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| 1 | Iron and liver fibrosis: Mechanistic and clinical aspects显示文摘Liver fibrosis is characterised by excessive deposition of extracellular matrix that interrupts normal liver functionality. It is a pathological stage in several untreated chronic liver diseases such as the iron overload syndrome hereditary haemochromatosis, viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and diabetes. Interestingly, regardless of the aetiology, iron-loading is frequently observed in chronic liver diseases. Excess iron can feed the Fenton reaction to generate unquenchable amounts of free radicals that cause grave cellular and tissue damage and thereby contribute to fibrosis. Moreover, excess iron can induce fibrosis-promoting signals in the parenchymal and non-parenchymal cells, which accelerate disease progression and exacerbate liver pathology. Fibrosis regression is achievable following treatment, but if untreated or unsuccessful, it can progress to the irreversible cirrhotic stage leading to organ failure and hepatocellular carcinoma, where resection or transplantation remain the only curative options. Therefore,understanding the role of iron in liver fibrosis is extremely essential as it can help in formulating iron-related diagnostic, prognostic and treatment strategies. These can be implemented in isolation or in combination with the current approaches to prepone detection, and halt or decelerate fibrosis progression before it reaches the irreparable stage. Thus, this review narrates the role of iron in liver fibrosis. It examines the underlying mechanisms by which excess iron can facilitate fibrotic responses. It describes the role of iron in various clinical pathologies and lastly,highlights the significance and potential of iron-related proteins in the diagnosis and therapeutics of liver fibrosis. | Kosha J Mehta Sebastien Je Farnaud Paul A Sharp | 2019 | World Journal of Gastroenterology2019，25，5： | 39 |
| 2 | 缺血性脑卒中和出血性脑卒中患者发病前后血压的变化显示文摘《中国高血压防治指南2010》指出,急性脑卒中的血压处理缺乏足够的临床试验证据,参考建议如下:急性脑卒中溶栓前血压应控制在<185/110mm Hg(1mm Hg=0.133kPa)。对急性缺血性脑卒中发病24h内血压升高的患者应谨慎处理,收缩压≥180mm Hg或舒张压≥100mm Hg或伴有严重心功能不全、主动脉夹层、高血压脑病者,一般不予降压。降压的合理目标是24h内血压降低约15%。有高血压病史且正在服用降压药物者,如神经功能平稳,可于脑卒中发病后24h开始使用降压药物。因此,了解脑卒中患者发病前后的血压情况对临床治疗有重要的意义。Fischer等研究者探讨缺血性脑卒中和出血性脑卒中患者发病前后血压的变化情况。结果表明,缺血性脑卒中患者发病后首次测量的收缩压低于出血性脑卒中。与发病前比较,缺血性脑卒中发病后收缩压略升高(约10.6mm Hg),24h内轻度降低(约13.6mm Hg);而出血性脑卒中发病后,收缩压明显升高(约40.7mm Hg),24h内明显下降(约41.1mm Hg)。出血性脑卒中发病前几天及几周的平均收缩压逐渐增加,而缺血性脑卒中无明显变化。出血性脑卒中患者发病3h内的最高收缩压比发病前高50.0 mm Hg,而缺血性脑卒中则低5.2mm Hg。综上所述,与发病前比较,出血性脑卒中发病后收缩压升高,而缺血性脑卒中无明显变化。 | Fischer U Cooney MT Bull LM Silver LE Chalmers J Anderson CS Mehta Z Rothwell PM 林东杰 叶鹏 | 2014 | 中华高血压杂志2014，22，4： | 13 |
| 3 | Magnetic anchor guidance for endoscopic submucosal dissection and other endoscopic procedures显示文摘Endoscopic submucosal dissection(ESD) is a wellestablished, minimally invasive treatment for superficial neoplasms of the gastrointestinal tract. The universal adoption of ESD has been limited by its slow learning curve, long procedure times, and high risk of complications. One technical challenge is the lack of a second hand that can provide traction, as in conventional surgery. Reliable tissue retraction that exposes the submucosal plane of dissection would allow for safer and more efficient dissection. Magnetic anchor guided endoscopic submucosal dissection(MAGESD) has potential benefits compared to other current traction methods. MAG-ESD offers dynamic tissue retraction independent of the endoscope mimicking a surgeon's 'second hand'. Two types of magnets can