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| 1 | Chaperone-mediated autophagy: roles in disease and aging显示文摘这评论集中于调停女伴的 autophagy (CMA ) ,在 lysosomes 贡献细胞内部的蛋白质的降级的解朊的系统之一。CMA 底层蛋白质有选择地通过在膜和奉献蛋白质 translocation 建筑群的双方定位的女伴的协调行动被指向到 lysosomes 和 translocated 进 lysosomal 腔。CMA 许可证的选择与在细胞的 transcriptional 程序的酶的新陈代谢的进程和子集为 CMA 支持一个调节角色的规章的目的预定了特定的蛋白质的降级。另外, CMA 通过移动贡献细胞的质量控制损坏或失灵蛋白质。这里,我们在 CMA 的分子的动力学,规定和生理学的理解描述最近的进展,并且在对象 neurodegeneration 和癌症那样的严重人的混乱的 CMA 机能障碍的贡献的支持讨论证据。 | Ana Maria Cuervo Esther Wong | 2014 | Cell Research2014，24，1： | 57 |
| 2 | Renin-angiotensin system in the pathogenesis of liver fibrosis显示文摘Hepatic fibrosis is considered a common response to many chronic hepatic injuries.It is a multifunctional process that involves several cell types,cytokines,chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem.In spite of many studies regarding the development of fibrosis,the understanding of the pathogenesis remains obscure.The hepatic tissue remodeling process is highly complex,resulting from the balance between collagen degradation and synthesis.Among the many mediators that take part in this process,the components of the Renin angiotensin system(RAS) have progressively assumed an important role.Angiotensin(Ang)□acts as a profibrotic mediator and Ang-(1-7),the newly recognized RAS component,appears to exert a counter-regulatory role in liver tissue.We briefly review the liver fibrosis process and current aspects of the RAS.This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis,focusing on the putative role of the ACE2-Ang-(1-7)-Mas receptor axis. | Regina Maria Pereira Robson Augusto Souza dos Santos Filipi Leles da Costa Dias Mauro Martins Teixeira Ana Cristina Simoes e Silva | 2009 | World Journal of Gastroenterology2009，15，21： | 37 |
| 3 | Current knowledge on esophageal atresia显示文摘Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is the most common congenital anomaly of the esophagus. The improvement of survival observed over the previous two decades is multifactorial and largely attributable to advances in neonatal intensive care, neonatal anesthesia, ventilatory and nutritional support, antibiotics, early surgical intervention, surgical materials and techniques. Indeed, mortality is currently limited to those cases with coexisting severe life-threatening anomalies. The diagnosis of EA is most commonly made during the first 24 h of life but may occur either antenatally or may be delayed. The primary surgical correction for EA and TEF is the best option in the absence of severe malformations. There is no ideal replacement for the esophagus and the optimal surgical treatment for patients with long-gap EA is still contro-versial. The primary complications during the postoperative period are leak and stenosis of the anastomosis, gastro-esophageal reflux, esophageal dysmotility, fistula recurrence, respiratory disorders and deformities of the thoracic wall. Data regarding long-term outcomes and follow-ups are limited for patients following EA/TEF repair. The determination of the risk factors for the complicated evolution following EA/TEF repair may positively impact long-term prognoses. Much remains to be studied regarding this condition. This manuscript provides a literature review of the current knowledge regarding EA. | Paulo Fernando Martins Pinheiro Ana Cristina Simoes e Silva Regina Maria Pereira | 2012 | World Journal of Gastroenterology2012，18，28： | 35 |
| 4 | Oral purgative and simethicone before small bowel capsule endoscopy显示文摘AIM:To evaluate small bowel cleansing quality,diagnostic yield and transit time,comparing three cleansing protocols prior to capsule endoscopy.METHODS:Sixty patients were prospectively enrolled and randomized to one of the following cleansing protocols:patients in Group A underwent a 24 h liquid diet and overnight fasting;patients in Group B followed protocol A and subsequently were administered 2 L of polyethylene glycol(PEG) the evening before the procedure;patients in Group C followed protocol B and were additionally administered 100 mg of simethicone 30 min prior to capsule ingestion.Small bowel cleansing was independently assessed by two experienced endoscopists and classified as poor,fair,good or excellent according to the proportion of small bowel mucosa under perfect conditions for visualization.When there was no agreement between the two endoscopists,the images were reviewed and discussed until a consensus was reached.The preparation was considered acceptable if > 50% or adequate if > 75% of the mucosa was in perfect cleansing condition.The amount of bubbles was assessed independently and it was considered significant if it prevented a correct interpretation of the images.Positive endoscopic findings,gastric emptying time(GET) and small bowel transit time(SBTT) were recorded for each examination.RESULTS:There was a trend favoring Group B in achieving an acceptable(including fair,good or