Gastric cancer (GC) is a leading cause of cancer-related mortality worldwide, with Helicobacter pylori (H. pylori) infection recognized as a significant risk factor. H. pylori infects approximately 50% of the global population, contributing to chronic gastritis, peptic ulcers, and the development of GC. The oncoprotein Gankyrin (PSMD10) has been implicated in various human cancers, including hepatocellular carcinoma, gastric cancer, and lung cancer, by modulating autophagy and inflammatory pathways.
Methods
In this study, we explored the role of Gankyrin in H. pylori-induced gastric tumorigenesis via a Swiss albino mouse xenograft model. Mice were subcutaneously injected with H. pylori-infected AGS cells with or without Gankyrin knockdown.
Results
We assessed tumor growth and inflammatory markers (TNF-α and IL-6) levels and Gankyrin's downstream signaling molecules (p53, pRb, and NF-κB). Our results demonstrated that Gankyrin knockdown significantly decreased tumor formation in Swiss albino mice engrafted with H. Pylori-infected AGS cells. Notably, treatment with cyclosporine A significantly decreased the expression of TNF-α in all the AGS-engrafted mice except the PBS group. Moreover, our results show that the downregulation of Gankyrin significantly elevated the expression of NF-κB, pRb, and p53.
Conclusion
These findings suggest that Gankyrin plays a crucial role in H. pylori-mediated GC progression by modulating inflammatory and tumor suppressor pathways. Targeting Gankyrin could provide a therapeutic strategy to mitigate the development of GC associated with H. pylori infection.
{"title":"Gankyrin Inhibition Can Control Helicobacter pylori Generated Gastric Cancer Using In Vivo Xenograft Models","authors":"Dharmendra Kashyap, Pranit Hemant Bagde, Siddharth Singh, Nidhi Varshney, Tarun Prakash Verma, Anamika Singh, Hamendra Singh Parmar, Hem Chandra Jha","doi":"10.1111/hel.70046","DOIUrl":"https://doi.org/10.1111/hel.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gastric cancer (GC) is a leading cause of cancer-related mortality worldwide, with <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection recognized as a significant risk factor. <i>H. pylori</i> infects approximately 50% of the global population, contributing to chronic gastritis, peptic ulcers, and the development of GC. The oncoprotein Gankyrin (PSMD10) has been implicated in various human cancers, including hepatocellular carcinoma, gastric cancer, and lung cancer, by modulating autophagy and inflammatory pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we explored the role of Gankyrin in <i>H. pylori</i>-induced gastric tumorigenesis via a Swiss albino mouse xenograft model. Mice were subcutaneously injected with <i>H. pylori</i>-infected AGS cells with or without Gankyrin knockdown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We assessed tumor growth and inflammatory markers (TNF-α and IL-6) levels and Gankyrin's downstream signaling molecules (p53, pRb, and NF-κB). Our results demonstrated that Gankyrin knockdown significantly decreased tumor formation in Swiss albino mice engrafted with <i>H. Pylori</i>-infected AGS cells. Notably, treatment with cyclosporine A significantly decreased the expression of TNF-α in all the AGS-engrafted mice except the PBS group. Moreover, our results show that the downregulation of Gankyrin significantly elevated the expression of NF-κB, pRb, and p53.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that Gankyrin plays a crucial role in <i>H. pylori</i>-mediated GC progression by modulating inflammatory and tumor suppressor pathways. Targeting Gankyrin could provide a therapeutic strategy to mitigate the development of GC associated with <i>H. pylori</i> infection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Young Sin Cho, Sun Moon Kim, Sun Hyung Kang, Hee Seok Moon, Jae Kyu Sung, Ki Bae Bang, Sung Hyeok Ryou, Ki Bae Kim, Hae Joung Sul, Seung-Woo Lee
Background
The increasing trend of clarithromycin resistance in Helicobacter pylori (H. pylori) is the primary cause of failure of standard triple therapy. Concomitant therapy is recommended as an alternative in regions with high rates of clarithromycin resistance. Recently, tailored therapies based on resistance testing have emerged as viable treatment approaches. We aimed to compare the eradication rates and adverse effects of concomitant and tailored therapies.
Materials and Methods
We enrolled 319 patients diagnosed with H. pylori infection using dual-priming oligonucleotide (DPO) polymerase chain reaction (PCR) tests conducted in six hospitals across the Daejeon and Chungcheong regions of Korea. Based on DPO-PCR results, patients were randomly assigned to either the concomitant therapy group (non-bismuth quadruple therapy) or the tailored therapy group (standard triple therapy for clarithromycin-sensitive cases and bismuth quadruple therapy for clarithromycin-resistant cases). Demographics, eradication success rates, adverse effects, and patient compliance were assessed. Data were analyzed using modified intention-to-treat (mITT) and per-protocol (PP) analyses.
Results
The eradication rate was significantly higher in the tailored therapy group than in the concomitant therapy group in PP analysis (92.62% vs. 85.21%, p = 0.026). The severity of adverse effects was significantly greater in the concomitant therapy group than in the tailored therapy group (p = 0.025).
