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Characteristics and advantages of adenoassociated virus vector-mediated gene therapy for neurodegenerative diseases 预览
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作者 Yuan Qu Yi Liu +2 位作者 Ahmed Fayyaz Noor Johnathan Tran Rui Li 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第6期931-938,共8页
Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons,even leading to the permanent loss of function.Gene therapy via gene replacement or ge... Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons,even leading to the permanent loss of function.Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients.Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system.This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system.Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration. 展开更多
关键词 nerve REGENERATION central nervous system gene therapy NEURODEGENERATIVE DISEASE viral vector ADENO-ASSOCIATED virus Alzheimer’s DISEASE Parkinson’s DISEASE Huntington’s DISEASE amyotrophic lateral SCLEROSIS spinal muscular atrophy neural REGENERATION
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Novel Imaging Approaches for the Diagnosis of Stable Ischemic Heart Disease in Women 预览
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作者 Viviany R.Taqueti,MD,MPH 《心血管创新与应用》 2019年第B02期375-389,共15页
Conventional recommendations for diagnostic testing for the evaluation of stable ischemic heart disease in women have largely paralleled those in men.Although they are designed primarily for the identifi cation of obs... Conventional recommendations for diagnostic testing for the evaluation of stable ischemic heart disease in women have largely paralleled those in men.Although they are designed primarily for the identifi cation of obstructive coronary artery disease(CAD),traditional approaches can lead to overtesting in women without differentiating who is truly at risk.Several unique factors related to the presentation,diagnosis,and underlying pathophysiology of stable ischemic heart disease in women necessitate a more specific approach to the assessment of their risk,complete with separate guidelines when appropriate.This overview highlights how advanced noninvasive imaging tools,including cardiac computed tomography angiography,positron emission tomography,and cardiac magnetic resonance imaging,are enabling very sensitive assessments of anatomic atherosclerotic plaque burden,macrovessel-and microvessel-related ischemia,and myocardial fi brosis,respectively.Moving forward,effective diagnostic testing will need to identify women at high risk of adverse cardiovascular events(not anatomically obstructive CAD per se)without overtesting those at low risk.Judicious application of novel imaging approaches will be critical to broadening the defi nitions of CAD and ischemia to better refl ect the whole spectrum of pathological phenotypes in women,including nonobstructive CAD and coronary microvascular dysfunction,and aid in the development of needed evidence-based strategies for their management. 展开更多
关键词 CORONARY MICROVASCULAR dysfunction nonobstructive CORONARY artery DISEASE stable ischemic HEART DISEASE HEART DISEASE in WOMEN cardiovascular IMAGING positron emission tomography
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Progression of carotid artery disease could stratify a risk of coronary artery disease patients with type 2 diabetes
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作者 Marijan Bosevski Pece Nikolovski +1 位作者 Lily Stojanovska Vasso Apostolopoulos 《生物化学与生物物理学报:英文版》 SCIE CAS CSCD 2019年第1期120-122,共3页
Diabetes is a common risk factor associated with coronary artery disease (CAD).Importantly,hereditary CAD cannot be discounted which accounts for about one quater of the cases [1].Carotid artery disease (CARD) shares ... Diabetes is a common risk factor associated with coronary artery disease (CAD).Importantly,hereditary CAD cannot be discounted which accounts for about one quater of the cases [1].Carotid artery disease (CARD) shares the same risk factors as CAD [2]. 展开更多
关键词 DISEASE CAROTID ARTERY DISEASE coronary ARTERY DISEASE patients with type 2 diabetes
Mitophagy links oxidative stress conditions and neurodegenerative diseases 预览
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作者 Ulfuara Shefa Na Young Jeong +4 位作者 In Ok Song Hyung-Joo Chung Dokyoung Kim Junyang Jung Youngbuhm Huh 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第5期749-756,共8页
Mitophagy is activated by a number of stimuli,including hypoxia,energy stress,and increased oxidative phosphorylation activity.Mitophagy is associated with oxidative stress conditions and central neurodegenerative dis... Mitophagy is activated by a number of stimuli,including hypoxia,energy stress,and increased oxidative phosphorylation activity.Mitophagy is associated with oxidative stress conditions and central neurodegenerative diseases.Proper regulation of mitophagy is crucial for maintaining homeostasis;conversely,inadequate removal of mitochondria through mitophagy leads to the generation of oxidative species,including reactive oxygen species and reactive nitrogen species,resulting in various neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,and amyotrophic lateral sclerosis.These diseases are most prevalent in older adults whose bodies fail to maintain proper mitophagic functions to combat oxidative species.As mitophagy is essential for normal body function,by targeting mitophagic pathways we can improve these disease conditions.The search for effective remedies to treat these disease conditions is an ongoing process,which is why more studies are needed.Additionally,more relevant studies could help establish therapeutic conditions,which are currently in high demand.In this review,we discuss how mitophagy plays a significant role in homeostasis and how its dysregulation causes neurodegeneration.We also discuss how combating oxidative species and targeting mitophagy can help treat these neurodegenerative diseases. 展开更多
