World Journal of Gastroenterology最新文献

{"title":"Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease","authors":"Aritoshi Koizumi, K. Kaji, Norihisa Nishimura, Shohei Asada, Takuya Matsuda, Misako Tanaka, Nobuyuki Yorioka, Y. Tsuji, Koh Kitagawa, Shinya Sato, T. Namisaki, Takemi Akahane, Hitoshi Yoshiji","doi":"10.3748/wjg.v30.i28.3428","DOIUrl":"https://doi.org/10.3748/wjg.v30.i28.3428","url":null,"abstract":"BACKGROUND\u0000 Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality, but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis. Peroxisome proliferator activated receptor (PPAR) α and δ play a key role in lipid metabolism and intestinal barrier homeostasis, which are major contributors to the pathological progression of ALD. Meanwhile, elafibranor (EFN), which is a dual PPARα and PPARδ agonist, has reached a phase III clinical trial for the treatment of metabolic dysfunction-associated steatotic liver disease and primary biliary cholangitis. However, the benefits of EFN for ALD treatment is unknown.\u0000 AIM\u0000 To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.\u0000 METHODS\u0000 ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol (EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly (1 mL/kg) for 8 weeks. EFN (3 and 10 mg/kg/day) was orally administered during the experimental period. Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis, fibrosis, and intestinal barrier integrity. The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.\u0000 RESULTS\u0000 The hepatic steatosis, apoptosis, and fibrosis in the ALD mice model were significantly attenuated by EFN treatment. EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells, primarily through PPARα activation. Moreover, EFN inhibited the Kupffer cell-mediated inflammatory response, with blunted hepatic exposure to lipopolysaccharide (LPS) and toll like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling. EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses. The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.\u0000 CONCLUSION\u0000 EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis, enhancing hepatocyte autophagic and antioxidant capacities, and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring non-invasive diagnostics for metabolic dysfunction-associated fatty liver disease","authors":"Biao Qu, Zheng Li","doi":"10.3748/wjg.v30.i28.3447","DOIUrl":"https://doi.org/10.3748/wjg.v30.i28.3447","url":null,"abstract":"The population with metabolic dysfunction-associated fatty liver disease (MAFLD) is increasingly common worldwide. Identification of people at risk of progression to advanced stages is necessary to timely offer interventions and appropriate care. Liver biopsy is currently considered the gold standard for the diagnosis and staging of MAFLD, but it has associated risks and limitations. This has spurred the exploration of non-invasive diagnostics for MAFLD, especially for steatohepatitis and fibrosis. These non-invasive approaches mostly include biomarkers and algorithms derived from anthropometric measurements, serum tests, imaging or stool metagenome profiling. However, they still need rigorous and widespread clinical validation for the diagnostic performance.","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tata-box-binding protein-associated factor 15 as a new potential marker in gastrointestinal tumors","authors":"G. Elpek","doi":"10.3748/wjg.v30.i28.3367","DOIUrl":"https://doi.org/10.3748/wjg.v30.i28.3367","url":null,"abstract":"In this editorial, the roles of tata-box-binding protein-associated factor 15 (TAF15) in oncogenesis, tumor behavior, and as a therapeutic target in cancers in the context of gastrointestinal (GI) tumors are discussed concerning the publication by Guo et al . TAF15 is a member of the FET protein family with a comprehensive range of cellular processes. Besides, evidence has shown that TAF15 is involved in many diseases, including cancers. TAF15 contributes to carcinogenesis and tumor behavior in many tumors. Besides, its relationship with the mitogen-activated protein kinases (MAPK) signaling pathway makes TAF15 a new target for therapy. Although, the fact that there is few studies investigating the expression of TAF15 constitutes a potential limitation in GI system, the association of TAF15 expression with aggressive tumor behavior and, similar to other organ tumors, the influence of TAF15 on the MAPK signaling pathway emphasize that this protein could serve as a new molecular biomarker to predict tumor behavior and target therapeutic intervention in GI cancers. In conclusion, more studies should be performed to better understand the prognostic and therapeutic role of TAF15 in GI tumors, especially in tumors resistant to therapy.","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-dimensional visualization technology for guiding one-step percutaneous transhepatic cholangioscopic lithotripsy for the treatment of complex hepatolithiasis","authors":"Y. Ye, Ya-Wen Cao, Rong-Qi Li, E. Li, Lei Yan, Zhao-Wei Ding, J. Fan, Ping Wang, Yi-Xiang Wu","doi":"10.3748/wjg.v30.i28.3393","DOIUrl":"https://doi.org/10.3748/wjg.v30.i28.3393","url":null,"abstract":"BACKGROUND\u0000 Biliary stone disease is a highly prevalent condition and a leading cause of hospitalization worldwide. Hepatolithiasis with associated strictures has high residual and recurrence rates after traditional multisession percutaneous transhepatic cholangioscopic lithotripsy (PTCSL).