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ADAMTS13 and von Willebrand factor are useful biomarkers for sorafenib treatment efficiency in patients with hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2019年第5期11卷 424-435页

作者： Hiroaki Takaya Tadashi Namisaki Naotaka Shimozato Kosuke Kaji Mitsuteru Kitade Kei Moriya shinya sato Hideto Kawaratani Takemi Akahane Masanori Matsumoto Hitoshi Yoshiji Third Department of Internal Medicine Nara Medical University Department of Blood Transfusion Medicine Nara Medical University

BACKGROUND Many advanced hepatocellular carcinoma(HCC) patients are receiving sorafenib treatment. Sorafenib reportedly improves overall survival(OS) significantly in patients with HCC. Prediction of sorafenib response and prognosis in patients with HCC receiving sorafenib treatment are important due to the potentially serious side effects of sorafenib. A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13(ADAMTS13) and von Willebrand factor(VWF) are associated with the pathophysiology of liver cirrhosis and HCC through their roles in hypercoagulability; they are also associated with angiogenesis via vascular endothelial growth factor(VEGF). The imbalance between ADAMTS13 and VWF was associated with prognosis of various cancers in patients undergoing *** To investigate ADAMTS13 and VWF as potential biomarkers for sorafenib response and prognosis in patients with HCC receiving sorafenib *** Forty-one patients with HCC receiving sorafenib treatment were included in this study. The initial daily sorafenib dose was 400 mg in all patients. ADAMTS13 activity(ADAMTS13:AC), VWF antigen(VWF:Ag), VEGF levels were determined by enzyme-linked immunosorbent assay. Univariate andmultivariate analyses were used to determine predictive factors for sorafenib response and prognosis in patients with HCC receiving sorafenib *** ADAMTS13:AC was significantly higher in patients with stable disease(SD),partial response(PR), and complete response(CR) than in those with progressive disease(PD)(P < 0.05). In contrast, VWF:Ag and the VWF:Ag/ADAMTS13:AC ratio were significantly lower in patients with SD, PR, and CR than in those with PD(P < 0.05 for both). Multivariate analysis showed that the VWF:Ag/ADAMTS13:AC ratio was the only predictive factor for sorafenib response and ADAMTS13:AC was the only prognostic factor in patients with HCC receiving sorafenib treatment. The patients with a low ADAMTS13:AC(<78.0) had significantly h

关键词： ADAMTS13 Von Willebrand factor Biomarkers Hepatocellular carcinoma Sorafenib

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Rifaximin ameliorates hepatic encephalopathy and endotoxemia without affecting the gut microbiome diversity

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World Journal of Gastroenterology 2017年第47期23卷 8355-8366页

作者： Kosuke Kaji Hiroaki Takaya Soichiro Saikawa Masanori Furukawa shinya sato Hideto Kawaratani Mitsuteru Kitade Kei Moriya Tadashi Namisaki Takemi Akahane Akira Mitoro Hitoshi Yoshiji Third Department of Internal Medicine Nara Medical University

AIM To determine the efficacy of rifaximin for hepatic encephalopathy(HE) with the linkage of gut microbiome in decompensated cirrhotic *** Twenty patients(12 men and 8 women; median age, 66.8 years; range, 46-81 years) with decompensated cirrhosis(Child-pugh score > 7) underwent cognitive neuropsychological testing, endotoxin analysis, and fecal microbiome assessment at baseline and after 4 wk of treatment with rifaximin 400 mg thrice a day. HE was determined by serum ammonia level and number connection test(NCT)-A. Changes in whole blood endotoxin activity(EA) was analyzed by endotoxinactivity assay. Fecal microbiome was assessed by 16 S ribosome RNA(rR NA) gene *** Treatment with rifaximin for 4 wk improved hyperammonemia(from 90.6 ± 23.9 μg/d L to 73.1 ± 33.1 μg/dL; P < 0.05) and time required for NCT(from 68.2 ± 17.4 s to 54.9 ± 20.3 s; P < 0.05) in patients who had higher levels at baseline. Endotoxin activity was reduced(from 0.43 ± 0.03 to 0.32 ± 0.09; P < 0.05) in direct correlation with decrease in serum ammonia levels(r = 0.5886, P < 0.05). No statistically significant differences were observed in the diversity estimator(Shannon diversity index) and major components of the gut microbiome between the baseline and after treatment groups(3.948 ± 0.548 at baseline vs 3.980 ± 0.968 after treatment; P = 0.544), but the relative abundances of genus Veillonella and Streptococcus were *** Rifaximin significantly improved cognition and reduced endotoxin activity without significantly affecting the composition of the gut microbiome in patients with decompensated cirrhosis.