excellent) level of cleansing(Group A:65%;Group B:83.3%;Group C:68.4%) [P = not significant(NS)] and favoring Group C in attaining an excellent level of cleansing(Group A:10%;Group B:16.7%;Group C:21.1%)(P = NS).The number of patients with an adequate cleansing of the small bowel,corresponding to an excellent or good classification,was 5(25%) in Group A,5(27.8%) in Group B and 4(21.1%) in Group C(P = 0.892).Conversely,7 patients(35%) in Group A,3 patients(16.7%) in Group B and 6 patients(31.6%) in Group C were considered to have poor small bowel cleansing(P = 0.417),with significant fluid or debris such that the examination was unreliable.The proportion of patients with a significant amount of bubbles was 50% in Group A,27.8% in Group B and 15.8% in Group C(P = 0.065).This was significantly lower in Group C when compared to Group A(P = 0.026).The mean GET was 27.8 min for Group A,27.2 min for Group B and 40.7 min for Group C(P = 0.381).The mean SBTT was 256.4 min for Group A,256.1 min for Group B and 258.1 min for Group C(P = 0.998).Regarding to the rate of complete examinations,the capsule reached the cecum in 20 patients(100%) in Group A,16 patients(88.9%) in Group B and 17 patients(89.5%) in Group C(P = 0.312).A definite diagnosis based on relevant small bowel endoscopic lesions was established in 60% of the patients in Group A(12 patients),44.4% in Group B(8 patients) and 57.8% in Group C(11 patients)(P = 0.587).CONCLUSION:Preparation with 2 L of PEG before small bowel capsule endoscopy(SBCE) may improve small bowel cleansing and the quality of visualization.Simethicone may further reduce intraluminal bubbles.No significant differences were found regarding GET,SBTT and the proportion of complete exploration or diagnostic yield among the three different cleansing protocols. | Bruno Joel Ferreira Rosa Mara Barbosa Joana Magalhes Ana Rebelo Maria Joo Moreira José Cotter | 2013 | World Journal of Gastrointestinal Endoscopy2013，5，2： | 21 |
| 5 | Partially defatted black soldier fly larva meal inclusion in piglet diets: effects on the growth performance, nutrient digestibility,blood profile, gut morphology and histological features显示文摘Background:The aim of this trial was to investigate the effects of different inclusion levels of a partially defatted black soldier fly (BSF,Hermetia illucens L.) larva meal on the growth performance,nutrient digestibility,blood profile,gut morphology and histological features of piglets.A total of 48 newly weaned piglets were individually weighed (initial body weight (IBW):6.1 ± 0.16 kg) and randomly allocated to 3 dietary treatments (4 boxes as replicates/treatment and 4 animals/box).BSF larva meal was included at increasing levels (0% [BSF0],5% [BSFS] and 10% [BSF10]) in isonitrogenous and isoenergetic diets formulated for two feeding phases:Ⅰ (from d 1 to d 23) and Ⅱ (from d 24 to d 61).The weight gain (WG),average daily gain (ADG),average daily feed intake (ADFI) and feed conversion ratio (FCR) were calculated for each feeding phase and for the whole trial.The haematochemical parameters and nutrient digestibility of the piglets were also evaluated.A total of 3 piglets per box were slaughtered on d 61 and the slaughtered piglets were submitted to morphometric investigations and histopathological examinations.Results:No overall significant differences were observed for growth performance (P > 0.05),except for the ADFI of phase Ⅱ,which showed a linear response to increasing BSF meal levels (P < 0.05,maximum for the BSF10 group).Dietary BSF meal inclusion did not significantly influence the blood profile,except as far as monocytes and neutrophils are concerned,and these showed a linear and quadratic response,respectively,to increasing BSF meal levels (P < 0.05,maximum for the BSF10 and BSF5 groups,respectively).On the other hand,the nutrient digestibility,gut morphology and histological features were not affected by dietary BSF meal inclusion (P > 0.05).Conclusions:The obtained results show that a partially defatted BSF larva meal can be used as a feed ingredient in diets for weaned piglets without negatively affecting their growth performance,nutrient digestibility,blood profile,gut morphology or histological features. | Ilaria Biasato Manuela Renna Francesco Gai Sihem Dabbou Marco Meneguz Giovanni Perona Silvia Martinez Ana Cristina Barroeta Lajusticia Stefania Bergagna Luca Sardi Maria Teresa Capucchio Enrico Bressan Andrea Dama Achille Schiavone Laura Gasco | 2019 | Journal of Animal Science and Biotechnology2019，10，3： | 19 |
