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12018加拿大心境障碍与焦虑障碍治疗协作组/国际双相障碍学会指南:双相障碍的管理显示文摘加拿大心境障碍与焦虑障碍治疗协作组(Canadian Network for Mood and Anxiety Treatments,CANMAT)曾于2005年发布了第1版双相障碍管理指南,并分别于2007、2009和2013年对该指南进行了更新,其中最近的2次更新是与国际双相障碍学会(International Society for Bipolar Disorders,ISBD)合作完成。2018版CANMAT/ISBD双相障碍治疗指南(以下简称指南)反映了自2005年首版指南发表以来本领域取得的重大进展,包括疾病诊断与疾病管理的更新以及药物治疗与心理治疗的近期研究进展。这些前沿进展中综合考虑了循证证据的级别,并基于治疗疗效、临床实践经验、安全性、耐受性和药物导致的转相风险等,对一线、二线及三线治疗方案进行了简明而清晰的推荐。本指南中新增内容涵盖了双相Ⅰ型障碍(BD-Ⅰ)的躁狂发作急性期、抑郁发作急性期和双相障碍维持期的一线及二线治疗推荐等级划分。这种对治疗推荐等级的划分综合考虑了治疗方法对双相障碍不同时相的影响,将进一步帮助临床医生做出基于循证证据的治疗决策。锂盐、喹硫平、双丙戊酸盐、阿塞那平、阿立哌唑、帕利哌酮、利培酮和卡利拉嗪单药或联合使用被推荐为躁狂发作急性期的一线治疗选择。BD-Ⅰ抑郁期的一线治疗选择包括喹硫平、鲁拉西酮、锂盐、拉莫三嗪单药,鲁拉西酮联合锂盐或双丙戊酸盐或拉莫三嗪辅助治疗。尽管急性期治疗有效的药物通常应继续用于BD-Ⅰ的维持期治疗,但也存在一些特殊情况(例如抗抑郁药)。现有数据表明,锂盐、喹硫平、双丙戊酸盐、拉莫三嗪、阿塞那平和阿立哌唑单药或联合治疗应被视为维持治疗的初始或更换治疗方案时的一线选择。除了探讨BD-Ⅰ的相关问题外,本指南中还对双相Ⅱ型障碍(BD-Ⅱ)的临床管理进行了系统回顾并给予治疗推荐,同时针对特殊人群也有相关推荐,如处于各个生殖周期的女性、儿童、青少年和老年人。此外,本指南中还讨论了特定精神疾病及共病(如物质滥用、焦虑障碍和代谢性疾病)的影响。最后,本指南中概述了安全性和药物监测的相关问题。CANMAT/ISBD工作组希望本指南能够成为全球临床医生的实用工具。Lakshmi N Yatham Sidney H Kennedy Sagar V Parikh Ayal Sehaffer David J Bond Benicio N Frey Verinder Sharma Benjamin I Goldstein Soham Rej Serge Beaulieu Martin Alda Glenda MaeQueen Roumen V Milev Arun Ravindran Claire O'Donovan Diane Mclntosh Raymond W Lam Gustavo Vazquez Flavio Kapczinski Roger S Melntyre Jan Kozicky Shigenobu Kanba Beny Lafer Trisha Suppes Joseph R Calabrese Eduard Vieta Gin Malhi Robert M Post Michael Berk 胡晨(译) 王刚(译) 2019中华精神科杂志2019,52,1:25
2MicroRNAs, development of Barrett’s esophagus, and progression to esophageal adenocarcinoma显示文摘Barrett's esophagus is a premalignant condition caused by gastroesophageal reflux. Once developed, it can progress through varying grades of dysplasia to esoph-ageal adenocarcinoma. Whilst it is well accepted that Barrett's esophagus is caused by gastroesophageal reflux, the molecular mechanisms of its pathogenesis and progression to cancer remain unclear. MicroRNAs (miRNAs) are short segments of RNA that have been shown to control the expression of many human genes. They have been implicated in most cellular processes, and the role of miRNAs in disease development is be-coming increasingly evident. Understanding altered miRNA expression is likely to help unravel the molecular mechanisms that underpin the development of Barrett's esophagus and its progression to cancer.Cameron M Smith David I Watson Michael Z Michael Damian J Hussey 2010World Journal of Gastroenterology2010,16,5:23
3Methylation-dependent loss of RIP3 expression in cancer represses programmed necrosis in response to chemotherapeutics显示文摘交往受体的蛋白质 kinase-3 (RIP3 或 RIPK3 ) 是执行 “ 的细胞的机械的必要部分; programmed”或 “ regulated”坏死。这里,我们证明那规划坏死响应许多化学疗法的代理人被激活并且贡献导致化疗的房间死亡。然而,我们证明那 RIP3 表情经常在化学疗法的死亡期间由于它的 transcriptional 开始地点, MLKL 的这样 RIP3 依赖的激活和下游地规划的坏死附近的 genomic methylation 是在癌症房间的 silenced 大部分被镇压。不过,有 hypomethylating 代理人的治疗恢复 RIP3 表示,并且从而以一种 RIP3 依赖的方式把敏感提升到 chemotherapeutics。RIP3 表示在 85% 乳癌病人与正常织物相比在肿瘤被减少,建议那 RIP3 缺乏断然在肿瘤生长 / 发展期间被选择。因为 hypomethylating 代理人在病人是相当容忍得好的,我们建议病人们可以从收到 hypomethylating 代理人与常规 chemotherapeutics 在治疗以前导致 RIP3 表示有益于的那 RIP3 缺乏的癌症。Gi-Bang Koo Michael J Morgan Da-Gyum Lee Woo-Jung Kim Jung-Ho Yoon Ja Seung Koo Seung I1 Kim Soo Jung Kim Mi Kwon Son Soon Still Hong Jean M Mulcahy Levy Daniel A Pollyea Craig T Jordan Pearlly Yan David Frankhouser Deedra Nicolet Kati Maharry Guido Marcucci Kyeong Sook Choi Hyeseong Cho ndrew Thorbum You-Sun Kim 2015Cell Research2015,25,6:20
