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| 1 | 美国国立老化研究所与阿尔茨海默病协会诊断指南写作组:阿尔茨海默病临床前阶段的定义显示文摘阿尔茨海默病(AD)的病理生理过程在痴呆诊断的多年前就开始了。这一长期的AD“临床前”阶段是治疗干预的关键机会,但需进一步阐明AD的病理级联过程和临床症状出现之间的联系。美国国立老化研究所和AD协会召集了一个国际工作组对AD生物标志物、流行病学和神经心理学的证据进行综述并提出建议,以确定能够预测由“正常”认知到轻度认知功能障碍(MCI)及AD痴呆的最佳预测指标。根据目前已有的主要科学证据,我们提出了一个概念性的框架和用于操作的研究标准,以通过纵向临床研究来验证和改进这些模型。这些建议仅用于研究目的,目前不涉及临床应用。我们希望这些建议能提供一个共识,以推进临床前AD的研究,最终推动更早期治疗干预的进展,使得一些疾病减缓药物的疗效发挥最大。 | Sperling RA Aisen PS Beckett LA Bennett DA Craft S Fagan AM Iwatsubo T Jack CR Jr Kaye J Montine TJ Park DC Reiman EM Rowe CC Siemers E Stern Y Yaffe K Carrillo MC Thies B Morrison-Bogorad M Wagster MV Phelps CH 贾建平(译) 郭起浩(译) 黄丽(译) 陆璐(译) 张逸驰(译) 邢怡(译) | 2012 | 中华神经科杂志2012，45，5： | 22 |
| 2 | Colon cancer-associated B2 Escherichia coli colonize gut mucosa and promote cell proliferation显示文摘AIM:To provide further insight into the characterization of mucosa-associated Escherichia coli(E.coli)isolated from the colonic mucosa of cancer patients.METHODS:Phylogroups and the presence of cyclomodulin-encoding genes of mucosa-associated E.coli from colon cancer and diverticulosis specimens weredetermined by PCR.Adhesion and invasion experiments were performed with I-407 intestinal epithelial cells using gentamicin protection assay.Carcinoembryonic antigen-related cell adhesion molecule 6(CEACAM6)expression in T84 intestinal epithelial cells was measured by enzyme-linked immunosorbent assay and by Western Blot.Gut colonization,inflammation and procarcinogenic potential were assessed in a chronic infection model using CEABAC10 transgenic mice.Cell proliferation was analyzed by real-time mRNA quantification of PCNA and immunohistochemistry staining of Ki67.RESULTS:Analysis of mucosa-associated E.coli from colon cancer and diverticulosis specimens showed that whatever the origin of the E.coli strains,86%of cyclomodulin-positive E.coli belonged to B2 phylogroup and most harbored polyketide synthase(pks)island,which encodes colibactin,and/or cytotoxic necrotizing factor(cnf)genes.In vitro assays using I-407 intestinal epithelial cells revealed that mucosa-associated B2 E.coli strains were poorly adherent and invasive.However,mucosa-associated B2 E.coli similarly to Crohn’s disease-associated E.coli are able to induce CEACAM6expression in T84 intestinal epithelial cells.In addition,in vivo experiments using a chronic infection model of CEACAM6 expressing mice showed that B2 E.coli strain11G5 isolated from colon cancer is able to highly persist in the gut,and to induce colon inflammation,epithelial damages and cell proliferation.CONCLUSION:In conclusion,these data bring new insights into the ability of E.coli isolated from patients with colon cancer to establish persistent colonization,exacerbate inflammation and trigger carcinogenesis. | Jennifer Raisch Emmanuel Buc Mathilde Bonnet Pierre Sauvanet Emilie Vazeille Amélie de Vallée Pierre Déchelotte Claude Darcha Denis Pezet Richard Bonnet Marie-Agnès Bringer Arlette Darfeuille-Michaud | 2014 | World Journal of Gastroenterology2014，20，21： | 12 |
| 3 | Microbial markers in colorectal cancer detection and/or prognosis显示文摘Colorectal cancer(CRC) is the second leading cause of cancer worldwide. CRC is still associated with a poor prognosis among patients with advanced disease. On the contrary, due to its slow progression from detectable precancerous lesions, the prognosis for patients with early stages of CRC is encouraging. While most robust methods are invasive and costly, actual patient-friendly screening methods for CRC suffer of lack of sensitivity and specificity. Therefore, the development of sensitive, non-invasive and cost-effective methods for CRC detection and prognosis are necessary for increasing the chances of a cure. Beyond its beneficial functions for the host, increasing evidence suggests that the intestinal microbiota is a key factor associated with carcinogenesis. Many clinical studies have reported a disruption in the gut microbiota