Tingting Hu , Wenqing Tang , Wandong Hong , Qingke Huang , Xuecheng Sun , Wenzhi Wu , Jie Zhang
{"title":"Spermine oxidase regulates liver inflammation and fibrosis through β-catenin pathway","authors":"Tingting Hu , Wenqing Tang , Wandong Hong , Qingke Huang , Xuecheng Sun , Wenzhi Wu , Jie Zhang","doi":"10.1016/j.clinre.2024.102421","DOIUrl":"10.1016/j.clinre.2024.102421","url":null,"abstract":"<div><h3>Background</h3><p>Spermine oxidase (SMOX), an inducible enzyme involved in the catabolic pathway of polyamine, was found to be upregulated in hepatocellular carcinoma and might be an important oncogene of it in our previous studies. This study attempted to further investigate its relationship with liver inflammation and fibrosis both in vitro and in vivo.</p></div><div><h3>Methods</h3><p>The effect of SMOX inhibition on LPS-induced inflammatory response in mouse liver cell line AML12 was validated by using small interfering RNA or SMOX inhibitor MDL72527. Western blotting and immunofluorescence were utilized to verify whether LPS could induce β-catenin to transfer into the nucleus and whether it could be reversed by interfering with the expression of SMOX or using SMOX inhibitor. Then, the SMOX inhibitor MDL72527 and SMOX knockout mice were used to verify the hypothesis above in vivo.</p></div><div><h3>Results</h3><p>The expression of SMOX could be induced by LPS in AML12 cells. The inhibition of SMOX could inhibit LPS-induced inflammatory response in AML12 cells. LPS could induce β-catenin transfer from cytoplasm to nucleus, while SMOX downregulation or inhibition could partially reverse this process. In vivo intervention with SMOX inhibitor MDL72527 or SMOX knockout mice could significantly improve the damage of liver function, reduce intrahepatic inflammation, inhibit the nuclear transfer of β-catenin in liver tissue, and alleviate carbon tetrachloride-induced liver fibrosis in mice.</p></div><div><h3>Conclusion</h3><p>SMOX can promote the inflammatory response and fibrosis of hepatocytes. It provides a new therapeutic strategy for hepatitis and liver fibrosis, inhibiting early liver cancer.</p></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"48 7","pages":"Article 102421"},"PeriodicalIF":2.6,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quiescent hepatic stellate cell activation in liver fibrosis: Have we found the right trigger yet?","authors":"Devaraj Ezhilarasan , Mustapha Najimi","doi":"10.1016/j.clinre.2024.102420","DOIUrl":"10.1016/j.clinre.2024.102420","url":null,"abstract":"","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"48 7","pages":"Article 102420"},"PeriodicalIF":2.6,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between primary biliary cholangitis with diabetes and cardiovascular diseases: A bidirectional multivariable Mendelian randomization study","authors":"","doi":"10.1016/j.clinre.2024.102419","DOIUrl":"10.1016/j.clinre.2024.102419","url":null,"abstract":"<div><h3>Background and aims</h3><p>Primary biliary cholangitis (PBC) is an autoimmune disease often accompanied by multisystem damage. This study aimed to explore the causal association between genetically predicted PBC and diabetes, as well as multiple cardiovascular diseases (CVDs).</p></div><div><h3>Methods</h3><p>Genome-wide association studies (GWAS) summary data of PBC in 24,510 individuals of European ancestry from the European Association for the Study of the Liver was used to identify genetically predicted PBC. We conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to estimate the impacts of PBC on diabetes (<em>N</em> = 17,685 to 318,014) and 20 CVDs from the genetic consortium (<em>N</em> = 171,875 to 1,030,836).</p></div><div><h3>Results</h3><p>SVMR provided evidence that genetically predicted PBC is associated with an increased risk of type 1 diabetes (T1D), type 2 diabetes (T2D), myocardial infarction (MI), heart failure (HF), hypertension, atrial fibrillation (AF), stroke, ischemic stroke, and small-vessel ischemic stroke. Additionally, there was no evidence of a causal association between PBC and coronary atherosclerosis. In the MVMR analysis, PBC maintained independent effects on T1D, HF, MI, and small-vessel ischemic stroke in most models.</p></div><div><h3>Conclusion</h3><p>Our findings revealed the causal effects of PBC on diabetes and 7 CVDs, and no causal relationship was detected between PBC and coronary atherosclerosis.