European Journal of Gastroenterology & Hepatology最新文献

{"title":"Development of a retinal vascular nomogram for predicting hepatitis B virus-related cirrhosis: insights into extrahepatic microcirculatory dysfunctions.","authors":"Xi Huang, Hua Wang, Jingxiong Hu, Manhang Cai, Yuesi Zhong","doi":"10.1097/MEG.0000000000003078","DOIUrl":"https://doi.org/10.1097/MEG.0000000000003078","url":null,"abstract":"<p><strong>Background: </strong>The progression of hepatitis B virus-related cirrhosis (HBC) is characterized by notable intrahepatic and extrahepatic microvascular alterations and dysfunctions. The retinal vasculature offers a noninvasive window to assess systemic microcirculation. This cross-sectional study aimed to evaluate retinal microcirculatory alterations in HBC and develop a retinal vascular nomogram for diagnosing HBC.</p><p><strong>Methods: </strong>We included 328 participants from two medical centers between March 2019 and October 2022. Multivariate logistic regression identified independent retinal predictors of HBC, and a nomogram was constructed. Associations between retinal parameters and clinical indicators of HBC were examined using univariate analyses.</p><p><strong>Results: </strong>Retinal vascular caliber, retinal vascular branching angle, and retinal vascular fractal dimension were independent predictors of HBC. The nomogram achieved an area under the receiver operating characteristic curve of 0.778, with a sensitivity of 77.5% and specificity of 65.5%. The model demonstrated good calibration (Hosmer-Lemeshow test, P = 0.376) and significant net benefit on decision curve analysis. Internal validation confirmed its reliability. Retinal vascular alterations correlated with indicators of portal hypertension and liver insufficiency.</p><p><strong>Conclusion: </strong>We developed a nomogram based on retinal vascular parameters to predict HBC, providing clinicians an intuitive, noninvasive diagnostic tool. The retinal microvascular alterations in HBC may reflect extrahepatic microcirculatory dysfunctions related to portal hypertension and liver insufficiency.</p>","PeriodicalId":11999,"journal":{"name":"European Journal of Gastroenterology & Hepatology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting causal relationships between inflammatory factors, plasma metabolites, and nonalcoholic fatty liver disease: a mediating Mendelian randomization study.","authors":"Dequan Zhong, Shizhan Deng, Yonggan Dong, Yanan Qian, Sudi Zhu, Mengxue Hu, Meng Liu, Kemeng Tan, Heng Tang","doi":"10.1097/MEG.0000000000003077","DOIUrl":"https://doi.org/10.1097/MEG.0000000000003077","url":null,"abstract":"<p><strong>Background: </strong>Nonalcoholic fatty liver disease (NAFLD), which affects approximately 25% of the global adult population, is a metabolic-associated hepatic disorder characterized by the interplay between inflammation and metabolism. Although evidence linking inflammatory factors and plasma metabolites to NAFLD progression, their causal relationships and mediating mechanisms remain unclear.</p><p><strong>Methods: </strong>This study employed a bidirectional Mendelian randomization (MR) approach combined with mediation analysis to investigate the causal relationships between inflammatory factors, plasma metabolites, and NAFLD. Summary data for 91 inflammatory factors and 1400 plasma metabolites were extracted from the genome-wide association studies databases and analyzed using MR. Mediation analysis was performed to examine whether the nine selected metabolites mediated the relationship between the eight inflammatory factors and NAFLD. All the analyses included tests for heterogeneity and pleiotropy.</p><p><strong>Results: </strong>This study identified 11 inflammatory factors and 110 plasma metabolites that were significantly associated with NAFLD. Mediation analysis revealed that specific metabolites, including pregnenetriol disulfate, alanine: asparagine ratio, and X-21471, mediate the relationship between inflammatory factors and NAFLD. Notably, X-21471 was identified as a shared mediator of both tumor necrosis factor receptor superfamily member 9 (TNFRSF9) and CCL20.</p><p><strong>Conclusion: </strong>This integrative MR mediation analysis delineates an inflammation-metabolism-NAFLD axis, in which specific metabolites (X-21471, pregnenetriol disulfate) transmit pro-inflammatory signals (TNFRSF9/CCL20) involved in NAFLD pathogenesis. These findings suggest that combined targeting of TNFRSF9 and X-21471 may represent a precise preventive strategy for high-risk populations with metabolic comorbidities.