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Biomarkers for the early diagnosis of hepatocellular carcinoma 被引量:83
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作者 Nobuhiro Tsuchiya Yu Sawada +3 位作者 Itaru Endo Keigo Saito Yasushi uemura Tetsuya Nakatsura 《World Journal of Gastroenterology》 SCIE CAS 2015年第37期10573-10583,共11页
Hepatocellular carcinoma(HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the5-year survival rate is ... Hepatocellular carcinoma(HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the5-year survival rate is > 70% if patients are diagnosed at an early stage. However, early diagnosis of HCC is complicated by the coexistence of inflammation and cirrhosis. Thus, novel biomarkers for the early diagnosis of HCC are required. Currently, the diagnosis of HCC without pathological correlation is achieved by analyzing serum α.fetoprotein levels combined with imaging techniques. Advances in genomics and proteomics platforms and biomarker assay techniques over the last decade have resulted in the identification of numerous novel biomarkers and have improved the diagnosis of HCC. The most promising biomarkers,such as glypican-3, osteopontin, Golgi protein-73 and nucleic acids including microRNAs, are most likely to become clinically validated in the near future. These biomarkers are not only useful for early diagnosis of HCC, but also provide insight into the mechanisms driving oncogenesis. In addition, such molecular insight creates the basis for the development of potentially more effective treatment strategies. In this article,we provide an overview of the biomarkers that are currently used for the early diagnosis of HCC. 展开更多
关键词 α-fetoprotein α-fetoprotein-L3 BIOMARKER Des-γ-car
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Eastern Asian endemic seed plant genera and their paleogeographic history throughout the Northern Hemisphere 被引量:52
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作者 Steven R. MANCHESTER Zhi-Duan CHEN +1 位作者 An-Ming LU Kazuhiko uemura 《Journal of Systematics and Evolution》 SCIE CSCD 北大核心 2009年第1期1-42,共42页
We review the fossil history of seed plant genera that are now endemic to eastern Asia. Although the majority of eastern Asian endemic genera have no known fossil record at all, 54 genera, or about 9%, are reliably kn... We review the fossil history of seed plant genera that are now endemic to eastern Asia. Although the majority of eastern Asian endemic genera have no known fossil record at all, 54 genera, or about 9%, are reliably known from the fossil record. Most of these are woody (with two exceptions), and most are today either broadly East Asian, or more specifically confined to Sino-Japanese subcategory rather than being endemic to the Sino-Himalayan area. Of the "eastern Asian endemic" genera so far known from the fossil record, the majority formerly occurred in Europe and/or North America, indicating that eastern Asia served as a late Tertiary or Quaternary refugium for taxa. Hence, many of these genera may have originated in other parts of the Northern Hemisphere and expanded their ranges across continents and former sea barriers when tectonic and climatic conditions allowed, leading to their arrival in eastern Asia. Although clear evidence for paleoendemism is provided by the gymnosperms Amentotaxus, Cathaya, Cephalotaxus, Cunninghamia, Cryptomeria, Glyptostrobus, Ginkgo, Keteleeria, Metasequoia, Nothotsuga, Pseudolarix, Sciadopitys, and Taiwania, and the angiosperms Cercidiphyllum, Choerospondias, Corylopsis, Craigia, Cyclocarya, Davidia, Dipelta, Decaisnea, Diplopanax, Dipteronia, Emmenopterys, Eucommia, Euscaphis, Hemiptelea, Hovenia, Koelreuteria, Paulownia, Phellodendron, Platycarya, Pteroceltis, Rehderodendron, Sargentodoxa, Schizophragma, Sinomenium, Tapiscia, Tetracentron, Toricellia, Trapella, and Trochodendron, we cannot rule out the possibility that neoendemism plays an important role especially for herbaceous taxa in the present-day flora of Asia, particularly in the Sino-Himalayan region. In addition to reviewing paleobotanical occurrences from the literature, we document newly recognized fossil occurrences that expand the geographic and stratigraphic ranges previously known for Dipelta, Pteroceltis, and Toricellia. 展开更多
关键词 CRETACEOUS eastern Asia ENDEMIC PALEOBOTANY phytogeography Tertiary.
