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| 1 | Diabetic nephropathy:Is it time yet for routine kidney biopsy?显示文摘Diabetic nephropathy(DN)is one of the most important long-term complications of diabetes.Patients with diabetes and chronic kidney disease have an increased risk of all-cause mortality,cardiovascular mortality,and kidney failure.The clinical diagnosis of DN depends on the detection of microalbuminuria.This usually occurs after the first five years from the onset of diabetes,and predictors of DN development and progression are being studied but are not yet implemented into clinical practice.Diagnostic tests are useful tools to recognize onset,progression and response to therapeutic interventions.Microalbuminuria is an indicator of DN,and it is considered the only noninvasive marker of early onset.However,up to now there is no diagnostic tool that can predict which patients will develop DN before any damage is present.Pathological renal injury is hard to predict only with clinical and laboratory findings.An accurate estimate of damage in DN can only be achieved by the histological analysis of tissue samples.At the present time,renal biopsy is indicated on patients with diabetes under the suspicion of the presence of nephropathies other than DN.Results from renal biopsies in patients with diabetes had made possible the classification of renal biopsies in three major groups associated with different prognostic features:diabetic nephropathy,non-diabetic renal disease(NDRD),and a superimposed non-diabetic condition on underlying diabetic nephropathy.In patients with type 2 diabetes with a higher degree of suspicion for NDRD,it is granted the need of a renal biopsy.It is important to identify and differentiate these pathologies at an early stage in order to prevent progression and potential complications.Therefore,a more extensive use of biopsy is advisable. | Maria L Gonzalez Suarez David B Thomas Laura Barisoni Alessia Fornoni | 2013 | World Journal of Diabetes2013，4，6： | 29 |
| 2 | Radioembolization for the treatment of unresectable hepatocellular carcinoma:A clinical review显示文摘Hepatocellular carcinoma(HCC)is the sixth most common cancer in the world.The majority of patients with HCC present with unresectable disease.These patients have historically had limited treatment options secondary to HCC demonstrating chemoresistance to the currently available systemic therapies.Additionally, normal liver parenchyma has shown intolerance to tumoricidal radiation doses,limiting the use of external beam radiation.Because of these limitations,novel percutaneous liver-directed therapies have emerged. The targeted infusion of radioactive microspheres (radioembolization)represents one such therapy. Radioembolization is a minimally invasive transcatheter therapy through which radioactive microspheres are infused into the hepatic arteries that supply tumor. Once infused,these microspheres traverse the hepatic vascular plexus and selectively implant within the tumor arterioles.Embedded within the arterioles, the 90Y impregnated microspheres emit high energy and low penetrating radiation doses selectively to the tumor.Radioembolization has recently shown promise for the treatment of patients with unresectable HCC. The objective of this review article is to highlight twocurrently available radioembolic devices(90Y,188Rh)and provide the reader with a recent review of the literature. | Saad M Ibrahim Robert J Lewandowski Kent T Sato Vanessa L Gates Laura Kulik Mary F Mulcahy Robert K Ryu Reed A Omary Riad Salem | 2008 | World Journal of Gastroenterology2008，14，11： | 14 |
| 3 | New therapeutic options opened by the molecular classification of gastric cancer显示文摘Gastric cancer(GC) is one of the most lethal and aggressive cancers, being the third cause of cancer related death worldwide. Even with radical gastrectomy and the latest generation of molecular chemotherapeutics, the numbers of recurrence and mortality remains high. This is due to its biological heterogeneity based on the interaction between multiple factors, from genomic to environmental factors, diet or infections with various pathogens. Therefore, understanding the molecular characteristics at a genomic level is critical to develop new treatment strategies. Recent advances in GC molecular classification