</p>","PeriodicalId":11999,"journal":{"name":"European Journal of Gastroenterology & Hepatology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histological disease progression in patients with metabolic dysfunction-associated steatotic liver disease using paired liver biopsy.","authors":"Dilara Turan Gokce, Merve Ekelik, Mesut Gumussoy, Saba Kiremitci, Emin Bodakci, Volkan Yilmaz, Tugce Guvenir, Serkan Duman, Zeynep Ellik, Mubin Ozercan, Erdem Er, Fatih Karakaya, Hale Sümer, Atilla Halil Elhan, Berna Savas, Ramazan Idilman","doi":"10.1097/MEG.0000000000003076","DOIUrl":"https://doi.org/10.1097/MEG.0000000000003076","url":null,"abstract":"<p><strong>Background and aims: </strong>The aims of the present study were to assess the histological evolution of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) using paired liver biopsies, identify the factors associated with fibrosis and clinical disease progression, and determine the relationship between histological progression and clinical outcomes.</p><p><strong>Methods: </strong>This was a single-center study. A total of 114 patients with MASLD who had at least two liver biopsies were included in the analysis.</p><p><strong>Results: </strong>From baseline to follow-up biopsy, 44% of patients showed histological progression. Fibrosis progressed in 28 patients, regressed in 21, and showed no change in 65. The proportion of metabolic dysfunction-associated steatohepatitis (MASH) increased from 83% to 90%, with 95% of MASH patients remaining MASH and 70% of MASL patients fulfilling MASH criteria at follow-up biopsy. Among MASL patients with progression, 87% had lobular inflammation at baseline. During the median follow-up of 10 years, half of the patients with MASLD showed clinical progression, with 73% having MASH at baseline. No new metabolic abnormality developed in patients with MASL who maintained MASL status at follow-up. Multivariable logistic regression analysis showed that baseline hypertension (Odds Ratio [OR]: 2.611, p = 0.024) and high serum ALT levels (OR: 2.815, p = 0.049) were predictors of clinical progression in patients with MASLD.</p><p><strong>Conclusions: </strong>Patients with MASLD, MASL, and MASH, exhibit disease progression. Hypertension and baseline abnormal liver injury test results are predictors of clinical disease progression in patients with MASLD.</p>","PeriodicalId":11999,"journal":{"name":"European Journal of Gastroenterology & Hepatology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative effectiveness and safety of second-line therapies and dosing regimens for advanced hepatocellular carcinoma: a network meta-analysis.","authors":"Xinming Lei, Kejie He, Yaqin Guo, Maoning Liu, Chengjiang Liu","doi":"10.1097/MEG.0000000000003070","DOIUrl":"https://doi.org/10.1097/MEG.0000000000003070","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated death globally. Second-line therapies are crucial for improving survival and quality of life among individuals suffering from advanced HCC who have not responded to first-line therapies. This study sought to evaluate the safety and efficacy of different second-line therapies for advanced HCC by network meta-analysis. A network meta-analysis was carried out on 26 randomized controlled trials comprising 10 368 people suffering from advanced HCC. The treatments evaluated included cabozantinib, pembrolizumab, brivanib, apatinib, and other targeted therapies. The principal results assessed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). The evaluation also encompassed adverse events (AEs) as well as those classified as grade 3-4 AEs. Cabozantinib 60 mg once daily (QD) demonstrated the most significant improvement in OS [mean difference (MD) = 3.36, 95% confidence interval (CI) = 2.01, 4.70] and PFS (MD = 3.26, 95% CI = 2.59, 3.94), ranking highest among the therapies evaluated. Brivanib 800 mg once daily (OD) was most effective in terms of ORR [odds ratio (OR) = 7.13, 95% CI = 1.42, 35.88], while apatinib 750 mg QD ranked highest for DCR (OR = 3.92, 95% CI = 1.76, 8.71). Codrituzumab 1600 mg administered every 2 weeks demonstrated the most advantageous health profile, markedly decreasing AEs and instances of grade 3-4 AEs. Pembrolizumab 200 mg administered every 3 weeks indicated good effectiveness. Alongside a tolerable safety profile, indicating its potential as a reasonable second-line treatment option. Cabozantinib 60 mg QD and pembrolizumab 200 mg Q3W arise as the most suitable second-line therapies alternatives for advanced HCC, offering substantial improvements in survival and disease control with manageable adverse effects. These findings support the integration of both targeted and immune therapies in handling of advanced HCC.</p>","PeriodicalId":11999,"journal":{"name":"European Journal of Gastroenterology & Hepatology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the molecular mechanism of Crohn's disease and rheumatoid arthritis: a bioinformatics and functional analysis approach.","authors":"Yunzheng Qin, Caiyu He, Ningxiang Zhong, Lin Guo, Zhongwei Yang, Jing Yu","doi":"10.1097/MEG.0000000000003068","DOIUrl":"https://doi.org/10.1097/MEG.0000000000003068","url":null,"abstract":"<p><strong>Background: </strong>Crohn's disease (CD) and rheumatoid arthritis (RA) are autoimmune diseases. CD is known to be closely associated with RA. However, the mechanisms underlying these relationships remain unclear. This study aimed to explore the common genetic features and potential molecular mechanisms of CD and RA.