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1Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies显示文摘Rheumatoid arthritis(RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages:(i) triggering,(ii) maturation,(iii) targeting, and(iv) fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies(including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs) remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA.Qiang Guo Yuxiang Wang Dan Xu Johannes Nossent Nathan J.Pavlos Jiake Xu 2018Bone Research2018,6,2:71
2Identification of serum proteins discriminating colorectal cancer patients and healthy controls using surface-enhanced laser desorption ionisation-time of flight mass spectrometry显示文摘瞄准:为颜色检测新浆液简历标记由浆液蛋白质与提高表面的激光解吸附作用 ionisation 介绍的表面的癌症(CRC )-- 飞行团分光术(SELDI-TOF MS ) 的时间。方法:二个独立浆液样品集合与 ProteinChip 技术独立被分析(集合 A:40 CRC+49 健康控制;集合 B:37 CRC+31 健康控制) ,有一个弱阳离子的使用的芯片交换一半和缓冲区 pH 5。差别的歧视的力量表示了蛋白质与一个分类树算法被估计。产生分类树的敏感和特性被盲目地从集合 B 并且反过来也如此从集合 A 把数据用于产生的树获得。CRC 浆液蛋白质侧面也与从胸的那些相比,卵巢,前列腺,和非小的房间肺癌症。结果:Mass-to-charge 比率(m/z ) 3.1x10 (3 ) , 3.3x10 (3 ) , 4.5x10 (3 ) , 6.6x10 (3 ) 和 28x10 (3 ) 在最好执行的分类树上被用作分类器。树敏感和特性在 65% 和 90% 之间。大多数这些歧视的 m/z 价值在调查的另外的瘤类型也是不同的。M/z 3.3x10 (3 ) ,在大多数树上的主要分类器,是 6.6x10 (3 ) 的一种二倍地控告的形式 -Da 蛋白质。后者作为 apolipoprotein C-I 被识别。M/z 3.1x10 (3 ) 作为 apolipoprotein A-I 作为白朊,和 m/z 28x10 (3 ) 的 N 终端碎片被识别。结论:分类树模式分析跟随的 SELDI-TOF MS 是为为 CRC 发现新浆液标记的一种合适的技术。Biomarkers 能与高敏感和特性在独立样品集合被识别并且 reproducibly 检测了。尽管为 CRC 不特定,这些简历标记在监视的疾病和治疗有一个潜在的角色。Judith YMN Engwegen Helgi H Helgason Annemieke Cats Nathan Harris Johannes MG Bonfrer Jan HM Schellens Jos H Beijnen 2006World Journal of Gastroenterology2006,12,10:45
3帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh 2021中华肿瘤防治杂志2021,28,24:49
4Chemical vapor deposition growth of monolayer MoSe2 nanosheets显示文摘Jonathan C. Shaw Hailong Zhou Yu Chen Nathan O. Weiss Yuan Liu Yu Huang Xiangfeng Duan 2014Nano Research2014,7,4:26
5Pathogenic mechanisms of pancreatitis显示文摘Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pan-creatitis characterized by marked stroma formation with a high number of infiltrating granulocytes(such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells(PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in pro-moting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways(i.e., Transforming growth factor-β/SMAD, mitogen--activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin(IL)-1, IL-1β, IL-6, IL--8 IL-10, IL-18, IL--33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for pancreatic pathogenesis.Murli Manohar Alok Kumar Verma Sathisha Upparahalli Venkateshaiah Nathan L Sanders Anil Mishra 2017World Journal of Gastrointestinal Pharmacology and Therapeutics2017,8,1:21
6肾脏病学的新创意:“肾脏疾病:改善全球预后”(KDIGO)显示文摘慢性肾脏病(CKD)是世界范围的医疗和公共卫生问题,并开始呈现流行性的特点.美国肾脏数据系统(USRDS)的数据提示,终末期肾衰的发病率呈上升趋势,因此对于这一问题的重视日益增加.根据近期USRDS登记系统提供的资料,世界范围内需要肾脏替代治疗(RRT)的终末期肾病(ESRD)患者数目持续上升,其中我国台湾、美国和日本最多(254~365人/100万人)[1].卡塔尔和巴斯克地区的儿童患病率最高,分别为33.7人/100万人和22.7人/100万人;在大于等于20岁患者中患病率最高的是卡塔尔、美国和台湾.在欧洲,德国的患病率最高,2000年为175人/100万人.在RRT仍在发展中的东欧,报道的患病率低于西欧[2].Norbert Lameire Garabed Eknoyan Rashad Barsoum Kai-Uwe Eckardt Adeera Levin Nathan Levin Francesco Locatelli Alison Macleod Raymond Vanholder Rowan Walker Haiyan Wang 张路霞 王海燕 2005中华肾脏病杂志2005,21,12:19
7对9~14岁儿童血脂影响因素的研究显示文摘目的 :了解长沙市北区儿童血脂水平及其影响因素。方法 :检测 4 34例 9~ 14岁健康儿童血清甘油三酯、胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇浓度 ,并与年龄、性别、家族史、饮食习惯、运动习惯、被动吸烟、身高、体重、体重指数、空腹血糖、收缩压、舒张压等相关和多因素回归分析。结果 :本年龄组儿童血脂水平较稳定 ,性别差异无显著性 ,血脂异常总检出率为2 3.72 %。家族史、饮食习惯、被动吸烟、运动习惯、体重指数、血糖和血压等因素与血脂浓度有不同程度的相关性。结论 :冠心病的独立危险因素———血脂异常在儿童时期已经存在 ,因此动脉粥样硬化的预防应从儿童时期开始。孙明 孙宏 邓华钊 周宏研 Nathan Wong 2002临床心血管病杂志2002,18,3:19
