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| 1 | Association of Fusobacterium nucleatum with immunity andmolecular alterations in colorectal cancer显示文摘The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6%(44/511), which was lower than that in United States cohort studies(13%). Similar to the United States studies, F. nucleatum positivityin Japanese colorectal cancers was significantly associated with microsatellite instability(MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets(i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain micro RNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. Micro RNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may provide insights for strategies to target microbiota, immune cells and tumor molecular alterations for colorectal cancer prevention and treatment. Further investigation is needed to clarify the association of Fusobacterium with T-cells and micro RNA expressions in colorectal cancer. | Katsuhiko Nosho Yasutaka Sukawa Yasushi Adachi Miki Ito Kei Mitsuhashi Hiroyoshi Kurihara Shinichi Kanno Itaru Yamamoto Keisuke Ishigami Hisayoshi Igarashi Reo Maruyama Kohzoh Imai Hiroyuki Yamamoto Yasuhisa Shinomura | 2016 | World Journal of Gastroenterology2016，22，2： | 44 |
| 2 | Role of autophagy in the pathogenesis of inflammatory bowel disease显示文摘Inflammatory bowel disease(IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system.Recently, some studies provided strong evidence that the process of autophagy affects several aspects of mucosal immune responses. Autophagy is a cellular stress response that plays key roles in physiological processes, such as innate and adaptive immunity, adaptation to starvation, degradation of aberrant proteins or organelles, antimicrobial defense, and protein secretion. Dysfunctional autophagy is recognized as a contributing factor in many chronic inflammatory diseases, including IBD. Autophagy plays multiple roles in IBD pathogenesis by altering processes that include intracellular bacterial killing, antimicrobial peptide secretion by Paneth cells, goblet cell function, proinflammatory cytokine production by macrophages, antigen presentation by dendritic cells, and the endoplasmic reticulum stress response in enterocytes. Recent studies have identified susceptibility genes involved in autophagy, such as NOD2, ATG16L1, and IRGM, and active research is ongoing all over the world. The aim of this review is a systematic appraisal of the current literature to provide a better understanding of the role of autophagy in the pathogenesis of IBD. Understanding these mechanisms will bring about new strategies for the treatment and prevention of IBD. | Tomoya Iida Kei Onodera Hiroshi Nakase | 2017 | World Journal of Gastroenterology2017，23，11： | 27 |
| 3 | Risk factors for bleeding after endoscopic mucosal resection显示文摘AIM: To clarify the risk factors for bleeding after endoscopic mucosal resection (EMR).METHODS: A total of 297 consecutive patients who underwent EMR were enrolled. Some of the patients had multiple lesions. Bleeding requiring endoscopic treatment was defined as bleeding after EMR. Odds ratios (OR) with 95% confidence intervals (CI), calculated by logistic regression with multivariate adjustments for covariates,were the measures of association.RESULTS: Of the 297 patients, 57 (19.2%) patients with bleeding after EMR were confirmed. With multivariate adjustment, the cutting method of ENR, diameter, and endoscopic pattern of the tumor were associated with the risk of bleeding after ENR. The multivariate-adjusted OR for bleeding after EMR using endoscopic aspiration mucosectomy was 3.07 (95%CI, 1.59-5.92) compared with strip biopsy. The multiple-adjusted OR for bleeding after EMR for the highest quartile (16-50 mm) of tumor diameter was 5.63 (95%CI, 1.84-17.23) compared with that for the lowest (4-7 mm). The multiple-adjusted OR for bleeding after EM R for depressed type of tumor was 4.21 (95%CI, 1.75-10.10) compared with elevated type.CONCLUSION: It is important to take tumor characteristics (tumor size and endoscopic pattern) and cutting method of EMR into consideration in predicting bleeding after ENR. | Masatsugu Shiba Kazuhide Higuchi Kaori Kadouchi Ai Montani Kazuki Yamamori Hirotoshi Okazaki Makiko Taguchi Tomoko Wada Atsushi Itani Toshio Watanabe Kazunari Tominaga Yoshihiro Fujiwara Tomoshige Hayashi Kei Tsumura Tetsuo Arakawa | 2005 | World Journal of Gastroenterology2005，11，46： | 25 |
