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| 1 | Autoimmune hepatitis,one disease with many faces:Etiopathogenetic,clinico-laboratory and histological characteristics显示文摘Autoimmune hepatitis(AIH) is an unresolving progressive liver disease of unknown etiology characterized byhypergammaglobulinemia,autoantibodies detection and interface hepatitis.Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical,laboratory and histological features,AIH diagnosis may be potentially difficult.Therefore,in this in-depth review we summarize the substantial progress on etiopathogenesis,clinical,serological and histological phenotypes of AIH.AIH has a global distribution affecting any age,both sexes and all ethnic groups.Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis.Hypergammaglobulinemia with selective elevation of IgG is found in most cases.Autoimmune attack is perpetuated,possibly via molecular mimicry,and favored by the impaired control of T-regulatory cells.Histology(interface hepatitis,emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic,are still the hallmark for a timely diagnosis.AIH remains a major diagnostic challenge.AIH should be considered in every case in the absence of viral,metabolic,genetic and toxic etiology of chronic or acute hepatitis.Laboratory personnel,hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient. | Nikolaos K Gatselis Kalliopi Zachou George K Koukoulis George N Dalekos | 2015 | World Journal of Gastroenterology2015，21，1： | 36 |
| 2 | 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 |
| 3 | Bone mineral density and disorders of mineral metabolism in chronic liver disease显示文摘AIM:To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis.METHODS:The study was performed on 72 Indian patients with cirrhosis(63 male, 9 female;aged < 50 years).Etiology of cirrhosis was alcoholism(n = 37), hepatitis B(n = 25) and hepatitis C(n = 10).Twenty-three patients belonged to Child class A, while 39 were in class B and 10 in class C.Secondary causes for metabolic bone disease and osteoporosis were ruled out.Sunlight exposure, physical activity and dietary constituents were calculated.Complete metabolic profiles were derived, and bone mineral density(BMD) was measured using dual energy X ray absorptiometry.Low BMD was defined as a Z score below-2.RESULTS:Low BMD was found in 68% of patients.Lumbar spine was the most frequently and severely affected site.Risk factors for low BMD included low physical activity, decreased sunlight exposure, and low lean body mass.Calcium intake was adequate, with unfavorable calcium:protein ratio and calcium:phosphorus ratio.Vitamin D deficiency was highly prevalent(92%).There was a high incidence of hypogonadism(41%).Serum estradiol level was elevated significantly in patients with normal BMD.Insulin-like growth factor(IGF) 1 and IGF binding protein 3 levels were below the age-related normal range in both groups.IGF-1 was signiflcantly lower in patients with low BMD.Serum osteocalcin level was low(68%) and urinary deoxypyridinoline to creatinine ratio was high(79%), which demonstrated low bone formation with high resorption.CONCLUSION:Patients with cirrhosis have low BMD.Contributory factors are reduced physical activity, low lean body mass, vitamin D def iciency and hypogonadism and low IGF-1 level. | Joe George Hosahithlu K Ganesh Shrikrishna Acharya Tushar R Bandgar Vyankatesh Shivane Anjana Karvat Shobna J Bhatia Samir Shah Padmavathy S Menon Nalini Shah | 2009 | World Journal of Gastroenterology2009，15，28： | 15 |