8MicroRNA-21 in the pathogenesis of acute kidney injury显示文摘Acute kidney injury(AKI),associated with significant mor-bidity and mortality,is widely known to involve epithelial apoptosis,excessive inflammation,and fibrosis in re-sponse to ischemia or reperfusion injury,which results in either chronic pathological changes or death.Therefore,it is imperative that investigations are conducted in order to fi nd effective,early diagnoses,and therapeutic targets needed to help prevent and treat AKI.However,the mech-anisms modulating the pathogenesis of AKI still remain largely undetermined.MicroRNAs(miRNAs),small non-coding RNA molecules,play an important role in several fundamental biological and pathological processes by a post transcriptional regulatory function of gene expres-sion.MicroRNA-21(miR-21)is a recently identifi ed,typi-cal miRNA that is functional as a regulator known to be involved in apoptosis as well as inflammatory and fi brotic signaling pathways in AKI.As a result,miR-21 is now considered a novel biomarker when diagnosing and treat-ing AKI.This article reviews the correlative literature and research progress regarding the roles of miR-21 in AKI.Ya-Feng Li Ying Jing Jielu Hao Nathan C Frankfort Xiaoshuang Zhou Bing Shen Xinyan Liu Lihua Wang Rongshan Li 2013Protein & Cell2013,4,11:18
9Phylogenetic alpha and beta diversity in tropical tree assemblages along regionalscale environmental gradients in northwest South America显示文摘Aims Environmental gradients are drivers of species diversity;however,we know relatively little about the evolutionary processes underlying these relationships.A potentially powerful approach to studying diversity gradients is to quantify the phylogenetic structure within and between assemblages arrayed along broad spatial and environmental gradients.Here,we evaluate the phylogenetic structure of plant assemblages along an environmental gradient with the expectation that the habitat specialization of entire lineages is an important evolutionary pattern influencing the structure of tree communities along environmental gradients.Methods We evaluated the effect of several environmental variables on the phylogenetic structure of plant assemblages in 145 plots distributed in northwestern South America that cover a broad environmental gradient.The phylogenetic alpha diversity was quantified for each plot and the phylogenetic beta diversity between each pair of plots was also quantified.Both the alpha and beta diversity measures were then related to spatial and environmental gradients in the study system.Important Findings We found that gradients in temperature and potential evapotranspiration have a strong relationship with the phylogenetic alpha diversity in our study system,with phylogenetic overdispersion in low temperatures and phylogenetic clustering at higher temperatures.Further,the phylogenetic beta diversity between two plots increases with an increasing difference in temperature,whereas annual precipitation was not a significant predictor of community phylogenetic turnover.We also found that the phylogenetic structure of the plots in our study system was related to the degree of seasonal flooding and seasonality in precipitation.In particular,more stressful environments such as dry forests and flooded forests showed phylogenetic clustering.Finally,in contrast with previous studies,we find that phylogenetic beta diversity was not strongly related to the spatial distance separating two forest plots,which may be the result of the importance of the three independent mountain ranges in our study system,which generate a high degree of environmental variation over very short distances.In conclusion,we found that environmental gradients are important drivers of both phylogenetic alpha and phylogenetic beta diversities in these forests over spatial distance.Sebastián González-Caro María Natalia Umaña Esteban Álvarez Pablo R.Stevenson Nathan G.Swenson 2014Journal of Plant Ecology2014,7,2:17