Conclusion
Considering the high eradication success rate and low severity of adverse effects, tailored therapy based on DPO-PCR is preferable to concomitant therapy without resistance testing for the treatment of H. pylori infection.
Trial Registration
Clinical Research Information Service (CRIS): KCT0004162
背景幽门螺杆菌（Helicobacter pylori， H. pylori）对克拉霉素耐药性的上升趋势是标准三联治疗失败的主要原因。在克拉霉素耐药率高的地区，建议采用联合治疗。最近，基于耐药性测试的量身定制疗法已成为可行的治疗方法。我们的目的是比较伴随治疗和定制治疗的根除率和不良反应。材料与方法采用双引物寡核苷酸（DPO）聚合酶链反应（PCR）方法，对大田和忠清地区6家医院诊断为幽门螺杆菌感染的319例患者进行了研究。根据DPO-PCR结果，患者被随机分配到合并治疗组（非铋四联治疗）或定制治疗组（克拉霉素敏感病例标准三联治疗，克拉霉素耐药病例铋四联治疗）。对人口统计学、根除成功率、不良反应和患者依从性进行了评估。使用改进的意向治疗（mITT）和方案分析（PP）对数据进行分析。结果在PP分析中，定制治疗组的根除率明显高于伴随治疗组（92.62% vs. 85.21%, p = 0.026）。合并治疗组不良反应严重程度显著高于定制治疗组（p = 0.025）。结论考虑到根除成功率高、不良反应严重程度低，基于DPO-PCR的个体化治疗比不进行耐药检测的联合治疗更适合幽门螺杆菌感染的治疗。临床研究信息服务中心（CRIS）： KCT0004162
{"title":"Comparison of Therapeutic Outcomes Between Concomitant Therapy and Tailored Therapy for Helicobacter pylori: A Multicenter, Prospective, and Randomized Study","authors":"Young Sin Cho, Sun Moon Kim, Sun Hyung Kang, Hee Seok Moon, Jae Kyu Sung, Ki Bae Bang, Sung Hyeok Ryou, Ki Bae Kim, Hae Joung Sul, Seung-Woo Lee","doi":"10.1111/hel.70040","DOIUrl":"https://doi.org/10.1111/hel.70040","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The increasing trend of clarithromycin resistance in <i>Helicobacter pylori</i> (<i>H. pylori</i>) is the primary cause of failure of standard triple therapy. Concomitant therapy is recommended as an alternative in regions with high rates of clarithromycin resistance. Recently, tailored therapies based on resistance testing have emerged as viable treatment approaches. We aimed to compare the eradication rates and adverse effects of concomitant and tailored therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We enrolled 319 patients diagnosed with <i>H. pylori</i> infection using dual-priming oligonucleotide (DPO) polymerase chain reaction (PCR) tests conducted in six hospitals across the Daejeon and Chungcheong regions of Korea. Based on DPO-PCR results, patients were randomly assigned to either the concomitant therapy group (non-bismuth quadruple therapy) or the tailored therapy group (standard triple therapy for clarithromycin-sensitive cases and bismuth quadruple therapy for clarithromycin-resistant cases). Demographics, eradication success rates, adverse effects, and patient compliance were assessed. Data were analyzed using modified intention-to-treat (mITT) and per-protocol (PP) analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The eradication rate was significantly higher in the tailored therapy group than in the concomitant therapy group in PP analysis (92.62% vs. 85.21%, <i>p</i> = 0.026). The severity of adverse effects was significantly greater in the concomitant therapy group than in the tailored therapy group (<i>p</i> = 0.025).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Considering the high eradication success rate and low severity of adverse effects, tailored therapy based on DPO-PCR is preferable to concomitant therapy without resistance testing for the treatment of <i>H. pylori</i> infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>Clinical Research Information Service (CRIS): KCT0004162</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V. Mishra, D. Dash, A. K. Panda, et al., “Efficacy of Lactobacillus spp. Supplementation in Helicobacter pylori Eradication: A Systematic Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis,” Helicobacter 29, no. 6 (2024): e70006, doi: https://doi.org/10.1111/hel.70006.
In the Abstract, Results (Sections 3.3–3.4), and GRADE evidence profile (Table 1), the risk ratio (RR) 95% CI values were mistakenly reported from Egger's regression 95% CI values (Table S3). Below, we provide a table of actual 95% CI values for RR as reported in the Forest plots (Figures 1–4).
We apologize for this error.