4Anterior knee pain following primary total knee arthroplasty显示文摘Despite improvements in technique and technology for total knee arthroplasty(TKA),anterior knee pain impacts patient outcomes and satisfaction.Addressing the prosthetic and surgical technique related causes of pain after TKA,specifically as it relates to anterior knee pain,can aid surgeons in addressing these issues with their patients.Design features of the femoral and patellar components which have been reported as pain generators include: Improper femoral as well as patellar component sizing or designs that result in patellofemoral stuffing; a shortened trochlear groove distance from the flange to the intercondylar box; and then surgical technique related issues resulting in: Lateral patellar facet syndrome; overstuffed patella/flange combination; asymmetric patellar resurfacing,improper transverse plane component rotation resulting in patellar subluxation/tilt.Any design consideration that allows impingement of extensor mechanism anatomical elements has the possibility of impacting outcome by becoming a pain generator.As the number of TKA procedures continues to increase,it is increasingly critical to develop improved,evidence based prostheses that maximize function and patient satisfaction while minimizing pain and other complications.David Shervin Katelyn Pratt Travis Healey Samantha Nguyen William M Mihalko Mouhanad M El-Othmani Khaled J Saleh 2015World Journal of Orthopedics2015,6,10:15
5上海26万妇女乳房自我检查随机试验显示文摘目的论证指导妇女进行乳房自我检查(BSE)是否能有效降低乳腺癌患者的死亡率。方法自1989年10月起,上海26.6万名年龄在30~64岁的妇女,随机进入指导组(132979名)和对照组(133085名)。在指导组,最初先由医务人员做规范的BSE手法演示,随后的4年中,使用BSE录像带进行二次强化教育,并定期进行BSE指导和在医务人员监察下进行BSE操作。本研究进行5年,全部活动均被记录。队列人群随访到2000年7月,乳腺癌患者的生存状况随访到2001年12月。统计分析采用Kaplan-Meier方法、Logrank检验以及Cox模型。结果指导组检出乳腺癌864例,其中死于乳腺癌133例;对照组检出乳腺癌896例,其中死于乳腺癌130例。两组乳腺癌病例的肿块大小、TNM分期和累积死亡率的差异均无统计学意义(P均>0.05)。但是指导组比对照组有较多和较小的纤维腺瘤被检出(P<0.01)。结论对人群开展BSE教育和指导,未能降低人群的乳腺癌死亡率;接受BSE教育的妇女比没有接受教育的妇女可检出较多的和较小的良性乳房肿块。高道利 David BThomas Roberta M Ray 王文婉 Charlene J Allison 陈范良 Peggy Porter 胡永伟 赵关林 潘雷达 李雯瑾 武春园 Zakia Coriaty Ilonka Evans 林明纲 Helge Stalsberg Steven Gself 2005中华肿瘤杂志2005,27,6:14
6miR-200 family expression is downregulated upon neoplastic progression of Barrett's esophagus显示文摘AIM: To investigate miR-200 family expression in Barrett's epithelium, gastric and duodenal epithelia, and esophageal adenocarcinoma. METHODS: Real-time reverse transcriptase-polymerase chain reaction was used to measure miR-200, ZEB1 and ZEB2 expression. Ingenuity Pathway Analysis of miR-200 targets was used to predict biological outcomes. RESULTS: Barrett's epithelium expressed lower levels of miR-141 and miR-200c than did gastric and duodenal epithelia (P < 0.001). In silico analysis indicated roles for the miR-200 family in molecular pathways that distinguish Barrett's epithelium from gastric and duodenalepithelia, and which control apoptosis and proliferation. All miR-200 members were downregulated in adenocarcinoma (P < 0.02), and miR-200c expression was also downregulated in non-invasive epithelium adjacent to adenocarcinoma (P < 0.02). The expression of all miR-200 members was lower in Barrett's epithelium derived high-grade dysplastic cell lines than in a cell line derived from benign Barrett's epithelium. We observed signif icant inverse correlations between miR-200 family expression and ZEB1 and ZEB2 expression in Barrett's epithelium and esophageal adenocarcinoma (P < 0.05). CONCLUSION: miR-200 expression might contribute to the anti-apoptotic and proliferative phenotype of Barrett's epithelium and regulate key neoplastic processes in this epithelium.Cameron M Smith David I Watson Mary P Leong George C Mayne Michael Z Michael Bas PL Wijnhoven Damian J Hussey 2011World Journal of Gastroenterology2011,17,8:13