</p><p><strong>Methods: </strong>Microarray data of CD and RA in the Gene Expression Omnibus database were downloaded. Weighted gene coexpression network analysis (WGCNA) was used to identify the coexpression modules related to CD and RA. The shared genes existing in CD and RA were subjected to gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using R software. The results were validated by differentially expressed genes (DEGs) analysis to enrich for common differential genes and unique genes in CD and RA. Based on CD-RA common hub genes, we explored the feasibility of developing new gene-antibody coupled targeted drugs for the treatment of CD-RA.</p><p><strong>Results: </strong>Enrichment analysis of gene modules identified through WGCNA revealed disease pathway models suggesting potential mechanisms of RA secondary to CD. Furthermore, we identified key shared pathogenic genes between CD and RA, such as S100P and IL2RB that may be important targets for the treatment of both diseases.</p><p><strong>Conclusion: </strong>The study is the first to reveal the key pathways underlying the shared pathogenesis of CD and RA, identify novel candidate genes that could serve as biomarkers or potential therapeutic targets. Finally, we propose new ideas for the development of gene-antibody coupled targeted drugs.</p>","PeriodicalId":11999,"journal":{"name":"European Journal of Gastroenterology & Hepatology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and risk factors of metabolic dysfunction-associated steatotic liver disease in patients with inflammatory bowel disease.","authors":"Tarek A Tamimi, Noor Abu-Farsakh, Saif Aldeen AlRyalat, Kinan Obeidat, Saif Dalla Ali, Haya Hameed, Sarah Aldabbagh, Ahmad Quzli, Jehad F AlSamhori, Awni T Abu-Sneineh, Zeid J Khitan, Yaser M Rayyan","doi":"10.1097/MEG.0000000000003067","DOIUrl":"https://doi.org/10.1097/MEG.0000000000003067","url":null,"abstract":"<p><strong>Aim: </strong>The purpose of our study was to evaluate the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and its associated risk factors in patients with inflammatory bowel disease (IBD).</p><p><strong>Methods: </strong>This was a retrospective chart review of patients who underwent treatment for IBD at Jordan University Hospital between January 2013 and 2022. Case finding methods and clinical chart reviews were used to evaluate the clinical profile of patients with IBD. Demographic, anthropometric, and biochemical data; endoscopic severity scores; and imaging were obtained.</p><p><strong>Results: </strong>A total of 367 patients with IBD were included: 194 with Crohn's disease and 173 with ulcerative colitis. MASLD was diagnosed through imaging in 152 (41.4%) and compared with 215 (58.6%) patients without MASLD. Univariate analysis revealed several factors associated with MASLD in patients with IBD: age, number of relapses, longer IBD duration (all P < 0.001), severity of Crohn's disease based on the simple endoscopic score for Crohn's disease (P = 0.05), Crohn's disease penetrating behavior based on the Montreal classification (P < 0.001), increased triglyceride level (P = 0.002), and the presence of diabetes mellitus and hypertension (P < 0.001). In the binary logistic regression analysis, increased number of relapses [P < 0.001, oddsratio (OR) = 1.526], penetrating disease behavior (P < 0.001, OR = 3.304), and presence of hypertension (P = 0.027, OR = 6.728) were independent risk factors associated with an increased risk of MASLD, while shorter disease duration was associated with a decreased risk of MASLD (P = 0.008, OR = 0.849).</p><p><strong>Conclusion: </strong>A substantial proportion of patients with IBD experienced concurrent MASLD. Increased IBD duration and number of relapses, penetrating Crohn's disease behavior, and presence of hypertension were independent risk factors associated with MASLD.</p>","PeriodicalId":11999,"journal":{"name":"European Journal of Gastroenterology & Hepatology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colorectal cancer mortality among Asian Americans: a disaggregated analysis from 2018 to 2023.","authors":"Muhammad Ali Tariq, Aeman Asrar, Hamza Amin","doi":"10.1097/MEG.0000000000003026","DOIUrl":"10.1097/MEG.0000000000003026","url":null,"abstract":"","PeriodicalId":11999,"journal":{"name":"European Journal of Gastroenterology & Hepatology","volume":"37 9","pages":"1088-1090"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between diabetes duration and risk of pancreatic cancer: a meta-analysis of observational studies.","authors":"Xuefeng Hua, Rongdang Fu, Ziwei Yin, Hui Gong","doi":"10.1097/MEG.0000000000003041","DOIUrl":"https://doi.org/10.1097/MEG.0000000000003041","url":null,"abstract":"<p><strong>Background: </strong>Prior studies have implicated diabetes as a risk factor for pancreatic cancer, yet the impact of diabetes progression on pancreatic cancer incidence remains unclear. We aim to assess pancreatic cancer risk across different stages of diabetes.