关键词 nerve regeneration MITOPHAGY central nervous system Alzheimer’s DISEASE Parkinson’s DISEASE Huntington’s DISEASE amyotrophic lateral SCLEROSIS oxidative SPECIES REACTIVE oxygen SPECIES REACTIVE nitrogen SPECIES
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Endoscopic response to tumor necrosis factor inhibitors predicts long term benefits in Crohn’s disease 预览
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作者 Ignacio Alfaro Maria Carme Masamunt +10 位作者 Nuria Planell Alicia López-García Jesús Castro Marta Gallego Rebeca Barastegui Angel Giner Alejandro Vara Azucena Salas Elena Ricart Julián Panés Ingrid Ordás 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第14期1764-1774,共11页
BACKGROUND Identifying predictors of therapeutic response is the cornerstone of personalized medicine. AIM To identify predictors of long-term mucosal healing (MH) in patients with Crohn's disease (CD) treated wit... BACKGROUND Identifying predictors of therapeutic response is the cornerstone of personalized medicine. AIM To identify predictors of long-term mucosal healing (MH) in patients with Crohn's disease (CD) treated with tumor necrosis factor α(TNF-α) inhibitors. METHODS Prospective single center study. Consecutive patients with clinically active CD requiring treatment with a TNF-α inhibitor were included. A baseline segmental CD Endoscopic Index of Severity (CDEIS)≥ 10 in at least one segment or the presence of ulcerations were required for inclusion. Clinical, biological and endoscopic data were obtained at baseline, weeks 14 and 46. Endoscopic response (ER) was defined as a decrease ≥ 50% from baseline CDEIS and MH as partial CDEIS ≤ 5 in all segments. RESULTS Of 62 patients were included. At baseline, median CD Activity Index and CDEIS were 201 and 6.7, respectively with a significant reduction after one year of treatment (53 and 3.0 respectively, P < 0.001). At week 14, 56% of patients achieved ER and 34% MH. At week 46, the corresponding percentages were 52% and 44%. Baseline disease characteristics or biomarkers did not predict MH. A decrease from baseline CDEIS at week 14 of at least 80% was the best predictor of MH at week 46 (59% sensitivity and 91% specificity;area under the curve = 0.778).CONCLUSION Clinical and biomarker data are not useful predictors of response to TNF-α inhibitors in CD, whereas ER to induction therapy, defined as 80% reduction in global CDEIS, is a robust predictor of long-term MH. Achievement of this endoscopic endpoint may be considered as a therapeutic target for anti-TNF-α therapy. 展开更多
关键词 Crohn’s DISEASE Endoscopy MUCOSAL HEALING Crohn’s DISEASE ENDOSCOPIC Index of SEVERITY Tumor NECROSIS factor
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Role of Chinese Herbal Medicines in Regulation of Energy Metabolism in Treating Cardiovascular Diseases
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作者 LI Jie GUAN Xuan-ke LIU Ru-xiu 《中国结合医学杂志:英文版》 SCIE CAS CSCD 2019年第4期307-315,共9页
Recently,studying myocardial energy metabolism pathways or improving myocardial metabolism through drugs is another effective strategy for treating ischemic heart disease.Many active components of Chinese herbal medic... Recently,studying myocardial energy metabolism pathways or improving myocardial metabolism through drugs is another effective strategy for treating ischemic heart disease.Many active components of Chinese herbal medicines(CHMs) have been found to modulate energy metabolism in myocardial cells,cerebral vascular cells,endothelial cells and tumour cells.This paper reviews the advances in studies on the active components of CHMs that modulating energy metabolism in treating cardiovascular diseases over the past five years. 展开更多
关键词 biologically active INGREDIENT Chinese HERBAL medicine CARDIOVASCULAR DISEASE ISCHEMIC HEART DISEASE HEART failure
Traditional Chinese medicine nursing protocols for leukorrheal disease(pelvic inflammatory disease) 预览
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作者 Editorial Board of Nursing of Integrated Traditional Chinese and Western Medicine 《中西医结合护理(中英文)》 2019年第1期217-223,共7页
Leukorrheal disease is an ascending infection of the female genital tract,with high morbidity among reproductive age women.Antibiotics are usually used to treat leukorrheal disease in clinic,but they can lead to a var... Leukorrheal disease is an ascending infection of the female genital tract,with high morbidity among reproductive age women.Antibiotics are usually used to treat leukorrheal disease in clinic,but they can lead to a variety of side effects if improper use or long-time use.In recent years,traditional Chinese medicine(TCM)has shown its unique advantages in the treatment of leukorrheal disease.This article mainly explored the key points of common syndromes,TCM nursing methods and health guidance of leukorrheal disease in order to further develop the advantages of TCM,improve its efficacy and standardized its nursing behavior. 展开更多
