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Impact of endothelial nitric oxide synthase activation on accelerated liver regeneration in a rat ALPPS model

World Journal of Gastroenterology 2023年第5期29卷 867-878页

作者： Hitoshi Masuo akira shimizu Hiroaki Motoyama Koji Kubota Tsuyoshi Notake Takahiro Yoshizawa Kiyotaka Hosoda Koya Yasukawa akira Kobayashi Yuji Soejima Division of Gastroenterological Hepato-Biliary-PancreaticTransplantation and Pediatric SurgeryDepartment of SurgeryShinshu University School of MedicineMatsumoto 390-8621Japan

BACKGROUND Although the associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)induces more rapid liver regeneration than portal vein embolization,the mechanism remains unclear.AIM To assess the influence of inflammatory cytokines and endothelial nitric oxide synthase(eNOS)activation on liver regeneration in ALPPS.METHODS The future liver remnant/body weight(FLR/BW)ratio,hepatocyte proliferation,inflammatory cytokine expression,and activation of the Akt-eNOS pathway were evaluated in rat ALPPS and portal vein ligation(PVL)models.Hepatocyte proliferation was assessed based on Ki-67 expression,which was confirmed using immunohistochemistry.The serum concentrations of inflammatory cytokines were measured using enzyme linked immune-solvent assays.The Akt-eNOS pathway was assessed using western blotting.To explore the role of inflammatory cytokines and NO,Kupffer cell inhibitor gadolinium chloride(GdCl3),NOS inhibitor N-nitro-arginine methyl ester(L-NAME),and NO enhancer molsidomine were administered intraperitoneally.RESULTS The ALPPS group showed significant FLR regeneration(FLR/BW:1.60%±0.08%,P<0.05)compared with that observed in the PVL group(1.33%±0.11%)48 h after surgery.In the ALPPS group,serum interleukin-6 expression was suppressed using GdCl3 to the same extent as that in the PVL group.However,the FLR/BW ratio and Ki-67 labeling index were significantly higher in the ALPPS group administered GdCl3(1.72%±0.19%,P<0.05;22.25%±1.30%,P<0.05)than in the PVL group(1.33%±0.11%and 12.78%±1.55%,respectively).Phospho-Akt Ser473 and phospho-eNOS Ser1177 levels were enhanced in the ALPPS group compared with those in the PVL group.There was no difference between the ALPPS group treated with L-NAME and the PVL group in the FLR/BW ratio and Ki-67 labeling index.In the PVL group treated with molsidomine,the FLR/BW ratio and Ki-67 labeling index increased to the same level as in the ALPPS group.CONCLUSION Early induction of inflammatory cytokines may not be pivotal for accelerated FLR regeneration a

关键词： Hepatectomy Nitric oxide Liver regeneration Cytokines NG-Nitroarginine methyl ester Molsidomine

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Tomographic particle image velocimetry measurement on three-dimensional swirling flow in dual-stage counter-rotating swirler

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Chinese Journal of Aeronautics 2024年第3期37卷 7-20页

作者： Yuyang ZHOU Ling DONG Mingtao SHANG Jibao LI akira RINOSHIKA Key Laboratory of Fluid Mechanics of Ministry of Education Beihang UniversityBeijing 100191China School of Mechanical and Automotive Engineering Shanghai University of Engineering ScienceShanghai 201620China AECC Commercial Aircraft Engine Co. Ltd.Shanghai 200241China Department of Mechanical Systems Engineering Yamagata UniversityYamagata 992-8510Japan

Three-Dimensional(3D)swirling flow structures,generated by a counter-rotating dualstage swirler in a confined chamber with a confinement ratio of 1.53,were experimentally investigated at Re=2.3×10^(5)using Tomographic Particle Image Velocimetry(Tomo-PIV)and planar Particle Image Velocimetry(PIV).Based on the analysis of the 3D time-averaged swirling flow structures and 3D Proper Orthogonal Decomposition(POD)of the Tomo-PIV data,typical coherent flow structures,including the Corner Recirculation Zone(CRZ),Central Recirculation Zone(CTRZ),and Lip Recirculation Zone(LRZ),were extracted.The counter-rotating dual-stage swirler with a Venturi flare generates the independence process of vortex breakdown from the main stage and pilot stage,leading to the formation of an LRZ and a smaller CTRZ near the nozzle outlet.The confinement squeezes the CRZ to the corner and causes a reverse rotation flow to limit the shape of the CTRZ.A large-scale flow structure caused by the main stage features an explosive breakup,flapping,and Precessing Vortex Core(PVC).The explosive breakup mode dominates the swirling flow structures owing to the expansion and construction of the main jet,whereas the flapping mode is related to the wake perturbation.Confinement limits the expansion of PVC and causes it to contract after the impacting area.