关键词： gut microbiome Hepatic encephalopathy Liver cirrhosis Endotoxin Rifaximin

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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 *** 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 ***,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 ***,the benefits of EFN for ALD treatment is *** To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse *** 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 ***(3 and 10 mg/kg/day)was orally administered during the experimental *** and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier *** EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based *** The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN *** promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARα***,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)*** improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory *** protective effect on intestinal bar

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

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Acylcarnitine: Useful biomarker for early diagnosis of hepatocellular carcinoma in non-steatohepatitis patients

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World Journal of Gastrointestinal Oncology 2019年第10期11卷 887-897页

作者： Hiroaki Takaya Tadashi Namisaki Mitsuteru Kitade Naotaka Shimozato Kosuke Kaji Yuki Tsuji Keisuke Nakanishi Ryuichi Noguchi Yukihisa Fujinaga Yasuhiko Sawada Soichiro Saikawa shinya sato Hideto Kawaratani Kei Moriya Takemi Akahane Hitoshi Yoshiji Third Department of Internal Medicine Nara Medical University

BACKGROUND Early diagnosis of hepatocellular carcinoma(HCC)is necessary to improve the prognosis of ***,the currently available tumor biomarkers are insufficient for the early detection of *** is essential in fatty acid metabolic pathways.A recent study reported that a high level of acylcarnitine may serve as a useful biomarker for the early diagnosis of HCC in steatohepatitis(SH)*** contrast,another study reported that the level of acetylcarnitine(AC2)-one of the acylcarnitine species-in non-SH patients with HCC was decreased vs that reported in those without *** To investigate the usefulness of acylcarnitine as a biomarker for the early diagnosis of HCC in non-SH *** Thirty-three non-SH patients(14 with HCC and 19 without HCC)were enrolled in this *** samples were obtained from patients at the time of *** levels of acylcarnitine and AC2 in the serum were determined through tandem mass *** levels of vascular endothelial growth factor(VEGF)and VEGF receptor 2(VEGFR-2)were determined by enzymelinked immunosorbent *** and multivariate analyses were used to determine early diagnostic factors of *** The level of acylcarnitine was significantly lower in non-SH patients with HCC vs those without HCC(P<0.05).In contrast,the level of lens culinaris agglutininreactive fraction ofα-fetoprotein(AFP)-AFP-L3%-was significantly higher in non-SH patients with HCC vs those without HCC(P<0.05).However,the levels of total carnitine,free carnitine,AFP,des-γ-carboxy prothrombin,VEGF,and VEGFR-2 were not different between patients with and without *** multivariate analysis showed that a low level of acylcarnitine was the only independent factor for the early diagnosis of *** patients with a low level of AC2 had a significantly higher level of VEGF vs those with a high level of AC2(P<0.05).CONCLUSION The metabolic pathways of fatty acids may differ between SH HCC and non-SH HCC

关键词： Acylcarnitine Acetylcarnitine Biomarker Hepatocellular carcinoma Angiogenesis Carnitine palmitoyltransferase 1 Oxidative stress

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Evapotranspiration and Removal Performance in the Treatment of High Salinity LandfilI-Leachate Using HSF

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Journal of Environmental Science and Engineering(B) 2016年第9期5卷 440-450页

作者： Tokuo Yano Kazuhiro Yamada Masatomo Nakayama Akiko Inoue-kohama shinya sato Keijiro Enari Department of Environment and Energy Tohoku Institute of Technology Sendai 982-8577 Japan Department of Civil Engineering and Management Tohoku Institute of Technology Sendai 982-85 77 Japan Sendai Kankyo Kaihatsu Co. Ltd. Sendai 989-3212 Japan

In this study, the water budget in the treatment of high salinity landfill-leachate was estimated and the influence of evapotranspiration （ET） on treatment performance was investigated. The salinity of the inside of horizontal subsurface flow constructed wetland （HSF） of the raw leachate inflow was 15.0± 3.4 ***/L which was in the level of the salinity of the survival limit of reed, and that of the double diluted leachate inflow was 9.3 ± 1.9 ***7L. There were large differences in the vegetation between HSF of the raw leachate inflow and that of the double diluted leachate inflow. The dense vegetation bed of double diluted leachate inflow during the growing season （April-October） provided a high ET and a large water loss, which made great contributions to the reduction of the outflow load of COD and T-N. The HSF with die-back reeds in the non-growing season （November-March） provided a slight ET and a small water loss and made less of a contribution to pollutant removal compared to the HSF with dense vegetation bed during the growing season. However, the HSF with die-back reeds during the non-growing season exhibited higher removal performance than the unplanted HSF.

