of phosphorus by using orange waste gel provided a hint for recovery of this natural resource, which eventually could meet the ever-increasing requirement for phosphorus. The overall results indicated that the incinerated sewage sludge ash can be treated with acid to efficiently recover phosphorus and thus can be considered a potentially renewable source of phosphorus. | Biplob Kumar Biswas Katsutoshi Inoue Hiroyuki Harada Keisuke Ohto Hidetaka Kawakita | 2009 | Journal of Environmental Sciences2009，21，12： | 20 |
| 17 | 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 |
| 18 | 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 |
| 19 | Suppression of experimental osteoarthritis by adenovirus-mediated double gene transfer显示文摘背景骨关节炎(OA ) 是一长期并且不治之症,缺乏的有效处理。基因治疗把一条激进的不同途径提供给关节炎的处理。尽管 OA 的病原学仍然保持不清楚,现在有可观的证据建议 thatinterleukin-1 (IL-1 ) 和肿瘤坏死因素 -- α(TNF- α) 是在 OA 的致病的主要调停人。这研究的目标是决定本地表示 ofinterleukin-1 受体对手(IL-1Ra ) 和可溶的肿瘤坏死因素的功效 -- α受体类型(sTNF-RI ) 我骨关节炎由在兔子的直接调停 adenoviral 的 intra 关节的基因交货当模特儿。包含 IL-1Ra 或 sTNF-RI 基因的方法 Adenoviral 向量被构造。中间的并行的系带的切除加中间的 meniscectomy 在 12 只新西兰白兔子的两后部的膝导致的 OAwas。在外科以后的五天,果汁饮料的约 1 x 10 个 ~8plaque 形式单位(pfu ) 没有病毒通过膝盖骨的腱被注入膝的联合空间。12 只操作兔子的一个总数被划分成四个组。三个试验性的兔子组收到了 1 X 10 ~ 编码任何一个 IL-1Ra (3 只兔子) 的侵入人体气管粘膜的病菌的 8 pfu, sTNF-RI (3rabbits ) 和在联合(3 只兔子) 的 sTNF-RI,进两个膝关节分别地。3 只兔子的 Aninflamed 控制组收到了进两个的 Ad-GFP 的 8 pfu 连接的约 1 x 10 ~ 。在侵入人体气管粘膜的病菌的注射以后的三天,每只兔子的两膝是通过膝盖骨的腱与盐溶液的 1 ml 变老的洗室。在白天 7 点,兔子被牺牲,并且膝是为 transgene 表示的效果变老,把并且分析的洗室。在恢复洗室年龄液体的 IL-1Ra andsTNF-RI 表示的层次用一个 cytokine ELISA 工具包被测量。Cartilagefrom 中间的大腿骨的髁和 synovium 的损害区域被修理,嵌入, sectioned 并且与 hematoxylin 和曙红和 toluidine 蓝色(软骨)( 软骨和 synovium ) 染色了。Thesamples 被评估的轻显微镜学和份量上检验。IL-1Ra 的结果 Intra-articulardelivery 导致了软骨降级的重要抑制,但是 affectsynovial 变化。相反,独自收到 sTNF-RI 的兔子膝关节没在软骨降级显示出更可检测的引出。然而, IL-1Ra 和 sTNF-RI 的两倍基因转移在滑膜炎导致了软骨降级和可见减小的更高的抑制。Thesedata 增加并且证实 IL-1Ra 有好 chondroprotective 性质,而是 TNF- α封锁在联合破坏上有小效果。在联合的两个对手的提高的治疗学的效果建议多重煽动性的 cytokines 的抑制的结论可能在对待 OA 独自是比任何一个 cytokine 的封锁更有效的。 | WANG Hai-jun YU Chang-long Kishi Hiroyuki Motoki Kazumi MAO Ze-bin Muraguchi Atsushi | 2006 | Chinese Medical Journal2006，，16： | 19 |
| 20 | Xanthogranulomatous cholecystitis:Difficulty in differentiating from gallbladder cancer显示文摘AIM: To compare cases of xanthogranulomatous cholecystitis(XGC) and advanced gallbladder cancer and discuss the differential diagnoses and surgical options.METHODS: From April 2000 to December 2013, 6 XGC patients received extended surgical resections. During the same period, 16 patients were proven to have gallbladder(GB) cancer, according to extended surgical resection. Subjects chosen for analysis in this study were restricted to cases of XGC with indistinct borders with the liver as it is often difficult to distinguish these patients from those with advanced GB cancer. We compared the clinical features and computed tomography findings between XGC and advanced GB cancer. The following clinical features were retrospectively assessed: age, gender, symptoms, and tumor markers. As albumin and the neutrophil/lymphocyte ratio(NLR) are prognostic in several cancers, we compared serum albumin levels and the NLR between the two groups. The computerized tomography findings were used to compare the two diseases, determine the coexistence of gallstones, the pattern of GB thickening(focal or diffuse), the presence of a hypoattenuated intramural nodule, and continuity of the mucosal line.RESULTS: Based on the preoperative image findings, we suspected GB carcinoma in all cases includingXGC in this series. In addition, by pathological examination, we found that the group of patients with XGC developed inflammatory disease after surgery. Patients with XGC tended to have abdominal pain(4/6, 67%). However, there was no significant difference in clinical symptoms, including fever, between the two groups. Serum albumin and NLR were also similar in the two groups. Serum tumor markers, such as carcinoembryonic antigen(CEA) and carbohydrate antigen 19-9(CA19-9), tended to increase in patients with GB cancer. However, no significant differences in tumor markers were identified. On the other hand, gallstones were more frequently observed in patients with XGC(5/6, 83%) than in patients with GB cancer(4/16, 33%)(P = 0.0116). A hypoattenuated intramural nodule was found in 3 patients with XGC(3/6, 50%), but in only 1 patient with GB cancer(1/16, 6%)(P = 0.0024). The GB thickness, continuous mucosal line, and bile duct dilatation showed no significant differences between XGC and GB cancer.CONCLUSION: Although XGC is often difficult to differentiate from GB carcinoma, it is possible to obtain an accurate diagnosis by careful intraoperative gross observation, and several intraoperative frozen sections. | Hideki Suzuki Satoshi Wada Kenichiro Araki Norio Kubo Akira Watanabe Mariko Tsukagoshi Hiroyuki Kuwano | 2015 | World Journal of Gastroenterology2015，21，35： | 18 |
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