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| 1 | 2018加拿大心境障碍与焦虑障碍治疗协作组/国际双相障碍学会指南:双相障碍的管理显示文摘加拿大心境障碍与焦虑障碍治疗协作组(Canadian Network for Mood and Anxiety Treatments,CANMAT)曾于2005年发布了第1版双相障碍管理指南,并分别于2007、2009和2013年对该指南进行了更新,其中最近的2次更新是与国际双相障碍学会(International Society for Bipolar Disorders,ISBD)合作完成。2018版CANMAT/ISBD双相障碍治疗指南(以下简称指南)反映了自2005年首版指南发表以来本领域取得的重大进展,包括疾病诊断与疾病管理的更新以及药物治疗与心理治疗的近期研究进展。这些前沿进展中综合考虑了循证证据的级别,并基于治疗疗效、临床实践经验、安全性、耐受性和药物导致的转相风险等,对一线、二线及三线治疗方案进行了简明而清晰的推荐。本指南中新增内容涵盖了双相Ⅰ型障碍(BD-Ⅰ)的躁狂发作急性期、抑郁发作急性期和双相障碍维持期的一线及二线治疗推荐等级划分。这种对治疗推荐等级的划分综合考虑了治疗方法对双相障碍不同时相的影响,将进一步帮助临床医生做出基于循证证据的治疗决策。锂盐、喹硫平、双丙戊酸盐、阿塞那平、阿立哌唑、帕利哌酮、利培酮和卡利拉嗪单药或联合使用被推荐为躁狂发作急性期的一线治疗选择。BD-Ⅰ抑郁期的一线治疗选择包括喹硫平、鲁拉西酮、锂盐、拉莫三嗪单药,鲁拉西酮联合锂盐或双丙戊酸盐或拉莫三嗪辅助治疗。尽管急性期治疗有效的药物通常应继续用于BD-Ⅰ的维持期治疗,但也存在一些特殊情况(例如抗抑郁药)。现有数据表明,锂盐、喹硫平、双丙戊酸盐、拉莫三嗪、阿塞那平和阿立哌唑单药或联合治疗应被视为维持治疗的初始或更换治疗方案时的一线选择。除了探讨BD-Ⅰ的相关问题外,本指南中还对双相Ⅱ型障碍(BD-Ⅱ)的临床管理进行了系统回顾并给予治疗推荐,同时针对特殊人群也有相关推荐,如处于各个生殖周期的女性、儿童、青少年和老年人。此外,本指南中还讨论了特定精神疾病及共病(如物质滥用、焦虑障碍和代谢性疾病)的影响。最后,本指南中概述了安全性和药物监测的相关问题。CANMAT/ISBD工作组希望本指南能够成为全球临床医生的实用工具。 | Lakshmi N Yatham Sidney H Kennedy Sagar V Parikh Ayal Sehaffer David J Bond Benicio N Frey Verinder Sharma Benjamin I Goldstein Soham Rej Serge Beaulieu Martin Alda Glenda MaeQueen Roumen V Milev Arun Ravindran Claire O'Donovan Diane Mclntosh Raymond W Lam Gustavo Vazquez Flavio Kapczinski Roger S Melntyre Jan Kozicky Shigenobu Kanba Beny Lafer Trisha Suppes Joseph R Calabrese Eduard Vieta Gin Malhi Robert M Post Michael Berk 胡晨(译) 王刚(译) | 2019 | 中华精神科杂志2019，52，1： | 25 |
| 2 | Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis显示文摘AIM To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis(PSC) and ulcerative colitis(UC).METHODS Stool samples were collected and relevant clinical data obtained from 106 study participants, 43 PSC patients with(n = 32) or without(n = 11) concomitant inflammatory bowel disease, 32 UC patients, and 31 healthy controls. The V3 and V4 regions of the 16 S ribosomal RNA gene were sequenced on Illumina Mi Seq platform to cover low taxonomic levels. Data were further processed in QIIME employing Ma As Lin and LEf Se tools for analysis of the output data.RESULTS Microbial profiles in both PSC and UC were characterized by low bacterial diversity and significant change in global microbial composition. Rothia, Enterococcus, Streptococcus, Veillonella, and three other genera were markedly overrepresented in PSC regardless of concomitant inflammatory bowel disease(IBD). Rothia, Veillonella and Streptococcus were tracked to the species level to identify Rothia mucilaginosa, Streptococcus infantus, S. alactolyticus, and S. equi along with Veillonella parvula and V. dispar. PSC was further characterized by decreased abundance of Adlercreutzia equolifaciens and Prevotella copri. Decrease in genus Phascolarctobacterium was linked to presence of colonic inflammation regardless of IBD phenotype. Akkermansia muciniphila, Butyricicoccus pullicaecorum and Clostridium colinum were decreased in UC along with genus Roseburia. Low levels of serum albumin were significantly correlated with enrichment of order Actinomycetales.CONCLUSION PSC is associated with specific gut microbes independently of concomitant IBD and several bacterial taxa clearly distinguish IBD phenotypes(PSC-IBD and UC). | Lukas Bajer Miloslav Kverka Martin Kostovcik Peter Macinga Jiri Dvorak Zuzana Stehlikova Jan Brezina Pavel Wohl Julius Spicak Pavel Drastich | 2017 | World Journal of Gastroenterology2017，23，25： | 22 |
| 3 | 世界腹腔间隙学会腹内高压和腹腔间隙综合征2013版专家共识与诊疗指南显示文摘随着人们对腹内压(intra-abdominal pressure,IAP)的重视,大量研究开始关注腹内高压(intraabdominal hypertension,IAH)和腹腔间隙综合征(abdominal compartment syndrome,ACS).世界腹腔间隙学会(The abdominal compartment society,WSACS)先后在2006年提出了IAH和ACS的专家共识,2007年发表了诊疗指南,2009年明确了疾病相关研究的推荐方向.2013年WSACS发布了新的IAH和ACS专家共识与诊疗指南.该指南由多学科专家共同参与制定,大部分是外科专家和重症监护专家.专家们首先明确24个临床医师关心的IAH和ACS问题,随后进行了系统有序的文献整理. | Andrew W.Kirkpatrick Derek J.Roberts Jan De Waele Roman Jaeschke Manu L.N.G.Malbrain Bart De Keulenaer Juan Duchesne Martin Bjorc Ari Leppaniemi | 2015 | 中华外科杂志2015，53，3： | 15 |
