Helicobacter pylori (H. pylori) colonizes the stomach and leads to the secretion of a vast range of cytokines by infiltrated leukocytes directing immune/inflammatory response against the bacterium. To regulate immune/inflammatory responses, suppressors of cytokine signaling (SOCS) proteins bind to multiple signaling components located downstream of cytokine receptors, such as Janus kinase (JAK), signal transducers and activators of transcription (STAT). Dysfunctional SOCS proteins in immune cells may facilitate the immune evasion of H. pylori, allowing the bacteria to induce chronic inflammation. Dysregulation of SOCS expression and function can contribute to the sustained H. pylori-mediated gastric inflammation which can lead to gastric cancer (GC) development. Among SOCS molecules, dysregulated expression of SOCS1, SOCS2, SOCS3, and SOCS6 were indicated in H. pylori-infected individuals as well as in GC tissues and cells. H. pylori-induced SOCS1, SOCS2, SOCS3, and SOCS6 dysregulation can contribute to the GC development. The expression of SOCS molecules can be influenced by various factors, such as epigenetic DNA methylation, noncoding RNAs, and gene polymorphisms. Modulation of the expression of SOCS molecules in gastric epithelial cells and immune cells can be considered to control gastric carcinogenesis as well as regulate antitumor immune responses, respectively. This review aimed to explain the interplay between H. pylori and SOCS molecules in GC development and immune response induction as well as to provide insights regarding potential therapeutic strategies modulating SOCS molecules.
{"title":"The Interplay Between Helicobacter pylori and Suppressors of Cytokine Signaling (SOCS) Molecules in the Development of Gastric Cancer and Induction of Immune Response","authors":"Abdollah Jafarzadeh, Zahra Jafarzadeh, Maryam Nemati, Akihiko Yoshimura","doi":"10.1111/hel.13105","DOIUrl":"10.1111/hel.13105","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Helicobacter pylori</i> (<i>H. pylori</i>) colonizes the stomach and leads to the secretion of a vast range of cytokines by infiltrated leukocytes directing immune/inflammatory response against the bacterium. To regulate immune/inflammatory responses, suppressors of cytokine signaling (SOCS) proteins bind to multiple signaling components located downstream of cytokine receptors, such as Janus kinase (JAK), signal transducers and activators of transcription (STAT). Dysfunctional SOCS proteins in immune cells may facilitate the immune evasion of <i>H. pylori</i>, allowing the bacteria to induce chronic inflammation. Dysregulation of SOCS expression and function can contribute to the sustained <i>H. pylori</i>-mediated gastric inflammation which can lead to gastric cancer (GC) development. Among SOCS molecules, dysregulated expression of SOCS1, SOCS2, SOCS3, and SOCS6 were indicated in <i>H. pylori</i>-infected individuals as well as in GC tissues and cells. <i>H. pylori</i>-induced SOCS1, SOCS2, SOCS3, and SOCS6 dysregulation can contribute to the GC development. The expression of SOCS molecules can be influenced by various factors, such as epigenetic DNA methylation, noncoding RNAs, and gene polymorphisms. Modulation of the expression of SOCS molecules in gastric epithelial cells and immune cells can be considered to control gastric carcinogenesis as well as regulate antitumor immune responses, respectively. This review aimed to explain the interplay between <i>H. pylori</i> and SOCS molecules in GC development and immune response induction as well as to provide insights regarding potential therapeutic strategies modulating SOCS molecules.</p>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"29 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456447","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}
Shu Sahara, Mitsushige Sugimoto, Masaki Murata, Eri Iwata, Takashi Kawai, Kazunari Murakami, Yoshio Yamaoka, Tadashi Shimoyama
Patients receiving hemodialysis (HD) often develop gastrointestinal diseases. Recently, although in general population, clinical guidelines for Helicobacter pylori have strongly recommended its eradication in patients to prevent gastric cancer, optimal eradication regimen and optimal dosage of drugs for patients receiving HD have not been established, due to possible incidence of adverse events. Some antimicrobial agents used in eradication therapy, particularly amoxicillin, can exacerbate renal dysfunction. Given the delayed pharmacokinetics of drugs in patients receiving HD compared with those in healthy individuals, drug regimen and dosage should be considered to minimize adverse effects. Although previous studies have investigated the benefits of eradication therapy for patients receiving HD, because most studies were small in terms of the number of enrolled patients, it is hard to show evidence. The numbers of eradication in HD patients have recently increased, and it is important to provide an optimal regimen. The consideration of eradication in patients undergoing HD with a reduction in the drug dose by 1/2–1/3 may prevent adverse events. Additionally, another important consideration is whether adverse events can be prevented while maintaining a similar eradication rate with reduced drug dosages. Recent meta-analysis findings indicate comparable eradication rates in patients receiving HD and healthy individuals, both with the same dosage regimen and at a reduced dosage regimen, with no significant differences (relative risk [RR] for successful eradication: 0.85 [95% confidence interval (CI): 0.48–1.50]). Unlike with the same dosage regimen (RR for adverse events: 3.15 [95% CI: 1.93–5.13]), the adverse events in the dosage reduction regimen were similar to those in healthy individuals (RR: 1.26 [95% CI: 0.23–6.99]). From a pharmacological perspective, the eradication regimen in patients receiving HD should consider the dosage (1/2–1/3 dosage), dosing number (bid), dosing timing of drugs (after HD), and susceptibility to antimicrobial agents.