关键词 leukorrheal DISEASE PELVIC INFLAMMATORY DISEASE MENSTRUATION chronic PAIN traditional Chinese medicine NURSING syndrome differentiation
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Analysis of chronic kidney disease staging with different estimated glomerular filtration rate equations in Chinese centenarians
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作者 Qiu-Xia Han Dong Zhang +9 位作者 Ya-Li Zhao Liang Liu Jing Li Fu Zhang Fu-Xin Luan Jia-Yu Duan Zhang-Suo Liu Guang-Yan Cai Xiang-Mei Chen Han-Yu Zhu 《中华医学杂志:英文版》 SCIE CAS CSCD 2019年第5期512-518,共7页
Background: Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations ... Background: Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations for staging CKD in a large sample of centenarians. Thus, this study aimed to investigate the differences in CKD staging with the most commonly used equations and to analyze sources of discrepancy. Methods: A total of 966 centenarians were enrolled in this study from June 2014 to December 2016 in Hainan province, China. The GFR with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study 1 (BIS1) equations were estimated. Agreement between these equations was investigated with the k statistic and Bland-Altman plots. Sources of discrepancy were investigated by partial correlation analysis. Results: The k values of the MDRD and CKD-EPI equations, MDRD and BIS1 equations, and CKD-EPI and BIS1 equations were 0.610, 0.253, and 0.381, respectively. Serum creatinine (Scr) explained 10.96%, 41.60% and 17.06% of the variability in these three comparisons, respectively. Serum uric acid (SUA) explained 3.65% and 5.43% of the variability in the first 2 comparisons, respectively. Gender was associated with significant differences in these 3 comparisons (P<0.001). Conclusions: The strengths of agreement between the MDRD and CKD-EPI equations were substantial, but those between the MDRD and BIS 1 equations and the CKD-EPI and BIS 1 equations were fair. The difference in CKD staging of the first 2 comparisons strongly depended on Scr, SUA and gender, and that of CKD-EPI and BIS1 equations strongly depended on Scr and gender. The incidence at various stages of CKD staging was quite different. Thus, a new equation that is more suitable for the elderly needs to be built in the future. 展开更多
关键词 CHINESE CENTENARIANS Estimated glomerular filtration rate Modification of Diet in Renal DISEASE EQUATION Chronic Kidney DISEASE Epidemiology Collaboration EQUATION Berlin INITIATIVE Study 1 EQUATION
Risk stratification for coronary artery disease in multi-ethnic populations:Are there broader considerations for cost efficiency? 预览
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作者 Pupalan Iyngkaran William Chan +5 位作者 Danny Liew Jalal Zamani John D Horowitz Michael Jelinek David L Hare James A Shaw 《世界方法学杂志》 2019年第1期1-19,共19页
Coronary artery disease(CAD)screening and diagnosis are core cardiac specialty services.From symptoms,autopsy correlations supported reductions in coronary blood flow and dynamic epicardial and microcirculatory corona... Coronary artery disease(CAD)screening and diagnosis are core cardiac specialty services.From symptoms,autopsy correlations supported reductions in coronary blood flow and dynamic epicardial and microcirculatory coronaries artery disease as etiologies.While angina remains a clinical diagnosis,most cases require correlation with a diagnostic modality.At the onset of the evidence building process much research,now factored into guidelines were conducted among population and demographics that were homogenous and often prior to newer technologies being available.Today we see a more diverse multi-ethnic population whose characteristics and risks may not consistently match the populations from which guideline evidence is derived.While it would seem very unlikely that for the majority,scientific arguments against guidelines would differ,however from a translational perspective,there will be populations who differ and importantly there are cost-efficacy questions,e.g.,the most suitable first-line tests or what parameters equate to an adequate test.This article reviews non-invasive diagnosis of CAD within the context of multi-ethnic patient populations. 展开更多
关键词 Cost efficacy CORONARY artery DISEASE CORONARY heart DISEASE ETHNICITY Outcomes Risk STRATIFICATION
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Transitions of care across hospital settings in patients with inflammatory bowel disease 预览
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作者 Leigh R Warren Jonathan M Clarke +3 位作者 Sonal Arora Mauricio Barahona Naila Arebi Ara Darzi 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第17期2122-2132,共11页