be used: electromagnets and permanent magnets. In this article we review the MAG-ESD technology, published work and studies of magnets in ESD. We also review the use of magnetic anchor guidance systems in natural orifice transluminal endoscopic surgery and the idea of magnetic non-contact retraction using surface ferromagentization. We discuss the current limitations, the future potential of MAG-ESD and the developments needed for adoption of this technology. | Mohamed Mortagy Neal Mehta Mansour A Parsi Seiichiro Abe Tyler Stevens John J Vargo Yutaka Saito Amit Bhatt | 2017 | World Journal of Gastroenterology2017，23，16： | 12 |
| 4 | Anti-tumor activity of thalidomide in refractory multiple myeloma显示文摘 | Singhal S Mehta J Desikan R | | 0，，： | 8 |
| 5 | RTOG 0211:a phase 1/2 study of radiation therapy with concurrent gefitinib for newly diagnosed glioblastoma patients显示文摘PURPOSE: To determine the safety and efficacy of gefitinib,an epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor,in combination with radiation for newly diagnosed glioblastoma(GBM) patients.METHODS AND MATERIALS: Between March 21,2002,and May 3,2004,Radiation Therapy Oncology Group(RTOG) 0211 enrolled 31 and 147GBM patients in the phase 1 and 2 arms,respectively.Treatment consisted of daily oral gefinitnib started at the time of conventional cranial radiation therapy(RT) and continued post RT for 18 months or until progression.Tissue microarrays from 68 cases were analyzed for EGFR expression.RESULTS: The maximum tolerated dose(MTD) of gefitinib was determined to be 500 mg in patients on non-enzyme-inducing anticonvulsant drugs(non-EIAEDs).All patients in the phase 2 component were treated at a gefitinib dose of 500 mg;patients receiving EIADSs could be escalated to 750 mg.The most common side effects of gefitinib in combination with radiation were dermatologic and gastrointestinal.Median survival was 11.5 months for patients treated per protocol.There was no overall survival benefit for patients treated with gefitinib + RT when compared with a historical cohort of patients treated with RT alone,matched by RTOG recursive partitioning analysis(RPA) class distribution.Younger age was significantly associated with better outcome.Per protocol stratification,EGFR expression was not found to be of prognostic value for gefitinib + RT-treated patients.CONCLUSIONS: The addition of gefitinib to RT is well tolerated.Median survival of RTOG 0211 patients treated with RT with concurrent and adjuvant gefitinib was similar to that in a historical control cohort treated with radiation alone. | Chakravarti A Wang M Robins HI Lautenschlaeger T Curran WJ Brachman DG Schultz CJ Choucair A Dolled-Filhart M Christiansen J Gustavson M Molinaro A Mischel P Dicker AP Bredel M Mehta M | 2013 | 中国神经肿瘤杂志2013，11，1： | 8 |
| 6 | Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial显示文摘 | David W Andrews Charles B Scott Paul W Sperduto Adam E Flanders Laurie E Gaspar Michael C Schell Maria Werner-Wasik William Demas Janice Ryu Jean-Paul Bahary Luis Souhami Marvin Rotman Minesh P Mehta Walter J Curran | 2004 | The Lancet . 2004 (9422)2004，，9422： | 2 |
