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Microbial markers in colorectal cancer detection and/or prognosis

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World Journal of Gastroenterology 2018年第22期24卷 2327-2347页

作者： Romain Villéger Amélie Lopès Julie Veziant johan gagnière Nicolas Barnich Elisabeth Billard Delphine Boucher Mathilde Bonnet Université Clermont Auvergne research Biologics Sanofi R&D Chirurgie digestive Centre Hospitalier Universitaire Université Clermont Auvergne Institut Universitaire de Technologie de Clermont-Ferrand

Colorectal cancer(CRC) is the second leading cause of cancer worldwide. CRC is still associated with a poor prognosis among patients with advanced disease. On the contrary, due to its slow progression from detectable precancerous lesions, the prognosis for patients with early stages of CRC is encouraging. While most robust methods are invasive and costly, actual patient-friendly screening methods for CRC suffer of lack of sensitivity and specificity. Therefore, the development of sensitive, non-invasive and cost-effective methods for CRC detection and prognosis are necessary for increasing the chances of a cure. Beyond its beneficial functions for the host, increasing evidence suggests that the intestinal microbiota is a key factor associated with carcinogenesis. Many clinical studies have reported a disruption in the gut microbiota balance and an alteration in the faecal metabolome of CRC patients, suggesting the potential use of a microbialbased test as a non-invasive diagnostic and/or prognostic tool for CRC screening. This review aims to discuss the microbial signatures associated with CRC known to date, including dysbiosis and faecal metabolome alterations, andthe potential use of microbial variation markers for noninvasive early diagnosis and/or prognostic assessment of CRC and advanced adenomas. We will finally discuss the possible use of these markers as predicators for treatment response and their limitations.

关键词： Colorectal cancer microbiota F.nucleatum Colibactin-producing E.coli prognostic markers diagnostic markers dysbiosis

Association of colorectal cancer with pathogenic Escherichia coli: Focus on mechanisms using optical imaging

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World Journal of Clinical Oncology 2016年第3期7卷 293-301页

作者： Julie Veziant johan gagnière Elodie Jouberton Virginie Bonnin Pierre Sauvanet Denis Pezet Nicolas Barnich Elisabeth Miot-Noirault Mathilde Bonnet UMR1071 Inserm/Université d’Auvergne and INRA USC2018 Clermont Université Service de Chirurgie Digestive Centre Hospitalier Universitaire UMR990 Inserm/Université d’Auvergne Clermont Université Service de Médecine Nucléaire Centre Jean Perrin

AIM: To investigate the molecular or cellular mechanisms related to the infection of epithelial colonic mucosa by pks-positive Escherichia coli(E. coli) using optical ***: We choose to evaluate the tumor metabolic activity using a fluorodeoxyglucose analogue as 2-deoxyglucosone fluorescent probes and to correlate it with tumoral volume(mm^3). Inflammation measuring myeloperoxidase(MPO) activity and reactive oxygen species production was monitored by a bioluminescent(BLI) inflammation probe and related to histological examination and MPO levels by enzyme-linked immunosorbent assay(ELISA) on tumor specimens. The detection and quantitation of these two signals were validated on a xenograft model of human colon adenocarcinoma epithelial cells(HCT116) in nude mice infected with a pks-positive E. coli. The inflammatory BLI signal was validated intra-digestively in the colitisCEABAC10 DSS models, which mimicked Crohn's disease. reSULTS: Using a 2-deoxyglucosone fluorescent probe, we observed a high and specific HCT116 tumor uptake in correlation with tumoral volume(P = 0.0036). Using the inflammation probe targeting MPO, we detected a rapid systemic elimination and a significant increase of the BLI signal in the pks-positive E. coli-infected HCT116 xenograft group(P re significantly higher(1556 ± 313.6 vs 234.6 ± 121.6 ng/m L P = 0.001) in xenografts infected with the pathogenic E. coli strain. Moreover, histological examination of tumor samples confirmed massive infiltration of pks-positive E. coli-infected HCT116 tumors by inflammatory cells compared to the uninfected group. These data showed that infection with the pathogenic E. coli strain enhanced inflammation and ROS production in tumors before tumor growth. Moreover, we demonstrated that the intra-digestive monitoring of inflammation is feasible in a reference colitis murine model(CEABAC10/DSS).CONCLUSION: Using BLI and fluorescence optical imaging, we provided