| 4 | Intracellular distribution of amyloid beta peptide and its relationship to the lysosomal system显示文摘Background:Amyloid beta peptide(Aβ)is the main component of extraneuronal senile plaques typical of Alzheimer’s disease(AD)brains.Although Aβis produced by normal neurons,it is shown to accumulate in large amounts within neuronal lysosomes in AD.We have recently shown that under normal conditions the majority of Aβis localized extralysosomally,while oxidative stress significantly increases intralysosomal Aβcontent through activation of macroautophagy.It is also suggested that impaired Aβsecretion and resulting intraneuronal increase of Aβcan contribute to AD pathology.However,it is not clear how Aβis distributed inside normal neurons,and how this distribution is effected when Aβsecretion is inhibited.Methods:Using retinoic acid differentiated neuroblastoma cells and neonatal rat cortical neurons,we studied intracellular distribution of Aβby double immunofluorescence microscopy for Aβ40 or Aβ42 and different organelle markers.In addition,we analysed the effect of tetanus toxin-induced exocytosis inhibition on the intracellular distribution of Aβ.Results:Under normal conditions,Aβwas found in the small cytoplasmic granules in both neurites and perikarya.Only minor portion of Aβwas colocalized with trans-Golgi network,Golgi-derived vesicles,early and late endosomes,lysosomes,and synaptic vesicles,while the majority of Aβgranules were not colocalized with any of these structures.Furthermore,treatment of cells with tetanus toxin significantly increased the amount of intracellular Aβin both perikarya and neurites.Finally,we found that tetanus toxin increased the levels of intralysosomal Aβalthough the majority of Aβstill remained extralysosomally.Conclusion:Our results indicate that most Aβis not localized to Golgi-related structures,endosomes,lysosomes secretory vesicles or other organelles,while the suppression of Aβsecretion increases intracellular intra-and extralysosomal Aβ. | Lin Zheng Angel Cedazo-Minguez Martin Hallbeck Fredrik Jerhammar Jan Marcusson Alexei Terman | 2012 | Translational Neurodegeneration2012，1，1： | 10 |
| 5 | Association between hepatitis B and metabolic syndrome:Current state of the art显示文摘Chronic hepatitis B(CHB)is a global health issue that increases the risk of liver cirrhosis and hepatocellular carcinoma in infected patients.Metabolic syndrome(Met S)is a disease endemic mostly to the developed countries.It is associated with high cardiovascular mortality and morbidity,diabetes mellitus as well as cancer.In this manuscript,we systematically review the published data on the relationship between Met S and CHB infection.Multiple studies have described highly variable correlations between CHB on one hand and Met S,non-alcoholic fatty liver disease and dyslipidemia on the other.No association between CHB and diabetes mellitus or atherosclerosis has been described as of now.The presence of Met S in patients infected with hepatitis B virus increases the risk of fibrosis,cirrhosis and hepatocellular carcinoma.Appropriate lifestyle,but also pharmacological interventions are needed to prevent the development of these complications. | Peter Jarcuska Sylvia Drazilova Jan Fedacko Daniel Pella Martin Janicko | 2016 | World Journal of Gastroenterology2016，22，1： | 8 |
