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| 1 | 染色体异常与男性不育显示文摘不育问题惊人地困扰着15%想要组建新家庭的人群。尽管如此,不育的分子遗传因素大多还不清楚。不过,越来越多不育遗传因素正逐渐被发现。本综述主要讨论目前了解的男性不育的染色体因素,尤其是染色体非整倍体、染色体组型的结构和数量异常和Y染色体微缺失。染色体非整倍体是人类流产和发育残疾的主要原因。非整倍体主要起源于母体,但是人们正在关注单精子注射的安全性,因为不育男性的精子非整倍体水平明显比起配偶高。染色体组型结构和数量异常的男性产生非整倍体精子的风险也越来越高。本文还综述了精子非整倍体如何被翻译至胚胎非整倍体,以及植入前基因诊断在这些病例中的应用。如果可能,文章还会做一下临床方面的建议,并讨论一些新兴的阵列技术在植入前基因诊断中使用以及在男性不育的潜在应用。 | Gary L Harton Helen G Tempest | 2012 | Asian Journal of Andrology2012，14，1： | 25 |
| 2 | Utility of serological markers in inflammatory bowel diseases: Gadget or magic?显示文摘为煽动性的肠疾病(IBD ) 的血清学标记的面板很快正在膨胀。尽管 anti-Saccharomyces 啤酒抗体(ASCA ) 和不正常的仙子细胞质的抗体(P-ANCA ) 仍然是的原子反 neutrophil 广泛地调查的大多数,试验性的数据的增加的数量在对各种各样的微生物引起的抗原指导的最新发现的抗体上是可得到的。对在当前的 IBD 诊断算法的各种各样的抗体的评价的角色由于他们的有限敏感经常是可疑的。相反,有疾病行为和显型的血清学标记的协会正在变得逐渐地生长得很好。越来越多的观察证实有 Crohn 在高乳头 ers 表示多重血清学标记的疾病的病人是更可能的有复杂的小肠疾病(例如苛评或穿孔) 并且没有,或与抗体的低乳头 ers,比那些在为外科的更高的风险。基于血清学反应创造同质的疾病亚群可以帮助开发更多的标准化治疗学的途径并且可以在 IBD 的 pathomechanism 的更好的理解帮助。进一步未来的临床的研究被需要在 IBD 建立 serologic 的临床的角色。 | Maria Papp Gary L Norman Istvan Altorjay Peter Laszlo Lakatos | 2007 | World Journal of Gastroenterology2007，13，14： | 24 |
| 3 | Golgi protein-73:A biomarker for assessing cirrhosis and prognosis of liver disease patients显示文摘BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells.As a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in hepatocytes.However,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in hepatocytes.So far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUANTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all patients.Two hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related disorders.The duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines.In particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of 632 patients(43.8%).GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4%vs 51.5%,P<0.001),decompensation of cirrhosis(60.3%vs 35.5%,P<0.001),presence of HCC(18.4%vs 7.9%,P<0.001)and advanced HCC stage(52.9%vs 14.8%,P=0.002).GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score[Area under the curve(AUC)(95%CI):0.909(0.885-0.934)vs 0.849(0.813-0.886),P=0.003].Combination of GP73 with APRI improved further the accuracy(AUC:0.925)compared to GP73(AUC:0.909,P=0.005)or APRI alone(AUC:0.849,P<0.001).GP73 levels were significantly higher in HCC patients compared to non-HCC[22.5(29.2)vs 16(20.3)units,P<0.001)and positively associated with BCLC stage[stage 0:13.9(10.8);stage A:17.1(16.8);stage B:19.6(22.3);stage C:32.2(30.8);stage D:45.3(86.6)units,P<0.001]and tumor dimensions[very early:13.9(10.8);intermediate:19.6(18.4);advanced:29.1(33.6)units,P=0.004].However,the discriminative ability for HCC diagnosis was relatively low[AUC(95%CI):0.623(0.570-0.675)].Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline,was prognostic of higher rates of decompensation(P=0.036),HCC development(P=0.08),and liver-related deaths(P<0.001)during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination.In combination with APRI,its diagnostic performance can be further improved.Most importantly,the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases. | Nikolaos K Gatselis Tamás Tornai Zakera Shums Kalliopi Zachou Asterios Saitis Stella Gabeta Roger Albesa Gary L Norman Mária Papp George N Dalekos | 2020 | World Journal of Gastroenterology2020，26，34： | 21 |