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胃癌预防亚太地区共识指南 被引量:37
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作者 Kwong Ming Fock Nick Talley +18 位作者 Paul Moayyedi Richard Hunt Takeshi Azuma Kentaro Sugano Shu Dong Xiao Shiu Kum Lam Khean Lee Goh Tsutomu Chiba Naomi uemura Jae G Kim Nayoung Kim Tiing Leong Ang Varocha Mahachai Hazel Mitchell Abdul Aziz Rani Jyh Ming Liou Ratha-korn Vilaichone Jose Sollanor 钱本余 《胃肠病学》 2008年第4期231-240,共10页
背景与目的:胃癌是亚太地区的主要健康负担之一,但对其预防策略尚缺乏共识。本共识会议旨在评价预防胃癌的策略。方法:多学科专家组应用德尔菲(Delphi)法制订共识条文,提呈相关数据,对证据等级、推荐强度以及共识水平予以分级。结果:幽... 背景与目的:胃癌是亚太地区的主要健康负担之一,但对其预防策略尚缺乏共识。本共识会议旨在评价预防胃癌的策略。方法:多学科专家组应用德尔菲(Delphi)法制订共识条文,提呈相关数据,对证据等级、推荐强度以及共识水平予以分级。结果:幽门螺杆菌(H.pylori)感染是非贲门胃腺癌必要但非充分的致病因子。盐的高摄入与胃癌强烈相关。新鲜果蔬对胃癌具有预防作用,但维生素和其他饮食补充并不能预防胃癌。H.pylori感染中的宿主-细菌相互作用导致不同类型的胃炎和胃酸分泌,从而决定疾病结局。胃癌阳性家族史是一个重要的危险因素。低血清胃蛋白酶原反映胃萎缩程度,可作为检出胃癌高危人群的标志物。H.pylori筛查和治疗被推荐作为减少高危人群胃癌危险性的一种策略,该策略在萎缩性胃炎发生前实施最为有效,但并不排除对胃癌高危人群的内镜监测。对胃癌低危人群不推荐行H.pylori筛查。H.pylori感染的一线治疗应遵循国家治疗指南。结论:高危人群中H.pylori筛查和根除策略可能会减少胃癌的发生率,本共识根据现有证据予以推荐。 展开更多
关键词 指南 幽门螺杆菌 预防
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Potentiality of immunotherapy against hepatocellular carcinoma 被引量:20
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作者 Nobuhiro Tsuchiya Yu Sawada +2 位作者 Itaru Endo Yasushi uemura Tetsuya Nakatsura 《World Journal of Gastroenterology》 SCIE CAS 2015年第36期10314-10326,共13页
Hepatocellular carcinoma(HCC),the predominant form of primary liver cancer,is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence,treatment options r... Hepatocellular carcinoma(HCC),the predominant form of primary liver cancer,is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence,treatment options remain limited for advanced HCC,and as a result prognosis continues to be poor. Current therapeutic options,surgery,chemotherapy and radiotherapy,have only modest efficacy. New treatment modalities to prolong survival and to minimize the risk of adverse response are desperately needed for patients with advanced HCC. Tumor immunotherapy is a promising,novel treatment strategy that may lead to improvements in both treatment-associated toxicity and outcome. The strategies have developed in part through genomic studies that have yielded candidate target molecules and in part through basic biology studies that have defined the pathways and cell types regulating immune response. Here,we summarize the various types of HCC immunotherapy and argue that the newfound field of HCC immunotherapy might provide critical advantages in the effort to improve prognosis of patients with advanced HCC. Already several immunotherapies,such as tumor-associated antigen therapy,immune checkpoint inhibitors and cell transfer immunotherapy,have demonstrated safety and feasibility in HCC patients. Unfortunately,immunotherapy currently has low efficacy in advanced stage HCC patients; overcoming this chal lenge will place immunotherapy at the forefront of HCC treatment,possibly in the near future. 展开更多
关键词 Cell TRANSFER IMMUNOTHERAPY CYTOKINE THERAPY Hepat
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Predictive findings forHelicobacter pylori-uninfected, -infected and -eradicated gastric mucosa: Validation study 被引量:17
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作者 Kazuhiro Watanabe Naoyoshi Nagata +9 位作者 Ryo Nakashima Etsuko Furuhata Takuro Shimbo Masao Kobayakawa Toshiyuki Sakurai Koh Imbe Ryota Niikura Chizu Yokoi Junichi Akiyama Naomi uemura 《World Journal of Gastroenterology》 SCIE CAS 2013年第27期4374-4379,共6页
AIM:To validate the usefulness of screening endoscopy findings for predictingHelicobacter pylori (H. pylori) infection status. METHODS:H. pylori infection status was determined by histology, serology, and the urea bre... AIM:To validate the usefulness of screening endoscopy findings for predictingHelicobacter pylori (H. pylori) infection status. METHODS:H. pylori infection status was determined by histology, serology, and the urea breast test in 77 consecutive patients who underwent upper endoscopy. Based on the findings, patients were categorized as H. pylori -uninfected, -infected, or -eradicated cases. Using six photos of certain sites in the stomach per case, we determined the presence or absence of the following endoscopic findings:regular arrangement of collecting venules (RAC), linear erythema, hemorrhage, fundic gland polyp (FGP), atrophic change, rugal hyperplasia, edema, spotty erythema, exudate, xanthoma, and mottled patchy erythema (MPE). The diagnostic odds ratio (DOR) and inter-observer agreement (Kappa value) for these 11 endoscopic findings used in the determination of H. pylori infection status were calculated. RESULTS:Of the 77 patients [32 men and 45 women; mean age (SD), 39.7 (13.4) years] assessed, 28 were H. pylori uninfected, 28 were infected, and 21 were eradicated. DOR values were significantly high (< 0.05) for the following H. pylori cases:uninfected cases with RAC (11.5), linear erythema (24.5), hemorrhage (4.1), and FGP (34.5); for infected cases with atrophic change (8.67), rugal hyperplasia (15.8), edema (14.2), spotty erythema (11.5), and exudate (3.52); and for eradicated cases with atrophic change (32.4) and MPE (103.0). Kappa values were excellent for FGP (0.93), good for RAC (0.63), hemorrhage (0.79), atrophic change (0.74), and MPE (0.75), moderate for linear erythema (0.51), rugal hyperplasia (0.49), edema (0.58), spotty erythema (0.47), and exudate (0.46), and poor for xanthoma (0.19). CONCLUSION:The endoscopic findings of RAC, hemorrhage, FGP, atrophic change, and MPE will be useful for predicting H. pylori infection status. 展开更多