balance and an alteration in the faecal metabolome of CRC patients, suggesting the potential use of a microbialbased test as a non-invasive diagnostic and/or prognostic tool for CRC screening. This review aims to discuss the microbial signatures associated with CRC known to date, including dysbiosis and faecal metabolome alterations, andthe potential use of microbial variation markers for noninvasive early diagnosis and/or prognostic assessment of CRC and advanced adenomas. We will finally discuss the possible use of these markers as predicators for treatment response and their limitations. | Romain Villéger Amélie Lopès Julie Veziant Johan Gagnière Nicolas Barnich Elisabeth Billard Delphine Boucher Mathilde Bonnet | 2018 | World Journal of Gastroenterology2018，24，22： | 10 |
| 4 | Role of CARD15,DLG5 and OCTN genes polymorphisms in children with inflammatory bowel diseases显示文摘AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predispo- sition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD). METHODS: Two hundred patients with Crohn’s disease (CD), 186 ulcerative colitis (UC) patients, 434 par- ents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes, IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus, and 113G/A variant of the DLG5 gene were evaluated. Potential correlations with clinical sub-phenotypes were investigated. RESULTS: Polymorphisms of CARD15 were significantly associated with CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P < 0.001). Homozygosis for both OCTN1/2 variants was more com- mon in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an in- creased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No association with the DLG5 variant was found. CD carriers of OCTN1/2 and DLG5 variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene-gene interaction was found. In UC patients, the TC haplotype was morefrequent (45.4%, P = 0.03), but no genotype/phenotype correlation was observed. CONCLUSION: Polymorphisms of CARD15 and OCTN genes, but not DLG5 are associated with pediatric on- set of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a weak influence on CD phenotype. | S Cucchiara A Latiano O Palmieri AM Staiano R D'Incà G Guariso G Vieni V Rutigliano O Borrelli MR Valvano V Annese | 2007 | World Journal of Gastroenterology2007，13，8： | 9 |
| 5 | D-二聚体预测稳定型冠状动脉性心脏病患者的长期病因特异性死亡率、心血管事件和癌症显示文摘交联纤维蛋白的降解产物D-二聚体是高凝状态和血栓形成事件的标志。D-二聚体水平中度升高与血管疾病患者静脉和动脉事件的风险相关。在缺血性疾病长期普伐他汀干预(long-term intervention with pravastatin in ischemic disease,LIPID)试验中,研究者在存在其他危险因素的背景下,评估了D-二聚体水平在预测长期血管转归、病因特异性死亡率和新发癌症中的作用。 | 刘青 叶鹏 Simes J Robledo KP White HD Espinoza D Stewart RA Sullivan DR Zeller T Hague W Nestel PJ Glasziou PP Keech AC Elliott J Blankenberg S Tonkin AM LIPID study investigators | 2018 | 中华高血压杂志2018，26，3： | 6 |
| 6 | Role of ischaemic preconditioning in liver regeneration following major liver resection and transplantation显示文摘Liver ischaemic preconditioning (IPC) is known to protect the liver from the detrimental effects of ischaemic-reperfusion injury (IRI), which contributes significantly to the morbidity and mortality following major liver surgery. Recent studies have focused on the role of IPC in liver regeneration, the precise mechanism of which are not completely understood. This review discusses the current understanding of the mechanism of liver regeneration and the role of IPC in this setting. Relevant articles were reviewed from the published literature using the Medline database. The search was performed using | D Gomez S Homer-Vanniasinkam AM Graham KR Prasad | 2007 | World Journal of Gastroenterology2007，13，5： | 5 |