BACKGROUND Inflammatory bowel disease (IBD) is a chronic, inflammatory disorder characterised by both intestinal and extra-intestinal pathology. Patients may receive both emergency and elective care from several provi... BACKGROUND Inflammatory bowel disease (IBD) is a chronic, inflammatory disorder characterised by both intestinal and extra-intestinal pathology. Patients may receive both emergency and elective care from several providers, often in different hospital settings. Poorly managed transitions of care between providers can lead to inefficiencies in care and patient safety issues. To ensure that the sharing of patient information between providers is appropriate, timely, accurate and secure, effective data-sharing infrastructure needs to be developed. To optimise inter-hospital data-sharing for IBD patients, we need to better understand patterns of hospital encounters in this group. AIM To determine the type and location of hospital services accessed by IBD patients in England. METHODS This was a retrospective observational study using Hospital Episode Statistics, a large administrative patient data set from the National Health Service in England. Adult patients with a diagnosis of IBD following admission to hospital were followed over a 2-year period to determine the proportion of care accessed at the same hospital providing their outpatient IBD care, defined as their ‘home provider’. Secondary outcome measures included the geographic distribution of patient-sharing, regional and age-related differences in accessing services, and type and frequency of outpatient encounters. RESULTS 95055 patients accessed hospital services on 1760156 occasions over a 2-year follow-up period. The proportion of these encounters with their identified IBD ‘home provider’ was 73.3%, 87.8% and 83.1% for accident and emergency, inpatient and outpatient encounters respectively. Patients living in metropolitan centres and younger patients were less likely to attend their ‘home provider’ for hospital services. The most commonly attended specialty services were gastroenterology, general surgery and ophthalmology. CONCLUSION Transitions of care between secondary care settings are common for patients with IBD. Effective systems of data-s 展开更多
关键词 Inflammatory bowel DISEASE Crohn's DISEASE Ulcerative colitis TRANSITIONS of CARE Continuity of CARE FRAGMENTATION Multi-morbidity
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Activated mTOR signaling pathway in myofibers with inherited metabolic defect might be an evidence for mTOR inhibition therapies
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作者 Jing-Wei Lyu Xue-Bi Xu +5 位作者 Kun-Qian Ji Na Zhang Yuan Sun Dan-Dan Zhao Yu-Ying Zhao Chuan-Zhu Yan 《中华医学杂志:英文版》 SCIE CAS CSCD 2019年第7期805-810,共6页
Background:Abnormally activated mechanistic target of rapamycin(mTOR)pathway has been reported in several model animals with inherited metabolic myopathies(IMMs).However,the profiles of mTOR pathway in skeletal muscle... Background:Abnormally activated mechanistic target of rapamycin(mTOR)pathway has been reported in several model animals with inherited metabolic myopathies(IMMs).However,the profiles of mTOR pathway in skeletal muscles from patients are still unknown.This study aimed to analyze the activity of mTOR pathway in IMMs muscles.Methods:We collected muscle samples from 25 patients with mitochondrial myopathy(MM),lipid storage disease(LSD)or Pompe disease(PD).To evaluate the activity of mTOR pathway in muscle specimens,phosphorylation of S6 ribosomal protein(p-S6)and p70S6 kinase(p-p70S6K)were analyzed by Western blotting and immunohistochemistry.Results:Western blotting results showed that p-p70S6K/p70S6K in muscles from LSD and MM was up-regulated when compared with normal controls(NC)(NC vs.LSD,U=2.000,P=0.024;NC vs.MM:U=6.000,P=0.043).Likewise,p-S6/S6 was also upregulated in muscles from all three subgroups of IMMs(NC vs.LSD,U=0.000,P=0.006;NC vs.PD,[7=0.000,P=0.006;NC vs.MM,U=1.000,P=0.007).Immunohistochemical study revealed that p-S6 was mainly expressed in fibers with metabolic defect.In MM muscles,most p-S6 positive fibers showed cytochrome C oxidase(COX)deficiency(U=5.000,P=0.001).In LSD and PD muscles,p-S6 was mainly overexpressed in fibers with intramuscular vacuoles containing lipid droplets(17=0.000,P=0.002)or basophilic materials(U=0.000,P=0.002).Conclusion:The mTOR pathway might be activated in myofibers with various metabolic defects,which might provide evidence for mTOR inhibition therapy in human IMMs. 展开更多
关键词 MTOR pathway Mitochondrial MYOPATHY Lipid storage DISEASE Pompe DISEASE
Nonalcoholic fatty liver disease prevalence in an Italian cohort of patients with hidradenitis suppurativa: A multi-center retrospective analysis 预览
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作者 Giovanni Damiani Sebastiano Leone +11 位作者 Kristen Fajgenbaum Nicola L Bragazzi Alessia Pacifico Rosalynn RZ Conic Paolo DM Pigatto Carlo Maiorana Pierpaolo Poli Emilio Berti Maria C Pace Piergiorgio Malagoli Vincenzo Bettoli Marco Fiore 《世界肝病学杂志:英文版(电子版)》 2019年第4期391-401,共11页
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) includes two distinct conditions, with different histologic features and prognosis: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Furthe... BACKGROUND Nonalcoholic fatty liver disease (NAFLD) includes two distinct conditions, with different histologic features and prognosis: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Furthermore, NASH is the more aggressive necro-inflammatory form, which may accumulate fibrosis and result in End stage liver disease (ESLD). NAFLD is also linked to systemic inflammatory conditions such as psoriasis. NAFLD is currently the most common cause of ESLD in Western countries, becoming a serious public health concern. Hidradenitis suppurativa (HS) is a systemic inflammatory/autoinflammatory disease of the terminal follicular