关键词： Evapotranspiration HSF high salinity landfill-leachate removal performance water budget.

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韩伯丰鼎铭与西周时期王命记录的变化

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黄河文明与可持续发展 2022年第1期19卷 105-109页

作者：佐藤信弥立命馆白川静记念东洋文字文化研究所

本文对新出西周金文韩伯丰鼎铭的内容理解与性格进行议论。该铭的“宕”字读为“居”,是占有某个土地之意,该铭很可能记述王朝命令付给韩伯土地。该铭的内容与土地转让金文师永盂、吴虎鼎类似,但是该铭不需要记述土地境界、有关官员等... 详细信息

本文对新出西周金文韩伯丰鼎铭的内容理解与性格进行议论。该铭的“宕”字读为“居”,是占有某个土地之意,该铭很可能记述王朝命令付给韩伯土地。该铭的内容与土地转让金文师永盂、吴虎鼎类似,但是该铭不需要记述土地境界、有关官员等详细的情况。该铭与师永盂、吴虎鼎的不同之处是反映西周早中期与中晚期金文的性格变化。整理研究西周金文成熟化的过程,韩伯丰鼎铭是很重要的资料之一。

关键词：韩伯丰鼎西周金文土地付与宕王命

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Design of Electrohydrodynamic Devices with Consideration of Electrostatic Energy

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Cyborg and Bionic Systems 2021年第1期2021卷 32-39页

作者： Tasuku sato shinya Sakuma Masato Hijikuro Shingo Maeda Masayuki Anyoji Yoko Yamanishi Kyushu University 744 MotookaNishi-kuFukuoka 819-0395Japan Kyushu University 6-1 Kasuga KoenKasuga-shiFukuoka 816-8580Japan Shibaura Institute of Technology 3-7-5 ToyosuKoto-kuTokyo 135-8548Japan

The importance of actuators that can be integrated with flexible robot structures and mechanisms has increased in recent years with the advance of soft *** particular,electrohydrodynamic(EHD)actuators,which have expandable integrability to adapt to the flexible motion of soft robots,have received much attention in the field of soft *** have deepened the understanding of steady states of EHD phenomena but nonsteady states are not well *** herein observe the development process of fluid in a microchannel adopting a Schlieren technique with the aid of a high-speed *** addition,we analyze the behavior of fluid flow in a microchannel that is designed to have pairs of parallel plate electrodes adopting a computational fluid dynamics *** indicate the importance of considering flow generated by electrostatic energy,which tends to be ignored in constructing and evaluating EHD devices,and by the body force generated by the ion-drag *** considering these effects,we estimate the development process of EHD flow and confirm the importance of considering the generation of vortices and their interactions inside the microchannel during the development of EHD devices.

关键词： EHD flow electrostatic

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Radiofrequency ablation in a porcine liver model:Effects of transcatheter arterial embolization with iodized oil on ablation time,maximum output,and coagulation diameter as well as angiographic characteristics

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World Journal of Gastroenterology 2007年第20期13卷 2841-2845页

作者： Motoki Nakai Morio sato shinya Sahara Nobuyuki Kawai Hirohiko Tanihata Masashi Kimura Masaki Terada Department of Radiology Hidaka General Hospi-tal116-2 SonoGobo ShiWakayama 644-8655Japan Department of Radiol-ogy Wakayama Medical University 811-1KimiideraWakayama ShiWakayama 641-8510Japan

AIM:To evaluate the effects of combined radiofrequen-cy ablation and transcatheter arterial embolization with iodized oil on ablation time,maximum output,coagula-tion diameter,and portal angiography in a porcine liver model. METHODS: Radiofrequency ablation (RFA) was applied to in vivo livers of 10 normal pigs using a 17-gauge 3.0 cm expandable LeVeen RF needle electrode with or with-out transcatheter arterial embolization (TAE) with iodized oil (n = 5). In each animal,2 areas in the liver were ab-lated. Direct portography was performed before and af-ter RFA. Ablation was initiated at an output of 30 W,and continued with an increase of 10 W per minute until roll-off occurred. Ablation time and maximum output until roll-off,and coagulated tissue diameter were compared between the 2 groups. Angiographic changes on portog-raphy before and after ablation were also reviewed. RESULTS: For groups with and without TAE with iodized oil,the ablation times until roll-off were 320.6 ± 30.9 seconds and 445.1 ± 35.9 seconds,respectively,maxi-mum outputs were 69.0 ± 7.38 W and 87.0 ± 4.83 W and maximal diameters of coagulation were 41.7 ± 3.85 mm and 33.2 ± 2.28 mm. Significant reductions of abla-tion time and maximum output,and significantly larger coagulation diameter were obtained with RFA following TAE with iodized oil compared to RFA alone. Portography after RFA following TAE with iodized oil revealed more occlusion of the larger portal branches than with RFA alone. CONCLUSION: RFA following TAE with iodized oil can increase the volume of coagulation necrosis with lower output and shorter ablation time than RFA alone in nor-mal pig liver tissue.

