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Multimodal pancreatic cancer detection using methylated DNA biomarkers in pancreatic juice and plasma CA 19-9: A prospective multicenter study. 利用胰液中甲基化 DNA 生物标记物和血浆 CA 19-9 进行多模式胰腺癌检测:一项前瞻性多中心研究。
IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-28 DOI: 10.1016/j.cgh.2024.07.048
Megan M L Engels, Calise K Berger, Douglas W Mahoney, Sanne A Hoogenboom, Dhruv Sarwal, Derk C F Klatte, Jaime De La Fuente, Sonal Gandhi, William R Taylor, Patrick H Foote, Karen A Doering, Adriana M Delgado, Kelli N Burger, Barham K Abu Dayyeh, Aliana Bofill-Garcia, Bhaumik Brahmbhatt, Vinay Chandrasekhara, Ferga C Gleeson, Victoria Gomez, Vivek Kumbhari, Ryan J Law, Frank J Lukens, Massimo Raimondo, Elizabeth Rajan, Andrew C Storm, Eric J Vargas Valls, Jeanin E van Hooft, Michael B Wallace, John B Kisiel, Shounak Majumder

Background and aims: In previous studies methylated DNA markers (MDMs) have been identified in pancreatic juice (PJ) for detecting pancreatic ductal adenocarcinoma (PDAC). In this prospective multicenter study, the sensitivity and specificity characteristics of this panel of PJ-MDMs was evaluated standalone and in combination with plasma CA 19-9.

Methods: Paired PJ and plasma were assayed from 88 biopsy-proven treatment naïve PDAC cases and 134 controls (normal pancreas: 53, chronic pancreatitis (CP): 23, intraductal papillary mucinous neoplasm (IPMN): 58). Bisulfite-converted DNA from buffered PJ was analyzed using long-probe quantitative amplified signal assay targeting 14 MDMs (NDRG4, BMP3, TBX15, C13orf18, PRKCB, CLEC11A, CD1D, ELMO1, IGF2BP1, RYR2, ADCY1, FER1L4, EMX1, and LRRC4) and a reference gene (methylated B3GALT6). Logistic regression was used to fit the previously identified 3-MDM PJ panel (FER1L4, C13orf18 and BMP3). Discrimination accuracy was summarized using area under the receiver operating characteristic curve (AUROC) with corresponding 95% confidence intervals.

Results: Methylated FER1L4 had the highest individual AUROC of 0.83 (95% CI: 0.78-0.89). The AUROC for the 3-MDM PJ + Plasma CA 19-9 model (0.95 (0.92-0.98))) was higher than both the 3-MDM PJ panel (0.87 (0.82-0.92)) and plasma CA 19-9 alone ((0.91 (0.87-0.96) (p=0.0002 and 0.0135, respectively). At a specificity of 88% (95% CI: 81-93%), the sensitivity of this model was 89% (80-94%) for all PDAC stages and 83% (64-94%) for stage I/II PDAC.

Conclusion: A panel combining PJ-MDMs and plasma CA19-9 discriminates PDAC from both healthy and disease control groups with high accuracy. This provides support for combining pancreatic juice and blood-based biomarkers for enhancing diagnostic sensitivity and successful early PDAC detection.