epithelium of the apocrine gland with a prevalence of 0.05% to 4.10%. Due to its systemic inflammatory behavior several comorbidities were recently associated, however liver ones were scarcely assessed. AIM To evaluate the prevalence and characteristics of NASH/NAFL in HS patients. METHODS This retrospective study is a sub-analysis of a larger study carried out in 4 Italian dermatological centers. In this cohort, there were 83 patients: 51 patients with HS only, 20 patients with HS/NAFL and 12 with HS/NASH. RESULTS Inflammatory comorbidities were present in 3.9% of HS only patients, 25% of HS/NAFL patients and 58.3% of HS/NASH patients (P < 0.001). Similarly, mean Autoinflammatory Disease Damage Index (ADDI) was significantly higher among patients with HS/NASH (5.3 ± 2.2, P < 0.001) compared to patients with HS/NAFL or HS only (2.8 ± 1.6 and 2.6 ± 1.4 respectively). Furthermore, ADDI correlates with IHS4 in HS, HS/NAFL and HS/NASH. Diabetic patients have higher Hurley score than not diabetic ones. Ultrasound examination was significantly different in the three groups. CONCLUSION HS patients displayed a high prevalence of NASH/NAFLD and ultrasound examination should be particularly addressed to patients that display high ADDI scores. 展开更多
关键词 Non-alcoholic steatohepatitis Non-alcoholic FATTY LIVER Nonalcoholic FATTY LIVER DISEASE End stage LIVER DISEASE Hidradenitis suppurativa
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Consecutive fecal calprotectin measurements for predicting relapse in pediatric Crohn’s disease patients 预览
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作者 Alice Jane Foster Matthew Smyth +3 位作者 Alam Lakhani Benjamin Jung Rollin F Brant Kevan Jacobson 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第10期1266-1277,共12页
BACKGROUND Asymptomatic children with Crohn’s disease(CD) require ongoing monitoring to ensure early recognition of a disease exacerbation.AIM In a cohort of pediatric CD patients, we aimed to assess the utility of s... BACKGROUND Asymptomatic children with Crohn’s disease(CD) require ongoing monitoring to ensure early recognition of a disease exacerbation.AIM In a cohort of pediatric CD patients, we aimed to assess the utility of serial fecal calprotectin measurements to detect intestinal inflammatory activity and predict disease relapse.METHODS In this prospective longitudinal cohort study, children with CD on infliximab therapy in clinical remission were included. Fecal calprotectin levels were assessed at baseline and at subsequent 2-5 visits. Clinical and biochemical disease activity were assessed using the Pediatric Crohn’s Disease Activity Index, Creactive protein and erythrocyte sedimentation rate at baseline and at visits over the following 18 mo.RESULTS 53 children were included and eighteen patients(34%) had a clinical disease relapse during the study. Baseline fecal calprotectin levels were higher in patients that developed symptomatic relapse (median(interquartile range), relapse 723μg/g(283-1758) vs 244 μg/g(61-627), P = 0.02)Fecal calprotectin levels > 250μg/g demonstrated good predictive accuracy of a clinical flare within 3 mo(area under the receiver operator curve was 0.86, 95% confidence limits 0.781 to 0.937).CONCLUSION Routine fecal calprotectin testing in children with CD in clinical remission is useful to predict relapse. Levels > 250 μg/g are a good predictor of relapse in the following 3 mo. This information is important to guide monitoring standards used in this population. 展开更多
关键词 FECAL CALPROTECTIN DISEASE RELAPSE BIOMARKER Crohn’s DISEASE Children
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Repositioning of dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 agonists as potential neuroprotective agents 预览
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作者 Shaker A.Mousa Bassam M.Ayoub 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第5期745-748,共4页
Repositioning of dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 receptor agonists is a breakthrough in the field of neural regeneration research increasing glucagon like peptide-1 bioavailability,hence ... Repositioning of dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 receptor agonists is a breakthrough in the field of neural regeneration research increasing glucagon like peptide-1 bioavailability,hence its neuroprotective activities.In this article,the authors suggest not only crossing blood-brain barrier and neurodegenerative disease as off target for dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 receptor agonists,but also for ophthalmic preparations for diabetic retinopathy,which may be the latest breakthrough in the field if prepared and used in an appropriate nano-formulation to target the retinal nerves.The relation of neurodegenerative diseases’different mechanisms to the dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 receptor agonists should be further examined in preclinical and clinical settings.The repositioning of already marketed antidiabetic drugs for neurodegenerative diseases should save the high cost of the time-consuming normal drug development process.Drug repositioning is a hot topic as an alternative to molecular target based drug discovery or therapeutic switching.It is a relatively inexpensive pathway due to availability of previous pharmacological and safety data.The glucagon like peptide-1 produced in brain has been linked to enhanced learning and memory functions as a physiologic regulator in central nervous system by restoring insulin signaling.Intranasal administration of all marketed gliptins(or glucagon like peptide-1 receptor agonists)may show enhanced blood-brain barrier crossing and increased glucagon like peptide-1 levels in the brain after direct crossing of the drug for the olfactory region,targeting the cerebrospinal fluid.Further blood-brain barrier crossing tests may extend dipeptidyl peptidase-4 inhibitors’effects beyond the anti-hyperglycemic control to intranasal spray,intranasal powder,or drops targeting the blood-brain barrier and neurodegenerative diseases with the most suitable formula.Moreover,novel nano-formulation is 展开更多