</p><p><strong>Methods: </strong>Employing a predefined search strategy, we conducted a literature review of electronic databases up to 29 February 2024. Extracting odds ratios (OR) and 95% confidence intervals (CIs) relevant to diabetes, we aimed to evaluate pancreatic cancer risk among diabetic patients and conduct subgroup analyses.</p><p><strong>Results: </strong>Our systematic review comprised 29 observational cohort studies with 25 million participants. We observed a 2.13-fold higher likelihood of pancreatic cancer among diabetic individuals compared with nondiabetic counterparts. Specifically, males with diabetes exhibited a greater pancreatic cancer risk than females; however, regional disparities in pancreatic cancer risk among diabetic patients were NS. Regarding diabetes duration, pooled ORs (95% CI) for pancreatic cancer risk were 2.41 (2.07-2.81) for 1-4 years, 1.67 (1.50-1.85) for 4-10 years, and 2.01 (1.81-2.22) for over 10 years.</p><p><strong>Conclusion: </strong>The results of this study confirm a significant association between diabetes and pancreatic cancer. Although there was no statistically significant difference in risk between different diabetes duration groups, diabetic patients overall face a higher risk of pancreatic cancer. Therefore, diabetic patients should undergo regular pancreatic cancer screening and take appropriate management measures to detect potential pancreatic cancer at an early stage.</p>","PeriodicalId":11999,"journal":{"name":"European Journal of Gastroenterology & Hepatology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of hepatic artery infusion chemotherapy conjunction with tyrosine kinase inhibitors and programmed death-1 inhibitors for unresectable/advanced hepatocellular carcinoma: a meta-analysis.","authors":"Yadi Xiao, Xiangbo Tao, Haitao Zhang, Xin Shi, Hongjian Zhao","doi":"10.1097/MEG.0000000000003012","DOIUrl":"10.1097/MEG.0000000000003012","url":null,"abstract":"<p><p>The safety and therapeutic efficiency of tyrosine kinase inhibitors (TKIs) and programmed death-1 (PD-1) inhibitors in combination with hepatic artery infusion chemotherapy (HAIC) for patients with unresectable/advanced hepatocellular carcinoma (HCC) require further investigation. This meta-analysis aimed to thoroughly investigate the safety and efficacy of this triple combination therapy based on currently available research. PubMed, Embase, Cochrane Library, Web of Science, VIP, Wan Fang, and China National Knowledge Infrastructure were searched. Outcomes included complete response (CR), partial response (PR), stable disease, overall survival, progression-free survival, and treatment/laboratory-related adverse events. Stata15.1 software was used for random/fixed-effect model analysis. Ten studies with 1108 patients were incorporated in the analysis. For efficacy, the triple combination therapy achieved an improved CR rate [relative risk (RR): 2.76, 95% confidence interval (CI): 1.43-5.33] and PR rate (RR: 1.70, 95% CI: 1.01-2.86) than the control group. Moreover, the triple combination therapy decreased the 44% risk of death [hazard ratio (HR): 0.56, 95% CI: 0.46-0.67] and 37% risk of disease progression (HR: 0.63, 95% CI: 0.53-0.75) compared with the control group. The triple combination therapy group and the control group did not exhibit a statistical difference in treatment- or laboratory-related adverse events. In the management of unresectable/advanced HCC, HAIC in conjunction with PD-1 inhibitors and TKI exhibits both safety and efficacy, providing a scientific basis for clinical practice.</p>","PeriodicalId":11999,"journal":{"name":"European Journal of Gastroenterology & Hepatology","volume":" ","pages":"993-1002"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paper Alert.","authors":"","doi":"10.1097/MEG.0000000000003054","DOIUrl":"https://doi.org/10.1097/MEG.0000000000003054","url":null,"abstract":"<p><p>A selection of interesting papers that were published in the month before our press date in major journals likely to report important results in gastroenterology and hepatology. Peter Hayes and John Plevris The Royal Infirmary, Edinburgh EH3 9YW, UK.</p>","PeriodicalId":11999,"journal":{"name":"European Journal of Gastroenterology & Hepatology","volume":"37 9","pages":"1092-1095"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}