背景和目的:以往的研究发现,胰液(PJ)中的甲基化DNA标记物(MDMs)可用于检测胰腺导管腺癌(PDAC)。在这项前瞻性多中心研究中,对这组 PJ-MDMs 的灵敏度和特异性特征进行了单独评估,以及与血浆 CA 19-9 联合评估:方法:对 88 例经活检证实的未接受过治疗的 PDAC 病例和 134 例对照(正常胰腺 53 例、慢性胰腺炎(CP)134 例)的配对 PJ 和血浆进行检测:方法:对 88 例经活检证实未接受过治疗的 PDAC 病例和 134 例对照组(正常胰腺:53 例;慢性胰腺炎(CP):23 例;导管内乳头状粘液瘤(IPMN):58 例)的配对 PJ 和血浆进行检测。使用长探针定量扩增信号分析法分析了缓冲 PJ 中的亚硫酸氢盐转化 DNA,该方法针对 14 个 MDMs(NDRG4、BMP3、TBX15、C13orf18、PRKCB、CLEC11A、CD1D、ELMO1、IGF2BP1、RYR2、ADCY1、FER1L4、EMX1 和 LRRC4)和一个参考基因(甲基化 B3GALT6)。逻辑回归用于拟合先前确定的 3-MDM PJ 面板(FER1L4、C13orf18 和 BMP3)。利用接收者工作特征曲线下面积(AUROC)和相应的 95% 置信区间总结了判别准确性:甲基化 FER1L4 的单个 AUROC 最高,为 0.83(95% CI:0.78-0.89)。3-MDM PJ + 血浆 CA 19-9 模型的 AUROC(0.95 (0.92-0.98) )高于 3-MDM PJ 面板(0.87 (0.82-0.92))和单独血浆 CA 19-9(0.91 (0.87-0.96) (分别为 p=0.0002 和 0.0135))。在特异性为88%(95% CI:81-93%)时,该模型对所有PDAC分期的灵敏度为89%(80-94%),对I/II期PDAC的灵敏度为83%(64-94%):结论:结合 PJ-MDMs 和血浆 CA19-9 的面板能准确区分 PDAC 与健康组和疾病对照组。这为结合胰液和血液中的生物标记物提高诊断灵敏度并成功检测早期 PDAC 提供了支持。
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引用次数: 0
Non-invasive hepatic steatosis and fibrosis indices predict differentially mortality in the adult Korean population. 非侵入性肝脂肪变性和肝纤维化指数可预测韩国成年人群的不同死亡率。
IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-25 DOI: 10.1016/j.cgh.2024.10.006
Young-Gyun Seo, Stergios A Polyzos, Kyung-Hee Park, Christos S Mantzoros

Background and aims: Since the association of hepatic fibrosis and steatosis non-invasive indices with mortality remain controversial, their association with all-cause, cardiovascular, cancer and liver-related mortality was evaluated in the Korean population.

Methods: In this registry-based, cohort study, data were retrieved from the Korea National Health and Nutrition Examination Survey and mortality data from the Korean Cause of Death data registry; 40,491 individuals followed-up for 8.6 years (median). Hepatic fibrosis was evaluated with alanine aminotransferase (AST)-to-platelet ratio index (APRI), body mass index-AST-to-alanine aminotransferase (ALT) ratio-diabetes mellitus (BARD) and metabolic dysfunction-associated fibrosis-5 (MAF-5) score, and steatosis was evaluated with liver fat score (LFS) and lipid accumulation product (LAP).

Results: Cox regression analysis showed that APRI (<1.0 vs. ≥1.0) was independently associated with all-cause (hazard ratio [HR] 3.84, 95% confidence interval [CI] 2.30-6.43, C-index 0.870), cancer (HR 4.21, 95%CI 1.88-9.45, C-index 0.866) and liver-related (HR 25.36, 95%CI 11.02-58.38, C-index 0.909) mortality. MAF-5 (<1.0 vs. ≥1.0) was independently associated with all-cause mortality (HR 1.50, 95%CI 1.10-2.03, C-index 0.868) and liver-related mortality (HR 8.35, 95%CI 3.58-19.46, C-index 0.911). LFS (<1.257 vs. ≥1.257), was independently associated with all-cause (HR 1.55, 95%CI 1.14-2.12, C-index 0.872) and liver-related (HR 7.00, 95%CI 1.63-29.96, C-index 0.887) mortality. LAP (<38.05 vs. ≥38.05) was independently associated with cardiovascular mortality (HR 2.23, 95%CI 1.40-3.58, C-index 0.898). BARD was not associated with mortality.

Conclusions: APRI, MAF-5, LFS were independently associated with all-cause mortality, LAP (cut-off 38.05) with cardiovascular mortality, APRI with cancer mortality, and APRI, MAF-5, LFS with liver-related mortality in the adult Korean population.