7Role of polyethylene particles in peri-prosthetic osteolysis:A review显示文摘There is convincing evidence that particles produced by the wear of joint prostheses are causal in the periprosthetic loss of bone,or osteolysis,which,if it progresses,leads to the phenomenon of aseptic loosening.It is important to fully understand the biology of this bone loss because it threatens prosthesis survival,and loosened implants can result in peri-prosthetic fracture,which is disastrous for the patient and presents a difficult surgical scenario.The focus of this review is the bioactivity of polyethylene(PE)particles,since there is evidence that these are major players in the development and progression of osteolysis around prostheses which use PE as the bearing surface.The review describes the biological consequences of interaction of PE particles with macrophages,osteoclasts and cells of the osteoblast lineage,including osteocytes.It explores the possible cellular mechanisms of action of PE and seeks to use the findings to date to propose potential nonsurgical treatments for osteolysis.In particular,a nonsurgical approach is likely to be applicable to implants containing newer,highly cross-linked PEs(HXLPEs),for which osteolysis seems to occur with much reduced PE wear compared with conventional PEs.The caveat here is that we know little as yet about the bioactivity of HXLPE particles and addressing this constitutes our next challenge.Gerald J Atkins David R Haynes Donald W Howie David M Findlay 2011World Journal of Orthopedics2011,2,10:11
8Bacterial biota in reflux esophagitis and Barrett's esophagus显示文摘AIM: To identify the bacterial flora in conditions such as Barrett's esophagus and reflux esophagitis to determine if they are similar to normal esophageal flora.METHODS: Using broad-range 16S rDNA PCR,esophageal biopsies were examined from 24 patients [9with normal esophageal mucosa, 12 with gastroesophageal reflux disease (GERD), and 3 with Barrett's esophagus].Two separate broad-range PCR reactions were performed for each patient, and the resulting products were cloned.In one patient with Barrett's esophagus, g9 PCR clones were analyzed.RESULTS: Two separate clones were recovered from each patient (total = 48), representing 24 different species, with 14 species homologous to known bacteria,5 homologous to unidentified bacteria, and 5 were not homologous (<97% identity) to any known bacterial 16S rDNA sequences. Seventeen species were found in the reflux esophagitis patients, 5 in the Barrett's esophagus patients, and 10 in normal esophagus patients.Further analysis concentrating on a single biopsy from an individual with Barrett's esophagus revealed the presence of 21. distinct bacterial species. Members of four phyla were represented, including Bacteroidetes,Firmicutes, Proteobacteria, and Actinobacteria.Microscopic examination of