provide the unique opportunity to improve GC therapy by exploiting the biomarkers and developing novel targeted therapy specific to each subtype. This article highlights the molecular characteristics of each subtype of gastric cancer that could be considered in shaping a therapeutic decision, and also presents the completed and ongoing clinical trials addressed to those targets. The implementation of the novel molecular classification system will allow a preliminary patient selection for clinical trials, a mandatory issue if it is desired to test the efficacy of a certain inhibitor to the given target. This will represent a substantial advance as well as a powerful tool for targeted therapy. Nevertheless, translating the scientific results into new personalized treatment opportunities is needed in order to improve clinical care, the survival and quality of life of patients with GC. | Mihaela Chivu-Economescu Lilia Matei Laura G Necula Denisa L Dragu Coralia Bleotu Carmen C Diaconu | 2018 | World Journal of Gastroenterology2018，24，18： | 14 |
| 4 | microRNAs: Fad or future of liver disease显示文摘microRNAs (miRs) are small non-coding RNAs that regulate both mRNA and protein expression of target genes, which results in alterations in mRNA stability or translation inhibition. miRs influence at least one third of all human transcripts and are known regulators of various important cellular growth and differentiation factors. miRs have recently emerged as key regulatory molecules in chronic liver disease. This review details recent contributions to the field of miRs that influence liver development and the broad spectrum of disease, from non-alcoholic fatty liver disease to fibrosis/cirrhosis, with particular emphasis on hepatic stellate cells and potential use of miRs as therapeutic tools. | Ashley M Lakner Herbert L Bonkovsky Laura W Schrum | 2011 | World Journal of Gastroenterology2011，17，20： | 13 |
| 5 | An integrated approach for increasing breeding efficiency in apple and peach in Europe显示文摘Despite the availability of whole genome sequences of apple and peach,there has been a considerable gap between genomics and breeding.To bridge the gap,the European Union funded the FruitBreedomics project(March 2011 to August 2015)involving 28 research institutes and private companies.Three complementary approaches were pursued:(i)tool and software development,(ii)deciphering genetic control of main horticultural traits taking into account allelic diversity and(iii)developing plant materials,tools and methodologies for breeders.Decisive breakthroughs were made including the making available of ready-to-go DNA diagnostic tests for Marker Assisted Breeding,development of new,dense SNP arrays in apple and peach,new phenotypic methods for some complex traits,software for gene/QTL discovery on breeding germplasm via Pedigree Based Analysis(PBA).This resulted in the discovery of highly predictive molecular markers for traits of horticultural interest via PBA and via Genome Wide Association Studies(GWAS)on several European genebank collections.FruitBreedomics also developed pre-breeding plant materials in which multiple sources of resistance were pyramided and software that can support breeders in their selection activities.Through FruitBreedomics,significant progresses were made in the field of apple and peach breeding,genetics,genomics and bioinformatics of which advantage will be made by breeders,germplasm curators and scientists.A major part of the data collected during the project has been stored in the FruitBreedomics database and has been made available to the public.This review covers the scientific discoveries made in this major endeavour,and perspective in the apple and peach breeding and genomics in Europe and beyond. | Francois Laurens Maria JoséAranzana Pere Arus Daniele Bassi Marco Bink Joan Bonany Andrea Caprera Luca Corelli-Grappadelli Evelyne Costes Charles-Eric Durel Jehan-Baptiste Mauroux Hélène Muranty Nelson Nazzicari Thierry Pascal Andrea Patocchi Andreas Peil Bénédicte Quilot-Turion Laura Rossini Alessandra Stella Michela Troggio Riccardo Velasco Eric van de Weg | 2018 | Horticulture Research2018，5，1： | 10 |
