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| 1 | Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis显示文摘Nonalcoholic fatty liver disease(NAFLD)/nonalcoholic steatohepatitis(NASH) is considered to be a hepatic manifestation of metabolic syndrome, and its incidence is rapidly increasing worldwide. It is currently the most common chronic liver disease. NASH can progress to liver cirrhosis and hepatocellular carcinoma, and may result in liver-related death. Currently, the principal treatment for NAFLD/NASH is lifestyle modification by diet and exercise. However, pharmacological therapy is indispensable because obese patients with NAFLD often have difficulty maintaining improved lifestyles. The pathogenesis of NAFLD/NASH has not been completely elucidated. However, insulin resistance, inflammatory cytokines, and oxidative stress are thought to be important in the development and/or progression of the disease. Currently, insulin sensitizers(thiazolidinediones) and antioxidants(vitamin E) seem to be the most promising therapeutic agents for NAFLD/NASH, and lipid-lowering drugs, pentoxifylline, angiotensin receptor blockers, and n-3 polyunsaturated fatty acids also have promise. However, there is a lack of consensus regarding the most effective and appropriate pharmacotherapy for NAFLD/NASH. Animal experiments suggest that herbal medicines and natural products may be promising therapeutic agents for NAFLD/NASH, but their efficacy and safety are yet to be investigated in human studies. In this paper, we review the existing and potential pharmacological therapies for NAFLD/NASH. | Yoshihisa Takahashi Keiichiro Sugimoto Hiroshi Inui Toshio Fukusato | 2015 | World Journal of Gastroenterology2015，21，13： | 41 |
| 2 | Continuous regional arterial infusion therapy with gabexate mesilate for severe acute pancreatitis显示文摘AIM: To evaluate the effi cacy of continuous regional arterial infusion therapy (CRAI) with gabexate mesilate and antibiotics for severe acute pancreatitis (SAP). METHODS: We conducted a prospective study on patients who developed SAP with or without CRAI. Out of 18 patients fulf illed clinical diagnostic criteria for SAP in Japan, 9 patients underwent CRAI, while 9 patients underwent conventional systemic protease inhibitor and antibiotics therapy (non-CRAI). CRAI was initiated within 72 h of the onset of pancreatitis. Gabexate mesilate (2400 mg/d) was continuously administered for 3 to 5 d. The clinical outcome including serum infl ammation-related parameters were examined. RESULTS: The duration of abdominal pain in the CRAI group was 1.9 ± 0.26 d, whereas that in the non-CRAI group was 4.3 ± 0.50. The duration of SIRS in the CRAI group was 2.2 ± 0.22 d, whereas that in the non- CRAI group was 3.2 ± 0.28. Abdominal pain and SIRS disappeared signifi cantly in a short period of time after the initiation of CRAI using gabexate mesilate. The average length of hospitalization signifi cantly differed between the CRAI and non-CRAI groups, 53.3 ± 7.9 d and 87.4 ± 13.9 d, respectively. During the first two weeks, levels of serum CRP and the IL6/IL10 ratio in the CRAI group tended to have a rapid decrease compared to those in the non-CRAI group. CONCLUSION: The present results suggest that CRAI using gabexate mesilate was effective against SAP. | Yoshifumi Ino Yoshiyuki Arita Tetsuro Akashi Toshinari Kimura Hisato Igarashi Takamasa Oono Masayuki Furukawa Ken Kawabe Keiichiro Ogoshi Jiro Ouchi Toshihiko Miyahara Ryoichi Takayanagi Tetsuhide Ito | 2008 | World Journal of Gastroenterology2008，14，41： | 20 |
