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Assessment of disease progression in patients with transfusion-associated chronic hepatitis C using transient elastography

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World Journal of Gastroenterology 2012年第12期18卷 1385-1390页

作者： Ryota Masuzaki Ryosuke Tateishi Haruhiko Yoshida Toru Arano Koji Uchino Kenichiro Enooku Eriko Goto Hayato Nakagawa Yoshinari Asaoka Yuji Kondo Tadashi Goto hitoshi ikeda Shuichiro Shiina Masao Omata Kazuhiko Koike Department of Gastroenterology Graduate School of MedicineThe University of Tokyo Department of Clinical Laboratory The University of Tokyo Hospital Yamanashi Prefectural Hospital Organization

AIM:To evaluate the relationship between liver stiffness and duration of infection in blood transfusion-associated hepatitis C virus (HCV) patients with or without hepatocellular carcinoma (HCC).METHODS:Between December 2006 and June 2008,a total of 524 transfusion-associated HCV-RNA positive patients with or without HCC were enrolled.Liver stiffness was obtained noninvasively by using Fibroscan (Echosens,Paris,France).The date of blood transfusion was obtained by interview.Duration of infection was derived from the interval between the date of bloodtransfusion and the date of liver stiffness measurement (LSM).Patients were stratified into four groups based on the duration of infection (17-29 years;30-39 years;40-49 years;and 50-70 years).The difference in liver stiffness between patients with and without HCC was assessed in each group.Multiple linear regression analysis was used to determine the factors associated with liver stiffness.RESULTS:A total of 524 patients underwent LSM.Eight patients were excluded because of unsuccessful measurements.Thus 516 patients were included in the current analysis (225 with HCC and 291 without).The patients were 244 men and 272 women,with a mean age of 67.8 ± 9.5 years.The median liver stiffness was 14.3 kPa (25.8 in HCC group and 7.6 in nonHCC group).The patients who developed HCC in short duration of infection were male dominant,having lower platelet count,with a history of heavier alcohol consumption,showing higher liver stiffness,and receiving blood transfusion at an old age.Liver stiffness was positively correlated with duration of infection in patients without HCC (r=0.132,P=0.024) but not in patients with HCC (r=-0.103,P=0.123).Liver stiffness was significantly higher in patients with HCC than in those without in each duration group (P < 0.0001).The factors significantly associated with high liver stiffness in multiple regression were age at blood transfusion (P < 0.0001),duration of infection (P=0.0015),and heavy alcohol consumption (P=0.043) CONCLUSION:Although liver

关键词：丙型肝炎评估患者病情慢性血相弹性瞬时

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The deep-space multi-object orbit determination system and its application to Hayabusa2’s asteroid proximity operations

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Astrodynamics 2020年第4期4卷 377-392页

作者： Hiroshi Takeuchi Kent Yoshikawa Yuto Takei Yusuke Oki Shota Kikuchi hitoshi ikeda Stefania Soldini Naoko Ogawa Yuya Mimasu Go Ono Fuyuto Terui Naoya Sakatani Manabu Yamada Toru Kouyama Shingo Kameda Takanao Saiki Yuichi Tsuda Institute of Space and A stronautical Science Japan A erospace Exploration AgencySagamihara 252-5210Japan The Graduate University for Aduanced Studies Hayama 240-0193Japan Research and Development Directorate Japan Aerospace Exploration AgencySagamihara 252-5210Japan University of Liverpool Liverpool L693BXUK Chiba Institute of Technology Narashino 275-0016Japan National Institute of Aduanced Industrial Science and Technology Koto-ku 135-0064Japan Rikkyo University Toshima-ku 171-8501Japan

The deep-space multi-object orbit determination system(DMOODS)and its application in the asteroid proximity operation of the Hayabusa2 mission are described.DMOODS was developed by the Japan Aerospace Exploration Agency(JAXA)for the primary purpose of determining the trajectory of deep-space spacecraft for JAXA’s planetary missions.The weighted least-squares batch filter is used for the orbit estimator of DMOODS.The orbit estimator supports more than 10 data types,some of which are used for relative trajectory measurements between multiple space objects including natural satellites and small bodies.This system consists of a set of computer programs running on Linux-based consumer PCs on the ground,which are used for orbit determination and the generation of radiometric tracking data,such as delta differential one-way ranging and doppler tracking data.During the asteroid proximity phase of Hayabusa2,this system played an essential role in operations that had very strict navigation requirements or operations in which few optical data were obtained owing to special constraints on the spacecraft attitude or distance from the asteroid.One example is orbit determination during the solar conjunction phase,in which the navigation accuracy is degraded by the effect of the solar corona.The large range bias caused by the solar corona was accurately estimated with DMOODS by combining light detection and ranging(LIDAR)and ranging measurements in the superior solar conjunction phase of Hayabusa2.For the orbiting operations of target markers and the MINERVA-II2 rover,the simultaneous estimation of six trajectories of four artificial objects and a natural object was made by DMOODS.This type of simultaneous orbit determination of multi-artificial objects in deep-space has never been accomplished before.