关键词： Colorectal carcinoma Escherichia coli Colibactin Myeloperoxidase In vivo optical imaging

Giant mucinous cystic adenoma with pancreatic atrophy mimicking dorsal agenesis of the pancreas

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World Journal of Gastrointestinal Surgery 2014年第3期6卷 42-46页

作者： johan gagnière Aurélien Dupré David Da Ines Lucie Tixier Denis Pezet Emmanuel Buc Department of Digestive and Hepatobiliary Surgery Cen-tre Hospitalier Universitaire Estaing Department of Radiology Cen-tre Hospitalier Universitaire Estaing

Mucinous cystic adenoma(MCA) of the pancreas is a rare benign cystic tumor with ovarian-like stroma and lack of communication with the pancreatic ductal sys-tem. The ovarian tissue is incorporated from the left gonad within the dorsal pancreas during embryogen-esis. Consequently, congenital dorsal agenesis of the pancreas(DAP) cannot be associated with MCA. We report the case of a giant MCA associated with atro-phy of the dorsal pancreas mimicking complete DAP. Pancreato-magnetic resonance imaging failed to iden-tify the dorsal pancreas but the absence of diabetes mellitus and compression of the splenic vein with major tributaries rectified the diagnosis of secondary atrophy of the distal pancreas. Unusual proximal location of the cyst in the pancreas may have induced chronic obstruc-tion of both the dorsal pancreatic duct and the splenic vein, with secondary atrophy of the distal pancreas.

关键词： Dorsal agenesis Pancreas Cystic tumor Diabetes Surgery

Gut microbiota imbalance and colorectal cancer

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World Journal of Gastroenterology 2016年第2期22卷 501-518页

作者： johan gagnière Jennifer Raisch Julie Veziant Nicolas Barnich Richard Bonnet Emmanuel Buc Marie-Agnès Bringer Denis Pezet Mathilde Bonnet Clermont Université UMR 1071 Inserm/Universitéd’Auvergne63000 Clermont-FerrandFrance INRA USC-201863000 Clermont-FerrandFrance Chirurgie Digestive Centre Hospitalier Universitaire63000 Clermont-FerrandFrance Bactériologie Centre Hospitalier Universitaire63000 Clermont-FerrandFrance Laboratoire d’Immunologie Institut Armand FrappierLaval H7V 1B7Canada INRA UMR 1324 CNRS UMR 6265Universitéde BourgogneCentre des Sciences du Goût et de l’AlimentationEye Nutrition and Signalling Research Group21000 DijonFrance

The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes(e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies.

关键词： Colorectal cancer Gut microbiota Dysbiosis Cyclomodulin Oxidative stress

Prognostication algorithm for non-cirrhotic non-B non-C hepatocellular carcinoma-a multicenter study under the aegis of the French Association of Hepato-Biliary Surgery and liver Transplantation

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Hepatobiliary Surgery and Nutrition 2023年第2期12卷 192-204,I0002-I0004页

作者： Charlotte Maulat Stéphanie Truant Christian Hobeika Louise Barbier Astrid Herrero Alexandre Doussot johan gagnière Édouard Girard Hadrien Tranchart Jean-Marc regimbeau David Fuks François Cauchy Mathieu Prodeau Antoine Notte Cyprien Toubert Ephrem Salamé Mehdi El Amrani Sandrine Andrieu Fabrice Muscari Jason Shourick Bertrand Suc Department of Digestive Surgery Hepatobiliary and Pancreatic Surgery and Liver Transplantation UnitToulouse University HospitalToulouseFrance Department of Digestive Surgery and Transplantation Claude-HuriezHospitalCHRU LilleLilleFrance CANTHER laboratory“Cancer Heterogeneity Plasticity and Resistance to Therapies”Inserm UMR-S1277 Teams“MucinsCancer and Drug Resistance”LilleFrance Department of Hepato-bilio-pancreatic Surgery and Liver Transplantation Beaujon HospitalAPHPClichyFrance Department of Digestive Surgery and Liver Transplantation Trousseau HospitalTours University HospitalToursFrance Department of Digestive Surgery and Liver Transplantation Saint Eloi HospitalMontpellier University HospitalMontpellierFrance Department of Digestive Surgery and Liver Transplantation Besançon University HospitalBesançonFrance Department of Digestive and Hepatobiliary Surgery University Hospital of Clermont-FerrandClermont-FerrandFrance U1071 Inserm/UniversitéClermont-Auvergne Clermont-FerrandFrance Department of Digestive Surgery and Emergency CHU Grenoble-AlpesGrenobleFrance Department of Mini-invasive Surgery Antoine Béclère HospitalAPHPClamartFrance Department of Digestive Surgery Amiens Picardie University Hospital and Picardie Jules Verne UniversityAmiensFrance Department of Digestive Surgery Institut Mutualiste MontsourisParisFrance Department of Epidemiology Toulouse University HospitalToulouseFrance