| 7 | High omega arachidonic acid/docosahexaenoic acid ratio induces mitochondrial dysfunction and altered lipid metabolism in human hepatoma cells显示文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD) is a common cause of liver disease worldwide and is a growing epidemic. A high ratio of omega-6 fatty acids to omega-3 fatty acids in the diet has been implicated in the development of NAFLD. However, the inflicted cellular pathology remains unknown. A high ratio may promote lipogenic pathways and contribute to reactive oxygen species(ROS)-mediated damage, perhaps leading to mitochondrial dysfunction.Therefore, these parameters were investigated to understand their contribution to NAFLD development.AIM To examine the effect of increasing ratios of omega-6:3 fatty acids on mitochondrial function and lipid metabolism mediators.METHODS Hep G2-derived VL-17 A cells were treated with normal(1:1, 4:1) and high(15:1,25:1) ratios of omega-6: omega-3 fatty acids [arachidonic acid(AA):docosahexaenoic acid(DHA)] at various time points. Mitochondrial activity and function were examined via MTT assay and Seahorse XF24 analyzer, respectively.Triglyceride accumulation was determined by using Enzy Chrom? and levels of ROS were measured by fluorescence intensity. Protein expression of the mediators of lipogenic, lipolytic and endocannabinoid pathways was assessed by Western blotting.RESULTS High AA:DHA ratio decreased mitochondrial activity(P < 0.01;up to 80%) and promoted intracellular triglyceride accumulation(P < 0.05;40%-70%).Mechanistically, it altered the mediators of lipid metabolism;increased the expression of stearoyl-Co A desaturase(P < 0.05;22%-35%), decreased the expression of peroxisome proliferator-activated receptor-alpha(P < 0.05;30%-40%) and increased the expression of cannabinoid receptor 1(P < 0.05;31%).Furthermore, the high ratio increased ROS production(P < 0.01;74%-115%) and reduced mitochondrial respiratory functions such as basal and maximal respiration, ATP production, spare respiratory capacity and proton leak(P < 0.01;35%-68%).CONCLUSION High AA:DHA ratio induced triglyceride accumulation, increased oxidative stress and disrupted mitochondrial functions. Stimulation of lipogenic and steroidal transcription factors may partly mediate these effects and contribute to NAFLD development. | Reem Ghazali Kosha J Mehta SW Annie Bligh Ihab Tewfik Dahn Clemens Vinood B Patel | 2020 | World Journal of Hepatology2020，12，3： | 2 |
| 8 | Gastric food retention at endoscopy is associated with severity of liver cirrhosis显示文摘BACKGROUND Gastrointestinal symptoms are prevalent in patients with cirrhosis.Cirrhotic patients have a known predilection to delayed gastric emptying compared to those without cirrhosis.However,the contributing factors have not been fully elucidated.Retained gastric food on esophagogastroduodenoscopy(EGD)has been used as a surrogate marker for delayed gastric emptying with reasonably high specificity.Therefore,we hypothesize that the frequency of retained gastric food contents at EGD will be higher in a cirrhotic population compared to a control population without liver disease.Additionally,we hypothesize that increased frequency of gastric food contents will be associated with increased severity of cirrhosis.AIM To determine the relative frequency of delayed gastric emptying among cirrhotics as compared to non-cirrhotics and to identify associated factors.METHODSWe performed a retrospective case-control study of cirrhotic subjects whounderwent EGD at an academic medical center between 2000 and 2015. Threehundred sixty-four patients with confirmed cirrhosis, who underwent a total of1044 EGDs for the indication of esophageal variceal screening or surveillance,were identified. During the same period, 519 control patients without liverdisease, who underwent a total of 881 EGDs for the indication of anemia, wereidentified. The presence of retained food on EGD was used as a surrogate fordelayed gastric emptying. The relative frequency of delayed gastric emptyingamong cirrhotics was