10Mitochondria in cancer:at the crossroads of life and death显示文摘Mitochondrial processes play an important role in tumor initiation and progression.In this review,we focus on three critical processes by which mitochondrial function may contribute to cancer:through alterations in glucose metabolism,the production of reactive oxygen species (ROS) and compromise of intrinsic apoptotic function.Alterations in cancer glucose metabolism include the Warburg effect,leading to a shift in metabolism away from aerobic respiration toward glycolysis,even when sufficient oxygen is present to support respiration.Such alterations in cellular metabolism may favor tumor cell growth by increasing the availability of biosynthetic intermediates needed for cellular growth and proliferation.Mutations in specific metabolic enzymes,namely succinate dehydrogenase,fumarate hydratase and the isocitrate dehydrogenases,have been linked to human cancer.Mitochondrial ROS may contribute to cancer via DNA damage and the activation of aberrant signaling pathways.ROS-dependent stabilization of the transcription factor hypoxia-inducible factor (HIF) may be a particularly important event for tumorigenesis.Compromised function of intrinsic apoptosis removes an important cellular safeguard against cancer and has been implicated in tumorigenesis,tumor metastasis,and chemoresistance.Each of the major mitochondrial processes is linked.In this review,we outline the connections between them and address ways these mitochondrial pathways may be targeted for cancer therapy.Vanessa C.Fogg Nathan J.Lanning Jeffrey P.MacKeigan 2011Chinese Journal of Cancer2011,30,8:16
11Management of distal humeral coronal shear fractures显示文摘Coronal shear fractures of the distal humerus are rare,complex fractures that can be technically challenging to manage. They usually result from a low-energy fall and direct compression of the distal humerus by the radial head in a hyper-extended or semi-flexed elbow or from spontaneous reduction of a posterolateral subluxation or dislocation. Due to the small number of soft tissue attachments at this site, almost all of these fractures are displaced. The incidence of distal humeral coronal shear fractures is higher among women because of the higher rate of osteoporosis in women and the difference in carrying angle between men and women. Distal humeral coronal shear fractures may occur in isolation, may be part of a complex elbow injury, or may be associated with injuries proximal or distal to the elbow. An associated lateral collateral ligament injury is seen in up to 40% and an associated radial head fracture is seen in up to 30% of these fractures. Given the complex nature of distal humeral coronal shear fractures, there is preference for operative management. Operative fixation leads to stable anatomic reduction, restores articular congruity, and allows initiation of early range-of-motion movements in the majority of cases. Several surgical exposure and fixation techniques are available to reconstruct the articular surface fol owing distal humeral coronal shear fractures. The lateral extensile approach and fixation with countersunk headless compression screws placed in an anterior-to-posterior fashion are commonly used. We have found a two-incision approach(direct anterior and lateral) that results in less soft tissue dissection and better outcomes than the lateral extensile approach in our experience. Stiffness, pain, articular incongruity, arthritis, and ulnohumeral instability may result if reduction is non-anatomic or if fixation fails.Shahram S Yari Nathan L Bowers Miguel A Craig Lee M Reichel 2015World Journal of Clinical Cases2015,3,5:15