接受血液透析（HD）的患者经常会患上胃肠道疾病。最近，尽管在普通人群中，幽门螺杆菌临床指南强烈建议患者根除幽门螺杆菌以预防胃癌，但由于可能发生的不良反应，接受血液透析患者的最佳根除方案和最佳用药剂量尚未确定。根除疗法中使用的一些抗菌药物，尤其是阿莫西林，会加重肾功能障碍。与健康人相比，接受血液透析患者的药物代谢动力学会有所延迟，因此应考虑药物治疗方案和剂量，以尽量减少不良反应。尽管之前的研究已经调查了根除疗法对接受血液透析患者的益处，但由于大多数研究的入选患者人数较少，因此很难拿出证据。最近，对 HD 患者进行根除治疗的人数有所增加，因此提供最佳治疗方案非常重要。在考虑对接受 HD 的患者进行根除治疗的同时，将药物剂量减少 1/2-1/3 可能会避免不良事件的发生。此外，另一个重要的考虑因素是，在减少药物剂量的情况下，能否在保持类似根除率的同时预防不良事件的发生。最近的荟萃分析结果表明，接受 HD 治疗的患者和健康人的根除率相当，无论是使用相同剂量方案还是减少剂量方案，都没有显著差异（成功根除的相对风险 [RR]：0.85 [95% 置信区间]）：0.85 [95% 置信区间 (CI)：0.48-1.50]）。与相同剂量方案不同（不良反应 RR：3.15 [95% CI：1.93-5.13]），减量方案的不良反应与健康人相似（RR：1.26 [95% CI：0.23-6.99]）。从药理学角度来看，接受 HD 治疗的患者的根除方案应考虑剂量（1/2-1/3 剂量）、给药次数（bid）、给药时间（HD 后）以及对抗菌药物的敏感性。
{"title":"Eradication Therapy for Helicobacter pylori Infection in Patients Receiving Hemodialysis: Review","authors":"Shu Sahara, Mitsushige Sugimoto, Masaki Murata, Eri Iwata, Takashi Kawai, Kazunari Murakami, Yoshio Yamaoka, Tadashi Shimoyama","doi":"10.1111/hel.13106","DOIUrl":"https://doi.org/10.1111/hel.13106","url":null,"abstract":"<div>\u0000 \u0000 <p>Patients receiving hemodialysis (HD) often develop gastrointestinal diseases. Recently, although in general population, clinical guidelines for <i>Helicobacter pylori</i> have strongly recommended its eradication in patients to prevent gastric cancer, optimal eradication regimen and optimal dosage of drugs for patients receiving HD have not been established, due to possible incidence of adverse events. Some antimicrobial agents used in eradication therapy, particularly amoxicillin, can exacerbate renal dysfunction. Given the delayed pharmacokinetics of drugs in patients receiving HD compared with those in healthy individuals, drug regimen and dosage should be considered to minimize adverse effects. Although previous studies have investigated the benefits of eradication therapy for patients receiving HD, because most studies were small in terms of the number of enrolled patients, it is hard to show evidence. The numbers of eradication in HD patients have recently increased, and it is important to provide an optimal regimen. The consideration of eradication in patients undergoing HD with a reduction in the drug dose by 1/2–1/3 may prevent adverse events. Additionally, another important consideration is whether adverse events can be prevented while maintaining a similar eradication rate with reduced drug dosages. Recent meta-analysis findings indicate comparable eradication rates in patients receiving HD and healthy individuals, both with the same dosage regimen and at a reduced dosage regimen, with no significant differences (relative risk [RR] for successful eradication: 0.85 [95% confidence interval (CI): 0.48–1.50]). Unlike with the same dosage regimen (RR for adverse events: 3.15 [95% CI: 1.93–5.13]), the adverse events in the dosage reduction regimen were similar to those in healthy individuals (RR: 1.26 [95% CI: 0.23–6.99]). From a pharmacological perspective, the eradication regimen in patients receiving HD should consider the dosage (1/2–1/3 dosage), dosing number (bid), dosing timing of drugs (after HD), and susceptibility to antimicrobial agents.</p>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"29 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141439679","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}
Due to irregular antibiotic use, the rate of antibiotic resistance to Helicobacter pylori (H. pylori) is increasing and varies from region to region. Therefore, for the purpose of further clarifying the changes in antibiotic resistance rates nowadays, we conducted a systematic review and meta-analysis to update and assess the 10-year trend of primary H. pylori antibiotic resistance rate to the commonly prescribed antibiotics worldwide.