each biopsy demonstrated bacteria in intimate association with the distal esophageal epithelium, suggesting that the presence of these bacteria is not transitory.CONCLUSION: These findings provide evidence for a complex, residential bacterial population in esophageal reflux-related disorders. While much of this biota is present in the normal esophagus, more detailed comparisons may help identify potential disease associations.Zhiheng Pei Liying Yang Richard M Peek Jr Steven M Levine David T Pride Martin J Blaser 2005World Journal of Gastroenterology2005,11,46:11
9Blood pressure gradients in cerebral arteries:a clue to pathogenesis of cerebral small vessel disease显示文摘rationale The role of hypertension in cerebral small vessel disease is poorly understood.At the base of the brain(the‘vascular centrencephalon’),short straight arteries transmit blood pressure directly to small resistance vessels;the cerebral convexity is supplied by long arteries with many branches,resulting in a drop in blood pressure.Hypertensive small vessel disease(lipohyalinosis)causes the classically described lacunar infarctions at the base of the brain;however,periventricular white matter intensities(WMIs)seen on MRI and WMI in subcortical areas over the convexity,which are often also called‘lacunes’,probably have different aetiologies.Objectives We studied pressure gradients from proximal to distal regions of the cerebral vasculature by mathematical modelling.Methods and results Blood flow/pressure equations were solved in an Anatomically Detailed Arterial Network(ADAN)model,considering a normotensive and a hypertensive case.Model parameters were suitably modified to account for structural changes in arterial vessels in the hypertensive scenario.Computations predict a marked drop in blood pressure from large and medium-sized cerebral vessels to cerebral peripheral beds.When blood pressure in the brachial artery is 192/113 mm Hg,the pressure in the small arterioles of the posterior parietal artery bed would be only 117/68 mm Hg.In the normotensive case,with blood pressure in the brachial artery of 117/75 mm Hg,the pressure in small parietal arterioles would be only 59/38 mm Hg.conclusion These findings have important implications for understanding small vessel disease.The marked pressure gradient across cerebral arteries should be taken into account when evaluating the pathogenesis of small WMIs on MRI.Hypertensive small vessel disease,affecting the arterioles at the base of the brain should be distinguished from small vessel disease in subcortical regions of the convexity and venous disease in the periventricular white matter.Pablo J Blanco Lucas O Müller J David Spence 2017Stroke & Vascular Neurology2017,2,3:9
10Involvement of eicosanoids in the pathogenesis of pancreatic cancer: the roles of cyclooxygenase-2 and 5-lipoxygenase显示文摘The interplay between inflammation and cancer progression is a growing area of research. A combination of clinical, epidemiological, and basic science investigations indicate that there is a relationship between inflammatory changes in the pancreas and neoplastic progression. Diets high in ω-6 polyunsaturated fatty acids provide increased substrate for arachidonic acid metabolism by cyclooxygenase-2(COX-2) and 5-lipoxygenase(5-LOX) to form eicosanoids. These eicosanoids directly contribute to pancreatic cancer cell proliferation. Both COX-2 and 5-LOX are upregulated in multiple cancer types, including pancreatic cancer. In vitro studies using pancreatic cancer cell lines have demonstrated upregulation of COX-2 and 5-LOX at both the mRNA and protein levels. When COX-2 and 5-LOX are blocked via a variety of mechanisms, cancer cell proliferation is abrogated both in vitro and in vivo.The mechanism of COX-2 has been shown to include effects on apoptosis as well as angiogenesis. 