| 4 | Relationship between post-ERCP pancreatitis and the change of serum amylase level after the procedure显示文摘AIM: To clarify the relationship between the change of serum amylase level and post-ERCP pancreatitis. METHODS: Between January 1999 and December 2002, 1291 ERCP-related procedures were performed. Serum amylase concentrations were measured before the procedure and 3, 6, and 24 h afterward. The frequency and severity of post-ERCP pancreatitis and the relationship between these phenomena and the change in amylase level were estimated. RESULTS: Post-ERCP pancreatitis occurred in 47 patients (3.6%). Pancreatitis occurred in 1% of patients with normal amylase levels 3 h after ERCP, and in 1%, 5%, 20%, 31% and 39% of patients with amylase levels elevated 1-2 times, 2-3 times, 3-5 times, 5-10 times and over 10 times the upper normal limit at 3 h after ERCP, respectively (level < 2 times vs ≥ 2 times, P < 0.001). Of the 143 patients with levels higher than the normal limit at 3 h after ERCP followed by elevation at 6 h, pancreatitis occurred in 26%. In contrast, pancreatitis occurred in 9% of 45 patients with a level higher than two times the normal limit at 3 h after ERCP followed by a decrease at 6 h (26% vs 9%, P < 0.05). CONCLUSION: Post-ERCP pancreatitis is frequently associated with an increase in serum amylase level greater than twice the normal limit at 3 h after ERCP with an elevation at 6 h. A decrease in amylase level at 6 h after ERCP suggests the unlikelihood of development of post-ERCP pancreatitis. | Kei Ito Naotaka Fujita Yutaka Noda Go Kobayashi Jun Horaguchi Osamu Takasawa Takashi Obana | 2007 | World Journal of Gastroenterology2007，13，28： | 19 |
| 5 | Optimal treatment for Siewert type Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction: A retrospective cohort study with long-term follow-up显示文摘AIM To determine the optimal treatment strategy for Siewert type Ⅱ and?Ⅲ?adenocarcinoma of the esophagogastric junction.METHODS We retrospectively reviewed the medical records of 83 patients with Siewert type?Ⅱ?and?Ⅲ?adenocarcinoma of the esophagogastric junction and calculated both an index of estimated benefit from lymph node dissection for each lymph node(LN) station and a lymph node ratio(LNR: ratio of number of positive lymph nodes to the total number of dissected lymph nodes). We used Cox proportional hazard models to clarify independent poor prognostic factors. The median duration of observation was 73 mo.RESULTS Indices of estimated benefit from LN dissection were as follows, in descending order: lymph nodes(LN) along the lesser curvature, 26.5; right paracardial LN, 22.8; left paracardial LN, 11.6; LN along the left gastric artery, 10.6. The 5-year overall survival(OS) rate was 58%. Cox regression analysis revealed that vigorous venous invasion(v2, v3)(HR = 5.99; 95%CI: 1.71-24.90) and LNR of > 0.16(HR = 4.29, 95%CI: 1.79-10.89) were independent poor prognostic factors for OS.CONCLUSION LN along the lesser curvature, right and left paracardial LN, and LN along the left gastric artery should be dissected in patients with Siewert type?Ⅱ?or?Ⅲ?adenoca rcinoma of the esophagogastric junction. Patients with vigorous venous invasion and LNR of > 0.16 should be treated with aggressive adjuvant chemotherapy to improve survival outcomes. | Kei Hosoda Keishi Yamashita Hiromitsu Moriya Hiroaki Mieno Masahiko Watanabe | 2017 | World Journal of Gastroenterology2017，23，15： | 19 |
