Nhu Thi Hanh Vu, Duc Trong Quach, Mai Ngoc Luu, Shunsuke Miyauchi, Naoki Ishiuchi, Doan Thi Nha Nguyen, Atsuo Yoshino, Yoshie Miyake, Yuri Okamoto, Shiro Oka, Toru Hiyama
Introduction: Uninvestigated dyspepsia (UD) and chronic constipation (CC) are common disorders of gut-brain interaction. However, limited research has assessed their risk factors in young adults, particularly the influence of family history. This study investigated the associated factors for UD and CC, focusing on family history among Japanese university students.
Methods: A cross-sectional study was conducted at Hiroshima University. UD and CC were diagnosed using the Rome IV criteria. Multivariate logistic regression was performed to identify associated factors of UD and CC.
Results: Among 10,500 individuals participating in the annual health checkup, 7,496 responded to the web-based questionnaire, and 5,386 completed it. The mean age of the participants was 21.1 ± 4.1 years, with a male-to-female ratio of 1:1.17. The prevalence of UD and CC was 7.3% and 13.7%, respectively. Family history was associated with both UD (odds ratio [OR]: 4.29; 95% confidence interval [CI]: 3.17-5.79) and CC (OR: 2.77; 95% CI: 2.31-3.31). Depression and physical inactivity were shared associated factors. Alcohol consumption (OR = 2.36; 95% CI: 1.15-4.83) and smoking (OR = 1.59; 95% CI: 1.02-2.49) were identified as associated factors for UD, while female sex (OR = 2.00; 95% CI: 1.69-2.36) and short sleep duration (OR = 1.28; 95% CI: 1.09-1.50) were associated with CC.
Conclusions: Family history was found to be a predominant factor associated with both UD and CC, with a relatively stronger association for UD. Our finding highlights the need to consider familial factors in future prevention and intervention strategies for UD and CC in young adults.
{"title":"Family History as a Dominant Risk Factor for Uninvestigated Dyspepsia and Chronic Constipation: A Rome IV-Based Study among Japanese University Students.","authors":"Nhu Thi Hanh Vu, Duc Trong Quach, Mai Ngoc Luu, Shunsuke Miyauchi, Naoki Ishiuchi, Doan Thi Nha Nguyen, Atsuo Yoshino, Yoshie Miyake, Yuri Okamoto, Shiro Oka, Toru Hiyama","doi":"10.1159/000548363","DOIUrl":"10.1159/000548363","url":null,"abstract":"<p><strong>Introduction: </strong>Uninvestigated dyspepsia (UD) and chronic constipation (CC) are common disorders of gut-brain interaction. However, limited research has assessed their risk factors in young adults, particularly the influence of family history. This study investigated the associated factors for UD and CC, focusing on family history among Japanese university students.</p><p><strong>Methods: </strong>A cross-sectional study was conducted at Hiroshima University. UD and CC were diagnosed using the Rome IV criteria. Multivariate logistic regression was performed to identify associated factors of UD and CC.</p><p><strong>Results: </strong>Among 10,500 individuals participating in the annual health checkup, 7,496 responded to the web-based questionnaire, and 5,386 completed it. The mean age of the participants was 21.1 ± 4.1 years, with a male-to-female ratio of 1:1.17. The prevalence of UD and CC was 7.3% and 13.7%, respectively. Family history was associated with both UD (odds ratio [OR]: 4.29; 95% confidence interval [CI]: 3.17-5.79) and CC (OR: 2.77; 95% CI: 2.31-3.31). Depression and physical inactivity were shared associated factors. Alcohol consumption (OR = 2.36; 95% CI: 1.15-4.83) and smoking (OR = 1.59; 95% CI: 1.02-2.49) were identified as associated factors for UD, while female sex (OR = 2.00; 95% CI: 1.69-2.36) and short sleep duration (OR = 1.28; 95% CI: 1.09-1.50) were associated with CC.</p><p><strong>Conclusions: </strong>Family history was found to be a predominant factor associated with both UD and CC, with a relatively stronger association for UD. Our finding highlights the need to consider familial factors in future prevention and intervention strategies for UD and CC in young adults.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-9"},"PeriodicalIF":3.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023091","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}
Background: Irritable bowel syndrome (IBS) affects 4.1% of the global population, posing a significant healthcare challenge due to its complex pathophysiology and limited treatment options. Gut microbiota-derived volatile organic compounds (VOCs) are increasingly recognized as key players in IBS, with the potential for noninvasive diagnostics and personalized management.
Summary: This review examines VOCs - such as short-chain fatty acids, hydrocarbons, and alcohols - as microbial metabolites influencing IBS through gut barrier function, inflammation, motility, and gut-brain signaling. Cross-sectional studies highlight the diagnostic accuracy of VOCs (area under the curve 0.76-0.99) in distinguishing IBS from healthy controls and conditions like inflammatory bowel disease, while longitudinal studies underscore their utility in predicting and reflecting microbial changes to microbiota-targeted therapies. Despite this promise, variability in study designs, methodological inconsistencies, and confounding factors hinder clinical translation.
Key messages: VOCs illuminate the microbial underpinnings of IBS and its gut-brain interactions, offering a pathway to precise diagnosis and treatment stratification. However, their full potential awaits standardized sampling, analytical protocols, and robust clinical trials to ensure reliability and applicability in IBS care.
