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| 1 | Apoptosis and non-alcoholic fatty liver diseases显示文摘The number of patients with nonalcoholic fatty liver diseases(NAFLD) including nonalcoholic steatohepatitis(NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma(HCC) and is one of the most serious health problems in the world. The mechanism through which NASH progresses is still largely unknown. Activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD/NASH. Apoptotic hepatocytes stimulate immune cells and hepatic stellate cells toward the progression of fibrosis in the liver through the production of inflammasomes and cytokines. Abnormalities in glucose and lipid metabolism as well as microbiota accelerate these processes. The production of reactive oxygen species, oxidative stress, and endoplasmic reticulum stress is also involved. Cell death, including apoptosis, seems very important in the progression of NAFLD and NASH. Recently, inhibitors of apoptosis have been developed as drugs for the treatment of NASH and may prevent cirrhosis and HCC. Increased hepatocyte apoptosis may distinguish NASH from NAFLD, and the improvement of apoptosis could play a role in controlling the development of NASH. In this review, the association between apoptosis and NAFLD/NASH are discussed. This review could provide their knowledge, which plays a role in seeing the patients with NAFLD/NASH in daily clinical practice. | Tatsuo Kanda Shunichi Matsuoka Motomi Yamazaki Toshikatsu Shibata Kazushige Nirei Hiroshi Takahashi Tomohiro Kaneko Mariko Fujisawa Teruhisa Higuchi Hitomi Nakamura Naoki Matsumoto Hiroaki Yamagami Masahiro Ogawa Hiroo Imazu Kazumichi Kuroda Mitsuhiko Moriyama | 2018 | World Journal of Gastroenterology2018，24，25： | 32 |
| 2 | Clinicopathological features of alpha-fetoprotein producing early gastric cancer with enteroblastic differentiation显示文摘AIM To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation(GCED).METHODS We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer(CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital.GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection rate.RESULTS Six cases(5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases(139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC(66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED(positivity, 83.3%), immunohistochemically.CONCLUSION Even in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological features of this highly malignant type of cancer. | Kohei Matsumoto Hiroya Ueyama Kenshi Matsumoto Yoichi Akazawa Hiroyuki Komori Tsutomu Takeda Takashi Murakami Daisuke Asaoka Mariko Hojo Natsumi Tomita Akihito Nagahara Yoshiaki Kajiyama Takashi Yao Sumio Watanabe | 2016 | World Journal of Gastroenterology2016，22，36： | 20 |
| 3 | Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer显示文摘AIM:To investigate human epidermal growth factor receptor 2(HER2)-phosphatidylinositol 3-kinase(PI3K)-vAkt murine thymoma viral oncogene homolog signaling pathway.METHODS:We analyzed 231 formalin-fixed,paraffinembedded gastric cancer tissue specimens from Japanese patients who had undergone surgical treatment.The patients' age,sex,tumor location,depth of invasion,pathological type,lymph node metastasis,and pathological stage were determined by a review of the medical records.Expression of HER2 was analyzed by immunohistochemistry(IHC) using the HercepTest TM kit.Standard criteria for HER2 positivity(0,1+,2+,and 3+) were used.Tumors that scored 3+ were considered HER2-positive.Expression of phospho Akt(pAkt) was also analyzed by IHC.Tumors were considered pAkt-positive when the percentage of positive tumor cells was 10% or more.PI3K,catalytic,alpha polypeptide(PIK3CA) mutations in exons 1,9 and 20 were analyzed by pyrosequencing.Epstein-Barr virus(EBV) infection was analyzed by in situ hybridization targeting EBV-encoded small RNA(EBER) with an EBER-RNA probe.Microsatellite instability(MSI) was analyzed by polymerase chain reaction using the mononucleotide markers BAT25 and BAT26.RESULTS:HER2 expression levels of 0,1+,2+ and 3+ were found in 167(72%),32(14%),12(5%) and 20(8.7%) samples,respectively.HER2 overexpression(IHC 3+) significantly correlated with intestinal histological type(15/20 vs 98 /205,P = 0.05).PIK3CA mutations were present in 20 cases(8.7%) and significantly correlated with MSI(10/20 vs 9/211,P < 0.01).The mutation frequency was high(21%) in T4 cancers and very low(6%) in T2 cancers.Mutations in exons 1,9 and 20 were detected in 5(2%),9(4%) and 