Materials and Methods
According to the PRISMA statement, we systematically searched electronic databases for studies that assessed rates of H. pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline published from 2013 to 2023. AHRQ was adopted to estimate methodological quality and publication bias in the included studies, and statistical analysis was performed using Stata 17.0.
Results
We identified 163 studies, comprising 47,002 isolates from 36 countries. The meta-analysis showed that the primary antibiotic resistance rate of H. pylori varied widely among antibiotics. Subgroup analysis showed higher rates of antibiotic resistance in the adult population than in children, and a general trend of increased resistance was observed from 2013 to 2023. There was considerable heterogeneity (I2 > 75%) among all analyses, which may be due to high variability in resistance rates across the global regions.
Conclusions
Resistance of H. pylori to antibiotics has reached alarming levels worldwide, which has a great effect on the efficacy of treatment. Local surveillance networks are required to select appropriate eradication regimens for each region.
{"title":"Global Primary Antibiotic Resistance Rate of Helicobacter pylori in Recent 10 years: A Systematic Review and Meta-Analysis","authors":"Yanhui Yu, Jing Xue, Fangbing Lin, Daming Liu, Wen Zhang, Shuying Ru, Feng Jiang","doi":"10.1111/hel.13103","DOIUrl":"10.1111/hel.13103","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Due to irregular antibiotic use, the rate of antibiotic resistance to <i>Helicobacter pylori</i> (<i>H. pylori</i>) is increasing and varies from region to region. Therefore, for the purpose of further clarifying the changes in antibiotic resistance rates nowadays, we conducted a systematic review and meta-analysis to update and assess the 10-year trend of primary <i>H. pylori</i> antibiotic resistance rate to the commonly prescribed antibiotics worldwide.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>According to the PRISMA statement, we systematically searched electronic databases for studies that assessed rates of <i>H. pylori</i> resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline published from 2013 to 2023. AHRQ was adopted to estimate methodological quality and publication bias in the included studies, and statistical analysis was performed using Stata 17.0.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 163 studies, comprising 47,002 isolates from 36 countries. The meta-analysis showed that the primary antibiotic resistance rate of <i>H. pylori</i> varied widely among antibiotics. Subgroup analysis showed higher rates of antibiotic resistance in the adult population than in children, and a general trend of increased resistance was observed from 2013 to 2023. There was considerable heterogeneity (<i>I</i><sup>2</sup> > 75%) among all analyses, which may be due to high variability in resistance rates across the global regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Resistance of <i>H. pylori</i> to antibiotics has reached alarming levels worldwide, which has a great effect on the efficacy of treatment. Local surveillance networks are required to select appropriate eradication regimens for each region.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"29 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426759","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}
{"title":"After 28 Years, Professor David Y. Graham Says Goodbye and Helicobacter Welcomes a New Editor","authors":"David Y. Graham MD","doi":"10.1111/hel.13099","DOIUrl":"10.1111/hel.13099","url":null,"abstract":"","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"29 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330784","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}
The optimal dosage of tetracycline remains unclear for Helicobacter pylori eradication. Frequent dosing requirements may decrease patient adherence and increase the incidence of adverse events, potentially reducing treatment efficacy. This study aimed to compare the efficacy of different tetracycline dosages in rescue treatment for H. pylori infection.
Methods
A total of 406 patients needing H. pylori rescue treatment were enrolled. Patients were randomized into two groups and received bismuth-containing quadruple therapies as follows: esomeprazole 40 mg twice daily, bismuth 220 mg twice daily, amoxicillin 1000 mg twice daily, and tetracycline 500 mg either three (TET-T group) or four (TET-F group) times daily. At least 6 weeks after treatment completion, a 13C-urea breath test was performed to evaluate H. pylori eradication.
Results
The intention-to-treat (ITT) eradication rates were 91.13% (185/203) and 90.15% (183/203) (p = 0.733), the modified ITT (MITT) eradication rates were 94.87% (185/195) and 95.31% (183/192) (p = 0.841), and the per-protocol (PP) eradication rates were 94.79% (182/192) and 95.21% (179/188) (p = 0.851) in the TET-T group and TET-F group, respectively. The eradication rates for the TET-T group were not inferior to those of the TET-F group in ITT, MITT, and PP analyses. The incidence of adverse effects was significantly lower in the TET-T group than in the TET-F group (23.65% vs. 33.50%, p = 0.028). No significant differences were observed in treatment compliance between the groups.
Conclusions
The dose of tetracycline administered three times daily showed comparable efficacy to that administered four times daily, while significantly reducing the incidence of adverse events. The combination of tetracycline and amoxicillin in bismuth-containing quadruple therapy achieved a high eradication rate in H. pylori rescue treatment.