| 6 | Therapies targeting cancer stem cells: Current trends and future challenges显示文摘Traditional therapies against cancer, chemo- and radiotherapy, have multiple limitations that lead to treatment failure and cancer recurrence. These limitations are related to systemic and local toxicity, while treatment failure and cancer relapse are due to drug resistance and self-renewal, properties of a small population of tumor cells called cancer stem cells(CSCs). These cells are involved in cancer initiation, maintenance, metastasis and recurrence. Therefore, in order to develop efficient treatments that can induce a longlasting clinical response preventing tumor relapse it is important to develop drugs that can specifically target and eliminate CSCs. Recent identification of surface markers and understanding of molecular feature associated with CSC phenotype helped with the design of effective treatments. In this review we discuss targeting surface biomarkers, signaling pathways that regulate CSCs self-renewal and differentiation, drug-efflux pumps involved in apoptosis resistance, microenvironmental signals that sustain CSCs growth, manipulation of mi RNA expression, and induction of CSCs apoptosis and differentiation, with specific aim to hamper CSCs regeneration and cancer relapse. Some of these agents are under evaluation in preclinical and clinical studies, most of them for using in combination with traditional therapies. The combined therapy using conventional anticancer drugs with CSCs-targeting agents, may offer a promising strategy for management and eradication of different types of cancers. | Denisa L Dragu Laura G Necula Coralia Bleotu Carmen C Diaconu Mihaela Chivu-Economescu | 2015 | World Journal of Stem Cells2015，7，9： | 10 |
| 7 | Titanium dioxide induced inflammation in the small intestine显示文摘AIM:To investigate the effects of titanium dioxide (TiO2) nanoparticles (NPTiO 2 ) and microparticles (MPTiO 2 ) on the inflammatory response in the small intestine of mice. METHODS: Bl 57/6 male mice received distilled water suspensions containing TiO 2 (100 mg/kg body weight) as NPTiO 2 (66 nm), or MPTiO 2 (260 nm) by gavage for 10 d, once a day; the control group received only distilled water. At the end of the treatment the duodenum, jejunum and ileum were extracted for assessment of cytokines, inflammatory cells and titanium content. The cytokines interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor necrosis factor-α (TNF-α), intracellular interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) were evaluated by enzyme-linked immunosorbent assay in segments of jejunum and ileum (mucosa and underlying muscular tissue). CD4 + and CD8 + T cells, natural killer cells, and dendritic cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin by immuno-histochemistry. The titanium content was determined by inductively coupled plasma atomic emission spectrometry. RESULTS: We found increased levels of T CD4 + cells (cells/mm 2 ) in duodenum:NP 1240 ± 139.4, MP 1070 ± 154.7 vs 458 ± 50.39 (P < 0.01); jejunum:NP 908.4 ± 130.3, MP 813.8 ± 103.8 vs 526.6 ± 61.43 (P < 0.05); and ileum:NP 818.60 ± 123.0, MP 640.1 ± 32.75 vs 466.9 ± 22.4 (P < 0.05). In comparison to the control group, the groups receiving TiO 2 showed a statistically significant increase in the levels of the inflammatory cytokines IL-12, IL-4, IL-23, TNF-α, IFN-γ and TGF-β. The cytokine production was more pronounced in the ileum (mean ± SE):IL-12: NP 33.98 ± 11.76, MP 74.11 ± 25.65 vs 19.06 ± 3.92 (P < 0.05); IL-4: NP 17.36 ± 9.96, MP 22.94 ± 7.47 vs 2.19 ± 0.65 (P < 0.05); IL-23: NP 157.20 ± 75.80, MP 134.50 ± 38.31 vs 22.34 ± 5.81 (P < 0.05); TNFα: NP 3.71 ± 1.33, MP 5.44 ± 1.67 vs 0.99± 019 (P < 0.05); IFNγ: NP 15.85 ± 9.99, MP 34.08 ± 11.44 vs 2.81 ± 0.69 (P < 0.05); and TGF-β: NP 780.70 ± 318.50, MP 1409.00 ± 502.20 vs 205.50 ± 63.93 (P < 0.05). CONCLUSION:Our findings indicate that TiO2 particles induce a Th1-mediated inflammatory response in the small bowel in mice. | Carolina Maciel Nogueira Walter Mendes de Azevedo Maria Lucia Zaidan Dagli Sérgio Hiroshi Toma AndréZonetti de Arruda Leite Maria Laura Lordello Iêda Nishitokukado Carmen Lúcia Ortiz-Agostinho Maria IrmaSeixas Duarte Marcelo Alves Ferreira Aytan Miranda Sipahi | 2012 | World Journal of Gastroenterology2012，18，34： | 8 |