| 4 | Hepatocellular carcinoma in non-alcoholic steatohepatitis:Current knowledge and implications for management显示文摘With the prevalence of hepatitis C virus expected to decline, the proportion of hepatocellular carcinoma(HCC) related to non-alcoholic steatohepatitis(NASH) is anticipated to increase exponentially due to the growing epidemic of obesity and diabetes. The annual incidence rate of developing HCC in patients with NASH-related cirrhosis is not clearly understood with rates ranging from 2.6%-12.8%. While multiple new mechanisms have been implicated in the development of HCC in NASH; further prospective long-term studies are needed to validate these findings. Recent evidence has shown a significant proportion of patients with non-alcoholic fatty liver disease and NASH progress to HCC in the absence of cirrhosis. Liver resection and transplantation represent curative therapeutic options in select NASHrelated HCC patients but have placed a significant burden to our healthcare resources and utilization. Currently NASH-related HCC is the fastest growing indication for liver transplant in HCC candidates. Increased efforts to implement effective screening and preventative strategies, particularly in non-cirrhotic NASH patients, are needed to reduce the future impact imposed by NASH-related HCC. | George Cholankeril Ronak Patel Sandeep Khurana Sanjaya K Satapathy | 2017 | World Journal of Hepatology2017，9，11： | 12 |
| 5 | Treatment responses in Asians and Caucasians with chronic hepatitis C infection显示文摘AIM:To conduct a multicentre retrospective review of virological response rates in Asians infected with genotype 1 chronic hepatitis C(CHC) treated with combination interferon and ribavirin and then to compare their responses to that among Caucasians.METHODS:Asian patients infected with genotype 1 CHC treated at 4 Australian centres between 2001 to 2005 were identified through hospital databases.Baseline demographic characteristics,biochemical,virological and histological data and details of treatment were collected.Sustained virological responses(SVR) in this cohort were then compared to that in Caucasian subjects,matched by genotype,age,gender and the stage of hepatic fibrosis.RESULTS:A total of 108 Asians with genotype 1 CHC were identified.The end of treatment response(ETR) for the cohort was 79% while the SVR was 67%.Due to the relatively advanced age of the Asian cohort,only sixty-four subjects could be matched with Caucasians.The ETR among matched Asians and Caucasians was 81% and 56% respectively(P=0.003),while the SVR rates were 73% and 36%(P <0.001) respectively.This difference remained significant after adjusting for other predictive variables. | Kenneth K Yan Marianne Guirgis Amany Zekry Thuy Dinh Anouk Dev Jacob George Alice Lee | 2008 | World Journal of Gastroenterology2008，14，21： | 12 |
| 6 | Effects of resveratrol in experimental and clinical non-alcoholic fatty liver disease显示文摘The prevalence of obesity and related conditions like non-alcoholic fatty liver disease(NAFLD) is increasing worldwide and therapeutic options are limited.Alternative treatment options are therefore intensively sought after.An interesting candidate is the natural polyphenol resveratrol(RSV) that activates adenosinmonophosphate-activated protein kinase(AMPK) and silent information regulation-2 homolog 1(SIRT1).In addition,RSV has known anti-oxidant and anti-inflammatory effects.Here,we review the current evidence for RSVmediated effects on NAFLD and address the different aspects of NAFLD and non-alcoholic steatohepatitis(NASH) pathogenesis with respect to free fatty acid(FFA) flux from adipose tissue,hepatic de novo lipogenesis,inadequate FFA β-oxidation and additional intra- and extrahepatic inflammatory and oxidant hits.We review the in vivo evidence from animal studies and clinical trials.The abundance of animal studies reports a decrease in hepatic triglyceride accumulation,liver weight and a general improvement in histological fatty liver changes,along with a reduction in circulating insulin,glucose and lipid levels.Some studies document AMPK or SIRT1 activation,and modulation of relevant markers of hepatic lipogenesis,inflammation and oxidation status.However,AMPK/SIRT1-independent actions are also likely.Clinical trials are scarce and have primarily been performed with a focus on overweight/obese participants without a focus on NAFLD/NASH and histological liver changes.Future clinical studies with appropriate design are needed to clarify the true impact of RSV treatment in NAFLD/NASH patients. | Sara Heebll Karen Louise Thomsen Steen B Pedersen Hendrik Vilstrup Jacob George Henning Grnbk | 2014 | World Journal of Hepatology2014，6，4： | 11 |