关键词 REPOSITIONING DPP-4 INHIBITORS GLP-1RA neural regeneration blood-brain barrier Parkinson’s DISEASE Alzheimer’s DISEASE diabetic retinopathy
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Comparison of the meibomian gland dysfunction in patients with chronic ocular graft-versus-host disease and Sj?gren’s syndrome
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作者 Won Choi Jun Young Ha +3 位作者 Ying Li Jung Han Choi Yong Sok Ji Kyung Chul Yoon 《国际眼科杂志:英文版》 SCIE CAS 2019年第3期393-400,共8页
AIM: To investigate the abnormalities in the meibomian gland in patients with dry eye disease(DED) associated with chronic ocular graft-versus-host disease(coGVHD) in comparison with Sj?gren’s syndrome(SS), a major f... AIM: To investigate the abnormalities in the meibomian gland in patients with dry eye disease(DED) associated with chronic ocular graft-versus-host disease(coGVHD) in comparison with Sj?gren’s syndrome(SS), a major form of aqueous deficient DED and meibomian gland dysfunction(MGD), a common cause of evaporative DED.METHODS: A total 135 eyes of 135 subjects included in this study: patients with DED associated with coGVHD(n=30), patients with SS(n=35), patients with MGD(n=35), and normal controls(n=35). All participants completed the Ocular Surface Disease Index(OSDI) questionnaire, ocular surface examination [Schirmer test, tear film breakup time(TFBUT), and ocular surface staining], and meibomian gland assessment (meiboscore(gland dropout detected on meibography using infrared camera of the Keratograph 5 M), meibum expressibility score(MES), meibum quality score(MQS), lid margin abnormality)In addition, correlations of meibomian gland characteristics with ocular surface parameters as well as disease severity score were investigated in coGVHD group.RESULTS: The coGVHD group showed significantly higher meiboscore, MES, and MQS than the other 3 groups(all P<0.05). In the coGVHD group, parameters of meibomian gland showed a significant correlation each other and those of ocular surface. The correlation between meibomian gland parameters and severity score of co GVHD was also established(meiboscore, r=0.62;MES, r=0.47;MQS, r=0.47;lid margin abnormality score, r=0.55;all P<0.05).CONCLUSION: Patients with DED associated with co GVHD show poorer gland morphology and worse glandfunction than other types of DED. In addition, meibomian gland damage is not only associated with ocular surface damage but also disease severity of coGVHD. 展开更多
关键词 CHRONIC OCULAR GRAFT-VERSUS-HOST DISEASE Sj?gren’s syndrome dry eye DISEASE meibomian GLAND DYSFUNCTION meibography
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Microstructural damage pattern of vascular cognitive impairment:a comparison between moyamoya disease and cerebrovascular atherosclerotic disease 预览
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作者 Jia-Bin Su Si-Da Xi +7 位作者 Shu-Yi Zhou Xin Zhang Shen-Hong Jiang Bin Xu Liang Chen Yu Lei Chao Gao Yu-Xiang Gu 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第5期858-867,共10页
Moyamoya disease and cerebrovascular atherosclerotic disease are both chronic ischemic diseases with similar presentations of vascular cognitive impairment.The aim of the present study was to investigate the patterns ... Moyamoya disease and cerebrovascular atherosclerotic disease are both chronic ischemic diseases with similar presentations of vascular cognitive impairment.The aim of the present study was to investigate the patterns of microstructural damage associated with vascular cognitive impairment in the two diseases.The study recruited 34 patients with moyamoya disease(age 43.9±9.2 years;20 men and 14 women,27 patients with cerebrovascular atherosclerotic disease(age:44.6±7.6 years;17 men and 10 women),and 31 normal controls(age 43.6±7.3 years;18 men and 13 women)from Huashan Hospital of Fudan University in China.Cognitive function was assessed using the Mini-Mental State Examination,long-term delayed recall of Auditory Verbal Learning Test,Trail Making Test Part B,and the Symbol Digit Modalities Test.Single-photon emission-computed tomography was used to examine cerebral perfusion.Voxel-based morphometry and tract-based spatial statistics were performed to identify regions of gray matter atrophy and white matter deterioration in patients and normal controls.The results demonstrated that the severity of cognitive impairment was similar between the two diseases in all tested domains.Patients with moyamoya disease and those with cerebrovascular atherosclerotic disease suffered from disturbed supratentorial hemodynamics.Gray matter atrophy in bilateral middle cingulate cortex and parts of the frontal gyrus was prominent in both diseases,but in general,was more severe and more diffuse in those with moyamoya disease.White matter deterioration was significant for both diseases in the genu and body of corpus callosum,in the anterior and superior corona radiation,and in the posterior thalamic radiation,but in moyamoya disease,it was more diffuse and more severe.Vascular cognitive impairment was associated with regional microstructural damage,with a potential link between,gray and white matter damage.Overall,these results provide insight into the pathophysiological nature of vascular cognitive impairment.This study was approved 展开更多