V. Mishra， D. Dash， A. K. Panda等，“补充乳酸杆菌对根除幽门螺杆菌的功效：随机对照试验的系统荟萃分析与试验序列分析”，《幽门螺杆菌》，第29期。6 (2024): e70006, doi: https://doi.org/10.1111/hel.70006.In摘要，结果（3.3-3.4节）和GRADE证据概要（表1），风险比（RR） 95% CI值错误地报告了Egger's回归95% CI值（表S3）。下面，我们提供了Forest图中报告的RR的实际95% CI值的表格（图1-4）。我们为这个错误道歉。
{"title":"Correction to “Efficacy of Lactobacillus spp. Supplementation in Helicobacter pylori Eradication: A Systematic Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis”","authors":"","doi":"10.1111/hel.70044","DOIUrl":"https://doi.org/10.1111/hel.70044","url":null,"abstract":"<p>V. Mishra, D. Dash, A. K. Panda, et al., “Efficacy of <i>Lactobacillus</i> spp. Supplementation in <i>Helicobacter pylori</i> Eradication: A Systematic Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis,” Helicobacter 29, no. 6 (2024): e70006, doi: https://doi.org/10.1111/hel.70006.</p><p>In the Abstract, Results (Sections 3.3–3.4), and GRADE evidence profile (Table 1), the risk ratio (RR) 95% CI values were mistakenly reported from Egger's regression 95% CI values (Table S3). Below, we provide a table of actual 95% CI values for RR as reported in the Forest plots (Figures 1–4).</p><p>We apologize for this error.</p>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hel.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074359","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: Is Tailored Bismuth Quadruple Therapy (With Clarithromycin or Furazolidone) Based on Fecal Molecular Susceptibility Testing in First-Line Helicobacter pylori Eradication Treatment More Effective? A Three-Arm, Multicenter Randomized Clinical Trial","authors":"Xinlu Ren, Zhiqiang Song","doi":"10.1111/hel.70043","DOIUrl":"https://doi.org/10.1111/hel.70043","url":null,"abstract":"","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143938992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoyan He, Han Chen, Fengdan Chen, Wei Su, Yan Wang, Die Hu, Jianwen Hu, Xiaoying Zhou
Background
Helicobacter pylori (H. pylori) infection has the capacity to alter the gut microbiota composition. There is a significant correlation between H. pylori infection and type 2 diabetes mellitus (T2DM). Further research is necessary to explore whether gut microbiota plays a role in the relationship between H. pylori and T2DM.
Method
Fecal samples were obtained from 44 patients with T2DM, including 20 who tested positive for H. pylori and 24 who tested negative. Intestinal microbiota composition was analyzed via 16S rRNA V3-V4 amplicon sequencing. Differences in microbial distribution and significant microbial biomarkers were identified between H. pylori positive and negative groups. A Spearman correlation analysis assessed the relationship between intestinal microbiota and glycemic parameters. Additionally, PICRUSt2 was used to predict intestinal bacterial functions.
Results
Results indicate that in H. pylori (+) T2DM patients, HbA1c levels were significantly higher (8.9% vs. 8.1%, p = 0.021), while both the C-peptide peak (3.70 vs. 5.98 ng/mL, p = 0.040) and fasting C-peptide levels (1.42 vs. 2.31 ng/mL, p = 0.008) were significantly lower compared to H. pylori (−) T2DM groups. A total of 11 colonic phyla and 100 genera were identified in all fecal samples. In groups positive for H. pylori, there was a significant enrichment of the phylum Proteobacteria, while the genera Lactobacillus, Butyricimonas, and Akkermansia were significantly reduced (all p < 0.05). Correlation analysis showed that the abundance of the genera Butyricimonas (p = 0.01) and Akkermansia (p = 0.048) were negatively correlated with fasting plasma glucose. KEGG pathway analysis indicated a significant enrichment of methylmalonyl-CoA mutase and succinyl-CoA in H. pylori-infected T2DM patients.
Conclusions
This study suggests that T2DM patients with H. pylori infection exhibit more impaired pancreatic islet function potentially due to H. pylori-induced alterations in the gut microbiota.