| 6 | Preventative effects of a probiotic, Lactobacillus salivarius ssp. salivarius, in the TNBS model of rat colitis显示文摘AIM: To investigate the intestinal anti-inflammatory effect and mechanism of a probiotic Lactobacillus sakuvarius ssp.salivariusCECT5713 in the TNBS model of rat colitis.METHODS: Female Wistar rats (180-200 g) were used in this study. A group of rats were administered orally the probiotic L. salivarius ssp. salivarius (5×108 CFU suspended in 0.5 mL of skimmed milk) daily for 3 wk. Two additional groups were used for reference, a non-colitic and a control colitic without probiotic treatment, which received orally the vehicle used to administer the probiotic. Two weeks after starting the experiment, the rats were rendered colitic by intracolonic administration of 10 mg of TNBS dissolved in 0.25 mL of 500 mL/L ethanol. One week after colitis induction, all animals were killed and colonic damage was evaluated both histologically and biochemically. The biochemical studies performed in colonic homogenates include determination of myeloperoxidase (MPO) activity,glutathione (GSH) content, leukotriene B4 (LTB4) and tumor necrosis factor α (TNF-α) levels, as well as inducible nitric oxide synthase (iNOS) expression. In addition, the luminal contents obtained from colonic samples were used for microbiological studies, in order to determine Lactobacilli and Bifidobacteria counts.RESULTS: Treatment of colitic rats with L. salivarius ssp.salivarius resulted in amelioration of the inflammatory response in colitic rats, when compared with the corresponding control group without probiotic treatment. This antiinflammatory effect was evidenced macroscopically by a significant reduction in the extent of colonic necrosis and/or inflammation induced by the administration of TNBS/ethanol (2.3+0.4 cm vs3.4+0.3 cm in control group,P<0.01) and histologically by improvement of the colonic architecture associated with a reduction in the neutrophil infiltrate in comparison with non-treated colitic rats. The latter was confirmed biochemically by a significant reduction of colonic MPO activity (105.3+26.0 U/g vs180.6±21.9 U/g, P<0.05), a marker of neutrophil infiltration. The beneficial effect was associated with an increase of the colonic GSH content (1 252±42 nmol/g vs 1 087+51 nmol/g, P<0.05),which is depleted in colitic rats, as a consequence of the oxidative stress induced by the inflammatory process. In addition, the treatment of colitic rats with L. salivarius resulted in a significant reduction of colonic TNF-α levels (509.4±68.2 pg/g vs782.9±60.1 pglg, P<0.01) and in a lower colonic iNOS expression, when compared to TNBS control animals without probiotic administration. Finally,treated colitic rats showed higher counts of Lactobacilli species in colonic contents than control colitic rats, whereas no differences were observed in Bifidobacteria counts.CONCLUSION: Administration of the probiotic L. salivarius ssp. salivarius CECT5713 facilitates the recovery of the inflamed tissue in the TNBS model of rat colitis, an effect associated with amelioration of the production of some of the mediators involved in the inflammatory response in the intestine, such as cytokines, including TNF-α and NO. This beneficial effect could be ascribed to its effect on the altered immune response that occurs in this inflammatory condition. | Laura Peran Desiree Camuesco Monica Comalada Ana Nieto Angel Concha Maria Paz Diaz-Ropero Monica Olivares Jordi Xaus Antonio Zarzuelo Julio Galvez | 2005 | World Journal of Gastroenterology2005，11，33： | 17 |
| 7 | Neuroinflammation and oxidative stress act in concert to promote neurodegeneration in the diabetic retina and optic nerve:galectin-3 participation显示文摘Diabetes is a lifelong disease characterized by glucose metabolic imbalance,in which low insulin levels or impaired insulin signaling lead to hyperglycemic state.Within 20 years of diabetes progression,95%of patients will have diabetic retinopathy,the leading cause of visual defects in working-age people worldwide.Although diabetes is considered a microvascular disease,recent studies have shown that neurodegeneration precedes vascular changes within the diabetic visual system,albeit its mechanisms are still under investigation.Neuroinflammation and oxidative stress are intrinsically related phenomena,since macrophage/microglia and astrocytes are the main sources of reactive oxygen species during central nervous system chronic degenerative diseases,and both pathological processes are increased in the visual system during diabetes.The present review will focus on recent findings of the contribution of oxidative stress derived from neuroinflammation in the early neurodegenerative aspects of the diabetic visual system and their relationship with galectin-3. | Henrique Rocha Mendonca Raul Carpi-Santos Karin da Costa Calaza Ana Maria Blanco Martinez | 2020 | Neural Regeneration Research2020，15，4： | 16 |