7(3%) cases,respectively.Two new types of PIK3CA mutation,R88Q and R108H,were found in exon1.All PIK3CA mutations were heterozygous missense singlebase substitutions,the most common being H1047R(6/20,30%) in exon20.Eighteen cancers(8%) were EBV-positive and this positivity significantly correlated with a diffuse histological type(13/18 vs 93/198,P = 0.04).There were 7 cases of lymphoepithelioma-like carcinomas(LELC) and 6 of those cases were EBV-positive(percent/EBV:6/18,33%;percent/all LELC:6/7,86%).pAkt expression was positive in 119(53%) cases but showed no correlation with clinicopathological characteristics.pAkt expression was significantly correlated with HER2 overexpression(16/20 vs 103/211,P < 0.01) but not with PIK3CA mutations(12/20 vs 107/211,P = 0.37) or EBV infection(8/18 vs 103/211,P = 0.69).The frequency of pAkt expression was higher in cancers with exon20 mutations(100%) than in those with exon1(40%) or exon9(56%) mutations.One case showed both HER2 overexpression and EBV infection and 3 cases showed both PIK3CA mutations and EBV infection.However,no cases showed both PIK3CA mutations and HER2 overexpression.One EBVpositive cancer with PIK3CA mutation(H1047R) was MSI-positive.Three of these 4 cases were positive for pAkt expression.In survival analysis,pAkt expression significantly correlated with a poor prognosis(hazard ratio 1.75;95%CI:1.12-2.80,P = 0.02).CONCLUSION:HER2 expression,PIK3CA mutations and EBV infection in gastric cancer were characterized.pAkt expression significantly correlates with HER2 expression and with a poor prognosis. | Yasutaka Sukawa Hiroyuki Yamamoto Katsuhiko Nosho Hiroaki Kunimoto Hiromu Suzuki Yasushi Adachi Mayumi Nakazawa Takayuki Nobuoka Mariko Kawayama Masashi Mikami Takashi Matsuno Tadashi Hasegawa Koichi Hirata Kohzoh Imai Yasuhisa Shinomura | 2012 | World Journal of Gastroenterology2012，18，45： | 19 |
| 4 | Xanthogranulomatous cholecystitis:Difficulty in differentiating from gallbladder cancer显示文摘AIM: To compare cases of xanthogranulomatous cholecystitis(XGC) and advanced gallbladder cancer and discuss the differential diagnoses and surgical options.METHODS: From April 2000 to December 2013, 6 XGC patients received extended surgical resections. During the same period, 16 patients were proven to have gallbladder(GB) cancer, according to extended surgical resection. Subjects chosen for analysis in this study were restricted to cases of XGC with indistinct borders with the liver as it is often difficult to distinguish these patients from those with advanced GB cancer. We compared the clinical features and computed tomography findings between XGC and advanced GB cancer. The following clinical features were retrospectively assessed: age, gender, symptoms, and tumor markers. As albumin and the neutrophil/lymphocyte ratio(NLR) are prognostic in several cancers, we compared serum albumin levels and the NLR between the two groups. The computerized tomography findings were used to compare the two diseases, determine the coexistence of gallstones, the pattern of GB thickening(focal or diffuse), the presence of a hypoattenuated intramural nodule, and continuity of the mucosal line.RESULTS: Based on the preoperative image findings, we suspected GB carcinoma in all cases includingXGC in this series. In addition, by pathological examination, we found that the group of patients with XGC developed inflammatory disease after surgery. Patients with XGC tended to have abdominal pain(4/6, 67%). However, there was no significant difference in clinical symptoms, including fever, between the two groups. Serum albumin and NLR were also similar in the two groups. Serum tumor markers, such as carcinoembryonic antigen(CEA) and carbohydrate antigen 19-9(CA19-9), tended to increase in patients with GB cancer. However, no significant differences in tumor markers were identified. On the other hand, gallstones were more frequently observed in patients with XGC(5/6, 83%) than in patients with GB cancer(4/16, 33%)(P = 0.0116). A hypoattenuated intramural nodule was found in 3 patients with XGC(3/6, 50%), but in only 1 patient with GB cancer(1/16, 6%)(P = 0.0024). The GB thickness, continuous mucosal line, and bile duct dilatation showed no significant differences between XGC and GB cancer.CONCLUSION: Although XGC is often difficult to differentiate from GB carcinoma, it is possible to obtain an accurate diagnosis by careful intraoperative gross observation, and several intraoperative frozen sections. | Hideki Suzuki Satoshi Wada Kenichiro Araki Norio Kubo Akira Watanabe Mariko Tsukagoshi Hiroyuki Kuwano | 2015 | World Journal of Gastroenterology2015，21，35： | 18 |