{"title":"Volatile Organic Compounds in Irritable Bowel Syndrome: Microbial Insights into Gut-Brain Dynamics and Clinical Applications.","authors":"Dinh Chuong Nguyen, Sutep Gonlachanvit, Thanikan Sukaram, Tanisa Patcharatrakul","doi":"10.1159/000548310","DOIUrl":"10.1159/000548310","url":null,"abstract":"<p><strong>Background: </strong>Irritable bowel syndrome (IBS) affects 4.1% of the global population, posing a significant healthcare challenge due to its complex pathophysiology and limited treatment options. Gut microbiota-derived volatile organic compounds (VOCs) are increasingly recognized as key players in IBS, with the potential for noninvasive diagnostics and personalized management.</p><p><strong>Summary: </strong>This review examines VOCs - such as short-chain fatty acids, hydrocarbons, and alcohols - as microbial metabolites influencing IBS through gut barrier function, inflammation, motility, and gut-brain signaling. Cross-sectional studies highlight the diagnostic accuracy of VOCs (area under the curve 0.76-0.99) in distinguishing IBS from healthy controls and conditions like inflammatory bowel disease, while longitudinal studies underscore their utility in predicting and reflecting microbial changes to microbiota-targeted therapies. Despite this promise, variability in study designs, methodological inconsistencies, and confounding factors hinder clinical translation.</p><p><strong>Key messages: </strong>VOCs illuminate the microbial underpinnings of IBS and its gut-brain interactions, offering a pathway to precise diagnosis and treatment stratification. However, their full potential awaits standardized sampling, analytical protocols, and robust clinical trials to ensure reliability and applicability in IBS care.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-10"},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999979","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}
Momen Mohamed Ibrahim, Bisher Sawaf, Noheir Ashraf Ibrahem Fathy Hassan, Momen Hassan Moussa, Mayar Ibrahim, Karam R Motawea, Muhammed Elhadi, Yaseen Alastal
Background: Azathioprine (AZA) is the standard treatment for both induction and maintenance of response in autoimmune hepatitis (AIH). However, lifelong administration is often required, and the combination therapy of prednisolone and azathioprine raises significant concerns regarding efficacy and tolerability, especially given the high relapse rates following AZA cessation. Consequently, there is a need to explore alternative treatment options. This systematic review and meta-analysis compared the efficacy and safety of mycophenolate mofetil (MMF) versus AZA, combined with prednisolone, for treating AIH.
Methods: PubMed, Cochrane, Scopus, and Web of Science were searched to identify randomized clinical trials and cohort studies comparing AZA and MMF for treating AIH. Four studies compared steroid withdrawal and complete biochemical response (CBR) between the MMF and AZA groups. Subgroup analyses were performed based on age (above and below 50 years) and IgG levels (above and below 2400 mg/dL). RevMan (version 5.4) software was used for meta-analysis.
Results: Four studies (three cohort studies and one RCT) comprising 505 patients were included in the final analysis. The pooled analysis showed a statistically significant association between the MMF group and increased CBR compared with the AZA group (RR = 1.44, 95% CI = 1.03 to 2.01, p-value = 0.03), with no significant difference between the two groups regarding steroid withdrawal. Subgroup analysis by age revealed a significant association between the MMF group and increased CBR in patients over 50 years (RR = 1.63, 95% CI = 1.00-2.64, p-value = 0.05). IgG subgroup analysis revealed a significant association between the MMF group and increased biochemical remission compared with the AZA group in patients with IgG levels of less than 2400 mg/dL (RR = 1.63, 95% CI = 1.00-2.64, p-value = 0.05).
Conclusion: The use of MMF was significantly associated with increased CBR compared to AZA in patients with AIH. Additionally, there was no significant association between the two groups regarding steroid withdrawal. Further research is needed to fully elucidate the optimal treatment strategy for AIH patients across different subpopulations.
背景:硫唑嘌呤(AZA)是诱导和维持自身免疫性肝炎(AIH)反应的标准治疗方法。然而,通常需要终身给药,强的松龙和硫唑嘌呤联合治疗引起了对疗效和耐受性的重大关注,特别是考虑到停用AZA后的高复发率。因此,有必要探索替代治疗方案。本系统综述和荟萃分析比较了霉酚酸酯(MMF)与AZA联合强的松龙治疗AIH的疗效和安全性。方法:检索PubMed、Cochrane、Scopus和Web of Science,以确定比较AZA和MMF治疗AIH的随机临床试验和队列研究。四项研究比较了MMF组和AZA组的类固醇停药和完全生化反应(CBR)。根据年龄(50岁以上及以下)和IgG水平(2400 mg/dL以上及以下)进行亚组分析。采用RevMan (version 5.4)软件进行meta分析。结果:4项研究(3项队列研究和1项随机对照试验)共505例患者纳入最终分析。合并分析显示,与AZA组相比,MMF组与CBR增加有统计学意义(RR = 1.44, 95% CI = 1.03 ~ 2.01, p值= 0.03),两组在类固醇停药方面无显著差异。年龄亚组分析显示,MMF组与50岁以上患者CBR增加之间存在显著相关性(RR = 1.63, 95% CI = 1.00-2.64, p值= 0.05)。IgG亚组分析显示,在IgG水平低于2400 mg/dL的患者中,与AZA组相比,MMF组与生化缓解增加之间存在显著相关性(RR = 1.63, 95% CI = 1.00-2.64, p值= 0.05)。结论:与AZA相比,MMF的使用与AIH患者CBR的增加显著相关。此外,两组在类固醇戒断方面没有显著的相关性。需要进一步的研究来充分阐明不同亚群AIH患者的最佳治疗策略。
{"title":"Comparative Efficacy of Mycophenolate Mofetil vs. Azathioprine in Autoimmune Hepatitis: A Systematic Review and Meta-Analysis.","authors":"Momen Mohamed Ibrahim, Bisher Sawaf, Noheir Ashraf Ibrahem Fathy Hassan, Momen Hassan Moussa, Mayar Ibrahim, Karam R Motawea, Muhammed Elhadi, Yaseen Alastal","doi":"10.1159/000548140","DOIUrl":"10.1159/000548140","url":null,"abstract":"<p><strong>Background: </strong>Azathioprine (AZA) is the standard treatment for both induction and maintenance of response in autoimmune hepatitis (AIH). However, lifelong administration is often required, and the combination therapy of prednisolone and azathioprine raises significant concerns regarding efficacy and tolerability, especially given the high relapse rates following AZA cessation. Consequently, there is a need to explore alternative treatment options. This systematic review and meta-analysis compared the efficacy and safety of mycophenolate mofetil (MMF) versus AZA, combined with prednisolone, for treating AIH.