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| 1 | Current status, problems, and perspectives of non-alcoholic fatty liver disease research显示文摘Non-alcoholic fatty liver disease(NAFLD) is a major chronic liver disease that can lead to liver cirrhosis, liver cancer, and ultimately death. NAFLD is pathologically classified as non-alcoholic fatty liver(NAFL) or non-alcoholic steatohepatitis(NASH) based on the existence of ballooned hepatocytes,although the states have been known to transform into each other. Moreover,since the detection of ballooned hepatocytes may be difficult with limited biopsied specimens, its clinical significance needs reconsideration. Repeated liver biopsy to assess histological NAFLD activity for therapeutic response is also impractical, creating the need for body fluid biomarkers and less invasive imaging modalities. Recent longitudinal observational studies have emphasized the importance of advanced fibrosis as a determinant of NAFLD outcome. Thus,identifying predictors of fibrosis progression and developing better screening methods will enable clinicians to isolate high-risk NAFLD patients requiring early intensive intervention. Despite the considerable heterogeneity of NAFLD with regard to underlying disease, patient age, and fibrosis stage, several clinical trials are underway to develop a first-in-class drug. In this review, we summarize the present status and future direction of NAFLD/NASH research towards solving unmet medical needs. | Naoki Tanaka Takefumi Kimura Naoyuki Fujimori Tadanobu Nagaya Michiharu Komatsu Eiji Tanaka | 2019 | World Journal of Gastroenterology2019，25，2： | 29 |
| 2 | Serum autotaxin levels are correlated with hepatic fibrosis and ballooning in patients with non-alcoholic fatty liver disease显示文摘AIM To examine the relationship between serum autotaxin(ATX) concentrations and clinicopathological findings in non-alcoholic fatty liver disease(NAFLD) patients.METHODS One hundred eighty-six NAFLD patients who had undergone liver biopsy between 2008 and 2017 were retrospectively enrolled.Serum samples were collected at the time of biopsy and ATX was measured by enzyme immunoassays.Sera obtained from 160 healthy,nonobese individuals were used as controls.Histological findings were graded according to an NAFLD scoring system and correlations with serum ATX were calculated by Spearman's test.Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve(AUC).Cut-off values were identified by the Youden index,and the nearest clinically applicable value to the cutoff was considered the optimal threshold for clinical convenience.RESULTS Serum ATX levels were significantly higher in NAFLD patients than in controls(0.86 mg/L vs 0.76 mg/L,P < 0.001) and correlated significantly with ballooning score and fibrosis stage(r = 0.36,P < 0.001 and r = 0.45,P < 0.001,respectively).Such tendencies were stronger in female patients.There were no remarkable relationships between ATX and serum alanine aminotransferase,lipid profiles,or steatosis scores.The AUC values of ATX for predicting the presence of fibrosis(≥ F1),significant fibrosis(≥ F2),severe fibrosis(≥ F3),and cirrhosis(F4),were all more than 0.70 in respective analyses.CONCLUSION Serum ATX levels may at least partially reflect histological severity in NAFLD. | Naoyuki Fujimori Takeji Umemura Takefumi Kimura Naoki Tanaka Ayumi Sugiura Tomoo Yamazaki Satoru Joshita Michiharu Komatsu Yoko Usami Kenji Sano Koji Igarashi Akihiro Matsumoto Eiji Tanaka | 2018 | World Journal of Gastroenterology2018，24，11： | 6 |