| 8 | Damage control orthopaedics: State of the art显示文摘Damage control orthopaedics(DCO) originally consisted of the provisional immobilisation of long bone-mainly femur-fractures in order to achieve the advantages of early treatment and to minimise the risk of complications, such as major pain, fat embolism, clotting, pathological inflammatory response, severe haemorrhage triggering the lethal triad, and the traumatic effects of major surgery on a patient who is already traumatised(the 'second hit' effect). In recent years, new locations have been added to the DCO concept, such as injuries to the pelvis, spine and upper limbs. Nonetheless, this concept has not yet been validated in well-designed prospective studies, and much controversy remains.Indeed, some researchers believe the indiscriminate application of DCO might be harmful and produce substantial and unnecessary expense. In this respect, too,normalised parameters associated with the acid-base system have been proposed,under a concept termed early appropriate care, in the view that this would enable patients to receive major surgical procedures in an approach offering the advantages of early total care together with the apparent safety of DCO. This paper discusses the diagnosis and treatment of severely traumatised patients managed in accordance with DCO and highlights the possible drawbacks of this treatment principle. | Enrique Guerado Maria Luisa Bertrand Juan Ramon Cano Ana María Cerván Adolfo Galán | 2019 | World Journal of Orthopedics2019，10，1： | 16 |
| 9 | Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis显示文摘AIM To perform a systematic review and meta-analysis on proton pump inhibitors(PPIs) therapy and the risk of Clostridium difficile infection(CDI). METHODS We conducted a systematic search of MEDLINE/Pub Med and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios(ORs) estimates with 95% confidence intervals(CIs) were calculated using the random effect. Heterogeneity was assessed by I^2 test and Cochran's Q statistic.Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale(NOS). RESULTS Fifty-six studies(40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI(pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control(OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort(OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted(OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted(OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter(OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter(OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years(OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years(OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses(test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies(I^2 = 85.4%, P < 0.001) as well as evidence of publication bias(funnel plot asymmetry test, P = 0.002). CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal. | Anca Trifan Carol Stanciu Irina Girleanu Oana Cristina Stoica Ana Maria Singeap Roxana Maxim Stefan Andrei Chiriac Alin Ciobica Lucian Boiculese | 2017 | World Journal of Gastroenterology2017，23，35： | 15 |
| 10 | Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice显示文摘In spite of advances in surgical care and rehabilitation,the consequences of spinal cord injury(SCI)ar still challenging.Several experimental therapeutic strategies have been studied in the SCI field,and recen advances have led to the development of therapies that may act on the inhibitory microenvironment.As sorted lineages of stem cells are considered a good treatment for SCI.This study investigated the effect o systemic transplantation of mesenchymal stem cells(MSCs)in a compressive SCI model.Here we presen results of the intraperitoneal route,which has not been used previously for MSC administration after comveI.WeafC57BL/6nt lmy atb spinal cord compression for 1 minute with a 30-g vascular clip.The animals were divided into five groups DMEM at 7 days after SCI),DMEM i.v.(intravenous injection of 500μL of DMEM at 7 days after SCI)The effects of MSCs transplantation in white matter sparing were analyzed by luxol fast blue staining.Th number of preserved fibers was counted in semithin sections stained with toluidine blue and the presenc of trophic factors was analyzed by immunohistochemistry.In addition,we analyzed the locomotor perfor mance with Basso Mouse Scale and Global Mobility Test.Our results showed white matter preservation and a larger number of preserved fibers in the MSC groups than in the DMEM groups.Furthermore,th MSC groups had higher levels of trophic factors(brain-derived neurotrophic factor,nerve growth factor neurotrophin-3 and neurotrophin-4)in the spinal cord and improved locomotor performance.Our result indicate that injection of MSCs by either intraperitoneal or intravenous routes results in beneficial out comes and can be elected as a choice for SCI treatment. | Bruna dos Santos Ramalho FernANDa Martins de Almeida Conrado Mendonca Sales Silmara de Lima Ana Maria Blanco Martinez | 2018 | Neural Regeneration Research2018，13，6： | 12 |
