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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 | 布南色林治疗精神分裂症的临床应用中日专家建议显示文摘第二代(非典型)抗精神病药布南色林对多巴胺D_(2)、D_(3)受体和5-HT_(2A)受体均有较高亲和力,而对肾上腺素α_(1)、5-HT_(2c)、组胺H_(1)、毒蕈碱M_(1)和M_(3)等受体亲和力较低。多项短期和长期临床研究显示:该药对精神分裂症的阳性症状、阴性症状均有较好疗效,并改善患者的部分认知症状和社会功能。本文在循证证据和多位中日专家临床用药经验基础上撰写,希望为临床精神科医生提供用药参考,帮助精神分裂症患者早日康复,回归社会。 | 于欣 司天梅 陆峥 石川 IYO Masaomi IWATA Nakao UENO Takefumi INADA Ken HORI Hikaru | 2021 | 中国心理卫生杂志2021，35，9： | 7 |
| 3 | 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 |
| 4 | 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 |
| 5 | 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 |
| 6 | 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 |
| 7 | Non-alcoholic fatty liver disease later diagnosed as myotonic dystrophy显示文摘BACKGROUND Myotonic dystrophy(MD)is sometimes accompanied by metabolic/endocrine disorders,including dyslipidemia,central obesity,and hypogonadism.Due to considerable individual differences in the severity and progression of myopathy,MD patients with minimal-to-mild muscle symptoms might be followed as having other diseases,such as non-alcoholic fatty liver disease(NAFLD).CASE SUMMARY A 40-year-old non-obese man without a history of regular ethanol consumption was referred to our hospital due to persistent liver dysfunction and hyperlipidemia.His body mass index was 23.4 kg/m2.Liver histology demonstrated macrovesicular steatosis,ballooned hepatocytes with eosinophilic inclusion bodies,and perisinusoidal fibrosis,leading to the diagnosis of nonalcoholic steatohepatitis(NASH).Although he had no discernable muscle pain or weakness,persistently high serum creatine kinase(CK)and myoglobin levels as well as the presence of frontal baldness,a hatched face,history of cataract surgery,and grip myotonia indicated the possibility of MD.Southern blotting of the patient’s DNA revealed the presence of CTG repeats,confirming the diagnosis.CONCLUSION When gastroenterologists encounter NAFLD/NASH patients,serum CK should be verified.If hyperCKemia,frontal baldness,a hatched face,history of cataract surgery,and grip myotonia are noted,the possibility of MD may be considered. | Naoki Tanaka Takefumi Kimura Naoyuki Fujimori Yasuyuki Ichise Kenji Sano Akira Horiuchi | 2020 | World Journal of Hepatology2020，12，9： | 3 |
| 8 | Impact of dendritic cell vaccines pulsed with Wilms’ tumour-1 peptide antigen on the survival of patients with advanced non-small cell lung cancers显示文摘 | Hidenori Takahashi Masato Okamoto Shigetaka Shimodaira Shun-ichi Tsujitani Masaki Nagaya Takefumi Ishidao Junji Kishimoto Yoshikazu Yonemitsu | 2012 | European Journal of Cancer2012，，： | 3 |
| 9 | Comparison of cerebral activation between motor execution and motor imagery of self-feeding activity显示文摘Motor imagery is defined as an act wherein an individual contemplates a mental action of motor execution without apparent action.Mental practice executed by repetitive motor imagery can improve motor performance without simultaneous sensory input or overt output.We aimed to investigate cerebral hemodynamics during motor imagery and motor execution of a self-feeding activity using chopsticks.This study included 21 healthy right-handed volunteers.The self-feeding activity task comprised either motor imagery or motor execution of eating sliced cucumber pickles with chopsticks to examine eight regions of interest:pre-supplementary motor area,supplementary motor area,bilateral prefrontal cortex,premotor area,and sensorimotor cortex.The mean oxyhemoglobin levels were detected using near-infrared spectroscopy to reflect cerebral activation.The mean oxyhemoglobin levels during motor execution were significantly higher in the left sensorimotor cortex than in the supplementary motor area and the left premotor area.Moreover,significantly higher oxyhemoglobin levels were detected in the supplementary motor area and the left premotor area during motor imagery,compared to motor execution.Supplementary motor area and premotor area had important roles in the motor imagery of self-feeding activity.Moreover,the activation levels of the supplementary motor area and the premotor area during motor execution and motor imagery are likely affected by intentional cognitive processes.Levels of cerebral activation differed in some areas during motor execution and motor imagery of a self-feeding activity.This study was approved by the Ethical Review Committee of Nagasaki University(approval No.18110801)on December 10,2018. | Moemi Matsuo Naoki Iso Kengo Fujiwara Takefumi Moriuchi Daiki Matsuda Wataru Mitsunaga Akira Nakashima Toshio Higashi | 2021 | Neural Regeneration Research2021，16，4： | 3 |
