Hepatology最新文献

{"title":"Palmitoylation-mediated exosomal trafficking of nuclear protein NAT10 potentiates liver fibrosis in MASH.","authors":"Yadi Wang, Liangliang Wu, Zhaozhi Li, Panfeng Huang, Yin Luo, Zhezhen Liao, Jiaoyang Li, Xiao Jiang, Jin Zhu, Shuyan Li, Li Ran, Fei Yang, Jianghua Liu, Yan Lu, Xinhua Xiao","doi":"10.1097/HEP.0000000000001785","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001785","url":null,"abstract":"<p><strong>Background aims: </strong>Liver fibrosis is the principal histological determinant of mortality in metabolic dysfunction-associated steatohepatitis (MASH), yet the mechanisms driving progression from steatosis to fibrosis remain incompletely defined and effective anti-fibrotic therapies are limited. Although hepatocyte-derived exosomes under lipotoxic stress promote hepatic stellate cell (HSC) activation, the pathogenic protein cargos remain undefined. This study sought to identify lipotoxicity-induced hepatocyte-derived exosomal proteins that drive MASH fibrogenesis and to define their mechanistic and therapeutic relevance.</p><p><strong>Approach results: </strong>Proteomic analysis of hepatocyte-derived exosomes from murine MASH livers and lipotoxic hepatocyte cultures identified N-acetyltransferase 10 (NAT10) as a stress-enriched exosomal cargo. ZDHHC23-mediated palmitoylation promoted NAT10 nuclear export and exosomal loading. Functional studies demonstrated that exosomal NAT10 drove fibrogenic signaling in HSCs by enhancing ac4C RNA acetylation and stabilizing Ddr2 mRNA. Hepatocyte-specific Nat10 deletion or administration of NAT10-deficient exosomes attenuated liver fibrosis, whereas hepatocyte Nat10 overexpression exacerbated fibrogenesis in an exosome-dependent manner. In human liver samples, increased NAT10 expression and elevated extranuclear-to-nuclear ratio correlated with fibrosis severity. Finally, hepatocyte-targeted GalNAc-siNat10 significantly ameliorated fibrosis in murine MASH models.</p><p><strong>Conclusions: </strong>This study links aberrant nuclear protein localization to subsequent exosome-mediated fibrogenic signaling in MASH and demonstrates that targeting this pathway, either by disrupting palmitoylation-dependent mislocalization or by hepatocyte-specific Nat10 inhibition, ameliorates liver fibrosis with concurrent metabolic benefit.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Buying time: Therapeutic plasma exchange as a bridge to transplant in acute-on-chronic liver failure.","authors":"Christina C Lindenmeyer","doi":"10.1097/HEP.0000000000001787","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001787","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing bevacizumab exposure in atezolizumab-based therapy for unresectable hepatocellular carcinoma: A nationwide real-world study.","authors":"Kaho Aoe, Toshifumi Tada, Atsushi Hiraoka, Tomomitsu Matono, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Takashi Nishimura, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Tanaka, Hidenori Toyoda, Chikara Ogawa, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Naganuma Atsushi, Hisashi Kosaka, Hidekatsu Kuroda, Yutaka Yata, Hiroki Nishikawa, Michitaka Imai, Tomoko Aoki, Hironori Ochi, Hideyuki Tamai, Shohei Komatsu, Takanori Matsuura, Yoshihide Ueda, Soo Ki Kim, Hideko Ohama, Fujimasa Tada, Shinichiro Nakamura, Yoshiko Nakamura, Osamu Yoshida, Kazuhiro Nouso, Asahiro Morishita, Norio Itokawa, Tomomi Okubo, Taeang Arai, Akemi Tsutsui, Takuya Nagano, Shinya Fukunishi, Kazunari Tanaka, Yuichi Koshiyama, Yuki Kanayama, Hidenao Noritake, Hirayuki Enomoto, Kosuke Matsui, Masaki Kaibori, Jumpei Okamura, Takumi Fukumoto, Yoichi Hiasa, Masatoshi Kudo, Takashi Kumada","doi":"10.1097/HEP.0000000000001781","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001781","url":null,"abstract":"<p><strong>Background aims: </strong>Atezolizumab plus bevacizumab (Atezo/Bev) is administered for unresectable hepatocellular carcinoma (HCC), with bevacizumab dosed by body weight, which may not adequately reflect body composition. This study evaluated the association between BSA-adjusted bevacizumab dosing, expressed as the bevacizumab-BSA index (BBI), and outcomes.