背景幽门螺杆菌（h.p ylori）感染能够改变肠道菌群组成。幽门螺杆菌感染与2型糖尿病（T2DM）有显著相关性。肠道菌群是否在幽门螺杆菌与T2DM的关系中发挥作用，还需要进一步的研究。方法对44例T2DM患者进行粪便标本采集，其中幽门螺旋杆菌阳性20例，阴性24例。通过16S rRNA V3-V4扩增子测序分析肠道菌群组成。在幽门螺杆菌阳性组和阴性组之间，微生物分布和显著的微生物生物标志物存在差异。Spearman相关分析评估了肠道微生物群与血糖参数之间的关系。此外，PICRUSt2被用于预测肠道细菌功能。结果与幽门螺杆菌（+）型T2DM组相比，HbA1c水平显著升高（8.9% vs. 8.1%, p = 0.021），而c肽峰值（3.70 vs. 5.98 ng/mL, p = 0.040）和空腹c肽水平（1.42 vs. 2.31 ng/mL, p = 0.008）均显著降低。所有粪便标本共鉴定出11个结肠门100个属。在幽门螺杆菌阳性的组中，变形杆菌门的数量显著增加，而乳酸杆菌、丁酸单胞菌和Akkermansia属的数量显著减少（p < 0.05）。相关分析显示，丁酸单胞菌属丰度（p = 0.01）和Akkermansia属丰度（p = 0.048）与空腹血糖呈负相关。KEGG通路分析显示，在幽门螺杆菌感染的T2DM患者中，甲基丙二酰辅酶a变化酶和琥珀酰辅酶a显著富集。结论：本研究表明，幽门螺杆菌感染的T2DM患者胰岛功能受损更严重，可能是由于幽门螺杆菌诱导的肠道微生物群改变。
{"title":"Characterization of Fecal Microbial Communities in Patients With Type 2 Diabetes Mellitus Combined With Helicobacter pylori Infection","authors":"Xiaoyan He, Han Chen, Fengdan Chen, Wei Su, Yan Wang, Die Hu, Jianwen Hu, Xiaoying Zhou","doi":"10.1111/hel.70041","DOIUrl":"https://doi.org/10.1111/hel.70041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>Helicobacter pylori</i> (<i>H. pylori</i>) infection has the capacity to alter the gut microbiota composition. There is a significant correlation between <i>H. pylori</i> infection and type 2 diabetes mellitus (T2DM). Further research is necessary to explore whether gut microbiota plays a role in the relationship between <i>H. pylori</i> and T2DM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Fecal samples were obtained from 44 patients with T2DM, including 20 who tested positive for <i>H. pylori</i> and 24 who tested negative. Intestinal microbiota composition was analyzed via 16S rRNA V3-V4 amplicon sequencing. Differences in microbial distribution and significant microbial biomarkers were identified between <i>H. pylori</i> positive and negative groups. A Spearman correlation analysis assessed the relationship between intestinal microbiota and glycemic parameters. Additionally, PICRUSt2 was used to predict intestinal bacterial functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Results indicate that in <i>H. pylori</i> (+) T2DM patients, HbA1c levels were significantly higher (8.9% vs. 8.1%, <i>p</i> = 0.021), while both the C-peptide peak (3.70 vs. 5.98 ng/mL, <i>p</i> = 0.040) and fasting C-peptide levels (1.42 vs. 2.31 ng/mL, <i>p</i> = 0.008) were significantly lower compared to <i>H. pylori</i> (−) T2DM groups. A total of 11 colonic phyla and 100 genera were identified in all fecal samples. In groups positive for <i>H. pylori</i>, there was a significant enrichment of the phylum <i>Proteobacteria</i>, while the genera <i>Lactobacillus</i>, <i>Butyricimonas</i>, and <i>Akkermansia</i> were significantly reduced (all <i>p</i> < 0.05). Correlation analysis showed that the abundance of the genera <i>Butyricimonas</i> (<i>p</i> = 0.01) and <i>Akkermansia</i> (<i>p</i> = 0.048) were negatively correlated with fasting plasma glucose. KEGG pathway analysis indicated a significant enrichment of methylmalonyl-CoA mutase and succinyl-CoA in <i>H. pylori</i>-infected T2DM patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study suggests that T2DM patients with <i>H. pylori</i> infection exhibit more impaired pancreatic islet function potentially due to <i>H. pylori</i>-induced alterations in the gut microbiota.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Duco T. Mülder, James F. O'Mahony, Dianqin Sun, Luuk A. van Duuren, Rosita van den Puttelaar, Matthias Harlass, Weiran Han, Robert J. Huang, Manon C. W. Spaander, Uri Ladabaum, Iris Lansdorp-Vogelaar
Background
Recent American College of Gastroenterology (ACG) guidelines recommend screening and eradicating Helicobacter pylori (H. pylori) in high-risk racial groups to prevent gastric cancer (GC), but do not provide guidance on the age to screen. We aimed to determine the optimal age for H. pylori screen-and-treat.
Materials and Methods
We developed a new microsimulation model, MISCAN-gastric, which was calibrated to SEER incidence and clinical studies on the natural history of GC. One-time screen-and-treat at ages 20–65 was compared to a no-screening scenario in terms of cumulative incidence reduction, number needed-to-screen (NNS) and number needed-to-treat (NNT) to prevent one GC case. The NNS represents the number of individuals that require testing to prevent one GC case, while the NNT reflects the number requiring treatment. The optimal age was investigated for a high-risk population subgroup (non-Hispanic [NH] Black males) and compared to other subgroups.
Results
Without screening, 332 noncardia GC cases occurred in a population of 100,000 NH Black males. H. pylori screen-and-treat reduced cumulative incidence by 43% when performed at age 20, but only by 5% when performed at age 65. The NNS was lowest at age 30 and increased markedly at older ages. The estimated NNS for test-ages 20, 30, 40, and 65 were 645, 563, 769, and 5487, respectively. The NNT was lowest at the youngest age (261) and increased with age to 448 at age 40 and 3681 at age 65. The NNT and NNS were substantially higher in groups with lower GC risk: the optimal NNT was four times higher in NH White females compared to non-Hispanic Black males.
