Hepatology Research最新文献

{"title":"Biopsy After Ablation: Expanding the Frontier of Genomic Insight.","authors":"Takuma Nakatsuka, Hayato Nakagawa, Mitsuhiro Fujishiro, Ryosuke Tateishi","doi":"10.1111/hepr.70006","DOIUrl":"https://doi.org/10.1111/hepr.70006","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690057","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":"Dynamic Early Survival Prediction Model for Hepatocellular Carcinoma Patients Treated With Atezolizumab and Bevacizumab: A Longitudinal Deep Learning Analysis.","authors":"Weiming Li, Xiaoqian Xu, Hao Wang, Shun Li, Lichen Shi, Cheng Huang, Hong You, Jidong Jia, Youwen He, Yuanyuan Kong","doi":"10.1111/hepr.70005","DOIUrl":"https://doi.org/10.1111/hepr.70005","url":null,"abstract":"<p><strong>Background: </strong>Atezolizumab combined with bevacizumab has become the standard first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC). Although this regimen offers statistically significant and clinically meaningful benefits, accurately predicting overall survival (OS) remains a challenge. This study aims to identify potential biomarkers to improve early OS prediction in patients with uHCC treated with atezolizumab and bevacizumab.</p><p><strong>Methods: </strong>A longitudinal survival analysis was conducted using data from the GO30140 and IMbrave150 trials. Multiple deep learning architectures for dynamic survival prediction in HCC (DynSurv-HCC) were evaluated to assess their prognostic performance.</p><p><strong>Results: </strong>Of 415 patients with unresectable HCC, 291 and 124 were randomly assigned to training and validation sets in a 7:3 ratio. The DynSurv-HCC model with the random survival forest (RSF) method outperformed other deep learning approaches. In the training set, the DynSurv-HCC model achieved AUCs of 0.93 (95% CI: 0.89-0.97), 0.91 (95% CI: 0.87-0.94), and 0.91 (95% CI: 0.84-0.96) at 6, 12, and 24 months, respectively. In the validation set, the model achieved an AUC of 0.90 (95% CI: 0.82-0.98) at 6 months. Importantly, the DynSurv-HCC model demonstrated robust and consistent predictive accuracy across varying etiologies and baseline α-fetoprotein (AFP) levels.</p><p><strong>Conclusions: </strong>The DynSurv-HCC model with RSF demonstrated promising early OS prediction in patients with HCC receiving atezolizumab and bevacizumab, regardless of etiology or baseline AFP levels. Our findings underscore its clinical potential in guiding personalized treatment strategies and enhancing prognostic assessments for patients with uHCC.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698416","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":"Efficacy and Safety of Glecaprevir/Pibrentasvir in Children Aged 3-11 Years With Chronic Hepatitis C: A Real-World, Prospective, Multicenter Study in Japan.","authors":"Tatsuki Mizuochi, Daiki Abukawa, Ayano Inui, Yoshihiro Azuma, Takako Suzuki, Hiroko Yagi, Hideki Kumagai, Sotaro Mushiake, Daisuke Tokuhara, Naoya Tsumura, Ken Kato, Yasuhito Tanaka, Hitoshi Tajiri","doi":"10.1111/hepr.70004","DOIUrl":"https://doi.org/10.1111/hepr.70004","url":null,"abstract":"<p><strong>Aim: </strong>Part 2 of the DORA study, an international clinical trial evaluating glecaprevir and pibrentasvir (G/P) treatment in children aged 3-11 years with chronic hepatitis C virus (HCV) infection, demonstrated high efficacy and safety. However, there is limited evidence regarding real-world use of G/P in this pediatric population. This prospective multicenter study in Japan evaluated the real-world efficacy and safety of G/P treatment in children aged 3-11 years with chronic HCV.</p><p><strong>Methods: </strong>Children aged 3-11 years with chronic HCV were prospectively enrolled and received a once-daily dose of G/P for either 8 or 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after treatment completion (SVR12). Safety was assessed through adverse events, laboratory tests, and growth measurements.</p><p><strong>Results: </strong>A total of 18 children (8 girls) from 9 pediatric centers in Japan were enrolled, with a median age of 9 years (range, 3-11). Genotype distribution was as follows: 1b (n = 3), 2a (n = 8), 2b (n = 5), 3a (n = 1), and unknown of Serotype 2 (n = 1). All participants were treatment-naïve and completed G/P treatment (17 for 8 weeks, 1 for 12 weeks). SVR12 was achieved in 17 patients (94%). Most adverse events were mild, with no serious events. Treatment led to significant reductions in serum alanine aminotransferase and Wisteria floribunda agglutinin-positive Mac-2 binding protein levels. No impairments in growth were observed.