</p><p><strong>Methods: </strong>PubMed, Cochrane, Scopus, and Web of Science were searched to identify randomized clinical trials and cohort studies comparing AZA and MMF for treating AIH. Four studies compared steroid withdrawal and complete biochemical response (CBR) between the MMF and AZA groups. Subgroup analyses were performed based on age (above and below 50 years) and IgG levels (above and below 2400 mg/dL). RevMan (version 5.4) software was used for meta-analysis.</p><p><strong>Results: </strong>Four studies (three cohort studies and one RCT) comprising 505 patients were included in the final analysis. The pooled analysis showed a statistically significant association between the MMF group and increased CBR compared with the AZA group (RR = 1.44, 95% CI = 1.03 to 2.01, p-value = 0.03), with no significant difference between the two groups regarding steroid withdrawal. Subgroup analysis by age revealed a significant association between the MMF group and increased CBR in patients over 50 years (RR = 1.63, 95% CI = 1.00-2.64, p-value = 0.05). IgG subgroup analysis revealed a significant association between the MMF group and increased biochemical remission compared with the AZA group in patients with IgG levels of less than 2400 mg/dL (RR = 1.63, 95% CI = 1.00-2.64, p-value = 0.05).</p><p><strong>Conclusion: </strong>The use of MMF was significantly associated with increased CBR compared to AZA in patients with AIH. Additionally, there was no significant association between the two groups regarding steroid withdrawal. Further research is needed to fully elucidate the optimal treatment strategy for AIH patients across different subpopulations.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Gel immersion endoscopy (GIE) is a technique used to maintain a clear view during gastric endoscopic submucosal dissection. We aimed to identify cases most likely to benefit from GIE for ESD bleeding by reviewing our clinical experience and determining the associated factors.
Methods: We retrospectively analyzed 470 lesions in 380 patients who underwent gastric ESD between October 2020 and March 2023. The patients were divided into conventional method (n = 433) and GIE groups (n = 37). We compared the clinical and pathological characteristics between the groups. Univariate and multivariate logistic regression analyses were used to identify factors associated with GIE use. Among the GIE group, hemostasis times under gas, water, and gel conditions were compared using the Kruskal-Wallis test.
Results: Multivariate analysis revealed that dialysis (odds ratio [OR]: 15.3), concurrent antiplatelet and anticoagulant use (OR: 9.5), and tumor location in the middle third (OR: 3.5), upper third (OR: 5.7), or remnant stomach (OR: 9.3) were independently associated with GIE use. No significant differences in overall hemostasis time were observed between gas, water, or gel. Of the nine bleeding events exceeding 300 s under gas immersion, seven achieved successful hemostasis by switching to GIE, with a median of 32 s to locate the source and 140 s to complete hemostasis.
Conclusion: Dialysis, combined antithrombotic use, and certain tumor locations were key factors influencing GIE for ESD bleeding. Although the overall hemostasis times did not differ, GIE may be particularly beneficial in high-risk scenarios.
{"title":"Dialysis, Antithrombotics, and Lesion Location: Who Benefits Most from Gel Immersion Endoscopy in Gastric Endoscopic Submucosal Dissection?","authors":"Hiroki Hayashi, Takeshi Kanno, Tomonori Yano, Kazuaki Akahoshi, Jun Owada, Hiromi Sekiguchi, Takashi Ueno, Yoshie Nomoto, Hisashi Fukuda, Haruo Takahashi, Yuji Ino, Hironori Yamamoto","doi":"10.1159/000548018","DOIUrl":"10.1159/000548018","url":null,"abstract":"<p><strong>Introduction: </strong>Gel immersion endoscopy (GIE) is a technique used to maintain a clear view during gastric endoscopic submucosal dissection. We aimed to identify cases most likely to benefit from GIE for ESD bleeding by reviewing our clinical experience and determining the associated factors.</p><p><strong>Methods: </strong>We retrospectively analyzed 470 lesions in 380 patients who underwent gastric ESD between October 2020 and March 2023. The patients were divided into conventional method (n = 433) and GIE groups (n = 37). We compared the clinical and pathological characteristics between the groups. Univariate and multivariate logistic regression analyses were used to identify factors associated with GIE use. Among the GIE group, hemostasis times under gas, water, and gel conditions were compared using the Kruskal-Wallis test.</p><p><strong>Results: </strong>Multivariate analysis revealed that dialysis (odds ratio [OR]: 15.3), concurrent antiplatelet and anticoagulant use (OR: 9.5), and tumor location in the middle third (OR: 3.5), upper third (OR: 5.7), or remnant stomach (OR: 9.3) were independently associated with GIE use. No significant differences in overall hemostasis time were observed between gas, water, or gel. Of the nine bleeding events exceeding 300 s under gas immersion, seven achieved successful hemostasis by switching to GIE, with a median of 32 s to locate the source and 140 s to complete hemostasis.</p><p><strong>Conclusion: </strong>Dialysis, combined antithrombotic use, and certain tumor locations were key factors influencing GIE for ESD bleeding. Although the overall hemostasis times did not differ, GIE may be particularly beneficial in high-risk scenarios.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-9"},"PeriodicalIF":3.6,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Duodenal laparoscopic and endoscopic cooperative surgery (D-LECS) is a promising hybrid approach to managing duodenal neoplasia, including superficial non-ampullary duodenal epithelial tumors (SNADETs) and subepithelial lesions (SELs). This approach aims to reduce adverse events (AEs), such as delayed perforation, often associated with endoscopic submucosal dissection (ESD). Combining laparoscopic techniques for duodenal stabilization with precise endoscopic resection, D-LECS may provide safer and more comprehensive treatment. However, few studies have compared the outcomes of D-LECS with those of ESD and full-thickness resection (FTR), and suitable endoscopic resection approaches for D-LECS remain unclear.