{"title":"Efficacy of Tetracycline Three Times Daily was Comparable to That of Four Times Daily for Helicobacter pylori Rescue Treatment: A Multicenter, Noninferiority, Randomized Controlled Trial","authors":"Zhongxue Han, Qiumei Zhang, Iqtida Ahmed Mirza, Yuming Ding, Xueping Nan, Qing Zhao, Ruili Li, Lidong Xu, Ning Zhang, Miao Duan, Shuyan Zeng, Qingzhou Kong, Wenlin Zhang, Hui Wang, Xiaoqi Wu, Xiuli Zuo, Yanqing Li, Yueyue Li","doi":"10.1111/hel.13102","DOIUrl":"10.1111/hel.13102","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The optimal dosage of tetracycline remains unclear for <i>Helicobacter pylori</i> eradication. Frequent dosing requirements may decrease patient adherence and increase the incidence of adverse events, potentially reducing treatment efficacy. This study aimed to compare the efficacy of different tetracycline dosages in rescue treatment for <i>H. pylori</i> infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 406 patients needing <i>H. pylori</i> rescue treatment were enrolled. Patients were randomized into two groups and received bismuth-containing quadruple therapies as follows: esomeprazole 40 mg twice daily, bismuth 220 mg twice daily, amoxicillin 1000 mg twice daily, and tetracycline 500 mg either three (TET-T group) or four (TET-F group) times daily. At least 6 weeks after treatment completion, a <sup>13</sup>C-urea breath test was performed to evaluate <i>H. pylori</i> eradication.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The intention-to-treat (ITT) eradication rates were 91.13% (185/203) and 90.15% (183/203) (<i>p</i> = 0.733), the modified ITT (MITT) eradication rates were 94.87% (185/195) and 95.31% (183/192) (<i>p</i> = 0.841), and the per-protocol (PP) eradication rates were 94.79% (182/192) and 95.21% (179/188) (<i>p</i> = 0.851) in the TET-T group and TET-F group, respectively. The eradication rates for the TET-T group were not inferior to those of the TET-F group in ITT, MITT, and PP analyses. The incidence of adverse effects was significantly lower in the TET-T group than in the TET-F group (23.65% vs. 33.50%, <i>p</i> = 0.028). No significant differences were observed in treatment compliance between the groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The dose of tetracycline administered three times daily showed comparable efficacy to that administered four times daily, while significantly reducing the incidence of adverse events. The combination of tetracycline and amoxicillin in bismuth-containing quadruple therapy achieved a high eradication rate in <i>H. pylori</i> rescue treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"29 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317017","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}
The formation of gallstones is often accompanied by chronic inflammation, and the mechanisms underlying inflammation and stone formation are not fully understood. Our aim is to utilize single-cell transcriptomics, bulk transcriptomics, and microbiome data to explore key pathogenic bacteria that may contribute to chronic inflammation and gallstone formation, as well as their associated mechanisms.
Methods
scRNA-seq data from a gallstone mouse model were extracted from the Gene Expression Omnibus (GEO) database and analyzed using the FindCluster() package for cell clustering analysis. Bulk transcriptomics data from patients with gallstone were also extracted from the GEO database, and intergroup functional differences were assessed using GO and KEGG enrichment analysis. Additionally, 16S rRNA sequencing was performed on gallbladder mucosal samples from asymptomatic patients with gallstone (n = 6) and liver transplant donor gallbladder mucosal samples (n = 6) to identify key bacteria associated with stone formation and chronic inflammation. Animal models were constructed to investigate the mechanisms by which these key pathogenic bacterial genera promote gallstone formation.
Results
Analysis of scRNA-seq data from the gallstone mouse model (GSE179524) revealed seven distinct cell clusters, with a significant increase in neutrophil numbers in the gallstone group. Analysis of bulk transcriptomics data from patients with gallstone (GSE202479) identified chronic inflammation in the gallbladder, potentially associated with dysbiosis of the gallbladder microbiota. 16S rRNA sequencing identified Helicobacter pylori as a key bacterium associated with gallbladder chronic inflammation and stone formation.
Conclusions
Dysbiosis of the gallbladder mucosal microbiota is implicated in gallstone disease and leads to chronic inflammation. This study identified H. pylori as a potential key mucosal resident bacterium contributing to gallstone formation and discovered its key pathogenic factor CagA, which causes damage to the gallbladder mucosal barrier. These findings provide important clues for the prevention and treatment of gallstones.
