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| 1 | 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 |
| 2 | 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 |
| 3 | Prokineticin-1 (Prok-1) works coordinately with glial cell line derived neurotrophic factor (GDNF) to mediate proliferation and differentiation of enteric neural crest cells显示文摘 | Ngan E S Shum C K Poon H C Sham M H Garcia-Barcelo M M Lui V C | 2008 | Biochim Biophys Acta2008，1783，： | 1 |
| 4 | Usefulness of procalcitonin levels in community-acquired pneumonia according to the patients outcome research team pneumonia severity index 显示文摘 | Masia M Gutierrez F Shum C | 2005 | Chest2005，128，4： | 1 |
| 5 | Aerodynamic Coefficients of Inclined Cylinders with Artificial Rivulet in Smooth flow 显示文摘 | Xu Y L Li Y L Shum K M | 2006 | Advances in Structural Engineering2006，9，2： | 1 |
| 6 | Usefulness of procalcitonin levels in community acquired pneumonia according to the patients outcome research team pneumonia severity index显示文摘 | Masia M Gutierrez F Shum C | 2005 | Chest2005，128，4： | 1 |
| 7 | A class of idempotent semirings,semirings显示文摘 | SEN M K GUO Y Q SHUM K P | 2000 | Semigroup Forum2000，60，： | 1 |
| 8 | Usefulness ofprocalcitonin levels in community-acquired pneumonia accordingto the patients outcome research team pneumonia severity index显示文摘 | Masia M Gutiarez F Shum C | 2005 | Chest2005，128，4： | 1 |
| 9 | The Role of Temporal Landmarks in Autobiographical Memory Processes显示文摘 | Shum M S | 1998 | Psychological Bulletin1998，124，3： | 1 |
| 10 | A Class of Idempotent Semirings 显示文摘 | Sen M K Guo Y Q Shum K P | 2000 | Semigroup Forum2000，60，： | 1 |
| 11 | Temporal variations in low degree zonal harmonics from starlette orbit analysis显示文摘 | Cheng M K Eanes R J Shum C K | 1989 | Geophys Res Lett1989，16，： | 1 |
| 12 | A novel method for analysis of soliton propagation in optical fibres 显示文摘 | Ghafouri-shira H Shum P Nagata M | 1995 | IEEE Journal of Quantum Electronics1995，31，1： | 1 |
| 13 | Determination of Long-term Changes in the Earth's Gravity Field from Satellite Laser Ranging Observations 显示文摘 | CHENG M K SHUM C K TAPLEY B D | 1997 | Journal of Geophysical Research1997，102，10： | 1 |
| 14 | Determination of long-term changes in the earth's gravity field from satellite laser ranging observations显示文摘 | Cheng M K Shum C K Tapley B D | 1997 | Journal of Geophysical Research1997，102，22： | 1 |
| 15 | Impact of the national trunk high-way sys- tem on accessibility in China显示文摘 | Li S M Shum Y M | 2001 | Journal of Transport Geography2001，9，1： | 1 |
| 16 | Bipolar Fuzzy K-algebras显示文摘 | Akram M Saeid A B Shum K P | | 0，，： | 1 |
| 17 | A randomized controlled trial exploring the effect of music on quality of life and depression in ol- der people with dementia显示文摘 | Cooke M Moyle W Shum D | 2010 | J Health Psychol2010，15，5： | 1 |
| 18 | Stacked annular-ring dielectric resonator antenna excited by axi-symmetric coaxial probe 显示文摘 | SHUM S M LUK K M | 1995 | IEEE Trans Antennas Propagat1995，43，8： | 1 |
| 19 | Speciation of Mercury and Lead Compounds by Microbore Column Liquid Chromatography-Inductively Cou-pled Plasma Mass Spectrom with Direct Injection Nebulization 显示文摘 | Shum S C K Pang H M Houk R S | 1992 | Anal Chem1992，64，： | 1 |
| 20 | Usefulness of Procalcitonin Levels in Community-acquired Pneumonia According to the Patients Outcome Research Team Pneumonia Severity Index显示文摘 | Masia M Gutierrez F Shum C | 2005 | Chest2005，128，4： | 1 |
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