5-LOX has been implicated in apoptosis. The use of COX-2 and 5-LOX inhibitors in clinical studies in patients with pancreatic cancer has been limited. Patient enrollment has been restricted to those with advanced disease which makes evaluation of these drugs as chemopreventive agents difficult. COX-2 and 5-LOX expression have been shown to be present during the early neoplastic changes of pancreatic cancer, well before progression to invasive disease. This indicates that the ideal role for these interventions is early in the disease process as preventive agents, perhaps in patients with chronic pancreatitis or hereditary pancreatitis.Lawrence M Knab Paul J Grippo David J Bentrem 2014World Journal of Gastroenterology2014,20,31:9
11Regulation of hematopoiesis and the hematopoietic stem cell niche by Wnt signaling pathways显示文摘造血的干细胞(HSC ) 是为所有系的血细胞的终生的产生负责的房间的一张稀罕人口。以便维持他们的数字, HSC 必须建立在自强的反对房间命运之间的平衡(在哪个作为 HSC 工作的能力被保留) 并且造血的区别的开始。Multiplesignaling 小径在 HSC 房间命运的规定被含有。小径的一个如此的集合是 ligands 的 Wnt 家庭激活的那些。Wnt 发信号小径玩关键角色 duringembryogenesis,这些小径的解除管制在稳固的肿瘤的形成被含有。发信号的 Wnt 也从多重纸巾在干细胞的规定起一个作用,例如胚胎、表皮、肠的干细胞。然而,在 HSCbiology 发信号的 Wnt 的功能仍然是争论的。在这评论,我们将讨论成年 HSC 的基本特征,集中于 HSCand 的规定并且它的规章的微型环境,“壁龛”它由表明小径的 Wnt 的壁龛。Michael J Nemeth David M Bodine 2007Cell Research2007,17,9:9
12牧草如何生长——植物生长与放牧管理之关联(英文)显示文摘适当管理饲料饲草资源的基本原则是理解多年生牧草如何生长。长期以来 ,对根系生长有了基本的了解 ,对去叶和环境对根系生长的影响也知之甚多。然而 ,对去叶、干旱及其他环境因素对多年生牧草的影响以及这些牧草对去叶的反应缺乏应有的理解。从牧草返青到开花 ,植物处于短枝阶段 ,适度放牧并不对多年生牧草的健康和活力造成危害 ,因为植物会弥补其失去的叶片。然而 ,当牧草从短枝向长枝阶段 (节间伸长和开花期 )转移时 ,碳水化合物主要用于节间伸长和开花过程。在开花后和休眠前期 ,碳水化合物主要向茎基和植物基部转移 ,以供来年新枝条的发育。因此 ,在花后和休眠前期 ,放牧系统必须被调节到“无放牧”状态。“无放牧”状态 ,如休息、轮牧、延迟轮牧和快速轮牧制 ,其价值在于这种定期的禁牧可提高多年生牧草的活力 ,改善草地的健康状况 ,并且在不利的环境条件下 。Ronald E Sosebee David B Wester J Carlos Villalobos Carlton M Britton Changgui Wan Hisham Nofal 2005草业学报2005,14,1:8
13Role of microbial dysbiosis in the pathogenesis of esophageal mucosal disease:A paradigm shift from acid to bacteria?显示文摘Genomic sequencing,bioinformatics,and initial speciation(e.g.,relative abundance)of the commensal microbiome have revolutionized the way we think about the“human”body in health and disease.The interactions between the gut bacteria and the immune system of the host play a key role in the pathogenesis of gastrointestinal diseases,including those impacting the esophagus.Although relatively stable,there are a number of factors that may disrupt the delicate balance between the luminal esophageal microbiome(EM)and the host.These changes are thought to be a product of age,diet,antibiotic and other medication use,oral hygiene,smoking,and/or expression of antibiotic products(bacteriocins)by other flora.These effects may lead to persistent dysbiosis which in turn increases the risk of local inflammation,systemic inflammation,and ultimately disease progression.Research has suggested that the etiology of gastroesophageal reflux disease-related esophagitis includes a cytokine-mediated