| 5 | Usefulness of noninvasive transient elastography for assessment of liver fibrosis stage in chronic hepatitis C显示文摘AIM:To evaluate the method of noninvasive transient elastography for assessment of histological stage of liver fibrosis in patients with chronic hepatitis C (CHC). METHODS: Two hundred and thirty-seven patients with CHC were included in this study. Liver biopsy was performed under ultrasonography on 217 of the patients, excluding twenty with clear clinical evidence of liver cirrhosis. Fifty subjects without liver disease were enrolled as a control group (stage 0). Twenty- five patients with sustained virological response (SVR) to interferon (IFN) therapy were also enrolled. These patients underwent liver biopsy before IFN therapy. Examination of liver stiffness (LS) was performed by elastography. RESULTS: Medians (50% levels) of LS were 4.1 (3.5-4.9), 6.3 (4.8-8.5), 8.8 (6.8-12.0), 14.6 (10.5-18.6), and 22.2 (15.4-28.0), respectively, in the fibrosis stages 0-4 (P < 0.001). LS was significantly correlated with four serum fibrosis markers. LS values in patients with SVR were 3.8 (3.5-5.6), 5.2 (4.4-6.8), 6.8 (6.1-7.6), and 6.1 (3.6-7.9), respectively, in the fibrosis stages 1-4. In all stages, LS for patients with SVR was significantly lower than that for patients who did not undergo IFN therapy. LS was significantly correlated with serum concentrations of hyaluronic acid, type Ⅳ collagen, type Ⅳ collagen 7S, and type Ⅲ procollagen N peptide. CONCLUSION: LS correlated well with the histologicalstage of fibrosis. Changes in liver fibrosis stage may thus be estimated noninvasively using transient elastography. | Tadashi Takeda Takahiro Yasuda Yuji Nakayama Mika Nakaya Megumi Kimura Mariko Yamashita Ayumi Sawada Koji Abo Setsuko Takeda Hiroki Sakaguchi Susumu Shiomi Hitoshi Asai Shuichi Seki | 2006 | World Journal of Gastroenterology2006，12，48： | 16 |
| 6 | Mixed methods and survey research in family medicine and community health显示文摘Many family medicine and community health researchers use surveys as an original research methodology.Our purpose is to illustrate how survey research provides an important form of quantitative research that can be effectively combined with qualitative data to form a mixed methods study.We first provide an overview of the key principles in survey research and in mixed methods research.We review the various ways that survey can be used in mixed methods studies,citing options such as beginning a study with a survey,using a survey as the second form of data collection,or combining a survey and a form of qualitative data in a single data collection procedure.Finally,we illustrate in a specific example six steps in conducting a mixed methods study using survey research.In a mixed methods study using a survey,primary care researchers should consider six steps.Step 1.Articulate the rationale for mixed methods study.Step 2.Detail quantitative and qualitative databases.Step 3.Identify a mixed methods design.Step 4.Analyse and report the results of the quantitative and qualitative databases.Step 5.Present and show integration.Step 6.Explicate the value of using mixed methods.The ability to combine and integrate survey research into a mixed methods study provides a more rigorous approach to research than conducting only a survey or conducting just a qualitative interview.While requiring skills beyond traditional survey approaches,surveys in primary care offers an opportunity for a high level of sophistication in research methodology. | John W Creswell Mariko Hirose | 2019 | Family Medicine and Community Health2019，7，2： | 16 |
| 7 | Efficacy of acupuncture during post-acute phase of rehabilitation after total knee arthroplasty显示文摘OBJECTIVE:The purpose of this study was to determine whether acupuncture is effective in reducing pain and swelling around the knee and improving range of motion(ROM) during the post-acute phase of rehabilitation after total knee arthroplasty(TKA).METHODS:Following TKA,80 knees in 80 patients were randomly assigned to either an acupuncture treatment group(Group A) or a control group(Group C).In Group A,the complementary treatment of acupuncture was performed three times/week from postoperative day 7 until postoperative day 21.Outcome measures were:i) pain as assessed by a visual analog scale;ii) reduction of swelling around the knee as indicated by its circumference at the center of the patella;and iii) ROM of the affected knee.RESULTS:Group A patients had significantly reduced pain and swelling around the knees and earlier recovery of ROM than did those in Group C.CONCLUSION:Acupuncture provides effective treatment during the post-acute phase of rehabilitation after TKA with respect to pain relief,reduction of swelling around the knee,and early recovery of ROM. | Yoshinori Mikashima Tadashi Takagi Taisuke Tomatsu Mariko Horikosh Katsunori Ikari Shigeki Momohara | 2012 | Journal of Traditional Chinese Medicine2012，32，4： | 11 |
