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通讯和计算机（中英文版） 2017年第2期14卷 73-83页

作者： Norikatsu Fujita Hiroshi Takeshita Sho Aoki Hirotada Fukae kazushige matsumoto Tomohiro Murakami Minoru Hoshino Ability Development Dept. Polytechnic University of Japan

Retreatment of patients with treatment failure of directacting antivirals: Focus on hepatitis C virus genotype 1b

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World Journal of Gastroenterology 2017年第46期23卷 8120-8127页

作者： Tatsuo Kanda kazushige Nirei Naoki matsumoto Teruhisa Higuchi Hitomi Nakamura Hiroaki Yamagami Shunichi Matsuoka Mitsuhiko Moriyama Division of Gastroenterology and Hepatology Department of Internal MedicineNihon University School of Medicine

The recent development of direct-acting antiviral agents(DAAs) against hepatitis C virus(HCV) infection could lead to higher sustained virological response(SVR) rates, with shorter treatment durations and fewer adverse events compared with regimens that include interferon. However, a relatively small proportion of patients cannot achieve SVR in the first treatment, including DAAs with or without peginterferon and/or ribavirin. Although retreatment with a combination of DAAs should be conducted for these patients, it is more difficult to achieve SVR when retreating these patients because of resistance-associated substitutions(RASs) or treatment-emergent substitutions. In Japan, HCV genotype 1 b(GT1 b) is founded in 70% of HCVinfected individuals. In this minireview, we summarize the retreatment regimens and their SVR rates for HCV GT1 b. It is important to avoid drugs that target the regions targeted by initial drugs, but next-generation combinations of DAAs, such as sofosbuvir/velpatasvir/voxilaprevir for 12 wk or glecaprevir/pibrentasvir for 12 wk, are proposed to be potential solution for the HCV GT1 b-infected patients with treatment failure, mainly on a basis of targeting distinctive regions. Clinicians should follow the new information and resources for DAAs and select the proper combination of DAAs for the retreatment of HCV GT1 b-infected patients with treatment failure.

关键词： Direct-acting antiviral agent Genotype 1b Hepatitis C virus Resistance-associated substitutions

Aberrant Eph B/ephrin-B expression in experimental gastric lesions and tumor cells

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World Journal of Gastroenterology 2015年第2期21卷 453-464页

作者： Shintaro Uchiyama Noritaka Saeki kazushige Ogawa Department of Veterinary Anatomy Graduate School of Life and Environmental SciencesOsaka Prefecture UniversityOsaka 598-8531Japan

AIM: To determine whether the expression profiles of Eph B receptor and ephrin-B ligand can be used as markers for dysplastic/oncogenic transformation in gastric ***: The protein expression and localization ofEph B and ephrin-B in normal, ulcerated regenerating, and dysplastic gastric mucosa were examined in a rat experimental model by immunolabeling, and m RNA expression was assessed in four human gastric carcinoma cell lines by reverse transcription-polymerase chain ***: Ephrin-B- and Eph B-expressing regions were divided along the pit-gland axis in normal gastric units. Eph B2 was transiently upregulated in the experimental ulcer, and its expression domain extended to gastric pits and/or the luminal surface where ephrin-B-expressing pit cells reside. Eph B2, B3, and B4 and ephrin-B1 were coexpressed in the experimental gastric dysplasia, and more than one ligand-receptor pair was highly expressed in each of the gastric carcinoma cell ***: Robust and stable coexpression of Eph B and ephrin-B is a feature common to experimentally induced gastric dysplasia and human gastric carcinoma cell lines as compared to normal gastric and ulcerated regenerating epithelia. Thus, Eph B/ephrin-B may be a useful marker combination for dysplastic/oncogenic transformation in gastric cancer.

关键词： Gastric ulcer Gastric dysplasia Gastric carcinoma

Design and Implementation of NAREGI SuperScheduler Based on the OGSA Architecture

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Journal of Computer Science & Technology 2006年第4期21卷 521-528页

作者： Satoshi Matsuoka Masayuki Hatanaka Yasumasa Nakano Yuji Iguchi Toshio Ohno kazushige Saga Hidemoto Nakada Global Scientific Information and Computing Center Tokyo Institute of Technology 2-12-10okayama Meguro-ku Tokyo 152-8550 Japan Center for Grid Research and Development National Institute of Informatics 1-105 Kanda-Jinbocho Chiyoda-ku Tokyo 101-0051 Japan Linux Software Development Div. Server Systems Unit. Fujitsu Limited 130 Miyamoto Numazu-shi Shizuoka410-0396 Japan Grid Technology Research Center National Institute of Advanced Industrial Science and Technology 1-18-13 Sotokanda Chiyoda-ku Tokyo 101-0021 Japan