| 6 | Vitamin A administration at birth promotes calf growth and intramuscular fat development in Angus beef cattle显示文摘Background: Marbling, or intramuscular fat, is an important factor contributing to the palatability of beef. Vitamin A, through its active metabolite, retinoic acid, promotes the formation of new fat cells(adipogenesis). As intramuscular adipogenesis is active during the neonatal stage, we hypothesized that vitamin A administration during the neonatal stage would enhance intramuscular adipogenesis and marbling.Methods: Angus steer calves(n = 30), in a completely randomized design, were randomly allotted to three treatment groups at birth, receiving 0, 150,000, or 300,000 IU of vitamin A at both birth and one month of age.A biopsy of the biceps femoris muscle was collected at two months of age. After weaning at 210 d of age, steers were fed a backgrounding diet in a feedlot until 308 d of age, when they were transitioned to a high concentrate finishing diet and implanted with trenbolone/estradiol/tylosin mixture. Steers were harvested at an average of 438 d of age. All diets were formulated to meet nutrient requirements.Results: Weaning weight and weight during the backgrounding phase were linearly increased(P < 0.05) by vitamin A level, though no difference in body weight was observed at harvest. Intramuscular fat of steers at 308 d of age, measured by ultrasound, quadratically increased(P < 0.05) with vitamin A level from 4.0±0.26 % to 4.9±0.26 %.Similarly, carcass marbling score in the ribeye quadratically increased(P < 0.05).Conclusion: Administration of vitamin A at birth increased weaning weight and enhanced marbling fat development.Thus, vitamin A administration provides a practical method for increasing marbling and early growth of beef cattle. | Corrine L.Harris Bo Wang Jeneane M.Deavila Jan R.Busboom Martin Maquivar Steven M.Parish Brent McCann Mark L.Nelson Min Du | 2018 | Journal of Animal Science and Biotechnology2018，9，4： | 7 |
| 7 | Noninvasive indocyanine green plasma disappearance rate predicts early complications,graft failure or death after liver transplantation显示文摘BACKGROUND:Early detection of graft malfunction or postoperative complications is essential to save patients and organs after orthotopic liver transplantation (OLT).Predictive tests for graft dysfunction are needed to enable earlier implementation of organ-saving interventions following transplantation.This study was undertaken to assess the value of indocyanine green plasma disappearance rates (ICG-PDRs) for predicting postoperative complications,graft dysfunction and patient survival following OLT.METHODS:Eighty-six patients undergoing OLT were included in this single-centre trial.ICG-PDR was assessed daily for the first 7 days following OLT.Endpoints were graft loss or death within 30 days and postoperative complications,graft loss,or death within 30 days.RESULTS:Postoperative complications of 31 patients included deaths (12 patients) or graft losses.ICG-PDR was significantly different in patients whose endpoints were graft loss or death beginning from day 3 and in those whose endpoints were graft loss,death,or postoperative complications beginning from day 4 after OLT.For day 7 measurements,receiver operating characteristic curve analysis revealed an ICG-PDR cut-off for predicting death or graft loss of 9.6% per min (a sensitivity of 75.0%,a specificity of 72.6%,positive predictive value 0.35 negative predictive value 0.94).For prediction of graft loss,death or postoperative complications,the ICG-PDR cut-off was 12.3%per min (a sensitivity of 68.9%,a specificity of 66.7%,positive predictive value 0.57,negative predictive value 0.77).CONCLUSIONS:ICG-PDR measurements on postoperative day 7 are predictive of early patient outcomes following OLT.The added value over that of routinely determined laboratory parameters is low. | Lutz Schneider Martin Spiegel Sebastian Latanowicz Markus A Weigand Jan Schmidt Jens Werner Wolfgang Stremmel Christoph Eisenbach | 2011 | Hepatobiliary & Pancreatic Diseases International2011，10，4： | 6 |