关键词： Coherent structures Dual-stage counter-rotating swirler cup Precessing vortex core Proper orthogonal decomposition Swirling flow Tomographic particle image velocimetry

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Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment

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World Journal of Gastroenterology 2023年第40期29卷 5566-5581页

作者： Aitoshi Hoshimoto Atsushi Tatsuguchi Ryohei Hamakubo Takayoshi Nishimoto Jun Omori Naohiko Akimoto Shu Tanaka Shunji Fujimori Tsutomu Hatori akira shimizu Katsuhiko Iwakiri Department of Gastroenterology Nippon Medical SchoolTokyo 113-8603Japan Department of Analytic Human Pathology Nippon Medical SchoolTokyo 113-8603Japan Department of Pathology Nippon Medical SchoolChiba Hokusoh HospitalChiba 270-1694Japan

BACKGROUND Comprehensive genomic analysis has shown that small bowel adenocarcinoma(SBA)has different genomic profiles from gastric and colorectal cancers.Hence,it is essential to establish chemotherapeutic regimens based on SBA characteristics.The expression of programmed cell death-ligand 1(PD-L1)and programmed cell death-ligand 2(PD-L2)in SBA is not fully understood.Anti-PD-L1/PD-1 therapy uses tumor-infiltrating lymphocytes(TILs);therefore,the status of TILs in the tumor microenvironment(TME)may influence their efficacy.The ratio of FoxP3+to CD8+T cells has been reported to be useful in predicting the prognosis of digestive system cancers.AIM To investigate the clinicopathological significance of PD-L1/2 expression according to the status of TILs in SBA tissues.METHODS We performed immunohistochemical analysis for PD-L1,PD-L2,CD8,FoxP3,and DNA mismatch repair(MMR)proteins using formalin-fixed,paraffin-embedded tissues from 50 patients diagnosed with primary SBA.The immunoreactivities of PD-L1 and PD-L2 were determined separately in tumor cells and tumor-infiltrating immune cells throughout the tumor center and invasive margins,and finally evaluated using the combined positive score(CPS).We assessed CD8+and FoxP3+T cells in the intratumoral and tumor-surrounding stroma.Subsequently,we calculated and summed the ratio of FoxP3 to CD8+T cell counts.Immune-related cell densities were graded as low or high.Immunohistochemical results were compared with clinicopathological factors and patient prognosis.The distribution of cancer-specific survival(CSS)was estimated using the Kaplan–Meier method,and the log-rank test was used to test for significant differences in CSS.A Cox proportional hazard model was also used to assess the effect of tumor variables on CSS.RESULTS PD-L1 expression was positive in 34%in tumor cells(T-PD-L1)and 54%in tumor-infiltrating immune cells(I-PDL1)of the cases examined.T-PD-L2 was positive in 34%and I-PD-L2 was positive in 42%of the cases.PD-L1 CPS≥10 and PD-L2 CPS≥10 were observed in 50%and

关键词： Small bowel adenocarcinoma Programmed cell death-ligand 1 Programmed cell death-ligand 2 Tumor microenvironment Tumor-infiltrating lymphocytes Regulatory T-cells

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Small-for-size syndrome in liver transplantation:Definition,pathophysiology and management

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Hepatobiliary & Pancreatic Diseases International 2020年第4期19卷 334-341页

作者： Yuichi Masuda Kazuki Yoshizawa Yasunari Ohno Atsuyoshi Mita akira shimizu Yuji Soejima Division of Gastroenterological Hepato-Biliary-PancreaticTransplantation and Pediatric SurgeryDepartment of SurgeryShinshu University School of Medicine3-1-1 AsahiMatsumotoNaganoJapan

