Gut MicrobesPub Date : 2024-09-21DOI: 10.1080/19490976.2024.2404141
Can Gao,Jinwen Wei,Changxu Lu,Lijie Wang,Dan Dong,Mingli Sun
{"title":"A new perspective in intestinal microecology: lifting the veil of exercise regulation of cardiometabolic diseases.","authors":"Can Gao,Jinwen Wei,Changxu Lu,Lijie Wang,Dan Dong,Mingli Sun","doi":"10.1080/19490976.2024.2404141","DOIUrl":"https://doi.org/10.1080/19490976.2024.2404141","url":null,"abstract":"Cardiometabolic diseases (CMDs), encompassing cardiovascular and metabolic dysfunctions, characterized by insulin resistance, dyslipidemia, hepatic steatosis, and inflammation, have been identified with boosting morbidity and mortality due to the dearth of efficacious therapeutic interventions. In recent years, studies have shown that variations in gut microbiota and its own metabolites can influence the occurrence of CMDs. Intriguingly, the composition and function of the gut microbiota are susceptible to exercise patterns, thus affecting inflammatory, immune, and metabolic responses within the host. In this review, we introduce the key mechanisms of intestinal microecology involved in the onset and development of CMDs, discuss the relationship between exercise and intestinal microecology, and then analyze the role of intestinal microecology in the beneficial effects of exercise on CMDs, aiming at elucidating the gut-heart axis mechanisms of exercise mediated protective effect on CMDs, building avenues for the application of exercise in the management of CMDs.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"20 1","pages":"2404141"},"PeriodicalIF":12.2,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gut MicrobesPub Date : 2024-09-18DOI: 10.1080/19490976.2024.2402550
Jason Goldsmith,Sarah Tomkovich,John G Auniņš,Barbara H McGovern,Jennifer C Mahoney,Brooke R Hasson,Christopher W J McChalicher,David S Ege
{"title":"End-to-end donor screening and manufacturing controls: complementary quality-based strategies to minimize patient risk for donor-derived microbiome therapeutics.","authors":"Jason Goldsmith,Sarah Tomkovich,John G Auniņš,Barbara H McGovern,Jennifer C Mahoney,Brooke R Hasson,Christopher W J McChalicher,David S Ege","doi":"10.1080/19490976.2024.2402550","DOIUrl":"https://doi.org/10.1080/19490976.2024.2402550","url":null,"abstract":"Advances in microbiome therapeutics have been motivated by a deeper understanding of the role that the gastrointestinal microbiome plays in human health and disease. The FDA approval of two stool-derived live biotherapeutic products (LBPs), REBYOTA® 150 mL enema (fecal microbiota, live-jslm; formerly RBX2660) and VOWST® oral capsules (fecal microbiota spores, live-brpk; formerly SER-109), for the prevention of recurrent CDI in adults following antibiotic treatment for recurrent CDI provides promise and insights for the development of LBPs for other diseases associated with microbiome dysfunction. Donor-derived products carry risk of disease transmission that must be mitigated through a robust donor screening program and downstream manufacturing controls. Most published recommendations for donor screening practices are prescriptive and do not include a systematic, risk-based approach for donor stool-derived products. A general framework for an end-to-end donor screening program is needed using risk management strategies for donor-derived microbiome therapeutic using a matrixed approach, combining the elements of donor screening with manufacturing controls that are designed to minimize risk to patients. A donor screening paradigm that incorporates medical history, physical examination, laboratory testing, and donor sample inspection are only the first steps in reducing risk of transmission of infectious agents. Manufacturing controls are the cornerstone of risk mitigation when screening unwittingly fails. Failure Mode and Effects Analysis (FMEA) can be used as a tool to assess for residual risk that requires further donor or manufacturing controls. Together, a well-reasoned donor program and manufacturing controls are complementary strategies that must be revisited and reexamined frequently with constant vigilance to mitigate risk to patients. In the spirit of full disclosure and informed consent, physicians should discuss any limitations in the donor screening and manufacturing processes with their patients prior to treatment with microbiome-based therapeutics.