Background:Liver resection and local ablation are the only curative treatment for non-cirrhotic hepatocellular carcinoma(HCC).Few data exist concerning the prognosis of patients resected for non-cirrhotic *** objectives of this study were to determine the prognostic factors of recurrence-free survival(RFS)and overall survival(OS)and to develop a prognostication algorithm for non-cirrhotic ***:French multicenter retrospective study including HCC patients with non-cirrhotic liver without underlying viral hepatitis:F0,F1 or F2 ***:A total of 467 patients were included in 11 centers from 2010 to ***-cirrhotic liver had a fibrosis score of F0(n=237,50.7%),F1(n=127,27.2%)or F2(n=103,22.1%).OS and RFS at 5 years were 59.2%and 34.5%,*** multivariate analysis,microvascular invasion and HCC differentiation were prognostic factors of OS and RFS and the number and size were prognostic factors of RFS(P10 cm(n=176,Group 2);>2 HCC regardless of size Conclusions:We developed a prognostication algorithm based on the number(≤or>2)and size(≤or>10 cm),which could be used as a treatment decision support concerning the need for perioperative *** case of bifocal HCC,surgery should not be a contraindication.

关键词： Hepatocellular carcinoma(HCC) non-cirrhotic liver prognostic factors recurrence-free survival(RFS) prognostication algorithm

Minimally invasive surgery for gastric cancer: A comparison between robotic, laparoscopic and open surgery

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World Journal of Gastroenterology 2017年第13期23卷 2376-2384页

作者： Amilcare Parisi Daniel reim Felice Borghi Ninh T Nguyen Feng Qi Andrea Coratti Fabio Cianchi Maurizio Cesari Francesca Bazzocchi Orhan Alimoglu johan gagnière Graziano Pernazza Simone D'Imporzano Yan-Bing Zhou Juan-Santiago Azagra Olivier Facy Steven T Brower Zhi-Wei Jiang Lu Zang Arda Isik Alessandro Gemini Stefano Trastulli Alexander Novotny Alessandra Marano Tong Liu Mario Annecchiarico Benedetta Badii Giacomo Arcuri Andrea Avanzolini Metin Leblebici Denis Pezet Shou-Gen Cao Martine Goergen Shu Zhang Giorgio Palazzini Vito D'Andrea Jacopo Desiderio Department of Digestive Surgery St.Mary's HospitalUniversity of Perugia Klinik und Poliklinik fuer Chirurgie Klinikum Rechts der IsarTechnical University Munich Department of Surgery General and Oncologic Surgery UnitSanta Croce e Carle Hospital Department of Surgery Division of Gastrointestinal SurgeryUniversity of CaliforniaIrvine Medical Center Gastrointestinal Surgery Tianjin Medical University General Hospital Division of Oncological and Robotic Surgery Department of OncologyCareggi University Hospital Unit of general and endocrine surgery Center of oncologic minimally invasive surgery(COMIS)Careggi University Hospital Department of General Surgery Hospital of Cittàdi CastelloUSL1 Umbria Department of General Surgery Division of GeneralGastroenterologic and Minimally Invasive SurgeryG.B.Morgagni Hospital Department of General Surgery School of MedicineIstanbul Medeniyet University Department of Digestive and Hepatobiliary Surgery Estaing University Hospital Department of Surgery Robotic General Surgery UnitSan Giovanni Addolorata Hospital Esophageal Surgery Unit Tuscany Regional Referral Center for the Diagnosis and Treatment of Esophageal DiseaseMedical University of Pisa Department of General Surgery The Affiliated Hospital of Qingdao University Unitédes Maladies de l'Appareil Digestif et Endocrine Centre Hospitalier de Luxembourg Service de Chirurgie Digestive et Cancérologique CHU Bocage Department of Surgical Oncology and HPB Surgery Englewood Hospital and Medical Center Department of General Surgery Jinling HospitalMedical SchoolNanjing University Department of Surgery Ruijin HospitalShanghai Jiaotong UniversitySchool of Medicine Department of General Surgery Erzincan UniversitySchool of Medicine Department of Surgical Science “La Sapienza”University Department of Digestive Surgery St.Mary's Hospital of Terni-University of Perugia