| 3 | Mild drinking habit is a risk factor for hepatocarcinogenesis in non-alcoholic fatty liver disease with advanced fibrosis显示文摘AIM The impact of mild drinking habit(less than 20 g/d of ethanol) on the clinical course of non-alcoholic fatty liver disease(NAFLD) has not been determined. We examined the influence of a mild drinking habit on liver carcinogenesis from NAFLD. METHODS A total of 301 patients who had been diagnosed as having NAFLD by liver biopsy between 2003 and 2016 [median age: 56 years, 45% male, 56% with nonalcoholic steatohepatitis, 26% with advanced fibrosis(F3-4)] were divided into the mild drinking group withe thanol consumption of less than 20 g/d(mild drinking group, n = 93) and the non-drinking group(n = 208). Clinicopathological features at the time of liver biopsy and factors related to hepatocellular carcinoma(HCC) occurrence were compared between the groups.RESULTS We observed significant differences in male prevalence(P = 0.01), platelet count(P = 0.04), and gammaglutamyl transpeptidase(P = 0.02) between the test groups. Over 6 years of observation, the HCC appearance rate was significantly higher in the mild drinking group(6.5% vs 1.4%, P = 0.02). Multivariate survival analysis using Cox's regression model revealed that hepatic advanced fibrosis(F3-4)(P < 0.01, risk ratio: 11.60), diabetes mellitus(P < 0.01, risk ratio: 89.50), and serum triglyceride(P = 0.04, risk ratio: 0.98) were factors significantly related to HCC in all NAFLD patients, while the effect of a drinking habit was marginal(P = 0.07, risk ratio: 4.43). In patients with advanced fibrosis(F3-4), however, a drinking habit(P = 0.04, risk ratio: 4.83), alpha-fetoprotein(P = 0.01, risk ratio: 1.23), and diabetes mellitus(P = 0.03, risk ratio: 12.00) were identified as significant contributors to HCC occurrence. CONCLUSION A mild drinking habit appears to be a risk factor for hepatocarcinogenesis in NAFLD patients, especially those with advanced fibrosis. | Takefumi Kimura Naoki Tanaka Naoyuki Fujimori Ayumi Sugiura Tomoo Yamazaki Satoru Joshita Michiharu Komatsu Takeji Umemura Akihiro Matsumoto Eiji Tanaka | 2018 | World Journal of Gastroenterology2018，24，13： | 6 |
| 4 | Association between endotoxemia and histological features of nonalcoholic fatty liver disease显示文摘AIM To assess whether surrogate biomarkers of endotoxemia were correlated with the histological features ofnonalcoholic fatty liver disease(NAFLD).METHODS One hundred twenty-six NAFLD patients who had undergone percutaneous liver biopsy were enrolled. Serum lipopolysaccharide(LPS)-binding protein(LBP) and anti-endotoxin core immunoglobulin G(Endo Cab Ig G) antibody concentrations at the time of liver biopsy were measured using the enzyme-linked immunosorbent assays to examine for relationships between biomarker levels and histological scores. RESULTS Serum LBP concentration was significantly increased in nonalcoholic steatohepatitis(NASH) patients as compared with nonalcoholic fatty liver(NAFL) subjects and was correlated with steatosis(r = 0.38, P < 0.0001) and ballooning scores(r = 0.23, P = 0.01), but not with the severity of lobular inflammation or fibrosis. Multivariate linear regression analysis revealed that LBP was associated with steatosis score and circulating C-reactive protein, aspartate aminotransferase, and fibrinogen levels. Serum Endo Cab Ig G concentration was comparable between NASH and NAFL patients. No meaningful correlations were detected between Endo Cab Ig G and histological findings. CONCLUSION LBP/Endo Cab Ig G were not correlated with lobular inflammation or fibrosis. More accurate LPS biomarkers are required to stringently assess the contribution of endotoxemia to conventional NASH. | Hiroyuki Kitabatake Naoki Tanaka Naoyuki Fujimori Michiharu Komatsu Ayaka Okubo Kyogo Kakegawa Takefumi Kimura Ayumi Sugiura Tomoo Yamazaki Soichiro Shibata Yuki Ichikawa Satoru Joshita Takeji Umemura Akihiro Matsumoto Masayoshi Koinuma Kenji Sano Toshifumi Aoyama Eiji Tanaka | 2017 | World Journal of Gastroenterology2017，23，4： | 5 |