| 8 | Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers显示文摘AIM: To clarify the expression and role of Ephrin receptor A4 (EphA4) in gastric cancer in relation to clinicopathological characteristics and the expression of fibroblast growth factor receptor 1 (FGFR1) and ephrin ligands. METHODS: Eleven gastric carcinoma cell lines, 24 paired surgical fresh specimens of gastric adenocarcinoma and adjacent nontumor tissue, 74 conventional formalin-fixed, paraffin-embedded tumor specimens, and 55 specimens spotted on tissue microarray (TMA) were analyzed. Reverse transcription-PCR (RT-PCR), real-time RT-PCR, immunohistochemistry, and cell growth assays were performed. RESULTS: Overexpression of EphA4 mRNA expres-sion was observed in 8 (73%) of 11 gastric cancer cell lines and 10 (42%) of 24 gastric cancer tissues. Over-expression of EphA4, analyzed by immunohistochemistry, was observed in 62 (48%) of 129 gastric cancer tissues. EphA4 overexpression, at the protein level, was significantly associated with depth of invasion and recurrence. EphA4 overexpression was also correlated with FGFR1 overexpression. Patients with EphA4-positive cancer had significantly shorter overall survival periods than did those with EphA4-negative cancer (P = 0.0008). The mRNAs for ephrin ligands were coexpressed in various combinations in gastric cancer cell lines and cancer tissues. Downregulation of EphA4 expression by siRNA in EphA4-overexpressing gastric cancer cell lines resulted in a significant decrease in cell growth. CONCLUSION: Our results suggest that overexpres-sion of EphA4 plays a role in gastric cancer. | Mariko Oki Hiroyuki Yamamoto Hiroaki Taniguchi Yasushi Adachi Kohzoh Imai Yasuhisa Shinomura | 2008 | World Journal of Gastroenterology2008，14，37： | 11 |
| 9 | Promoted differentiation of cynomolgus monkey ES cells into hepatocyte-like cells by co-culture with mouse fetal liver-derived cells显示文摘AIM: To explore whether a co-culture of cynomolgus monkey embryonic stem (cES) cells with embryonic liver cells could promote their differentiation into hepatocytes. METHODS: Mouse fetal liver-derived cells (MFLCs) were prepared as adherent cells from mouse embryos on embryonic d (ED) 14, after which undifferentiated cES cells were co-cultured with MFLCs. The induction of cES cells along a hepatic lineage was examined in MFLC- assisted differentiation, spontaneous differentiation, and growth factors (GF) and chemicals-induced differentiations (GF-induced differentiation) using retinoic acid, leukemia inhibitory factor (LIF), FGF2, FGF4, hepatocyte growth factor (HGF), oncostatin M (OSM), and dexamethasone. RESULTS: The mRNA expression of α-fetoprotein, albumin (ALB), α-1-antitrypsin, and hepatocyte nuclear factor 4α was observed earlier in the differentiating cES cells co-cultured with MFLCs, as compared to cES cells undergoing spontaneous differentiation and those subjected to GF-induced differentiation. The expression of cytochrome P450 7a1, a possible marker for embryonic endoderm-derived mature hepatocytes, was only observed in cES cells that had differentiated in a co-culture with MFLCs. Further, the disappearance of Oct3/4, a representative marker of an undifferentiated state, was noted in cells co-cultured with MFLCs, but not in those undergoing spontaneous or GF-induced differentiation. Immunocytochemical analysis revealed an increased ratio of ALB-immunopositive cells among cES cells co-cultured with MFLCs, while glycogen storageand urea synthesis were also demonstrated. CONCLUSION: MFLCs showed an ability to induce cES cells to differentiate toward hepatocytes. The co-culture system with MFLCs is a useful method for induction of hepatocyte-like cells from undifferentiated cES cells. | Ko Saito Masahide Yoshikawa Yukiteru Ouji Kei Moriya Mariko Nishiofuku Shigehiko Ueda Noriko Hayashi Shigeaki Ishizaka Hiroshi Fukui | 2006 | World Journal of Gastroenterology2006，12，42： | 11 |