| 10 | Fenofibrate suppresses growth of the human hepatocellular carcinoma cell via PPARα-independent mechanisms显示文摘 | Daisuke Yamasaki Natsuko Kawabe Hitomi Nakamura Keisuke Tachibana Kenji Ishimoto Toshiya Tanaka Hiroyuki Aburatani Juro Sakai Takao Hamakubo Tatsuhiko Kodama Takefumi Doi | 2011 | European Journal of Cell Biology2011，，8： | 2 |
| 11 | Gastrointestinal stromal tumor presenting with prominent calcification显示文摘We present a rare case of a gastrointestinal stromal tumor (GIST) in the stomach with prominent calcifica-tion at presentation. A 61-year-old woman visited our hospital because of epigastric discomfort. A spherical calcified lesion with a diameter of about 30 mm was incidentally shown in the left upper quadrant on an abdominal X-ray. Computed tomography demonstrated that the tumor was growing from the upper gastric body, with calcification in the peripheral ring area. A laparoscopic partial gastrectomy was performed, and the resected specimen revealed a well-circumscribed tumor with exophytic growth from the gastric muscularis propria. Microscopic examination revealed spindle- shaped tumor cells with calcification and hemorrhage. Additionally, positive immunoreactivity of the tumor to KIT and CD34 and a low mitotic index resulted in the diagnosis of very low risk GIST. There are a few case reports of heavily calcified GIST, although solitary or punctate calcification of primary GIST has been reported in several case series. Dystrophic calcification of necrotic or degenerative tissue is the supposed cause of primary calcified GISTs. In contrast, appearance of calcification after administration of imatinib mesylate, which may be one indicator of disease response, is possibly caused by a different mechanism. | Naoki Izawa Takeshi Sawada Ryuichi Abiko Daisuke Kumon Mami Hirakawa Mika Kobayashi Nobuyuki Obinata Masahito Nomoto Tadateru Maehata Shun-ichi Yamauchi Takefumi Kouro Takashi Tsuda Satoshi Kitajima Hiroshi Yasuda Keiichi Tanaka Ichiro Tanaka Masahiro Hoshikawa Masayuki Takagi Fumio Itoh | 2012 | World Journal of Gastroenterology2012，18，39： | 2 |
| 12 | Prognostic relevance of KRAS and BRAF mutations in Japanese patients with colorectal cancer显示文摘 | Ryota Nakanishi Jun Harada Munkhbold Tuul Yan Zhao Koji Ando Hiroshi Saeki Eiji Oki Takefumi Ohga Hiroyuki Kitao Yoshihiro Kakeji Yoshihiko Maehara | 2013 | International Journal of Clinical Oncology2013，，6： | 2 |
| 13 | Prognostic factors related to add-on dendritic cell vaccines on patients with inoperable pancreatic cancer receiving chemotherapy: a multicenter analysis显示文摘 | Masanori Kobayashi Shigetaka Shimodaira Kazuhiro Nagai Masahiro Ogasawara Hidenori Takahashi Hirofumi Abe Mitsugu Tanii Masato Okamoto Sun-ichi Tsujitani Seiichi Yusa Takefumi Ishidao Junji Kishimoto Yuta Shibamoto Masaki Nagaya Yoshikazu Yonemitsu | 2014 | Cancer Immunology, Immunotherapy2014，，： | 2 |
| 14 | Hepatic portal venous gas in pancreatic solitary metastasis from an esophageal squamous cell carcinoma显示文摘BACKGROUND:Hepatic portal venous gas(HPVG) is a rare entity commonly associated with intestinal necrosis and fatal outcome,and various underlying diseases have been reported.Pancreatic solitary metastasis without local extension is also rare in esophageal squamous cell carcinoma.METHODS:This report describes an interesting and unusual case of HPVG arising from pancreatic tumor.Autopsy revealed pathogenesis of HPVG and synchronous tumors of the esophagus and pancreas.RESULTS:A 73-year-old man developed synchronous double tumor in the esophagus and pancreas several months before acute abdomen and his death,which were generated by HPVG.Autopsy revealed that HPVG was caused by gastric wall infarction owing to expansion of an isolated pancreatic metastasis from esophageal squamous cell carcinoma.CONCLUSIONS:This is the first case of HPVG that was derived from pancreatic tumor infiltration.If he had been diagnosed with solitary pancreatic metastasis from esophageal squamous cell carcinoma in the first time,he might have an option for chemotherapy,which could let him live longer. | Takeshi Sawada Yasushi Adachi Manabu Noda Kimishige Akino Takefumi Kikuchi Hiroaki Mita Yoshifumi Ishii Takao Endo | 2013 | Hepatobiliary & Pancreatic Diseases International2013，12，1： | 2 |