</p><p><strong>Approach results: </strong>This retrospective study included 1,507 unresectable HCC patients treated with Atezo/Bev at 30 Japanese institutions. BBI was the ratio of actual to standard dose per BSA. Restricted cubic spline analyses identified the optimal BBI range. Outcomes were compared among BBI groups. Spline analysis revealed a nonlinear association between BBI and overall survival (OS), with an optimal BBI range of 106-121%. Accordingly, the patients were classified into Under (n=924), Target (n=522), and Over (n=61) groups. The median progression-free survival (PFS) was significantly longer in the Target group than in the non-Target group (10.3 vs. 6.5 months, p<0.001), and the median OS was prolonged (24.9 vs. 19.2 months, p=0.008). Multivariable analysis demonstrated that the Target BBI group was independently associated with improved PFS (hazard ratio [HR], 0.807; 95% confidence interval [CI], 0.715-0.910; p<0.001) and OS (HR, 0.850; 95% CI, 0.733-0.985; p=0.031). The objective response rate was significantly higher in the Target group (p=0.023), while treatment-related adverse event rates were comparable across the BBI groups, with no significant differences in proteinuria, hypertension, or other toxicities.</p><p><strong>Conclusions: </strong>BSA-adjusted bevacizumab dosing was associated with improved efficacy without increased toxicity in patients with unresectable HCC treated with Atezo/Bev.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the interaction between metabolic dysfunction and alcohol-associated hepatitis: A global study.","authors":"Vania Cari, María Ignacia Perez, Ignacio Tellez, Francisco Idalsoaga, Arun Valsan, Gowripriya Nair, Kriti Soni, S Fisher Rhoads, Jorge Arnold, Maria Ayala-Valverde, Carolina Ramirez-Cadiz, Prasun K Jalal, Mohamad Ali Ibrahim, Mohamed A Elfeki, Juan Pablo Roblero, Daniela Simian, Jose Antonio Velarde-Ruiz Velasco, Jacqueline Cordova, Fátima Higuera-de-la-Tijera, Rita Silva, Cristina Melo Rocha, Roberta C Araujo, Guilherme Massote Fontani, Gustavo Henrique Pereira, Fernando Bessone, Mario Tanno, Ayelen Kisch, Manuel Mendizabal, Sebastian Marciano, Gonzalo Gomez-Perdiguero, Pedro Montes, Patricia Guerra Salazar, Geraldine Ramos, Kristina R Chacko, Lubomir Skladaný, Rakhi Maiwall, Douglas Simonetto, Arun J Sanyal, Vijay H Shah, Ashwani K Singal, Winston Dunn, Patrick S Kamath, Rohit Loomba, Marco Arrese, Ramon Bataller, Luis Antonio Díaz, Juan Pablo Arab","doi":"10.1097/HEP.0000000000001780","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001780","url":null,"abstract":"<p><strong>Introduction: </strong>Although the role of cardiometabolic risk factors (CMRF) has been characterized in steatotic liver disease, their role in the severity of alcohol-associated hepatitis (AH) remains unclear. We aimed to evaluate the impact of CMRF on mortality.</p><p><strong>Methods: </strong>Multinational prospective cohort study (2015-2024) including hospitalized patients with severe AH across 32 centers in 14 countries. Diagnosis of AH was made using the NIAAA criteria. Analyses included adjusted competing-risk models by age, sex, ethnicity, history of cirrhosis, CMRF, corticosteroid use, MELD, and ACLF grade, with liver transplantation as a competing risk.</p><p><strong>Results: </strong>936 participants were included; mean age 48±11.2 years, and 88.9% were male. At least one CMRF was present in 46.6%; median body mass index (BMI) was 24.2 kg/m2 [IQR: 22.8-28.2], prevalence of diabetes 17.6%, hypertension 16.5%, and dyslipidemia 5.8%. Median MELD was 24.4 [19.3-31.4], 86.7% had severe AH, and 180-day survival was 72.9%. Survival did not differ by CMRF status (log-rank p=0.453). In adjusted competing-risk models, higher age (sHR 1.02; 95%CI:1.01-1.04), greater alcohol intake (per g/day; sHR 1.001; 95%CI:1.000-1.002), MELD (sHR 1.04; 95%CI:1.01-1.06), and ACLF grade 2-3 (sHR 2.34 and 4.34) predicted mortality. However, no individual CMRF independently increased mortality. A prespecified non-linear BMI analysis showed modestly lower mortality between 25-40 kg/m², with a higher risk above 40 kg/m².</p><p><strong>Conclusion: </strong>Among patients with severe AH, metabolic dysfunction was not associated with increased mortality. Although a higher BMI was associated with slightly lower mortality in AH, this may reflect better nutritional status rather than a true protective effect.