| 8 | 多器官床旁即时超声在新型冠状病毒肺炎中的应用:国际专家共识显示文摘新型冠状病毒肺炎(简称新冠肺炎,COVID-19)自首次报道以来,已造成全球超一亿人感染,给各国的公共卫生体系造成了巨大威胁。新冠肺炎的临床表现以呼吸系统体征和症状为主,80%的患者症状轻微,约5%为危重症患者,常表现为急性呼吸窘迫综合征(ARDS)。前期,由于缺乏相关研究,面对日益紧迫的临床困境,医务人员不得不借鉴采取一些经验性措施以应对疫情。 | 王臻(译) Arif Hussain Gabriele Via Lawrence Melniker Alberto Goffi Guido Tavazzi Luca Neri Tomas Villen Richard Hoppmann Francesco Mojoli Vicki Noble Laurent Zieleskiewicz Pablo Blanco Irene W.Y.Ma Mahathar Abd.Wahab Abdulmohsen Alsaawi Majid AI Salamah Martin Balik Diego Barca Karim Bendjelid Belaid Bouhemad Pablo Bravo-Figueroa Raoul Breitkreutz Juan Calderon Jim Connolly Roberto Copetti Francesco Corradi Anthony J.Dean AndréDenault Deepak Govil Carmela Graci Young-Rock Ha Laura Hurtado Toru Kameda Michael Lanspa Christian B Laursen Francis Lee Rachel Liu Massimiliano Meineri Miguel Montorfano Peiman Nazerian Bret P.Nelson Aleksandar N.Neskovic Ramon Nogue Adi Osman JoséPazeli Elmo Pereira-Junior Tomislav Petrovic Emanuele Pivetta Jan Poelaert Susanna Price Gregor Prosen Shalim Rodriguez Philippe Rola Colin Royse Yale Tung Chen Mike Wells Adrian Wong Wang Xiaoting Wang Zhen Yaseen Arabi | 2021 | 中国呼吸与危重监护杂志2021，20，2： | 5 |
| 9 | Subcycle control of terahertz waveform polarization using all-optically induced transient metamaterials显示文摘Coherent radiation with frequencies ranging from 0.3 to 30 THz has recently become accessible using femtosecond laser technology.These terahertz(THz)waves have already been applied in spectroscopy and imaging and can be manipulated using static optical elements such as lenses,polarizers and filters.However,ultrafast modulation of THz radiation is required as well,for instance,in short-range wireless communication or for preparing shaped THz transients for the coherent control of numerous material excitations.Here,we demonstrate an all-optically created transient metamaterial that allows us to manipulate the polarization of THz waveforms with subcycle switch-on times.The polarization-modulated pulses are potentially interesting for controlling elementary motions such as the vibration of crystal lattices,the rotation of molecules and the precession of spins. | N Kamaraju Andrea Rubano Linke Jian Surajit Saha T Venkatesan Jan Notzold R Kramer Campen Martin Wolf Tobias Kampfrath | 2014 | Light(Science & Applications)2014，3，1： | 5 |
| 10 | Stromal Elements Act to Restrain, Rather Than Support, Pancreatic Ductal Adenocarcinoma显示文摘 | Andrew D. Rhim Paul E. Oberstein Dafydd H. Thomas Emily T. Mirek Carmine F. Palermo Stephen A. Sastra Erin N. Dekleva Tyler Saunders Claudia P. Becerra Ian W. Tattersall C. Benedikt Westphalen Jan Kitajewski Maite G. Fernandez-Barrena Martin E. Fernandez- | 2014 | Cancer Cell2014，，： | 5 |
| 11 | Helicobacter pylori infection and other bacteria in pancreatic cancer and autoimmune pancreatitis显示文摘Helicobacter pylori(H.pylori)is an infectious agent influencing as much as 50%of the world’s population.It is the causative agent for several diseases,most especially gastric and duodenal peptic ulcer,gastric adenocarcinoma and mucosaassociated lymphoid tissue lymphoma of the stomach.A number of other,extragastric manifestations also are associated with H.pylori infection.These include neurological disorders,such as Alzheimer’s disease,demyelinating multiple sclerosis and Parkinson’s disease.There is also evidence for a relationship between H.pylori infection and such dermatological diseases as psoriasis and rosacea as well as a connection with infection and open-angle glaucoma.Generally little is known about the relationship between H.pylori infection and diseases of the pancreas.Most evidence about H.pylori and its potential role in the development of pancreatic diseases concerns pancreatic adenocarcinoma and autoimmune forms of chronic pancreatitis.There is data(albeit not fully consistent)indicating modestly increased pancreatic cancer risk in H.pylori-positive patients.The pathogenetic mechanism of this increase is not yet fully elucidated,but several theories have been proposed.Reduction of antral Dcells in H.pylori-positive patients causes a suppression of somatostatin secretion that,in turn,stimulates increased secretin secretion.That stimulates pancreatic growth and thus increases