背景和目的:由于肝纤维化和脂肪变性非侵入性指数与死亡率的关系仍存在争议,因此在韩国人群中评估了它们与全因死亡率、心血管死亡率、癌症死亡率和肝脏相关死亡率的关系:在这项以登记为基础的队列研究中,数据来自韩国国民健康与营养调查,死亡率数据来自韩国死因数据登记;40 491 人接受了 8.6 年(中位数)的随访。肝纤维化用丙氨酸氨基转移酶(AST)-血小板比值指数(APRI)、体重指数-AST-丙氨酸氨基转移酶(ALT)比值-糖尿病(BARD)和代谢功能障碍相关纤维化-5(MAF-5)评分进行评估,脂肪变性用肝脏脂肪评分(LFS)和脂质累积乘积(LAP)进行评估:结果:Cox 回归分析表明,APRI(结论:APRI、MAF-5、LAP结果:Cox 回归分析表明,在韩国成年人群中,APRI、MAF-5 和 LFS 与全因死亡率独立相关,LAP(临界值 38.05)与心血管死亡率独立相关,APRI 与癌症死亡率独立相关,APRI、MAF-5 和 LFS 与肝脏相关死亡率独立相关。
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引用次数: 0
Anti-integrin αvβ6 autoantibodies are increased in PSC patients with concomitant IBD and correlate with liver disease severity. 伴有 IBD 的 PSC 患者体内抗整合素 αvβ6 自身抗体增加,并与肝病严重程度相关。
IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-25 DOI: 10.1016/j.cgh.2024.10.005
Hannah Bloemen, Alexandra E Livanos, Adrielly Martins, Richard Dean, Ana Catarina Bravo, Arno R Bourgonje, Michael Tankelevich, Jake Herb, Judy Cho, André Anastácio Santos, Cecília M P Rodrigues, Francesca Petralia, Jean-Frederic Colombel, Christopher L Bowlus, Thomas Schiano, Joana Torres, Cynthia Levy, Saurabh Mehandru

Background and aims: Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are found in more than 50% of individuals with ulcerative colitis (UC). We aimed to determine the prevalence of anti-αvβ6 in patients with primary sclerosing cholangitis (PSC) and their association with liver disease severity.

Methods: Four cohorts of pre-liver transplant PSC patients were recruited. Patients with inflammatory bowel disease (IBD) and healthy controls (HC) served as comparators. Total IgG and anti-αvβ6 levels were measured using enzyme-linked immunosorbent assay (ELISA). Olink® inflammation panel was run on a subset of samples. Multivariable linear regression analysis was performed to assess the association between anti-αvβ6 and indices of liver disease severity.

Results: A total of 137 PSC patients (including 76 with PSC-UC, 33 with PSC-Crohn's disease (CD) and 28 with PSC alone) and 160 controls (including 91 with IBD and 69 HC) were enrolled. Anti-αvβ6 levels were significantly higher in PSC-UC and PSC-CD compared to PSC alone (p<0.0001 and 0.003) and HC (p<0.0001 and p<0.0001). However, anti-αvβ6 levels in PSC alone were not increased compared to HC. In patients with PSC-IBD, anti-αvβ6 levels correlated with markers of liver disease severity including alkaline phosphatase level (r=0.32, p=0.004), the revised Mayo PSC risk score (r=0.25, p=0.02) and liver stiffness measurement (r=0.43, p=0.008) after adjusting for age, gender, race/ethnicity and IBD subtype. Additionally, anti-αvβ6 levels were associated with markers of systemic inflammation and tissue remodeling.

Conclusion: Anti-αvβ6 autoantibodies identify a subset of PSC patients with concomitant IBD.

背景和目的:50%以上的溃疡性结肠炎(UC)患者体内存在抗整合素αvβ6自身抗体(抗αvβ6)。我们的目的是确定原发性硬化性胆管炎(PSC)患者中抗αvβ6的流行率及其与肝病严重程度的关系:方法:招募了四组肝移植前的原发性硬化性胆管炎患者。方法:招募了四组肝移植前的 PSC 患者,以炎症性肠病(IBD)患者和健康对照组(HC)作为比较组。使用酶联免疫吸附试验(ELISA)测量总 IgG 和抗αvβ6 水平。对部分样本进行了 Olink® 炎症检测。进行了多变量线性回归分析,以评估抗αvβ6与肝病严重程度指数之间的关联:结果:共纳入了137名PSC患者(包括76名PSC-UC患者、33名PSC-克罗恩病(CD)患者和28名单纯PSC患者)和160名对照组(包括91名IBD患者和69名HC患者)。PSC-UC和PSC-CD患者的抗αvβ6水平明显高于单纯PSC患者(p结论:PSC-UC和PSC-CD患者的抗αvβ6水平明显高于单纯PSC患者:抗αvβ6自身抗体可识别合并有IBD的PSC患者。
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引用次数: 0
Secondhand Smoke Exposure and Metabolic Dysfunction-Associated Steatotic Liver Disease in US Adolescents. 美国青少年二手烟暴露与代谢功能障碍相关的脂肪肝。
IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-25 DOI: 10.1016/j.cgh.2024.08.049
Donghee Kim, Brandon J Perumpail, Pojsakorn Danpanichkul, Karn Wijarnpreecha, Aijaz Ahmed
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引用次数: 0
Prevalence of Gastroparesis in Chronic Pancreatitis and Predictive Factors: A Machine Learning Prediction Model. 慢性胰腺炎胃痉挛的患病率和预测因素:机器学习预测模型
IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-25 DOI: 10.1016/j.cgh.2024.09.023
Daryl Ramai, Chun-Wei Pan, David M Troendle, Marcello Maida, Antonio Facciorusso, Jorge D Machicado
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引用次数: 0
Long-term Effectiveness and Safety of Risankizumab in Patients with Crohn's Disease from a Large Tertiary Center. 一家大型三级医疗中心的利桑珠单抗对克罗恩病患者的长期有效性和安全性
IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-24 DOI: 10.1016/j.cgh.2024.09.027
Adar Zinger, David Choi, Natalie Choi, Evan Fear, Zachary Fine, Russell D Cohen, David T Rubin