{"title":"Helicobacter pylori CagA Promotes the Formation of Gallstones by Increasing the Permeability of Gallbladder Epithelial Cells","authors":"Jingjing Yu, Yuanhang He, Wenchao Yao, Tianming Liu, Xuxu Liu, Yi Zheng, Chenjun Hao, Dongbo Xue","doi":"10.1111/hel.13100","DOIUrl":"10.1111/hel.13100","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The formation of gallstones is often accompanied by chronic inflammation, and the mechanisms underlying inflammation and stone formation are not fully understood. Our aim is to utilize single-cell transcriptomics, bulk transcriptomics, and microbiome data to explore key pathogenic bacteria that may contribute to chronic inflammation and gallstone formation, as well as their associated mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>scRNA-seq data from a gallstone mouse model were extracted from the Gene Expression Omnibus (GEO) database and analyzed using the FindCluster() package for cell clustering analysis. Bulk transcriptomics data from patients with gallstone were also extracted from the GEO database, and intergroup functional differences were assessed using GO and KEGG enrichment analysis. Additionally, 16S rRNA sequencing was performed on gallbladder mucosal samples from asymptomatic patients with gallstone (<i>n</i> = 6) and liver transplant donor gallbladder mucosal samples (<i>n</i> = 6) to identify key bacteria associated with stone formation and chronic inflammation. Animal models were constructed to investigate the mechanisms by which these key pathogenic bacterial genera promote gallstone formation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Analysis of scRNA-seq data from the gallstone mouse model (GSE179524) revealed seven distinct cell clusters, with a significant increase in neutrophil numbers in the gallstone group. Analysis of bulk transcriptomics data from patients with gallstone (GSE202479) identified chronic inflammation in the gallbladder, potentially associated with dysbiosis of the gallbladder microbiota. 16S rRNA sequencing identified <i>Helicobacter pylori</i> as a key bacterium associated with gallbladder chronic inflammation and stone formation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Dysbiosis of the gallbladder mucosal microbiota is implicated in gallstone disease and leads to chronic inflammation. This study identified <i>H. pylori</i> as a potential key mucosal resident bacterium contributing to gallstone formation and discovered its key pathogenic factor CagA, which causes damage to the gallbladder mucosal barrier. These findings provide important clues for the prevention and treatment of gallstones.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"29 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317076","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}
Chen Zhang, Ya-Bin Qi, Ruo-Bing Hu, Lu Xu, Xiao-Ting Li, Jing Ma, Qiao-Qiao Shao, Mohammed Awadh Abdun, Ishtiaq Ur Rahman, Wen-Jun Shi, Fu-Qiang Li, Jian-Jie Yu, Ming-Kai Yuan, Qi Chen, Hong Lu, Song-Ze Ding
Background
The overall benefits of the newly introduced family-based Helicobacter pylori (H. pylori) infection control and management (FBCM) and screen-and-treat strategies in preventing multiple upper gastrointestinal diseases at national level in China have not been explored. We investigate the cost-effectiveness of these strategies in the whole Chinese population.
Materials and Methods
Decision trees and Markov models of H. pylori infection-related non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), and gastric cancer (GC) were developed to simulate the cost-effectiveness of these strategies in the whole 494 million households in China. The main outcomes include cost-effectiveness, life years (LY), quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER).
Results
When compared with no-screen strategy, both FBCM and screen-and-treat strategies reduced the number of new cases of NUD, PUD, PUD-related deaths, and the prevalence of GC, and cancer-related deaths. The costs saved by these two strategies were $1467 million and $879 million, quality-adjusted life years gained were 227 million and 267 million, and life years gained were 59 million and 69 million, respectively. Cost-effectiveness analysis showed that FBCM strategy costs −$6.46/QALY and −$24.75/LY, and screen-and-treat strategy costs −$3.3/QALY and −$12.71/LY when compared with no-screen strategy. Compared to the FBCM strategy, the screen-and-treat strategy reduced the incidence of H. pylori-related diseases, added 40 million QALYs, and saved 10 million LYs, but at the increased cost of $588 million. Cost-effectiveness analysis showed that screen-and-treat strategy costs $14.88/QALY and $59.5/LY when compared with FBCM strategy. The robustness of the results was also verified.
Conclusions
Both FBCM and screen-and-treat strategies are highly cost-effective in preventing NUD, PUD, and GC than the no-screen strategy in Chinese families at national level. As FBCM strategy is more practical and efficient, it is expected to play a more important role in preventing familial H. pylori infection and also serves as an excellent reference for other highly infected societies.