AIM To investigate the role of minimally invasive surgery for gastric cancer and determine surgical, clinical, and oncological *** This is a propensity score-matched case-control study, comparing three treatment arms: robotic gastrectomy(RG), laparoscopic gastrectomy(LG), open gastrectomy(OG). Data collection started after sharing a specific study protocol. Data were recorded through a tailored and protected web-based system. Primary outcomes: harvested lymph nodes, estimated blood loss, hospital stay, complications rate. Among the secondary outcomes, there are: operative time, R0 resections, POD of mobilization, POD of starting liquid diet and soft solid diet. The analysis includes the evaluation of type and grade of postoperative complications. Detailed information of anastomotic leakages is also *** The present analysis was carried out of 1026 gastrectomies. To guarantee homogenous distribution of cases, patients in the RG, LG and OG groups were 1:1:2 matched using a propensity score analysis with a caliper = 0.2. The successful matching resulted in a total sample of 604 patients(RG = 151; LG = 151; OG = 302). The three groups showed no differences in all baseline patients characteristics, type of surgery(P = 0.42) and stage of the disease(P = 0.16). Intraoperative blood loss was significantly lower in the LG(95.93 ± 119.22) and RG(117.91 ± 68.11) groups compared to the OG(127.26 ± 79.50, P = 0.002). The mean number of retrieved lymph nodes was similar between the RG(27.78 ± 11.45), LG(24.58 ± 13.56) and OG(25.82 ± 12.07) approach. A benefit in favor of the minimally invasive approaches was found in the length of hospital stay(P rent(P = 0.78) between *** Laparoscopic and robotic surgery can be safely performed and proposed as possible alternative to open surgery. The main highlighted benefit is a faster postoperative functional recov

关键词： Gastric cancer Gastrectomy Minimally invasive surgery Robotic Robot-assisted Laparoscopy

Mapping and understanding degradation of alpine wetlands in the northern Maloti-Drakensberg, southern Africa

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Journal of Mountain Science 2024年第9期21卷 2956-2966页

作者： johan van TOL Department of Soil Crop and Climate SciencesUniversity of the Free StateBloemfontein 9300South Africa

The alpine terrestrials of the Maloti-Drakensberg in southern Africa play crucial roles in ecosystem functions and livelihoods,yet they face escalating degradation from various factors including overgrazing and climate *** study employs advanced Digital Soil Mapping(DSM)techniques coupled with remote sensing to map and assess wetland coverage and degradation in the northern *** model achieved high accuracies of 96%and 92%for training and validation data,respectively,with Kappa statistics of 0.91 and 0.83,marking a pioneering automated attempt at wetland mapping in this *** attributes such as terrain wetness index(TWI)and valley depth(VD)exhibit significant positive correlations with wetland coverage and erosion gully density,Channel Network Depth and slope were negative *** density analysis revealed terrain attributes as dominant factors driving degradation,highlighting the need to consider catchment-specific susceptibility to *** challenge traditional assumptions which mainly attribute wetland degradation to external forces such as livestock overgrazing,ice rate activity and climate *** sensitivity map produced could serve as a basis for Integrated Catchment Management(ICM)projects,facilitating tailored conservation *** research should expand on this work to include other highland areas,explore additional covariates,and categorize wetlands based on hydroperiod and sensitivity to *** comprehensive study underscores the potential of DSM and remote sensing in accurately assessing and managing wetland ecosystems,crucial for sustainable resource management in alpine regions.