关键词 Diagnostic odds ratio Endoscopic finding ERADICATION therapy HELICOBACTER PYLORI Inter-observer AGREEMENT
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Decreased phagocytic activity of Kupffer cells in a rat nonalcoholic steatohepatitis model 被引量:12
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作者 Tatsuhiro Tsujimoto Hideto Kawaratani +6 位作者 Toshiyuki Kitazawa Toshiko Hirai Hajime Ohishi Mitsuteru Kitade Hitoshi Yoshiji Masahito uemura Hiroshi Fukui 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第39期6036-6043,共8页
AIM: To investigate Kupffer cell dynamics and phagocytic activity,using a rat nonalcoholic steatohepatitis (NASH) model. METHODS: Male F344 rats were fed either a control diet or a choline-deficient L-amino acid-defin... AIM: To investigate Kupffer cell dynamics and phagocytic activity,using a rat nonalcoholic steatohepatitis (NASH) model. METHODS: Male F344 rats were fed either a control diet or a choline-deficient L-amino acid-defined (CDAA) diet,followed by contrast enhanced ultrasonography (CEUS) using Levovist. The uptake of latex beads by the Kupffer cells was determined by fluorescent microscopy. The status of the Kupffer cells was compared between the two groups,using the immunohistochemical staining technique. RESULTS: After 4 or more wk of the CDAA diet,CEUS examination revealed a decrease in the signal intensity,20 min after intravenous Levovist. Fluorescent microscopic examination showed that the uptake of latex beads by the Kupffer cells was reduced at week 1 and 2 in the study group,compared with the controls,with no further reduction after 3 wk. Immunohistochemical staining revealed no significant difference in the Kupffer cell counts between the control group and the CDAA group. CONCLUSION: CEUS examination using Levovist demonstrated reduced contrast effect and phagocytic activity in the liver parenchymal phase,although the Kupffer cell numbers were unchanged,indicating reduced phagocytic function of the Kupffer cells in the rat NASH model. We believe that CEUS examination using Levovist is a useful screening modality,which can detect NASH in fatty liver patients. 展开更多
关键词 Nonalcoholic steatohepatitis Kupffer cells Contrast enhanced ultrasonography LEVOVIST Ultrasound contrast agent Phagocytic activity
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Crosstalk between angiogenesis, cytokeratin-18, and insulin resistance in the progression of non-alcoholic steatohepatitis 被引量:9
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作者 Mitsuteru Kitade Hitoshi Yoshiji +15 位作者 Ryuichi Noguchi Yasuhide Ikenaka Kosuke Kaji Yusaku Shirai Masaharu Yamazaki Masahito uemura Junichi Yamao Masao Fujimoto Akira Mitoro Masahisa Toyohara Masayoshi Sawai Motoyuki Yoshida Chie Morioka Tatsuhiro Tsujimoto Hideto Kawaratani Hiroshi Fukui 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第41期5193-5199,共7页
AIM: To elucidate the possible crosstalk between angiogenesis, cytokeratin-18 (CK-18), and insulin resistance (IR) especially in patients with non-alcoholic steatohepatitis (NASH).METHODS: Twenty-eight patients with N... AIM: To elucidate the possible crosstalk between angiogenesis, cytokeratin-18 (CK-18), and insulin resistance (IR) especially in patients with non-alcoholic steatohepatitis (NASH).METHODS: Twenty-eight patients with NASH and 11 with simple fatty liver disease (FL) were enrolled in this study and underwent clinicopathological examination. The measures of angiogenesis, CK-18, and IR employed were CD34-immunopositive vessels, CK-18immunopositive cells, and homeostasis model assessment of IR (HOMA-IR), respectively. The correlations of these factors with NASH were elucidated.RESULTS: Significant development of hepatic neovascularization was observed only in NASH, whereas almost no neovascularization could be observed in FL and healthy liver. The degree of angiogenesis was almost parallel to liver fibrosis development, and both parameters were positively correlated. Similarly, CK-18expression and HOMA-R were signifi cantly increased in NASH as compared with FL and healthy liver. Furthermore, CK-18 and HOMA-IR were also positively correlated with the degree of neovascularization. CONCLUSION: These results indicate that the crosstalk between angiogenesis, CK-18, and IR may play an important role in the onset and progression of NASH. 展开更多
关键词 ANGIOGENESIS Cytokeratin-18 Fatty liver Insulin resistance Non-alcoholic steatohepatitis Liver fibrosis
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Screening serum hepatocellular carcinoma-associated proteins by SELDI-based protein spectrum analysis 被引量:8