{"title":"Family-based Helicobacter pylori infection control and management strategy and screen-and-treat strategy are highly cost-effective in preventing multiple upper gastrointestinal diseases in Chinese population at national level","authors":"Chen Zhang, Ya-Bin Qi, Ruo-Bing Hu, Lu Xu, Xiao-Ting Li, Jing Ma, Qiao-Qiao Shao, Mohammed Awadh Abdun, Ishtiaq Ur Rahman, Wen-Jun Shi, Fu-Qiang Li, Jian-Jie Yu, Ming-Kai Yuan, Qi Chen, Hong Lu, Song-Ze Ding","doi":"10.1111/hel.13063","DOIUrl":"10.1111/hel.13063","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The overall benefits of the newly introduced family-based <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection control and management (FBCM) and screen-and-treat strategies in preventing multiple upper gastrointestinal diseases at national level in China have not been explored. We investigate the cost-effectiveness of these strategies in the whole Chinese population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Decision trees and Markov models of <i>H. pylori</i> infection-related non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), and gastric cancer (GC) were developed to simulate the cost-effectiveness of these strategies in the whole 494 million households in China. The main outcomes include cost-effectiveness, life years (LY), quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>When compared with no-screen strategy, both FBCM and screen-and-treat strategies reduced the number of new cases of NUD, PUD, PUD-related deaths, and the prevalence of GC, and cancer-related deaths. The costs saved by these two strategies were $1467 million and $879 million, quality-adjusted life years gained were 227 million and 267 million, and life years gained were 59 million and 69 million, respectively. Cost-effectiveness analysis showed that FBCM strategy costs −$6.46/QALY and −$24.75/LY, and screen-and-treat strategy costs −$3.3/QALY and −$12.71/LY when compared with no-screen strategy. Compared to the FBCM strategy, the screen-and-treat strategy reduced the incidence of <i>H. pylori</i>-related diseases, added 40 million QALYs, and saved 10 million LYs, but at the increased cost of $588 million. Cost-effectiveness analysis showed that screen-and-treat strategy costs $14.88/QALY and $59.5/LY when compared with FBCM strategy. The robustness of the results was also verified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Both FBCM and screen-and-treat strategies are highly cost-effective in preventing NUD, PUD, and GC than the no-screen strategy in Chinese families at national level. As FBCM strategy is more practical and efficient, it is expected to play a more important role in preventing familial <i>H. pylori</i> infection and also serves as an excellent reference for other highly infected societies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"29 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317075","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}
Yongkang Lai, Foqiang Liao, Jiulong Zhao, Chunping Zhu, Yi Hu, Zhaoshen Li
Background
Educational initiatives on Helicobacter pylori (H. pylori) constitute a highly effective approach for preventing its infection and establishing standardized protocols for its eradication. ChatGPT, a large language model, is a potentially patient-friendly online tool capable of providing health-related knowledge. This study aims to assess the accuracy and repeatability of ChatGPT in responding to questions related to H. pylori.
Materials and Methods
Twenty-one common questions about H. pylori were collected and categorized into four domains: basic knowledge, diagnosis, treatment, and prevention. ChatGPT was utilized to individually answer the aforementioned 21 questions. Its responses were independently assessed by two experts on H. pylori. Questions with divergent ratings were resolved by a third reviewer. Cohen's kappa coefficient was calculated to assess the consistency between the scores of the two reviewers.
Results
The responses of ChatGPT on H. pylori-related questions were generally satisfactory, with 61.9% marked as “completely correct” and 33.33% as “correct but inadequate.” The repeatability of the responses of ChatGPT to H. pylori-related questions was 95.23%. Among the responses, those related to prevention (comprehensive: 75%) had the best response, followed by those on treatment (comprehensive: 66.7%), basic knowledge (comprehensive: 60%), and diagnosis (comprehensive: 50%). In the “treatment” domain, 16.6% of the ChatGPT responses were categorized as “mixed with correct or incorrect/outdated data.” However, ChatGPT still lacks relevant knowledge regarding H. pylori resistance and the use of sensitive antibiotics.
Conclusions
ChatGPT can provide correct answers to the majority of H. pylori-related queries. It exhibited good reproducibility and delivered responses that were easily comprehensible to patients. Further enhancement of real-time information updates and correction of inaccurate information will make ChatGPT an essential auxiliary tool for providing accurate H. pylori-related health information to patients.
{"title":"Exploring the capacities of ChatGPT: A comprehensive evaluation of its accuracy and repeatability in addressing helicobacter pylori-related queries","authors":"Yongkang Lai, Foqiang Liao, Jiulong Zhao, Chunping Zhu, Yi Hu, Zhaoshen Li","doi":"10.1111/hel.13078","DOIUrl":"10.1111/hel.13078","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Educational initiatives on <i>Helicobacter pylori</i> (<i>H. pylori</i>) constitute a highly effective approach for preventing its infection and establishing standardized protocols for its eradication. ChatGPT, a large language model, is a potentially patient-friendly online tool capable of providing health-related knowledge. This study aims to assess the accuracy and repeatability of ChatGPT in responding to questions related to <i>H. pylori.</i></p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Twenty-one common questions about <i>H. pylori</i> were collected and categorized into four domains: basic knowledge, diagnosis, treatment, and prevention. ChatGPT was utilized to individually answer the aforementioned 21 questions. Its responses were independently assessed by two experts on <i>H. pylori</i>. Questions with divergent ratings were resolved by a third reviewer. Cohen's kappa coefficient was calculated to assess the consistency between the scores of the two reviewers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The responses of ChatGPT on <i>H. pylori</i>-related questions were generally satisfactory, with 61.9% marked as “completely correct” and 33.33% as “correct but inadequate.” The repeatability of the responses of ChatGPT to <i>H. pylori</i>-related questions was 95.23%. Among the responses, those related to prevention (comprehensive: 75%) had the best response, followed by those on treatment (comprehensive: 66.7%), basic knowledge (comprehensive: 60%), and diagnosis (comprehensive: 50%). In the “treatment” domain, 16.6% of the ChatGPT responses were categorized as “mixed with correct or incorrect/outdated data.” However, ChatGPT still lacks relevant knowledge regarding <i>H. pylori</i> resistance and the use of sensitive antibiotics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ChatGPT can provide correct answers to the majority of <i>H. pylori</i>-related queries. It exhibited good reproducibility and delivered responses that were easily comprehensible to patients. Further enhancement of real-time information updates and correction of inaccurate information will make ChatGPT an essential auxiliary tool for providing accurate <i>H. pylori</i>-related health information to patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"29 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310614","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}
Potassium-competitive acid blockers have demonstrated enormous potential in the eradication treatment of Helicobacter pylori infection, with tegoprazan being one of the representatives. The available data on the safety and efficacy of tegoprazan in dual therapy are limited.