</p><p><strong>Conclusions: </strong>In real-world clinical practice, G/P treatment demonstrated high efficacy and good tolerability in children aged 3-11 years with chronic HCV.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682464","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":"Development of Simplified Risk Assessment Scoring System for Sarcopenia in Patients With Chronic Liver Disease.","authors":"Atsushi Hiraoka, Hideko Ohama, Fujimasa Tada, Yuka Kimura, Ayaka Nakamura, Kazuya Murakawa, Takuya Matsuda, Kana Matsuoka, Kanako Kato, Kei Onishi, Hirofumi Izumoto, Shogo Kitahata, Kozue Kanemitsu-Okada, Tomoe Kawamua, Taira Kuroda, Hideki Miyata, Eiji Tsubouchi, Osamu Yoshida, Masashi Hirooka, Masanori Abe, Bunzo Matsuura, Tomoyuki Ninomiya, Sachiyo Yoshio, Yoichi Hiasa","doi":"10.1111/hepr.70002","DOIUrl":"https://doi.org/10.1111/hepr.70002","url":null,"abstract":"<p><strong>Background/aim: </strong>Secondary sarcopenia is frequently observed in patients with chronic liver disease (CLD), and simple and practical assessment tools in aging society are limited. This study aimed to develop a risk scoring system based on the geriatric nutritional risk index (GNRI) to identify muscle abnormalities in patients with CLD.</p><p><strong>Materials/methods: </strong>Retrospective analysis was carried out on 1181 Japanese patients with CLD (median age 70 years; male:female = 748:433 and Child-Pugh A:B:C = 1029:129:23). LC was noted in 684. Handgrip strength decline (HGSD) and muscle volume loss (MVL) were evaluated using cutoffs established by the Japan Society of Hepatology.</p><p><strong>Results: </strong>The proposed scoring system (SDGS-L) was developed using logistic analysis. Factors included abnormal GNRI (< 98) (odds ratio [OR] 4.69), elderly (65-74 years and OR 2.62), late-stage elderly (≥ 75 years and OR 6.34), and female gender (OR 2.16), with points assigned based on OR values: 1 point for OR ≦ 3 and 2 points for OR > 3. Sarcopenia/HGSD/MVL prevalence increased with risk scores: 2.3%/13.8%/7.4%, 8.3%/25.8%/19.7%, 21.2%/29.3%/19.2%, and 37.0%/28.6%/18.0% for low (score 0/1), moderate (score 2), high (score 3), and super-high (score 4/5) scores, respectively (p < 0.001). GNRI cutoffs for HGS decline and muscle volume loss were 101.5 (AUC 0.675) and 97.7 (AUC 0.742). Significant correlations of GNRI with HGS and skeletal muscle index (SMI) were observed in males (r = 0.365)/(r = 0.493) and females (r = 0.297)/(r = 0.462) (each p < 0.001).</p><p><strong>Conclusion: </strong>The SDGS-L scoring system provides a simple cost-effective tool for predicting sarcopenia and muscle abnormalities in patients with CLD, enabling early intervention without specialized equipment.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667535","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":"Lipolysis-Stimulated Lipoprotein Receptor Gene Variants as a Cause of Progressive Familial Intrahepatic Cholestasis: A Case Report.","authors":"Yugo Takaki, Shuichiro Umetsu, Yoshihiko Sugino, Takahiro Yamashita, Takehiko Doi, Kazuo Imagawa, Shogo Ito, Yutaro Mihara, Hisamitsu Hayashi, Ayano Inui","doi":"10.1111/hepr.70003","DOIUrl":"https://doi.org/10.1111/hepr.70003","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the genetic and molecular mechanisms underlying intrahepatic cholestasis associated with lipolysis-stimulated lipoprotein receptor (LSR) deficiency and to evaluate its potential role in conditions similar to progressive familial intrahepatic cholestasis (PFIC).</p><p><strong>Case presentation: </strong>We studied a 4-year-old girl with no significant perinatal history who presented with symptoms of cholestasis-pruritus, poor weight gain, and darkened skin-by 6 months of age. Laboratory tests revealed mild cholestasis with elevated total bile acids and normal gamma-glutamyl transferase (GGT). A liver biopsy revealed chronic cholestasis and mild fibrosis. Whole-exome sequencing identified two compound heterozygous variants in the LSR gene, and immunostaining confirmed reduced LSR expression in the liver. The patient showed persistent cholestasis, normal GGT, and a clinical presentation suggestive of PFIC. Genetic testing revealed LSR gene variants, including a likely pathogenic duplication, confirming LSR deficiency. Despite treatment with ursodeoxycholic acid (UDCA), her pruritus persisted and growth remained stunted. Developmental delays were primarily noted in language acquisition.