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作者 Jie-Feng Cui Yin-Kun Liu +5 位作者 Hai-Jun Zhou Xiao-Nan Kang Cheng Huang Yi-Feng He Zhao-You Tang Toshimasa uemura 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第8期1257-1262,共6页
AIM: To find out potential serum hepatocellular carcinoma (HCC)-associated proteins with low molecular weight and low abundance 13y SELDI-based serum protein spectra analysis, that will have much application in the... AIM: To find out potential serum hepatocellular carcinoma (HCC)-associated proteins with low molecular weight and low abundance 13y SELDI-based serum protein spectra analysis, that will have much application in the diagnosis or differentiated diagnosis of HCC, as well as giving a better understanding of the mechanism of hepato-card nogenesis.METHODS: Total serum samples were collected with informed consent from 81 HCC patients with HBV(+)/ cirrhosis(+), 36 cirrhosis patients and 43 chronic hepatitis B patients. Serum protein fingerprint profiles were first generated by selected WCX2 protein chip capture integrating with SELDI-TOF-MS, then normalized and aligned by Ciphergen SELDI Software 3.1.1 with Biomarker Wizard..Comparative analysis of the intensity of corresponding protein fingerprint peaks in normalized protein spectra, some protein peaks with significant difference between H.CC and cirrhosis or chronic hepatitis B were found.RESULTS: One hundred and twenty-eight serum protein peaks betweeri.2000 and 30000Da were identified under the condition of signal-to-noise 〉 5 and minimum threshold for cluster 〉 20%. Eighty-seven of these proteins were showed significant differences in intensity between HCC and cirrhosis (P 〈 0.05). Of the above differential proteins, 45 proteins had changes greater than two-fold, including 15 upregulated proteins and 30 downregulated proteins i.n HCC serum. Between HCC and chronic hepatitis B, 9 of 52 differential proteins (P 〈 0.05) had intensities of more than two-fold, including 2 upregulated proteins and 7 downregulated proteins in HCC serum. Between cirrhosis and chronic hepatitis B, 28 of 79 significant differential proteins (P 〈 0.05) changes greater than two-fold in intensity, including 17 upregulated proteins and 11 downregulated proteins in cirrhosis serum. For the analysis of these leading differential proteins in subtraction difference mode among three diseases, the five common downregulated proteins in HCC serum (M/Z 2870, 3 展开更多
关键词 Hepatocellular carcinoma SELDI-TOF-MS
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Mathematical Modeling of Possibility Markov Chains by Possibility Theory
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作者 Yoshiki uemura Takemura Kazuhisa Kenji Kita 《Applied Mathematics》 2024年第8期499-507,共9页
Statistical regression models are input-oriented estimation models that account for observation errors. On the other hand, an output-oriented possibility regression model that accounts for system fluctuations is propo... Statistical regression models are input-oriented estimation models that account for observation errors. On the other hand, an output-oriented possibility regression model that accounts for system fluctuations is proposed. Furthermore, the possibility Markov chain is proposed, which has a disidentifiable state (posterior) and a nondiscriminable state (prior). In this paper, we first take up the entity efficiency evaluation problem as a case study of the posterior non-discriminable production possibility region and mention Fuzzy DEA with fuzzy constraints. Next, the case study of the ex-ante non-discriminable event setting is discussed. Finally, we introduce the measure of the fuzzy number and the equality relation and attempt to model the possibility Markov chain mathematically. Furthermore, we show that under ergodic conditions, the direct sum state can be decomposed and reintegrated using fuzzy OR logic. We had already constructed the Possibility Markov process based on the indifferent state of this world. In this paper, we try to extend it to the indifferent event in another world. It should be noted that we can obtain the possibility transfer matrix by full use of possibility theory. 展开更多
关键词 Possibility Markov Chain Ergodic Condition Direct Sum State Prior Indiscriminate State Posterior Discriminatory State
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Post-polypectomy bleeding and thromboembolism risks associated with warfarin vs direct oral anticoagulants 被引量:6
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作者 Naohiro Yanagisawa Naoyoshi Nagata +6 位作者 Kazuhiro Watanabe Tatsuhiro Iida Mariko Hamada Sakurako Kobayashi Takuro Shimbo Junichi Akiyama Naomi uemura 《World Journal of Gastroenterology》 SCIE CAS 2018年第14期1540-1549,共10页