the risk of carcinogenesis.Alternatively,H.pylori,as a part of microbiome dysbiosis and the so-called oncobiome,is proven to be associated with pancreatic adenocarcinoma development via the promotion of cellular proliferation.The role of H.pylori in the inflammation characteristic of autoimmune pancreatitis seems to be explained by a mechanism of molecular mimicry among several proteins(mostly enzymes)of H.pylori and pancreatic tissue.Patients with autoimmune pancreatitis often show positivity for antibodies against H.pylori proteins.H.pylori,as a part of microbiome dysbiosis,also is viewed as a potential trigger of autoimmune inflammation of the pancreas.It is precisely these relationships(and associated equivocal conclusions)that constitute a center of attention among pancreatologists,immunologists and pathologists.In order to obtain clear and valid results,more studies on sufficiently large cohorts of patients are needed.The topic is itself sufficiently significant to draw the interest of clinicians and inspire further systematic research.Next-generation sequencing could play an important role in investigating the microbiome as a potential diagnostic and prognostic biomarker for pancreatic cancer. | Lumir Kunovsky Petr Dite Petr Jabandziev Jiri Dolina Jitka Vaculova Martin Blaho Martina Bojkova Jana Dvorackova Magdalena Uvirova Zdenek Kala Jan Trna | 2021 | World Journal of Gastrointestinal Oncology2021，13，8： | 5 |
| 12 | Lrp1 in osteoblasts controls osteoclast activity and protects against osteoporosis by limiting PDGF–RANKL signaling显示文摘Skeletal health relies on architectural integrity and sufficient bone mass, which are maintained through a tightly regulated equilibrium of bone resorption by osteoclasts and bone formation by osteoblasts. Genetic studies have linked the gene coding for low-density lipoprotein receptor-related protein1(Lrp1) to bone traits but whether these associations are based on a causal molecular relationship is unknown. Here, we show that Lrp1 in osteoblasts is a novel regulator of osteoclast activity and bone mass.Mice lacking Lrp1 specifically in the osteoblast lineage displayed normal osteoblast function but severe osteoporosis due to highly increased osteoclast numbers and bone resorption. Osteoblast Lrp1 limited receptor activator of NF-κB ligand(RANKL) expression in vivo and in vitro through attenuation of platelet-derived growth factor(PDGF-BB) signaling. In co-culture, Lrp1-deficient osteoblasts stimulated osteoclastogenesis in a PDGFRβ-dependent manner and in vivo treatment with the PDGFR tyrosine kinase inhibitor imatinib mesylate limited RANKL production and led to complete remission of the osteoporotic phenotype. These results identify osteoblast Lrp1 as a key regulator of osteoblast-to-osteoclast communication and bone mass through a PDGF–RANKL signaling axis in osteoblasts and open perspectives to further explore the potential of PDGF signaling inhibitors in counteracting bone loss as well as to evaluate the importance of functional LRP1 gene variants in the control of bone mass in humans. | Alexander Bartelt Friederike Behler-Janbeck F.Timo Beil Till Koehne Brigitte Müller Tobias Schmidt Markus Heine Laura Ochs Tayfun Yilmaz Martin Dietrich Jan P.Tuckermann Michael Amling Joachim Herz Thorsten Schinke Joerg Heeren Andreas Niemeier | 2018 | Bone Research2018，6，1： | 5 |