| 10 | Nitrative and oxidative DNA damage in intrahepatic cholangiocarcinoma patients in relation to tumor invasion显示文摘AIM: Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine(8-oxodG) formation has been implicated in initiation and/or promotion of inflammation-mediated carcinogenesis.The aim of this study is to clarify whether these DNA lesions participate in the progression of intrahepatic cholangiocarcinoma.METHODS: We investigated the relation of the formation of 8-nitroguanine and 8-oxodG and the expression of hypoxia-inducible factor-1α (HIF-1α) with tumor invasion in 37 patients with intra-hepatic cholangiocarcinoma.RESULTS: Immunohistochemical analyses revealed that 8-nitroguanine and 8-oxodG formation occurred to a much greater extent in cancerous tissues than in non-cancerous tissues. HIF-1α could be detected in cancerous tissues in all patients, suggesting low oxygen tension in the tumors.HIF-1α expression was correlated with inducible nitric oxide synthase (iNOS) expression (r= 0.369 and P = 0.025)and 8-oxodG formation (r = 0.398 and P = 0.015).Double immunofluorescence study revealed that iNOS and HIF-1α co-localized in cancerous tissues. Notably, the formation of 8-oxodG was correlated significantly with lymphatic invasion (r = 0.386 and P= 0.018). Moreover, 8-nitroguanine and 8-oxodG in non-cancerous tissues were associated significantly with neural invasion (P = 0.042and P = 0.026, respectively). These results suggest that reciprocal activation between HIF-1α and iNOS mediates persistent DNA damage, which induces tumor invasiveness via mutations, resulting in poor prognosis.CONCLUSION: The formation of 8-nitroguanine and 8-oxodG plays an important role in multiple steps of genetic changes leading to tumor progression, including invasiveness. | Somchai Pinlaor Banchob Sripa Ning Ma Yusuke Hiraku Puangrat Yongvanit Sopit Wongkham Chawalit Pairojkul Vajarabhongsa Bhudhisawasdi Shinji Oikawa Mariko Murata Reiji Semba Shosuke Kawanishi | 2005 | World Journal of Gastroenterology2005，11，30： | 9 |
| 11 | Hunt for the tipping point during endocrine resistance process in breast cancer by dynamic network biomarkers显示文摘Acquired drug resistance is the major reason why patients fail to respond to cancer therapies.It is a challenging task to deter.mine the tipping point of endocrine resistance and detect the associated molecules.Derived from new systems biology theory, the dynamic network biomarker (DNB) method is designed to quantitatively identify the tipping point of a drastic system transition and can theoretically identify DNB genes that play key roles in acquiring drug resistance.We analyzed time-course mRNA sequence data generated from the tamoxifen-treated estrogen receptor (ER)-positive MCF-7 cell line, and identified the tipping point of endocrine resistance with its leading molecules.The results show that there is interplay between gene mutations and DNB genes, in which the accumulated mutations eventually affect the DNB genes that subsequently cause the change of transcriptional landscape, enabling full-blown drug resistance. Survival analyses based on clinical datasets validated that the DNB genes were associated with the poor survival of breast cancer patients.The results provided the detection for the pre-resistance state or early signs of endocrine resistance.Our predictive method may greatly benefit the scheduling of treatments for complex diseases in which patients are exposed to considerably different drugs and may become drug resistant. | Rui Liu Jinzeng Wang Masao Ukai Ki Sewon Pei Chen Yutaka Suzuki Haiyun Wang Kazuyuki Aihara Mariko Okada-Hatakeyama Luonan Chen | 2019 | Journal of Molecular Cell Biology2019，11，8： | 7 |
| 12 | Improved techniques for double-balloon-enteroscopy-assisted endoscopic retrograde cholangiopancreatography显示文摘AIM: To investigate the clinical outcome of double balloon enteroscopy (DBE)-assisted endoscopic retrograde cholangiopancreatography (DB-ERCP) in patients with altered gastrointestinal anatomy. METHODS: Between September 2006 and April 2011, 47 procedures of DB-ERCP were performed in 28 patients with a Roux-en-Y total gastrectomy (n = 11), Billroth Ⅱ gastrectomy (n = 15), or Roux-en-Y anastomosis with hepaticojejunostomy (n = 2). DB-ERCP was performed using a short-type DBE combined with several technical innovations such as using an endoscope attachment, marking by submucosal tattooing,selectively applying contrast medium, and CO2 insufflations. RESULTS: The papilla of Vater or hepaticojejunostomy site was reached in its entirety with a 96% success rate (45/47 procedures). There were no