| 7 | Alterations in the function of circulating mononuclear cells derived from patients with Crohn’s disease treated with mastic显示文摘AIM: To assess the effects of mastic administration on cytokine production of circulating mononuclear cells of patients with active Crohn's disease (CD). METHODS: The study was conducted in patients with established mildly to moderately active CD, attending the outpatient clinics of the hospital, and in healthy controls. Recruited to a 4 wk treatment with mastic caps (6 caps/d, 0.37 g/cap) were 10 patients and 8 controls, all of who successfully completed the protocol. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), macrophage migration inhibitory factor (MIF) and intracellular antioxidant glutathione (GSH) were evaluated in peripheral blood mononuclear cells (PBMC) before and after treatment. RESULTS: Treating CD patients with mastic resulted in the reduction of TNF-α secretion (2.1 ± 0.9 ng/mL vs 0.5 ± 0.4 ng/mL, P = 0.028). MIF release was signif icantly increased (1.2 ± 0.4 ng/mL vs 2.5 ± 0.7 ng/mL, P = 0.026) meaning that random migration and chemotaxis of monocytes/macrophages was inhibited. No signifi cant changes were observed in IL-6, MCP-1 and GSH concentrations. CONCLUSION: This study shows that mastic acts as an immunomodulator on PBMC, acting as a TNF-α inhibitor and a MIF stimulator. Although further double-blind, placebo-controlled studies in a large number of patients is required to clarify the role of this natural product, this f inding provides strong evidence that mastic might be an important regulator of immunity in CD. | Andriana C Kaliora Maria G Stathopoulou John K Triantaf illidis George VZ Dedoussis Nikolaos K Andrikopoulos | 2007 | World Journal of Gastroenterology2007，13，45： | 8 |
| 8 | Flecainide: Current status and perspectives in arrhythmia management显示文摘Flecainide acetate is a class IC antiarrhythmic agent and its clinical efficacy has been confirmed by the results of several clinical trials. Nowadays, flecainide is recommended as one of the first line therapies for pharmacological conversion as well as maintenance of sinus rhythm in patients with atrial fibrillation and/or supraventricular tachycardias. Based on the Cardiac Arrhythmia Suppression Trial study results, flecainide is not recommended in patients with structural heart disease due to high proarrhythmic risk. Recent data support the role of flecainide in preventing ventricular tachyarrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia associated both with ryanodine receptor and calsequestrin mutations. We herein review the current clinical data related to flecainide use in clinical practice and some concerns about its role in the management of patients with coronary artery disease. | George K Andrikopoulos Sokratis Pastromas Stylianos Tzeis | 2015 | World Journal of Cardiology2015，7，2： | 8 |
| 9 | Primary biliary cirrhosis in HBV and HCV patients:Clinical characteristics and outcome显示文摘AIM: To present the characteristics, management and outcome of patients with hepatitis B virus(HBV) or hepatitis C virus(HCV) infections concurrent with primary biliary cirrhosis(PBC).METHODS: Since January 2001 to September 2009,we retrospectively evaluated the medical records of all HBV(n = 1493) and HCV patients(n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC(8 HCV and PBC; follow-up: 61 ± 37 mo and 9 HBV and PBC; follow-up: 57 ± 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of PBC.RESULTS: HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients,while one third(5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV(56.1 ± 11.2vs 68.5 ± 10.3, respectively, P < 0.05). At initial clinical and histological assessment the majority of patients were cirrhotics(10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency(87.5% vs33.3% in PBC and HBV; P < 0.05). The patients with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during follow-up.CONCLUSION: PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC. | Eirini I Rigopoulou Kalliopi Zachou Nikolaos K Gatselis Georgia Papadamou George K Koukoulis George N Dalekos | 2013 | World Journal of Hepatology2013，5，10： | 7 |
| 10 | 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 |
| 11 | Chios mastic treatment of patients with active Crohn's disease显示文摘AIM: To evaluate the effectiveness of mastic administra-tion on the clinical course and plasma inflammatory me-diators of patients with active Crohn’s disease (CD).METHODS: This pilot study was conducted in patients with established mild to moderately active CD, attend-ing the outpatient clinics of the hospital, and in healthy controls. Ten patients and 8 controls were recruited for a 4-wk treatment with mastic caps (6 caps/d, 0.37 g/cap). All patients successfully completed the protocol. CD Ac-tivity Index (CDAI), Nutritional Risk Index (NRI), C-re-active protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), and total antioxidant potential (TAP) were evaluated in the plasma at baseline and at the end of the treatment period. Results were expressed as mean values ± SE and P < 0.05 was considered to indicate statistical significance.RESULTS: Patients exhibited significant reduction of CDAI (222.9 ± 18.7 vs 136.3 ± 12.3, P = 0.05) as com-pared to pretreament values. Plasma IL-6 was signifi-cantly decreased (21.2 ± 9.3 pg/mL vs 7.2 ± 2.8 pg/ mL, P = 0.027), and so did CRP (40.3 ± 13.1 mg/mL vs 19.7 ± 5.5, P = 0.028). TAP was significantly increased (0.15 ± 0.09 vs 0.57 ± 0.15 mmol/L uric acid, P = 0.036). No patient or control exhibited any kind of side effects. CONCLUSION: The results suggest that mastic signifi-cantly decreased the activity index and the plasma levels of IL-6 and CRP in patients with mildly to moderately ac-tive CD. Further double-blind, placebo-controlled studies in a larger number of patients are required to clarify the role of this natural product in the treatment of patients with CD. | Andriana C Kaliora Maria G Stathopoulou John K Triantafillidis George VZ Dedoussis Nikolaos K Andrikopoulos | 2007 | World Journal of Gastroenterology2007，13，5： | 7 |
| 12 | Hepatitis B virus reactivation in hepatitis B virus surface antigen negative patients receiving immunosuppression: A hidden threat显示文摘AIM: To present the characteristics and the course of a series of anti- hepatitis B virus core antibody (HBc) antibody positive patients, who experienced hepatitis B virus (HBV) reactivation after immunosuppression. METHODS: We retrospectively evaluated in our tertiary centers the medical records of hepatitis B virus surface antigen (HBsAg) negative patients who suffered from HBV reactivation after chemotherapy or immunosuppression during a 3-year period (2009-2011). Accordingly, the clinical, laboratory and virological characteristics of 10 anti-HBc (+) anti-HBs (-)/HBsAg (-) and 4 anti-HBc (+)/antiHBs (+)/HBsAg (-) patients, who developed HBV reactivation after the initiation of chemotherapy or immunosuppressive treatment were analyzed. Quantitative determination of HBV DNA during reactivation was performed in all cases by a quantitative real time polymerase chain reaction kit (COBAS Taqman HBV Test; cut-off of detection: 6 IU/mL). RESULTS: Twelve out of 14 patients were males; median age 74.5 years. In 71.4% of them the primary diagnosis was hematologic malignancy; 78.6% had received rituximab (R) as part of the immunosuppressive