| 7 | Prevalence and risk factors of asymptomatic hepatitis C virus infection in Egyptian children显示文摘AIM: To identify the prevalence, risk factors and manifestations of asymptomatic hepatitis C virus (HCV) infection in Egyptian children. METHODS: Children at the age of 1-9 years were screened for HCV antibodies and alanine aminotransferase (ALT) levels. Every child with elevated ALT and/or detectable HCV antibodies was tested for HCV RNA by RT-PCR and compared with two negative controls for risk factors and signs and symptoms of liver disease.RESULTS: We screened 1042 children, six of them had elevated ALT, negative HCV antibody and positive RNA, likely representing acute hepatitis C cases. Fifteen children were HCV seropositive, 5 of them were HCV RNA positive. Asymptomatic HCV infection was present in 2.02% (positive results for either HCV antibodies or HCV-RNA or both). Symptoms such as diarrhea, abdominal pain, history of fatigue and school absence because of illness and risk factors such as dental care were significantly more common among HCV positive cases than among controls. None of the HCV positive children was diagnosed as having signs of advanced liver disease upon clinical or ultrasonographic examination. CONCLUSION: Asymptomatic HCV infection is detectable in 2.02% Egyptian children. | MS El-Raziky M El-Hawary G Esmat AM Abouzied N El-Koofy N Mohsen S Mansour A Shaheen M Abdel Hamid H El-Karaksy | 2007 | World Journal of Gastroenterology2007，13，12： | 4 |
| 8 | Human urotensinⅡis a potent vasoconstrictory and agonist for the orphan receptor GPR14 显示文摘 | Ames R S Sarau H M Chambers J K | 1999 | Nature1999，401，6750： | 3 |
| 9 | 脂质组学改善传统危险因素预测的2型糖尿病患者的心血管事件显示文摘临床脂质测定并未显示出糖尿病或心血管病相关的脂质代谢改变的复杂性。脂质组学则能够评估可作为疾病风险潜在标志物的数百种脂质种类。方法:纳入来自糖尿病治疗和血管保护行动。 | 刘莉 叶鹏 Alshehry ZH Mundra PA Barlow CK Mellett NA Wong G McConville MJ Simes J Tonkin AM Sullivan DR Barnes EH Nestel PJ Kingwell BA Marre M Neal B Poulter NR Rodgers A Williams B Zoungas S Hillis GS Chalmers J Woodward M Meikle PJ | 2016 | 中华高血压杂志2016，24，10： | 3 |
| 10 | 青年急性心肌梗死住院患者的20年趋势及性别差异显示文摘老年人发生急性心肌梗死(AMI)存在性别差异已众所周知。但青年AMI发生率和相关危险因素在性别分布上是否存在差异的研究却很少。Arora等在美国4个社区开展的动脉粥样硬化风险(ARIC)研究,对AMI入院情况进行监测并分类评估。其研究人群为35至54岁年轻患者,并从患者病历中提取诊疗信息。结果显示:1995至2014年,共抽取了28732份加权AMI住院患者,其中8737人(30%)是年轻人。年轻AMI入院患者总体比例从1995—1999年的27%上升到2010—2014年的32%(P=0.002),其中年轻女性的增幅最大。在年轻AMI患者中,有高血压病史的比例从59%上升至73%(P<0.001),有糖尿病病史的比例从25%上升至35%(P<0.001)。与年轻男性相比,发生急性心肌梗死的年轻女性多为黑人,并且有更大的共病负担。年轻女性接受基于指南治疗的概率更低,包括降脂、非阿司匹林抗血小板治疗、β受体阻滞剂治疗、冠状动脉造影和冠状动脉血管重建。研究提示,需要更好地了解这些性别差异的潜在因素,以改善对年轻AMI患者的护理。 | Arora S Stouffer GA Kucharska-Newton AM 王德征(编译) | 2020 | 中华预防医学杂志2020，54，1： | 3 |
| 11 | Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: An individual subject meta-analysis显示文摘AIM To confirm previous conclusions on Saccharomyces cerevisiae(S. cerevisiae) CNCM I-3856 for irritable bowel syndrome(IBS) management.METHODS An individual patient data meta-analysis was performed on two randomized clinical trials studying the effect of S. cerevisiae CNCM I-3856 supplementation on gastrointestinal(GI) symptoms in IBS subjects. A total of 579 IBS subjects were included. Outcomes were the daily Likert scale scores of abdominal pain/discomfort and bloating [area under the curve(AUC) and weekly means], responder status, and bowel movements(stool frequency and consistency). Statistical analyses were conducted in Intent to Treat(ITT) population, IBS-C subjects and IBS-C subjects with an abdominal pain/discomfort score higher than or equal to 2 at baseline('IBS-C ≥ 2 subpopulation').RESULTS S. cerevisiae CNCM I-3856 significantly improved abdominal pain/discomfort and bloating during the second month of supplementation [AUC(W5-W8)]with improvement up to the minimal clinically relevant threshold of 10%: a 12.3% reduction of abdominal pain/discomfort in the ITT population compared to the Placebo group(P = 0.0134) has been observed. In the IBS-C ≥ 2 subpopulation, there were a 13.1% reduction of abdominal pain/discomfort and a 14.9% reduction of bloating compared to the Placebo group(P = 0.0194 and P = 0.0145, respectively). GI symptoms significantly decreased during supplementation but no statistical differences were reported between groups at the end of the supplementation period. Responder status was defined as a subject