| 5 | Microstructure and mechanical properties of ZrO_2(Y_2O_3)-Al_2O_3 nanocomposites prepared by spark plasma sintering显示文摘Zirconia (yttria)-alumina ceramic nanocomposites were fabricated from different powders by spark plasma sintering (SPS). One powder was a commercially available nanocomposite powder TZP-3Y20A, consisting of 3 mol% yttria-stabilized zirconia (3-YSZ) reinforced with 20 wt% alumina, and the other, used as a comparison, was a conventional mechanically mixed powder 3YSZ-20A, a blend made of 3 mol% yttria-stabilized zirconia powder ZrO2 (3Y) and 20 wt% -alumina powder. The effect of the sintering tem- perature on the densification, the sintering behavior, the mechanical properties and the microstructure of the composites was investigated. The results showed that the density increased with increasing sintering temperature, and thus, the mechanical properties were strengthened because of the increased densification. The nanocomposite powder TZP-3Y20A was easily sintered, and good mechanical properties were achieved as compared with the powder from the conventional mechanically mixed method, the maximum flexural strength and fracture toughness of which were 967 MPa and 5.27 MPa m1/2, respectively. | Shufeng Li Hiroshi Izui Michiharu Okano Weihua Zhang Taku Watanabe | 2012 | Particuology2012，10，3： | 5 |
| 6 | Computer Predictions and Experimental Verification of Residual Stresses and Distortion in Carburizing-Quenching of Steel显示文摘In this paper, the carburizing-quenching process of carbon steel is analyzed with computer simulation which is based on the metallo-thermo-mechanical theory and finite element analysis coupled temperature, phase transformation and stress/strain fields. The residual stresses and distortion of a steel cylinder during carburizing quenching process were predicted and compared with experimental data. From the prediction results, improvement of hardness and strength of the cylinder component in carburizing-quenching process was verified. | Dong- Ying Ju, Michiharu Narazaki , Hirofumi Kamisugi , Haruyoshi Hirano 1 . Department of Mechanical Engineering, Saitama Institute of Technology, Saitama, Japan 2 . Department of Mechanical Systems Engineering, Utsunomiya University, Utsunomiya, Japan 3 | 2000 | Journal of Shanghai Jiaotong university(Science)2000，5，1： | 4 |
| 7 | Mutations of pre-core and basal core promoter before and after hepatitis B e antigen seroconversion显示文摘AIM: To investigate the role of pre-core and basal core promoter(BCP) mutations before and after hepatitis Be antigen(HBe Ag) seroconversion.METHODS: The proportion of pre-core(G1896A) and basal core promoter(A1762T and G1764A) mutant viruses and serum levels of hepatitis B virus(HBV) DNA, hepatitis B surface antigen(HBs Ag), and HB core-related antigen were analyzed in chronic hepatitis B patients before and after HBe Ag seroconversion(n = 25), in those who were persistently HBe Ag positive(n = 18), and in those who were persistently anti-HBe positive(n = 43). All patients were infected with HBV genotype C and were followed for a median of 9 years.RESULTS: Although the pre-core mutant became predominant(24% to 65%, P = 0.022) in the HBe Ag seroconversion group during follow-up, the proportion of the basal core promoter mutation did not change. Median HBV viral markers were significantly higher in patients without the mutations in an HBe Ag positive status(HBV DNA: P = 0.003; HBs Ag: P < 0.001; HB core-related antigen: P = 0.001). In contrast, HBV DNA(P = 0.012) and HBs Ag(P = 0.041) levels were significantly higher in patients with the pre-core mutation in an anti-HBe positive status.CONCLUSION: There is an opposite association of the pre-core mutation with viral load before and after HBe Ag seroconversion in patients with HBV infection. | Nozomi Kamijo Akihiro Matsumoto Takeji Umemura Soichiro Shibata Yuki Ichikawa Takefumi Kimura Michiharu Komatsu Eiji Tanaka | 2015 | World Journal of Gastroenterology2015，21，2： | 4 |
| 8 | Efficacy of tolvaptan in patients with refractory ascites in a clinical setting显示文摘AIM: To elucidate the efficacies of tolvaptan(TLV) as a treatment for refractory ascites compared with conventional treatment. METHODS: We retrospectively enrolled 120 refractory ascites patients between January 1, 2009 and September 31, 2014. Sixty patients were treated with oral TLV at a starting dose of 3.75 mg/d in addition to sodium restriction(> 7 g/d), albumin infusion(10-20 g/wk), and standard diuretic therapy(20-60 mg/d furosemide and 25-50 mg/d spironolactone) and 60 patients with large volume paracentesis in addition to sodium restriction(less than 7 g/d), albumin infusion(10-20 g/wk), and standard