AIM To verify the validity of the endoscopy guidelines for patients taking warfarin or direct oral anticoagulants(DOAC).METHODS We collected data from 218 patients receiving oral anticoagulants(73 DOAC users, 145 warf... AIM To verify the validity of the endoscopy guidelines for patients taking warfarin or direct oral anticoagulants(DOAC).METHODS We collected data from 218 patients receiving oral anticoagulants(73 DOAC users, 145 warfarin users) and 218 patients not receiving any antithrombotics(age-and sexmatched controls) who underwent polypectomy.(1) We evaluated post-polypectomy bleeding(PPB) risk in patients receiving warfarin or DOAC compared with controls;(2) we assessed the risks of PPB and thromboembolism between three AC management methods: Discontinuing AC with heparin bridge(HPB)(endoscopy guideline recommendation), continuing AC, and discontinuing AC without HPB.RESULTS PPB rate was significantly higher in warfarin users and DOAC users compared with controls(13.7% and 13.7% vs 0.9%, P < 0.001), but was not significantly different between rivaroxaban(13.2%), dabigatran(11.1%), and apixaban(13.3%) users. Two thromboembolic events occurred in warfarin users, but none in DOAC users. Compared with the continuing anticoagulant group, the discontinuing anticoagulant with HPB group(guideline recommendation) had a higher PPB rate(10.8% vs 19.6%, P = 0.087). These findings were significantly evident in warfarin but not DOAC users. One thrombotic event occurred in the discontinuing anticoagulant with HPB group and the discontinuing anticoagulant without HPB group; none occurred in the continuing anticoagulant group.CONCLUSION PPB risk was similar between patients taking warfarin and DOAC. Thromboembolism was observed in warfarin users only. The guideline recommendations for HPB should be re-considered. 展开更多
关键词 High-risk ENDOSCOPIC procedures Novel oral ANTICOAGULANTS ENDOSCOPIC guideline validation Postprocedure gastrointestinal BLEEDING
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Bisphenol A in combination with TNF-a selectively induces Th2 cell-promoting dendritic cells in vitro with an estrogen-like activity 被引量:6
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作者 Hongchuan Guo Tianyi Liu +13 位作者 Yasushi uemura Shunchang Jiao Deqing Wang Zilin Lin Yayoi Narita Motoharu Suzuki Narumi Hirosawa Yasuko Ichihara Osamu Ishihara Hirosato Kikuchi Yasushi Sakamoto Satoru Senju Qiuhang Zhang Feng Ling 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2010年第3期227-234,共8页
Bisphenol A(BPA)is a monomer used in manufacturing a wide range of chemical products,including epoxy resins and polycarbonate.BPA,an important endocrine disrupting chemical that exerts estrogen-like activities,is dete... Bisphenol A(BPA)is a monomer used in manufacturing a wide range of chemical products,including epoxy resins and polycarbonate.BPA,an important endocrine disrupting chemical that exerts estrogen-like activities,is detectable at nanomolar levels in human serum worldwide.The pregnancy associated doses of 17b-estradiol(E2)plus tumor-necrosis factor-a(TNF-a)induce distorted maturation of human dendritic cells(DCs)that result in an increased capacity to induce T helper(Th)2 responses.The current study demonstrated that the presence of BPA during DC maturation influences the function of human DCs,thereby polarizing the subsequent Th response.In the presence of TNF-a,BPA treatment enhanced the expression of CC chemokine ligand 1(CCL1)in DCs.In addition,DCs exposed to BPA/TNF-a produced higher levels of IL-10 relative to those of IL-12p70 on CD40 ligation,and preferentially induced Th2 deviation.BPA exerts the same effect with E2 at the same dose(0.01–0.1 mM)with regard to DC-mediated Th2 polarization.These findings imply that DCs exposed to BPA will provide one of the initial signals driving the development and perpetuation of Th2-dominated immune response in allergic reactions. 展开更多
关键词 bisphenol A dendritic cells Th1/2 human
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他克莫司诱导的骨髓间充质干细胞成骨细胞分化和体内骨形成 被引量:6
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作者 董健 戴文达 +2 位作者 方涛林 林红 Toshimasa uemura 《中华医学杂志》 CAS CSCD 北大核心 2007年第3期190-194,共5页
目的研究免疫抑制剂他克莫司(FK506)对大鼠骨髓来源的间充质干细胞(MSC)的成骨细胞分化诱导,及对 MSCs 结合多孔β三磷酸钙(β-TCP)的体内成骨作用。方法原代 MSCs 按实验目的随机分组。对照组生长培养液中加入 L-抗坏血酸-2-磷酸(AsAp... 目的研究免疫抑制剂他克莫司(FK506)对大鼠骨髓来源的间充质干细胞(MSC)的成骨细胞分化诱导,及对 MSCs 结合多孔β三磷酸钙(β-TCP)的体内成骨作用。方法原代 MSCs 按实验目的随机分组。对照组生长培养液中加入 L-抗坏血酸-2-磷酸(AsAp)和β-甘油磷酸(β-GP);FK506处理组在对照组基础上加入50 nmol/L FK506。实验分成体外体内两部分相继进行。体外实验细胞分别于培养第4、8、12、16大时行碱件磷酸酶(APase)活性,钙含量,扫描电镜和骨钙素 mRNANorthern 印迹分析;体内实验将细胞载入多孔β-TCP 立方块形成 MSCs/β-TCP 复合物,继续成骨诱导培养2周后植入大鼠背部皮下,4周和8周后取出复合物作组织学检查。结果 FK506处理组碱性磷酸酶活性、钙含量、骨钙素 mRNA 均明显高于对照组(均 P<0.05);体内成骨情况亦明显优于对照组。结论免疫抑制剂 FKS06能显著促进大鼠骨髓来源间充质干细胞(MSCs)的体外成骨细胞分化和动物体内继续成骨的作用,并提示 FK506可作为一种新型成骨生长因子,在临床有潜在的应用价值。 展开更多
关键词 髓样组细胞 他克莫司结合蛋白质类 骨生成
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Innate immune reactivity of the liver in rats fed a choline-deficient L-amino-acid-defined diet 被引量:5
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作者 Hideto Kawaratani Tatsuhiro Tsujimoto +4 位作者 Toshiyuki Kitazawa Mitsuteru Kitade Hitoshi Yoshiji Masahito uemura Hiroshi Fukui 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第43期6655-6661,共7页
