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Natural regression of fibrosis in chronic hepatitis B

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World Journal of Gastroenterology 2016年第24期22卷 5459-5466页

作者： Shogo Ohkoshi Haruka Hirono Kazuhiko Watanabe katsuhiko hasegawa Kenya Kamimura Masahiko Yano Department of Internal Medicine School of Life Dentistry at Niigata The Nippon Dental University Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University

The fibrosis of liver cirrhosis was considered to be irreversible before the anti-viral drugs showed that it is reversible when they lead to continuous suppression of viral replication and inflammation. However, several reports previously showed that fibrosis of type B liver cirrhosis was almost completely absorbed after the natural remission of chronic inflammation. This phenomenon might not be limited to exceptional patients, but rather occur commonly, considering the dynamic clinical features of chronic hepatitis B(CHB), where inactive carrier stage normally follows aggravation of hepatitis and progression of fibrosis at the time of HBe Ag seroconversion. Thus, fibrosis levels of CHB as a hepatocellular carcinoma(HCC)-surveillance marker, particularly those of the inactive stage, could be underestimated, because some of them might have been(pre)cirrhotic in the past and recovered with the natural regression of fibrosis. We argue that cirrhosisinduced HCC mechanisms, rather than direct action of viral genome, may be more common than generally considered in CHB patients. This may have some impact on reconsidering the surveillance rationale for HCC in CHB, from where advanced HCCs tended to be missed. In addition, a molecular marker to assess the cancer-prone characteristics of the liver will definitely be needed to resolve the issue.

关键词： Chronic hepatitis B Cirrhosis Spontaneous remission Regression of fibrosis Occult hepatitis B infection Hepatocellular carcinoma surveillance of hepatitis B virus

Impact of continuous positive airway pressure therapy for nonalcoholic fatty liver disease in patients with obstructive sleep apnea

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World Journal of Clinical Cases 2021年第19期9卷 5112-5125页

作者： Haruka Hirono Kazuhiko Watanabe katsuhiko hasegawa Masaki Kohno Shuji Terai Shogo Ohkoshi Department of Internal Medicine The Nippon Dental University School of Life Dentistry at NiigataNiigata 951-8580Japan The Center for Dental Sleep Medicine The Nippon Dental University Niigata HospitalNiigata 951-8580Japan Division of Gastroenterology and Hepatology Graduate School of Medical and Dental SciencesNiigata UniversityNiigata 951-8510Japan

BACKGROUND Obstructive sleep apnea(OSA)has been suggested as an independent risk factor for nonalcoholic fatty liver disease(NAFLD),and continuous positive airway pressure(CPAP)is the first-line therapy for *** To clarify the efficacy of effective CPAP therapy on NAFLD of OSA patients by serum markers and transient elastography(TE)using FibroScan®(Echosens,Paris,France).METHODS We prospectively enrolled 123 consecutive patients with OSA who met the indications for *** fibrosis and steatosis were assessed using *** and after 6 mo of CPAP therapy,serum markers and TE were assessed for all *** mean usage rate of CPAP therapy for 6 mo was arbitrarily calculated in each patient and expressed as“mean compliance index”(m-CI).RESULTS In 50 OSA patients with NAFLD,both aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels were significantly decreased after 6 mo of CPAP *** analysis showed that decreased body weight(BW),decreased body mass index(BMI),decreased AST level,decreased hemoglobin A1c,and high m-CI were significantly related with improved ALT *** multivariate regression model adjusted for quantities of BW change during 6 mo of CPAP therapy,high m-CI tended to improve ALT level(P=0.051).All 17 OSA patients with NAFLD,high m-CI and no BMI changes showed significant improvements in AST and ALT ***,no significant changes in TE data or serum fibrosis markers were *** Some NAFLD could be associated with chronic intermittent hypoxia due to OSA independent of BW *** those cases,adequate reoxygenation from effective CPAP therapy may improve NAFLD.