NAREGI is a 5-year Japanese National Grid Project during 2003--2007, whose chief aim is to develop a set of grid middleware to serve as a basis for future e-Science. NAREGI also aims to lead the way in standardization of grid middleware, based on the OGSA architecture. Its super-scheduler is based on the proposed OGSA-EMS Architecture, in that it becomes the first working implementation that implements the documented component relationships within the OGSA-EMS architecture document v.l.0. Through the efforts and experience in the design and implementation, it has been confirmed that the documented OGSA-EMS architecture is quite feasible, but will require significant amount of refinement and speed improvements to finalize its detailed specifications. The super-scheduler also supports co-allocation across multiple sites to support automated execution of grid-based MPIs that execute across machines. Such a resource allocation requires sophisticated interactions between the OGSA-EMS components not covered in the current OGSA-EMS architecture, some of which are non-trivial. Overall, job scheduling with OGSA-EMS has proven to not only work, but also that its job allocation and execution time is within reasonable bounds.

关键词： grid scheduling resource management open grid services architecture OGSA

Apoptosis and non-alcoholic fatty liver diseases

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World Journal of Gastroenterology 2018年第25期24卷 2661-2672页

作者： 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 Division of Gastroenterology and Hepatology Department of Medicine Nihon University School of Medicine

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.

关键词： Apoptosis Autophagy c-Jun N-terminal kinase Nonalcoholic fatty liver diseases Nonalcoholic steatohepatitis

Long-term outcomes of autoimmune pancreatitis

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World Journal of Gastroenterology 2016年第34期22卷 7760-7766页

作者： Tsukasa Ikeura Hideaki Miyoshi Masaaki Shimatani kazushige Uchida Makoto Takaoka Kazuichi Okazaki Department of Gastroenterology and Hepatology Kansai Medical University

Autoimmune pancreatitis(AIP) has been considered a favorable-prognosis disease; however,currently,there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation,exocrine insufficiency,and endocrine insufficiency are observed in 5%-41%,34%-82%,and 38%-57% of patients having the disease. Furthermore,the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term followup. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients,careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed.

关键词： Autoimmune pancreatitis Outcome Cancer Prognosis

Application of artificial intelligence in hepatology:Minireview

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Artificial Intelligence in Gastroenterology 2020年第1期1卷 5-11页

作者： Ryota Masuzaki Tatsuo Kanda Reina Sasaki Naoki matsumoto kazushige Nirei Masahiro Ogawa Mitsuhiko Moriyama Division of Gastroenterology and Hepatology Department of MedicineNihon University School of MedicineTokyo 173-8610Japan

With the rapid advancements in computer science,artificial intelligence(AI)has become an intrinsic part of our daily life and clinical *** concepts of AI,such as machine learning,deep learning,and big data,are extensively used in clinical and basic *** this review,we searched for the articles in PubMed and summarized recent developments of AI concerning hepatology while focusing on the diagnosis and risk assessment of liver *** is widely conducted for the routine surveillance of hepatocellular carcinoma along with tumor ***-aided diagnosis is useful in the detection of tumors and characterization of space-occupying *** prognosis of hepatocellular carcinoma can be estimated via AI using large-scale and highquality training *** prevalence of nonalcoholic fatty liver disease is increasing worldwide and pivotal concern in the field is who will progress and develop hepatocellular *** AI studies require a large dataset,including laboratory or radiological findings and outcome *** will be useful in reducing medical errors,supporting clinical decisions,and predicting clinical ***,cooperation between AI and humans is expected to improve healthcare.

关键词： Artificial intelligence Deep learning Machine learning Hepatocellular carcinoma Prognosis Computer-aided diagnosis

Histopathology of type C liver disease for determining hepatocellular carcinoma risk factors

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World Journal of Gastroenterology 2013年第30期19卷 4887-4896页

作者： Hiroshi Matsumura kazushige Nirei Hitomi Nakamura Teruhisa Higuchi Yasuo Arakawa Masahiro Ogawa Naohide Tanaka Mitsuhiko Moriyama Division of Gastroenterology and Hepatology Department of MedicineNihon University School of MedicineTokyo173-8610Japan

AIM:To evaluate the histopathological findings of type C liver disease to determine risk factors for development of hepatocellular carcinoma(HCC).METHODS:We studied 232 patients,who underwent liver biopsy for type C chronic liver disease between 1992 and 2009,with sustained virological response(SVR)after interferon *** patients were divided into two groups according to the F stage 0+1+2 group(n = 182)and F3+4 group(n = 50).We prospectively observed and compared the incidence of HCC of the patients with SVR in the F0+1+2 and F3+4 ***,the background factors and liver histopathological findings,including the degree of fibrosis,F stage,inflammation,necrosis,bile duct obstruction,fat deposition,and degree of irregular regeneration(IR)of hepatocytes,were correlated with the risk of developing ***:HCC developed in three of 182(1.6%)patients in the F0+1+2 group,and four of 50(8.0%)in the F3+4 *** cumulative incidence of HCC in the former group was found to be significantly lower than in the F3+4 group(log rank test P = 0.0224).The presence of atypical hepatocytes among IR of hepatocytes in the F3+4 group resulted in a higher cumulative incidence of HCC,and was significantly correlated with risk of HCC development(RR = 20.748,95%CI:1.335-322.5,P = 0.0303).CONCLUSION:Atypical hepatocytes among the histopathological findings of type C liver disease may be an important risk factor for HCC development along with progression of liver fibrosis.