| 11 | WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells Neurotrauma and mesenchymal stem cells treatment:From experimental studies to clinical trials显示文摘Mesenchymal stem cell(MSC)therapy has attracted the attention of scientists and clinicians around the world.Basic and pre-clinical experimental studies have highlighted the positive effects of MSC treatment after spinal cord and peripheral nerve injury.These effects are believed to be due to their ability to differentiate into other cell lineages,modulate inflammatory and immunomodulatory responses,reduce cell apoptosis,secrete several neurotrophic factors and respond to tissue injury,among others.There are many pre-clinical studies on MSC treatment for spinal cord injury(SCI)and peripheral nerve injuries.However,the same is not true for clinical trials,particularly those concerned with nerve trauma,indicating the necessity of more well-constructed studies showing the benefits that cell therapy can provide for individuals suffering the consequences of nerve lesions.As for clinical trials for SCI treatment the results obtained so far are not as beneficial as those described in experimental studies.For these reasons basic and pre-clinical studies dealing with MSC therapy should emphasize the standardization of protocols that could be translated to the clinical set with consistent and positive outcomes.This review is based on pre-clinical studies and clinical trials available in the literature from 2010 until now.At the time of writing this article there were 43 and 36 pre-clinical and 19 and 1 clinical trials on injured spinal cord and peripheral nerves,respectively. | Ana Maria Blanco Martinez Camila de Oliveira Goulart Bruna dos Santos Ramalho Júlia Teixeira Oliveira Fernanda Martins Almeida | 2014 | World Journal of Stem Cells2014，6，2： | 11 |
| 12 | Relationship between angiotensin-(1-7) and angiotensin Ⅱ correlates with hemodynamic changes in human liver cirrhosis显示文摘AIM:To measure circulating angiotensins at different stages ofhuman cirrhosis and to further evaluate a possible relationship between renin angiotensin system (RAS) components and hemodynamic changes.METHODS: Patients were allocated into 4 groups: mild-to-moderate liver disease (MLD), advanced liver disease (ALD), patients undergoing liver transplantation, and healthy controls. Blood was collected to determine plasma renin activity (PRA), angiotensin (Ang) , Ang Ⅱ, and Ang-(1-7) levels using radioimmunoassays. During liver transplantation, hemodynamic parameters were determined and blood was simultaneously obtained from the portal vein and radial artery in order to measure RAS components.RESULTS: PRA and angiotensins were elevated in ALD when compared to MLD and controls (P < 0.05). In contrast, Ang was signicantly reduced in MLD. Ang-(1-7)/Ang Ⅱ ratios were increased in MLD when compared to controls and ALD. During transplantation, Ang Ⅱ levels were lower and Ang-(1-7)/Ang Ⅱ ratios were higher in the splanchnic circulation than in the peripheral circulation (0.52 ± 0.08 vs 0.38 ± 0.04, P < 0.02), whereas the peripheral circulating Ang /Ang ratio was elevated in comparison to splanchnic lev-els (0.18 ± 0.02 vs 0.13 ± 0.02, P < 0.04). Ang-(1-7)/Ang Ⅱ ratios positively correlated with cardiac output (r= 0.66) and negatively correlated with systemic vascular resistance (r =-0.70).CONCLUSION: Our ndings suggest that the relation-ship between Ang-(1-7) and Ang Ⅱmay play a role in the hemodynamic changes ofhuman cirrhosis. | Walkíria Wingester Vilas-Boas Antnio Ribeiro-Oliveira Jr Regina Maria Pereira Renata da Cunha Ribeiro Jerusa Almeida Ana Paula Nadu Ana Cristina Simoes e Silva Robson Augusto Souza dos Santos | 2009 | World Journal of Gastroenterology2009，15，20： | 11 |
| 13 | Clinical presentation and early predictors for poor outcomes in pediatric myocarditis:A retrospective study显示文摘BACKGROUND Myocarditis is an important cause of morbidity and mortality in children, leading to long-term sequelae including chronic congestive heart failure, dilated cardiomyopathy, heart transplantation, and death. The initial diagnosis of myocarditis is usually based on clinical presentation, but this widely ranges from the severe sudden onset of a cardiogenic shock to asymptomatic patients. Early recognition is essential in order to monitor and start supportive treatment prior to the development of severe adverse events. Of note, many cases of fulminant myocarditis are usually misdiagnosed as otherwise minor conditions during the weeks before the unexpected deterioration.AIM To provide diagnostic clues to make an early recognition of pediatric myocarditis.To investigate early predictors for poor outcomes.METHODS We conducted a retrospective cross-sectional single-center study from January 2008 to November 2017 at the Pediatric Department of our institution, including children < 18-years-old diagnosed with myocarditis. Poor outcome was defined as the occurrence of any of the following facts: death, heart transplant, persistent left ventricular systolic dysfunction or dilation at hospital discharge(early poor outcome), or after 1 year of follow-up(late poor outcome). We analyzed different clinical features and diagnostic test