关键词： orbit determination optical navigation gravity measurements superior solar conjunction delta differential one-way ranging(delta-DOR)

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Induction of ischemic tolerance in rat liver via reduced nicotinamide adenine dinucleotide phosphate oxidase in Kupffer cells

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World Journal of Gastroenterology 2007年第38期13卷 5071-5078页

作者： Kazuaki Tejima Masahiro Arai hitoshi ikeda Tomoaki Tomiya Mikio Yanase Yukiko Inoue Takako Nishikawa Naoko Watanabe Natsuko Ohtomo Masao Omata Kenji Fujiwara Department of Gastroenterology University of Tokyo 7-3-1 Hongo Bunkyo-ku Tokyo 113-8655 Japan Department of Gastroenterology Toshiba General Hospital 6-3-22 Higashiooi Shinagawa-ku Tokyo 140-8522 Japan Yokohama Rosai Hospital 3211 Kozukue-cho Kouhoku-ku Yokohama-shi Kanagawa 222-0036 Japan

AIM: To elucidate the mechanisms of hepatocyte preconditioning by H2O2 to better understand the pathophysiology of ischemic preconditioning. METHODS: The in vitro effect of H2O2 pretreatment was investigated in rat isolated hepatocytes subjected to anoxia/reoxygenation. Cell viability was assessed with propidium iodide fluorometry. In other experiments, rat livers were excised and subjected to warm ischemia/ reperfusion in an isolated perfused liver system to determine leakage of liver enzymes. Preconditioning was performed by H2O2 perfusion, or by stopping the perfusion for 10 min followed by 10 min of reperfusion. To inhibit Kupffer cell function or reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, gadolinium chloride was injected prior to liver excision, or diphenyleneiodonium, an inhibitor of NADPH oxidase, was added to the perfusate, respectively. Histological detection of oxygen radical formation in Kupffer cells was performed by perfusion with nitro blue tetrazolium. RESULTS: Anoxia/reoxygenation decreased hepatocyte viability compared to the controls. Pretreatment with H2O2 did not improve such hepatocyte injury. In liver perfusion experiments, however, H2O2 preconditioning reduced warm ischemia/reperfusion injury, which wasreversed by inhibition of Kupffer cell function or NADPH oxidase. Histological examination revealed that H2O2 preconditioning induced oxygen radical formation in Kupffer cells. NADPH oxidase inhibition also reversed hepatoprotection by ischemic preconditioning. CONCLUSION: H2O2 preconditioning protects hepato- cytes against warm ischemia/reperfusion injury via NADPH oxidase in Kupffer cells, and not directly. NADPH oxidase also mediates hepatoprotection by ischemic preconditioning.

关键词：肝移植动物模型肝损伤治疗方法

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Hayabusa2’s station-keeping operation in the proximity of the asteroid Ryugu

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Astrodynamics 2020年第4期4卷 349-375页

作者： Yuto Takei Takanao Saiki Yukio Yamamoto Yuya Mimasu Hiroshi Takeuchi hitoshi ikeda Naoko Ogawa Fuyuto Terui Go Ono Kent Yoshikawa Tadateru Takahashi Hirotaka Sawada Chikako Hirose Shota Kikuchi Atsushi Fuji Takahiro Iwata Satoru Nakazawa Masahiko Hayakawa Ryudo Tsukizaki Satoshi Tanaka Masanori Matsushita Osamu Mori Daiki Koda Takanobu Shimada Masanobu Ozaki Masanao Abe Satoshi Hosoda Tatsuaki Okada Hajime Yano Takaaki Kato Seiji Yasuda Kota Matsushima Tetsuya Masuda Makoto Yoshikawa Yuichi Tsuda Japan Aerospace Exploration Agency Sagarmihara 252-5210Japan The Graduate University for Advanced Studies Sagarmihara 252-5210Japan NEC Aerospace Systems LtdFruchu 183-8502Japan NEC Corporation Puchu 183-8501Japan