| 15 | Do liver metastases from gastric cancer contraindicate aggressive surgical resection?A 14-year single-center experience显示文摘BACKGROUND Advanced gastric cancer(GC)with liver metastasis is often characterized by multiple and bilobular metastases and may also be associated with extrahepatic metastatic lesions.Hence,many physicians consider that radical surgeries are contraindicated for liver metastases from GC(LMGC).According to the 2017 Japanese treatment guideline for GC,a smaller number of liver metastases without unresectable factors may be an indication for liver resection(LR)with curability.The actual 5-year overall survival(OS)rate ranges from 0 to 0.37.AIM To present the institutional indications for LR for LMGC and identify important factors for prognostic outcomes.METHODS In total,30 patients underwent LR for LMGC during a 14-year period,and we evaluated the clinical,surgical,and oncological findings.In all patients,radical surgery with intentional lymphadenectomy was performed for the primary GC.The median follow-up duration after the initial LR was 33.7 mo,and three patients with no recurrence died of causes unrelated to the LMGC.The OS and recurrence-free survival rates after the initial LR were assessed.RESULTS Seventeen patients had metachronous LMGC.The initial LR achieved curability in 29 patients.Perioperative chemotherapy was introduced in 23 patients.The median greatest LMGC dimension was 30 mm,and the median number of LMGC was two.Twenty-two patients had unilobular LMGC.The 5-year OS and recurrence-free survival rates were 0.48 and 0.28,respectively.The median survival duration and recurrence-free duration after the initial LR were 16.8 and 8.6 mo,respectively.Twenty-one patients developed recurrence after the initial LR.Additional surgeries for recurrence were performed in nine patients,and these surgeries clearly prolonged the patients’survival.Pathological serosal invasion was an independent predictor of a poor prognostic outcome after the initial LR.Aggressive LR may be indicated for carefully selected patients with LMGC.CONCLUSION Our results of LR for LMGC seem acceptable.Additional surgeries for recurrence after the initial LR might prolong OS.Pathological serosal invasion is important for poor prognostic outcomes. | Takefumi Yazawa Tomohide Hori Hidekazu Yamamoto Hideki Harada Michihiro Yamamoto MasahiroYamada Masaki Tani Asahi Sato Yasuyuki Kamada Ryotaro Tani Ryuhei Aoyama Yudai Sasaki MasazumiZaima | 2020 | World Journal of Gastrointestinal Pharmacology and Therapeutics2020，11，5： | 2 |
| 16 | Advantages of totally laparoscopic distal gastrectomy over laparoscopically assisted distal gastrectomy for gastric cancer显示文摘 | Osamu Ikeda Yoshihisa Sakaguchi Yoshiro Aoki Norifumi Harimoto Jyunya Taomoto Takaaki Masuda Takefumi Ohga Eisuke Adachi Yasushi Toh Takeshi Okamura Hideo Baba | 2009 | Surgical Endoscopy2009，，10： | 2 |
| 17 | Cytopathic effects and local immune responses in repeated neoadjuvant HSV-tk+ ganciclovir gene therapy for prostate cancer显示文摘Objective:Cytopathic effects and local immune response were analyzed histologically in prostatic cancer(PCa)with in situ herpes simplex virus-thymidine kinase(HSV-tk)/ganciclovir(GCV)gene therapy(GT).Methods:Four high-risk PCa patients who received HSV-tk/GCV GT were investigated.After two cycles of intraprostatic injection of HSV-tk and administration of GCV,radical prostatectomy was performed.Formalin-fixed,paraffin-embedded sections were evaluated using immunohistochemistry.PCa with hormone therapy(HT,n=3)or without neoadjuvant therapy(NT,n=4)that were equivalent in terms of risk were also examined as reference.Immunoreactively-positive cells were counted in at least three areas in cancer tissue.Labeling indices(LI)were calculated as percentage values.Results:ssDNA LI in GT increased,indicating apoptosis,as well as tumor-infiltrating lymphocytes and CD68-positive macrophages,compared with their biopsies.GT cases showed significantly higher numbers of single-stranded DNA(ssDNA)LI,CD4/CD8-positive T cells and CD68-positive macrophages including M1/M2 macrophages than HT or NT cases.However,there was no significant difference in CD20-positive B cells among the types of case.There were strong correlations between CD8+T cells and CD68+macrophages(ρ=0.656,p<0.0001)as well as CD4+T cells and CD20+B cells(ρ=0.644,p<0.0001)in PCa with GT.Conclusions:Enhanced cytopathic effect and local immune response might be indicated in PCa patients with HSV-tk/GCV gene therapy. | Nobuyuki Yanagisawa Takefumi Satoh Ken-ichi Tabata Hideyasu Tsumura Yasutomo Nasu Masami Watanabe Timothy C.Thompson Isao Okayasu Yoshiki Murakumo Shiro Baba Masatsugu Iwamura | 2021 | Asian Journal of Urology2021，8，3： | 1 |
| 18 | Poly(arylene ether)s containing superacid groups as proton exchange membranes 显示文摘 | Mikami Takefumi Miyatake Kenji Watanabe Masahiro | 2010 | ACS Appl Mater Interfaces2010，2，6： | 1 |
| 19 | Factors influencing morbidity in patients undergoing transurethral resection of the prostate显示文摘 | Toyoaki Uchida Makoto Ohori Shigehiro Soh Takefumi Sato Masatsugu Iwamura Teruaki Ao Ken Koshiba | 1999 | Urology1999，，1： | 1 |
| 20 | Propofol and midazolam inhibit gastric emptying and gastrointestinal transit in mice 显示文摘 | Takefumi I Takashi A Makiko Y | 2004 | Anesth Analg2004，99，： | 1 |
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