AIM: To investigate the innate immune reactivity of tumor necrosis factor-alpha (TNF-α), Toll-like receptor 4 (TLR4), and CD14 in the liver of non-alcoholic steatohepatitis (NASH) model rats. METHODS: Male F3... AIM: To investigate the innate immune reactivity of tumor necrosis factor-alpha (TNF-α), Toll-like receptor 4 (TLR4), and CD14 in the liver of non-alcoholic steatohepatitis (NASH) model rats. METHODS: Male F344 rats were fed a cholinedeficient L-amino-acid-defined (CDAA) diet. The rats were killed after 4 or 8 wk of the diet, and their livers were removed for immunohistochemical investigation and RNA extraction. The liver specimens were immunostained for TNF-α, TLR4, and CD14. The gene expressions of TNF-α, TLR4, and CD14 were determined by reverse-transcriptase polymerase chain reaction (RT-PCR). Kupffer cells were isolated from the liver by Percoll gradient centrifugation, and were then cultured to measure TNF-α production. RESULTS: The serum and liver levels of TNF-~ in the CDAA-fed rats increased significantly as compared with the control group, as did the immunohistochemical values and gene expressions of TNF-α, TLR4, and CD14 with the progression of steatohepatitis. TNF-α production from the isolated Kupffer cells of the CDAAfed rats was elevated by lipopolysaccharide stimulation. CONCLUSION: The expressions of TNF-α, TLR4, and CD14 increased in the NASH model, suggesting that 展开更多
关键词 Nonalcoholic steatohepatitis Kupffer cells Toll-like receptor 4 CD14 ENDOTOXINS Tumor necrosisfactor-alpha
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Validation study of postoperative liver failure and mortality risk scores after liver resection for perihilar cholangiocarcinoma 被引量:5
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作者 Takehiro Noji Satoko uemura +10 位作者 Jimme KWiggers Kimitaka Tanaka Yoshitsugu Nakanishi Toshimichi Asano Toru Nakamura Takahiro Tsuchikawa Keisuke Okamura Pim BOlthof William RJarnagin Thomas Mvan Gulik Satoshi Hirano 《Hepatobiliary Surgery and Nutrition》 SCIE 2022年第3期375-385,共11页
Background:Surgery for perihilar cholangiocarcinoma(PHCC)remains a challenging procedure with high morbidity and mortality.The Academic Medical Center(Amsterdam UMC)and Memorial Sloan Kettering Cancer Center proposed ... Background:Surgery for perihilar cholangiocarcinoma(PHCC)remains a challenging procedure with high morbidity and mortality.The Academic Medical Center(Amsterdam UMC)and Memorial Sloan Kettering Cancer Center proposed a postoperative mortality risk score(POMRS)and post-hepatectomy liver failure score(PHLFS)to predict patient outcomes.This study aimed to validate the POMRS and PHLFS for PHCC patients at Hokkaido University.Methods:Medical records of 260 consecutive PHCC patients who had undergone major hepatectomy with extrahepatic bile duct resection without pancreaticoduodenectomy at Hokkaido University between March 2001 and November 2018 were evaluated to validate the PHLFS and POMRS.Results:The observed risks for PHLF were 13.7%,24.5%,and 39.8%for the low-risk,intermediate-risk,and high-risk groups,respectively,in the study cohort.A receiver-operator characteristic(ROC)analysis revealed that the PHLFS had moderate predictive value,with an analysis under the curve(AUC)value of 0.62.Mortality rates based on the POMRS were 1.7%,5%,and 5.1%for the low-risk,intermediate-risk,and high-risk groups,respectively.The ROC analysis demonstrated an AUC value of 0.58.Conclusions:This external validation study showed that for PHLFS the threshold for discrimination in an Eastern cohort was reached(AUC>0.6),but it would require optimization of the model before use in clinical practice is acceptable.The POMRS were not applicable in the eastern cohort.Further external validation is recommended. 展开更多
关键词 Perihilar cholangiocarcinoma(PHCC) post operative mortality score post-hepatectomy liver failure score(PHLFS) validation study
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Combined treatment of vitamin K_2 and angiotensin-converting enzyme inhibitor ameliorates hepatic dysplastic nodule in a patient with liver cirrhosis 被引量:5
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作者 Hitoshi Yoshiji Ryuichi Noguchi +14 位作者 Masaharu Yamazaki Yasuhide Ikenaka Masayoshi Sawai Masatoshi Ishikawa Hideto Kawaratani Tsuyoshi Mashitani Mitsuteru Kitade Kosuke Kaji Masahito uemura Junichi Yamao Masao Fujimoto Akira Mitoro Masahisa Toyohara Motoyuki Yoshida Hiroshi Fukui 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第23期3259-3261,共3页
Although it is well known that the hepatocellular carcinoma (HCC) is an ominous complication in patients with liver cirrhosis, there has been no approved drug to prevent the development of HCC to date. We previously r... Although it is well known that the hepatocellular carcinoma (HCC) is an ominous complication in patients with liver cirrhosis, there has been no approved drug to prevent the development of HCC to date. We previously reported that the combined treatment of vitamin K2 (VK) and angiotensin-converting enzyme inhibitor (ACE-I) significantly suppressed the experimental hepatocarcinogenesis. A 66-year-old Japanese woman with hepatitis C virus (HCV)-related liver cirrhosis developed a dysplastic nodule in the liver detected by enhanced computed tomography along with elevation of the tumor markers, namely, alpha-fetoprotein (AFP) and lectin-reactive demarcation (AFP-L3), suggesting the presence of latent HCC. After oral administration of VK and ACE-I, the serum levels of both AFP and AFP-L3 gradually decreased without any marked alteration of the serum aminotransferase activity. After one-year treatment, not only the serum levels of AFP and AFP-L3 returned to the normal ranges, but also the dysplastic nodule disappeared. Since both VK and ACE-I are widely used without serious side effects, this combined regimen may become a new strategy for chemoprevention against HCC. 展开更多