findings in order to provide diagnostic clues for myocarditis in children. Multivariable stepwise logistic regression analysis was performed using all variables that had been selected by univariate analysis to determine independent factors that predicted a poor early or late outcome in our study population.RESULTS A total of 42 patients [69% male; median age of 8(1.5-12) years] met study inclusion criteria. Chest pain(40%) was the most common specific cardiac symptom. Respiratory tract symptoms(cough, apnea, rhinorrhea)(38%),shortness of breath(35%), gastrointestinal tract symptoms(vomiting, abdominal pain, diarrhea)(33%), and fever(31%) were the most common non-cardiac initial complaints. Tachycardia(57%) and tachypnea(52%) were the most common signs on the initial physical exam followed by nonspecific signs of respiratory tract infection(44%) and respiratory distress(35%). Specific abnormal signs of heart failure such as heart murmur(26%), systolic hypotension(24%), gallop rhythm(20%), or hepatomegaly(20%) were less prevalent. Up to 43% of patients presented an early poor outcome, and 16% presented a late poor outcome. In multivariate analysis, an initial left ventricular ejection fraction(LVEF) < 30%remained the only significant predictor for early [odds ratio(OR)(95%CI) = 21(2-456), P = 0.027) and late [OR(95%CI) = 8(0.56-135), P = 0.047) poor outcome in children with myocarditis. LVEF correlated well with age(r = 0.51, P = 0.005),days from the initiation of symptoms(r =-0.31, P = 0.045), and N-terminal probrain natriuretic peptide levels(r = 0.66, P < 0.001), but not with troponin T(r =-0.05, P = 0.730) or C-reactive protein levels(r =-0.13, P = 0.391). N-terminal probrain natriuretic peptide presented a high diagnostic accuracy for LVEF < 30% on echocardiography with an area under curve of 0.931(95%CI: 0.858-0.995, P <0.001). The best cut-off point was 2000 pg/mL with a sensitivity of 90%,specificity of 81%, positive predictive value of 60%, and negative predictive value of 96%.CONCLUSION The diagnosis of myocarditis in children is challenging due to the heterogeneous and unspecific clinical presentation. The presence of LVEF < 30% on echocardiography on admission was the major predictor for poor outcomes.Younger ages, a prolonged course of the disease, and N-terminal pro-brain natriuretic peptide levels could help to identify these high-risk patients. | Moises Rodriguez-Gonzalez Maria Isabel Sanchez-Codez Manuel Lubian-Gutierrez Ana Castellano-Martinez | 2019 | World Journal of Clinical Cases2019，7，5： | 11 |
| 14 | TLR2 and TLR4 polymorphisms influence m RNA and protein expression in colorectal cancer显示文摘AIM: To evaluate the effect of promoter region polymorphisms of toll-like receptor(TLR)2-196 to-174 del and TLR4-1607T/C(rs10759932) on m RNA and protein expression in tumor tissue and of TLR4+896A/G(rs4986790) on colorectal cancer(CRC) risk.METHODS: The TLR2-196 to-174 del polymorphism was investigated using allele-specific polymerase chain reaction(PCR) and the TLR4-1607T/C and TLR4+896A/G by PCR-restriction fragment length p o l y m o r p h i s m( R F L P). W e g e n o t y p e d 4 3 4 D N A samples from 194 CRC patients and 240 healthy individuals. The m RNA relative quantification(RQ) was performed in 40 tumor tissue samples by quantitative PCR Taq Man assay, using specific probes for TLR2 and TLR4 genes, and ACTB and GAPDH reference geneswere used as endogenous controls. Protein expression was analyzed by immunohistochemistry with specific primary antibodies.RESULTS: No association was found for TLR4-1607T/C and TLR4+896A/G by three statistical models(logadditive, dominant and recessive). However, based on dominant and log-additive models, the polymorphic variant TLR2-196 to-174 del was associated with increased CRC risk [dominant: odds ratio(OR) = 1.72, 95%CI: 1.03-2.89; P = 0.038 and log-additive: OR =1.59, 95%CI: 1.02-2.48; P = 0.039]. TLR2 m RNA expression was increased in tumor tissue(RQ = 2.36) when compared to adjacent normal tissue(RQ = 1; P < 0.0001), whereas the TLR4 m RNA showed a basal expression(RQ = 0.74 vs RQ = 1, P = 0.452). Immunohistochemistry analysis of TLR2 and TLR4 protein expression was concordant with the findings of m RNA expression. In addition, the TLR2-196 to-174 del variant carriers showed m RNA relative expression 2.19 times higher than wild-genotype carriers. The TLR2 protein expression was also higher for the TLR2-196 to-174 del variant carriers [117 ± 10 arbitrary unit(a.u.) vs 95 ± 4 a.u., P = 0.03]. However, for the TLR4-1607T/C polymorphism no significant difference was found for both m RNA(P = 0.56) and protein expression(P = 0.26).CONCLUSION: Our findings suggest that TLR2-196 to-174 del polymorphism increases TLR2 m RNA expression and is associated with higher CRC risk, indicating an important role in CRC genetic susceptibility. | Marcela Alcantara Proenca Juliana Garcia de Oliveira Aline Cristina Targa Cadamuro Maysa Succi Joao Gomes Netinho Eny Maria Goloni-Bertolo érika Cristina Pavarino Ana Elizabete Silva | 2015 | World Journal of Gastroenterology2015，21，25： | 9 |