| 6 | Distinct memory traces for two visual features in the Drosophila brain显示文摘 | Gang Liu Holger Seiler Ai Wen Troy Zars Kei Ito Reinhard Wolf Martin Heisenberg Li Liu | 2006 | 中国生物学文摘2006，20，3： | 17 |
| 7 | Pneumatosis cystoides intestinalis following alpha-glucosidase inhibitor treatment:A case report and review of the literature显示文摘A 69-year-old man was diagnosed as having myasthenia gravis (MG) in September 2004,and treated with thymectomy and prednisolone. He was then diagnosed as having steroid-induced diabetes mellitus,and received sulfonylurea (SU) therapy in May 2005. An alpha-glucosidase inhibitor (αGI) was added in March 2006,resulting in good glycemic control. He experienced symptoms of abdominal distention,increased flatus,and constipation in October 2007,and was admitted into our hospital in late November with hematochezia. Plain abdominal radiography revealed small linear radiolucent clusters in the wall of the colon. Computed tomography (CT) showed intramural air in the sigmoid colon. Colonoscopy revealed multiple smooth surfaced hemispherical protrusions in the sigmoid colon. The diagnosis of pneumatosis cystoides intestinalis (PCI) was made on the basis of these findings. As the αGI voglibose was suspected as the cause of this patient's PCI,treatment was conservative,ceasing voglibose,with fasting and fluid supplementation. The patient progressed well,and was discharged 2 wk later. Recently,several reports of PCI associated with αGI therapy have been published,predominantly in Japan where αGIs are commonly used. If the use of αGIs becomes more widespread,we can expect more reports of this condition on a global scale. The possibility of PCI should be considered in diabetic patients complaining of gastrointestinal symptoms,and the gastrointestinal tract should be thoroughly investigated in these patients. | Tatsuhiro Tsujimoto Erika Shioyama Kei Moriya Hideto Kawaratani Yasuyo Shirai Masahisa Toyohara Akira Mitoro Jun-ichi Yamao Hisao Fujii Hiroshi Fukui | 2008 | World Journal of Gastroenterology2008，14，39： | 16 |
| 8 | Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease显示文摘Non-alcoholic fatty liver disease(NAFLD) is a common health problem with a high mortality burden due to its liver- and vascular-specific complications. It is associated with obesity, high-fat diet as well as with type 2 diabetes mellitus(T2DM) and metabolic syndrome(MetS).Impaired hepatic fatty acid(FA) turnover together with insulin resistance are key players in NAFLD pathogenesis. Peroxisome proliferator-activated receptors(PPARs)are involved in lipid and glucose metabolic pathways.The novel concept is that the activation of the PPARαsubunit may protect from liver steatosis. Fenofibrate, by activating PPARα, effectively improves the atherogenic lipid profile associated with T2DM and MetS. Experimental evidence suggested various protective effects of the drug against liver steatosis. Namely, fenofibraterelated PPARα activation may enhance the expression of genes promoting hepatic FA β-oxidation. Furthermore, fenofibrate reduces hepatic insulin resistance. It also inhibits the expression of inflammatory mediators involved in non-alcoholic steatohepatitis pathogenesis.These include tumor necrosis factor-α, intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1and monocyte chemoattractant protein-1. Consequently, fenofibrate can limit hepatic macrophage infiltration. Other liver-protective effects include decreased oxidative stress and improved liver microvasculature function. Experimental studies showed that fenofibrate can limit liver steatosis associated with high-fat diet,T2DM and obesity-related insulin resistance. Few studies showed that these benefits are also relevant even in the clinical setting. However, these have certain limitations. Namely, these were uncontrolled, their sample size was small, fenofibrate was used as a part of multifactorial approach, while histological data were absent.In this context, there is a need for large prospective studies, including proper control groups and full assessment of liver histology. | Michael S Kostapanos Anastazia Kei Moses S Elisaf | 2013 | World Journal of Hepatology2013，5，9： | 16 |