Conclusion
H. pylori screen-and-treat maximized population benefits when performed before age 40, emphasizing the need for early interventions. When performed at the optimal age, the benefits of H. pylori screen-and-treat may outweigh the harms for high-risk racial groups.
{"title":"The Optimal Age of Helicobacter pylori Screen-and-Treat for Gastric Cancer Prevention in the United States","authors":"Duco T. Mülder, James F. O'Mahony, Dianqin Sun, Luuk A. van Duuren, Rosita van den Puttelaar, Matthias Harlass, Weiran Han, Robert J. Huang, Manon C. W. Spaander, Uri Ladabaum, Iris Lansdorp-Vogelaar","doi":"10.1111/hel.70039","DOIUrl":"https://doi.org/10.1111/hel.70039","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Recent American College of Gastroenterology (ACG) guidelines recommend screening and eradicating <i>Helicobacter pylori</i> (<i>H. pylori</i>) in high-risk racial groups to prevent gastric cancer (GC), but do not provide guidance on the age to screen. We aimed to determine the optimal age for <i>H. pylori</i> screen-and-treat.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We developed a new microsimulation model, MISCAN-gastric, which was calibrated to SEER incidence and clinical studies on the natural history of GC. One-time screen-and-treat at ages 20–65 was compared to a no-screening scenario in terms of cumulative incidence reduction, number needed-to-screen (NNS) and number needed-to-treat (NNT) to prevent one GC case. The NNS represents the number of individuals that require testing to prevent one GC case, while the NNT reflects the number requiring treatment. The optimal age was investigated for a high-risk population subgroup (non-Hispanic [NH] Black males) and compared to other subgroups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Without screening, 332 noncardia GC cases occurred in a population of 100,000 NH Black males. <i>H. pylori</i> screen-and-treat reduced cumulative incidence by 43% when performed at age 20, but only by 5% when performed at age 65. The NNS was lowest at age 30 and increased markedly at older ages. The estimated NNS for test-ages 20, 30, 40, and 65 were 645, 563, 769, and 5487, respectively. The NNT was lowest at the youngest age (261) and increased with age to 448 at age 40 and 3681 at age 65. The NNT and NNS were substantially higher in groups with lower GC risk: the optimal NNT was four times higher in NH White females compared to non-Hispanic Black males.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p><i>H. pylori</i> screen-and-treat maximized population benefits when performed before age 40, emphasizing the need for early interventions. When performed at the optimal age, the benefits of <i>H. pylori</i> screen-and-treat may outweigh the harms for high-risk racial groups.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hel.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914519","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}
Hanmei Yuan, Yuetong Li, Hui Wu, Jin Zhang, Tingting Xia, Bin Li, Chao Wu
Background
Helicobacter pylori (H. pylori) infection is one of the most important risk factors for chronic gastritis, gastric ulcers, and gastric cancer. Mast cells act as a crucial regulator in bacterial infection. The mechanisms underlying mast cell activation and their role in H. pylori infection remain poorly understood.
Materials and Methods
In gastric mucosal tissue, the number of mast cells, G-protein-coupled receptor 171 (GPR171) and CCL2 expression were detected by immunohistochemistry (IHC) or immunofluorescence between H. pylori-negative and H. pylori-positive patients. Mast cells were co-cultured with H. pylori, and transcriptome sequencing, RT-qPCR, and Western blotting (WB) were performed to identify receptors involved in mast cell activation. WB, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays were conducted to investigate the molecular mechanism by which HIF-1α regulates GPR171 expression. Lentiviral knockdown, ELISA, WB, and IHC were used to evaluate the role of GPR171 during H. pylori infection. An in vivo mouse model of H. pylori infection was employed to assess the effects of GPR171 blockade on CCL2 expression and gastric mucosal inflammation.
Results
In the study, we found that mast cell numbers were greatly increased and correlated with the severity of inflammation in H. pylori-infected patients. We found a new receptor, GPR171, was upregulated and involved in mast cell activation upon H. pylori infection. Furthermore, H. pylori infection induced the expression of GPR171 by promoting the activation of hypoxia-inducible factor 1 alpha (HIF-1α), which directly bound to hypoxia response elements in the GPR171 promoter and regulated its transcriptional activity. Blockade or loss of GPR171 in mast cells partially inhibited CCL2 secretion via the ERK1/2 signaling pathway. In the human gastric mucosa, CCL2 derived from mast cells was associated with gastric inflammation during H. pylori infection. In vivo murine studies indicated that H. pylori infection significantly upregulated CCL2 expression, while GPR171 inhibition partially reduced CCL2 levels and alleviated gastric mucosal inflammation.
Conclusions
We provide a novel mechanism that H. pylori activates mast cells to promote gastric inflammation.