</p></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"48 7","pages":"Article 102419"},"PeriodicalIF":2.6,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sinomenine hydrochloride improves DSS-induced colitis in mice through inhibition of the TLR2/NF-κB signaling pathway","authors":"","doi":"10.1016/j.clinre.2024.102411","DOIUrl":"10.1016/j.clinre.2024.102411","url":null,"abstract":"<div><h3>Background</h3><p>Sinomenine hydrochloride (SH) has anti-inflammatory and immunosuppressive effects, and its effectiveness in inflammatory diseases, such as rheumatoid arthritis, has been demonstrated. However, whether SH has a therapeutic effect on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice and its mechanism of action have not been clarified. This study aimed to investigate the therapeutic effects and mechanism of action of SH on UC.</p></div><div><h3>Methods</h3><p>Twenty-four mice were randomly divided into control, model, SH low-dose (SH-L, 20mg/kg), and SH high-dose (SH-H, 60mg/kg) groups with six mice in each group. Disease activity index (DAI), colonic mucosal damage index, and colonic histopathology scores were calculated. The expression levels of related proteins, genes, and downstream inflammatory factors in the Toll-like receptor 2/NF-κB (TLR2/NF-κB) signaling pathway were quantified.</p></div><div><h3>Results</h3><p>SH inhibited weight loss, decreased DAI and histopathological scores, decreased the expression levels of TLR2, MyD88, P-P65, P65 proteins, and TLR2 genes, and also suppressed the expression of inflammatory factors TNF-α, IL-1 β, and IL-6 in the peripheral blood of mice.</p></div><div><h3>Conclusion</h3><p>The therapeutic effect of SH on DSS-induced UC in mice may be related to the inhibition of the TLR2/NF-κB signaling pathway.</p></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"48 7","pages":"Article 102411"},"PeriodicalIF":2.6,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Validation of a novel BCM model for recurrence risk prediction after mucosectomy of colorectal lateral spreading tumors in a European cohort","authors":"","doi":"10.1016/j.clinre.2024.102414","DOIUrl":"10.1016/j.clinre.2024.102414","url":null,"abstract":"<div><h3>Background and aim</h3><p>Piecemeal endoscopic mucosal resection (pEMR) is the best approach to resect large lateral spreading tumors (LST, > 20 mm width). However, it is associated with early recurrence (ER) and late recurrence (LR). This study aims to assess the risk factors associated with ER and LR and to validate different predictive scores (SMSA, SERT, and BCM) in identifying the risk of ER and LR after LST resected by pEMR in a European cohort.</p></div><div><h3>Methods</h3><p>Retrospective observational cohort study, based on a prospectively collected database, of large LST submitted to pEMR.</p></div><div><h3>Results</h3><p>A total of 108 patients were included in the study and the incidence rates of ER and LR were 22 % and 8 %, respectively. The lesion's size, SERT, and BCM scores were independent predictor factors of ER (p-value < 0.05), while the lesion's site and BCM score were independent predictor factors of LR (p-value < 0.05). For the prediction of ER, the SERT score (cut-off > 1) presented the highest AUROC (0.758 vs 0.697 from BCM and 0.647 from SMSA). Regarding LR, the BCM model (cut-off > 2) presented the highest AUROC (0.817 vs 0.708 from SERT and 0.691 from SMSA).</p></div><div><h3>Conclusions</h3><p>We present the first external validation of the three scores mentioned in an European cohort. SERT and BCM scores had an acceptable performance in predicting ER and LR. However, the BCM model was the only score that proved to be an independent predictor of both ER and LR, proving to be valuable for both applications.</p></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"48 7","pages":"Article 102414"},"PeriodicalIF":2.6,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2210740124001359/pdfft?md5=47eed855fd539a9f88672e646e19e76d&pid=1-s2.0-S2210740124001359-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Strong association between sarcopenic obesity and non-alcoholic fatty liver disease: An observational study with ISarcoPRM algorithm","authors":"","doi":"10.1016/j.clinre.2024.102412","DOIUrl":"10.1016/j.clinre.2024.102412","url":null,"abstract":"<div><h3>Background</h3><p>In recent times, sarcopenia and non-alcoholic fatty liver disease (NAFLD) have garnered widespread attention in public health. Nevertheless, the relationship between sarcopenia and NAFLD remains uncertain. This study investigated the association between NAFLD and sarcopenia in the elderly population.</p></div><div><h3>Methods</h3><p>In this cross-sectional study, 1099 adults aged 60 and older participated. The participants were classified based on their body composition, and the International Society of Physical and Rehabilitation Medicine's diagnostic algorithm (ISarcoPRM) was utilized to diagnose sarcopenia, while the fatty liver index was utilized to diagnose NAFLD. Binary logistic regression analysis determined the correlation between NAFLD and sarcopenia.