| 4 | Cartilage oligomeric matrix protein: A novel non-invasive marker for assessing cirrhosis and risk of hepatocellular carcinoma显示文摘AIM: To assess serum cartilage oligomeric matrix protein(COMP) as a marker of cirrhosis and risk of progression to hepatocellular carcinoma(HCC). METHODS: A COMP enzyme-linked immunosorbentassay was used to test 187 patients with chronic liver diseases at the time point of first evaluation. The selected patients included 72 with chronic hepatitis B infection, 75 with chronic hepatitis C infection, 22 with primary biliary cirrhosis, 7 with autoimmune hepatitis type 1, and 11 with alcoholic liver disease. Demographic, biochemical, histological and clinical characteristics of the patients were recorded at the first evaluation. One hundred and forty-seven patients were followed for a median [interquartile range(IQR)] duration of 96.5(102) mo. The clinical, biochemical and histological data, as well as the development of cirrhosis, HCC according to internationally accepted criteria and in case of death, a liver-related cause during the follow-up period, were recorded at the electronic database of our clinic. COMP determination was also performed in 43 healthy individuals who served as the control study group.RESULTS: COMP positivity(> 15 U/L) was detected in 22%-36% among chronic liver disease groups. Strikingly, almost 83% of COMP-positive patients were cirrhotic at baseline, independently of cause of liver disease. Among the patients who developed HCC during follow-up, 73.7%(14/19) were COMP positive at baseline. COMP positivity was significantly associated with older age(P < 0.001), advanced fibrosis(P = 0.001) and necroinflammatory activity(P = 0.001), higher aspartate aminotransferase(P < 0.001), alanine aminotransferase(P < 0.02), γ-glutamyl transpeptidase(P = 0.003), alkaline phosphatase(P = 0.001), bilirubin(P < 0.05), international normalized ratio(P = 0.002) and alpha-fetoprotein levels(P < 0.02), and lower albumin(P < 0.001), and platelet count(P = 0.008). COMP levels [median(IQR)] were significantly higher in cirrhotics compared to non-cirrhotics [13.8(7.9) U/L vs 9.8(4.6) U/L, respectively; P < 0.001]. On multivariate logistic regression analysis, COMP-positivity was independently associated only with cirrhosis(OR = 4.40, 95%CI: 1.33-14.69, P = 0.015). Kaplan-Meier analysis showed that COMP positivity was significantly associated with HCC development(P = 0.007) and higher incidence of liver-related death(P < 0.001). CONCLUSION: Elevated COMP levels are strongly associated with cirrhosis and HCC progression. Serum COMP is a new promising non-invasive biomarker for HCC risk assessment in surveillance programs. | Gary L Norman Nikolaos K Gatselis Zakera Shums Christos Liaskos Dimitrios P Bogdanos George K Koukoulis George N Dalekos | 2015 | World Journal of Hepatology2015，7，14： | 7 |
| 5 | 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 |
| 6 | Gut barrier failure biomarkers are associated with poor disease outcome in patients with primary sclerosing cholangitis显示文摘AIM To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis(PSC) patients.METHODS Sera of 67 PSC patients [median age(range): 32(5-79) years, concomitant IBD: 67% and cirrhosis: 20%] were assayed for the presence of antibodies against to F-actin(AAA Ig A/Ig G) and gliadin(AGA Ig A/Ig G)] and for serum level of intestinal fatty acid-binding protein(I-FABP) by ELISA. Markers of lipopolysaccharide(LPS) exposure [LPS binding protein(LBP)] and various antimicrobial antibodies [anti-OMP Plus Ig A and endotoxin core Ig A antibody(Endo CAb)] were also determined. Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up [median: 99(14-106) mo]. One hundred and fifty-three healthy subjects(HCONT) and 172 ulcerative colitis(UC) patients were the controls. RESULTS A total of 28.4%, 28.0%, 9% and 20.9% of PSC patients were positive for AAA Ig A, AAA Ig G, AGA Ig A and AGA Ig G, respectively. Frequencies of AAA Ig A and AAA Ig G(P < 0.001, for both) and AGA Ig G(P = 0.01, for both) but not AGA Ig A were significantly higher compared to both of the HCONT and the UC groups. In survival analysis, AAA Ig A-positivity was revealed as an independent predictor of poor disease outcome after adjusting either for the presence of cirrhosis [HR = 