Hepatology Communications最新文献

{"title":"Parental liver disease mortality is associated with unfavorable outcomes in patients with alcohol-associated hepatitis.","authors":"Wanzhu Tu, Samer Gawrieh, Lauren Nephew, Craig McClain, Qing Tang, Srinivasan Dasarathy, Vatsalya Vatsalya, Douglas A Simonetto, Carla Kettler, Gyongyi Szabo, Bruce Barton, Yunpeng Yu, Patrick S Kamath, Arun J Sanyal, Laura Nagy, Mack C Mitchell, Suthat Liangpunsakul, Vijay H Shah, Naga Chalasani, Ramon Bataller","doi":"10.1097/HC9.0000000000000666","DOIUrl":"10.1097/HC9.0000000000000666","url":null,"abstract":"<p><strong>Background: </strong>How parental alcohol use disorder and liver disease-related mortality influence the risk and the outcomes of alcohol-associated hepatitis (AH) in the offspring is unknown.</p><p><strong>Methods: </strong>We analyzed data from 2 prospective observational studies of AH cases and heavy drinking controls (HDCs). Family history of parental alcohol use disorder and liver disease mortality was assessed at the study entry. Logistic regression and Cox proportional hazard models were used to assess the influences of family history on AH development and outcome.</p><p><strong>Results: </strong>Data from 1356 participants in two prospective cohorts (926 AH cases and 430 HDC) were combined and analyzed. Parental alcohol use disorder was found in 56.9% of AH cases and 61.1% of HDC; parental death due to liver disease was reported in 7.5% of AH cases and 5.7% of HDC. Multivariable logistic regression showed that parental liver disease-related mortality was associated with more than a doubled risk of AH development in the offspring after controlling for their demographic characteristics and drinking behavior (OR=2.26, 95% CI: [1.22, 4.20]). Moreover, among the AH cases, having a parent die of liver disease significantly increased the 90-day mortality of study participants after adjusting for the effects of other risk factors (HR=2.26, 95% CI: [1.05, 4.86]).</p><p><strong>Conclusions: </strong>The study highlights the influences of parental death due to liver disease on AH development and mortality. Identifying patients at risk of AH through family history might help facilitate discussions on reducing alcohol consumption.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Critical commentary on the study comparing TIPS, tunneled peritoneal catheter, and ascites pump in refractory ascites.","authors":"Sarah L Schütte, Benjamin Maasoumy, Tammo L Tergast","doi":"10.1097/HC9.0000000000000726","DOIUrl":"10.1097/HC9.0000000000000726","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholangiocarcinoma cells direct fatty acids to support membrane synthesis and modulate macrophage phenotype.","authors":"Michele Dei Cas, Stefania Mantovani, Barbara Oliviero, Aida Zulueta, Linda Montavoci, Monica Falleni, Delfina Tosi, Camillo Morano, Sara Penati, Annalisa Chiocchetti, Riccardo Sinella, Camilla Barbero Mazzucca, Matteo Donadon, Cristiana Soldani, Gaetano Piccolo, Matteo Barabino, Paolo Pietro Bianchi, Marcello Maestri, Ana Lleo, Jesus M Banales, Mario U Mondelli, Anna Caretti","doi":"10.1097/HC9.0000000000000717","DOIUrl":"10.1097/HC9.0000000000000717","url":null,"abstract":"<p><strong>Background and aims: </strong>Cholangiocarcinoma (CCA) is a globally rare, increasingly incident cancer. Metabolic reprogramming is common in cancer cells, and altered lipid homeostasis favors tumor development and progression. Previous studies have described lipid deregulation in HCC cells, while in CCA, the lipidome profile is still poorly characterized.</p><p><strong>Methods: </strong>We used liquid chromatography-tandem mass spectrometry to examine the lipid level profile of intrahepatic CCA (iCCA) and non-tumor surrounding tissue from patients, as well as in patients' and healthy controls' sera.</p><p><strong>Results: </strong>All lipid classes were upregulated in tumor specimens and iCCA-derived sera. Newly synthesized fatty acids (FAs) accumulated in iCCA and were only marginally directed to mitochondrial β-oxidation and scarcely folded in lipid droplets as neutral species. Metabolic flux assay showed that FAs were instead redirected toward plasma membrane formation and remodeling, being incorporated into phospholipids and sphingomyelin. A distinct lipid droplet and macrophage distribution was revealed by immunohistochemistry and Imaging Mass Cytometry. Lipid droplets were fewer in iCCA than in normal tissue and present mainly in the intratumoral fibrous septa and in M2 macrophages. Monocytes modified their lipid content and phenotype in the presence of iCCA cells, and the same effect could be recapitulated by FA supplementation.