| 15 | Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide显示文摘Long-acting glucagon-like peptide-1(GLP-1) analogues marketed for type 2 diabetes(T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2 D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors(GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions(e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2 D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation(thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2 D, stroke and Alzheimer disease(AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss, microglia inhibition, behavior and cognition, and in AD biomarkers. Herein, we discuss the GLP-1 action through the gut-brain axis, the hormone's regulation of some autonomic functions and liraglutide's neuroprotective potential. | Emanuel Monteiro Candeias Inês Carolina Sebastio Susana Maria Cardoso Sónia Catarina Correia Cristina Isabel Carvalho Ana Isabel Plácido Maria Sancha Santos Catarina Resende Oliveira Paula Isabel Moreira Ana Isabel Duarte | 2015 | World Journal of Diabetes2015，6，6： | 9 |
| 16 | Autoimmune hepatitis and anti-tumor necrosis factor alpha therapy:A single center report of 8 cases显示文摘This article describes cases of anti-tumor necrosis factor(TNF)-α-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of medical records was performed in our center, in order to detect cases of autoimmune hepatitis(AIH) associated with anti-TNF biologic agents. We describe and analyze eight cases of AIH following anti-TNF therapy, 7 with infliximab and 1 with adalimumab. A distinction should be made between induction of autoimmunity and clinically evident autoimmune disease. Liver biopsy is useful in detecting the role of the TNF-α antagonist in the development of AIH. The lack of relapse after discontinuing immunosuppressive therapy favors, as in this case series, an immune-mediated drug reaction as most patients with AIH have a relapse after treatment is suspended. Although AIH related to anti-TNF therapy is rare, a baseline immunological panel along with liver function tests should be performed in all patients with autoimmune disease before starting biologics. | Susana Rodrigues Susana Lopes Fernando Magro Hélder Cardoso Ana Maria Horta e Vale Margarida Marques Eva Mariz Miguel Bernardes Joanne Lopes Fátima Carneiro Guilherme Macedo | 2015 | World Journal of Gastroenterology2015，21，24： | 9 |
| 17 | Clinical and pathological characterization of epstein-barr virus-associated gastric carcinomas in portugal显示文摘AIM To determine the prevalence of epstein-barr virus(eb V)-associated gastric carcinomas in the North Region of Portugal and to study its clinicopathological characteristics. METHODS We have performed a retrospective study including a total of 179 consecutive patients with gastric cancer(GC) submitted to gastrectomy during 2011 at the Portuguese Oncology Institute of Porto. Clinical and pathological data was collected from individual clinical records and inserted on a database with unique codification. Tumour tissues were collected from the institutional tumour bank. eb V was detected by in situ hybridization for the detection of eb V-encoded small RNAs(ebe Rs) and eb V latent proteins(LMP1 and LMP2 A) were detected by immunohistochemistry.RESULTS The analysis showed that eb V-associated gastric carcinomas(eb Va GC) represents 8.4%(15/179) of all GC cases, with a significant differential distribution among histological types(P < 0.001): 100%(3/3) of medullary carcinomas, 100%(1/1) of adenosquamous carcinoma, 8.7%(8/92) of tubular adenocarcinomas, 8.0%(2/25) of mixed carcinomas and 2%(1/51) in poorly cohesive carcinomas. The analysis revealed a higher predominance of eb Va GC in the upper third and middle(cardia, fundus and body) of the stomach(P = 0.041), a significant lower number of regional lymph nodes invasion(P = 0.025) and a tendency for better prognosis(P = 0.222). eb V latent protein expression revealed that all eb Va GC cases were LMP1-negative, nevertheless 6 cases(40%) expressed LPM2 A, which reveals that these cases show a distinct eb V-Latency profile(latency II-like).CONCLUSION eb Va GC represents 8.4% of all GC in the North Region of Portugal. The eb V-infected patients have specific clinic-pathological features that should be further explored to develop new strategies of management and treatment. | Joana Ribeiro Andreia Oliveira Mariana Malta Claudia Oliveira Fernanda Silva Ana Galaghar Luís Pedro Afonso Maria Cassiano Neves Rui Medeiros Pedro Pimentel-Nunes Hugo Sousa | 2017 | World Journal of Gastroenterology2017，23，40： | 9 |