compared to non-cirrhotics. Characteristics of patients withand without retained food on EGD were compared using univariable andmultivariable logistic regression analysis to identify associated factors.RESULTSOverall, 40 (4.5%) patients had evidence of retained food on EGD. Cirrhotics weremore likely to have retained food on EGD than non-cirrhotics (9.1% vs 1.4%, P <0.001). Characteristics associated with retained food on univariable analysisincluded age less than 60 years (12.6% vs 5.2%, P = 0.015), opioid use (P = 0.004),Child-Pugh class C (24.1% Child-Pugh class C vs 6.4% Child-Pugh class A, P =0.007), and lower platelet count (P = 0.027). On multivariate logistic regressionanalysis, in addition to the presence of cirrhosis (adjusted OR = 5.83;95%CI: 2.32-14.7, P < 0.001), diabetes mellitus (types 1 and 2 combined) (OR = 2.34;95%CI:1.08-5.06, P = 0.031), opioid use (OR = 3.08;95%CI: 1.29-7.34, P = 0.011), andChild-Pugh class C (OR = 4.29;95%CI: 1.43-12.9, P = 0.01) were also associatedwith a higher likelihood of food retention on EGD.CONCLUSIONCirrhotics have a higher frequency of retained food at EGD than non-cirrhotics.Decompensated cirrhosis, defined by Child-Pugh class C, is associated with ahigher likelihood of delayed gastric emptying. | David B Snell Shirley Cohen-Mekelburg Russell Weg Gaurav Ghosh Adam P Buckholz Amit Mehta Xiaoyue Ma Paul J Christos Arun B Jesudian | 2019 | World Journal of Hepatology2019，11，11： | 2 |
| 9 | Antitumor activity of thalidomide in refractory multiple myeloma显示文摘 | Singhal S Mehta J Desikan R | 1999 | N Engl J Med1999，341，21： | 1 |
| 10 | Marked anti-tumor effect from anti-angiogenesis therapy with thalidomide in high risk refractory multiple myeloma显示文摘 | Mehta J Eddiemon P | 1998 | Blood1998，92，1： | 1 |
| 11 | Large-scale sequence analysis of avian influenza isolates显示文摘 | Obenauer J C Denson J Mehta P K | 2006 | Science2006，311，5767： | 1 |
| 12 | Medullary thyroid cancer: early detection and novel treatments显示文摘 | Roman S Mehta P Sosa J A | 2009 | Curr Opin Oncol2009，21，1： | 1 |
| 13 | Surgical interventions for age-related cataract显示文摘 | Riaz Y Mehta J S Wormald R | 2006 | Cochrane Database Syst Rev2006，18，00： | 1 |
| 14 | Oligosaccharide side chains on human secretory IgA serve as receptors for ricin 显示文摘 | Mantis N J Farrant SA Mehta S | 2004 | J Immunol2004，172，11： | 1 |
| 15 | A staged treatment plan for the management of Type II and Type IIIA open ealeaneus fractures显示文摘 | Mehta S Mirza A J Dunbar RP | 2010 | J Orthop Tranma2010，24，3： | 1 |
| 16 | Postoperative pain expe rience: results from a national survery suggest postoperative pain continues to be undermanaged 显示文摘 | Apfelbaum J L Chert C Mehta SS | 2003 | Anesth Analg2003，97，2： | 1 |
| 17 | Nephron-sparing nephrecto- myforgiant renal angiomyolipoma associated with lymphangioleiomy Omatosis显示文摘 | Tsu TH 0'Hara J Mehta A | 2002 | Urology2002，59，1： | 1 |
| 18 | Fluid balance in patients withacute kidney injury: emerging concepts显示文摘 | Godin M Bouchard J Mehta RL | 2013 | Nephron Clin Pract2013，123，34： | 1 |
| 19 | Early predictive bio- markers for postpartum depression point to a role for estrogen re- ceptor signaling显示文摘 | Mehta D Newport D J Frishman G | 2014 | Psychol Med2014，44，11： | 1 |
| 20 | Detection of elevated right ventricular extracellular volume in pulmonary hypertension using Accelerated and Navigator-Gated Look-Locker Imaging for Cardiac T1 Estimation (ANGLE) cardiovascular magnetic resonance 显示文摘 | MEHTA B B AUGER D A GONZALEZ J A | 2015 | J Cardiovasc Magn Reson2015，17，1： | 1 |
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