关键词： Nonalcoholic fatty liver disease Obstructive sleep apnea Continuous positive airway pressure Chronic intermittent hypoxia Transient elastography

Contributions of transgenic mouse studies on the research of hepatitis B virus and hepatitis C virus-induced hepatocarcinogenesis

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World Journal of Hepatology 2015年第28期7卷 2834-2840页

作者： Shogo Ohkoshi Haruka Hirono Kazuhiko Watanabe katsuhiko hasegawa Masahiko Yano Department of Internal Medicine School of Life Dentistry at Niigata the Nippon Dental University Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University

Transgenic mouse technology has enabled the investigation of the pathogenic effects, including those on development, immunological reactions and carcinogenesis, of viral genes directly in living organism in a real-time manner. Although viral hepatocarcinogenesis comprises multiple sequences of pathological events, that is, chronic necroinflammation and the subsequent regeneration of hepatocytes that induces the accumulation of genetic alterations and hepatocellular carcinoma(HCC), the direct action of viral proteins also play significant roles. The pathogenesis of hepatitis B virus X and hepatitis C virus(HCV) core genes has been extensively studied by virtue of their functions as a transactivator and a steatosis inducer, respectively. In particular, the mechanism of steatosis in HCV infection and its possible association with HCC has been well studied using HCV core gene transgenic mouse models. Although transgenic mouse models have remarkable advantages, they are intrinsically accompanied by some drawbacks when used to study human diseases. Therefore, the results obtained from transgenic mouse studies should be carefully interpreted in the context of whether or not they are well associated with human pathogenesis.

关键词： Transgenic mouse Hepatocarcinogenesis Hepatitis C virus Hepatitis B virus X Hepatitis B virus Hepatitis C virus core protein Steatosis

Features of hepatocellular carcinoma in cases with autoimmune hepatitis and primary biliary cirrhosis

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World Journal of Gastroenterology 2009年第2期15卷 231-239页

作者： Takuya Watanabe Kenji Soga Haruka Hirono katsuhiko hasegawa Koichi Shibasaki Hirokazu Kawai Yutaka Aoyagi Department of Internal Medicine and Gastroenterology Medical Hospital The Nippon Dental University School of Life Dentistry at Niigata 1-8 Hamauracho Chu-o-ku Niigata 951-8580 Japan Department of Gastroen-terology Niigata University Graduate School of Medical and Dental Sciences 1-757 Asahimachi Chu-o-ku Niigata 951-8510 Japan

AIM: To characterize the clinical features of hepatocellular carcinoma (HCC) associated with autoimmune liver disease, we critically evaluated the literature on HCC associated with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). METHODS: A systematic review of the literature was conducted using the Japana Centra Revuo Medicina database which produced 38 cases of HCC with AIH (AIH-series) and 50 cases of HCC with PBC (PBC-series). We compared the clinical features of these two sets of patients with the general Japanese HCC population. RESULTS: On average, HCC was more common in men than in women with AIH or PBC. While many patients underwent chemolipiodolization (CL) or transcatheter arterial embolization (TAE) (AIH-series: P = 0.048 (vs operation), P = 0.018 (vs RFA, PEIT); PBC-series: P = 0.027 (vs RFA, PEIT), others refused therapeutic interventions [AIH-series: P = 0.038 (vs RFA, PEIT); PBC-series: P = 0.003 (vs RFA, PEIT)].Liver failure was the primary cause of death among patients in this study, followed by tumor rupture. The survival interval between diagnosis and death was fairly short, averaging 14 ± 12 mo in AIH patients and 8.4 ± 14 mo in PBC patients. CONCLUSION: We demonstrated common clinical features among Japanese cases of HCC arising from AIH and PBC.

关键词： Autoimmune hepatitis Autoimmune liver disease Hepatocellular carcinoma Literature review Primary biliary cirrhosis

Regenerative medicine using dental pulp stem cells for liver diseases

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2017年第1期8卷 1-6页

作者： Shogo Ohkoshi Hajime Hara Haruka Hirono Kazuhiko Watanabe katsuhiko hasegawa Department of Internal Medicine School of Life Dentistry at NiigataNippon Dental UniversityChuo-ku 951-8580Japan

Acute liver failure is a refractory disease and its pro-gnosis, if not treated using liver transplantation, is extremely poor. It is a good candidate for regenerative medicine, where stem cell-based therapies play a central role. Mesenchymal stem cells(MSCs) are known to differentiate into multiple cell lineages including hepatocytes. Autologous cell transplant without any foreign gene induction is feasible using MSCs, thereby avoiding possible risks of tumorigenesis and immune rejection. Dental pulp also contains an MSC population that differentiates into hepatocytes. A point worthy of special mention is that dental pulp can be obtained from deciduous teeth during childhood and can be subsequently harvested when necessary after deposition in a tooth bank. MSCs have not only a regenerative capacity but also act in an anti--inflammatory manner via paracrine mechanisms. Promising efficacies and difficulties with the use of MSC derived from teeth are summarized in this review.