关键词： Hepatocellular carcinoma Irregular regeneration of hepatocytes Liver fibrosis Type C chronic liver disease Histopathology of liver biopsy

Effect of intracranial hypertension on cerebral hemorrhage induced autonomic nerve imbalance

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Neural Regeneration Research 2007年第3期2卷 175-178页

作者： Xuelong Jin Wenli Jing Fengxia Yan Zhaoqiang Zhang Fengjun Lǚ Shuiqing Jing Na Sun kazushige Mizoguchi Department of Physiology School of Basic Medical Sciences Tianjin Medical University Tianjin 300070 China Departrnent of Physiology Chengde Medical College Chengde 067000 Hebei Province China Department of Geriatric Medicine National Center for Geriatrics and Gerontology Japan

BACKGROUND： Cerebral hemorrhage can cause the imbalance of nerve function, whereas its mechanism and main impact factors are still not quite clear. OBJECTIVE： To explore the rules about the changes of intracranial pressure in brainstem hemorrhage and internal capsule hemorrhage, and analyze the role of intracranial hypertension in the changes of nerve function caused by cerebral hemorrhage. DESIGN： A self-controlled trial. SETTING： Department of Physiology, Tianjin Medical University. MATERIALS： Sixty-five healthy male Japanese white rabbits with long ears （1.5-1.8 kg） were supplied and fed by the Department of Animal Experiment of Tianjin Medical University. The RM6240B biological signal collecting and processing system was used. METHODS： The experiments were conducted in the Department of Physiology, Tianjin Medical University from August 2001 to May 2006. ① The rabbits were anesthetized, then fixed onto the brain stereotaxic apparatus, and afterwards fenestration on skull and intubation to lateral ventricle were *** dynamic changes of intracranial pressure were monitored continuously. Rabbits were infused with autologous arterial blood （0.3 mL） into midbrain corpora quadrigemina inferior colliculus to induce model of acute brainstem hemorrhage; models of internal capsule hemorrhage were established by infusing autologous arterial blood into internal capsule. ② The dynamic intracranial pressures under the above conditions were recorded continuously with the RM6240B biological signal collecting and processing system. ③ An animal model of persistent intracranial hypertension was established by infusion of physiologic saline into lateral ventricle. ④ The changes of the intensity of autonomic nerve discharge were analyzed, using the biological signal collecting and processing system before and after hemorrhage and under persistent intracranial hypertension.⑤ Ten animal models of internal capsule hemorrhage and 10 of bminstem hemorrhage were selected respecti

关键词： autonomic nervous system cerebral hemorrhage intracranial pressure

Hydrogen and methane gases are frequently detected in the stomach

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World Journal of Gastroenterology 2006年第19期12卷 3088-3091页

作者： Yoshihisa Urita Susumu Ishihara Tatsuo Akimoto Hiroto Kato Noriko Hara Yoshiko Honda Yoko Nagai kazushige Nakanishi Nagato Shimada Motonobu Sugimoto Kazumasa Miki Department of General Medicine and Emergency Care Toho University School of Medicine Omori HospitalTokyoJapan Division of Gastroenterology and Hepatology Department of Internal Medicine Toho University School of MedicineOmori HospitalTokyoJapan

AIM： To investigate the incidence of bacterial overgrowth in the stomach by using a new endoscopic method in which intragastric hydrogen and methane gases are collected and analyzed. METHODS： Studies were performed in 490 consecutive patients undergoing esophagogastroscopy, At endoscopy, we intubated the stomach without inflation by air, and 20 mL of intragastric gas was collected through the biopsy channel using a 30 mL syringe, Intragastric hydrogen and methane concentrations were immediately measured by gaschromatography, H pylori infection was also determined by serology. RESULTS： Most of intragastric hydrogen and methane levels were less than 15 ppm （parts per million）. The median hydrogen and methane values （interquartile range） were 3 （1-8） ppm and 2 （1-5） ppm, respectively. The high hydrogen and methane levels for indication of fermentation were decided if the patient had the values more than 90 percentile range in each sample. When a patient had a high level of hydrogen or methane in one or more samples, the patient was considered to have fermentation. The overall incidence of intragastric fermentation was 15.4% （73/473）, Intragastric methane levels were higher in the postoperative group than in other groups. None of the mean hydrogen or methane values was related to Hpylori infection. CONCLUSION： Hydrogen and methane gases are more frequently detected in the stomach than expected, regardless of the presence of abdominal symptoms. Previous gastric surgery influences on the growth of methaneproducing bacteria in the fasting stomach.

关键词： Intragastric gases Hydrogen Methane Helicobacter pylori