| 9 | Non-invasive determination of hepatic steatosis by acoustic structure quantification from ultrasound echo amplitude显示文摘AIM:To use leptin-deficient(ob/ob) mice with demonstrated differences in steatosis levels to test a new diagnostic method using the acoustical structure quantification(ASQ) mode and the associated analytical parameter,'focal disturbance ratio'(FD-ratio).METHODS:Nine ob/ob mice,at 5,8,and 12 wk of age(n = 3 in each age group),were used as models for hepatic steatosis.Echo signals obtained from ultrasonography in the mice were analyzed by ASQ,which uses a statistical analysis of echo amplitude to estimate inhomogeneity in the diagnostic region.FD-ratio,as calculated from this analysis,was the focus of the present study.FD-ratio and fat droplet areas and sizes were compared between age groups.RESULTS:No fibrosis or inflammation was observed in any of the groups.The fat droplet area significantly(P < 0.01) increased with age from 1.25% ± 0.28% at 5 wk to 31.07% ± 0.48% at 8 wk to 51.69% ± 3.19% at 12 wk.The median fat droplet size also significantly(P < 0.01) increased with age,from 1.33(0.55-10.52) m at 5 wk,2.82(0.61-44.13) m at 8 wk and 6.34(0.66-81.83) m at 12 wk.The mean FD-ratio was 0.42 ± 0.11 at 5 wk,0.11 ± 0.05 at 8 wk,and 0.03 ± 0.02 at 12 wk.The FD-ratio was significantly lower at 12 wk than at 5 wk and 8 wk(P < 0.01).A significant negative correlation was observed between the FD-ratio and either the fat droplet area(r =-0.7211,P = 0.0017) or fat droplet size(r =-0.9811,P = 0.0052).CONCLUSION:This tool for statistical analysis of signals from ultrasonography using the FD-ratio can be used to accurately quantify fat in vivo in an animal model of hepatic steatosis,and may serve as a quantitative biomarker of hepatic steatosis. | Hidekatsu Kuroda Keisuke Kakisaka Naohisa Kamiyama Takayoshi Oikawa Mio Onodera Kei Sawara Kanta Oikawa Ryujin Endo Yasuhiro Takikawa Kazuyuki Suzuki | 2012 | World Journal of Gastroenterology2012，18，29： | 15 |
| 10 | Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer显示文摘AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability(MSI) status in Japanese colorectal cancer(CRC) population.METHODS: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage Ⅰ-Ⅲ CRC and examined associations of these mutations with disease-free survival(DFS) and overall survival(OS) using uni- and multivariate Cox proportional hazards models.RESULTS: KRAS and BRAF mutations were detected in 312(38%) of 812 and 40(5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males(P = 0.02), while the presence of BRAF mutations was significantly associated with the female gender(P = 0.006), proximal tumor location(P < 0.001), mucinous or poorly differentiated histology(P < 0.001), and MSI-high tumors(P < 0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS(HR = 1.35; 95%CI: 1.03-1.75) and OS(HR = 1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS(HR = 2.20; 95%CI: 1.19-4.06) and OS(HR = 2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS.CONCLUSION: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, inJapanese patients with curatively resected CRC. | Shigenori Kadowaki Miho Kakuta Shuhei Takahashi Akemi Takahashi Yoshiko Arai Yoji Nishimura Toshimasa Yatsuoka Akira Ooki Kensei Yamaguchi Keitaro Matsuo Kei Muro Kiwamu Akagi | 2015 | World Journal of Gastroenterology2015，21，4： | 14 |