关键词 Vitamin K2 ACE inhibitor Hepatocellular carcinoma VEGF ANGIOGENESIS
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Constipation, hard stools, fecal urgency, and incomplete evacuation, but not diarrhea is associated with diabetes and its related factors 被引量:5
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作者 Noriko Ihana-Sugiyama Naoyoshi Nagata +7 位作者 Ritsuko Yamamoto-Honda Eiko Izawa Hiroshi Kajio Takuro Shimbo Masafumi Kakei Naomi uemura Junichi Akiyama Mitsuhiko Noda 《World Journal of Gastroenterology》 SCIE CAS 2016年第11期3252-3260,共9页
AIM: To determine the bowel symptoms associated with diabetes and diabetes-related factors after excluding gastrointestinal (GI) organic diseases.METHODS: Participants were 4738 (603 diabetic and 4135 non-diabetic) pa... AIM: To determine the bowel symptoms associated with diabetes and diabetes-related factors after excluding gastrointestinal (GI) organic diseases.METHODS: Participants were 4738 (603 diabetic and 4135 non-diabetic) patients who underwent colonoscopy and completed a questionnaire. On the day of pre-colonoscopy, 9 symptoms (borborygmus, abdominal distension, increased flatus, constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete evacuation) were prospectively evaluated on a 7-point Likert scale. The test-retest reliability of the bowel symptom scores from the baseline and second questionnaires was analyzed using kappa statistics. Associations between bowel symptom scores and diabetes or diabetes-related factors were analyzed by a rank-ordered logistic model adjusted for related confounders, and odds ratios (ORs) were estimated.RESULTS: In multivariate analysis, constipation [adjusted odds ratio (AOR) = 1.57, CI: 1.33-1.85, P &#x0003c; 0.01] and hard stools (AOR = 1.56, CI: 1.33-1.84, P &#x0003c; 0.01) were associated with diabetes, and fecal urgency (AOR = 1.16, CI: 0.99-1.37, P = 0.07) and incomplete evacuation (AOR = 1.16, CI: 1.00-1.36, P = 0.06) were marginally associated with diabetes. These symptoms remained associated even after excluding organic GI diseases on colonoscopy. Test-retest reliability of symptom score with a mean duration of 3.2 mo was good (mean kappa, 0.69). Associations of symptoms with diabetes-related factors were found; constipation with HbA1c &#x02265; 8.0% (AOR = 2.11, CI: 1.19-3.73), body mass index (BMI) &#x0003c; 25 (AOR = 2.11, CI: 1.22-3.66), and insulin use (AOR = 1.90, CI: 1.08-3.36); hard stools with diabetes duration (AOR = 1.03, CI: 1.00-1.07); fecal urgency with BMI &#x0003c; 25 (AOR = 1.73, CI: 1.00-2.98); and incomplete evacuation with BMI &#x0003c; 25 (AOR = 2.60, CI: 1.52-4.43), serum creatinine level (AOR = 1.27, CI: 1.10-1.47), and insulin use (AOR = 1.92, CI: 1.09-3.38).CONCLUSION: Diabetes is associated with constipation, hard stools, fecal u 展开更多
关键词 Functional bowel disease Gastrointestinal symptom rating scale Decreased passage of stools Diabetic complications
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Value of a new stick-type rapid urine test for the diagnosis of Helicobacter pylori infection in the Vietnamese population 被引量:4
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作者 Duc T Quach Toru Hiyama +5 位作者 Fumio Shimamoto Quang D Le Linh X Ho Nhu HT Vu Masaharu Yoshihara Naomi uemura 《World Journal of Gastroenterology》 SCIE CAS 2014年第17期5087-5091,共5页
AIM: To assess the value of a new test for the diagnosis of Helicobacter pylori (H. pylori) infection, Rapirun<sup>&#x000ae;</sup>H. pylori Antibody Stick (Rapirun<sup>&#x000ae;</sup> S... AIM: To assess the value of a new test for the diagnosis of Helicobacter pylori (H. pylori) infection, Rapirun<sup>&#x000ae;</sup>H. pylori Antibody Stick (Rapirun<sup>&#x000ae;</sup> Stick), in a Vietnamese population. 展开更多
关键词 Helicobacter pylori Urine test Rapirun® Stick Vietnamese Rapid urease test
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Cryptogenic cirrhosis in the region where obesity is not prevalent 被引量:4
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作者 Hideyuki Kojima Shinya Sakurai +5 位作者 Masahiko Matsumura Norie Umemoto Masahito uemura Hiroyo Morimoto Yasuhiro Tamagawa Hiroshi Fukui 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第13期2080-2085,共6页