regimen. The median time from last chemotherapy schedule till HBV reactivation for 10 out of 11 patients who received R was 3 (range 2-17) mo. Three patients (21.4%) deteriorated, manifesting ascites and hepatic encephalopathy and 2 (14.3%) of them died due to liver failure. CONCLUSION: HBsAg-negative anti-HBc antibody positive patients can develop HBV reactivation even 2 years after stopping immunosuppression, whereas prompt antiviral treatment on diagnosis of reactivation can be lifesaving. | Kalliopi Zachou Alexandros Sarantopoulos Nikolaos K Gatselis Themistoklis Vassiliadis Stella Gabeta Aggelos Stefos Asterios Saitis Panagiota Boura George N Dalekos | 2013 | World Journal of Hepatology2013，5，7： | 6 |
| 13 | It is safe to use transdermal glyceryl trinitrate to lower blood pressure in patients with acute ischaemic stroke with carotid stenosis显示文摘Background There is concern that blood pressure(BP)lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the presence of carotid stenosis.We assessed the effect of glyceryl trinitrate(GTN)in patients with carotid stenosis using data from the Efficacy of Nitric Oxide in Stroke(ENOS)Trial.Methods ENOS randomised 4011 patients with acute stroke and raised systolic BP(140-220 mm Hg)to transdermal GTN or no GTN within 48 hours of onset.Those on prestroke antihypertensives were also randomised to stop or continue their medication for 7 days.The primary outcome was the modified Rankin Scale(mRS)at day 90.Ipsilateral carotid stenosis was split:<30%;30-<50%;50-<70%;≥70%.Data are ORs with 95%CIs adjusted for baseline prognostic factors.results 2023(60.5%)ischaemic stroke participants had carotid imaging.As compared with<30%,≥70%ipsilateral stenosis was associated with an unfavourable shift in mRS(worse outcome)at 90 days(OR 1.88,95%CI 1.44 to 2.44,p<0.001).Those with≥70%stenosis who received GTN versus no GTN had a favourable shift in mRS(OR 0.56,95%CI 0.34 to 0.93,p=0.024).In those with 50-<70%stenosis,continuing versus stopping prestroke antihypertensives was associated with worse disability,mood,quality of life and cognition at 90 days.Clinical outcomes did not differ across bilateral stenosis groups.Conclusions Following ischaemic stroke,severe ipsilateral carotid stenosis is associated with worse functional outcome at 90 days.GTN appears safe in ipsilateral or bilateral carotid stenosis,and might improve outcome in severe ipsilateral carotid stenosis. | Jason P Appleton Lisa J Woodhouse Andrew Belcher Daniel Bereczki Eivind Berge Valeria Caso Hui Meng Chang Hanne K Christensen Ronan Collins John Gommans Ann C Laska George Ntaios Serefnur Ozturk Gillian M Sare Szabolcs Szatmari Yongjun Wang Joanna M Wardlaw Nikola Sprigg Philip M Bath for the ENOS investigators | 2019 | Stroke & Vascular Neurology2019，4，1： | 6 |
| 14 | CD8:Adhesion Molecule,Co-Receptor and Immuno-Modulator显示文摘CD8 is a cell surface glycoprotein found in cytotoxic T lymphocytes, which are important components in cellular immunity, esp. In the immune response to cancer and chronic infections. There are two forms of CD8,either as an αα homodimer or αβ heterodimer. It acts as an 'assistant' or co-receptor in the function of cytotoxic T cells where specific immunity is mediated by interaction of specific T cell receptor (αβTCR) and its ligand peptide major histocompatibility complex (pMHC). CD8 also binds to pMHC but away from the interface of pMHC and TCR contact, thereof no influence on the specificity of this interaction. If the TCR and CD8 bind to the same pMHC at the same time, CD8 is defined as a co-receptor, functioning through its signalling via its cytoplasmic tyrosine phosphorylation pathway; if CD8 binds to pMHC independently of the TCR, it is defined as an adhesion molecule. At present, the co-receptor function theory is dominated in the field.Recent study has also shown that murine CD8αα binds to TL antigen, an MHC homologue, therefore acts as an immuno-modulator. In this review, we discuss these current understandings of the three aspects of the CD8 functions and their structural basis. | David K Cole George F Gao | 2004 | Cellular & Molecular Immunology2004，1，2： | 4 |