who experienced a decrease of 1 arbitrary unit(a.u.) or 50% of the abdominal discomfort score from baseline for at least 2 wk out of the last 4 wk of the study. A significant difference between groups was reported in the ITT population, when considering the first definition: subjects in the Active group had 1.510 higher odds to be a responder(reduction of 1 a.u. of abdominal pain/discomfort) compared with subjects in the Placebo group(P = 0.0240). At the end of supplementation period, stool consistency in the Active group of the ITT population was significantly improved and classified as 'normal' compared to Placebo(respectively 3.13 ± 1.197 a.u. vs 2.58 ± 1.020 a.u., P = 0.0003). Similar results were seen in the IBS-C ≥ 2 subpopulation(Active group: 3.14 ± 1.219 a.u. vs Placebo group: 2.59 ± 1.017 a.u., P = 0.0009).CONCLUSION This meta-analysis supports previous data linking S. cerevisiae I-3856 and improvement of GI symptoms, in IBS overall population and in the IBS-C and IBS-C ≥ 2 subpopulations. | Amélie Cayzeele-Decherf Fanny Pélerin Sébastien Leuillet Benoit Douillard Béatrice Housez Murielle Cazaubiel Gunnard K Jacobson Peter Jüsten Pierre Desreumaux | 2017 | World Journal of Gastroenterology2017，23，2： | 2 |
| 12 | 高密度脂蛋白可追踪脑卒中恢复情况显示文摘前瞻性队列研究质疑高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)在脑卒中风险预测中的价值。该文旨在探讨长期功能恢复与高密度脂蛋白(high density lipoprotein,HDL)蛋白质组和功能的关系。方法与结果:测定急性缺血性脑卒中后2个时间点(24小时,35例;96小时,20例)和35例对照组HDL蛋白组成和功能(胆固醇流出能力)的变化。 | Plubell DL Fenton AM Rosario S Bergstrom P Wilmarth PA Clark WM Zakai NA Quinn JF Minnier J Alkayed NJ Fazio S Pamir N 刘青(译) 刘莉(摘/审校) | 2020 | 中华高血压杂志2020，28，11： | 2 |
| 13 | 重组脊髓灰质炎病毒用于治疗复发胶质母细胞瘤(英文)显示文摘Background The prognosis of patients with recurrent World Health Organization(WHO)grade IV malignant glioma is dismal,and there is currently no effective therapy.We conducted a dose-finding and toxicity study in this population of patients,evaluating convection-enhanced,intratumoral delivery of the recombinant nonpathogenic polio-rhinovirus chimera(PVSRIPO).PVSRIPO recognizes the poliovirus receptor CD155,which is widely expressed in neoplastic cells of solid tumors and in major components of the tumor microenvironment.Methods We enrolled consecutive adult patients who had recurrent supratentorial WHO grade IV malignant glioma,confirmed on histopathological testing,with measurable disease(contrast-enhancing tumor of≥1 cm and≤5.5 cm in the greatest dimension).The study evaluated seven doses,ranging between 107 and 1010 50%tissue-culture infectious doses(TCID50),first in a dose-escalation phase and then in a dose-expansion phase.Results From May 2012 through May 2017,a total of 61 patients were enrolled and received a dose of PVSRIPO.Dose level-1(5.0×107TCID50)was identified as the phase 2 dose.One dose-limiting toxic effect was observed;a patient in whom dose level 5(1010TCID50)was administered had a grade 4 intracranial hemorrhage immediately after the catheter was removed.To mitigate locoregional inflammation of the infused tumor with prolonged glucocorticoid use,dose level 5 was deescalated to reach the phase 2 dose.In the dose-expansion phase,19%of the patients had a PVSRIPO-related adverse event of grade 3 or higher.Overall survival among the patients who received PVSRIPO reached a plateau of 21%(95%confidence interval,11 to 33)at 24 months that was sustained at 36 months.Conclusions Intratumoral infusion of PVSRIPO in patients with recurrent WHO grade IV malignant glioma confirmed the absence of neurovirulent potential.The survival rate among patients who receivedPVSRIPO immunotherapy was higher at 24 and 36 months than the rate among historical controls. | Desjardins A Gromeier M Herndon JE 2nd Beaubier N Bolognesi DP Friedman AH Friedman HS McSherry F Muscat AM Nair S Peters KB Randazzo D Sampson JH Vlahovic G Harrison WT McLendon RE Ashley D Bigner DD | 2018 | 中华神经外科疾病研究杂志2018，17，4： | 2 |
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