| 3 | Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome显示文摘Hutchinson-Gilford 早衰症候群(HGPS ) 和沃纳症候群(WS ) 是二最好描绘的人的 progeroid 症候群。HGPS 被一个点变化在 lamin A (LMNA ) 基因引起,导致截断的蛋白质 productprogerin 的生产。WS 被变化在 WRN 基因引起,编码 loss-of-function RecQ DNA helicase。这里,由基因编辑,我们创造了 isogenic 人的胚胎的干细胞(转换字符) 与异质接合(G608G/+) 或同型结合(G608G/G608G ) LMNA 变化和 biallelic WRN 大美人为为 HGPS 和 WS 致病建模,分别地。当转换字符和 endothelial 房间(EC ) 没介绍早熟的老朽的任何特征时, HGPS 间充质、 WS 间充质的干细胞(MSC ) 与不同动力学显示出联系老化的显型。当 HGPS-MSCs 展出了迟了发作的尖锐早衰 characterisitcs 时, WS-MSCs 有早发作的温和早衰显型。一起拿,我们的学习比较并且形成对照不同病理 underpinning 二早衰混乱,并且提供可靠干细胞为病理学、生理的老化识别新治疗学的策略的基于的模型。 | Zeming Wu Weiqi Zhang Moshi Song Wei Wang Gang Wei Wei Li Jinghui Lei Yu Huang Yanmei Sang Piu Chan Chang Chen Jing Qu Keiichiro Suzuki Juan Carlos Izpisua Belmonte Guang-Hui Liu | 2018 | Protein & Cell2018，9，4： | 15 |
| 4 | Genetic enhancement in cultured human adult stem cells conferred by a single nucleotide recoding显示文摘 | Jiping Yang Jingyi Li Keiichiro Suzuki Xiaomeng Liu Jun Wu Weiqi Zhang Ruotong Ren Weizhou Zhang Piu Chan Juan Carlos Izpisua Belmonte Jing Qu Fuchou Tang Guang-Hui Liu | 2017 | Cell Research2017，27，9： | 12 |
| 5 | CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs显示文摘 | Lixia Wang Fei Yi Lina Fu Jiping Yang Si Wang Zhaoxia Wang Keiichiro Suzuki Liang Sun Xiuling Xu Yang Yu Jie Qiao Juan Carlos Izpisua Belmonte Ze Yang Yun Yuan Jing Qu Guang-Hui Liu | 2017 | Protein & Cell2017，8，5： | 10 |
| 6 | Endoscopic therapy for early gastric cancer: Standard techniques and recent advances in ESD显示文摘The technique of endoscopic submucosal dissection(ESD)is now a well-known endoscopic therapy for early gastric cancer.ESD was introduced to resect large specimens of early gastric cancer in a single piece.ESD can provide precision of histologic diagnosis and can also reduce the recurrence rate.However,the drawback of ESD is its technical difficulty,and,consequently,it is associated with a high rate of complications,the need for advanced endoscopic techniques,and a lengthy procedure time.Various advances in the devices and techniques used for ESD have contributed to overcoming these drawbacks. | Keiichiro Kume | 2014 | World Journal of Gastroenterology2014，20，21： | 10 |
| 7 | Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction显示文摘Cockayne syndrome(CS)is a rare autosomal recessive inherited disorder characterized by a variety of clinical features,including increased sensitivity to sunlight,progressive neurological abnormalities,and the appearance of premature aging.However,the pathogenesis of CS remains unclear due to the limitations of current disease models.Here,we generate integration-free induced pluripotent stem cells(iPSCs)from fibroblasts from a CS patient bearing mutations in CSB/ERCC6 gene and further derive isogenic genecorrected CS-iPSCs(GC-iPSCs)using the CRISPR/Cas9 system.CS-associated phenotypic defects are recapitulated in CS-iPSC-derived mesenchymal stem cells(MSCs)and neural stem cells(NSCs),both of which display increased susceptibility to DNA damage stress.Premature aging defects in CS-MSCs are rescued by the targeted correction of mutant ERCC6.We next map the transcriptomic landscapes in CS-iPSCs and GC-iPSCs and their somatic stem cell derivatives(MSCs and NSCs)in the absence or presence of ultraviolet(UV)and replicative stresses,revealing