| 15 | Primary biliary cirrhosis-specific autoantibodies in first degree relatives of Greek primary biliary cirrhosis patients显示文摘AIM:To determine the prevalence and significance of primary biliary cirrhosis (PBC)-specific autoantibodies in firstdegree relatives (FDRs) of Greek PBC patients. METHODS:The presence of antimitochondrial antibodies (AMA) and PBCspecific antinuclear antibodies (ANA) were determined using indirect immunofluores-cence assays, dot-blot assays, and molecularly based enzyme-linked immunosorbent assays in 101 asymp-tomatic for liver-related symptoms FDRs of 44 PBCpatients. In order to specify our results, the same investigation was performed in 40 healthy controls and in a disease control group consisting of 40 asymptomatic for liver-related symptoms FDRs of patients with other autoimmune liver diseases namely, autoimmune hepati-tis-1 or primary sclerosing cholangitis (AIH-1/PSC). RESULTS: AMA positivity was observed in 19 (only 4 with abnormal liver function tests) FDRs of PBC patients and none of the healthy controls. The preva-lence of AMA was significantly higher in FDRs of PBC patients than in AIH-1/PSC FDRs and healthy controls [18.8%, 95% confidence interval (CI):12%-28.1% vs 2.5%, 95% CI:0.1%-14.7%, P = 0.01; 18.8%, 95% CI:12%-28.1% vs 0%, 95% CI: 0%-10.9%, P = 0.003, respectively]. PBC-specific ANA positivity was observed in only one FDR from a PSC patient. Multivariate analysis showed that having a proband with PBC independently associated with AMA positivity (odds ratio: 11.24, 95% CI:1.27-25.34, P = 0.03) whereas among the investigated comorbidities and risk factors, a positive past history for urinary tract infections (UTI) was also independently associated with AMA detection in FDRs of PBC patients (odds ratio:3.92, 95% CI:1.25-12.35,P = 0.02). CONCLUSION:In FDRs of Greek PBC patients, AMA prevalence is significantly increased and independently associated with past UTI. PBC-specific ANA were not detected in anyone of PBC FDRs. | Theodoros A Zografos Nikolaos Gatselis Kalliopi Zachou Christos Liaskos Stella Gabeta George K Koukoulis George N Dalekos | 2012 | World Journal of Gastroenterology2012，18，34： | 4 |
| 16 | Non-alcoholic fatty liver disease and the metabolic syndrome:Effects of weight loss and a review of popular diets,Are low carbohydrate diets the answer?显示文摘非酒精的脂肝疾病(NAFLD ) 包含大量导致脂肪的肝损伤,从相对良性的脂肪变性到肝硬化和肝失败。肥胖和抗胰岛素性的存在强烈与非酒精的脂肝被联系并且在它上交谈更大的风险组织学地病沉重期。当这疾病的流行继续在肥胖和新陈代谢的症候群与上升同时升起,在医疗职业有一颗成长担心。治疗选择被限制,饮食的重量损失经常被劝告。少脂饮食是困难的遵守,最近的研究为重量损失和改善抗胰岛素性显示出低糖类食谱的潜力。因此远,没有学习在 NAFLD 上评估了低糖类食谱的效果。未来研究将被要求关于营养的足够和这些食谱的长期的副作用探讨这个问题和其它。 | Harjot K Gill George Y Wu | 2006 | World Journal of Gastroenterology2006，12，3： | 4 |
| 17 | A hypothesis for treating inflammation and oxidative stress with hydrogen sulfide during age-related macular degeneration显示文摘Age-related macular degeneration(AMD) is a leading cause of blindness and is becoming a global crisis since affected people will increase to 288 million by 2040.Genetics,age,diabetes,gender,obesity,hypertension,race,hyperopia,iris-color,smoking,sun-light and pyroptosis have varying roles in AMD,but oxidative stress-induced inflammation remains a significant driver of pathobiology.Eye is a unique organ as it contains a remarkable oxygengradient that generates reactive oxygen species(ROS) which upregulates inflammatory pathways.ROS becomes a source of functional and morphological impairments in retinal pigment epithelium(RPE),endothelial cells and retinal ganglion cells.Reports demonstrated that hydrogen sulfide(H_2S) acts as a signaling molecule and that it may treat ailments.Therefore,we propose a novel hypothesis that H_2S may restore