Background:Since the first success in an adult patient,living donor liver transplantation(LDLT)has become an universally used procedure.Small-for-size syndrome(SFSS)is a well-known complication after partial LT,especially in cases of adult-to-adult LDLT.The definition of SFSS slightly varies among transplant physicians.The use of a partial liver graft has risks of SFSS development.Persistent portal vein(PV)hypertension and PV hyper-perfusion after LT were identified as the main factors.Hence,various approaches were explored to modulate PV flow and decrease PV pressure in order to alleviate this syndrome.Herein,the definition,clinical symptoms,pathophysiology,basic research,as well as preventive and treatment strategies for SFSS are reviewed based on an extensive review of the literature and on our own experiences.Data sources:The articles were collected through PubMed using search terms“liver transplantation”,“living donor liver transplantation”,“living liver donation”,“partial graft”,“small-for-size graft”,“small-forsize syndrome”,“graft volume”,“remnant liver”,“standard liver volume”,“graft to recipient body weight ratio”,“sarcopenia”,“porcine”,“swine”,and“rat”.English publications published before March 31,2020 were included in this review.Results:Many transplant surgeons performed PV flow modulation,including portocaval shunt,splenic artery ligation and splenectomy.With these techniques,patient outcome has been improved even when using a"small"graft.Other factors,such as preoperative recipients’nutritional and skeletal muscle status,graft congestion,and donor factors,were also identified as risk factors which all have been addressed using various strategies.Conclusions:The surgical approach controlling PV flow and pressure could help to prevent SFSS especially in severely ill recipients.In the absence of efficacious medications to resolve SFSS,conservative treatments,including aggressive fluid balance correction for massive ascites,anti-microbiological therapy to prevent or control sepsis and intensive nutrit

关键词： Liver transplantation Living donor liver transplantation Small-for-size graft Small-for-size syndrome

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Gallbladder Burkitt's lymphoma mimicking gallbladder cancer:A case report

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World Journal of Gastroenterology 2022年第6期28卷 675-682页

作者： Kiyotaka Hosoda akira shimizu Koji Kubota Tsuyoshi Notake Hikaru Hayashi Koya Yasukawa Kentaro Umemura Atsushi Kamachi Takamune Goto Hidenori Tomida Shiori Yamazaki Yuri Narusawa Naoko Asano Takeshi Uehara Yuji Soejima Division of Gastroenterological Hepato-Biliary-PancreaticTransplantation and Pediatric SurgeryDepartment of SurgeryShinshu University School of MedicineMatsumoto 390-8621Japan Department of Laboratory Medicine Shinshu University School of MedicineMatsumoto 390-8621Japan

BACKGROUND Malignant lymphoma is a rare form of gallbladder malignancy.Most of these malignancies are diffuse large B-cell lymphomas or mucosa-associated lymphoid tissue-type lymphomas;however,Burkitt’s lymphoma of the gallbladder is extremely rare,and only two previous reports are available in the literature.Herein,we report a rare case of Burkitt’s lymphoma of the gallbladder mimicking gallbladder adenocarcinoma.CASE SUMMARY An 83-year-old man with no abdominal complaints was found to have a gallbladder tumor and periportal lymph node enlargement on computed tomography(CT)performed for hypertension screening.His laboratory data revealed slightly elevated serum levels of carcinoembryonic antigen and soluble interleukin 2 receptor.Imaging examinations revealed two irregular and contrastenhanced masses extending into the gallbladder lumen,but these did not infiltrate the serosa.Moreover,a periportal lymph node had enlarged to 30 mm.Based on these findings,we diagnosed the patient as having gallbladder adenocarcinoma with lymph node metastasis,which was treated using bile duct resection with gallbladder bed resection and periportal lymph node dissection.However,the patient was finally diagnosed as having Burkitt’s lymphoma.Although the surgical margin was pathologically negative,recurrence was noted at the hepatic radical margin and superior pancreaticoduodenal lymph nodes on positron emission tomography/CT soon after discharge.Thus,he was referred to a hematologist and started receiving treatment with reduced-dose cyclophosphamide,doxorubicin,vincristine,and prednisone.CONCLUSION Burkitt’s lymphoma can occur in the gallbladder.Biopsy can be useful in cases with findings suggestive of gallbladder malignant lymphoma.