{"title":"HIF-1α-Induced GPR171 Expression Mediates CCL2 Secretion by Mast Cells to Promote Gastric Inflammation During Helicobacter pylori Infection","authors":"Hanmei Yuan, Yuetong Li, Hui Wu, Jin Zhang, Tingting Xia, Bin Li, Chao Wu","doi":"10.1111/hel.70042","DOIUrl":"https://doi.org/10.1111/hel.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>Helicobacter pylori</i> (<i>H. pylori</i>) infection is one of the most important risk factors for chronic gastritis, gastric ulcers, and gastric cancer. Mast cells act as a crucial regulator in bacterial infection. The mechanisms underlying mast cell activation and their role in <i>H. pylori</i> infection remain poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In gastric mucosal tissue, the number of mast cells, G-protein-coupled receptor 171 (GPR171) and CCL2 expression were detected by immunohistochemistry (IHC) or immunofluorescence between <i>H. pylori</i>-negative and <i>H. pylori</i>-positive patients. Mast cells were co-cultured with <i>H. pylori</i>, and transcriptome sequencing, RT-qPCR, and Western blotting (WB) were performed to identify receptors involved in mast cell activation. WB, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays were conducted to investigate the molecular mechanism by which HIF-1α regulates GPR171 expression. Lentiviral knockdown, ELISA, WB, and IHC were used to evaluate the role of GPR171 during <i>H. pylori</i> infection. An in vivo mouse model of <i>H. pylori</i> infection was employed to assess the effects of GPR171 blockade on CCL2 expression and gastric mucosal inflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the study, we found that mast cell numbers were greatly increased and correlated with the severity of inflammation in <i>H. pylori-</i>infected patients. We found a new receptor, GPR171, was upregulated and involved in mast cell activation upon <i>H. pylori</i> infection. Furthermore, <i>H. pylori</i> infection induced the expression of GPR171 by promoting the activation of hypoxia-inducible factor 1 alpha (HIF-1α), which directly bound to hypoxia response elements in the GPR171 promoter and regulated its transcriptional activity. Blockade or loss of GPR171 in mast cells partially inhibited CCL2 secretion via the ERK1/2 signaling pathway. In the human gastric mucosa, CCL2 derived from mast cells was associated with gastric inflammation during <i>H. pylori</i> infection. In vivo murine studies indicated that <i>H. pylori</i> infection significantly upregulated CCL2 expression, while GPR171 inhibition partially reduced CCL2 levels and alleviated gastric mucosal inflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We provide a novel mechanism that <i>H. pylori</i> activates mast cells to promote gastric inflammation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hel.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905010","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}
Tegoprazan, a new class of drugs, is a potassium-competitive acid blocker (P-CAB) that inhibits gastric H+/K+-ATPase through a different mechanism than proton pump inhibitor. Tetracycline also has anti-Helicobacter pylori properties. However, only a few randomized controlled trials (RCTs) have investigated the efficacy of tegoprazan and tetracycline-containing quadruple therapy (TTQT) for treating H. pylori infections, which this RCT explored.
Methods
This multicenter RCT included treatment-naïve adults with H. pylori infection who received 7 or 14 days of TTQT (50-mg tegoprazan, 220-mg bismuth potassium citrate, and 1000-mg amoxicillin twice daily with 500-mg tetracycline four times daily). The primary outcome was the eradication rate; secondary endpoints included the incidence of adverse events, treatment compliance, and regimen costs.
Results
The study included 258 patients. The eradication rates in the 7- and 14-day groups were 90.70% (117/129, 95% confidence interval [CI]: 83.98%–94.89%) and 91.47% (118/129, 95% CI: 84.90%–95.45%), respectively, in the intention-to-treat analysis (difference: −0.78%; −7.01%–8.58%; noninferiority p < 0.001); 92.86% (117/126, 95% CI: 86.50%–96.48%) and 93.65% (118/126, 95% CI: 87.47%–97.02%), respectively, in the modified intention-to-treat analysis (difference: 0.79%; 95% CI: −6.36%–7.99%; noninferiority p < 0.001); and 94.35% (117/124, 95% CI: 88.29%–97.50%) and 95.12% (117/123, 95% CI: 89.24%–98.00%), respectively, in the per-protocol analysis (difference: −0.77%; 95% CI: −5.91%–7.48%; noninferiority p < 0.001). Significantly fewer adverse events occurred in the 7-day group than in the 14-day group (22.48% vs. 35.67%, p = 0.020). Treatment compliance did not differ between the two groups.
Conclusions
The 7- and 14-day TTQT efficacies for the first-line treatment of H. pylori infection were comparable, and fewer adverse effects occurred in the 7-day group. This trial has been registered at Clinical Trials.gov (NCT05997433).