| 8 | High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes显示文摘Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening(HTS) data for 3 762 distinct global gene knockout(KO) mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type(WT) cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging,ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass: 23 previously reported genes(Calcr, Cebpb, Crtap, Dcstamp, Dkk1, Duoxa2, Enpp1, Fgf23, Kiss1/Kiss1 r, Kl(Klotho),Lrp5, Mstn, Neo1, Npr2, Ostm1, Postn, Sfrp4, Slc30a5, Slc39a13, Sost, Sumf1, Src, Wnt10b), five novel genes extensively characterized(Cldn18, Fam20 c, Lrrk1, Sgpl1, Wnt16), five novel genes with preliminary characterization(Agpat2, Rassf5, Slc10a7, Slc26a7, Slc30a10) and three novel undisclosed genes coding for potential osteoporosis drug targets. | Robert Brommage Jeff Liu Gwenn M Hansen Laura L Kirkpatrick David G Potter Arthur T Ss Brian Zambrowicz David R Powell Peter Vogel | 2014 | Bone Research2014，2，3： | 7 |
| 9 | Counter-regulatory phosphatases TNAP and NPP1 temporally regulate tooth root cementogenesis显示文摘Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone.Biomineralization is regulated by the ratio of inorganic phosphate(Pi) to mineral inhibitor pyrophosphate(PPi), where local Piand PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase(TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1(NPP1). The focus of this study was to define the roles of these phosphatases in cementogenesis. TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the Enpp1 null mouse increased acellular cementum, with little effect on cellular cementum.Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas Enpp1 gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPienvironment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPihave little effect on cellular cementum formation, though matrix mineralization is affected. | Laura E Zweifler Mudita K Patel Francisco H Nociti Jr Helen F Wimer Jose L Milln Martha J Somerman Brian L Foster | 2015 | International Journal of Oral Science2015，7，1： | 5 |
| 10 | Mental and physical symptoms associated with lower social support for patients with hepatitis C显示文摘AIM: To systematically examine the impact of the hepatitis C virus (HCV) diagnosis on patients' level of social support in a large-scale study. METHODS: Patients evaluated and treated for HCV in a tertiary referral center were enrolled in a cross-sectional study. Demographic data, functional and emotional status as measured by the Hospital Anxiety and Depression Scale (HAD) and the Sickness Impact Profile (SIP), severity of liver disease, mode of acquisition, and physical and psychiatric comorbidities were collected from patients or abstracted from the medical record. All participants completed a semi-structured interview, addressing questions of social support. RESULTS: A total of 342 patients (mean age 45.2 years; 37% women) were enrolled. Ninety-two (27%) patients described lower levels of support by family and friends. Nearly half of the participants (45%) noted the loss of at least one relationship due to the disease. Fears related to transmitting the disease (25%) were common and often associated with ignorance or even discrimination by others (19%). Nearly one fifth of the patients did not share information about their disease with others to avoid being stigmatized. Lower levels of social support were significantly associated with living alone, being unemployed, being excluded from antiviral therapy, having psychiatric comorbidities, contracting HCV through intravenous drug use, having high levels of anxiety and depression as measured by the HAD and negative mood state as measured by the SIP. Patients reporting lower levels of social support also noted more physical symptoms as measured by the SIP. CONCLUSION: Patients with hepatitis C often face significant social problems, ranging from social isolation to familial stress. The most common concerns reflect a limited insight of patients and their relatives and friends about the disease, the risk factors for its spread, and about potential consequences. Our data suggest that educational interventions targeting support persons and the stressors identified in our findings may lessen or alleviate the social strains patients with hepatitis C experience. | Julie A Blasiole Laura Shinkunas Douglas R LaBrecque Robert M Arnold Susan L Zickmund | 2006 | World Journal of Gastroenterology2006，12，29： | 5 |