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"12 1","pages":"2402550"},"PeriodicalIF":12.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gut microbiota-derived butyrate selectively interferes with growth of carbapenem-resistant Escherichia coli based on their resistance mechanism.","authors":"Eva Happ,Kora Schulze,Zinia Afrin,Sabrina Woltemate,Pia Görner,Stefan Ziesing,Dirk Schlüter,Robert Geffers,Volker Winstel,Marius Vital","doi":"10.1080/19490976.2024.2397058","DOIUrl":"https://doi.org/10.1080/19490976.2024.2397058","url":null,"abstract":"We investigated consequences of resistance acquisition in Escherichia coli clinical isolates during anaerobic (continuous culture) growth and examined their sensitivity to butyrate, a hallmark metabolite of healthy gut microbiota. Strains were stratified based on carrying either a carbapenemase (CARB) or displaying porin malfunctioning (POR). POR displayed markedly altered growth efficiencies, lower membrane stability and increased sensitivity to butyrate compared with CARB. Major differences in global gene expression between the two groups during anaerobic growth were revealed involving increased expression of alternative substrate influx routes, the stringent response and iron acquisition together with lower expression of various stress response systems in POR. Longitudinal analyses during butyrate wash-in showed common responses for all strains as well as specific features of POR that displayed strong initial \"overshoot\" reactions affecting various stress responses that balanced out over time. Results were partly reproduced in a mutant strain verifying porin deficiencies as the major underlying mechanism for results observed in clinical isolates. Furthermore, direct competition experiments confirmed butyrate as key for amplifying fitness disadvantages based on porin malfunctioning. Results provide new (molecular) insights into ecological consequences of resistance acquisition and can assist in developing measures to prevent colonization and infection based on the underlying resistance mechanism.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"13 1","pages":"2397058"},"PeriodicalIF":12.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular serotyping of diarrheagenic Escherichia coli with a MeltArray assay reveals distinct correlation between serotype and pathotype.","authors":"Chen Du,Yiqun Liao,Congcong Ding,Jiayu Huang,Shujuan Zhou,Yiyan Xu,Zhaohui Yang,Xiaolu Shi,Yinghui Li,Min Jiang,Le Zuo,Minxu Li,Shengzhe Bian,Na Xiao,Liqiang Li,Ye Xu,Qinghua Hu,Qingge Li","doi":"10.1080/19490976.2024.2401944","DOIUrl":"https://doi.org/10.1080/19490976.2024.2401944","url":null,"abstract":"Diarrheagenic Escherichia coli serotypes are associated with various clinical syndromes, yet the precise correlation between serotype and pathotype remains unclear. A major barrier to such studies is the reliance on antisera-based serotyping, which is culture-dependent, low-throughput, and cost-ineffective. We have established a highly multiplex PCR-based serotyping assay, termed the MeltArray E. coli serotyping (EST) assay, capable of identifying 163 O-antigen-encoding genes and 53 H-antigen-encoding genes of E. coli. The assay successfully identified serotypes directly from both simulated and real fecal samples, as demonstrated through spike-in validation experiments and a retrospective study. In a multi-province study involving 637 E. coli strains, it revealed that the five major diarrheagenic pathotypes have distinct serotype compositions. Notably, it differentiated 257 Shigella isolates into four major Shigella species, distinguishing them from enteroinvasive E. coli based on their distinct serotype profiles. The assay's universality was further corroborated by in silico analysis of whole-genome sequences from the EnteroBase. We conclude that the MeltArray EST assay represents a paradigm-shifting tool for molecular serotyping of E. coli, with potential routine applications for comprehensive serotype analysis, disease diagnosis, and outbreak detection.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"5 1","pages":"2401944"},"PeriodicalIF":12.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gut MicrobesPub Date : 2024-09-17DOI: 10.1080/19490976.2024.2399213