Background and aims: Risankizumab is a selective IL23 inhibitor approved for the treatment of Crohn's disease (CD). We report a large long-term real-world experience with risankizumab in CD.

Methods: We performed a prospective monitoring of clinical outcomes in patients in our center who started treatment with risankizumab. Patients with active luminal disease who had at least 12 weeks of follow-up were included in the effectiveness analysis. Harvey-Bradshaw Index (HBI) as well as C-reactive protein (CRP) and fecal calprotectin (FCP) were used to monitor disease activity. Primary outcomes were clinical remission and steroid-free clinical remission rates at weeks 12, 26, and 52. Univariate analysis followed by a multivariate analysis using a logistic regression model was performed to identify predictors of steroid-free clinical remission at one year. All patients who started treatment with risankizumab for any indication were included in the safety analysis.

Results: 134 patients were included in the effectiveness analysis. 70 (52%) were ustekinumab-experienced. Clinical remission rates were 69%, 64%, and 54% at weeks 12, 26, and 52, respectively. Steroid-free clinical remission rates at 12, 26, and 52 weeks were 58%, 58%, and 50% respectively. Remission rates in ustekinumab-experienced patients were not statistically lower compared to naïve patients, and in a multivariate analysis, prior ustekinumab treatment was not associated with lower odds of achieving steroid-free clinical remission at one year. Adverse effects were assessed in 243 patients and were consistent with previous literature.

Conclusions: This large real-world experience with risankizumab with long-term follow-up demonstrates effectiveness and safety in patients with CD; there was comparable effectiveness in ustekinumab-naïve and ustekinumab-experienced patients.

背景和目的:利桑珠单抗是一种选择性IL23抑制剂,已被批准用于治疗克罗恩病(CD)。我们报告了利坦珠单抗治疗克罗恩病的大量长期实际经验:我们对本中心开始使用利坦单抗治疗的患者的临床疗效进行了前瞻性监测。疗效分析包括至少随访 12 周的活动性管腔疾病患者。哈维-布拉德肖指数(HBI)以及C反应蛋白(CRP)和粪便钙蛋白(FCP)用于监测疾病活动性。主要结果是第12、26和52周的临床缓解率和无类固醇临床缓解率。先进行单变量分析,然后使用逻辑回归模型进行多变量分析,以确定一年后无类固醇临床缓解的预测因素。所有因任何适应症开始接受利桑珠单抗治疗的患者均纳入安全性分析:134名患者被纳入有效性分析。70人(52%)有使用乌司替尼的经验。第12、26和52周的临床缓解率分别为69%、64%和54%。12周、26周和52周的无类固醇临床缓解率分别为58%、58%和50%。有乌司替库单抗治疗经验的患者的缓解率与无经验患者相比并没有统计学意义上的降低,而且在一项多变量分析中,之前接受过乌司替库单抗治疗的患者在一年后获得无类固醇临床缓解的几率也没有降低。对243名患者的不良反应进行了评估,结果与之前的文献一致:利坦珠单抗在CD患者中的长期随访显示了其有效性和安全性;对乌司他珠单抗无效患者和有乌司他珠单抗治疗经验患者的疗效相当。
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引用次数: 0
Multi-dimensional patient-reported outcomes and quality of life at diagnosis of IBD: A population-based inception cohort study. 确诊 IBD 时患者报告的多维结果和生活质量:基于人群的初始队列研究。
IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-24 DOI: 10.1016/j.cgh.2024.08.047
Mohamed Attauabi, Gorm Roager Madsen, Flemming Bendtsen, Jakob Benedict Seidelin, Johan Burisch

Background and aims: Patient-reported outcomes (PROs) are pivotal in assessing treatment efficacy and estimating the burden of inflammatory bowel diseases (IBD). We investigated PROs at the time of IBD diagnosis.