Methods: We retrospectively reviewed records of 80 patients who underwent D-LECS for duodenal neoplasia at our institution between 2011 and 2024. Fifty-six patients underwent D-LECS with ESD for SNADETs (ESD group), whereas 24 underwent D-LECS with FTR for 16 SELs and 8 SNADETs (FTR group). All patients underwent en bloc resection, showing an overall R0 resection rate of 92.5%.
Results: There was no significant difference in overall incidence of Clavien-Dindo grade II or higher AEs between the ESD and FTR groups. However, the ESD group tended to have fewer cases of delayed gastric emptying and higher inflammatory response (p = 0.087 and p = 0.063, respectively). One patient in the FTR group experienced delayed perforation and 2 patients in the ESD group experienced delayed bleeding. However, these events were not significant.
Conclusions: Both D-LECS with ESD and FTR were effective and safe. D-LECS with ESD may be a more suitable approach for SNADETs, whereas D-LECS with FTR is preferable for SELs.
{"title":"Current Management of Laparoscopic and Endoscopic Cooperative Surgery for Duodenal Neoplasia: Suitable Endoscopic Resection Approaches.","authors":"Hiroyuki Yamamoto, Shoichi Yoshimizu, Masaru Hayami, Kosuke Tanaka, Makoto Tamamushi, Koyo Kido, Wataru Kurihara, Chika Fukuyama, Yusuke Horiuchi, Toshiyuki Yoshio, Toshiaki Hirasawa, Souya Nunobe","doi":"10.1159/000547890","DOIUrl":"10.1159/000547890","url":null,"abstract":"<p><strong>Introduction: </strong>Duodenal laparoscopic and endoscopic cooperative surgery (D-LECS) is a promising hybrid approach to managing duodenal neoplasia, including superficial non-ampullary duodenal epithelial tumors (SNADETs) and subepithelial lesions (SELs). This approach aims to reduce adverse events (AEs), such as delayed perforation, often associated with endoscopic submucosal dissection (ESD). Combining laparoscopic techniques for duodenal stabilization with precise endoscopic resection, D-LECS may provide safer and more comprehensive treatment. However, few studies have compared the outcomes of D-LECS with those of ESD and full-thickness resection (FTR), and suitable endoscopic resection approaches for D-LECS remain unclear.</p><p><strong>Methods: </strong>We retrospectively reviewed records of 80 patients who underwent D-LECS for duodenal neoplasia at our institution between 2011 and 2024. Fifty-six patients underwent D-LECS with ESD for SNADETs (ESD group), whereas 24 underwent D-LECS with FTR for 16 SELs and 8 SNADETs (FTR group). All patients underwent en bloc resection, showing an overall R0 resection rate of 92.5%.</p><p><strong>Results: </strong>There was no significant difference in overall incidence of Clavien-Dindo grade II or higher AEs between the ESD and FTR groups. However, the ESD group tended to have fewer cases of delayed gastric emptying and higher inflammatory response (p = 0.087 and p = 0.063, respectively). One patient in the FTR group experienced delayed perforation and 2 patients in the ESD group experienced delayed bleeding. However, these events were not significant.</p><p><strong>Conclusions: </strong>Both D-LECS with ESD and FTR were effective and safe. D-LECS with ESD may be a more suitable approach for SNADETs, whereas D-LECS with FTR is preferable for SELs.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-6"},"PeriodicalIF":3.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854848","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}
Introduction: The aim of the study was to explore the molecular mechanism of E3 ubiquitin ligase neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L) regulating high-glucose and high-fat-induced ferroptosis in hepatocytes via modulation of transforming growth factor (TGF)-β1/Smad signaling pathway.
Methods: Hepatocytes THLE-2 were cultured in high-glucose and high-fat medium to establish an in vitro nonalcoholic fatty liver disease model. This study detected cellular lipid deposition, cell viability, cellular superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA), ferrous iron (Fe2+), reactive oxygen species (ROS) levels, and cellular mitochondrial membrane potential (MMP). Meanwhile, cellular NEDD4L, GPX4, ACSL4, SLC7A11, TGF-β1, TβRII, and p-Smad2/3 levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. In addition, TGF-β1-TβRII and NEDD4L-TβRII interactions were evaluated by co-immunoprecipitation.