关键词： Dental pulp Mesenchymal stem cell Regenerative medicine Liver disease Tooth bank

Complex-Valued Neural Networks:A Comprehensive Survey

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IEEE/CAA Journal of Automatica Sinica 2022年第8期9卷 1406-1426页

作者： ChiYan Lee Hideyuki hasegawa Shangce Gao Faculty of Engineering University of ToyamaToyama 930-8555Japan

Complex-valued neural networks(CVNNs)have shown their excellent efficiency compared to their real counterparts in speech enhancement,image and signal *** throughout the years have made many efforts to improve the learning algorithms and activation functions of *** CVNNs have proven to have better performance in handling the naturally complex-valued data and signals,this area of study will grow and expect the arrival of some effective improvements in the ***,there exists an obvious reason to provide a comprehensive survey paper that systematically collects and categorizes the advancement of *** this paper,we discuss and summarize the recent advances based on their learning algorithms,activation functions,which is the most challenging part of building a CVNN,and ***,we outline the structure and applications of complex-valued convolutional,residual and recurrent neural ***,we also present some challenges and future research directions to facilitate the exploration of the ability of CVNNs.

关键词： Complex activation function complex backpropagation algorithm complex-valued learning algorithm complex-valued neural network deep learning

Reproducibility and Validity of a Chinese Food Frequency Questionnaire

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Biomedical and Environmental Sciences 2010年第S1期23卷 1-38页

作者： Water WILLETT Kyoko hasegawa Department of Nutrition Harvard School of Public Health Kagawa Nutrition University

Objectives This study was design to develop a semi-quantitative Chinese Food Frequency Questionnaire （FFQ） and to conduct a validation study for the questionnaire. Methods Based on the survey experience in recent years, a new Chinese food frequency questionnaire （FFQ） with 149 items in 17 food categories was developed. A validation study on this new FFQ was conducted in Jiangsu and Beijing of China between 1999 and 2001. The period of study covered 1 year and the FFQ was validated by comparing with data obtained by a six repeated 24-hour recalls for 3 consecutive days, or a totally 18-day 24- hour recall throughout the year. A total of 271 healthy adult subjects were enrolled in the study. Food and nutrient intakes measured by the 18-day dietary recalls and food frequency questionnaires （FFQs） were computed in the National Institute for Nutrition and Food Safety, China CDC using the existing nutrition database. The average daily intake of foods and nutrients over the 18-day recall was used to compare with FFQ1 and FFQ2, which was conducted at the beginning and the end of the year, respectively. All statistical analyses were carried out using SAS software version 6.12.

关键词： FFQ Reproducibility and Validity of a Chinese Food Frequency Questionnaire

A technique utilizing chemical reagents for direct measurement of temperature at a local area and its engineering applications

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Acta Mechanica Sinica 2009年第2期25卷 149-160页

作者： M.Saka T.hasegawa Department of Nanomechanics Tohoku University

Temperature is one of the physical quantifies through which quantitative evaluation of the safety and reliability of industrial products can be achieved, and this has been used widely in practice. Under any environmental condifion, regardless of the size of the object to be inspected, accurate and reliable measurement of temperature is of great practical importance. This review article presents a simple and direct method of temperature measurement, that can be applied to the local areas with difficulty in measuring the temperature by using normal thermometers. In the present article, two different application examples are demonstrated. One addresses the study of the electromigration of solders which are used as bonding metals in electronic devices （micro-structures）. The application of the method to the shaft of a motor used in heavy industrial fields is explained as the second.

关键词： Temperature measurement Chemicalreagents Melting point Temperature distribution

Retinal ganglion cell protection by hop-flower extract as a novel neuroprotective strategy for glaucoma

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Neural Regeneration Research 2022年第6期17卷 1267-1268页

作者： Tomoko hasegawa Hanako Ohashi Ikeda Department of Ophthalmology and Visual Sciences Kyoto University Graduate School of MedicineKyotoJapan Research Fellow of Japan Society for the Promotion of Science TokyoJapan

In glaucoma,a leading cause of blindness,retinal ganglion cells are progressively *** pressure reduction is the only established treatment for glaucoma(Collaborative Normal-Tension Glaucoma Study Group,1998;Vass et al.,2007).However,in some cases,visual field loss progresses despite sufficiently reduced intraocular pressure(Collaborative Normal-Tension Glaucoma Study Group,1998;Killer and Pircher,2018).While intraocular pressure and age are known risk factors for glaucoma(Ernest et al.,2013),the underlying mechanisms of glaucoma progression are not fully understood.

关键词： glaucoma al. protective