diuretic therapy(20-120 mg/d furosemide and 25-150 mg/d spironolactone). Patient demographics and laboratory data, including liver function, were not matched due to the small number of patients. Continuous variables were analyzed by unpaired t-test or paired t-test. Fisher's exact test was applied in cases comparing two nominal variables. We analyzed factors affecting clinical outcomes using receiver operating characteristic curves and multivariate regression analysis. We also used multivariate Cox's proportional hazard regression analysis to elucidate the risk factors that contributed to the increased incidence of ascites.RESULTS: TLV was effective in 38(63.3%) patients. The best cut-off values for urine output and reduced urine osmolality as measures of refractory ascites improvement were > 1800 mL within the first 24 h and > 30%, respectively. Multivariate regression analysis indicated that > 25% reduced urine osmolality [odds ratio(OR) = 20.7; P < 0.01] and positive hepatitis C viral antibodies(OR = 5.93; P = 0.05) were positively correlated with an improvement of refractory ascites, while the total bilirubin level per 1.0 mg/dL(OR = 0.57;P = 0.02) was negatively correlated with improvement. In comparing the TLV group and controls, only the serum sodium level was significantly lower in the TLV group(133 mE q/L vs 136 mE q/L; P = 0.02). However, there were no significant differences in the other parameters between the two groups. The cumulative incidence rate was significantly higher in the control group with a median incidence time of 30 d in the TLV group and 20 d in the control group(P = 0.01). Cox hazard proportional multivariate analysis indicated that the use of TLV(OR = 0.58; P < 0.01), uncontrolled liver neoplasms(OR = 1.92; P < 0.01), total bilirubin level per 1.0 mg/dL(OR = 1.10; P < 0.01), and higher sodium level per 1.0 m Eq/L(OR = 0.94; P < 0.01) were independent factors that contributed to incidence. CONCLUSION: Administration of TLV results in better control of refractory ascites and reduced the incidence of additional invasive procedures or hospitalization compared with conventional ascites treatments. | Takamasa Ohki Koki Sato Tomoharu Yamada Mari Yamagami Daisaku Ito Koki Kawanishi Kentaro Kojima Michiharu Seki Nobuo Toda Kazumi Tagawa | 2015 | World Journal of Hepatology2015，7，12： | 4 |
| 9 | Single-nucleotide polymorphisms in HORMAD1 may be a risk factor for azoospermia caused by meiotic arrest in Japanese patients显示文摘基因机制作为一些男不孕的一个原因被含有,还糟糕被理解。成熟分裂为复制对细菌房间和必需品唯一。synaptonemal 建筑群是为染色体配对,分离和再结合的一个批评部件。因为猛烈雄的老鼠是不肥沃的, Hormad1 为哺乳动物的 gametogenesis 是必要的。在早 pachytene 阶段和 synaptonemal 建筑群的 Hormad1 缺乏的睾丸展览 meiotic 拘捕不能被设想。为了分析人的 HORMAD1 基因缺点与人的精子缺乏被联系的假设,由 meiotic 拘捕引起了, mutational 分析被诊断,精子缺乏源于 meiotic 的 30 个日本人的直接顺序分析在所有编码区域执行拘捕。由顺序分析,三个多型性地点,单个核苷酸多型性 1 (c。163A > G ) , SNP2 (c。501T > G ) 并且 SNP3 (c。918C > T ) ,在 exons 被发现 3, 8 和 10。有精子缺乏和 80 个正常的证明怀孕的、肥沃的人的 30 个病人为 HORMAD1 多型性被分析。SNP1 和 SNP2 与人的精子缺乏由完全的早 meiotic 拘捕引起了被联系(P< 0.05 ) 。我们建议 HORMAD1 让必要 meiotic 在人的精子发生工作。 | Toshinobu Miyamoto Aldra Tsujimura Yasushi Miyagawa Eitetsu Koh Mikio Namiki Michiharu Horikawa Yasuaki Saijo Kazuo Sengoku | 2012 | Asian Journal of Andrology2012，14，4： | 3 |
| 10 | Micromolar sodium fluoride mediates anti-osteoclastogenesis in Porphyromonas gingivalis-induced alveolar bone loss显示文摘Osteoclasts are bone-specific multinucleated cells generated by the differentiation of monocyte/macrophage lineage precursors.Regulation of osteoclast differentiation is considered an effective therapeutic approach to the treatment of bone-lytic diseases.Periodontitis is an inflammatory disease characterized by extensive bone resorption. In this study, we investigated the effects of sodium fluoride(Na F) on osteoclastogenesis induced by Porphyromonas gingivalis, an important colonizer of the oral cavity that has been implicated in periodontitis. Na F strongly inhibited the P. gingivalis-induced alveolar bone loss. That effect was accompanied by decreased levels of cathepsin K, interleukin(IL)-1β, matrix metalloproteinase 9(MMP9), and tartrate-resistant acid