| 11 | Patients'perspectives on smoking and inflammatory bowel disease:An online survey in collaboration with European Federation of Crohn's and Ulcerative Colitis Associations显示文摘BACKGROUNDSmoking has detrimental effects on Crohn’s disease (CD) activity while data onulcerative colitis (UC) are conflicting. Little is known about the use and impact ofalternative smoking products in inflammatory bowel diseases (IBD).AIMTo understand the patients’ perceptions of the impact of smoking on their IBDand to assess differences between CD and UC patients.METHODSThe questionnaire was developed by Philip Morris Products SA in cooperationwith European Federation of Crohn's and Ulcerative Colitis Associations. Thefinal survey questionnaire consisted of 41 questions divided in 8 categories: (1)Subject screener;(2) Smoking history;(3) Background information;(4) IBD diseasebackground;(5) Current disease status;(6) Current therapeutics and medications;and (7) Current nicotine/cigarettes use and awareness of the impacts of smokingon IBD. The questionnaire was submitted online from 4th November 2019 to 11th March 2020 through the European Federation of Crohn's and Ulcerative ColitisAssociations website to IBD patients who were current smokers or had a historyof smoking.RESULTSIn total 1050 IBD patients speaking nine languages participated to the survey.Among them, 807 (76.9%) patients declared to have ever smoked or consumed analternative smoking product, with a higher proportion of current cigarettesmokers among CD patients (CD: 63.1% vs UC: 54.1%, P = 0.012). About twothirdsof the participants declared to have ever stopped cigarette smoking andrestarted (67.0%), with a significantly higher proportion among UC patientscompared to CD patients (73.1% vs 62.0%, P = 0.001). We also found significantdifferences between CD and UC patients in the awareness of the healthconsequences of smoking in their disease and in the perceived impact of smokingon disease activity, for both cigarettes and alternative smoking products.CONCLUSIONThis survey found significant differences between CD and UC patients in bothawareness and perception of the impact of smoking on their disease. Furtherefforts should be done to encourage smoking cessation for all IBD patients,including UC patients. | Catherine Le Berre Laura Loy Sanna Lönnfors Luisa Avedano Daniele Piovani | 2020 | World Journal of Gastroenterology2020，26，29： | 4 |
| 12 | High prevalence of vitamin A deficiency in Crohn's disease patients according to serum retinol levels and the relative dose-response test显示文摘AIM:To assess the vitamin A status of patients with Crohn's disease(CD) by evaluating serum retinol levels and the relative dose response(RDR) test(liver retinol stores).METHODS:Vitamin A nutritional status was measured by serum retinol obtained by high performance liquid chromatography and the RDR test for evaluation of the hepatic stores.Body composition was performed by densitometry by dual-energy X-ray absorptiometry.Vitamin A dietary intake was assessed from a semiquantitative food frequency questionnaire.RESULTS:This study included 38 CD patients and 33 controls.Low serum retinol concentrations were detected in 29% of CD patients vs 15% in controls(P < 0.005).The RDR test was positive in 37% of CD patients vs 12% in controls,which indicated inadequate hepatic vitamin A stores(P < 0.005).Individuals with hypovitaminosis A had lower BMI and body fat compared with those without this deficiency.There was no association between vitamin A deficiency and its dietary intake,ileal location,presence of disease activity and prior bowel resections.CONCLUSION:Patients with CD have higher prevalence of vitamin A deficiency,as assessed by two independent methods. | Márcia Soares-Mota Tianny A Silva Luanda M Gomes Marco AS Pinto Laura MC Mendon?a Maria Lúcia F Farias Tiago Nunes Andrea Ramalho Cyrla Zaltman | 2015 | World Journal of Gastroenterology2015，21，5： | 4 |
| 13 | FOLFIRINOX and translational studies: Towards personalized therapy in pancreatic cancer显示文摘Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase Ⅲ trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARClevels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microR NAs as predictive biomarkers. | Chiara Caparello Laura L Meijer Ingrid Garajova Alfredo Falcone Tessa Y Le Large Niccola Funel Geert Kazemier Godefridus J Peters Enrico Vasile Elisa Giovannetti | 2016 | World Journal of Gastroenterology2016，22，31： | 4 |