Results: High-glucose and high-fat treatment led to ferroptosis in hepatocytes, manifested by decreased cell viability, SOD activity, and GSH level, increased MDA, Fe2+, and ROS levels, and reduced MMP. High-glucose and high-fat treatment downregulated NEDD4L expression in hepatocytes; by contrast, overexpression of NEDD4L alleviated ferroptosis in hepatocytes. NEDD4L inhibited TGF-β1 signaling by mediating TβRII ubiquitination and degradation. Besides, suppressed TGF-β1/Smad signaling pathway alleviated ferroptosis in hepatocytes, and NEDD4L could regulate hepatocyte ferroptosis by mediating TGF-β1/Smad signaling pathway.
Conclusion: NEDD4L can inhibit high-glucose and high-fat-induced ferroptosis in hepatocytes through suppressing the TGF-β1/Smad signaling pathway via mediating TβRII ubiquitination and degradation.
目的:探讨E3泛素连接酶神经前体细胞表达发育下调4样细胞(NEDD4L)通过调节转化生长因子(TGF)-β1/Smad信号通路调控高糖、高脂诱导肝细胞铁下垂的分子机制。方法:在高糖高脂培养基中培养肝细胞THLE-2,建立体外非酒精性脂肪肝(NAFLD)模型。本研究检测了细胞脂质沉积、细胞活力、细胞超氧化物歧化酶(SOD)活性、谷胱甘肽(GSH)、丙二醛(MDA)、亚铁(Fe2+)、活性氧(ROS)水平和细胞线粒体膜电位(MMP)。同时采用实时荧光定量pcr和western blot检测细胞内NEDD4L、GPX4、ACSL4、SLC7A11、TGF-β1、t -β rii和p-Smad2/3水平。此外,通过共免疫沉淀法评估TGF-β1- t -β rii和nedd4l - t -β rii的相互作用。结果:高糖高脂处理导致肝细胞铁下垂,表现为细胞活力、SOD活性、GSH水平下降,MDA、Fe2+、ROS水平升高,MMP降低。高糖高脂治疗下调肝细胞NEDD4L表达;相反,过表达NEDD4L可减轻肝细胞铁下垂。NEDD4L通过介导t -β rii泛素化和降解抑制TGF-β1信号传导。抑制TGF-β1/Smad信号通路可减轻肝细胞铁下垂,NEDD4L可通过介导TGF-β1/Smad信号通路调节肝细胞铁下垂。结论:NEDD4L通过介导TβRII泛素化和降解,抑制TGF-β1/Smad信号通路,从而抑制高糖、高脂诱导的肝细胞铁凋亡。
{"title":"E3 Ubiquitin Ligase NEDD4L Regulates the TGF-β1/Smad Signaling Pathway to Mediate High-Glucose and High-Fat-Induced Ferroptosis of Hepatocytes.","authors":"Fang Li, Jiayi Yao, Jianhua Yao, Yusen Mou, Dan Li, Limin Wei","doi":"10.1159/000547407","DOIUrl":"10.1159/000547407","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of the study was to explore the molecular mechanism of E3 ubiquitin ligase neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L) regulating high-glucose and high-fat-induced ferroptosis in hepatocytes via modulation of transforming growth factor (TGF)-β1/Smad signaling pathway.</p><p><strong>Methods: </strong>Hepatocytes THLE-2 were cultured in high-glucose and high-fat medium to establish an in vitro nonalcoholic fatty liver disease model. This study detected cellular lipid deposition, cell viability, cellular superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA), ferrous iron (Fe2+), reactive oxygen species (ROS) levels, and cellular mitochondrial membrane potential (MMP). Meanwhile, cellular NEDD4L, GPX4, ACSL4, SLC7A11, TGF-β1, TβRII, and p-Smad2/3 levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. In addition, TGF-β1-TβRII and NEDD4L-TβRII interactions were evaluated by co-immunoprecipitation.</p><p><strong>Results: </strong>High-glucose and high-fat treatment led to ferroptosis in hepatocytes, manifested by decreased cell viability, SOD activity, and GSH level, increased MDA, Fe2+, and ROS levels, and reduced MMP. High-glucose and high-fat treatment downregulated NEDD4L expression in hepatocytes; by contrast, overexpression of NEDD4L alleviated ferroptosis in hepatocytes. NEDD4L inhibited TGF-β1 signaling by mediating TβRII ubiquitination and degradation. Besides, suppressed TGF-β1/Smad signaling pathway alleviated ferroptosis in hepatocytes, and NEDD4L could regulate hepatocyte ferroptosis by mediating TGF-β1/Smad signaling pathway.</p><p><strong>Conclusion: </strong>NEDD4L can inhibit high-glucose and high-fat-induced ferroptosis in hepatocytes through suppressing the TGF-β1/Smad signaling pathway via mediating TβRII ubiquitination and degradation.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-15"},"PeriodicalIF":3.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759453","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}
Background: Helicobacter pylori (H. pylori) eradication reduces the risk of gastric cancer development and is effective in patients with chronic atrophic gastritis. Recently, an increase in gastric cancer incidence has been observed in daily clinical practice in patients who have undergone H. pylori eradication. Therefore, continuous surveillance endoscopy is important for detecting gastric cancer after H. pylori eradication. In addition, endoscopic findings may differ between non-eradication and post-eradication gastric cancer. Magnifying endoscopy with narrow band imaging (ME-NBI) has been useful for the diagnosis of post-eradication gastric cancer, regardless of the histological type. However, there have been no comprehensive reports in this regard. Here, we aimed to clarify the characteristics of ME-NBI findings in gastric cancer following H. pylori eradication.