12Indirect traumatic optic neuropathy:modeling optic nerve injury in the context of closed head trauma显示文摘Traumatic optic neuropathy:Traumatic brain injury is one of the leading causes of disability and mortality in the United States.It impacts people of all ages and demographics,particularly younger males and members of the military.Vision loss is commonly associated with traumatic brain injuries of all severities and can leave patients permanently disabled.This vision loss can be caused by injury to the visual system at multiple levels,including the eyes,optic nerves,and many different sites in the brain and brainstem(Sen,2017).Despite the far-reaching effects of visual impairment after traumatic brain injury,its incidence after traumatic brain injury is not well measured,and few successful treatments have been identified or implemented.Emma G.Burke Shelby M.Cansler Nathan K.Evanson 2019Neural Regeneration Research2019,14,4:14
13Iron and non-alcoholic fatty liver disease显示文摘The mechanisms that promote liver injury in non-alcoholic fatty liver disease(NAFLD) are yet to be thoroughly elucidated. As such, effective treatment strategies are lacking and novel therapeutic targets are required. Iron has been widely implicated in the pathogenesis of NAFLD and represents a potential target for treatment. Relationships between serum ferritin concentration and NAFLD are noted in a majority of studies, although serum ferritin is an imprecise measure of iron loading. Numerous mechanisms for a pathogenic role of hepatic iron in NAFLD have been demonstrated in animal and cell culture models. However, the human data linking hepatic iron to liver injury in NAFLD is less clear, with seemingly conflicting evidence, supporting either an effect of iron in hepatocytes or within reticulo-endothelial cells. Adipose tissue has emerged as a key site at which iron may have a pathogenic role in NAFLD. Evidence for this comes indirectly from studies that have evaluated the role of adipose tissue iron with respect to insulin resistance. Adding further complexity, multiple strands of evidence support an effect of NAFLD itself on iron metabolism. In this review, we summarise the human and basic science data that has evaluated the role of iron in NAFLD pathogenesis.Laurence J Britton V Nathan Subramaniam Darrell HG Crawford 2016World Journal of Gastroenterology2016,22,36:14
146min步行试验中不同指令对行走距离的影响显示文摘6min步行试验(6-minwalktest,6MWT)作为测定心肺功能的一种方法,一直以使患者走的尽可能远为目标,然而,特定的步行指令对患者6MWT测定的影响尚不清楚。方法:纳入肺动脉高压(pulmonaryarterialhypertension,PAH)、特发性肺间质纤维化(idiopathicpulmonaryfibrosis,IPF)和其他类型的间质性肺疾病(interstitiallungdisease,ILD)患者,刘莉 叶鹏 Weir NA Brown AW Shlobin OA Smith MA Reffett T Battle E Ahmad S Nathan SD 2014中华高血压杂志2014,22,2:13
15Recent advances in electrochemistry of sulfide mineral flotation显示文摘The electrochemical basis for understanding the interaction of thiol collectors with sulfide minerals is reviewed. Spectroscopic techniques are being increasingly applied to augment electrochemical studies and provide unequivocal identification of species formed at mineral surfaces in flotation systems. These include X ray photoelectron, Fourier transform infrared spectroscopy and, more recently, surface enhanced Raman scattering spectroscopy. The progress that has been made in the application of electrochemical measurement to monitor and control flotation plants is also considered.R.Woods Faculty of Science and Technology, Griffith University, Nathan Campus, Queensland 4111, Australia 2000中国有色金属学会会刊:英文版2000,10,S1:12