significant differences in the success rate of reaching the blind end with a DBE among Roux-en-Y total gastrectomy (96%), Billroth Ⅱ reconstruction (94%), or pancreatoduodenectomy (100%), respectively (P = 0.91). The total successful rate of cannulation and contrast enhancement of the target bile duct in patients whom the blind end was reached with a DBE was 40/45 procedures (89%). Again, there were no significant differences in the success rate of cannulation and contrast enhancement of the target bile duct with a DBE among Roux-en-Y total gastrectomy (88 %), Billroth Ⅱ reconstruction (89%), or pancreatoduodenectomy (100%), respectively (P = 0.67). Treatment was achieved in all 40 procedures (100%) in patients whom the contrast enhancement of the bile duct was successful. Common endoscopic treatments were endoscopic biliary drainage (24 procedures) and extraction of stones (14 procedures). Biliary drainage was done by placement of plastic stents. Stones extraction was done by lithotomy with the mechanical lithotripter followed by extraction with a basket or by the balloon pull-through method. Endoscopic sphincterotomy was performed in 14 procedures with a needle precutting knife using a guidewire. The mean total duration of the procedure was 93.6 ± 6.8 min and the mean time required to reach the papilla was 30.5 ± 3.7 min. The mean time required to reach the papilla tended to be shorter in Billroth Ⅱ reconstruction (20.9 ± 5.8 min) than that in Roux-en-Y total gastrectomy (37.1 ± 4.9 min) but there was no significant difference (P = 0.09). A major complication occurred in one patient (3.5%); perforation of the long limb in a patient with Billroth Ⅱ anastomosis.CONCLUSION: Short-type DBE combined with several technical innovations enabled us to perform ERCP in most patients with altered gastrointestinal anatomy. | Takashi Osoegawa Yasuaki Motomura Kazuya Akahoshi Naomi Higuchi Yoshimasa Tanaka Terumasa Hisano Souichi Itaba Junya Gibo Mariko Yamada Masaru Kubokawa Yorinobu Sumida Hirotada Akiho Eikichi Ihara Kazuhiko Nakamura | 2012 | World Journal of Gastroenterology2012，18，46： | 7 |
| 13 | Inducible nitric oxide synthase polymorphism is associated with the increased risk of differentiated gastric cancer in a Japanese population显示文摘AIM: To examine the association of inducible nitric oxide synthase (iNOS) C150T polymorphism with gastric cancer, as well as with gastric atrophy and H pylori seropositivity. METHODS: A single nucleotide polymorphism of iNOS C150T was examined for 454 Japanese health checkup examinees (126 males and 328 females) aged 35 to 85 years without a history of cancer and 202 gastric cancer patients (134 males and 68 females) aged 33 to 94 years with pathologically confirmed diagnosis of gastric adenocarcinoma. RESULTS: The iNOS C150T polymorphism was not associated with gastric atrophy or with H pylori seropositivity. The odds ratio (OR) of the C/T + T/T for gastric cancer was increased without statistical significance (OR=1.19, 95% confidence interval (CI): 0.68-2.08). In the differentiated subgroup (n = 113), however, the OR of the C/T genotype for gastric cancer was significant (OR = 2.02, 95% CI: 1.04-3.92) relative to the C/C genotype. In addition, considering the location of gastric cancer (n = 105), there were significant differences between the controls and non-cardia group with the OR of 2.13 (95% CI: 1.08-4.18) for C/T and 1.94 (95% CI: 1.00-3.78) for C/T + T/T. CONCLUSION: The iNOS C150T polymorphism is associated with the risk of H pylori-related gastric cancerin a Japanese population. This polymorphism may play an important role in increasing the risk of gastric cancer in Asian countires with the highest rates of gastric cancer. | Yasuyuki Goto Takafumi Ando Mariko Naito Hidemi Goto Nobuyuki Hamajima | 2006 | World Journal of Gastroenterology2006，12，39： | 6 |
| 14 | Post-polypectomy bleeding and thromboembolism risks associated with warfarin vs direct oral anticoagulants显示文摘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. | Naohiro Yanagisawa Naoyoshi Nagata Kazuhiro Watanabe Tatsuhiro Iida Mariko Hamada Sakurako Kobayashi Takuro Shimbo Junichi Akiyama Naomi Uemura | 2018 | World Journal of Gastroenterology2018，24，14： | 6 |