关键词： Digital Soil Mapping Gully density Integrated catchment management remote sensing Wetland degradation

The origin of the suspended particulate matter in the seagrass meadow of tropical waters, an evidence of the stable isotope signatures

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Acta Oceanologica Sinica 2019年第1期38卷 136-143页

作者： A'an johan Wahyudi Afdal research Center for Oceanography Indonesian Institute of Sciences

Suspended particulate matter(SPM) has been known as an important variable in the organic matter flow of coastal ecosystem. Half of burial carbon in seagrass meadows is contributed by allochthonous sources that compose the SPM such as phytoplankton, seagrass detritus, marine snow aggregates and terrestrially derived particles. Each composition of the SPM contributes different roles and is important to be identified, for instance,the exact contribution of seagrass detritus will be useful for determination of carbon export through the detritus form in seagrass meadows. Here, the SPM of seagrass meadows is studied in Bintan Island and the Selayar Archipelago. The aim of this research is to determine the source origin of the SPM using a stable isotope *** order to fulfill this aim, the objectives are defined as:(1) to specify the stable isotope signature(δ13C and δ15N)of the SPM, and(2) to determine the proportional distribution of the SPM's prospectus sources. The result shows that the possibility of the source origin of the SPM includes a seagrass fraction(Enhalus acoroides and Thalassia hemprichii), terrestrial C4 plant, macroalgae, and terrestrial C3 plant. The SPM lies between the marine-and terrigenous-end members. However, it seems that the SPM is more to be terrigenous-end and *** to a Bayesian mixing model, the terrestrial C4 has the highest contribution of the SPM at all sites except Barugaia and Pasi Island in Selayar(i.e., the highest contribution of the SPM is from the detritus of E. acoroides).The second contribution has been contributed by either seagrass detritus(E. acoroides or Th. hemprichii) or terrestrial C3 plant. The finding of this study indicates that there is a strong influence of the terrigenous sources in the SPM of the seagrass meadows.

关键词： suspended particulate matter stable isotope source origin seagrass ecosystems

Gut health,stress,and immunity in neonatal dairy calves:the host side of host-pathogen interactions

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Journal of Animal Science and Biotechnology 2021年第1期12卷 49-63页

作者： johan.S.Osorio Dairy and Food Science Department South Dakota State University113 H Alfred Dairy Science HallBrookingsSD 57007USA

The cumulative evidence that perinatal events have long-lasting ripple effects through the life of livestock animals should impact future nutritional and management recommendations at the farm level. The implications of fetal programming due to malnutrition, including neonatal survival and lower birth weights, have been characterized,particularly during early and mid-gestation, when placental and early fetal stages are being developed. The accelerated fetal growth during late pregnancy has been known for some time, while the impact of maternal stressors during this time on fetal development and by extent its postnatal repercussions on health and performance are still being *** stressors during late pregnancy cannot only influence colostrogenesis but also compromise adequate intestinal development in the fetus, thus, that further limits the newborn's ability to absorb nutrients, bioactive compounds, and immunity(i.e., immunoglobulins, cytokines, and immune cells) from colostrum. These negative effects set the newborn calf to a challenging start in life by compromising passive immunity and intestinal maturation needed to establish a mature postnatal mucosal immune system while needing to digest and absorb nutrients in milk or milk replacer. Besides the dense-nutrient content and immunity in colostrum, it contains bioactive compounds such as growth factors, hormones, and cholesterol as well as molecular signals or instructions [e.g., microRNAs(miRNAs) and long non-coding RNAs(lncRNAs)] transferred from mother to offspring with the aim to influence postnatal gut maturation. The recent change in paradigm regarding prenatal materno-fetal microbiota inoculation and likely the presence of microbiota in the developing fetus intestine needs to be addressed in future research in ruminants. There still much to know on what prenatal or postnatal factors may predispose neonates to become susceptible to enteropathogens(e.g., enterotoxigenic Escherichia coli), causing

关键词： Dairy calves Fecal RNA Neonatal diarrhea