</p><p><strong>Conclusions: </strong>This case suggests that LSR deficiency may contribute to a PFIC-like condition, thus broadening our understanding of the genetic causes of intrahepatic cholestasis. Children presenting with PFIC-like symptoms but without mutations in known PFIC genes should be evaluated for LSR deficiency. Further research is needed to elucidate LSR's role in liver function and its potential classification as a new PFIC subtype, \"PFIC-14.\"</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659045","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":"Cachexia and Type 2 Diabetes Mellitus Are Independent Factors for Mortality in Patients With Cirrhosis.","authors":"Takao Miwa, Goki Suda, Ryosuke Tateishi, Tatsunori Hanai, Masatsugu Ohara, Yasuhiro Hagiwara, Shinji Unome, Kazuya Okushin, Mina Nakagawa, Naoya Sakamoto, Masahito Shimizu","doi":"10.1111/hepr.70001","DOIUrl":"https://doi.org/10.1111/hepr.70001","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144617389","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":"The Impact of Inflammatory Markers on Prognosis in Advanced Chronic Liver Disease: Insights From a Prospective Cohort Study.","authors":"Jing Liu, Sumeng Li, Yanan Liu, Fengqin Zhou, Jun Wu, Xin Zheng","doi":"10.1111/hepr.14238","DOIUrl":"https://doi.org/10.1111/hepr.14238","url":null,"abstract":"<p><strong>Background: </strong>Limited research has explored the prognostic significance of the neutrophil-percentage-to-albumin ratio (NPAR), derived neutrophil-to-lymphocyte ratio (dNLR), and systemic immune-inflammation index (SII) in individuals with advanced chronic liver disease (ACLD). This study aimed to examine the association between these inflammatory markers and 90-day transplant-free mortality among patients with ACLD.</p><p><strong>Methods: </strong>We prospectively recruited hospitalized patients with ACLD from the tertiary teaching hospital. Cox regressions were used to determine the associations between NPAR, dNLR, SII, and mortality.</p><p><strong>Results: </strong>A total of 412 patients with ACLD were included in this study. The 90-day transplant-free mortality increased with higher levels of NPAR, dNLR, and SII. In multivariate analysis, higher NPAR, dNLR, and SII were independently associated with an increased risk of mortality in patients with ACLD after adjustment for confounders. After the adjustment for covariables, the risk of 90-day transplant-free mortality in ACLD patients increased by 66% and 18% for every unit increase in NPAR (OR: 1.66, 95% CI 1.09-2.53) and dNLR (OR: 1.18, 95% CI 1.01-1.38), respectively (p < 0.05). The patients with NPAR < 3.5 (OR: 3.65, 95% CI 1.30-10.27) and dNLR < 3.5 (OR: 2.40, 95% CI 1.19-4.86) had the highest risk. Subgroup analysis revealed that NPAR, dNLR, and SII demonstrated a strong correlation with 90-day transplant-free mortality in both acute decompensation and acute-on-chronic liver failure populations. Subsequent analysis showed a significant association between NPAR, dNLR, SII, and 90-day transplant-free mortality in patients presenting with ascites, infection, and gastrointestinal hemorrhage.</p><p><strong>Conclusions: </strong>Increased NPAR, dNLR, and SII were independently correlated with a higher risk of mortality in patients with ACLD.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144617390","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":"Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Increases in Patients With Obstructive Jaundice through the Activation of Hepatic Stellate Cells by Bile Acids.","authors":"Norihiro Ishii, Kenichiro Araki, Dolgormaa Gantumur, Ryosuke Fukushima, Takayuki Okuyama, Takaomi Seki, Haruka Okami, Kei Hagiwara, Kouki Hoshino, Shunsuke Kawai, Mariko Tsukagoshi, Takamichi Igarashi, Norio Kubo, Ken Shirabe","doi":"10.1111/hepr.14236","DOIUrl":"https://doi.org/10.1111/hepr.14236","url":null,"abstract":"<p><strong>Background: </strong>Mac-2 binding protein glycosylation isomer (M2BPGi) is a reliable serum marker for assessing liver fibrosis and is secreted by hepatic stellate cells (HSCs). However, M2BPGi is a known marker of dynamic fluctuations that reflects liver fibrosis, and factors including liver injury and hepatocyte regeneration. Obstructive jaundice (OJ) causes bile acid accumulation and subsequent liver injury. We aimed to evaluate the changes in M2BPGi levels in patients with OJ and elucidate whether HSC activation by bile acids increases M2BPGi levels.