Zhen-Ping Zou,Ju-Ling Li,Yi-Fan Zhang,Ying Zhou,Bang-Ce Ye
{"title":"Empowering probiotics with high xanthine transport for effective hyperuricemia management.","authors":"Zhen-Ping Zou,Ju-Ling Li,Yi-Fan Zhang,Ying Zhou,Bang-Ce Ye","doi":"10.1080/19490976.2024.2399213","DOIUrl":"https://doi.org/10.1080/19490976.2024.2399213","url":null,"abstract":"Hyperuricemia, a prevalent metabolic disorder, poses a susceptibility to various complications. The conventional pharmacotherapeutic approaches for hyperuricemia often entail notable adverse effects, posing substantial clinical challenges. Hence, the imperative lies in the development of novel, safe and effective strategies for preventing and treating hyperuricemia. Here, we developed a probiotic Escherichia coli Nissle 1917 strain, designated as YES301, which contains a rationally designed xanthine importer XanQ, enabling efficient uptake of xanthine and hypoxanthine, consequently leading to reduced serum uric acid concentrations and amelioration of renal impairments in a murine model of hyperuricemia. Importantly, YES301 exhibited a therapeutic efficacy comparable to allopurinol, a conventional uric acid-lowering agent, and manifesting fewer adverse effects and enhanced biosafety. These findings highlight the promising potential of engineered probiotics in the management of hyperuricemia through reducing intestinal purine levels.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"50 1","pages":"2399213"},"PeriodicalIF":12.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gut MicrobesPub Date : 2024-09-17DOI: 10.1080/19490976.2024.2402543
Theresa Neuper,Tobias Frauenlob,Hieu-Hoa Dang,Peter W Krenn,Gernot Posselt,Christof Regl,Nikolaus Fortelny,Veronika Schäpertöns,Michael S Unger,Gunda Üblagger,Daniel Neureiter,Iris Mühlbacher,Michael Weitzendorfer,Franz Singhartinger,Klaus Emmanuel,Christian G Huber,Silja Wessler,Fritz Aberger,Jutta Horejs-Hoeck
{"title":"ADP-heptose attenuates Helicobacter pylori-induced dendritic cell activation.","authors":"Theresa Neuper,Tobias Frauenlob,Hieu-Hoa Dang,Peter W Krenn,Gernot Posselt,Christof Regl,Nikolaus Fortelny,Veronika Schäpertöns,Michael S Unger,Gunda Üblagger,Daniel Neureiter,Iris Mühlbacher,Michael Weitzendorfer,Franz Singhartinger,Klaus Emmanuel,Christian G Huber,Silja Wessler,Fritz Aberger,Jutta Horejs-Hoeck","doi":"10.1080/19490976.2024.2402543","DOIUrl":"https://doi.org/10.1080/19490976.2024.2402543","url":null,"abstract":"Sophisticated immune evasion strategies enable Helicobacter pylori (H. pylori) to colonize the gastric mucosa of approximately half of the world's population. Persistent infection and the resulting chronic inflammation are a major cause of gastric cancer. To understand the intricate interplay between H. pylori and host immunity, spatial profiling was used to monitor immune cells in H. pylori infected gastric tissue. Dendritic cell (DC) and T cell phenotypes were further investigated in gastric organoid/immune cell co-cultures and mechanistic insights were acquired by proteomics of human DCs. Here, we show that ADP-heptose, a bacterial metabolite originally reported to act as a bona fide PAMP, reduces H. pylori-induced DC maturation and subsequent T cell responses. Mechanistically, we report that H. pylori uptake and subsequent DC activation by an ADP-heptose deficient H. pylori strain depends on TLR2. Moreover, ADP-heptose attenuates full-fledged activation of primary human DCs in the context of H. pylori infection by impairing type I IFN signaling. This study reveals that ADP-heptose mitigates host immunity during H. pylori infection.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"27 1","pages":"2402543"},"PeriodicalIF":12.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gut MicrobesPub Date : 2024-09-17DOI: 10.1080/19490976.2024.2399360