The Japanese interplanetary probe Hayabusa2 was launched on December 3,2014 and the probe arrived at the vicinity of asteroid 162173 Ryugu on June 27,2018.During its 1.4 years of asteroid proximity phase,the probe successfully accomplished numbers of record-breaking achievements including two touchdowns and one artificial cratering experiment,which are highly expected to have secured surface and subsurface samples from the asteroid inside its sample container for the first time in history.The Hayabusa2 spacecraft was designed not to orbit but to hover above the asteroid along the sub Earth line.This orbital and geometrical configuration allows the spacecraft to utilize its high-gain antennas for telecommunication with the ground station on Earth while pointing its scientific observation and navigation sensors at the asteroid.This paper focuses on the regular station-keeping operation of Hayabusa2,which is called“home position”(HP)-keeping operation.First,together with the spacecraft design,an operation scheme called HP navigation(HPNAV),which includes a daily trajectory control and scientific observations as regular activities,is introduced.Following the description on the guidance,navigation,and control design as well as the framework of optical and radiometric navigation,the results of the HP-keeping operation including trajectory estimation and delta-V planning during the entire asteroid proximity phase are summarized and evaluated as a first report.Consequently,this paper states that the HP.keeping operation in the framework of HPNAV had succeeded without critical incidents,and the number of trajectory control delta-V was planned fficiently throughout the period.

关键词： small body mission station-keeping guidance,navigation,and control(GNC) optical and radiometric navigation

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小梁切开术治疗进展期青光眼的长期结果

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美国医学会眼科杂志（中文版） 2005年第2期17卷 120-121页

作者： Hanako ikeda hitoshi Ishigooka Tonmyuki Muto Hidenobu Tanihara Makoto Nagata 陆遥（译）

目的：说明小梁切开术治疗原发性和继发性进展期青光眼的长期结果。方法：89例进展期青光眼患者的149只眼进行了小梁切除术，对这些患者进行回顾性研究。在随访和最后检查时测定眼压、成功率、视力和视野。

关键词：青光眼患者小梁切开术长期结果进展期治疗小梁切除术继发性原发性回顾性检查时

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Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

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World Journal of Gastroenterology 2024年第28期30卷 3428-3446页

作者： Aritoshi Koizumi Kosuke Kaji Norihisa Nishimura Shohei Asada Takuya Matsuda Misako Tanaka Nobuyuki Yorioka Yuki Tsuji Koh Kitagawa Shinya Sato Tadashi Namisaki Takemi Akahane hitoshi Yoshiji Department of Gastroenterology Nara Medical UniversityKashihara 634-8521Japan

BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cell

关键词： Liver fibrosis Ethanol Gut barrier function Apoptosis Autophagy Peroxisome proliferator activated receptor

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On systematic development of FSI solvers in the context of particle methods

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Journal of Hydrodynamics 2022年第3期34卷 395-407页

作者： Abbas Khayyer hitoshi Gotoh Yuma Shimizu Department of Civil and Earth Resources Engineering Kyoto UniversityKyotoJapan

This paper presents a review on state-of-the-art of developments corresponding to fluid-structure interaction(FSI)solvers developed within the context of particle methods.The paper reviews and highlights the potential robustness of entirely Lagrangian meshfree FSI solvers in reproducing FSI corresponding to extreme events and portrays the future perspectives for systematic developments towards reliable engineering applications with respect to rapid advances in technology and emergence of so-called advanced materials that can result in complex and highly non-linear structural responses.Accordingly,the paper highlights the necessity for reproduction of comprehensive structural responses,including viscoelastic,elastoplastic and progressive damages/failures,by the advanced FSI solvers developed within the context of particle methods.In this regard,extensions of the structure model are suggested to be conducted in a variationally consistent framework to ensure stability,accuracy and physical reliability including thermodynamic consistency.The paper reviews basics of mathematical and numerical modelling for entirely Lagrangian meshfree hydroelastic FSI solvers and presents a brief background on extensions of such solvers towards reproducing viscoelastic structural responses.Some preliminary numerical results on structural viscoelasticity achieved by an extended Hamiltonian SPH(HSPH)model are presented.This vision paper also concisely portrays the future perspectives for systematic development of particle-based FSI solvers.

关键词： Fluid-structure interaction(FSI) entirely Lagrangian meshfree smoothed particle hydrodynamics(SPH) Hamiltonian SPH(HSPH) viscoelasticity

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Comparison of the effects of submerged laser peening,cavitation peening and shot peening on the improvement of the fatigue strength of magnesium alloy AZ31

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Journal of Magnesium and Alloys 2023年第5期11卷 1592-1607页

作者： hitoshi Soyama Chieko Kuji Yiliang Liao Department of Finemechanics Tohoku University6-6-01 AobaAramakiAoba-kuSendai 980-8579Japan Department of Industrial and Manufacturing Systems Engineering Iowa State University2529 Union Dr.AmesIA 50011United States of America