Methods: The Short Inflammatory Bowel Disease Questionnaire (SIBDQ), IBD-Disability Index (IBD-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and disease activity-related PROs were assessed in the Copenhagen IBD Inception Cohort, a prospective, population-based cohort of patients newly diagnosed with IBD between May 2021 and May 2023.

Results: A total of 203 UC and 116 CD patients were recruited. At diagnosis, 160 (78.8%) and 99 (85.3%) patients with UC and CD, respectively, reported moderate-to-severe impairment in at least one PRO (p=0.18), with 89 (43.8%) and 74 (63.8%), respectively, reporting moderate-to-severe impairment in at least two PROs (p<0.01). Being female, the disease extent of UC, and extraintestinal manifestations were associated with impaired PROs. There were no differences found according to CD phenotype. FACIT-F, IBD-DI, and SIBDQ scores showed weak, but significant, correlations with the Mayo Endoscopic Score in UC, and the FACIT-F score with C-reactive protein (CRP). In CD, SIBDQ, IBD-DI, and FACIT-F correlated moderately with CRP and fecal calprotectin, but not with the endoscopic severity of CD. None of the PROs correlated with iron, ferritin, or vitamin D levels. Among the most prevalent symptoms reported were fatigue, abdominal pain, urgency, and passing of blood in both CD and UC.

Conclusion: We found a substantial patient-reported disease burden in newly diagnosed IBD, underscoring the importance of vigilant PRO monitoring in clinical practice.

Funding: This study was funded by an unrestricted grant from the Novo Nordisk Fonden.

背景和目的:患者报告结果(PROs)对于评估治疗效果和估计炎症性肠病(IBD)的负担至关重要。我们对确诊 IBD 时的患者报告结果进行了调查:方法:我们在哥本哈根 IBD 初诊队列中评估了短式炎症性肠病问卷(SIBDQ)、IBD-残疾指数(IBD-DI)、慢性疾病治疗疲劳功能评估(FACIT-F)以及疾病活动相关的 PROs:结果:共招募了 203 名 UC 和 116 名 CD 患者。在确诊时,分别有 160 名(78.8%)和 99 名(85.3%)UC 和 CD 患者报告至少一项 PRO 存在中度至重度损伤(P=0.18),分别有 89 名(43.8%)和 74 名(63.8%)患者报告至少两项 PRO 存在中度至重度损伤(P结论:我们发现,在新诊断的 IBD 患者中,患者报告的疾病负担很重,这强调了在临床实践中警惕性监测 PRO 的重要性:本研究由诺和诺德基金会(Novo Nordisk Fonden)无限制资助。
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引用次数: 0
Outcomes of Long-term Tumor Necrosis Factor Alpha Inhibitor Therapy Beyond 10 Years in Inflammatory Bowel Disease. 炎症性肠病患者长期接受肿瘤坏死因子α抑制剂治疗十年后的疗效。
IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-24 DOI: 10.1016/j.cgh.2024.09.018
Quinten Dicken, Mmeyeneabasi Omede, Ashwin N Ananthakrishnan
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引用次数: 0
Letter Response to: Hernandez-Rocha C et al, Clin Gastroenterol Hepatol 2024. 信件回复:Hernandez-Rocha C 等人,Clin Gastroenterol Hepatol 2024。
IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-24 DOI: 10.1016/j.cgh.2024.09.026
Emily K Wright, Michael A Kamm
{"title":"Letter Response to: Hernandez-Rocha C et al, Clin Gastroenterol Hepatol 2024.","authors":"Emily K Wright, Michael A Kamm","doi":"10.1016/j.cgh.2024.09.026","DOIUrl":"10.1016/j.cgh.2024.09.026","url":null,"abstract":"","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496181","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}
引用次数: 0
Dysphagia Megalatriensis. Megalatriensis 吞咽困难症。
IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-10-24 DOI: 10.1016/j.cgh.2024.08.050
Zehra Naseem, Arjun Chatterjee, Yi Qin
{"title":"Dysphagia Megalatriensis.","authors":"Zehra Naseem, Arjun Chatterjee, Yi Qin","doi":"10.1016/j.cgh.2024.08.050","DOIUrl":"https://doi.org/10.1016/j.cgh.2024.08.050","url":null,"abstract":"","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496259","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}
引用次数: 0
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Clinical Gastroenterology and Hepatology
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