| 11 | Pancreatic guidewire placement for achieving selective biliary cannulation during endoscopic retrograde cholangio-pancreatography显示文摘AIM: To investigate the frequency and risk factors for acute pancreatitis after pancreatic guidewire placement (P-GW) in achieving cannulation of the bile duct during endoscopic retrograde cholangio-pancreatography (ERCP). METHODS: P-GW was performed in 113 patients in whom cannulation of the bile duct was difficult. The success rate of biliary cannulation, the frequency and risk factors of post-ERCP pancreatitis, and the frequency of spontaneous migration of the pancreatic duct stent were investigated. RESULTS: Selective biliary cannulation with P-GW was achieved in 73% of the patients. Post-ERCP pancreatitis occurred in 12% (14 patients: mild, 13; moderate, 1). Prophylactic pancreatic stenting was attempted in 59% of the patients. Of the 64 patients who successfully underwent stent placement, three developed mild pancreatitis (4.7%). Of the 49 patients without stent placement, 11 developed pancreatitis (22%: mild, 10; moderate, 1). Of the five patients in whom stent placement was unsuccessful, two developed mild pancreatitis. Univariate and multivariate analyses revealed no pancreatic stenting to be the only significant risk factor for pancreatitis. Spontaneous migration of the stent was observed within two weeks in 92% of the patients who had undergone pancreatic duct stenting.CONCLUSION: P-GW is useful for achieving selective biliary cannulation. Pancreatic duct stenting after P-GW can reduce the incidence of post-ERCP pancreatitis, which requires evaluation by means of prospective randomized controlled trials. | Kei Ito Naotaka Fujita Yutaka Noda Go Kobayashi Takashi Obana Jun Horaguchi Osamu Takasawa Shinsuke Koshita Yoshihide Kanno | 2008 | World Journal of Gastroenterology2008，14，36： | 14 |
| 12 | The definition of effective emissivity of land surface at the scale of remote sensing pixels显示文摘Remote sensing (RS) of land surface temperature (LST) is a very challenging problem at the present development stage of RS science. Tremendous efforts have been devoted to atmosphere correction and temperature emissivity separation (TES) of new LST product algorithms. However, the mechanism of directionality of thermal emission from land surface remains unknown, and even worse, there are confusions on the definition of the effective emissivity of land surface at the scale of RS pixels. The mechanism of directionality of thermal emission | LI Xiaowen and WANG Jindi Research Center for Remote Sensing and GIS, Beijing Normal Unirersity, Keying 100875, China Center for Remote Sensing, Boston Univ. , MA02215, USA | 1999 | Chinese Science Bulletin1999，44，23： | 14 |
| 13 | Rifaximin ameliorates hepatic encephalopathy and endotoxemia without affecting the gut microbiome diversity显示文摘AIM To determine the efficacy of rifaximin for hepatic encephalopathy(HE) with the linkage of gut microbiome in decompensated cirrhotic patients.METHODS Twenty patients(12 men and 8 women; median age, 66.8 years; range, 46-81 years) with decompensated cirrhosis(Child-pugh score > 7) underwent cognitive neuropsychological testing, endotoxin analysis, and fecal microbiome assessment at baseline and after 4 wk of treatment with rifaximin 400 mg thrice a day. HE was determined by serum ammonia level and number connection test(NCT)-A. Changes in whole blood endotoxin activity(EA) was analyzed by endotoxinactivity assay. Fecal microbiome was assessed by 16 S ribosome RNA(rR NA) gene sequencing.RESULTS Treatment with rifaximin for 4 wk improved hyperammonemia(from 90.6 ± 23.9 μg/d L to 73.1 ± 33.1 μg/dL; P < 0.05) and time required for NCT(from 68.2 ± 17.4 s to 54.9 ± 20.3 s; P < 0.05) in patients who had higher levels at baseline. Endotoxin activity was reduced(from 0.43 ± 0.03 to 0.32 ± 0.09; P < 0.05) in direct correlation with decrease in serum ammonia levels(r = 0.5886, P < 0.05). No statistically significant differences were observed in the diversity