5.15(1.27-20.86), P = 0.022 or for the Mayo risk score(HR = 4.24(0.99-18.21), P = 0.052]. AAA Ig A-positivity was significantly associated with higher frequency of antimicrobial antibodies(P < 0.001 for Endo Cab Ig A and P = 0.012 for anti-OMP Plus Ig A) and higher level of the enterocyte damage marker(median I-FABP_(AAA Ig A pos vs neg): 365 vs 166 pg/m L, P = 0.011), but not with serum LBP level. CONCLUSION Presence of Ig A type AAA identified PSC patients with progressive disease. Moreover, it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage further highlighting the importance of the gut-liver interaction in PSC. | Tamas Tornai Eszter Palyu Zsuzsanna Vitalis Istvan Tornai David Tornai Peter Antal-Szalmas Gary L Norman Zakera Shums Gabor Veres Antal Dezsofi Gabriella Par Alajos Par Peter Orosz Ferenc Szalay Peter Laszlo Lakatos Maria Papp | 2017 | World Journal of Gastroenterology2017，23，29： | 5 |
| 7 | Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion显示文摘Ischaemia-reperfusion injury(IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells(LSEC). Recent evidence suggests that LSEC coordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion(NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI. | Yuri L Boteon Richard Laing Hynek Mergental Gary M Reynolds Darius F Mirza Simon C Afford Ricky H Bhogal | 2017 | World Journal of Gastroenterology2017，23，48： | 4 |
| 8 | Outcomes of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding显示文摘AIM:To evaluate weight loss and surgical outcomes of Roux-en-Y gastric bypass(RYGB)and laparoscopic adjustable gastric band(LAGB).METHODS:Data relating to changes in body mass index(BMI)and procedural complications after RYGB(1995-2009;n=609;116M:493F;42.4±0.4 years)or LAGB(2004-2009;n=686;131M:555F;37.2±0.4years)were extracted from prospective databases.RESULTS:Pre-operative BMI was higher in RYGB than LAGB patients(46.8±7.1 kg/m2vs 40.4±4.2 kg/m2,P<001);more patients with BMI<35 kg/m2underwent LAGB than RYGB(17.1%vs 4.1%,P<0.0001).BMI decrease was greater after RYGB.There were direct relationships between weight loss and pre-operative BMI(P<0.001).Although there was no difference in weight loss between genders during the first 3-year post-surgery,male LAGB patients had greater BMI reduction than females(-8.2±4.3 kg/m2vs-3.9±1.9kg/m2,P=0.02).Peri-operative complications occurred more frequently following RYGB than LAGB(8.0%vs0.5%,P<0.001);majority related to wound infection.LAGB had more long-term complications requiring corrective procedures than RYGB(8.9%vs 2.1%,P<0.001).Conversion to RYGB resulted in greater BMI reduction(-9.5±3.8 kg/m2)compared to removal and replacement of the band(-6.0±3.0 kg/m2).Twelve months post-surgery,fasting glucose,total cholesterol and low density lipoprotein levels were significantly lower with the magnitude of reduction greater in RYGB patients.CONCLUSION:RYGB produces substantially greater weight loss than LAGB.Whilst peri-operative complications are greater after RYGB,long-term complication rate is higher following LAGB. | Nam Q Nguyen Philip Game Justin Bessell Tamara L Debreceni Melissa Neo Carly M Burgstad Pennie Taylor Gary A Wittert | 2013 | World Journal of Gastroenterology2013，19，36： | 3 |
| 9 | 烧伤的流行病学、人口统计学及结局特点显示文摘 | John L Hunt Gary F Purdue 王劭宏(译) | 2008 | 中华损伤与修复杂志(电子版)2008，3，1： | 3 |
| 10 | DNA vaccination of infants in the presence of maternal antibody: a measles model in the primate显示文摘 | Mary Premenko-Lanier Paul A Rota Gary Rhodes David Verhoeven Dan H Barouch Nicholas W Lerche Norman L Letvin William J Bellini Michael B McChesney | 2003 | Virology2003，，1： | 2 |
| 11 | Inflammation and Alzheimer’s disease显示文摘 | Haruhiko Akiyama Steven Barger Scott Barnum Bonnie Bradt Joachim Bauer Greg M Cole Neil R Cooper Piet Eikelenboom Mark Emmerling Berndt L Fiebich Caleb E Finch Sally Frautschy W.S.T Griffin Harald Hampel Michael Hull Gary Landreth Lih–Fen Lue Robert Mrak | 2000 | Neurobiology of Aging2000，，3： | 2 |