关键词： Gallbladder Malignant lymphoma Burkitt’s lymphoma Gallbladder cancer Lymphadenopathy Case report

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Pan-cancer analysis of RNA 5-methylcytosine reader (ALYREF)

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Oncology Research 2024年第3期32卷 503-515页

作者： XING YE ZHOUTING TUO KAI CHEN RUICHENG WU JIE WANG QINGXIN YU LUXIA YE akira MIYAMOTO KOO HAN YOO CHI ZHANG WURAN WEI DENGXIONG LI DECHAO FENG Samuel Oschin Comprehensive Cancer Institute Department of MedicineDepartment of Biomedical SciencesCedars-Sinai Medical CenterLos AngelesCA90048USA Department of Urology The Second Afiliated Hospital of Anhui Medical UniversityHefei230601China Department of Urology Institute of UrologyWest China HospitalSichuan UniversityChengdu610041China Department of Pathology Ningbo Diagnostic Pathology Center Ningbo315021China Department of Public Research Platfom Taizhou Hospital of Zhejiang Province Afliated to Wenzhou Medical UniversityLinhai317000China Department of Rehabilitation West Kyushu UniversityKanzaki shi842-8585Japan Department of Urology Kyung Hee UniversitySeoul446701South Korea Department of Rehabilitation The Afliated Hospital of Southwest Medical UniversityLuwzhou646000China

The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic technologies.This study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer analysis,enhancing understanding of this gene's role in cancer.We observed differential ALYREF expression between tumor and normal samples,correl ating strongly with prognosis in various cancers,particularly kidney renal papillary cell carcinoma(KIRP)and liver hepatocellular carcinoma(LIHC).ALYREF showed a negative correlation with most tumor-infitrating cells in lung squamous cell carcinoma(LUSC)and lymphoid neoplasm difuse large B-cell lymphoma(DLBC),while positive correlations were noted in IIHC,kidney chromophobe(KICH),mesothelioma(MESO),KIRP,pheochromocytoma and paraganglioma(PARD),and glioma(GBMLGG).Aditionally,ALYREF expression was closely associated with tumor heterogeneity,stemness indices,and a high mutation rate in TP53 across these cancers.In conclusion,ALYREF may serve as an oncogenic biomarker in numerous cancers,meriting further research attention.

关键词： Pan-cancer RNA 5-methylcytosine ALYREF Immwno-oncological efects

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The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

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International Journal of Oral Science 2024年第1期16卷 154-162页

作者： Yutaro Ando Masayuki Tsukasaki Nam Cong-Nhat Huynh Shizao Zang Minglu Yan Ryunosuke Muro Kazutaka Nakamura Masatsugu Komagamine Noriko Komatsu Kazuo Okamoto Kenta Nakano Tadashi Okamura akira Yamaguchi Kazuyuki Ishihara Hiroshi Takayanagi Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Department of Microbiology Tokyo Dental College2-1-14 Kanda-Misaki-choChiyoda-kuTokyoJapan Oral Health Science Center Tokyo Dental College2-9-18Kanda-Misaki-choChiyodakuTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Unit of Prosthodontics Laboratory of Oral-Maxillofacial Biology Faculty of Odonto-StomatologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam Department of Oral and Maxillofacial Surgery Department of Sensory and Motor System MedicineGraduate School of MedicineThe University of TokyoTokyoJapan Division of Rheumatology Department of Internal MedicineKeio University School of MedicineTokyoJapan Department of Laboratory Animal Medicine Research InstituteNational Center for Global Health and MedicineTokyoJapan

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

关键词： period neutrophil destruction

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Diameter Measurements of the Upper Parts of Trees Using an Ultra-Telephoto Digital Photography System

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Open Journal of Forestry 2014年第4期4卷 316-326页