phosphatase,which were up-regulated during P. gingivalis-induced osteoclastogenesis. Consistent with the in vivo anti-osteoclastogenic effect,Na F inhibited osteoclast formation caused by the differentiation factor RANKL(receptor activator of nuclear factor kB ligand)and macrophage colony-stimulating factor(M-CSF). The RANKL-stimulated induction of the transcription factor nuclear factor of activated T cells(NFAT) c1 was also abrogated by Na F. Taken together, our data demonstrate that Na F inhibits RANKL-induced osteoclastogenesis by reducing the induction of NFATc1, ultimately leading to the suppressed expression of cathepsin K and MMP9.The in vivo effect of Na F on the inhibition of P. gingivalis-induced osteoclastogenesis strengthens the potential usefulness of Na F for treating periodontal diseases. | Ujjal K Bhawal Hye-Jin Lee Kazumune Arikawa Michiharu Shimosaka Masatoshi Suzuki Toshizo Toyama Takenori Sato Ryota Kawamata Chieko Taguchi Nobushiro Hamada Ikuo Nasu Hirohisa Arakawa Koh Shibutani | 2015 | International Journal of Oral Science2015，7，4： | 3 |
| 11 | Preliminary Study to Identify Criterion for Quench Crack Prevention by Computer Simulation显示文摘A criterion for preventing quench cracks has not been established although much research has been conducted in this field. A few predictions of cracking have been recently reported using simulated results of heat treatment processes. However, these results were insufficient to predict crack generation clearly because the mechanism relates not only to stress distributions in the parts but also to material characteristics. Systematic studies by the combination of experiment and simulation are therefore required to reliably identify a criterion for crack prevention by computer simulation. As a preliminary work before starting the full-scale research, a review of quench cracking research was conducted and existing test methods were classified. Several test results for cylindrical specimens were simulated for considering a cause of the crack generation. Lastly a tentative plan was made for the future research. | Kyozo Arimoto Fumiaki Ikuta Takashi Horino Shigeyuki Tamura Michiharu Narazaki Yoshio Mikita | 2004 | 材料热处理学报2004，25，5： | 2 |
| 12 | Long‐term outcome of Japanese patients with type 1 autoimmune hepatitis显示文摘 | Kaname Yoshizawa Akihiro Matsumoto Tetsuya Ichijo Takeji Umemura Satoru Joshita Michiharu Komatsu Naoki Tanaka Eiji Tanaka Masao Ota Yoshihiko Katsuyama Kendo Kiyosawa Masanori Abe Morikazu Onji | 2012 | Hepatology2012，，： | 2 |
| 13 | PCR-based molecular markers in Asiatic hybrid lily显示文摘 | MASUMI Y HIROMI A MICHIHARU N | 2002 | Scientia Horticuhure2002，，96： | 1 |
| 14 | Microbial degradation of poly(butylene succinate)by Fusarium solaniin soil environments显示文摘 | Michiharu Abe Koji Kobayashi Naoya Honma | 2010 | Polymer Degradation and Stability2010，95，： | 1 |
| 15 | Characteristic fungi observed in fermentation process for puer tea显示文摘 | Michiharu A Naohiro T Yoshito I | 2008 | Inter J of Food Microbiology2008，124，： | 1 |
| 16 | Non-invasive blood glucose measurement by Fourier transform infrared spectroscopic analysis through the mucous membrane of the lip:application of a chalcogenide optical fiber system显示文摘 | Takero Uemura Kenro Nishida Michiharu Sakakida Kenshi Ichinose Seiya Shimoda Motoaki Shichiri | 1999 | Frontiers of medical and biological engineering1999，9，2： | 1 |
| 17 | Qubit neuron according to quantum circuit for XOR problem显示文摘 | Michiharu Maeda Masaya Suenaga Hiromi Miyajima | 2006 | Applied Mathematics and Computation2006，，2： | 1 |
| 18 | Out Particling of Rolling Bearings Lubricated with Urea and Fluorine Based Greases显示文摘 | Michiharu Naka | 2000 | Lubrication Engineering2000，，9： | 1 |
| 19 | Characteristic fungi observed in the fermentation process for Puer tea显示文摘 | Michiharu Abe Naohiro Takaoka Yoshito Idemoto | | 0，，02： | 1 |
| 20 | Characteristic fungi observed in the fermentation process for Puer tea显示文摘 | Michiharu A Takaoka | 2008 | International Journal of Food Microbiology2008，24，2： | 1 |
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