J Buttar,E Kon,A Lee,G Kaur,G Lunken
{"title":"Effect of diet on the gut mycobiome and potential implications in inflammatory bowel disease.","authors":"J Buttar,E Kon,A Lee,G Kaur,G Lunken","doi":"10.1080/19490976.2024.2399360","DOIUrl":"https://doi.org/10.1080/19490976.2024.2399360","url":null,"abstract":"The gut microbiome is a complex, unique entity implicated in the prevention, pathogenesis, and progression of common gastrointestinal diseases. While largely dominated by bacterial populations, advanced sequencing techniques have identified co-inhabiting fungal communities, collectively referred to as the mycobiome. Early studies identified that gut inflammation is associated with altered microbial composition, known as gut dysbiosis. Altered microbial profiles are implicated in various pathological diseases, such as inflammatory bowel disease (IBD), though their role as a cause or consequence of systemic inflammation remains the subject of ongoing research. Diet plays a crucial role in the prevention and management of various diseases and is considered to be an essential regulator of systemic inflammation. This review compiles current literature on the impact of dietary modulation on the mycobiome, showing that dietary changes can alter the fungal architecture of the gut. Further research is required to understand the impact of diet on gut fungi, including the metabolic pathways and enzymes involved in fungal fermentation. Additionally, investigating whether dietary modulation of the gut mycobiome could be utilized as a therapy in IBD is essential.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"2 1","pages":"2399360"},"PeriodicalIF":12.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gut MicrobesPub Date : 2024-09-17DOI: 10.1080/19490976.2024.2402544
Torsten P M Scheithauer,Roy C Montijn,Arnout Mieremet
{"title":"Gut microbe-host interactions in post-COVID syndrome: a debilitating or restorative partnership?","authors":"Torsten P M Scheithauer,Roy C Montijn,Arnout Mieremet","doi":"10.1080/19490976.2024.2402544","DOIUrl":"https://doi.org/10.1080/19490976.2024.2402544","url":null,"abstract":"Post-COVID syndrome (PCS) patients have reported a wide range of symptoms, including fatigue, shortness of breath, and diarrhea. Particularly, the presence of gastrointestinal symptoms has led to the hypothesis that the gut microbiome is involved in the development and severity of PCS. The objective of this review is to provide an overview of the role of the gut microbiome in PCS by describing the microbial composition and microbial metabolites in COVID-19 and PCS. Moreover, host-microbe interactions via the microbiota-gut-brain (MGB) and the microbiota-gut-lung (MGL) axes are described. Furthermore, we explore the potential of therapeutically targeting the gut microbiome to support the recovery of PCS by reviewing preclinical model systems and clinical studies. Overall, current studies provide evidence that the gut microbiota is affected in PCS; however, diversity in symptoms and highly individual microbiota compositions suggest the need for personalized medicine. Gut-targeted therapies, including treatments with pre- and probiotics, have the potential to improve the quality of life of affected individuals.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"34 1","pages":"2402544"},"PeriodicalIF":12.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gut MicrobesPub Date : 2024-09-17DOI: 10.1080/19490976.2024.2402547
Ning Li,Xinyan Han,Ming Ruan,Fei Huang,Liu Yang,Tianhao Xu,Huijun Wang,Hui Wu,Songshan Shi,Yongjun Wang,Xiaojun Wu,Shunchun Wang