16Anticoagulation with direct thrombin inhibitors during extracorporeal membrane oxygenation显示文摘Use of extracorporeal membrane oxygenation to support patients with critical cardiorespiratory illness is increasing.Systemic anticoagulation is an essential element in the care of extracorporeal membrane oxygenation patients.While unfractionated heparin is the most commonly used agent,unfractionated heparin is associated with several unique complications that can be catastrophic in critically ill patients,including heparin-induced thrombocytopenia and acquired antithrombin deficiency.These complications can result in thrombotic events and subtherapeutic anticoagulation.Direct thrombin inhibitors(DTIs)are emerging as alternative anticoagulants in patients supported by extracorporeal membrane oxygenation.Increasing evidence supports DTIs use as safe and effective in extracorporeal membrane oxygenation patients with and without heparininduced thrombocytopenia.This review outlines the pharmacology,dosing strategies and available protocols,monitoring parameters,and special use considerations for all available DTIs in extracorporeal membrane oxygenation patients.The advantages and disadvantages of DTIs in extracorporeal membrane oxygenation relative to unfractionated heparin will be described.Barry Burstein Patrick M Wieruszewski Yan-Jun Zhao Nathan Smischney 2019World Journal of Critical Care Medicine2019,8,6:12
17Phylofloristics:an example from the Lesser Antilles显示文摘Aims The last decade has seen many plant ecologists integrating phylogenetic analysis into ecology to explain patterns of species cooccurrence and compositional similarity across assemblages.Despite the advances in this area,there are still some challenges that need to be addressed.One challenge is that most of the phylogenetic studies of plant assemblages have focused only on a small proportion of all of the vascular plants that co-occur(e.g.woody plants),while much of the remaining co-occurring flora has been ignored.Methods Here we introduce an analytical approach that we term phylofloristics that analyzes the compositional similarity of floras in relation to spatial and environmental gradients to understand their assembly.As an illustration,we assembled a large phylogenetic tree for the flora of the Lesser Antilles and evaluated the patterns of floristic and phylofloristic similarity among the island-specific floras.We analyzed the relationship of these similarities with spatial and environmental distance and compared the results for non-endemic and endemic lineages.Important Findings The results show a major influence of environmental heterogeneity on the assembly of island floras and far less evidence for the importance of dispersal limitation of lineages and species.This study highlights the importance of incorporating broader taxonomic sampling to improve our understanding of assembly processes in ecology.We expect future phylofloristic studies will improve the approach we have taken by generating more refined phylogenetic trees and by incorporating phylogeographic information.Nathan G.Swenson María N.Umaña 2014Journal of Plant Ecology2014,7,2:12
18Rotator cuff tears: An evidence based approach显示文摘Lesions of the rotator cuff(RC) are a common occurrence affecting millions of people across all parts of the globe. RC tears are also rampantly prevalent with an agedependent increase in numbers. Other associated factors include a history of trauma, limb dominance, contralateral shoulder, smoking-status, hypercholesterolemia, posture and occupational dispositions. The challenge lies in early diagnosis since a high proportion of patients are asymptomatic. Pain and decreasing shoulder power and function should alert the heedful practitioner in recognizing promptly the onset or aggravation of existing RC tears. Partial-thickness tears(PTT) can be bursalsided or articular-sided tears. Over the course of time, PTT enlarge and propagate into full-thickness tears(FTT) and develop distinct chronic pathological changes due to muscle retraction, fatty infiltration and muscle atrophy. These lead to a reduction in tendon elasticity and viability. Eventually, the glenohumeral joint