inflammatory component and is,therefore,not merely the result of esophageal mucosal exposure to corrosives(i.e.,acid).Emerging evidence also suggests that the EM plays a major role in the pathogenesis of disease by inciting an immunogenic response which ultimately propagates the inflammatory cascade.Here,we discuss the potential role for manipulating the EM as a therapeutic option for treating the root cause of various esophageal disease rather than just providing symptomatic relief(i.e.,acid suppression).Steve M D'Souza Kevin Houston Lauren Keenan Byung Soo Yoo Parth J Parekh David A Johnson 2021World Journal of Gastroenterology2021,27,18:8
14Current and future applications of magnetic resonance imaging and spectroscopy of the brain in hepatic encepha-lopathy显示文摘肝的脑病(他) 普通 neuro 精神病学的畸形,它从肝细胞失败或 portosystemic 与肝疾病和结果复杂化病人的功课正在推延。表明他是广泛地可变的并且从温和无临床症状的骚乱包含一个系列到深昏迷。研究兴趣集中于传播导出勇气的毒素的角色,特别地氨,胀大的大脑的开发和在导致全球 CNS 消沉和混乱功能的服的 neurotransmitter 系统的变化。直到最近,服的功能的直接调查有在人是困难的。然而,当磁性的回声光谱学( 1H 太太)检测的质子在大脑生物化学变化时,新磁性的回声成像( MRI )技术在大脑体积( coregistered MRI )和损害大脑功能( fMRI )提供对变化的评价的一个非侵略的工具,包括服的 osmolytes 的直接测量,例如 myoinositol ,充斥管理对细胞的动态平衡内在的过程的使挫折和夫酸安,包括细胞内部的水的累积。这些细胞内部的 osmolytes 的集中与 hyperammonaemia 改变。有 neuropsychiatric 缺陷并且自从先生系列的严厉的检测太太的代谢物畸形相互关联向正常术后疗法回来,技术可能具有在客观耐心的监视并且在估计各种各样的治疗政体的有效性的使用。VP Bob Graver M Alex Dresner Daniel M Forton Serena Counsell David J Larkman Nayna Patel Howard C Thomas Simon D Taylor-Robinson 2006World Journal of Gastroenterology2006,12,19:8
15Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience显示文摘AIM To evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting.METHODS We performed a retrospective analysis of treatment outcomes among treatment-na?ve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent's Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate(TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemicalresponse, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus(HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/m L. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen(HBe Ag)/HB surface antigen loss and seroconversion over time.RESULTS Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo(range 3-114). Mean age was 46(24-78) years, 64(70%) were male and 77(84%) were of Asian origin. 55(60%) patients were treatment-na?ve and 62 patients(67%) were HBe Ag-negative. Complete virological suppression was achieved by 45/65(71%) patients at 12 mo, 37/46(80%) at 24 mo and 25/28(89%) at 36 mo. Partial virological response(HBV DNA 20-2000 IU/m L) was achieved by 89/92(96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level(OR = 0.897, 95%CI: 0.833-0.967, P = 0.0046) and HBe Ag positive status(OR = 0.373, 95%CI: 0.183-0.762, P = 0.0069). There was no difference in response comparing treatment-na?ve and treatment-experienced patients. Three episodes of virological breakthrough occurred in the setting of noncompliance. Tenofovir therapy was well tolerated.CONCLUSION Tenofovir is an efficacious, safe and well-tolerated treatment in an Australian real-world tertiary care setting. Our data are similar to the reported experience from registration trials.Grace C Lovett Tin Nguyen David M Iser Jacinta A Holmes Robert Chen Barbara Demediuk Gideon Shaw Sally J Bell Paul V Desmond Alexander J Thompson 2017World Journal of Hepatology2017,9,1:7