</p><p><strong>Conclusions: </strong>Our results reveal a profound alteration in the lipid content of iCCA tissues and demonstrate that FA accumulation prompts iCCA aggressiveness by supporting membrane biogenesis, generating bioactive lipids that boost proliferation, and by modifying macrophage phenotype.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HCC surveillance in hepatitis C: A longitudinal algorithm improves alpha-fetoprotein screening.","authors":"Tracey L Marsh, Janet M Johnston, Chriss Homan, Lisa J Townshend-Bulson, Nicole J Kim, Trang VoPham, Xiaohong Li, Qianchuan He, Brian J McMahon, George N Ioannou, Ziding Feng","doi":"10.1097/HC9.0000000000000719","DOIUrl":"10.1097/HC9.0000000000000719","url":null,"abstract":"<p><strong>Background: </strong>Surveillance for HCC remains important after hepatitis C cure. Improved sensitivity of screening with alpha-fetoprotein (AFP) by using a parametric empirical Bayes (PEB) algorithm, which incorporates an individual patient's longitudinal AFP measurements, was previously demonstrated in a retrospective analysis of clinical trial data prior to widespread hepatitis C cure.</p><p><strong>Methods: </strong>We analyzed de-identified data extracted from the medical records of participants in the Alaska Hepatitis C Study, which aims to enroll all Alaska Native persons living in Alaska with a history of hepatitis C.We compared the performance characteristics of AFP as a screening test using the PEB method versus a fixed cutoff (FC) method in an observational setting, separately for HCC surveillance in active and cured hepatitis C.</p><p><strong>Results: </strong>The PEB and FC methods were applied to AFP levels from participants with F3/F4 fibrosis who had active hepatitis C (173 no HCC, 14 HCC) or after they achieved hepatitis C cure (162 no HCC, 12 HCC). Compared to a fixed 20 ng/mL cutoff, demonstrating 91.2% specificity in active hepatitis C, PEB increased sensitivity from 64.3% to 71.4%. After cure, a fixed 7.2 ng/mL cutoff demonstrated 91.2% specificity, and PEB increased sensitivity from 58.3% to 91.7%.</p><p><strong>Conclusions: </strong>The PEB algorithm can increase sensitivity and lead to earlier detection of HCC among patients with F3/F4 fibrosis, both in active and even more so in cured hepatitis C. Lower AFP levels after cure indicate that for either PEB or FC methods, screening parameters, such as cutoffs for a target specificity, should be specified separately by hepatitis C treatment status for HCC surveillance.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HBV-specific T-cell function is nonenhanced by tenofovir-induced decline in HBV viremia or HBsAg titer in chronic hepatitis B.","authors":"Daniel Traum, David K Wong, Daryl T Lau, Richard K Sterling, Norah A Terrault, Mandana Khalili, Abdus S Wahed, William M Lee, Timothy M Block, Anna S F Lok, Kyong-Mi Chang","doi":"10.1097/HC9.0000000000000694","DOIUrl":"https://doi.org/10.1097/HC9.0000000000000694","url":null,"abstract":"<p><strong>Background: </strong>Chronic hepatitis B is associated with virus-specific and global T-cell dysfunction. We hypothesized that therapeutic reduction in serum HBV DNA, ALT, and HBsAg would restore HBV-specific T-cell function and modify T-cell regulatory phenotype, with associated posttreatment ALT flare.</p><p><strong>Methods: </strong>HBV-specific T-cell lymphoproliferative responses and global T-cell phenotype were prospectively examined at baseline, weeks 24, 48, 192, 216, and 240 in 34 adults with immune-active chronic hepatitis B treated with 192 weeks of tenofovir alone (n=21) or combined with pegylated interferon (PegIFN) in the first 24 weeks (n=13). HBV-specific T-cell IFNγ responses at weeks 0, 24, and 48 were examined by ELISpot assay ex vivo in 24 patients. Posttreatment flare was defined by serum ALT >5 times the upper limit of normal.