| 13 | Health-related quality of life in high-grade glioma patients显示文摘Gliomas are malignant primary brain tumors and yet incurable. Palliation and the maintenance or improvement of the patient's quality of life is therefore of main importance. For that reason, health-related quality of life(HRQoL) has become an important outcome measure in clinical trials, next to traditional outcome measures such as overall and progression-free survivals, and radiological response to treatment. HRQoL is a multidimensional concept covering physical, psychological, and social domains, as well as symptoms induced by the disease and its treatment. HRQoL is assessed by using self-reported, validated questionnaires. Various generic HRQoL questionnaires, which can be supplemented with a brain tumor- specific module, are available. Both the tumor and its treatment can have a negative effect on HRQoL. However, treatment with surgery, radiotherapy, chemotherapy, and supportive treatment may also improve patients' HRQoL, in addition to extending survival. It is expected that the impact of HRQoL measurements in both clinical trials and clinical practice will increase. Hence, it is important that HRQoL data are collected, analyzed, and interpreted correctly. Methodological issues such as selection bias and missing data may hamper the interpretation of HRQoL data and should therefore be accounted. In clinical trials, HRQoL can be used to assess the benefits of a new treatment strategy, which should be weighed carefully against the adverse effects of that treatment. In daily clinical practice, HRQoL assessments of an individual patient can be used to inform physicians about the impact of a specific treatment strategy, and it may facilitate the communication between the physicians and the patients. | Linda Dirven Neil K.Aaronson Jan J.Heimans Martin J.B.Taphoorn | 2014 | Chinese Journal of Cancer2014，33，1： | 4 |
| 14 | Partial external biliary diversion in bile salt export pump deficiency: Association between outcome and mutation显示文摘AIM To investigate the relation of two different mutations to the outcome of partial external biliary diversion(PEBD)in severe bile salt export pump(BSEP) deficiency.METHODS Mutations in the gene encoding BSEP leading to severe BSEP deficiency in two unrelated patients were identified by genomic sequencing. Native liver biopsies and transiently transfected human embryonic kidney(HEK) 293 cells expressing either wild-type or mutated BSEP were subjected to immunofluorescence analysis to assess BSEP transporter localization. Bile acid profiles of patient and control bile samples were generated by ultra-performance liquid chromatographytandem mass spectrometry. Wild-type and mutant BSEP transport of [~3H]-labeled taurocholate(TC) and taurochenodeoxycholate(TCDC) was assessed by vesicular transport assays.RESULTS A girl(at 2 mo) presented with pruritus, jaundice and elevated serum bile salts(BS). PEBD stabilized liver function and prevented liver transplantation. She was heterozygous for the BSEP deletion p.T919 del and the nonsense mutation p.R1235 X. At the age of 17 years relative amounts of conjugated BS in her bile were normal, while total BS were less than 3% as compared to controls. An unrelated boy(age 1.5 years) presenting with severe pruritus and elevated serum BS was heterozygous for the same nonsense and another missense mutation, p.G1032 R. PEBD failed to alleviate pruritus, eventually necessitating liver transplantation. BS concentration in bile was about 5% of controls. BS were mainly unconjugated with an unusual low amount of chenodeoxycholate derivatives(< 5%). The patients' native liver biopsies showed canalicular BSEP expression. Both BSEP p.T919 del and p.G1032 R were localized in the plasma membrane in HEK293 cells. In vitro transport assays showed drastic reduction of transport by both mutations. Using purified recombinant BSEP as quantifiable reference, per-molecule transport rates for TC and TCDC were determined to be 3 and 2 BS molecules per wild-type BSEP transporter per minute, respectively.CONCLUSION In summary, our findings suggest that residual function of BSEP as well as substrate specificity influence the therapeutic effectiveness of PEBD in progressive familial intrahepatic cholestasis type 2(PFIC-2). | Philipp Ellinger Jan Stindt Carola Droge Katharina Sattler Claudia Stross Stefanie Kluge Diran Herebian Sander HJ Smits Martin Burdelski Sebastian Schulz-Jürgensen Antje Ballauff Jan Schulte am Esch Ertan Mayatepek Dieter Haussinger Ralf Kubitz Lutz Schmitt | 2017 | World Journal of Gastroenterology2017，23，29： | 4 |