</p><p><strong>Methods: </strong>In total, 220 patients who underwent pancreatobiliary surgery were analyzed; the M2BPGi levels before and after biliary drainage were evaluated in 60 patients with OJ. Activation of HSCs (LX-2 cells) treated with bile acids (cholic acid, deoxycholic acid, and lithocholic acid) and the subsequent secretion of M2BPGi were evaluated by western blotting and coimmunoprecipitation.</p><p><strong>Results: </strong>M2BPGi levels were significantly higher in patients with OJ, strongly correlating with total bilirubin levels in laboratory data. Among the 60 patients with OJ, 51 showed decreased M2PBGi levels after biliary drainage; nine showed increased levels, even after biliary drainage. Cholangitis during biliary drainage was more common in patients with increased M2BPGi levels. Cholic acid-treated LX-2 cells upregulated α-SMA expression and M2BPGi secretion in culture media relative to non-treated LX-2 cell.</p><p><strong>Conclusions: </strong>M2BPGi levels are significantly higher in patients with than without OJ due to the activation of HSCs by bile acids. M2BPGi levels are improved by biliary drainage, and the presence of prolonged liver dysfunction, and inflammation (such as cholangitis) appears to induce prolonged M2BPGi elevation.</p><p><strong>Trial registration: </strong>HS2023-100.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583767","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":"Response to Letter to ''Circulating Myostatin Levels as a Prognostic Biomarker in Patients With Acute Liver Failure and Late-Onset Hepatic Failure''.","authors":"Manabu Hayashi, Kazumichi Abe, Hiromasa Ohira","doi":"10.1111/hepr.70000","DOIUrl":"https://doi.org/10.1111/hepr.70000","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575370","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":"Effect of Tirzepatide Treatment on Hepatic Biomarkers in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease and Type 2 Diabetes Mellitus.","authors":"Taeang Arai, Masanori Atsukawa, Chikako Nagao, Zento Yamada, Takahiro Rokugo, Kenta Suzuki, Michika Kitamura, Tetsuyuki Higashi, Kaori Koyano, Yuta Hasegawa, Tadamichi Kawano, Hiroki Ono, Yuji Yoshida, Tomomi Okubo, Korenobu Hayama, Ai Nakagawa-Iwashita, Norio Itokawa, Chisa Kondo, Mototsugu Nagao, Masato Iwabu, Katsuhiko Iwakiri","doi":"10.1111/hepr.14241","DOIUrl":"https://doi.org/10.1111/hepr.14241","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to clarify the impact of tirzepatide as a treatment for Type 2 diabetes mellitus (T2DM) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).</p><p><strong>Methods: </strong>This single-arm, prospective, observational pilot study included 16 patients with MASLD and T2DM who were treated with tirzepatide. Of these, 13 patients completed 48 weeks of treatment. Tirzepatide was initiated at a dose of 2.5 mg once weekly for 4 weeks, and dose adjustments were left to the discretion of the attending physician based on efficacy and adverse events.</p><p><strong>Results: </strong>Significant improvements in body weight, liver enzymes, and hemoglobin A1c were found at Week 12 and were sustained throughout the 48-week treatment period compared with baseline values (all p < 0.05). Controlled attenuation parameter significantly decreased from baseline to 48 weeks (p < 0.05). Changes in body weight were correlated with changes in alanine aminotransferase levels (r = 0.57, p < 0.05) but not with changes in controlled attenuation parameter (r = 0.45, p = 0.12). The results of noninvasive tests for fibrosis, including Type IV collagen 7s, Wisteria floribunda agglutinin-positive Mac-2-binding protein, the fibrosis-4 index, and the liver stiffness measurement, significantly decreased from baseline to 48 weeks (all p < 0.05). Most adverse events were transient Grades 1-2 gastrointestinal symptoms, including nausea (5 patients, 31.3%), diarrhea (3 patients, 18.8%), and constipation (2 patients, 12.5%).</p><p><strong>Conclusions: </strong>Tirzepatide treatment for T2DM in patients with MASLD significantly improved liver steatosis and injury, surrogate markers of liver fibrosis, and diabetes status, and reduced body weight.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567379","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}