To investigate the improvement in the fatigue strength of magnesium alloy by peening methods,magnesium alloy AZ31 was treated by submerged laser peening(SLP),cavitation peening(CP),and shot peening(SP),and the fatigue properties were evaluated by a plane bending fatigue test.In the case of SLP,both the impact induced by laser ablation(LA)and that caused by laser cavitation(LC),which developed after LA,were used.In the present study,the fatigue life at a constant bending stress was examined to determine the suitable coverage.It was found that the fatigue strengths at N=10^(7)for the SLP,CP,and SP specimens treated by each optimum condition were 56%,18%,and 16%higher,respectively,than that of the non-peened(NP)specimen,which was 97 MPa.The key factors in the improvement of fatigue strength by peening methods were work hardening and the introduction of compressive residual stress.

关键词： Magnesium alloy Fatigue strength Laser peening Cavitation peening Shot peening

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Chronic heat stress induces renal fibrosis and mitochondrial dysfunction in laying hens

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畜牧与生物技术杂志:英文版 2023年第5期14卷 2002-2011页

作者： Fumika Nanto‑Hara Makoto Yamazaki hitoshi Murakami Haruhiko Ohtsu Division of Meat Animal and Poultry Research Institute of Livestock and Grassland ScienceNational Agriculture and Food Research Organization(NILGS)2 IkenodaiTsukubaIbaraki 305‑0901Japan

Background Heat stress in laying hens negatively affects egg production and shell quality by disrupting the homeo-stasis of plasma calcium and phosphorus levels.Although the kidney plays an important role in calcium and phos-phorus homeostasis,evidence regarding the effect of heat stress on renal injury in laying hens is yet to be elucidated.Therefore,the aim of this study was to evaluate the effects of chronic heat stress on renal damage in hens during laying periods.Methods A total of 16 white-leghorn laying hens(32 weeks old)were randomly assigned to two groups(n=8).One group was exposed to chronic heat stress(33°C for 4 weeks),whereas the other group was maintained at 24°C.Results Chronic heat exposure significantly increased plasma creatinine and decreased plasma albumin levels(P<0.05).Heat exposure also increased renal fibrosis and the transcription levels of fibrosis-related genes(COLA1A1,αSMA,and TGF-β)in the kidney.These results suggest that renal failure and fibrosis were induced by chronic heat exposure in laying hens.In addition,chronic heat exposure decreased ATP levels and mitochondrial DNA copy number(mtDNA-CN)in renal tissue,suggesting that renal mitochondrial dysfunction occurs under conditions of heat stress.Damaged mitochondria leak mtDNAs into the cytosol and mtDNA leakage may activate the cyclic GMP-AMP synthase(cGAS)stimulator of interferon genes(STING)signaling pathway.Our results showed that chronic heat exposure activated the cGAS-STING pathway as indicated by increased expression of MDA5,STING,IRF7,MAVS,and NF-κB levels.Furthermore,the expression of pro-inflammatory cytokines(IL-12)and chemokines(CCL4 and CCL20)was upregulated in heat-stressed hens.Conclusions These results suggest that chronic heat exposure induces renal fibrosis and mitochondrial damage in laying hens.Mitochondrial damage by heat stress may activate the mtDNA-cGAS-STING signaling and cause subse-quent inflammation,which contributes to the progression of renal fibrosis and dysfunction.

关键词： cGAS-STING Heat stress Laying hens Mitochondrial DNA Renal fibrosis

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Ablation for Benign Liver Tumors:Current Concepts and Limitations

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Journal of Clinical and Translational Hepatology 2023年第1期11卷 244-252页

作者： hitoshi Maruyama Maki Tobari Hiroaki Nagamatsu Tadashi Yamaguchi Shuichiro Shiina Department of Gastroenterology Juntendo UniversityTokyoJapan Center for Frontier Medical Engineering Chiba UniversityChibaJapan

Percutaneous ablation under imaging guidance is a curative treatment that can induce complete tumor necrosis with advantages of minimal invasiveness and a low risk of complications.Thermal ablation,which includes radiofrequency ablation and microwave ablation,is a representative technique that has sufficient antitumor effects in cases of hepatocellular carcinoma with≤3 lesions measuring≤3 cm and preserved liver function.The short-and long-term outcomes of patients are comparable with those achieved with surgical resection.Despite their nonmalignant nature,some benign liver tumors require treatment for symptoms caused by the presence of the tumor and/or continuous enlargement.Ablation may be the treatment of choice because it has lower burden on patients than surgical treatment.This review describes the recent concepts,progress,and limitations of ablation-based treatment for benign liver tumors.

关键词： Liver tumor Radiofrequency ablation Microwave ablation Benign

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