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 belapectin for the prevention of esophageal varices in patients with MASH cirrhosis: The randomized, placebo-controlled NAVIGATE trial.","authors":"Naga Chalasani, Raj Vuppalanchi, Mazen Noureddin, Mitchell L Shiffman, Eric Lawitz, Edward Mena, Nadege T Gunn, Laura Ladron de Guevara, Hesham Elgouhari, Rifaat Safadi, Khurram Jamil, Stephen A Harrison, Naim Alkhouri","doi":"10.1097/HEP.0000000000001774","DOIUrl":"10.1097/HEP.0000000000001774","url":null,"abstract":"<p><strong>Background and aims: </strong>Belapectin reduced variceal development in a subgroup of patients with MASH cirrhosis. We report the efficacy and safety of belapectin in patients with MASH cirrhosis and portal hypertension without varices at baseline.</p><p><strong>Approach and results: </strong>NAVIGATE was a global Phase 2b trial. Patients were randomized to intravenous (IV) belapectin 2 or 4 mg/kg lean body weight or placebo for 18 months stratified by type 2 diabetes. The primary endpoint was the incidence of varices with esophagogastroduodenoscopy (EGD) or a composite endpoint (new varices, intercurrent events or discontinuation) at 18 months with belapectin versus placebo in the Full Analysis Set (FAS). In a pre-specified analysis, new varices were evaluated in all patients who underwent EGD at baseline and 18 months. Per Protocol population was patients treated for 18 months with EGD at 18 months. Of 357 randomized patients, 291 completed treatment. Baseline characteristics were comparable across cohorts. In the FAS, 17.8% with placebo versus 10.1% with belapectin 2 mg/kg developed varices, a 43.2% reduction ( p =0.13). In the per-protocol population (PP), varices occurred in 22.3% with placebo versus 11.3% with belapectin 2 mg/kg, a 50% reduction (unadjusted p =0.04). Belapectin 4 mg/kg had no significant effect on variceal development. For the composite endpoint at 18 months, no significant difference was observed between belapectin 2 mg/kg ( p =0.14) or 4 mg/kg ( p =0.261) and placebo in the FAS. Belapectin was well tolerated with no safety signals.</p><p><strong>Conclusion: </strong>Belapectin 2 mg/kg lowered development of new varices in MASH cirrhosis and portal hypertension.</p><p><strong>Registered at clinicaltrialsgov: </strong>NCT04365868.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: The treatment options for de novo perihilar cholangiocarcinoma require more details.","authors":"Yawen Dong, Zhihao Li, Gregory J Gores, Julie K Heimbach, Rory L Smoot, Timucin Taner, Patrick P Starlinger","doi":"10.1097/HEP.0000000000001497","DOIUrl":"10.1097/HEP.0000000000001497","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E139-E140"},"PeriodicalIF":15.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BMN 349, a small molecule inhibitor of Z alpha-1 antitrypsin polymerization, increases secretion and reduces intrahepatic inclusions in a mouse model of disease.","authors":"Britta Handyside, Heather Wenzel, Donald Mackenzie, Catherine Chang, Annie Greenslade, Jeremy Van Vleet, Brian Heglar, Joseph C Chen, Lening Zhang, Kevin Larimore, Huiyu Zhou, Iva Trantcheva, Lawrence Sims, Kristin Evans, Sylvia Fong, Gyanendra Kumar, Kavya Annu, Riccardo Ronzoni, James A Irving, Bing Wang, Stuart Bunting, David A Lomas","doi":"10.1097/HEP.0000000000001778","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001778","url":null,"abstract":"<p><strong>Background and aims: </strong>Alpha-1 antitrypsin (AAT), encoded by the SERPINA1 gene, is primarily synthesized in the liver and secreted into the blood. The SERPINA1 Z allele encodes Z-AAT (Glu342Lys), a variant that self-associates into polymers that are retained in hepatocytes and trigger inflammation and hepatic injury. Targeting and preventing Z-AAT polymerization allows a therapy to directly address the pathophysiology of AAT deficiency (AATD) associated liver disease.</p><p><strong>Approach and results: </strong>A structure-based design approach was used to develop BMN 349, a small molecule polymerization blocker capable of stabilizing Z-AAT to prevent new polymerization and promote hepatic clearance. BMN 349 bound Z-AAT ~150 times faster in vitro than wild-type M-AAT and promoted secretion and reduced polymer levels in a cell model of Z-AAT deficiency. Crystallography with M-AAT showed that BMN 349 partially displaces a region involved in polymerization, the reactive center loop proximal hinge. Oral dosing in female PiZ transgenic mice with 20-200 mg/kg/day BMN 349 for 30 days was associated with dose-dependent increases in total plasma Z-AAT and concurrent decrease in circulating and liver Z-AAT polymers relative to vehicle-treated controls. Histopathologic and proteomic assessments of liver and plasma samples from these mice showed doses ≥100 mg/kg/day of BMN 349 reduced liver inflammation and improved liver health biomarkers after 30 days.