AIM: Recent studies have demonstrated that obesity is the common feature of cryptogenic cirrhosis (CC) and non-alcoholic steatohepatitis. However, there is little information on CC in the region where obesity is no... AIM: Recent studies have demonstrated that obesity is the common feature of cryptogenic cirrhosis (CC) and non-alcoholic steatohepatitis. However, there is little information on CC in the region where obesity is not prevalent, METHODS: The clinical features, and the liver-related morbidity and mortality of CC were analyzed in Japan where the prevalence of obesity is low. Among 652 cirrhotic patients, we identified 29 patients (4.4%) with CC. Of these, 24 CC patients who were followed up for more than 6 months were compared in a case-control study with age-, sex-, and Child-Pugh score-matched controls having cirrhosis of viral etiology. RESULTS: Obesity (BMI≥25 kg/m^2), diabetes mellitus, and hypertriglyceridemia were more frequent, and the visceral fat area was larger in the CC patients than in the controls. The indices of insulin resistance were higher and the serum aminotransferase levels were lower in the CC patients than in the controls. Logistic regression analysis identified the elevated hemoglobin A1c, BMI ≥ 25 kg/m^2, and normal aminotransferase levels as independent predictors of CC. Kaplan-Meier analysis demonstrated lower occurrence of hepatocellular carcinoma and higher survival rate in the CC than in the controls in contrast to the similar cumulatlve probability of liverrelated morbidity between those groups.CONCLUSION: CC more frequently presents with the clinical features suggestive of non-alcoholic steatohepatitis compared with controls even in the region where obesity is not prevalent. The lower occurrence of hepatocellular carcinoma and higher survival rate may indicate an indolent clinical course in CC as compared with viral cirrhosis. 展开更多
关键词 Ke Cryptogenic cirrhosis Viral cirrhosis Nonalcoholic steatohepatitis Hepatocellular carcinoma Case-control study
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FK506对骨髓间充质干细胞体外成骨活性的诱导 被引量:4
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作者 董健 方涛林 +3 位作者 孙源 戴文达 李云飞 Toshimasa uemura 《中华创伤杂志》 CAS CSCD 北大核心 2006年第10期775-778,共4页
目的研究免疫抑制剂FKS06在体外对大鼠骨髓来源的间充质干细胞(MSCs)成骨诱导能力以及FK506成骨诱导的量效关系。方法MSCs在不同条件下培养16d:(1)对照组(C组)- (基础培养液):含L-抗坏血酸-2-磷酸(AsAp)和β-甘油磷酸(β-GP)的α-MEM... 目的研究免疫抑制剂FKS06在体外对大鼠骨髓来源的间充质干细胞(MSCs)成骨诱导能力以及FK506成骨诱导的量效关系。方法MSCs在不同条件下培养16d:(1)对照组(C组)- (基础培养液):含L-抗坏血酸-2-磷酸(AsAp)和β-甘油磷酸(β-GP)的α-MEM培养液;(2)基础培养液加入地塞米松(D组);(3)基础培养液加入FK506(F组);(4)基础培养液加入地塞米松和FKS06(FD组)。通过测定干细胞形态、细胞增殖、碱性磷酸酶(ALP)活性、钙化结节染色和骨钙素基因表达等,评价FK506对MSCs的成骨诱导能力。结果FK506能促进大鼠MSCs增殖、成骨细胞分化,明显诱导钙化结节形成,显著提高ALP活性和骨钙素mRNA的表达。FK506与地塞米松具有协同成骨诱导作用,当α-MEM中含0.25mmol/L AsAp、10mmol/Lβ-甘油磷酸、10nmol/L地塞米松和50nmol/L FK506时可获得最佳成骨效应。结论FK506具有强大成骨诱导能力,可以用作骨诱导因子。 展开更多
关键词 间充质干细胞 骨生成 组织工程 FK506
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Hand-assisted laparoscopic restorative proctocolectomy for ulcerative colitis 被引量:4
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作者 Norimitsu Shimada Hiroki Ohge +7 位作者 Raita Yano Naoki Murao Norifumi Shigemoto Shinnosuke Uegami Yusuke Watadani Kenichiro uemura Yoshiaki Murakami Taijiro Sueda 《World Journal of Gastrointestinal Surgery》 SCIE CAS 2016年第8期578-582,共5页
AIM To evaluate the utility of hand-assisted laparoscopic restorative proctocolectomy(HALS-RP) compared with the conventional open procedure(OPEN-RP).METHODS Fifty-one patients who underwent restorative total proctoco... AIM To evaluate the utility of hand-assisted laparoscopic restorative proctocolectomy(HALS-RP) compared with the conventional open procedure(OPEN-RP).METHODS Fifty-one patients who underwent restorative total proctocolectomy with rectal mucosectomy and ileal pouch anal anastomosis between January 2008 and July 2015 were retrospectively analyzed.Twentythree patients in the HALS-RP group and twentyfour patients in the OPEN-RP group were compared.Four patients who had purely laparoscopic surgery were excluded.Restorative total proctocolectomy was performed with mucosectomy and a hand-sewn ilealpouch-anal anastomosis.Preoperative comorbidities,intraoperative factors such as blood loss and operative time,postoperative complications,and postoperative course were compared between two groups.RESULTS Patients in both groups were matched with regards to patient age,gender,and American Society of Anesthesiologists score.There were no significant differences in extent of colitis,indications for surgery,preoperative comorbidities,and preoperative medications in the two groups.The median operative time for the HALS-RP group was 369(320-420) min,slightly longer than the OPEN-RP group at 355(318-421) min; this was not statistically significant.Blood loss was significantly less in HALS-RP [300(230-402) m L] compared to OPEN-RP [512(401-1162) m L,P = 0.003].Anastomotic leakage was noted in 3 patients in the HALS-RP group and 2 patients in the OPEN-RP group(13% vs 8.3%,NS).The rates of other postoperative complications and the length of hospital stay were not different between the two groups.CONCLUSION HALS-RP can be performed with less blood loss and smaller skin incisions.This procedure is a feasible technique for total proctocolectomy for ulcerative colitis. 展开更多
关键词 HAND-ASSISTED LAPAROSCOPIC SURGERY ULCERATIVE COLITIS LAPAROSCOPIC SURGERY PROCTOCOLECTOMY
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