Summary: In differentiated- and mixed-type cancers (a mixture of differentiated and undifferentiated type), the cancer may be covered by noncancerous epithelium following H. pylori eradication; however, abnormalities can still be detected using ME-NBI. Therefore, ME-NBI is suitable for the diagnosis of post-eradication gastric cancer. In undifferentiated-type cancer, ME-NBI is more useful in diagnosing post-eradication gastric cancer than non-eradicated gastric cancer because of the clear contrast between cancerous and noncancerous areas following eradication. In addition, when non-eradicated gastric cancer is detected, rather than performing endoscopic submucosal dissection (ESD) or gastrectomy without eradication, it is beneficial to start patients on eradication therapy immediately and diagnose the disease extent with ME-NBI without awaiting the results of the eradication assessment and performing ESD or gastrectomy. This approach is expected to prevent misdiagnosis of the tumor size and reduce the positivity of the horizontal margin in ESD or gastrectomy.
Key messages: The number of post-eradication gastric cancer cases is expected to increase in comparison to non-eradicated gastric cancer cases, as H. pylori eradication is being widely used in chronic atrophic gastritis cases. Therefore, the diagnosis of post-eradication gastric cancer using ME-NBI is expected to gain importance in daily clinical practice.
{"title":"Characteristics of Magnifying Endoscopy with Narrow Band Imaging Findings in Gastric Cancer after <italic>Helicobacter pylori</italic> Eradication.","authors":"Yusuke Horiuchi, Noriko Yamamoto","doi":"10.1159/000547574","DOIUrl":"10.1159/000547574","url":null,"abstract":"<p><strong>Background: </strong>Helicobacter pylori (H. pylori) eradication reduces the risk of gastric cancer development and is effective in patients with chronic atrophic gastritis. Recently, an increase in gastric cancer incidence has been observed in daily clinical practice in patients who have undergone H. pylori eradication. Therefore, continuous surveillance endoscopy is important for detecting gastric cancer after H. pylori eradication. In addition, endoscopic findings may differ between non-eradication and post-eradication gastric cancer. Magnifying endoscopy with narrow band imaging (ME-NBI) has been useful for the diagnosis of post-eradication gastric cancer, regardless of the histological type. However, there have been no comprehensive reports in this regard. Here, we aimed to clarify the characteristics of ME-NBI findings in gastric cancer following H. pylori eradication.</p><p><strong>Summary: </strong>In differentiated- and mixed-type cancers (a mixture of differentiated and undifferentiated type), the cancer may be covered by noncancerous epithelium following H. pylori eradication; however, abnormalities can still be detected using ME-NBI. Therefore, ME-NBI is suitable for the diagnosis of post-eradication gastric cancer. In undifferentiated-type cancer, ME-NBI is more useful in diagnosing post-eradication gastric cancer than non-eradicated gastric cancer because of the clear contrast between cancerous and noncancerous areas following eradication. In addition, when non-eradicated gastric cancer is detected, rather than performing endoscopic submucosal dissection (ESD) or gastrectomy without eradication, it is beneficial to start patients on eradication therapy immediately and diagnose the disease extent with ME-NBI without awaiting the results of the eradication assessment and performing ESD or gastrectomy. This approach is expected to prevent misdiagnosis of the tumor size and reduce the positivity of the horizontal margin in ESD or gastrectomy.</p><p><strong>Key messages: </strong>The number of post-eradication gastric cancer cases is expected to increase in comparison to non-eradicated gastric cancer cases, as H. pylori eradication is being widely used in chronic atrophic gastritis cases. Therefore, the diagnosis of post-eradication gastric cancer using ME-NBI is expected to gain importance in daily clinical practice.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-10"},"PeriodicalIF":3.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689540","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}
Cheng-Long Wang, Xiang-Yu Sui, Yi Zeng, Jia-Yi Wu, Jun-Jie Xing, Song Zhang, Jia-Hui Wei, Kevin Chang, Yi-Ta Wu, Zhao-Shen Li, Sheng-Bing Zhao, Yu Bai, En-Da Yu
Background: Colorectal neoplasia poses a severe health threat worldwide. The accurate measurement of polyp size is essential for risk stratification, selecting polypectomy techniques, and determining the surveillance interval.
Summary: The methods routinely used for measuring polyp size, including objective ex vivo measurement, subjective visual estimation by an endoscopist, and objective precise measurement using endoscopic instruments, all have limitations. Therefore, the integration of artificial intelligence (AI) with endoscopy has been explored as a promising method for measuring the size of colorectal polyps. However, current AI systems are limited to endoscopic reference media or nonprospective real-time measurements. Consequently, AI-assisted endoscopy for precise, real-time automatic measurement of colorectal polyp size holds great promise for the future. Nevertheless, further extensive studies are necessary.
Key messages: This review focuses on summarizing the advancements in colorectal polyp size research and further explores the potential of AI-assisted measurements.