</p><p><strong>Results: </strong>Tenofovir therapy did not promote sustained induction of HBV-specific T-cell proliferative responses, regardless of PegIFN therapy or decreased serum HBsAg, HBV DNA, or ALT levels. Instead, HBV-specific T-cell IFNγ responses declined significantly by 48 weeks of therapy (p=0.008). Posttreatment ALT flare was associated with higher baseline %PD1+/CD8 (p=0.019), %PD1+/CD4 (p=0.039), and %CTLA4+/CD4 (p=0.003) T cells compared to non-flares, but without associated HBsAg loss or increased HBV-specific T-cell responsiveness.</p><p><strong>Conclusion: </strong>HBV-specific T-cell function was not restored after 192 weeks of tenofovir therapy and did not correlate with HBsAg levels before, during, or after therapy. Baseline global T-cell regulatory phenotype was a predictor for ALT flare post-therapy without associated HBsAg decline. These findings support the need for more novel immune-modulatory approaches to enhance HBV-specific T-cell responsiveness.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12088633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of pruritus in primary sclerosing cholangitis: Analysis of the consortium for autoimmune liver disease registry.","authors":"Richard Dean, Maryam Yazdanfar, Joseph Zepeda, Cynthia Levy, Craig Lammert, Daniel Pratt, Stuart C Gordon, Lisa Forman, David N Assis, Ashleigh McGirr, Megan McLaughlin, Sumanta Mukherjee, Usha Gungabissoon, Christopher L Bowlus","doi":"10.1097/HC9.0000000000000703","DOIUrl":"10.1097/HC9.0000000000000703","url":null,"abstract":"<p><strong>Background: </strong>Cholestasis from primary sclerosing cholangitis (PSC) frequently causes pruritus. However, the prevalence of pruritus and its management have not been well studied. Investigating the Cholestatic Pruritus of Primary Sclerosing Cholangitis (ItCh-PSC) includes a retrospective medical record review to determine the prevalence, severity, and treatment patterns of pruritus.</p><p><strong>Methods: </strong>Data was collected at 5 academic medical centers in the United States. Medical records were searched for the terms \"itch\" and \"pruritus\" and data abstracted related to itch severity, number of encounters, and treatment.</p><p><strong>Results: </strong>Among 724 patients with PSC, 359 (50%) of patients had a documented history of pruritus, including 40%, 39%, and 21% with mild, moderate, or severe itch. Itch was less common in those with small ducts compared to large duct PSC (p=0.02) and more frequent in those of Hispanic versus non-Hispanic ethnicity (p=0.001). Compared to patients with mild itch, patients with moderate or severe itch were younger, and had more elevated liver biochemistries, more encounters with itch, and more frequently prescribed 2 or more anti-pruritic medications. Bile acid-binding resins were prescribed in 36%, hydroxyzine in 23%, rifampin in 11%, and fenofibrate in 4% of patients with any itch. The prevalence and severity of pruritus were not affected by cirrhosis, hepatic decompensation, or inflammatory bowel disease.</p><p><strong>Conclusion: </strong>Itch is common in patients with PSC and is often associated with multiple prescriptions of antipruritic agents. Effective treatments for pruritus in patients with PSC remain an unmet need.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcription reveals hepatocyte-to-cholangiocyte reprogramming and biliary gene profile in biliary atresia.","authors":"Lingdu Meng, Min Du, Haodong Li, Fanyang Kong, Jiajian Yang, Rui Dong, Shan Zheng, Gong Chen, Zhen Shen, Junfeng Wang","doi":"10.1097/HC9.0000000000000710","DOIUrl":"10.1097/HC9.0000000000000710","url":null,"abstract":"<p><strong>Background: </strong>Ductular reaction (DR), characterized by the expansion of biliary epithelial cells in the portal area, is a typical hepatic pathology for biliary atresia (BA). The cellular source and function of DR remain poorly understood. Herein, we performed single-cell RNA sequencing (scRNA-seq) in BA to resolve the complexity of DR in BA.</p><p><strong>Methods: </strong>A total of 4 BA and 3 normal control livers underwent scRNA-seq. The epithelial cells were extracted from all cells for further analysis. The cell types, functions, and differentiational trajectory of epithelial cells were determined. The biliary markers and transcription factors (TFs) were identified by combing public bulk and scRNA-seq data and validated by immunohistochemistry.