\u0000 AIM\u0000 To study one-step PTCSL using the percutaneous transhepatic one-step biliary fistulation (PTOBF) technique guided by three-dimensional (3D) visualization.\u0000 METHODS\u0000 This was a retrospective, single-center study analyzing, 140 patients who, between October 2016 and October 2023, underwent one-step PTCSL for hepatolithiasis. The patients were divided into two groups: The 3D-PTOBF group and the PTOBF group. Stone clearance on choledochoscopy, complications, and long-term clearance and recurrence rates were assessed.\u0000 RESULTS\u0000 Age, total bilirubin, direct bilirubin, Child-Pugh class, and stone location were similar between the 2 groups, but there was a significant difference in bile duct strictures, with biliary strictures more common in the 3D-PTOBF group (P = 0.001). The median follow-up time was 55.0 (55.0, 512.0) days. The immediate stone clearance ratio (88.6% vs 27.1%, P = 0.000) and stricture resolution ratio (97.1% vs 78.6%, P = 0.001) in the 3D-PTOBF group were significantly greater than those in the PTOBF group. Postoperative complication (8.6% vs 41.4%, P = 0.000) and stone recurrence rates (7.1% vs 38.6%, P = 0.000) were significantly lower in the 3D-PTOBF group.\u0000 CONCLUSION\u0000 Three-dimensional visualization helps make one-step PTCSL a safe, effective, and promising treatment for patients with complicated primary hepatolithiasis. The perioperative and long-term outcomes are satisfactory for patients with complicated primary hepatolithiasis. This minimally invasive method has the potential to be used as a substitute for hepatobiliary surgery.","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of colorectal cancer screening strategies: New insights","authors":"Magie Tamraz, Najib Al Ghossaini, Sally Temraz","doi":"10.3748/wjg.v30.i28.3361","DOIUrl":"https://doi.org/10.3748/wjg.v30.i28.3361","url":null,"abstract":"In this editorial, we discuss the article by Agatsuma et al . We concentrate specifically on the current routinely used screening tests recommended by society guidelines and delve into the significance of early diagnosis of colorectal cancer (CRC) and its substantial impact on both incidence and mortality rates. Screening is highly recommended, and an early diagnosis stands out as the most crucial predictor of survival for CRC patients. Therefore, it is essential to identify and address the barriers hindering adherence to screening measures, as these barriers can vary among different populations. Furthermore, we focus on screening strategy optimization by selecting high-risk groups. Patients with comorbidities who regularly visit hospitals have been diagnosed at an early stage, showing no significant difference compared to patients undergoing regular screening. This finding highlights the importance of extending screening measures to include patients with comorbidities who do not routinely visit the hospital.","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GATIS score for predicting the prognosis of rectal neuroendocrine neoplasms: A Chinese multicenter study of 12-year experience","authors":"Xin-Yu Zeng, Ming Zhong, Guo-Le Lin, Cheng-Guo Li, Wei-Zhong Jiang, Wei Zhang, Li-Jian Xia, Maojun Di, Hongxue Wu, Xiaofeng Liao, Yueming Sun, Minhao Yu, Kai-Xiong Tao, Yong Li, Rui Zhang, Peng Zhang","doi":"10.3748/wjg.v30.i28.3403","DOIUrl":"https://doi.org/10.3748/wjg.v30.i28.3403","url":null,"abstract":"BACKGROUND\u0000 There is currently a shortage of accurate, efficient, and precise predictive instruments for rectal neuroendocrine neoplasms (NENs).\u0000 AIM\u0000 To develop a predictive model for individuals with rectal NENs (R-NENs) using data from a large cohort.\u0000 METHODS\u0000 Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China. Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival, and two nomograms were constructed.\u0000 RESULTS\u0000 A total of 1408 patients with R-NENs were included. Tumor grade, T stage, tumor size, age, and a prognostic nutritional index were important risk factors for prognosis. The GATIS score was calculated based on these five indicators. For overall survival prediction, the respective C-indexes in the training set were 0.915 (95% confidence interval: 0.866-0.964) for overall survival prediction and 0.908 (95% confidence interval: 0.872-0.944) for progression-free survival prediction. According to decision curve analysis, net benefit of the GATIS score was higher than that of a single factor. The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods.\u0000 CONCLUSION\u0000 The GATIS score had a good predictive effect on the prognosis of patients with R-NENs, with efficacy superior to that of the World Health Organization grade and TNM stage.","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of neoadjuvant multimodal therapy in the setting of locally advanced hepatocellular carcinoma","authors":"Daniele Ferraro, Federica Falaschi, Luca Nazzaro, Giovanni Vennarecci","doi":"10.3748/wjg.v30.i28.3452","DOIUrl":"https://doi.org/10.3748/wjg.v30.i28.3452","url":null,"abstract":"Immunotherapy and the implementation of more aggressive treatment schemes for locally advanced hepatocellular carcinomas have expanded the boundaries of curative options. Because of these advancements, patients who were once considered beyond the aim of a cure are now eligible for liver transplantation and resection.","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perianal disease in inflammatory bowel disease: Broadening treatment and surveillance strategies for anal cancer","authors":"Tatiana Pacheco, Sara Monteiro, Luísa Barros, Jorge Silva","doi":"10.3748/wjg.v30.i28.3373","DOIUrl":"https://doi.org/10.3748/wjg.v30.i28.3373","url":null,"abstract":"The perianal disease affects up to one-third of individuals with Crohn's disease (CD), causing disabling symptoms and significant impairment in quality of life, particularly for those with perianal fistulising CD (PFCD). The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing. Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents, endoscopic procedures and surgical techniques that show promising results. Among these, mesenchymal stem cells injection is a particularly hopeful therapy. In addition to the burden of fistulas, individuals with perianal CD may face an increased risk of developing anal cancer. This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes. Currently, there is no established formal anal screening programme. In this review, we provide an overview of the current state of the art in managing PFCD, including novel medical, endoscopic and surgical approaches. The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD, intending to propose a risk-based surveillance algorithm. The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positive health: An integrated quantitative approach in patients with chronic gastrointestinal and hepato-pancreatico-biliary disorders","authors":"Anja H W M Lemlijn-Slenter, Karolina AP Wijnands, Gijs van der Hamsvoort, L. P. V. Iperen, Nico Wolter, Angelique E de Rijk, Ad AM Masclee","doi":"10.3748/wjg.v30.i28.3418","DOIUrl":"https://doi.org/10.3748/wjg.v30.i28.3418","url":null,"abstract":"BACKGROUND\u0000 The concept of positive health (PH) supports an integrated approach for patients by taking into account six dimensions of health. This approach is especially relevant for patients with chronic disorders. Chronic gastrointestinal and hepato-pancreatico-biliary (GI-HPB) disorders are among the top-6 of the most prevalent chronically affected organ systems. The impact of chronic GI-HPB disorders on individuals may be disproportionally high because: (1) The affected organ system frequently contributes to a malnourished state; and (2) persons with chronic GI-HPB disorders are often younger than persons with chronic diseases in other organ systems.\u0000 AIM\u0000 To describe and quantify the dimensions of PH in patients with chronic GI-HPB disorders.\u0000 METHODS\u0000 Prospective, observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GI-HPB disorder attending the Outpatient Department of the Maastricht University Medical Center. Validated questionnaires and data from patient files were used to quantify the six dimensions of PH. Internal consistency was tested with McDonald’s Omega. Zero-order Pearson correlations and t -tests were used to assess associations and differences. A P value < 0.05 was considered significant.\u0000 RESULTS\u0000 The GI-HPB patients scored significantly worse in all dimensions of PH compared to control data or norm scores from the general population. Regarding quality of life, participation and daily functioning, GI-HPB patients scored in the same range as patients with chronic disorders in other organ systems, but depressive symptoms (in 35%) and malnutrition (in 45%) were more frequent in patients with chronic GI-HPB disorders. Intercorrelation scores between the six dimensions were only very weak to weak, forcing us to quantify each domain separately.\u0000 CONCLUSION\u0000 All six dimensions of PH are impaired in the GI-HPB patients. Malnutrition and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population: A prospective, multicenter, randomized, two-stage study","authors":"Xue-Ping Huang, Yi-Juan Liu, Shao-Wei Lin, Yan-Feng Shao, Feng Qiu, Qing-Wu Qiu, Zhangkun Xu, Jin-Xian Chen, Lianghuo Chen, Zhenqun Lin, Wen-Hua Dai, Ming-Qing Zhang, Qi Jiang, Zhongqin Xiao, Xian-Xing Cheng, Xiangyan Zhang, Wen-Bin You, Wei Chen, Long-Qin Li, Weixing Lin, Yong-Fu Wang, Fu-Jin Lai, Longqun Chen, Zhong-Hua Huang, Wen-Qi Zheng, Jin-Qi Wei, Zhi-Hui Lin","doi":"10.3748/wjg.v30.i27.3304","DOIUrl":"https://doi.org/10.3748/wjg.v30.i27.3304","url":null,"abstract":"BACKGROUND\u0000 The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori ) is controversial.\u0000 AIM\u0000 To evaluate the efficacy of VAT in the Chinese population.\u0000 METHODS\u0000 This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori -infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778.\u0000 RESULTS\u0000 In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001).\u0000 CONCLUSION\u0000 VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori -infected patients in Fujian.","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141818094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}