experiences a series of degenerative alterations- cuff tear arthropathy. To avert this, a vigilant clinician must utilize and corroborate clinical skill and radiological findings to identify tear progression. Modern radio-diagnostic means of ultrasonography and magnetic resonance imaging provide excellent visualization of structural details and are crucial in determining further course of action for these patients. Physical therapy along with activity modifications, antiinflammatory and analgesic medications form the pillars of nonoperative treatment. Elderly patients with minimal functional demands can be managed conservatively and reassessed at frequent intervals. Regular monitoring helps in isolating patients who require surgical interventions. Early surgery should be considered in younger, active and symptomatic, healthy patients. In addition to being costeffective, this helps in providing a functional shoulder witha stable cuff. An easily reproducible technique of maximal strength and sturdiness should by chosen among the armamentarium of the shoulder surgeon. Grade 1 PTTs do well with debridement while more severe lesions mandate repair either by trans-tendon technique or repair following conversion into FTT. Early repair of repairable FTT can avoid appearance and progression of disability and weakness. The choice of surgery varies from surgeon-to-surgeon with arthroscopy taking the lead in the current scenario. The double-row repairs have an edge over the single-row technique in some patients especially those with massive tears. Stronger, costeffective and improved functional scores can be obtained by the former. Both early and delayed postoperative rehabilitation programmes have led to comparable outcomes. Guarded results may be anticipated in patients in extremes of age, presence of comorbidities and severe tear patters. Overall, satisfactory results are obtained with timely diagnosis and execution of the appropriate treatment modality.Senthil Nathan Sambandam Vishesh Khanna Arif Gul Varatharaj Mounasamy 2015World Journal of Orthopedics2015,6,11:11
19Phylogenetic beta diversity in tropical forests: Implications for the roles of geographical and environmental distance显示文摘社区汇编的各种各样的机械学的理论被建议了从基于壁龛的理论到中立理论。在种系发生的上下文的贝它差异的分析能为这些假设测试许多提供一个优秀机会。我们在巴拿马在热带树社区分析了种系发生的贝它差异的模式测试几个社区集会假设。特别地,在社区之间的种系发生的不同能被地理或环境的距离向解释的度能分别地为随机或确定的集会过程产出支持。因此,我们检验了:在社区和它从那的离开的度之中的种系发生的类似的距离腐烂的存在在一个空模型下面期望的(i) ;并且(ii ) 在预言社区的种系发生的不同的地理对环境的距离的相对重要性。我们发现了社区的种系发生的作文的类似与地理距离和环境坡度腐烂了的证据。空模型证据证明在学习系统的那贝它差异是种系发生地非随机的。我们的结果加亮本地生态的机制的角色不仅包括环境过滤和竞争排除,而且 biogeographical 过程象在组织种系发生的周转的种形成,疏开限制,和壁龛进化那样。这些结果也在组织种类差异模式强调壁龛保守主义的重要性。Jin-Long ZHANG Nathan G. SWENSON Sheng-Bin CHEN Xiao-Juan LIU Zong-Shan LI Ji-Hong HUANG Xiang-Cheng MI Ke-Ping MA 2013Journal of Systematics and Evolution2013,51,1:11
20Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction显示文摘Zika 病毒(ZIKV ) 的最近的爆发为治疗学加亮迫切需要。朊酶建筑群 NS2B-NS3 在 flaviviral polyprotein 处理期间起必要作用,并且因此代表一个吸引人的药目标。这里,我们开发了裂口酶识别直接指向 flavivirus NS2B-NS3 相互作用的 orthosteric 禁止者的基于互补的高产量的屏蔽试金。由屏蔽一个总数 2 816 同意了并且 investigational 药,我们识别了三个有势力候选人, temoporfin, niclosamide,和 nitazoxanide,,有 nanomolar 力量的 flavivirus NS2B-NS3 相互作用禁止者。显著地,在老鼠的在人的胎盘、神经的祖先房间的大多数有势力化合物, temoporfin,不是仅仅禁止的 ZIKV 复制,而且阻止的导致 ZIKV 的 viremia 和死亡当模特儿。结构的停靠建议 temoporfin 潜在地绑保持批评 NS2B 残余的 NS3 衣袋,因此禁止以一种非竞争的方式处理的 flaviviral polyprotein。当这些药已经在 USA 或另外的国家在另外的指示任何一个为临床的使用被同意了,他们由 ZIKV 和另外的 flaviviruses 为感染的管理代表有希望、容易开发的治疗。Zhong Li Matthew Brecher Yong-Qiang Deng Jing Zhang Srilatha Sakamuru Binbin Liu Ruili Huang Cheri A Koetzner Christina A Allen Susan A Jones Haiying Chen Na-Na Zhang Min Tian Fengshan Gao Qishan Lin Nilesh Banavali Jia Zhou Nathan Boles Menghang Xia Laura D Kramer Cheng-Feng Qin Hongmin Li 2017Cell Research2017,27,8:11
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