that defects in DNA repair account for CS pathologies.Moreover,we generate autologous GC-MSCs free of pathogenic mutation under a cGMP(Current Good Manufacturing Practice)-compliant condition,which hold potential for use as improved biomaterials for future stem cell replacement therapy for CS.Collectively,our models demonstrate novel disease features and molecular mechanisms and lay a foundation for the development of novel therapeutic strategies to treat CS. | Si Wang Zheying Min Qianzhao Ji Lingling Geng Yao Su Zunpeng Liu Huifang Hu Lixia Wang Weiqi Zhang Keiichiro Suzuiki Yu Huang Puyao Zhang Tie-Shan Tang Jing Qu Yang Yu Guang-Hui Liu Jie Qiao | 2020 | Protein & Cell2020，11，1： | 7 |
| 8 | Endoscopic mucosal resection and endoscopic submucosal dissection for early gastric cancer:Current and original devices显示文摘Compared with endoscopic submucosal dissection(ESD),endoscopic mucosal resection(EMR) is easier to perform and requires less time for treatment.However,EMR has been replaced by ESD,because achieving en bloc resection of specimens > 20 mm in diameter is difficult with EMR.The technique of ESD was introduced to resect large specimens of early gastric cancer in a single piece.ESD can provide precise histological diagnosis and can also reduce the rate of recurrence,but has a high level of technical difficulty,and is consequently associated with a high rate of complications,a need for advanced endoscopic techniques,and a lengthy procedure time.To overcome disadvantages in both EMR and ESD,various advances have been made in submucosal injections,knives,other accessories,and in electrocoagulation systems. | Keiichiro Kume | 2009 | World Journal of Gastrointestinal Endoscopy2009，1，1： | 6 |
| 9 | Autoimmune pancreatitis with IgG4-positive plasma cell infiltration in salivary glands and biliary tract显示文摘A 62-year-old male was referred to our hospital because of liver dysfunction, diffuse pancreatic swelling, and trachelophyma. At admission, the patient was free of pain.Physical examination showed enlarged and palpable bilateral submandibular masses, but no palpable mass or organomegaly in the abdomen. Laboratory findings were as follows: total protein 90 g/L with γ-globulin of 37.3% (33 g/L), total bilirubin 4 mg/L, aspartate aminotransferase 39 IU/L, alanine aminotransferase 67 IU/L, γ-glutamyl transpeptidase 1 647 IU/L, and amylase 135 IU/L. Autoantibodies were negative, and tumor markers were within the normal range. Serum IgG4 level was markedly elevated (18 900 mg/L). Computed tomography (CT) showed diffuse swelling of the pancreas and dilatation of both common and intra-hepatic bile ducts. Endoscopic retrograde pancreatography (ERP) revealed diffuse irregular and narrow main pancreatic duct and stenosis of the lower common bile duct. Biopsy specimens from the pancreas, salivary gland and liver showed marked periductal IgG4-positive plasma cell infiltration with fibrosis. We considered this patient to be autoimmune pancreatitis (AIP) with fibrosclerosis of the salivary gland and biliary tract, prescribed prednisolone at an initial dose of 40 mg/d. Three months later, the laboratory data improved almost to normal. Abdominal CT reflected prominent improvement in the pancreatic lesion. Swelling of the salivary gland also improved. At present, the patient is on 10 mg/d of prednisolone without recurrence of the pancreatitis. We present here a case of AIP with fibrosclerosis of salivary gland and biliary tract. | Masashi Taguchi Gentaro Aridome Shintaro Abe Keiichiro Kume Mitsuo Tashiro Mitsuyoshi Yamamoto Yasuyuki Kihara Hayato Nakamura Makoto Otsuki | 2005 | World Journal of Gastroenterology2005，11，35： | 5 |