{"title":"Colorectal Polyp Size Measurement Faces Infinite Possibilities: Artificial Intelligence Is the Key.","authors":"Cheng-Long Wang, Xiang-Yu Sui, Yi Zeng, Jia-Yi Wu, Jun-Jie Xing, Song Zhang, Jia-Hui Wei, Kevin Chang, Yi-Ta Wu, Zhao-Shen Li, Sheng-Bing Zhao, Yu Bai, En-Da Yu","doi":"10.1159/000547299","DOIUrl":"10.1159/000547299","url":null,"abstract":"<p><strong>Background: </strong>Colorectal neoplasia poses a severe health threat worldwide. The accurate measurement of polyp size is essential for risk stratification, selecting polypectomy techniques, and determining the surveillance interval.</p><p><strong>Summary: </strong>The methods routinely used for measuring polyp size, including objective ex vivo measurement, subjective visual estimation by an endoscopist, and objective precise measurement using endoscopic instruments, all have limitations. Therefore, the integration of artificial intelligence (AI) with endoscopy has been explored as a promising method for measuring the size of colorectal polyps. However, current AI systems are limited to endoscopic reference media or nonprospective real-time measurements. Consequently, AI-assisted endoscopy for precise, real-time automatic measurement of colorectal polyp size holds great promise for the future. Nevertheless, further extensive studies are necessary.</p><p><strong>Key messages: </strong>This review focuses on summarizing the advancements in colorectal polyp size research and further explores the potential of AI-assisted measurements.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-11"},"PeriodicalIF":3.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Esophageal cancer-associated fistula is strongly linked to elevated mortality. This study aims to investigate the impact of endoscopic closure on outcomes in patients with esophageal cancer-related fistula.
Methods: We retrospectively analyzed the clinical data of patients with esophageal cancer-related fistula. These patients were categorized into endoscopic closure group and conservative treatment group. The Clinical Pulmonary Infection Score (CPIS) gap, duration of hospitalization, ICU admission rates, in-hospital mortality rates, and hospitalization costs were compared between endoscopic group and conservative group. Additionally, factors associated with post-fistula survival and healing were assessed.
Results: Univariate and multivariate COX regression analyses revealed that endoscopic closure could significantly improve short-term pulmonary infections based on CPIS gap (3 vs. 2; p = 0.004) but did not influence survival or fistula healing outcomes, and the hospitalization costs were elevated (USD 6,653 vs. USD 3,350; p = 0.005). Subgroup analysis focusing on esophagotracheal fistulas was also consistent with these results. Protective factors associated with improved survival prognosis included higher albumin levels (HR = 0.928, 95% CI: 0.875-0.984, p = 0.012), absence of bloodstream infections (positive blood culture [HR = 23.055, 95% CI: 5.193-102.357, p < 0.001]), non-T4 stage (T4 stage [HR = 1.792, 95% CI: 1.052-3.052, p = 0.032]), and no distant metastasis (distant metastasis [HR = 2.122, 95% CI: 1.127-3.996, p = 0.020]). Cervical esophageal fistula (upper [HR = 0.154, 95% CI: 0.041-0.570, p = 0.005]; middle [HR = 0.128, 95% CI: 0.027-0.609, p = 0.010]; lower [HR = 0.218, 95% CI: 0.052-0.902, p = 0.036]) was significantly associated with improved fistula healing outcomes, while a history of radiotherapy (HR = 0.265, 95% CI: 0.089-0.788, p = 0.017) was a risk factor for esophageal fistula healing.
Conclusion: Our study indicates that multiple factors are significantly associated with the prognosis of patients with esophageal fistula. Endoscopic closure treatment effectively manages short-term infections, but it associates with higher hospitalization costs and does not significantly enhance long-term healing or survival prognosis.
{"title":"The Impact of Endoscopic Closure Treatment on Outcomes in Patients with Esophageal Cancer-Associated Fistula: A Retrospective Analysis.","authors":"Qijie Dai, Xian Zhao, Weipeng Lu, Yitian Wang, Jiepeng Cen, Heqing Tao, Liang Peng","doi":"10.1159/000547231","DOIUrl":"10.1159/000547231","url":null,"abstract":"<p><strong>Introduction: </strong>Esophageal cancer-associated fistula is strongly linked to elevated mortality. This study aims to investigate the impact of endoscopic closure on outcomes in patients with esophageal cancer-related fistula.</p><p><strong>Methods: </strong>We retrospectively analyzed the clinical data of patients with esophageal cancer-related fistula. These patients were categorized into endoscopic closure group and conservative treatment group. The Clinical Pulmonary Infection Score (CPIS) gap, duration of hospitalization, ICU admission rates, in-hospital mortality rates, and hospitalization costs were compared between endoscopic group and conservative group. Additionally, factors associated with post-fistula survival and healing were assessed.</p><p><strong>Results: </strong>Univariate and multivariate COX regression analyses revealed that endoscopic closure could significantly improve short-term pulmonary infections based on CPIS gap (3 vs. 2; p = 0.004) but did not influence survival or fistula healing outcomes, and the hospitalization costs were elevated (USD 6,653 vs. USD 3,350; p = 0.005). Subgroup analysis focusing on esophagotracheal fistulas was also consistent with these results. Protective factors associated with improved survival prognosis included higher albumin levels (HR = 0.928, 95% CI: 0.875-0.984, p = 0.012), absence of bloodstream infections (positive blood culture [HR = 23.055, 95% CI: 5.193-102.357, p < 0.001]), non-T4 stage (T4 stage [HR = 1.792, 95% CI: 1.052-3.052, p = 0.032]), and no distant metastasis (distant metastasis [HR = 2.122, 95% CI: 1.127-3.996, p = 0.020]). Cervical esophageal fistula (upper [HR = 0.154, 95% CI: 0.041-0.570, p = 0.005]; middle [HR = 0.128, 95% CI: 0.027-0.609, p = 0.010]; lower [HR = 0.218, 95% CI: 0.052-0.902, p = 0.036]) was significantly associated with improved fistula healing outcomes, while a history of radiotherapy (HR = 0.265, 95% CI: 0.089-0.788, p = 0.017) was a risk factor for esophageal fistula healing.</p><p><strong>Conclusion: </strong>Our study indicates that multiple factors are significantly associated with the prognosis of patients with esophageal fistula. Endoscopic closure treatment effectively manages short-term infections, but it associates with higher hospitalization costs and does not significantly enhance long-term healing or survival prognosis.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-10"},"PeriodicalIF":3.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682214","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}
Background: Superficial non-ampullary duodenal epithelial tumors (SNADETs) were previously considered rare. However, the widespread use of health checkup endoscopy, improvements in endoscopic imaging and heightened awareness of SNADETs among endoscopists have recently led to an increase in their detection rate. Particularly for large SNADETs, the possibility of including cancer must be considered, and thus, complete and reliable resection is essential. Although surgical resection has traditionally been the standard treatment, its high invasiveness has led to increased interest in less invasive endoscopic treatments. Nevertheless, due to the unique anatomical and physiological features of the duodenum, endoscopic treatment in the duodenum remains highly challenging and presents many technical difficulties.