| 12 | Comprehensive review of autoantibodies in patients with hyper-IgM syndrome显示文摘Hyper-immunoglobulin M syndrome is an X-linked primary immunodeficiency disease caused by mutations in the CD40 ligand gene.The CD40 ligand has been recently highlighted as playing a key role in the pathogenesis of primary biliary cholangitis.In the present study,we assessed an extensive set of serum autoantibodies in a series of well-defined patients with hyper-immunoglobulin M syndrome.Serum,liver-related and liver-not-related autoantibodies IgG,IgM and IgA were tested by ELISA and standard indirect immunofluorescence in HEp-2 cells in 13 Tunisian patients(8 males and 5 females,aged 1–12 years)with hyper-immunoglobulin M syndrome during 1995–2012 and,as controls,21 age-and gender-matched blood donors.The level of IgM antibody against MIT3 was significantly higher in patients than in controls(35.8 vs 10.7,P=0.002).Half of the hyperimmunoglobulin M syndrome patients were found to be anti-MIT3 IgM positive vs none of the controls(Po0.0001).Twenty-three percent of patients were found to be anti-sp100 antibody positive vs only 0.05%of controls.By immunofluorescence,92.3%of patients were MIT3 IgM positive vs none of the controls.In conclusion,the IgM class of anti-MIT3 antibodies was shown to be present by both ELISA and immunofluorescence in most of the patients with hyper-immunoglobulin M syndrome.The presence of the hallmark of primary biliary cholangitis,a disease where the CD40 ligand is a key player,in an immunodeficiency disease caused by mutations in the CD40 ligand gene is very intriguing and opens new scenarios in understanding the immune pathogenesis of primary biliary cholangitis. | Mohamed-Ridha Barbouche Qubo Chen Marco Carbone Imen Ben-Mustapha Zakera Shums Mehdi Trifa Federica Malinverno Francesca Bernuzzi Haiyan Zhang Nourhen Agrebi Gary L Norman Christopher Chang M Eric Gershwin Pietro Invernizzi | 2018 | Cellular & Molecular Immunology2018，15，6： | 2 |
| 13 | Predictors of progression in Barrett’s esophagus III: baseline flow cytometric variables显示文摘 | Peter S Rabinovitch Gary Longton Patricia L Blount Douglas S Levine Brian J Reid | 2001 | The American Journal of Gastroenterology2001，，11： | 2 |
| 14 | Predictors of progression in Barrett’s esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression显示文摘 | Brian J Reid Laura J Prevo Patricia C Galipeau Carissa A Sanchez Gary Longton Douglas S Levine Patricia L Blount Peter S Rabinovitch | 2001 | The American Journal of Gastroenterology2001，，10： | 2 |
| 15 | 对钙和磷的进一步研究显示文摘 | 宋建国 Gary L Cromwell Merlin D Lindemann | 2002 | 国外畜牧学(猪与禽)2002，，6： | 2 |
| 16 | Cancer Genome Scanning in Plasma: Detection of Tumor-Associated Copy Number Aberrations, Single-Nucleotide Variants, and Tumoral Heterogeneity by Massively Parallel Sequencing显示文摘 | Chan K C Allen Jiang Peiyong Zheng Yama W L Liao Gary J W Sun Hao Wong John Siu Shing Shun N Chan Wing C Chan Stephen L Chan Anthony T C Lai Paul B S Chiu Rossa W K Lo Y M D | 2013 | Clinical Chemistry2013，，1： | 2 |
| 17 | Sewage measured by the faecal (2) sterol , coprostanol 显示文摘 | Gary L A Steven C C | 1995 | Wat Res1995，29，6： | 1 |
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| 19 | Marked improvement of PAC and BAG cloning is achieved using electroelution of pulsed-field gelseperated partial digested of genomic DNA显示文摘 | Scott J S Yuko O Gary W L | 1997 | Nucleic Acids Res1997，25，： | 1 |
| 20 | Realizing the hydrogen future: the International energy agency's efforts to advance hydrogen energy technologies显示文摘 | Carolyn C E Gary S Andreas L | 2003 | Int J Hydrogen Energy2003，28，： | 1 |
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