</p><p><strong>Conclusions: </strong>This study is the first to demonstrate a reduction in Z-AAT polymer burden without altering protein expression. Improvements in liver inflammation and function following BMN 349 treatment support further investigations of its therapeutic benefits for AATD liver disease.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Burden of fatty liver and hepatic fibrosis in persons with HIV: A diverse cross-sectional US multicenter study.","authors":"Samer Gawrieh, Jordan E Lake, Paula Debroy, Julia A Sjoquist, Montreca Robison, Mark Tann, Fatih Akisik, Surya S Bhamidipalli, Chandan K Saha, Kimon Zachary, Gregory K Robbins, Samir K Gupta, Raymond T Chung, Naga Chalasani, Kathleen E Corey","doi":"10.1097/HEP.0000000000001717","DOIUrl":"10.1097/HEP.0000000000001717","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E160-E161"},"PeriodicalIF":15.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A narrative review of lifestyle management guidelines for metabolic dysfunction-associated steatotic liver disease.","authors":"Dana Ivancovsky Wajcman, Christopher J Byrne, John F Dillon, Paul N Brennan, Marcela Villota-Rivas, Zobair M Younossi, Alina M Allen, Javier Crespo, Lynn H Gerber, Jeffrey V Lazarus","doi":"10.1097/HEP.0000000000001058","DOIUrl":"10.1097/HEP.0000000000001058","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic dysfunction-associated steatotic liver disease management guidelines have been published worldwide; we aimed to summarize, categorize, and compare their lifestyle intervention recommendations.</p><p><strong>Approach and results: </strong>We searched metabolic dysfunction-associated steatotic liver disease/NAFLD management guidelines published between January 1, 2013, and June 31, 2024, through databases including PubMed/MEDLINE, Cochrane, and CINAHL. In total, 35 qualifying guidelines were included in the final analysis. Guideline recommendations were categorized into 5 domains (ie, weight reduction goals, physical activity, nutrition, alcohol, and tobacco smoking) and were ranked based on how frequently they appeared. A recommendation was defined as widely adopted if recommended in ≥24 (≥66.6%) of the guidelines. These included increasing physical activity; reducing body weight by 7%-10% to improve steatohepatitis and/or fibrosis; restricting caloric intake; undertaking 150-300 or 75-150 minutes/week of moderate or vigorous-intensity physical activity, respectively; and decreasing consumption of commercially produced fructose. The least mentioned topics, in ≤9 of the guidelines, evaluated environmental determinants of health, mental health, referring patients for psychological or cognitive behavioral therapy, using digital health interventions, and assessing patients' social determinants of health.</p><p><strong>Conclusions: </strong>Most guidelines recommend weight reduction through physical activity and improving nutrition, as these have proven positive effects on health outcomes when sustained. However, gaps regarding mental health and the social and environmental determinants of metabolic dysfunction-associated steatotic liver disease were found. To optimize behavioral modifications and treatment, we recommend carrying out studies that will provide further evidence on social support, environmental factors, and mental health, as well as further exploring digital health interventions.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1303-1325"},"PeriodicalIF":15.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor: The treatment options for de novo perihilar cholangiocarcinoma require more details.","authors":"Qin Zeng, Danna Xie, Qiao Zhou, Baolin Qian","doi":"10.1097/HEP.0000000000001496","DOIUrl":"10.1097/HEP.0000000000001496","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E137-E138"},"PeriodicalIF":15.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}