Summary: This review provides a comprehensive overview of current endoscopic treatment options for large SNADETs, including conventional endoscopic mucosal resection (C-EMR), underwater endoscopic mucosal resection (U-EMR), cold snare endoscopic mucosal resection (CS-EMR), endoscopic submucosal dissection (ESD), and laparoscopic-endoscopic cooperative surgery, incorporating the latest clinical findings. While C-EMR, U-EMR, and CS-EMR are associated with lower technical difficulty and favorable safety, they tend to show lower en bloc resection rates and higher recurrence rates for large SNADETs when compared to ESD. In contrast, ESD offers higher en bloc resection rates but carries a greater risk of complications due to its technical complexity. To overcome these limitations, several techniques have been developed, such as the pocket-creation method, water pressure method, improved closure strategies for mucosal defects, and drainage with endoscopic nasobiliary and pancreatic drainage to prevent exposure to pancreatic juice and bile.
Key messages: Multiple endoscopic strategies are available for the treatment of large SNADETs. However, due to the rarity of the disease and variation in institutional expertise, a standardized treatment strategy has not yet been established. Endoscopic treatment for large SNADETs is technically very challenging and carries a high risk. Therefore, careful consideration of the indication for each treatment method, along with a full understanding of their respective advantages and disadvantages, is essential. In recent years, the safety of endoscopic resection has been gradually improving due to various technical innovations and better management of adverse events, making ESD, which offers a high en bloc resection rate, an increasingly reasonable treatment option.
{"title":"Current Management of Duodenal Neoplasia: Endoscopic Treatment for Large Superficial Non-Ampullary Duodenal Epithelial Tumor.","authors":"Kurato Miyazaki, Naohisa Yahagi, Motohiko Kato","doi":"10.1159/000547461","DOIUrl":"10.1159/000547461","url":null,"abstract":"<p><strong>Background: </strong>Superficial non-ampullary duodenal epithelial tumors (SNADETs) were previously considered rare. However, the widespread use of health checkup endoscopy, improvements in endoscopic imaging and heightened awareness of SNADETs among endoscopists have recently led to an increase in their detection rate. Particularly for large SNADETs, the possibility of including cancer must be considered, and thus, complete and reliable resection is essential. Although surgical resection has traditionally been the standard treatment, its high invasiveness has led to increased interest in less invasive endoscopic treatments. Nevertheless, due to the unique anatomical and physiological features of the duodenum, endoscopic treatment in the duodenum remains highly challenging and presents many technical difficulties.</p><p><strong>Summary: </strong>This review provides a comprehensive overview of current endoscopic treatment options for large SNADETs, including conventional endoscopic mucosal resection (C-EMR), underwater endoscopic mucosal resection (U-EMR), cold snare endoscopic mucosal resection (CS-EMR), endoscopic submucosal dissection (ESD), and laparoscopic-endoscopic cooperative surgery, incorporating the latest clinical findings. While C-EMR, U-EMR, and CS-EMR are associated with lower technical difficulty and favorable safety, they tend to show lower en bloc resection rates and higher recurrence rates for large SNADETs when compared to ESD. In contrast, ESD offers higher en bloc resection rates but carries a greater risk of complications due to its technical complexity. To overcome these limitations, several techniques have been developed, such as the pocket-creation method, water pressure method, improved closure strategies for mucosal defects, and drainage with endoscopic nasobiliary and pancreatic drainage to prevent exposure to pancreatic juice and bile.</p><p><strong>Key messages: </strong>Multiple endoscopic strategies are available for the treatment of large SNADETs. However, due to the rarity of the disease and variation in institutional expertise, a standardized treatment strategy has not yet been established. Endoscopic treatment for large SNADETs is technically very challenging and carries a high risk. Therefore, careful consideration of the indication for each treatment method, along with a full understanding of their respective advantages and disadvantages, is essential. In recent years, the safety of endoscopic resection has been gradually improving due to various technical innovations and better management of adverse events, making ESD, which offers a high en bloc resection rate, an increasingly reasonable treatment option.</p>","PeriodicalId":11315,"journal":{"name":"Digestion","volume":" ","pages":"1-15"},"PeriodicalIF":3.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682213","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}