estimator(Shannon diversity index) and major components of the gut microbiome between the baseline and after treatment groups(3.948 ± 0.548 at baseline vs 3.980 ± 0.968 after treatment; P = 0.544), but the relative abundances of genus Veillonella and Streptococcus were lowered.CONCLUSION Rifaximin significantly improved cognition and reduced endotoxin activity without significantly affecting the composition of the gut microbiome in patients with decompensated cirrhosis. | Kosuke Kaji Hiroaki Takaya Soichiro Saikawa Masanori Furukawa Shinya Sato Hideto Kawaratani Mitsuteru Kitade Kei Moriya Tadashi Namisaki Takemi Akahane Akira Mitoro Hitoshi Yoshiji | 2017 | World Journal of Gastroenterology2017，23，47： | 14 |
| 14 | 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 |
| 15 | Effects of essential oils on performance,egg quality, nutrient digestibility and yolk fatty acid profile in laying hens显示文摘The study was conducted to investigate the effect of essential oils on performance, egg quality, nutrient digestibility and yolk fatty acid profile in laying hens. A total of 960 Lohmann laying hens aged 53 weeks were enrolled, under 4 different treatment diets supplemented with 0, 50.100 and 150 mg/kg essential oils(Enviva EO, Dupont Nutrition Biosciences ApS, Denmark), respectively. Each treatment was replicated8 times with 30 birds each. Birds were fed dietary treatment diets for 12 weeks(54 to 65 weeks). For data recording and analysis, a 12-week period was divided into 3 periods of 4 weeks' duration each: period 1(54 to 57 weeks), period 2(58 to 61 weeks), and period 3(62 to 65 weeks). For the diet supplemented with Enviva EO, hen-day egg production and the feed conversion ratio(FCR) were significantly improved(P < 0.05) at weeks 58 to 61, and the eggshell thickness was significantly increased(P < 0.05) at week 65.However, egg production, egg weight, feed intake, FCR and other egg quality parameters(albumen height, Haugh unit, egg yolk color and eggshell strength) were not affected by the dietary treatment. In addition, compared with the control diet, protein digestibility in the 100 mg/kg Enviva EO treatment group was significantly increased(P < 0.05), and fat digestibility in the 100 and 150 mg/kg Enviva EO treatment groups was significantly decreased(P < 0.05), but Enviva EO had no effect on energy apparent digestibility. Saturated fatty acid(SFA) and monounsaturated fatty acid(MUFA) gradually decreased and polyunsaturated fatty acid(PUFA) increased with Enviva EO supplementation, but the difference was not significant. The data suggested that the supplementation of essential oils(Enviva EO) in laying hen diet did not show a significant positive effect on performance and yolk fatty acid composition but it tended to increase eggshell thickness and protein digestibility, especially at the dose of 50 mg/kg. | Xuemei Ding Yang Yu Zhuowei Su Keying Zhang | 2017 | Animal Nutrition2017，，2： | 10 |
| 16 | Acinar cell injury induced by inadequate unfolded protein response in acute pancreatitis显示文摘Acute pancreatitis (AP) is an inflammatory disorder of pancreatic tissue initiated in injured acinar cells. Severe AP remains a significant challenge due to the lack of effective treatment. The widely-accepted autodigestion theory of AP is now facing challenges, since inhibiting protease activation has negligible effectiveness for AP treatment despite numerous efforts. Furthermore, accumulating evidence supports a new concept that malfunction of a self-protective mechanism, the unfolded protein response(UPR), is the driving force behind the pathogenesis of AP. The UPR is induced by endoplasmic reticulum(ER) stress, a disturbance frequently found in acinar cells, to prevent the aggravation of ER stress that can otherwise lead to cell injury. In addition, the UPR's signaling pathways control NFκB activation and autophagy flux, and these dysregulations cause