{"title":"Prebiotic inulin controls Th17 cells mediated central nervous system autoimmunity through modulating the gut microbiota and short chain fatty acids.","authors":"Ning Li,Xinyan Han,Ming Ruan,Fei Huang,Liu Yang,Tianhao Xu,Huijun Wang,Hui Wu,Songshan Shi,Yongjun Wang,Xiaojun Wu,Shunchun Wang","doi":"10.1080/19490976.2024.2402547","DOIUrl":"https://doi.org/10.1080/19490976.2024.2402547","url":null,"abstract":"Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination occurring in the central nervous system (CNS). Inulin is a common prebiotic that can improve metabolic disorders by modulating the gut microbiota. However, its capacity to affect CNS autoimmunity is poorly recognized. Experimental autoimmune encephalomyelitis (EAE) is a classical mouse model of MS. Herein, we found that oral administration of inulin ameliorated the severity EAE in mice, accompanied by reductions in inflammatory cell infiltration and demyelination in the CNS. These reductions were associated with decreased proportion and numbers of Th17 cells in brain and spleen. Consistent with the findings, the serum concentrations of IL-17, IL-6, and TNF-α were reduced in inulin treated EAE mice. Moreover, the proliferation of auto-reactive lymphocytes, against MOG35-55 antigen, was attenuated ex vivo. Mechanistically, inulin treatment altered the composition of gut microbiota. It increased Lactobacillus and Dubosiella whereas decreased g_Prevotellaceae_NK3B31_group at the genus level, alongside with elevated concentration of butyric acid in fecal content and serum. In vitro, butyrate, but not inulin, could inhibit the activation of MOG35-55 stimulated lymphocytes. Furthermore, fecal microbiota transplantation assay confirmed that fecal contents of inulin-treated normal mice had an ameliorative effect on EAE mice. In contrast, antibiotic cocktail (ABX) treatment diminished the therapeutic effect of inulin in EAE mice as well as the reduction of Th17 cells, while supplementation with Lactobacillus reuteri restored the amelioration effect. These results confirmed that the attenuation of inulin on Th17 cells and inflammatory demyelination in EAE mice was dependent on its modulation on gut microbiota and metabolites. Our findings provide a potential therapeutic regimen for prebiotic inulin supplementation in patients with multiple sclerosis.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"197 1","pages":"2402547"},"PeriodicalIF":12.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gut MicrobesPub Date : 2024-09-16DOI: 10.1080/19490976.2024.2393270
Kallie E Hays,Jacob M Pfaffinger,Rebecca Ryznar
{"title":"The interplay between gut microbiota, short-chain fatty acids, and implications for host health and disease.","authors":"Kallie E Hays,Jacob M Pfaffinger,Rebecca Ryznar","doi":"10.1080/19490976.2024.2393270","DOIUrl":"https://doi.org/10.1080/19490976.2024.2393270","url":null,"abstract":"Short-chain fatty acids (SCFAs) - acetate, propionate, and butyrate - are important bacterial fermentation metabolites regulating many important aspects of human physiology. Decreases in the concentrations of any or multiple SCFAs are associated with various detrimental effects to the host. Previous research has broadly focused on gut microbiome produced SCFAs as a group, with minimal distinction between acetate, propionate, and butyrate independently, each with significantly different host effects. In this review, we comprehensively delineate the roles of these SCFAs with emphasis on receptor affinity, signaling pathway involvement, and net host physiologic effects. Butyrate is highlighted due to its unique role in gastrointestinal-associated functions, especially maintaining gut barrier integrity. Butyrate functions by promoting epithelial tight junctions, serving as fuel for colonocyte ATP production, and modulating the immune system. Interaction with the immune system occurs locally in the gastrointestinal tract and systemically in the brain. Investigation into research conducted on butyrate production pathways and specific bacterial players involved highlights a unique risk associated with use of gram-positive targeted antibiotics. We review and discuss evidence showing the relationship between the butyrate-producing gram-positive genus, Roseburia, and susceptibility to commonly prescribed, widely used gram-positive antibiotics. Considering gut microbiome implications when choosing antibiotic therapy may benefit health outcomes in patients.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"5 1","pages":"2393270"},"PeriodicalIF":12.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}