homeostasis in the eyes thereby reducing damage caused by oxidative injury and inflammation.Since H_2S has been shown to be a powerful antioxidant because of its free-radicals' inhibition properties in addition to its beneficial effects in age-relatedconditions,therefore,patients may benefit from H_2S salubrious effects not only by minimizing their oxidant and inflammatory injuries to retina but also by lowering retinal glutamate excitotoxicity. | Akash K George Mahavir Singh Rubens Petit Homme Avisek Majumder Harpal S SANDhu Suresh C Tyagi | 2018 | International Journal of Ophthalmology(English edition)2018，11，5： | 3 |
| 18 | Diagnosis of autoimmune gastritis by high resolution magnification endoscopy显示文摘胃的萎缩的内视镜的可视化通常不与常规内视镜检查法是可行的。放大内视镜检查法是有用的分析潜水艇没有织物的上皮的微脉管的建筑学以及粘膜表面微观结构活体检视。用这种技术,我们能描述正常胃的微脉管系统模式,我们也在自体免疫的萎缩性胃炎的二种情况中识别了典型模式。 | George K Anagnostopoulos Krish Ragunath Anthony Shonde Christopher J Hawkey | 2006 | World Journal of Gastroenterology2006，12，28： | 3 |
| 19 | 半边旗活性物质5F对非小细胞肺癌NCI-H460细胞IκKβ、IκB、p65及p50 mRNA表达的影响显示文摘目的从NF-κB信号通路着手探讨半边旗活性物质5F诱导非小细胞肺癌NCI-H460细胞凋亡发生的机制。方法MTT法检测5F对NCI-H460细胞的生长抑制作用;用半定量RT-PCR方法检测NCI-H460细胞IκKβ、IκB、p65及p50mRNA表达水平的变化。结果5F抑制NCI-H460细胞的生长,其效果与5F的质量浓度和作用时间相关,24、48、72h的IC50分别为:21.40、4.52、1.02μg/mL;100μg/mL5F作用NCI-H460细胞6h后能引起IκKβ和IκBmRNA表达水平显著降低(P<0.05);p65和p50mRNA水平在作用3h就发生明显减少(P<0.05)。结论5F诱导NCI-H460细胞凋亡的机制可能是通过抑制核因子-κB(NF-κB)信号通路来实现的。 | 刘义 CHEN George G 吕应年 HSIN Michael K Y UNDERWOOD Malcolm J 梁念慈 | 2010 | 中草药2010，41，3： | 3 |
| 20 | Novel role of STAT3 in microglia-dependent neuroinflammation after experimental subarachnoid haemorrhage显示文摘Background and purpose Signal transducer and activator of transcription 3(STAT3)may contribute to the proinflammation in the central nervous system diseases by modulating the microglial responses.Thus,this study was intended to investigate the effect of STAT3 on microglia-dependent neuroinflammation and functional outcome after experimental subarachnoid haemorrhage(SAH).Methods The SAH model was established by endovascular perforation in the mouse.Real-time PCR(RtPCR)and western blot were used to examine the dynamic STAT3 signalling pathway responses after SAH.To clarify the role of the STAT3 signalling pathway in the microglia-dependent neuroinflammation after SAH,the microglia-specific STAT3 knockout(KO)mice were generated by the Cre-LoxP system.The neurological functions were assessed by Catwalk and Morris water maze tests.Neuronal loss after SAH was determined by immunohistochemistry staining.Microglial polarisation status after STAT3 KO was then examined by RtPCR and immunofluorescence.Results The STAT3 and Janus kinase-signal transducer 2 activated immediately with the upregulation and phosphorylation after SAH.Downstream factors and related mediators altered dynamically and accordingly.Microglial STAT3 deletion ameliorated the neurological impairment and alleviated the early neuronal loss after SAH.To investigate the underlying mechanism,we examined the microglial reaction after STAT3 KO.STAT3 deletion reversed the increase of microglia after SAH.Loss of STAT3 triggered the early morphological changes of microglia and primed microglia from M1 to M2 polarisation.Functionally,microglial STAT3 deletion suppressed the SAH-induced proinflammation and promoted the anti-inflammation in the early phase.Conclusions STAT3 is closely related to the microglial polarisation transition and modulation of microglia-dependent neuroinflammation.Microglial STAT3 deletion improved neurological function and neuronal survival probably through promoting M2 polarisation and anti-inflammatory responses after SAH.STAT3 may serve as a promising therapeutic target to alleviate early brain injury after SAH. | Zhiyuan Vera Zheng Junfan Chen Hao Lyu Sin Yu Erica Lam Gang Lu Wai Yee Chan George K C Wong | 2022 | Stroke & Vascular Neurology2022，7，1： | 3 |
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