| 18 | Chronic exposure to ethanol causes steatosis and inflammation in zebrafish liver显示文摘AIM To evaluate the effects of chronic exposure to ethanol in the liver and the expression of inflammatory genesin zebrafish.METHODS Zebrafish(n = 104),wild type,adult,male and female,were divided into two groups:Control and ethanol(0.05 v/v).The ethanol was directly added into water;tanks water were changed every two days and the ethanol replaced.The animals were fed twice a day with fish food until satiety.After two and four weeks of trial,livers were dissected,histological analysis(hematoxilineosin and Oil Red staining) and gene expression assessment of adiponectin,adiponectin receptor 2(adipor2),sirtuin-1(sirt-1),tumor necrosis factor-alpha(tnf-a),interleukin-1b(il-1b) and interleukin-10(il-10) were performed.Ultrastructural evaluations were conducted at fourth week.RESULTS Exposing zebrafish to 0.5% ethanol developed intense liver steatosis after four weeks,as demonstrated by oil red staining.In ethanol-treated animals,the main ultrastructural changes were related to cytoplasmic lipid particles and droplets,increased number of rough endoplasmic reticulum cisterns and glycogen particles.Between two and four weeks,hepatic mR NA expression of il-1b,sirt-1 and adipor2 were upregulated,indicating that ethanol triggered signaling molecules which are key elements in both hepatic inflammatory and protective responses.Adiponectin was not detected in the liver of animals exposed and not exposed to ethanol,and il-10 did not show significant difference.CONCLUSION Data suggest that inflammatory signaling and ultrastructural alterations play a significant role during hepatic steatosis in zebrafish chronically exposed to ethanol. | Ana Claudia Reis Schneider Cleandra Gregório Carolina Uribe-Cruz Ranieli Guizzo Tais Malysz Maria Cristina Faccioni-Heuser Larisse Longo Themis Reverbel da Silveira | 2017 | World Journal of Hepatology2017，9，8： | 7 |
| 19 | 大气二氧化氮与每日总死亡率、心血管和呼吸系统疾病死亡率的短期关联:398个城市的多中心分析显示文摘目的:采用统一的分析方案,评估全球多个国家/地区的二氧化氮(NO_(2))与总死亡率、心血管和呼吸系统疾病死亡率之间的短期关联。研究设计:采用两阶段的时间序列分析方法、过度离散的广义线性模型和多水平meta分析。研究地点:22个低到高收入国家/地区的398个城市。主要结局指标:1973—2018年逐日总死亡人数(6280万人)、心血管疾病死亡人数(1970万人)和呼吸系统疾病死亡人数(550万人)。结果:平均而言,NO_(2)浓度在滞后1天(前1天)每增加10μg/m^(3),会导致总死亡率、心血管和呼吸系统疾病死亡率分别增加0.46%(95%可信区间0.36%~0.57%)、0.37%(0.22%~0.51%)、0.47%(0.21%~0.72%)。在对共污染物(PM_(10)、PM_(2.5)、臭氧、二氧化硫和一氧化碳)进行调整后,这些关联仍然很稳定。所有3种死因的暴露-反应曲线几乎是线性的,没有明显的阈值。在398个城市中,可归因于高过假定零水平的NO_(2)浓度造成的死亡比例为1.23%(95%可信区间0.96%~1.51%)。结论:这项多中心研究提供了关于NO_(2)短期暴露与总死亡率、心血管和呼吸系统死亡风险之间的独立和线性关联的关键证据,说明通过加强NO_(2)的控制和监管限制标准,可获得人群水平的健康收益。 | 孟夏 刘聪(校) 陈仁杰 郑湃(译) 阚海东(校) Francesco Sera Ana Vicedo-Cabrera Ai Milojevic Maria Guo Yuming Tong Shilu Micheline de Sousa Zanotti Stagliorio Coelh Paulo Hilario Nascimento Saldiva Eric Lavigne Patricia Matus Correa Nicolas Valdes Ortega Samuel Osorio Garcia Jan Kysely Ales Urban Hans Orru Marek Maasikmets Jouni J K Jaakkola Niilo Ryti Veronika Huber Alexandra Schneider Klea Katsouyanni Antonis Analitis Masahiro Hashizume Yasushi Honda Chris Fook Sheng Ng Baltazar Nunes João Paulo Teixeira Iulian Horia Holobaca Simona Fratianni Ho Kim Aurelio Tobias Carmeníniguez Bertil Forsberg ChristoferÅström Martina S Ragettli Yue-Liang Leon Guo Shih-Chun Pan Shanshan Li Michelle L Bell Antonella Zanobetti Joel Schwartz Tangchun Wu Antonio Gasparrini | 2021 | 英国医学杂志中文版2021，24，8： | 7 |
| 20 | Beneficial effects of saffron(Crocus sativus L.) in ocular pathologies, particularly neurodegenerative retinal diseases显示文摘Saffron(Crocus sativus L.)has been traditionally used in food preparation and as a medicinal plant.It currently has numerous therapeutic properties attributed to it,such as protection against ischemia,as well as anticonvulsant,antidepressant,anxiolytic,hypolipidemic,anti-atherogenic,anti-hypertensive,antidiabetic,and anti-cancer properties.In addition,saffron has remarkable beneficial properties,such as anti-apoptotic,anti-inflammatory and antioxidant activities,due to its main metabolites,among which crocin and crocetin stand out.Furthermore,increasing evidence underwrites the possible neuroprotective role of the main bioactive saffron constituents in neurodegenerative diseases,such as Parkinson’s and Alzheimer’s diseases,both in experimental models and in clinical studies in patients.Currently,saffron supplementation is being tested for ocular neurodegenerative pathologies,such as diabetic retinopathy,retinitis pigmentosa,age-related macular degeneration and glaucoma,among others,and shows beneficial effects.The present article provides a comprehensive and up to date report of the investigations on the beneficial effects of saffron extracts on the main neurodegenerative ocular pathologies and other ocular diseases.This review showed that saffron extracts could be considered promising therapeutic agents to help in the treatment of ocular neurodegenerative diseases. | Jose A.Fernandez-Albarral Rosa de Hoz Ana I.Ramirez Ines Lopez-Cuenca Elena Salobrar-Garcia Maria D.Pinazo-Duran Jose M.Ramirez Juan J.Salazar | 2020 | Neural Regeneration Research2020，15，8： | 6 |
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