</p></div><div><h3>Results</h3><p>Of the 1099 participants, 213 (58.2 %) males and 480 (65.5 %) females were afflicted with NAFLD. After adjusting for other clinical factors, exercise was found to decrease the likelihood of NAFLD in females (but not in males) by approximately 70 % [relative risk (<em>RR</em>): 0.312<em>,</em> 95 % confidence interval (CI): 0.182–0.547]. In addition, sarcopenia was not discerned as a risk factor for NAFLD in either gender (both <em>p</em> > 0.05). However, obesity increased the likelihood of NAFLD in males by 27.5 (95 % CI: 10.4–73.1) and in females by 28.1 (95 % CI: 17.1–46.4), and sarcopenic obesity increased the likelihood of NAFLD by 49.5 (95 % CI: 11.1–219.1) in males and 35.5 (95 % CI: 18.5–68.2) in females (all <em>p</em> < 0.001).</p></div><div><h3>Conclusion</h3><p>Our study suggests that sarcopenia is not a risk factor for NAFLD in non-obese elderly subjects. However, a strong association was observed between obesity, especially sarcopenic obesity, and NAFLD. Regular physical activity seems protective for NAFLD in older females.</p></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"48 7","pages":"Article 102412"},"PeriodicalIF":2.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meng Tao , Xiaojun Wang , Jing Han , Li Cao , Jianwei Li , Shuguo Zheng
{"title":"A new classification and laparoscopic treatment of extrahepatic choledochal cyst","authors":"Meng Tao , Xiaojun Wang , Jing Han , Li Cao , Jianwei Li , Shuguo Zheng","doi":"10.1016/j.clinre.2024.102413","DOIUrl":"10.1016/j.clinre.2024.102413","url":null,"abstract":"<div><h3>Background</h3><p>Prior typing methods fail to provide predictive insights into surgical complexities for extrahepatic choledochal cyst (ECC). This study aims to establish a new classification system for ECC through clustering of imaging results. Additionally, it seeks to compare the differences among the identified ECC types and assess the levels of surgical difficulty.</p></div><div><h3>Methods</h3><p>The imaging data of 124 patients were automatically grouped through a K-means clustering analysis. According to the characteristics of the new grouping, corrections and interventions were carried out to establish a new classification. Demographic data, clinical presentations, surgical parameters, complications, reoperation, and prognostic indicators were analyzed according to different types. Factors contributing to prolonged surgical time were also evaluated.</p></div><div><h3>Results</h3><p>A new classification system of ECC: Type A (upper segment), Type B (middle segment), Type C (lower segment), and Type D (entire bile duct). The incidences of comorbidities (calculus or infection) were significantly different (<em>P</em> = 0.000, <em>P</em> = 0.002). Additionally, variations in the incidence of postoperative biliary stricture were statistically significant (<em>P</em> = 0.046). The operative time was significantly different between groups (<em>P</em> = 0.001). Age, BMI > 30, classification, and the presence of combined stones exhibit a significant association with prolonged operative time (<em>P</em> = 0.002, <em>P</em> = 0.000, <em>P</em> = 0.011, <em>P</em> = 0.011).</p></div><div><h3>Conclusion</h3><p>In conclusion, our utilization of machine learning-driven cluster analysis has enabled the creation of a novel extrahepatic biliary dilatation typology. This classification, in conjunction with factors like age, combined stone occurrence, and obesity, significantly influences the complexity of laparoscopic choledochal cyst surgery, offering valuable insights for improved surgical treatment.</p></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"48 7","pages":"Article 102413"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xu-Long Shen , Xiao-Ting Zhou , Min Ren , Xin Shi , Hai-Zhen Zhang , Yu Wang , Min Yang
{"title":"Modified Zhizhu Pill improves the loperamide-induced slow transit constipation via gut microbiota and neurotransmitters in microbiota-gut-brain axis","authors":"Xu-Long Shen , Xiao-Ting Zhou , Min Ren , Xin Shi , Hai-Zhen Zhang , Yu Wang , Min Yang","doi":"10.1016/j.clinre.2024.102410","DOIUrl":"10.1016/j.clinre.2024.102410","url":null,"abstract":"<div><h3>Background</h3><p>Slow-transmission constipation is a type of intractable constipation with unknown etiology and unclear pathogenesis.</p></div><div><h3>Objective</h3><p>The intention of this study was to evaluate the therapeutic effect and possible mechanism of Modified Zhizhu Pills on loperamide-induced slow transit constipation.