| 15 | Histological grading and staging of chronic hepatitis显示文摘 | Kamal Ishak Amelia Baptista Leonardo Bianchi Francesco Callea Jan De Groote Fred Gudat Helmut Denk Valeer Desmet Gerhard Korb Roderick N.M. MacSween M.James Phillips Bernard G. Portmann Hemming Poulsen Peter J. Scheuer Martin Schmid Heribert Thaler | 1995 | Journal of Hepatology1995，，6： | 4 |
| 16 | Indole phytoalexin derivatives induce mitochondrialmediated apoptosis in human colorectal carcinoma cells显示文摘AIM To investigate the mechanism of the antiproliferative effect of synthetic indole phytoalexin derivatives on human colorectal cancer cell lines.METHODS Changes in cell proliferation and the cytotoxic effect of the tested compounds on human colorectal cancer cell lines and human fibroblasts were evaluated using MTS and Brd U assay,allowing us to choose the most potent substance.Cell cycle alterations were analyzed using flow cytometric analysis.The apoptosis-inducing effect of compound K-453 on the HCT116 cell line was examined with annexin V/PI double staining using flow cytometry,as well as acridine orange/propidium iodide(AO/PI)staining.The flow cytometry method also allowed us to measure changes in levels or activation states of other factors associated with apoptosis,such as poly(ADP-ribose)polymerase(PARP),caspase-3 and-9,cytochrome c,Bcl-2 family proteins,and also the integrity of the mitochondrial membrane.To evaluate activity of the transcription factors and proteins involved in signaling pathways we used Western blot analysis together with flow cytometry.RESULTS Among the ten tested compounds,compound K-453{(±)-trans-1,2-dimethoxy-2’-(3,5-bis-trifluoromethylphenylamino)spiro{indoline-3,5’[4’,5’]dihydrothiazol}exhibited the most potent activity with IC50=32.22±1.14μmol/L in human colorectal HCT116 cells and was thus selected for further studies.Flow cytometric analysis revealed a K-453-induced increase in the population of cells with sub-G1 DNA content,which is considered as a marker of apoptotic cell death.The apoptosis-inducing effect of compound K453 was also confirmed by annexin V/PI double staining and AO/PI staining.The apoptosis was associated with the loss of mitochondrial membrane potential,PARP cleavage,caspase-3 and caspase-9 activation,release of cytochrome c,as well as changes in the levels of Bcl-2family members.Moreover,flow cytometry showed that compound K-453 stimulates phosphorylation of p38MAPK but decreases phosphorylation of Akt and Erk1/2.Activation of p38 MAPK was also confirmed using Western blot analysis.This analysis also revealed downregulation of NF-κB1(p50)and Rel A(p65)proteins and the loss of their anti-apoptotic activity.CONCLUSION In our study compound K-453 exhibited an antiproliferative effect by induction of intrinsic apoptosis as well as modulation of several signaling pathways. | Viera Tischlerova Martin Kello Mariana Budovska Jan Mojzis | 2017 | World Journal of Gastroenterology2017，23，24： | 4 |
| 17 | Histological grading and staging of chronic hepatitis显示文摘 | Kamal Ishak Amelia Baptista Leonardo Bianchi Francesco Callea Jan De Groote Fred Gudat Helmut Denk Valeer Desmet Gerhard Korb Roderick N.M. MacSween M.James Phillips Bernard G. Portmann Hemming Poulsen Peter J. Scheuer Martin Schmid Heribert Thaler | 1995 | Journal of Hepatology1995，，6： | 4 |