| 10 | CRISPR/Cas9 and TALE: beyond cut and paste显示文摘基于核酸酶的染色体编辑证明了是为疾病建模和基因治疗的一个强大、有希望的工具。在 CRISPR/Cas 和故事的最近的进展显示他们能也被用作基因表示的一个指向的管理者,以及为照亮特定的 chromosomal 结构或 genomic 区域被利用。 | Liping Deng Ruotong Ren Jun Wu Keiichiro Suzuki Juan Carlos Izpisua Belmote Guang-Hui Liu | 2015 | Protein & Cell2015，6，3： | 4 |
| 11 | Visualization of aging-associated chromatin alterations with an engineered TALE system显示文摘在实时房间的特定的 genomic loci 的可视化在多样的生物过程期间是为在染色质建筑学的动态变化的调查的一个前提,例如细胞的老化。然而,当前的精确 genomic 成像方法被缺乏妨碍荧光灯有高特性和 signal-to-noise 的探针形成对照。我们发现那常规抄写像使活跃之物的受动器(故事) 趋于形成蛋白质总数,从而在成像应用程序损害他们的性能。通过屏蔽,我们发现有故事的那熔化 thioredoxin 阻止了总数形成,开基于故事的 genomic 成像的完整的力量。用熔化 thioredoxin 的故事(TTALE ) ,我们在各种各样的 genomic loci 完成了高质量的成像并且观察联系老化(epi ) 在在人和老鼠早衰模型的 telomeres 和着丝点的 genomic 改变。重要地,我们鉴别 ribosomal DNA 的摩擦为人的老化作为一个分子的标记重复。我们的学习为精确在 vitro 并且在 vivo 监视染色质动力学建立一个简单、柔韧的成像方法。 | Ruotong Ren Liping Deng Yanhong Xue Keiichiro Suzuki Weiqi Zhang Yang Yu Jun Wu Liang Sun Xiaojun Gong Huiqin Luan Fan Yang Zhenyu Ju Xiaoqing Ren Si Wang Hong Tang Lingling Geng Weizhou Zhang Jian Li Jie Qiao Tao Xu Jing Qu Guang-Hui Liu | 2017 | Cell Research2017，27，4： | 4 |
| 12 | Induced neural stem cells: a new tool for studying neural development and neurological disorders显示文摘 | Guang-Hui Liu Fei Yi Keiichiro Suzuki Jing Qu Juan Carlos Izpisua Belmonte | 2012 | Cell Research2012，22，7： | 4 |
| 13 | Establishment of hepatic and neural differentiation platforms of Wilson’s disease specific induced pluripotent stem cells显示文摘The combination of disease-specific human induced pluripotent stem cells(iPSC)and directed cell differentiation offers an ideal platform for modeling and studying many inherited human diseases.Wilson’s disease(WD)is a monogenic disorder of toxic copper accumulation caused by pathologic mutations of the ATP7B gene.WD affects multiple organs with primary manifestations in the liver and central nervous system(CNS).In order to better investigate the cellular pathogenesis of WD and to develop novel therapies against various WD syndromes,we sought to establish a comprehensive platform to differentiate WD patient iPSC into both hepatic and neural lineages.Here we report the generation of patient iPSC bearing a Caucasian population hotspot mutation of ATP7B.Combining with directed cell differentiation strategies,we successfully differentiated WD iPSC into hepatocyte-like cells,neural stem cells and neurons.Gene expression analysis and cDNA sequencing confirmed the expression of the mutant ATP7B gene in all differentiated cells.Hence we established a platform for studying both hepatic and neural abnormalities of WD,which may provide a new tool for tissue-specific disease modeling and drug screening in the future. | Fei Yi Jing Qu Mo Li Keiichiro Suzuki Na Young Kim Guang-Hui Liu Juan Carlos Izpisua Belmonte | 2012 | Protein & Cell2012，3，11： | 3 |