{"title":"Seven-Day Versus 14-Day Tegoprazan and Tetracycline-Containing Quadruple Therapy for First-Line Eradication of Helicobacter pylori Infection: A Randomized, Open-Label, Noninferiority Trial","authors":"Xue-Ping Nan, Hong-Yu Zhao, Lei-Na Guo, Rui-Qi Zheng, Xi-Lan Wang, Yong-Fen Wang, Yan-Hua Su, Wen-Rong Geng, Xiu-Lan Liu, Hai-Miao Xu, Ke-Lun Zhou, Yu-Ting Guo, Jian-Hua Cao, Zhong-Xue Han, Qing-Zhou Kong, Xiu-Li Zuo, Yan-Qing Li, Yue-Yue Li","doi":"10.1111/hel.70036","DOIUrl":"https://doi.org/10.1111/hel.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Tegoprazan, a new class of drugs, is a potassium-competitive acid blocker (P-CAB) that inhibits gastric H+/K+-ATPase through a different mechanism than proton pump inhibitor. Tetracycline also has anti-<i>Helicobacter pylori</i> properties. However, only a few randomized controlled trials (RCTs) have investigated the efficacy of tegoprazan and tetracycline-containing quadruple therapy (TTQT) for treating <i>H. pylori</i> infections, which this RCT explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This multicenter RCT included treatment-naïve adults with <i>H. pylori</i> infection who received 7 or 14 days of TTQT (50-mg tegoprazan, 220-mg bismuth potassium citrate, and 1000-mg amoxicillin twice daily with 500-mg tetracycline four times daily). The primary outcome was the eradication rate; secondary endpoints included the incidence of adverse events, treatment compliance, and regimen costs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included 258 patients. The eradication rates in the 7- and 14-day groups were 90.70% (117/129, 95% confidence interval [CI]: 83.98%–94.89%) and 91.47% (118/129, 95% CI: 84.90%–95.45%), respectively, in the intention-to-treat analysis (difference: −0.78%; −7.01%–8.58%; noninferiority <i>p</i> < 0.001); 92.86% (117/126, 95% CI: 86.50%–96.48%) and 93.65% (118/126, 95% CI: 87.47%–97.02%), respectively, in the modified intention-to-treat analysis (difference: 0.79%; 95% CI: −6.36%–7.99%; noninferiority <i>p</i> < 0.001); and 94.35% (117/124, 95% CI: 88.29%–97.50%) and 95.12% (117/123, 95% CI: 89.24%–98.00%), respectively, in the per-protocol analysis (difference: −0.77%; 95% CI: −5.91%–7.48%; noninferiority <i>p</i> < 0.001). Significantly fewer adverse events occurred in the 7-day group than in the 14-day group (22.48% vs. 35.67%, <i>p</i> = 0.020). Treatment compliance did not differ between the two groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The 7- and 14-day TTQT efficacies for the first-line treatment of <i>H. pylori</i> infection were comparable, and fewer adverse effects occurred in the 7-day group. This trial has been registered at Clinical Trials.gov (NCT05997433).</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji-Yan Li, Ji-Chun Song, Xia Tian, Yun-Hua Liu, Xiang-Wu Ding, Ya Lin, Zhen-Yu Zhang, Hai Zhang, De-Min Li, Xiao-Wei Huang, Yun-Lian Hu, Li Li, Hong-Tian Li, Chao-Qun Huang, Pei-Yuan Li
Background
High-Dose Dual Therapy With Amoxicillin Has Shown Advantages to Eradicate Helicobacter pylori (H. pylori), but Not for Penicillin-Allergic Patients. It Is Recommended That Cefuroxime Could Be an Alternative, but Whether Cefuroxime Could Be Used in Dual Therapy Has Not Been Reported. This Study Aimed to Compare the Efficacy, Safety, and Compliance of Cefuroxime-Based Dual Therapy (CDT) With Cefuroxime-Based Bismuth Quadruple Therapy (CQT) to Treat H. pylori Infection.
Materials and Methods
The Prospective, Multicenter, Open-Label, Randomized Controlled Trial Was Conducted to Enroll Patients With Treatment-Naive H. pylori Infection From 9 Institutions. Patients Were Randomly Assigned to CDT Group (Cefuroxime 500 Mg Three Times/Day and Vonoprazan 20 Mg Twice/Day) or CQT Group (Cefuroxime 500 Mg Twice/Day, Levofloxacin 500 Mg Once/Day, Vonoprazan 20 Mg Twice/Day, and Bismuth 220 Mg Twice/Day), both for 14 Days.
Results
700 Patients (350 per Group) Were Enrolled. In the Intention-To-Treat Analysis, Eradication Rates Were 76.0% and 86.3% in CDT Group and CQT Group (P = 0.001). In the Modified Intention-To-Treat Analysis, Eradication Rates Were 78.9% and 89.1% (P < 0.001). In the Per-Protocol Analysis, Eradication Rates Were 80.2% and 91.2% (P < 0.001). The Incidence of Adverse Events Was Significantly Lower in CDT Group Than CQT Group (14.4% vs. 29.8%, P < 0.001). Non-inferiority Was Confirmed Between CDT and CQT Group (All P > 0.025). Compliance Was Good in Both Groups (96.0% vs. 92.8%, P = 0.073). Poor Adherence Was a Risk Factor for Reducing the Efficacy in Both Groups.
Conclusions
CQT Was More Effective Than CDT for H. pylori Eradication, Which Might Be Recommended for Penicillin-Allergic Patients. If There Were Contraindications or Intolerance of CQT, CDT Would Be an Alternative.