16Three-dimensional perfused human in vitro model of nonalcoholic fatty liver disease显示文摘AIM To develop a human in vitro model of non-alcoholic fatty liver disease(NAFLD), utilising primary hepatocytes cultured in a three-dimensional(3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids(FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factorbinding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantlyreduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known antisteatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture medium.CONCLUSION The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds.Tomasz Kostrzewski Terri Cornforth Sophie A Snow Larissa Ouro-Gnao Cliff Rowe Emma M Large David J Hughes 2017World Journal of Gastroenterology2017,23,2:6
17Laparoscopic sleeve gastrectomy:More than a restrictive bariatric surgery procedure?显示文摘Sleeve gastrectomy(SG) is a restrictive bariatric surgery technique that was first used as part of restrictive horizontal gastrectomy in the original Scopinaro type biliopancreatic diversion. Its good results as a single technique have led to a rise in its use, and it is currently the second most performed technique worldwide. SG achieves clearly better results than other restrictive techniques and is comparable in some aspects to the Roux-en-Y gastric bypass, the current gold standard in bariatric surgery. These benefits have been associated with different pathophysiologic mechanisms unrelated to weight loss such as increased gastric emptying and intestinal transit, and activation of hormonal mechanisms such as increased GLP-1 hormone and decreased ghrelin. The aim of this review was to highlight the salient aspects of SG regarding its historical evolution, pathophysiologic mechanisms, main results, clinical applications and perioperative complications.David Benaiges Antonio Más-Lorenzo Albert Goday José M Ramon Juan J Chillarón Juan Pedro-Botet Juana A Flores-Le Roux 2015World Journal of Gastroenterology2015,21,41:6
18Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial显示文摘Pierre J Guillou Philip Quirke Helen Thorpe Joanne Walker David G Jayne Adrian MH Smith Richard M Heath Julia M Brown 2005The Lancet . 2005 (9472)2005,,9472:6
19Protective role of PI3-kinase/Akt/eNOS signaling in mechanical stress through inhibition of p38 mitogenactivated protein kinase in mouse lung显示文摘Xin-qi PENG Mahendra DAMARLA Jarrett SKIRBALL Stephanie NONAS Xiao-ying WANG Eugenia J HAN Emile J HASAN Xuan CAO Adel BOUEIZ Rachel DAMICO Rubin M TUDER Alfred M SClUTO Dana R ANDERSON Joe GNGARCIA David A KASS Paul M HASSOUN Jun-tian ZHANG 2010Acta Pharmacologica Sinica2010,31,2:6
20针对患者利益的机器学习和人工智能研究:在透明性、可重复性、伦理和有效性等方面的20个关键问题显示文摘机器学习(ML)、人工智能(AI)和其他现代统计方法正为利用先前尚未开发且极速增长的数据资源提供新的机会,以期让患者获益。尽管目前正在进行许多有前景的研究,特别是在图像方面,但就文献整体而言还缺乏透明度、对可重复性清晰的阐述、对潜在伦理问题的探究,以及对有效性的明确验证。这些问题的存在有许多原因,其中最重要的一点(为此我们提供了初步解决方案)就是当前缺乏针对ML和AI的最佳实践指南。我们认为从事研究的跨学科团队和应用ML/AI影响健康的项目,将因解决有关透明度、可重复性、伦理和有效性(TREE)的一系列问题而受益。这里提出的20个关键问题为研究团队提供了一个研究设计、实施和报告框架;帮助编辑和同行评审专家评估文献的贡献;让患者、临床医生和政策制定者评估新发现可能会给患者带来的获益。Sebastian Vollmer Bilal A Mateen Gergo Bohner Franz J Kirdly Rayid Ghani Pall Jonsson Sarah Cumbers Adrian Jonas Katherine S L McAllister Puja Myles David Granger Mark Birse Richard Branson Karel G M Moons Gary S Collins John P A Chris Holmes Harry Hemingwayp 李峰(译) 徐磊(校) 赵邑(校) 2020英国医学杂志中文版2020,23,9:5
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