| 14 | Development of a novel endoscopic manipulation system: The Endoscopic operation robot显示文摘AIM: To develop and evaluate the endoscopic operation robot (EOR). The EOR is a robot system designed specifically for remote manipulation of the scope during gastrointestinal endoscopy by a seated endoscopist. METHODS: Total colonoscopy examinations using a colonoscopy training model were performed compared conventional insertion by manual manipulation and remote-controlled insertion, using the EOR. The author investigated the time taken for each of the 50 examinations. RESULTS: The median insertion time (in minutes) for each 10 examinations (EOR vs manual manipulation) was 73.70 ± 25.37 vs 3.77 ± 1.34 in the first group, 38.40 ± 6.24 vs 3.40 ± 0.97 in the second group, 27.6 ± 4.01 vs 2.70 ± 0.95 in the third group, 23.8 ± 3.65 vs 3.10 ± 0.88 in the fourth group, and 22.9 ± 5.02 vs 2.60 ± 1.08 in the fifth group.CONCLUSION: The study suggested the possibility of the clinical application of the EOR. | Keiichiro Kume Takeshi Kuroki Takahiro Sugihara Masafumi Shinngai | 2011 | World Journal of Gastrointestinal Endoscopy2011，3，7： | 3 |
| 15 | Sepsis caused by endoscopic clipping for colonic diverticular bleeding: A rare complication显示文摘We herein report the rare complication of sepsis caused by endoscopic clipping for colonic diverticular bleeding. A 78-year-old man with a 12-h history of near syncope and painless hematochezia was admitted to our hospital. Following the transfusion of 4 U of blood and continued hematochezia, a colonoscopy was performed. Active bleeding was seen as continuous arterial spurting from a single diverticulum located in the middle ascending colon. This diverticulum was seamed by four endoclips. The next day, the patient became febrile with a temperature of 39.2℃. Laboratory data included a white blood cell count of 18 100/mm3 and a C-reactive protein level of 3.4 mg/dL. He was diagnosed with sepsis since Escherichia coli was detected in the blood culture. Antibiotics were started. Four days later his fever had improved and laboratory data improved 9 d later. | Keiichiro Kume Masahiro Yamasaki Ichiro Yoshikawa | 2009 | World Journal of Gastroenterology2009，15，30： | 3 |
| 16 | Outcome in disappearing colorectal cancer liver metastases during oxaliplatin-basedchemotherapy显示文摘 | Tomojiro Ono Hideyuki Ishida Kensuke Kumamoto Norimichi Okada Keiichiro Ishibashi | 2012 | Oncology Letters2012，，5： | 2 |
| 17 | Proliferative activity of intrahepatic colorectal metastases after preoperative hemihepatic portal vein embolization显示文摘 | Norihiro Kokudo Keiichiro Tada Makoto Seki Hirotoshi Ohta Kaoru Azekura Masashi Ueno Keiichiro Ohta Toshiharu Yamaguchi Toshiki Matsubara Takashi Takahashi Toshifusa Nakajima Tetsuichiro Muto Takaaki Ikari Akio Yanagisawa Yo Kato | 2001 | Hepatology2001，，2： | 2 |
| 18 | Long-term outcomes of extended radical resection combined with intraoperative radiation therapy for pancreatic cancer显示文摘 | Hiroshi Takamori Takehisa Hiraoka Keiichiro Kanemitsu Tatsuya Tsuji Hiroshi Tanaka Akira Chikamoto Kei Horino Toru Beppu Masahiko Hirota Hideo Baba | 2008 | Journal of Hepato - Biliary - Pancreatic Surgery2008，，6： | 2 |
| 19 | 安倍经济学之辩显示文摘对日本已经持续十年之久的通货紧缩而言,安倍经济学是一场重大的奇袭之战。安倍经济学的理论基础并不一定受到普遍认可,从这个意义上看,该经济学的确是实验性政策。
安倍经济学由三支"箭"组成。第一支箭是宽松的货币政策。日本央行行长黑田东彦(HaruhikoKuroda)形容该货币政策是"远远超出了理性范围"。第二支箭是财政刺激,增加了总额为13万亿日元(超过1400亿美元)的财政预算。 | 小林庆一郎(Keiichiro Kobayashi) 田姗姗(翻译) | 2013 | 中国经济报告2013，，7： | 2 |
| 20 | Minute gastric carcinoid tumor with regional lymph node metastasis显示文摘 | Toshihiko Shinohara Shigekazu Ohyama Hideki Nagano Nozomi Amaoka Keiichiro Ohta Toshiki Matsubara Toshiharu Yamaguchi Akio Yanagisawa Yo Kato Tetsuichiro Muto | 2003 | Gastric Cancer2003，，4： | 2 |
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