关键词 nerve REGENERATION vascular cognitive impairment MOYAMOYA DISEASE CEREBROVASCULAR atherosclerotic DISEASE magnetic resonance IMAGING diffusion tensor IMAGING gray matter volume tract-based spatial statistics SINGLE-PHOTON emission computed tomography neural REGENERATION
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Upper gastrointestinal tract involvement of pediatric inflammatory bowel disease: A pathological review 预览
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作者 Dua Abuquteish Juan Putra 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第16期1928-1935,共8页
Upper gastrointestinal (UGI) tract involvement of inflammatory bowel disease (IBD) is commonly seen in pediatric patients. Upper endoscopy is included in the routine workup of children with suspected IBD to enhance th... Upper gastrointestinal (UGI) tract involvement of inflammatory bowel disease (IBD) is commonly seen in pediatric patients. Upper endoscopy is included in the routine workup of children with suspected IBD to enhance the diagnosis and management of these patients. Currently, childhood IBD is classified into ulcerative colitis (UC), atypical UC, Crohn’s disease (CD) and IBD unclassified. Histologic confirmation of UGI tract involvement, in particular the presence of epithelioid (non-caseating) granulomas, is helpful in confirming the diagnosis of IBD and its classification. Herein, we reviewed selected IBD-associated UGI tract manifestations in children. Lymphocytic esophagitis, seen predominantly in CD, is histologically characterized by increased intraepithelial lymphocytes (> 20 in one high-power field) in a background of mucosal injury with absence of granulocytes. Focally enhanced gastritis is a form of gastric inflammation in pediatric IBD marked by a focal lymphohistiocytic pit inflammation with or without granulocytes and plasma cells in a relatively normal background gastric mucosa. Duodenal inflammation seen in children with IBD includes cryptitis, villous flattening, increased intraepithelial lymphocytes, and lamina propria eosinophilia. Finally, epithelioid granulomas not associated with ruptured gland/crypt are a diagnostic feature of CD. The clinicopathologic correlation and differential diagnosis of each microscopic finding are discussed. Clinicians and pathologists should be cognizant of the utility and limitations of these histologic features. 展开更多
关键词 PEDIATRIC Inflammatory bowel DISEASE LYMPHOCYTIC ESOPHAGITIS Focally enhanced gastritis EPITHELIOID GRANULOMA Crohn’s DISEASE Ulcerative colitis
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Do patients with gastroesophageal reflux disease and somatoform tendencies benefit from antireflux surgery? 预览
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作者 Hans Friedrich Fuchs Benjamin Babic +3 位作者 Karl-Hermann Fuchs Wolfram Breithaupt Gabor Varga Frauke Musial 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第3期388-397,共10页
BACKGROUND The clinical presentation of gastroesophageal reflux disease(GERD)shows a large symptom variation also in different intensities among patients.As several studies have shown,there is a large overlap in the s... BACKGROUND The clinical presentation of gastroesophageal reflux disease(GERD)shows a large symptom variation also in different intensities among patients.As several studies have shown,there is a large overlap in the symptomatic spectrum between proven GERD and other disorders such as dyspepsia,functional heartburn and/or somatoform disorders.AIM To prospectively evaluate the GERD patients with and without somatoform disorders before and after laparoscopic antireflux surgery.METHODS In a tertiary referral center for foregut surgery over a period of 3 years patients with GERD,qualifying for the indication of laparoscopic antireflux surgery,were investigated prospectively regarding their symptomatic spectrum in order to identify GERD and associated somatoform disorders.Assessment of symptoms was performed by an instrument for the evaluation of somatoform disorders[Somatoform Symptom Index(SSI)>17].Quality of life was evaluated by Gastrointestinal Quality of Life Index(GIQLI).RESULTS In 123 patients an indication for laparoscopic antireflux surgery was established and in 43 patients further medical therapy was suggested.The portion of somatoform tendencies in the total patient population was 20.48%(34 patients).Patients with a positive SSI had a preoperative GIQLI of 77(32-111).Patients with a normal SSI had a GIQLI of 105(29-140)(P<0.0001).In patients with GERD the quality of life could be normalized from preoperative reduced values of GIQLI 102(47-140)to postoperative values of 117(44-144).In patients with GERD and somatoform disorders,the GIQLI was improved from preoperative GIQLI 75(47-111)to postoperative 95(44-122)(P<0.0043).CONCLUSION Patients with GERD and associated somatoform disorders have significantly worse levels of quality of life.The latter patients can also benefit from laparoscopic fundoplication,however they will not reach a normal level. 展开更多