</p></div><div><h3>Methods</h3><p>The effects of the Modified Zhizhu Pill were evaluated in a rat model of constipation induced by subcutaneous administration of loperamide. Fecal parameters (fecal count, fecal water content, and fecal hardness) were measured in constipated rats. The substance, target, and pathway basis of the Modified Zhizhu Pill on constipation was investigated using network pharmacology. The microflora in rats was determined. Serum neurotransmitters (acetylcholine and 5-hydroxytryptamine) were measured in rats and their relationship with the gut microbiota was assessed.</p></div><div><h3>Results</h3><p>Modified Zhizhu Pill increased the number of bowel movements and fecal water content, and decreased fecal hardness and transit time. Network pharmacological analysis showed that Modified Zhizhu Pill can target multiple constipation-related targets and pathways through multiple potential active ingredients. Modified Zhizhu Pill alleviated loperamide-induced microbiota dysbiosis. Modified Zhizhu Pill increased serum 5-hydroxytryptamine and acetylcholine. The increase in serum 5-hydroxytryptamine and acetylcholine was associated with rat gut microbiota.</p></div><div><h3>Conclusion</h3><p>These results suggest that Modified Zhizhu Pill may increase intestinal motility and ultimately relieve constipation by improving microecological dysbiosis and neurotransmission.</p></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"48 7","pages":"Article 102410"},"PeriodicalIF":2.6,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Imaging-based assessment of sarcopenia in patients with compensated advanced chronic liver disease: One step further","authors":"Maxime Ronot","doi":"10.1016/j.clinre.2024.102409","DOIUrl":"10.1016/j.clinre.2024.102409","url":null,"abstract":"","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"48 7","pages":"Article 102409"},"PeriodicalIF":2.6,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Catherine A Chapin , Tamir Diamond , Adriana Perez , Portia A Kreiger , Kathleen M Loomes , Edward M Behrens , Estella M Alonso
{"title":"Identification of pediatric activated T-cell hepatitis using clinical immune studies","authors":"Catherine A Chapin , Tamir Diamond , Adriana Perez , Portia A Kreiger , Kathleen M Loomes , Edward M Behrens , Estella M Alonso","doi":"10.1016/j.clinre.2024.102407","DOIUrl":"10.1016/j.clinre.2024.102407","url":null,"abstract":"<div><h3>Background and aims</h3><p>The majority of indeterminate pediatric acute liver failure (PALF) cases are secondary to immune dysregulation, labeled activated T-cell hepatitis (TC<img>Hep). We aimed to describe a cohort of children with acute severe hepatitis and PALF and define how clinical immune labs may help identify the TC<img>Hep group.</p></div><div><h3>Methods</h3><p>Retrospective review of children with acute hepatitis and PALF between March 2020 and August 2022. Patients were classified as known diagnosis, indeterminate hepatitis (IND-Hep), or TC<img>Hep (defined by liver biopsy with predominant CD8 T-cell inflammation or development of aplastic anemia).</p></div><div><h3>Results</h3><p>124 patients were identified: 83 with known diagnoses, 16 with TC<img>Hep, and 25 with IND-Hep. Patients with TC<img>Hep had significantly increased median total bilirubin levels (7.5 mg/dL (IQR 6.8–8.9) vs 1.5 mg/dL (IQR 1.0–3.6), <em>p</em> < 0.0001), soluble interleukin-2 receptor levels (4512 IU/mL (IQR 4073–5771) vs 2997 IU/mL (IQR 1957–3237), <em>p</em> = 0.02), and percent of CD8+ <em>T</em>-cells expressing perforin (14.5 % (IQR 8.0–20.0) vs 1.0 % (IQR 0.8–1.0), <em>p</em> = 0.004) and granzyme (37.5 % (IQR 15.8–54.8) vs 4.0 % (IQR 2.5–5.5), <em>p</em> = 0.004) compared to IND-Hep patients. Clinical flow cytometry showed that TC<img>Hep patients had significantly increased percent CD8+ <em>T</em> cells (29.0 % (IQR 24.5–33.5) vs 23.6 % (IQR 19.8–25.8), <em>p</em> = 0.04) and HLA-DR+ (16.0 % (IQR 14.5–24.5) vs 2.7 (1.8–5.3), <em>p</em> < 0.001) compared to IND-Hep patients indicative of increase in CD8+ <em>T</em> cells that are activated.</p></div><div><h3>Conclusions</h3><p>Peripheral blood clinical immune studies demonstrate increased markers of CD8 T-cell activation, proliferation, and cytotoxic function for TC<img>Hep patients. These readily available immune function labs can be used to help distinguish patients with TC<img>Hep from those with other causes. This provides a non-invasive tool for early detection of potential TC<img>Hep before progression to liver failure.</p></div>","PeriodicalId":10424,"journal":{"name":"Clinics and research in hepatology and gastroenterology","volume":"48 7","pages":"Article 102407"},"PeriodicalIF":2.6,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}