| 14 | PrP^C-related signal transduction is influenced by copper, membrane integrity and the alpha cleavage site显示文摘铜绑定,抛锚膜的、细胞的 prion 蛋白质(PrPC ) 有二个组成的劈开地点生产不同 N 终端和 C 终端碎片(N1/C1 和 N2/C2 ) 。用表示也人的 PrPC,鼠标 PrPC 或鼠标 PrPC 的 RK13 房间带 3F4 epitope,这研究在 endoproteolytic 劈开和一个通常认为的 PrPC 函数上探索了 PrPC 主要顺序的影响,地图 kinase 信号 transduction,响应外长的铜与或没有使不安的膜环境。PrPC 主要顺序,特别在 N1/C1 劈开地点附近,看起来在这个地点和细胞外的调整信号的 kinase 1/2 (ERK1/2 ) phosphorylation 影响解朊作用的基础层次,与处理激活增加与基础 ERK1/2 表明一种反的关系。人的 PrPC 独自响应铜显示出增加的 N1/C1 劈开,由特定的 p38 和 JNK/SAPK phosphorylation 伴随了。到加扣押胆固醇的抗菌素 filipin 的铜的联合暴露导致了一只老鼠信号蛋白质 phosphorylation 的 PrPC 特定的实质的增加,由 N1/C1 劈开的增加伴随了。怀有人的 N1/C1 劈开地点的老鼠 PrPC 基础地并且响应铜假定更似人类的侧面并且改变了膜环境。我们的结果证明在 N1/C1 劈开地点附近的 PrPC 主要顺序影响在这个地点处理的 endoproteolytic,它显得连接了基础地并且响应铜印射 kinase 信号 transduction。进一步,主要顺序看起来响应外长的刺激在 PrPC 相关的信号 transduction 的忠实上授与 N1/C1 劈开和膜完整的相互的依赖。 | Cathryn L Haigh | 2009 | Cell Research2009，19，9： | 4 |
| 15 | Nutritional and health benefits of semi-elemental diets: A comprehensive summary of the literature显示文摘AIM:To critically review and summarize the literature on nutritional and health outcomes of semi-elemental formulations on various nutritionally vulnerable patient populations who are unable to achieve adequate nutrition from standard oral diets.METHODS:We conducted a comprehensive literature search of Pubmed and Embase databases.We manually screened articles that examined nutritional and health outcomes(e.g.,growth,disease activity,gastrointestinal impairment,mortality,and economic impact)among various patient groups receiving semi-elemental diets.This review focused on full-text articles of randomized controlled clinical trials and other intervention studies,but pertinent abstracts and case studies were also included.Results pertaining primarily to tolerance,digestion,and absorption were summarized for each patient population in this systematic review.RESULTS:Results pertaining primarily to tolerance,digestion,and absorption were summarized for each patient population.The efficacy of semi-elemental whey hydrolyzed protein(WHP)diet have been reported in various nutritionally high risk patient populations including-Crohn’s disease,short bowel syndrome,acute and chronic pancreatitis,cerebral palsy,cystic fibrosis,cerebrovascular accidents,human immunodeficiency virus,critically ill,and geriatrics.Collectively,the evidence from the medical literature indicates that feeding with a semi-elemental diet performs as well or better than parenteral or amino acid based diets in terms of toler-ance,digestion,and nutrient assimilation measures across various disease conditions.CONCLUSION:Based on this comprehensive review of the literature,patient populations who have difficulty digesting or absorbing standard diets may be able to achieve improved health and nutritional outcomes through the use of semi-elemental WHP diets. | Dominik D Alexander Lauren C Bylsma Laura Elkayam Douglas L Nguyen | 2016 | World Journal of Gastrointestinal Pharmacology and Therapeutics2016，7，2： | 3 |
| 16 | FK506对实验性卒中疗效的系统评价和Meta分析显示文摘FK506是治疗急性卒中的一种候选用药。决定一种药物是否可以用于临床试验,应当以全面的、无偏倚的动物实验数据的评估为依据,同时还应考虑到这些数据的局限性。这种评估不但应包括药物疗效,而且也应包括药效在体内的特征和局限性。本研究应用系统评价和Meta分析的方法对FK506在卒中动物模型中保护作用的证据进行评价。总共纳入了29个描述了实验步骤的研究,包括1759只动物。结果显示,FK506疗效的点估计值(结局指标的改善)是31.3%[95%CI(0.272-0.354)]。在采用氯胺酮麻醉和短暂性脑缺血的动物实验中,FK506的疗效更高,在使用大鼠,合并其他疾病的动物及仅以梗死面积为疗效指标的实验中,FK506疗效较低。已发表的实验研究质量均接近临床试验标准,但在高质量的研究中,FK506的疗效较低。FK506在实验性脑卒中的研究中,虽然显示出有明显的疗效,但是应注意由于研究质量和可能的发表偏倚等冈素的影响,FK506的疗效可能被过高估计。 | Malcolm R Macleod Tori O’Collins Laura L Horky David W Howells Geoffrey A Donnan 段建钢 | 2006 | 中国循证医学杂志2006，6，6： | 3 |