关键词 GASTROESOPHAGEAL REFLUX DISEASE ANTIREFLUX surgery Laparoscopic FUNDOPLICATION Somatization GASTROESOPHAGEAL REFLUX DISEASE symptoms
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Cardiometabolic risk through an integrative classification combining physical activity and sedentary behavior in European adolescents:HELENA study
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作者 Carlos Cristi-Montero Palma Chillon +7 位作者 Idoia Labayen Jose A.Casajus Marcela Gonzalez-Gross Jeremy Vanhelst Yannis Manios Luis A.Moreno Francisco B.Ortega Jonatan R.Ruiz 《运动与健康科学:英文版》 SCIE 2019年第1期55-62,共8页
Purpose: This study aims to compare adolescents’ cardiometabolic risk score through an integrative classification of physical activity(PA),which involves the combination of moderate-to-vigorous physical activity(MVPA... Purpose: This study aims to compare adolescents’ cardiometabolic risk score through an integrative classification of physical activity(PA),which involves the combination of moderate-to-vigorous physical activity(MVPA) and sedentary behavior(SB).Methods: A cross-sectional study derived from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study database(2006-2008) was conducted in adolescents(n = 548;boys, 47.3%;14.7 ± 1.2 years) from 10 European cities. MVPA and SB were objectively measured using accelerometry. Adolescents were divided into 4 categories according to MVPA(meeting or not meeting the international recommendations) and the median of SB time(above or below sex-and age-specific median) as follows: High-SB & Inactive, Low-SB & Inactive,High-SB & Active, and Low-SB & Active. A clustered cardiometabolic risk score was computed using the homeostatic model assessment, systolic blood pressure, triglycerides, total cholesterol/high-density lipoprotein cholesterol, sum 4 skinfolds, and cardiorespiratory fitness(CRF).Analyses of covariance were performed to discern differences on cardiometabolic risk scores among PA categories and each health component.Results: The cardiometabolic risk score was lower in adolescents meeting the MVPA recommendation and with less time spent in SB in comparison to the high-SB & Inactive group(p < 0.05). However, no difference in cardiometabolic risk score was established between High-SB or Low-SB groups in inactive adolescents. It is important to note that CRF was the only variable that showed a significant modification(higher)when children were compared from the category of physically inactive with "active" but not from high-to low-SB.Conclusion: Being physically active is the most significant and protective outcome in adolescents to reduce cardiometabolic risk. Lower SB does not exhibit a significant and extra beneficial difference. 展开更多
关键词 Accelerometry CARDIOVASCULAR DISEASE EXERCISE METABOLIC DISEASE SEDENTARY lifestyles
Inflammation and cardiovascular disease 预览
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作者 Christina G Katsiari Dimitrios P Bogdanos Lazaros I Sakkas 《世界转化医学杂志》 2019年第1期1-8,共8页
Cardiovascular disease(CVD)has been associated with the so-called traditional risk factors,such as hypertension,hypercholesterolemia and cigarette smoking.Chronic inflammation,exemplified by elevated high sensitivity ... Cardiovascular disease(CVD)has been associated with the so-called traditional risk factors,such as hypertension,hypercholesterolemia and cigarette smoking.Chronic inflammation,exemplified by elevated high sensitivity C-reactive protein,has been added to these risk factors for CVD as non-traditional risk factor.There are two aspects in this association.The first is whether inflammation plays a pathogenic role in traditional risk factors-mediated CVD or it is just an epiphenomenon.The second is whether chronic inflammation caused by an inflammatory disease has any impact on CVD.Accumulated data have shown that inflammation has a central and inciting role in the development of atherosclerosis leading to increased CVD risk.How inflammation contributes to CVD is a topic of continuous research where mechanisms involving both innate and adaptive immune pathways are involved.Endothelial dysfunction,oxidative stress in vascular endothelial cells,macrophage accumulation,formation of inflammasome,production of tumor necrosis factor(TNF)-a,IL-1 and IL-6 characterize the inflammatory process leading to atherogenesis.Recently clonal hematopoiesis of indeterminate potential represents a surprising and novel mechanism underlying atherogenesis.Data from chronic rheumatic inflammatory diseases exemplify the complexity of mechanisms leading to increased CVD,while they also provide evidence that anti-inflammatory biologic drugs,such as anti-TNF and anti-IL6 agents,could control atherogenesis and ameliorate CVD risk.Recent groundbreaking work using biologic anti-IL-1b therapy to treat men and women who have had a prior heart attack provides the best proof of the pathogenic contribution of inflammation in the development of CVD. 展开更多
关键词 Cardiovascular DISEASE Coronary artery DISEASE ATHEROSCLEROSIS INFLAMMATION INNATE IMMUNITY Adaptive IMMUNITY BIOLOGIC drugs
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