| 15 | Randomized controlled trial of bipolar diathermy vs ultrasonic scalpel for closed hemorrhoidectomy显示文摘AIM:To compare hemorrhoidectomy with a bipolar electrothermal device or hemorrhoidectomy using an ultrasonically activated scalpel.METHODS:Sixty patients with grade Ⅲ or Ⅳ hemorrhoids were prospectively randomized to undergo closed hemorrhoidectomy assisted by bipolar diathermy(group 1) or hemorrhoidectomy with the ultrasonic scalpel(group 2).Operative data were recorded,and patients were followed at 1,3,and 6 wk to evaluate complications.Independent assessors were assigned to obtain postoperative pain scores,oral analgesic requirement and satisfaction scores.RESULTS:Reduced intraoperative blood loss median 0.9 mL(95% CI:0.8-3.7) vs 4.6 mL(95% CI:3.8-7.0),P = 0.001 and a short operating time median 16(95% CI:14.6-18.2) min vs 31(95% CI:28.1-35.3) min,P < 0.0001 was observed in group 1 compared with group 2.There was a trend towards lower postoperative pain scores on day 1 group 1 median 2(95% CI:1.8-3.5) vs group 2 median 3(95% CI:2.6-4.2),P = 0.135.Reduced oral analgesic requirement during postoperative 24 h after operation median 1(95% CI:0.4-0.9) tablet vs 1(95% CI:0.9-1.3) tablet,P = 0.006 was observed in group 1 compared with group 2.There was no difference between the two groups in the degree of patient satisfaction or number of postoperative complications.CONCLUSION:Bipolar diathermy hemorrhoidectomy is quick and bloodless and,although as painful as closed hemorrhoidectomy with the ultrasonic scalpel,is associated with a reduced analgesic requirement immediately after operation. | Akira Tsunoda Haruki Sada Takuya Sugimoto Nobuyasu Kano Mariko Kawana Tadanori Sasaki Hideki Hashimoto | 2011 | World Journal of Gastrointestinal Surgery2011，3，10： | 6 |
| 16 | H pylori seropositivity and cytokine gene polymorphisms显示文摘AIM: To investigate whether the pro- and anti-inflammatory cytokine gene polymorphisms, IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G, interact with smoking and drinking habits to influence infection with H pylori.METHODS: The subjects were 410 Japanese transit company employees. C-reactive protein and conventional cardiovascular risk factors were evaluated. Serum anti-H pylori antibodies were measured. The genotypes of IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G polymorphisms were determined by allelic discrimination using fluorogenic probes and a 5′nuclease assay.RESULTS: In gender- and age-adjusted logistic analyses, the subjects with TNF-857T/T had a significantly lower odds ratio (OR) for H pylori seropositivity (reference -857C/C; OR = 0.15, 95% CI: 0.03-0.59, P = 0.007). After stratification according to smoking and drinking status, among never-smokers, the subjects with IL1B-511C/T had a significantly lower OR (reference -511C/C; OR = 0.30, 95% CI: 0.10-0.90, P = 0.032). Among drinkers in the 1-5 times/wk category, the subjects with IL1B-511T/T had a significantly lower OR (reference C/C; OR = 0.38, 95% CI: 0.16-0.95, P = 0.039), and the subjects with IL1B-31C/T and T/T had a significantly higher OR (reference C/C; C/T: OR = 2.59, 95% CI, P = 0.042: 1.04-6.47; C/C: OR = 3.17, 95% CI: 1.23-8.14, P = 0.017). Among current smokers, the subjects withIL6-634C/G had a significantly higher OR (reference C/C; OR = 2.28, 95% CI: 1.13-4.58, P = 0.021). However, the interactions terms between the aforementioned genotypes and lifestyles were not statistically significant.CONCLUSION: Contrary to previous findings, the results herein suggest that the TNF-857T/T genotype may be protective against chronic infection with H pylori. Drinking and smoking habits may influence the effect of cytokine gene polymorphisms. Further studies are required to clarify the effects of the pro- and anti-inflammatory cytokine polymorphisms and gene-environmental interactions on H pylori infection. | Yasuaki Saijo Eiji Yoshioka Tomonori Fukui Mariko Kawaharada Fumihiro Sata Hirokazu Sato Reiko Kishi | 2007 | World Journal of Gastroenterology2007，13，33： | 5 |
| 17 | Transcriptional factors, Mafs and their biological roles显示文摘The Maf family of transcription factors is characterized by a typical b Zip structure; these transcription factors act as important regulators of the development and differentiation of many organs and tissues, including the kidney. The Maf family consists of two subgroups that are characterized according to their structure: large Maf transcription factors and small Maf transcriptionfactors. The large Maf subgroup consists of four proteins, designated as MAFA, MAFB, c-MAF and neural retina-specific leucine zipper. In particular, MAFA is a distinct molecule that has been attracting the attention of researchers because it acts as a strong transactivator of insulin, suggesting that Maf transcription factors are likely to be involved in systemic energy homeostasis. In this review, we focused on the regulation of glucose/energy balance by Maf transcription factors in various organs. | Mariko Tsuchiya Ryoichi Misaka Kosaku Nitta Ken Tsuchiya | 2015 | World Journal of Diabetes2015，6，1： | 5 |