Materials and Methods
The multicenter, noninferiority, randomized-controlled trial was conducted from May 2023 to March 2024. Treatment-naive subjects were randomly assigned (1:1) to enter either the tegoprazan–amoxicillin (TA) group (tegoprazan 50 mg twice daily and amoxicillin 750 mg four times daily) or the esomeprazole–amoxicillin (EA) group (esomeprazole 20 mg and amoxicillin 750 mg all four times daily), with a duration for 14 days. The primary outcome was eradication rate as determined by 13C-urea breath test, including per-protocol (PP) analysis and intention-to-treat (ITT) analysis. Secondary outcomes were adverse events and compliance.
Results
A total of 368 individuals were included in the randomization. The eradication rates in the EA group and the TA group were 84.2% and 85.8%, respectively, according to an ITT analysis (p = 0.77), and 88.5% and 88.2%, respectively, according to PP analysis (p = 1.00). The eradication rates for the TA group were not inferior to those of the EA group in both PP (p = 0.0023) and ITT analyses (p = 0.0009). There were no significant statistical differences in the incidence of adverse events and compliance between the two groups. The multivariate logistic regression analysis revealed that poor compliance increased the risk of eradication failure (p < 0.001).
Conclusions
Dual therapy containing tegoprazan is safe and effective to be considered as a clinical first-line treatment option, but further optimization involving antimicrobial susceptibility testing and adjustments in dosage and frequency is warranted.
{"title":"Fourteen-Day Tegoprazan–Amoxicillin Dual Therapy as the First-Line Treatment of Helicobacter pylori Infection (SHARE2301): A Multicenter, Noninferiority, Randomized Clinical Trial","authors":"Qingzhou Kong, Iqtida Ahmed Mirza, Xiaoqian Zhang, Xiaohui Song, Xiaowei Li, Qiumei Zhang, Lidong Xu, Yuting Guo, Yanan Yu, Xiuli Zuo, Yanqing Li, Yueyue Li","doi":"10.1111/hel.13098","DOIUrl":"10.1111/hel.13098","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Potassium-competitive acid blockers have demonstrated enormous potential in the eradication treatment of <i>Helicobacter pylori</i> infection, with tegoprazan being one of the representatives. The available data on the safety and efficacy of tegoprazan in dual therapy are limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>The multicenter, noninferiority, randomized-controlled trial was conducted from May 2023 to March 2024. Treatment-naive subjects were randomly assigned (1:1) to enter either the tegoprazan–amoxicillin (TA) group (tegoprazan 50 mg twice daily and amoxicillin 750 mg four times daily) or the esomeprazole–amoxicillin (EA) group (esomeprazole 20 mg and amoxicillin 750 mg all four times daily), with a duration for 14 days. The primary outcome was eradication rate as determined by <sup>13</sup>C-urea breath test, including per-protocol (PP) analysis and intention-to-treat (ITT) analysis. Secondary outcomes were adverse events and compliance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 368 individuals were included in the randomization. The eradication rates in the EA group and the TA group were 84.2% and 85.8%, respectively, according to an ITT analysis (<i>p</i> = 0.77), and 88.5% and 88.2%, respectively, according to PP analysis (<i>p</i> = 1.00). The eradication rates for the TA group were not inferior to those of the EA group in both PP (<i>p</i> = 0.0023) and ITT analyses (<i>p</i> = 0.0009). There were no significant statistical differences in the incidence of adverse events and compliance between the two groups. The multivariate logistic regression analysis revealed that poor compliance increased the risk of eradication failure (<i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Dual therapy containing tegoprazan is safe and effective to be considered as a clinical first-line treatment option, but further optimization involving antimicrobial susceptibility testing and adjustments in dosage and frequency is warranted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov ID: NCT05870683.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"29 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295964","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}
Vladimir Talayev, Maria Svetlova, Irina Zaichenko, Elena Voronina, Olga Babaykina, Natalia Neumoina, Ksenia Perfilova
Background
Helicobacter pylori (H. pylori) can evade the host's immune response and persist for a long time on the gastric mucosa. T helper (Th) cells appear to be involved in the control of H. pylori bacteria but promote mucosal inflammation. In contrast, regulatory T cells (Tregs) may reduce inflammation but promote H. pylori persistence. CC motif chemokine receptor 6 (CCR6) is involved in the migration of various cells into inflamed gastric mucosa. In this study, we examined CCR6+ Th cells and CCR6+ Tregs during H. pylori infection in humans.