关键词： Liver Radiofrequency ablation Transcatheter arterial embolization Iodized oil Angiography Hepatocellular carcinoma

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Ruptured high flow gastric varices with an intratumoral arterioportal shunt treated with balloon-occluded retrograde transvenous obliteration during temporary balloon occlusion of a hepatic artery

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World Journal of Gastroenterology 2006年第33期12卷 5404-5407页

作者： Motoki Nakai Morio sato Hirohiko Tanihata Tetsuo Sonomura shinya Sahara Nobuyuki Kawai Masashi Kimura Masaki Terada Department of Radiology Hidaka General Hospital 116-2 Sono Gobo Shi Wakayama 644-8655 Japan Department of Radiology Wakayama Medical University 811-1 Kimiidera Wakayama Shi Wakayama 641-8510 Japan

A patient presented with hematemesis due to gastric variceal bleeding with an intratumoral arterioportal shunt. Contrast-enhanced CT revealed gastric varices and hepatocellular carcinoma with tumor thrombi in the right portal vein. Angiography and angio-CT revealed a marked intratumoral arterioportal shunt accompanied with reflux into the main portal vein and gastric varices. Balloon-occluded retrograde venography from the gastro-renal shunt showed no visualization of gastric varices due to rapid blood flow through the intratumoral arterioportal shunt. The hepatic artery was temporarily occluded with a balloon catheter to reduce the blood flow through the arterioportal shunt, and then concurrent balloon-occluded retrograde transvenous obliteration （BRTO） was achieved. Vital signs stabilized immediately thereafter, and contrast-enhanced CT revealed thrombosed gastric varices. Worsening of hepatic function was not recognized. BRTO combined with temporary occlusion of the hepatic artery is a feasible interventional procedure for ruptured high flow gastric varices with an intratumoral arterioportal shunt.

关键词： Gastric varices Hepatocellular carcinoma Arterioportal shunt Balloon-occluded retrogradeobliteration Hematemesis

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Transhepatic catheter-directed thrombolysis for portal vein thrombosis after partial splenic embolization in combination with balloon-occluded retrograde transvenous obliteration of splenorenal shunt

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World Journal of Gastroenterology 2006年第31期12卷 5071-5074页

作者： Motoki Nakai Morio sato shinya Sahara Nobuyuki Kawai Masashi Kimura Yoshimasa Maeda Yumiko Ibata Katsuhiko Higashi Department of RadiologyWakayama Medical University 811-1KimiideraWakayama ShiWakayama 641-8510Japan the First Department of Internal MedicineHidaka General Hospital 116-2 SonoGobo ShiWakayama 644-8655Japan

A 66-year-old woman underwent partial splenic embolization （PSE） for hypersplenisrn with idiopathic portal hypertension （IPH）. One week later, contrast-enhanced CT revealed extensive portal vein thrombosis （PVT） and dilated portosystemic shunts. The PVT was not dissolved by the intravenous administration of urokinase. The right portal vein was canulated via the percutaneous transhepatic route under ultrasonic guidance and a 4 Fr. straight catheter was advanced into the portal vein through the thrombus. Transhepatic catheter-directed thrombolysis was performed to dissolve the PVT and a splenorenal shunt was concurrently occluded to increase portal blood flow, using balloon-occluded retrograde transvenous obliteration （BRTO） technique. Subsequent contrast-enhanced CT showed good patency of the portal vein and thrombosed splenorenal shunt. Transhepatic catheter-directed thrombolysis combined with BRTO is feasible and effective for PVT with portosystemic shunts.

关键词： Portal vein thrombosis Idiopathic portal hypertension Partial splenic embolization Portosystemic shunts Transhepatic catheter-directed thrombolysis Balloon-occluded retrograde transvenous obliteration

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