| 18 | Embryonic stem cells develop into hepatocytes after intrasplenic transplantation in CCl_4-treated mice显示文摘AIM: To transplant undifferentiated embryonic stem (ES) cells into the spleens of carbon tetrachloride (CCl4)-treated mice to determine their ability to differentiate into hepatocytes in the liver. METHODS: CCl4, 0.5 mL/kg body weight, was injected into the peritoneum of C57BL/6 mice twice a week for 5 wk. In group 1 (n = 12), 1 x 105 undifferentiated ES cells (0.1 mL of 1 x 106/mL solution), genetically labeled with GFP, were transplanted into the spleens 1 d after the second injection. Group 2 mice (n = 12) were injected with 0.2 mL of saline twice a week, instead of CCl4, and the same amount of ES cells was transplanted into the spleens. Group 3 mice (n = 6) were treated with CCl4 and injected with 0.1 mL of saline into the spleen, instead of ES cells. Histochemical analyses of the livers were performed on post-transplantation d (PD) 10, 20, and 30. RESULTS: Considerable numbers of GFP-immunopositive cells were found in the periportal regions in group 1 mice (CCl4-treated) on PD 10, however, not in those untreated with CCl4 (group 2). The GFP-positive cells were also immunopositive for albumin (ALB), alpha-1 antitrypsin, cytokeratin 18, and hepatocyte nuclear factor 4 alpha on PD 20. Interestingly, most of the GFP-positive cells were immunopositive for DLK, a hepatoblast marker, on PD 10. Although very few ES-derived cells were demonstrated immunohistologically in the livers of group 1 mice on PD 30, improvements in liver fibrosis were observed. Unexpectedly, liver tumor formation was not observed in any of the mice that received ES cell transplantationduring the experimental period. CONCLUSION: Undifferentiated ES cells developed into hepatocyte-like cells with appropriate integration into tissue, without uncontrolled cell growth. | Kei Moriya Masahide Yoshikawa Ko Saito Yukiteru Ouji Mariko Nishiofuku Noriko Hayashi Shigeaki Ishizaka Hiroshi Fukui | 2007 | World Journal of Gastroenterology2007，13，6： | 5 |
| 19 | Long‐term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection显示文摘 | Tetsuya Hosaka Fumitaka Suzuki Masahiro Kobayashi Yuya Seko Yusuke Kawamura Hitomi Sezaki Norio Akuta Yoshiyuki Suzuki Satoshi Saitoh Yasuji Arase Kenji Ikeda Mariko Kobayashi Hiromitsu Kumada | 2013 | Hepatology2013，，： | 5 |
| 20 | Contrast-enhanced ultrasonographic findings of serum amyloid A-positive hepatocellular neoplasm: Does hepatocellular adenoma arise in cirrhotic liver?显示文摘Hepatocellular adenoma(HCA) was recently classified into four pathological subtypes. There have been few studies describing the findings of contrast-enhanced ultrasonography(CEUS) of each type. Our case concerns a 78-year-old man who had undergone routine medical check-ups for hepatitis C for 11 years. Abdominal ultrasonography showed a 28 mm, hypo-echoic mass in the segment 4 of the liver. His integrating amount of drinking was 670 kg convert into ethanol. CEUS with Sonazoid demonstrated mild uniform hypo-enhancement with inflow of microbubbles from the periphery of the tumor in the arterial phase, and heterogeneously hypo-enhancement in the post vascular phase. Because the mass increased in size within 3 mo, a well differentiated hepatocellular carcinoma was suspected, and hepatic resection was performed. Microscopic findings showed homogeneous cell proliferation with low grade atypia, infiltration of inflammatory cells, ductular reactions, fatty deposit in part, and sinusoidal dilation. Immunohistochemistry revealed geographic positive for serum amyloid A(SAA), focal positive for glutaminesynthetase, diffuse and strong positive for C-reactive protein, and positive for liver-type fatty acid binding protein. These pathological features corresponded to that of an inflammatory HCA. However, we could not make a clear diagnosis, because HCAs were defined as not to arise in cirrhotic liver. Finally, this tumor was diagnosed as a SAA positive hepatocellular neoplasm. | Mariko Kumagawa Naoki Matsumoto Yukinobu Watanabe Midori Hirayama Takao Miura Hiroshi Nakagawara Masahiro Ogawa Shunichi Matsuoka Mitsuhiko Moriyama Tadatoshi Takayama Masahiko Sugitani | 2016 | World Journal of Hepatology2016，8，26： | 4 |
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