acinar cell inflammatory injury in AP, but with poorly understood mechanisms. We therefore summarize the protective role of the UPR in AP, propose mechanistic models of how inadequate UPR could promote NFκB's pro-inflammatory activity and impair autophagy's protective function in acinar cells, and discuss its relevance to current AP treatment. We hope that insight provided in this review will help facilitate the research and management of AP. | Kaylene Barrera Albert Stanek Kei Okochi Zuzanna Niewiadomska Cathy Mueller Peiqi Ou Devon John Antonio E Alfonso Scott Tenner Chongmin Huan | 2018 | World Journal of Gastrointestinal Pathophysiology2018，9，2： | 9 |
| 17 | Differentiation of embryonic stem cells into insulin-producing cells promoted by Nkx2.2 gene transfer显示文摘AIM: To investigate the ability of a genetically altered embryonic stem (ES) cell line to generate insulin-producing cells in vitro following transfer of the Nkx2.2 gene.METHODS: Hamster Nkx2.2 genes were transferred into mouse ES cells. Parental and Nkx2.2-transfected ES cells were initiated toward differentiation in embryoid body (EB)culture for 5 d and the resulting EBs were transferred to an attached culture system. Dithizone (DTZ), a zincchelating agent known to selectively stain pancreatic beta cells, was used to detect insulin-producing cells.The outgrowths were incubated in DTZ solution (final concentration, 100 μg/mL) for 15 min before being examined microscopically. Gene expression of the endocrine pancreatic markers was also analyzed by RT-PCR. In addition, insulin production was determined immunohistochemically and its secretion was examined using an ELISA.RESULTS: DTZ-stained cellular clusters appeared after approximately 14 d in the culture of Nkx2.2-transfected ES cells (Nkx-ES cells), which was as much as 2 wk earlier, than those in the culture of parental ES cells (wt-ES). The frequency of DTZ-positive cells among total cultured cells on day 28 accounted for approximately 1.0% and 0.1% of the Nkx-ES- and wt-ES-derived EB outgrowths, respectively. The DTZ-positive cellular clusters were found to be immunoreactive to insulin, while the gene expressions of pancreatic-duodenal homeobox 1(PDX1), proinsulin 1 and proinsulin 2 were observed in the cultures that contained DTZ-positive cellular clusters.Insulin secretion was also confirmed by ELISA, whereas glucose-dependent secretion was not demonstrated.CONCLUSION: Nkx2.2-transfected ES cells showed an ability to differentiate into insulin-producing cells. | Akira Shiroi Shigehiko Ueda Yukiteru Ouji Ko Saito Kei Moriya Yuko Sugie Hiroshi Fukui Shigeaki Ishizaka Masahide Yoshikawa | 2005 | World Journal of Gastroenterology2005，11，27： | 9 |
| 18 | Diffusion-weighted MRI in abdominal oncology:Clinical applications显示文摘Diffusion-weighted magnetic resonance imaging(DWI) provides image contrast that is different from that obtained by conventional magnetic resonance techniques.Although previously,DWI has been used to evaluate various diseases of the central nervous system,several technical advances have expanded the clinical applications of DWI beyond the central nervous system.As a result,many reports have been published on the use of DWI in abdominal diseases.Particularly,abdominal DWI has now being focused on evaluation of patients with abdominal cancer.DWI can be used for pretreatment tumor detection,characterization including predicting tumor response to therapy,monitoring tumor response during therapy,and follow-up study after treatment to detect possible tumor recurrence. | Reiji Sugita Kei Ito Naotaka Fujita Shoki Takahashi | 2010 | World Journal of Gastroenterology2010，16，7： | 8 |