| 18 | Dubin-Johnson syndrome coinciding with colon cancer and atherosclerosis显示文摘Hyperbilirubinemia has been presumed to prevent the process of atherogenesis and cancerogenesis mainly by decreasing oxidative stress.Dubin-Johnson syndrome is a rare,autosomal recessive,inherited disorder characterized by biphasic,predominantly conjugatedhyperbilirubinemia with no progression to end-stage liver disease.The molecular basis in Dubin-Johnson syndrome is absence or deficiency of human canalicular multispecific organic anion transporter MRP2/cMOAT caused by homozygous or compound heterozygous mutation(s) in ABCC2 located on chromosome 10q24.Clinical onset of the syndrome is most often seen in the late teens or early adulthood.In this report,we describe a case of previously unrecognized Dubin-Johnson syndrome caused by two novel pathogenic mutations (c.2360_2366delCCCTGTC and c.3258+1G>A),coinciding with cholestatic liver disease in an 82-year-old male patient.The patient,suffering from advanced atherosclerosis with serious involvement of coronary arteries,developed colorectal cancer with nodal metastases.The subsequent findings do not support the protective role of Dubin-Johnson type hyperbilirubinemia. | Eva Sticova Milan Elleder Helena Hulkova Ondrej Luksan Martin Sauer Irena Wunschova-Moudra Jan Novotny Milan Jirsa | 2013 | World Journal of Gastroenterology2013，19，6： | 4 |
| 19 | Neonatal vitamin A injection promotes cattle muscle growth and increases oxidative muscle fibers显示文摘Background: Vitamin A and its metabolite,retinoic acid(RA),are important regulators of cell differentiation and organ morphogenesis.Its impact on beef cattle muscle growth remains undefined.Method: Angus steer calves were administrated with 0(control) or 150,000 IU vitamin A(retinyl palmitate in glycerol,i.m.) per calf at birth and 1 month of age.At 2 months of age,a biopsy of the Biceps femoris muscle was obtained to analyze the immediate effects of vitamin A injection on myogenic capacity of muscle cells.The resulting steers were harvested at 14 months of age.Results: Vitamin A administration increased cattle growth at 2 months.At 2 months of age,Vitamin A increased PAX7 positive satellite cells and the expression of myogenic marker genes including PAX7,MYF5,MYOD and MYOG.Muscle derived mononuclear cells were further isolated and induced myogenesis in vitro.More myotubes and a higher degree of myogenesis was observed in vitamin A groups.Consistently,vitamin A increased Latissimus dorsi(LD) muscle fiber size at harvest.In addition,vitamin A increased the ratio of oxidative type I and type IIA fibers and reduced the glycolic type IIX fibers.Furthermore,we found that RA,a key bioactive metabolite of vitamin A,activated PPARGC1 A promoter,which explains the upregulated expression of PPARGC1 A in skeletal muscle.Conclusion: Vitamin A administration to neonatal calves enhanced postnatal muscle growth by promoting myogenesis and increasing satellite cell density,accompanied with a shift to oxidative muscle fibers. | Bo Wang Wei Nie Xing Fu Jeanene M de Avila Yannan Ma Mei-Jun Zhu Martin Maquivar Steven M Parish Jan R Busboom Mark L Nelson Min Du | 2019 | Journal of Animal Science and Biotechnology2019，10，1： | 3 |
| 20 | 小P值并不能保证可靠结果:以帕金森病的静息态脑功能成像元分析为例显示文摘Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because of the large number of voxels in the brain,multiple comparison correction(MCC)must be performed to reduce false positive rates,and a smaller P value(usually including either liberal or stringent MCC)is widely recommended[1]. | 贾熙泽 赵娜 董昊铭 孙家伟 Marek Barton Roxana Burciu Nicolas Carrière Antonio Cerasa 陈博宇 陈俊 Stephen Coombes Luc Defebvre Christine Delmaire Kathy Dujardin Fabrizio Esposito 范国光 Federica Di Nardo 冯怡萱 Brett W.Fling Saurabh Garg Moran Gilat Martin Gorges Shu-Leong Ho Fay B.Horak 胡晓 胡晓飞 黄飚 黄沛钰 贾泽娟 Christina Jones Jan Kassubek Lenka Krajcovicova Ajay Kurani 李静 李晴 刘爱萍 刘波 刘虎 刘卫国 Renaud Lopes 娄毓婷 罗巍 Tara Madhyastha 毛妮妮 Grainne McAlonan Martin J.McKeown Shirley Pang Andrea Quattrone Irena Rektorova Alessia Sarica 商慧芳 James M.Shine Priyank Shukla Tomas Slavicek 宋潇鹏 Gioacchino Tedeschi Alessandro Tessitore David Vaillancourt 王健 王珏 Z.Jane Wang 魏鲁庆 邬霞 徐晓俊 闫磊 杨靓 杨万群 姚乃琳 张得龙 张久权 张敏鸣 张艳玲 周彩红 严超赣 左西年 Mark Hallett 吴涛 臧玉峰 | 2021 | Science Bulletin2021，66，21： | 3 |
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