</p><p><strong>Results: </strong>ScRNA-seq identified the existence of biliary reprogramming in BA, and the reprogrammed cells expressed both hepatocyte and cholangiocyte markers. When compared with hepatocytes, genes of epithelial-mesenchymal transition, fibrosis, inflammation, and RNA metabolism were enriched in cholangiocytes and upregulated in BA. Pseudotime analysis depicted a differentiation trajectory from hepatocytes across reprogrammed cells to cholangiocytes in BA. Matrix metalloproteinase 7 (MMP7), VTCN1, and LAMC2 were identified as the biliary markers, and KLF5 and HNF1B were determined as the biliary TFs in BA. All the biliary markers and TFs were upregulated in BA when compared with controls.</p><p><strong>Conclusions: </strong>Dissecting the cellular source and function of cholangiocytes is essential to understand the pathological role of DR in BA. The identified specific biliary markers and TFs provide important insights into its potential diagnosis and mechanism exploration for BA in the future.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: Refining risk stratification in hepatic encephalopathy-External validation of the BABS score in European cohorts.","authors":"Nadja G Østberg, Gabriele Berg-Beckhoff, Lea L Grønkjær, Elise Jonasson, Eva Maria Schleicher, Simon J Gairing, Christian Labenz, Mette M Lauridsen","doi":"10.1097/HC9.0000000000000688","DOIUrl":"10.1097/HC9.0000000000000688","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Awareness of metabolic dysfunction-associated steatotic liver disease (MASLD) in 4 major cities in the United States.","authors":"Jeffrey V Lazarus, Trenton M White, Alina M Allen, Silvana Pannain, Naim Alkhouri, Meena B Bansal, Michael Charlton, Brett E Fortune, Yehuda Handelsman, Scott Isaacs, Ira M Jacobson, Sonal Kumar, Melina I Manolas, Mazen Noureddin, Mary E Rinella, Norah Terrault, Ayman El-Mohandes","doi":"10.1097/HC9.0000000000000704","DOIUrl":"https://doi.org/10.1097/HC9.0000000000000704","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HBV core protein enhances WDR46 stabilization to upregulate NUSAP1 and promote HCC progression.","authors":"Fanyun Kong, Ensi Bao, Yujie Zhong, Yuxin Wang, Ruyu Liu, Huanyang Zhang, Lu Yang, Rong Jiang, Xuanke Liu, Chen Li, Xiangye Liu, Xiucheng Pan, Kuiyang Zheng, Hongjuan You, Renxian Tang","doi":"10.1097/HC9.0000000000000680","DOIUrl":"10.1097/HC9.0000000000000680","url":null,"abstract":"<p><strong>Background: </strong>The HBV core protein (HBC) is crucial for the progression of HCC. WD repeat-containing (WDR) 46 (WDR46) is implicated in the development of different tumors. Nevertheless, whether WDR46 is controlled by HBC to drive hepatocarcinogenesis remains unclear.</p><p><strong>Methods: </strong>Different HCC cohorts, immunohistochemical staining, and bioinformatics analysis were utilized to estimate the clinical correlation between WDR46 and HBV-associated HCC. Western blotting, co-immunoprecipitation, chromatin immunoprecipitation, and oncology functional assays were performed to evaluate the effect of HBC on WDR46 in upregulating nucleolar spindle-associated protein 1 (NUSAP1), the influence of WDR46 on HBC-mediated HCC cell biological functions, and the mechanisms of WDR46 upregulation mediated by HBC to increase NUSAP1.</p><p><strong>Results: </strong>WDR46 expression was elevated in HBV-related HCC in a HBC-dependent manner. Overexpression of WDR46 is closely linked to severe prognosis of tumors. Functionally, WDR46 contributes to HBC-induced cell growth and migration in vitro and in vivo. Furthermore, HBC enhanced WDR46 protein stabilization by hampering the interaction between WDR46 and TRIM25, thereby decreasing WDR46 ubiquitination. NUSAP1, a DNA replication-related molecule, is a vital downstream target of WDR46. Relying on WDR46, HBC promoted NUSAP1 upregulation to modulate the biological functions of HBC in HCC cells. Importantly, HBC enhanced the interaction between WDR46 and the transcription factor c-Myc to facilitate c-Myc recruitment to the NUSAP1 promoter, leading to the increase of NUSAP1 transcription.</p><p><strong>Conclusions: </strong>Our comprehensive data provides new insights into the mechanisms responsible for HBC-induced hepatocarcinogenesis. WDR46 and its downstream molecule, NUSAP1, may act as novel therapeutic targets for HBV-related tumors.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}