| 19 | Change in arterial tumor perfusion is an early biomarker of lenvatinib efficacy in patients with unresectable hepatocellular carcinoma显示文摘BACKGROUND Lenvatinib is one of the first-line tyrosine kinase inhibitors used for unresectable hepatocellular carcinoma(HCC). In the present study, we evaluated the potential of early changes in the time-intensity curve(TIC) of arterial phase on contrastenhanced ultrasound(CEUS) as early imaging biomarkers of lenvatinib efficacy.AIM To evaluate the potential of the early changes in the TIC of CEUS as early imaging biomarkers of lenvatinib efficacy in patients with unresectable HCC.METHODS We analyzed 20 consecutive patients with unresectable HCC treated with lenvatinib from March to November 2018. Tumor response at 8 wk was assessed by computed tomography using the modified Response Evaluation Criteria in Solid Tumors(m RECIST). CEUS was performed at baseline before treatment(Day 0) and on day 7(Day 7), and the images were analyzed in the arterial phase for 20 seconds after the contrast agent arrived at the target tumor. Three perfusion parameters were extracted from the TICs: the slope of wash-in(Slope),time to peak(TTP) intensity, and the total area under the curve(AUC) during wash-in. The rate of change in the TIC parameters between Day 0 and Day 7 was compared between treatment responders and non-responders based on m RECIST.RESULTS The rate of change for all TIC parameters showed significant differences between the responders(n = 9) and non-responders(n = 11)(Slope, P = 0.025; TTP, P =0.004; and AUC, P = 0.0003). The area under the receiver operating curve values for slope, TTP, and AUC for the prediction of responders were 0.805, 0.869, and0.939, respectively.CONCLUSION CEUS may be useful for the early prediction of tumor response to lenvatinib therapy in patients with unresectable HCC. | Hidekatsu Kuorda Tamami Abe Yudai Fujiwara Takuya Okamoto Miki Yonezawa Hiroki Sato Kei Endo Takayoshi Oikawa Kei Sawara Yasuhiro Takikawa | 2019 | World Journal of Gastroenterology2019，25，19： | 8 |
| 20 | Quantitation of HBsAg predicts response to entecavir therapy in HBV genotype C patients显示文摘AIM:To analysis the factors that predict the response to entecavir therapy in chronic hepatitis patients with hepatitis B virus (HBV) genotype C. METHODS:Fifty patients [hepatitis B e antigen (HBeAg)-negative:HBeAg-positive = 26:24] with HBV genotype C, who received nave entecavir therapy for > 2 years, were analyzed. Patients who showed HBV DNA levels ≥ 3.0 log viral copies/mL after 2 years of entecavir therapy were designated as slow-responders, while those that showed < 3.0 log copies/mL were termed rapid- responders. Quantitative hepatitis B surface antigen (HBsAg) levels (qHBsAg) were determined by the Architect HBsAg QT immunoassay. Hepatitis B core-related antigen was detected by enzyme immunoassay. Pre-C and Core promoter mutations were determined using by polymerase chain reaction (PCR). Drug-resistance mutations were detected by the PCR-Invader method. RESULTS:At year 2, HBV DNA levels in all patients in the HBeAg-negative group were < 3.0 log copies/mL. In contrast, in the HBeAg-positive group, 41.7% were slow-responders, while 58.3% were rapid-responders. No entecavir-resistant mutants were detected in the slow-responders. When the pretreatment factors were compared between the slow-and rapid-responders; the median qHBsAg in the slow-responders was 4.57 log IU/mL, compared with 3.63 log IU/mL in the rapid-responders (P < 0.01). When the pretreatment factors predictive of HBV DNA-negative status at year 2 in all 50 patients were analyzed, HBeAg-negative status, low HBV DNA levels, and low qHBsAg levels were significant (P < 0.01). Multivariate analysis revealed that the low qHBsAg level was the most significant predictive factor (P = 0.03). CONCLUSION:Quantitation of HBsAg could be a useful indicator to predict response to entecavir therapy. | Etsuro Orito Kei Fujiwara Hiroshi Kanie Tesshin Ban Tomonori Yamada Katsumi Hayashi | 2012 | World Journal of Gastroenterology2012，18，39： | 8 |
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