| 17 | Proteomic analysis for developing new biomarkers of hepatocellular carcinoma显示文摘AIM: To identify new markers of hepatocellular carcinoma (HCC) using a proteomic analysis. METHODS: Patients with liver cirrhosis of the three most frequent etiologies: hepatitis C virus, hepatitis B virus and alcoholic liver disease, were included in the study. The samples were analysed by 2D-electrophoresis in order to determine the differential protein expression. The proteins were separated according to the charge in immobilized pH 3-10 gradient strips and then by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins of interest were excised, digested with trypsin and the resulting peptides were separated and identified. RESULTS: Three differentially expressed apolipoproteins (Apo) were identified based on the protein profile using proteomic techniques: Apo-A1, Apo-A4 and Apo-E. Apo-A4 levels were significantly lower in HCC than in non-HCC patients regardless of etiology (P < 0.01). Multivariate logistic regression showed that Apo-A4 and Apo-A1 were the only independent factors related to HCC diagnosis (P < 0.05). The receiver operating characteristic (ROC) curve including both Apo-A4 and Apo-A1 showed an area under the ROC of 0.944 (P < 0.001), a sensitivity of 0.89 and a specificity of 0.81 for diagnosis of HCC. CONCLUSION: Apo-A4 and Apo-A1 may be used clinically as biomarkers of HCC with a high sensibility and specificity. These findings may provide additional insights into the mechanism of HCC development and progression. | Maria Pleguezuelo Laura M Lopez-Sanchez Antonio Rodriguez-Ariza Jose L Montero Javier Briceno Ruben Ciria Jordi Muntane Manuel de la Mata | 2010 | World Journal of Hepatology2010，2，3： | 3 |
| 18 | Fecal Transplantation, Through Colonoscopy, Is Effective Therapy for Recurrent Clostridium difficile Infection显示文摘 | Eero Mattila Raija Uusitalo–Sepp?l? Maarit Wuorela Laura Lehtola Heimo Nurmi Matti Ristikankare Veikko Moilanen Kimmo Salminen Maaria Sepp?l? Petri S. Mattila Veli–Jukka Anttila Perttu Arkkila | 2012 | Gastroenterology2012，，3： | 3 |
| 19 | Downregulation of the Basic Peroxidase Isoenzyme from Zinnia elegans by Gibberellic Acid显示文摘Hypocotyl formation during the epigeal germination of seedlings is under strict hormonal regulation. In a 3 d old Zinnia elegans seedling system, gibberellic acid (GA3) exerts an opposite effect to that exerted by light on hypocotyl photomorphogenesis because GA3 promotes an etiolated-like growth with an inhibition of radial (secondary) growth. For this reason, the effect of GA3 on the basic peroxidase isoenzyme from Z. elegans (ZePrx), an enzyme involved in hypocotyl lignin biosynthesis, was studied. The results showed that GA3 reduces ZePrx activity, similarly to the way in which it reduces seedling secondary growth. This hormonal response is supported by the analysis of the ZePrx promoter, which contains four types of GA3-responsive cis-elements: the W Box/O2S; the Pyr Box; the GARE; and the Amy Box. Taken together, these results suggest that ZePrx is directly regulated by GA3, with this effect matching the inhibitory effect of GA on the hypocotyl secondary growth. | María Josefa López Núez-Flores Jorge Gutirrez Laura V.Gómez-Ros Esther Novo Uzal Mariana Sottomayor Alfonso Ros Barceló | 2010 | Journal of Integrative Plant Biology2010，52，2： | 3 |
| 20 | Legalon-SIL downregulates HCV core and NS5A in human hepatocytes expressing full-length HCV显示文摘AIM: To determine the effect of Legalon-SIL (LS) on hepatitis C virus (HCV) core and NS5A expression and on heme oxygenase-1 (HMOX-1) and its transcriptional regulators in human hepatoma cells expressing full length HCV genotype 1b. METHODS: CON1 cells were treated with 50 μmol/L or 200 μmol/L LS. Cells were harvested after 2, 6 and 24 h. HCV RNA and protein levels were determined by quantitative real-time polymerase chain reaction and Western blotting, respectively. RESULTS: HCV RNA (core and NS5A regions) wasdecreased after 6 h with LS 200 μmol/L (P < 0.05). Both 50 and 200 μmol/L LS decreased HCV RNA levels [core region (by 55% and 88%, respectively) and NS5A region (by 62% and 87%, respectively) after 24 h compared with vehicle (dimethyl sulphoxide) control (P < 0.01). Similarly HCV core and NS5A protein were decreased (by 85%, P < 0.01 and by 65%, P < 0.05, respectively) by LS 200 μmol/L. Bach1 and HMOX-1 RNA were also downregulated by LS treatment (P < 0.01), while Nrf2 protein was increased (P < 0.05).CONCLUSION: Our results demonstrate that treatment with LS downregulates HCV core and NS5A expression in CON1 cells which express full length HCV genotype 1b, and suggests that LS may prove to be a valuable alternative or adjunctive therapy for the treatment of HCV infection. | Marjan Mehrab-Mohseni Hossein Sendi Nury Steuerwald Sriparna Ghosh Laura W Schrum Herbert L Bonkovsky | 2011 | World Journal of Gastroenterology2011，17，13： | 3 |
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