作者： akira shimizu Shigeki Yamada Yuichiro Arita Forestry and Forest Products Research Institute Tsukuba Japan Kyushu Research Centre Forestry and Forest Products Research Institute Kumamoto Japan Ogunimachi Forestry Cooperative Oguni-Machi Japan

We develop a new technique to measure the exact upper diameters of trees that is comparatively simple and inexpensive. We can measure the diameters of entire tree trunks efficiently and with high precision. The system uses a digital camera with a ~15 - 30× telephoto lens to take a photograph that can be used for measuring the diameter of the upper part of a comparatively slender tree trunk. Since this method requires a measuring distance and the height of the target point in the image, a range finder capable of measuring angles was combined with the main digiscoping system. A range finder sensor uses a laser and makes a 360 degree angle of observation possible. The diameter of a target position of the objective tree can be obtained by measuring the digital image using image editing software and calculations from spreadsheet software. We focus on the Japanese cedar species in the southwestern part of Japan. Photographic measurements were obtained prior to thinning. The estimates that we obtained largely agree with the true measurements of all trees. With regard to the estimated accuracy of all measured trees, the maximum error ratio was 7.0% (1.45 cm), with a ~2% - 4% error for most of the estimated results. Although the absolute value of the estimation error was 1.87 cm (5.3%) at the maximum (9.87 m in height and 35.5 cm in diameter), an estimation accuracy of <1 cm was reproduced in almost all measurements except for the extreme hypertrophy portion by butt swelling.

关键词： Digital Camera Image Editing Software Magnifications Spotting Scope Taper Curve Upper Diameter

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赴日清人书法与江户时代日本对中国书法的接受

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故宫博物院院刊 2024年第6期 111-123,151页

作者：松浦章许浩日本关西大学郑州大学外国语与国际关系学院

江户时代日本推崇儒学,涌现出一批喜好汉文化的文人。在书法领域,相对于“和样”书法,日本人对具有中国书法特征的“唐样”书风更加青睐。由于江户日本实行闭关锁国政策,每年定期赴日的仅有前往长崎贸易的清代商船船主、乘员等,其中不... 详细信息

江户时代日本推崇儒学,涌现出一批喜好汉文化的文人。在书法领域,相对于“和样”书法,日本人对具有中国书法特征的“唐样”书风更加青睐。由于江户日本实行闭关锁国政策,每年定期赴日的仅有前往长崎贸易的清代商船船主、乘员等,其中不乏精通书法者。部分日本文人为了得到善书者墨迹,专门造访长崎,请教书法知识。这些书法最能展示当时中国书法的真实面貌,称得上是学习“唐样”书风的首选。

关键词：江户时代 “唐样”书风唐船船主接受中日书法交流

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Prediction of the Site Index for a Subtropical Broad-Leaved Forest on Okinawa Island Using Topographic Factor

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Open Journal of Forestry 2018年第3期8卷 267-282页

作者： Asako Miyamoto Ryuichi Terazono Makoto Sano akira shimizu Forestry and Forest Products Research Institute Tsukuba Japan Okinawa Prefecture Forest Resources Research Centre Nago Japan Kyushu Research Center Forest and Forest Products Research Institute Kumamoto Japan

Subtropical “Yambaru” forest, situated in the northern part of Okinawa Island of Japan, has a precious ecosystem inhabited by many endemic species. However, this region is also the center for forestry on Okinawa. Therefore, sustainable forestry activities should take into consideration the natural environment. To contribute to sustainable forest management in the region, we conducted prediction of the site index at fine-scale resolution by using multiple regression analysis with easily calculated topographic factors. For the multiple regression analysis with site index as a dependent variable, three topographic factors (the effective relief, openness, and elevation) were adopted as independent variables. Approximately 68% of the variance was explained, and the effective relief was the variable with the greatest influence. This means that it is possible to predict forest productivity at a finer scale of resolution than ever before. For sustainable forest management of sites where environmental conservation and forestry are conflicting, it is useful to estimate the site index at the finest scale of resolution practically available in the field. It might be possible to improve estimation accuracy by examining further environmental factors in the future.

关键词： Forest Productivity Forest Management Digital Elevation Model (DEM) Ge-ographic Information Systems (GIS)

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