Materials and Methods
Isolation of cells from blood and mucosal biopsies, magnetic separation of В cells, CD4+ and CD4+CCR6+CD45RO+ T cells, antigen-specific activation, B cell response in vitro, flow cytometry, determination of CD4+CD25hiFoxP3+ Tregs and various groups of Th cells.
Results
CD4+CCR6+ blood lymphocytes from healthy donors included Th cells and Tregs. These CCR6+ Th cells produced proinflammatory cytokines and also stimulated plasma cell maturation and antibody production in vitro. H. pylori gastritis and peptic ulcer disease were associated with an increase in the number of circulate CD4+CCR6+CD45RO+ cells and the percentage of Th1, Th17 and Th1/17 cells in this lymphocyte subgroup. In H. pylori-positive patients, circulating CD4+CCR6+ cells contained a higher proportion of H. pylori-specific cells compared with their CD4+CCR6− counterparts. H. pylori infection strongly increased the content of CD4+ lymphocytes in the inflamed gastric mucosa, with the majority of these CD4+ lymphocytes expressing CCR6. CD4+CCR6+ lymphocytes from H. pylori-infected stomach included Tregs and in vivo activated T cells, some of which produced interferon-γ without ex vivo stimulation.
Conclusion
H. pylori infection causes an increase in the number of mature CD4+CCR6+ lymphocytes in the blood, with a pro-inflammatory shift in their composition and enrichment of the gastric mucosa with CD4+CCR6+ lymphocytes, including CCR6+ Th1 cells and Tregs.
{"title":"CCR6+ T helper cells and regulatory T cells in the blood and gastric mucosa during Helicobacter pylori infection","authors":"Vladimir Talayev, Maria Svetlova, Irina Zaichenko, Elena Voronina, Olga Babaykina, Natalia Neumoina, Ksenia Perfilova","doi":"10.1111/hel.13097","DOIUrl":"10.1111/hel.13097","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>Helicobacter pylori</i> (<i>H. pylori</i>) can evade the host's immune response and persist for a long time on the gastric mucosa. T helper (Th) cells appear to be involved in the control of <i>H. pylori</i> bacteria but promote mucosal inflammation. In contrast, regulatory T cells (Tregs) may reduce inflammation but promote <i>H. pylori</i> persistence. CC motif chemokine receptor 6 (CCR6) is involved in the migration of various cells into inflamed gastric mucosa. In this study, we examined CCR6<sup>+</sup> Th cells and CCR6<sup>+</sup> Tregs during <i>H. pylori</i> infection in humans.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Isolation of cells from blood and mucosal biopsies, magnetic separation of В cells, CD4<sup>+</sup> and CD4<sup>+</sup>CCR6<sup>+</sup>CD45RO<sup>+</sup> T cells, antigen-specific activation, B cell response in vitro, flow cytometry, determination of CD4<sup>+</sup>CD25<sup>hi</sup>FoxP3<sup>+</sup> Tregs and various groups of Th cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CD4<sup>+</sup>CCR6<sup>+</sup> blood lymphocytes from healthy donors included Th cells and Tregs. These CCR6<sup>+</sup> Th cells produced proinflammatory cytokines and also stimulated plasma cell maturation and antibody production in vitro. <i>H. pylori</i> gastritis and peptic ulcer disease were associated with an increase in the number of circulate CD4<sup>+</sup>CCR6<sup>+</sup>CD45RO<sup>+</sup> cells and the percentage of Th1, Th17 and Th1/17 cells in this lymphocyte subgroup. In <i>H. pylori</i>-positive patients, circulating CD4<sup>+</sup>CCR6<sup>+</sup> cells contained a higher proportion of <i>H. pylori</i>-specific cells compared with their CD4<sup>+</sup>CCR6<sup>−</sup> counterparts. <i>H. pylori</i> infection strongly increased the content of CD4<sup>+</sup> lymphocytes in the inflamed gastric mucosa, with the majority of these CD4<sup>+</sup> lymphocytes expressing CCR6. CD4<sup>+</sup>CCR6<sup>+</sup> lymphocytes from <i>H. pylori-</i>infected stomach included Tregs and in vivo activated T cells, some of which produced interferon-γ without ex vivo stimulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p><i>H. pylori</i> infection causes an increase in the number of mature CD4<sup>+</sup>CCR6<sup>+</sup> lymphocytes in the blood, with a pro-inflammatory shift in their composition and enrichment of the gastric mucosa with CD4<sup>+</sup>CCR6<sup>+</sup> lymphocytes, including CCR6<sup>+</sup> Th1 cells and Tregs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"29 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179195","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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