Trail Registration
ChiCTR2300071210
背景：大剂量阿莫西林双重治疗对根除幽门螺杆菌有优势，但对青霉素过敏患者无效。推荐头孢呋辛作为替代方案，但头孢呋辛是否可用于双重治疗尚未见报道。本研究旨在比较头孢呋辛双重治疗（CDT）与头孢呋辛铋四联治疗（CQT）治疗幽门螺杆菌感染的疗效、安全性和依从性。材料与方法本研究采用前瞻性、多中心、开放标签、随机对照试验，纳入来自9家医院的初治疗幽门螺杆菌感染患者。患者被随机分配到CDT组（头孢呋辛500 Mg 3次/天，Vonoprazan 20 Mg 2次/天）或CQT组（头孢呋辛500 Mg 2次/天，左氧氟沙星500 Mg 1次/天，Vonoprazan 20 Mg 2次/天，铋220 Mg 2次/天），疗程均为14天。结果入组患者700例，每组350例。在意向治疗分析中，CDT组和CQT组的根除率分别为76.0%和86.3% （P = 0.001）。在修正意向治疗分析中，根除率分别为78.9%和89.1% （P < 0.001）。在Per-Protocol Analysis中，根除率分别为80.2%和91.2% （P < 0.001）。CDT组不良事件发生率明显低于CQT组（14.4% vs 29.8%, P < 0.001）。CDT组与CQT组间无劣效性（P > 0.025）。两组依从性均良好（96.0% vs. 92.8%, P = 0.073）。依从性差是降低两组疗效的危险因素。结论CQT对幽门螺杆菌的根除效果优于CDT，可推荐用于青霉素过敏患者。如果有禁忌症或CQT不耐受，CDT将是一种选择。跟踪注册ChiCTR2300071210
{"title":"Comparison of Cefuroxime-Based Dual Therapy With Quadruple Therapy in Helicobacter pylori-Infected Treatment-Naive Patients: A Prospective, Multicenter, Randomized Controlled Trial","authors":"Ji-Yan Li, Ji-Chun Song, Xia Tian, Yun-Hua Liu, Xiang-Wu Ding, Ya Lin, Zhen-Yu Zhang, Hai Zhang, De-Min Li, Xiao-Wei Huang, Yun-Lian Hu, Li Li, Hong-Tian Li, Chao-Qun Huang, Pei-Yuan Li","doi":"10.1111/hel.70037","DOIUrl":"https://doi.org/10.1111/hel.70037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>High-Dose Dual Therapy With Amoxicillin Has Shown Advantages to Eradicate <i>Helicobacter pylori</i> (<i>H. pylori</i>), but Not for Penicillin-Allergic Patients. It Is Recommended That Cefuroxime Could Be an Alternative, but Whether Cefuroxime Could Be Used in Dual Therapy Has Not Been Reported. This Study Aimed to Compare the Efficacy, Safety, and Compliance of Cefuroxime-Based Dual Therapy (CDT) With Cefuroxime-Based Bismuth Quadruple Therapy (CQT) to Treat <i>H. pylori</i> Infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>The Prospective, Multicenter, Open-Label, Randomized Controlled Trial Was Conducted to Enroll Patients With Treatment-Naive <i>H. pylori</i> Infection From 9 Institutions. Patients Were Randomly Assigned to CDT Group (Cefuroxime 500 Mg Three Times/Day and Vonoprazan 20 Mg Twice/Day) or CQT Group (Cefuroxime 500 Mg Twice/Day, Levofloxacin 500 Mg Once/Day, Vonoprazan 20 Mg Twice/Day, and Bismuth 220 Mg Twice/Day), both for 14 Days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>700 Patients (350 per Group) Were Enrolled. In the Intention-To-Treat Analysis, Eradication Rates Were 76.0% and 86.3% in CDT Group and CQT Group (<i>P</i> = 0.001). In the Modified Intention-To-Treat Analysis, Eradication Rates Were 78.9% and 89.1% (<i>P</i> < 0.001). In the Per-Protocol Analysis, Eradication Rates Were 80.2% and 91.2% (<i>P</i> < 0.001). The Incidence of Adverse Events Was Significantly Lower in CDT Group Than CQT Group (14.4% vs. 29.8%, <i>P</i> < 0.001). Non-inferiority Was Confirmed Between CDT and CQT Group (All <i>P</i> > 0.025). Compliance Was Good in Both Groups (96.0% vs. 92.8%, <i>P</i> = 0.073). Poor Adherence Was a Risk Factor for Reducing the Efficacy in Both Groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CQT Was More Effective Than CDT for <i>H. pylori</i> Eradication, Which Might Be Recommended for Penicillin-Allergic Patients. If There Were Contraindications or Intolerance of CQT, CDT Would Be an Alternative.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trail Registration</h3>\u0000 \u0000 <p>ChiCTR2300071210</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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