L Vázquez, R Cabrera-Rubio, J Tamames, B Mayo, A B Flórez
{"title":"Assessment of short-read shotgun sequencing and microbiome analysis of faecal samples to discriminate between equol producers and non-producers.","authors":"L Vázquez, R Cabrera-Rubio, J Tamames, B Mayo, A B Flórez","doi":"10.3920/BM2022.0027","DOIUrl":"10.3920/BM2022.0027","url":null,"abstract":"<p><p>Among the isoflavones and isoflavone-derived metabolites, equol, which in the human gut is synthesised from daidzein by minority bacterial populations, shows the strongest estrogenic and antioxidant activity. The beneficial effects on human health of isoflavone consumption might be partially or indeed totally attributable to this equol. Although some of the bacterial strains involved in its formation have been identified, the interplay between the composition and functionality of the gut microbiota and equol producer phenotype has hardly been studied. In this study, after shotgun metagenomic sequencing, different pipelines for the taxonomic and functional annotation of sequencing data were used in the search for similarities and differences in the faecal metagenome of equol-producing (n=3) and non-producing (n=2) women, with special focus on equol-producing taxa and their equol-associated genes. The taxonomic profiles of the samples differed significantly depending on the analytical method followed, although the microbial diversity detected by each tool was very similar at the phylum, genus and species levels. Equol-producing taxa were detected in both equol producers and non-producers, but no correlation between the abundance of equol-producing taxa and the equol producing/non-producing phenotype was found. Indeed, functional metagenomic analysis was unable to identify the genes involved in equol production, even in samples from equol producers. By aligning equol operons with the collected metagenomics data, a small number of reads mapping to equol-associated sequences were recognised in samples from both equol producers and equol non-producers, but only two reads mapping onto equol reductase-encoding genes in a sample from an equol producer. In conclusion, the taxonomic analysis of metagenomic data might not be suitable for detecting and quantifying equol-producing microbes in human faeces. Functional analysis of the data might provide an alternative. However, to detect the genetic makeup of the minority gut populations, more extensive sequencing than that achieved in the present study might be required.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"255-268"},"PeriodicalIF":3.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9753421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B H Mullish, D R Michael, T S Webberley, D John, G Ramanathan, S F Plummer, D Wang, J R Marchesi
{"title":"The gastrointestinal status of healthy adults: a <i>post hoc</i> assessment of the impact of three distinct probiotics.","authors":"B H Mullish, D R Michael, T S Webberley, D John, G Ramanathan, S F Plummer, D Wang, J R Marchesi","doi":"10.3920/BM2022.0092","DOIUrl":"10.3920/BM2022.0092","url":null,"abstract":"<p><p>There is a growing awareness that supplementation with probiotic bacteria can impart beneficial effects during gastrointestinal disease, but less is known about the impact of probiotics on healthy subjects. Here, we report the outcomes of a <i>post hoc</i> analysis of recorded daily gastrointestinal events and bowel habits completed by healthy adults participating in a placebo-controlled, single-centre, randomised, double-blind, quadruple-arm probiotic tolerability study. Extensive screening ensured the healthy status of subjects entering the study and during a 2-week pre-intervention run-in period, a burden of gastrointestinal events (stomach pains, indigestion, acid reflux, stomach tightening, nausea and vomiting, stomach rumbling, bloating, belching and flatulence) was identified suggesting GI discomfort within the population. In the subsequent 12-week intervention period with 3 distinct probiotic formulations and a matched-placebo, reductions in the incidence rates of bloating, borborygmus, stomach pains, slow faecal transit and incomplete defecations were observed in the probiotic groups compared to the placebo. These results highlighted differing responses among the probiotic formulations tested and indicated potential anti-constipation effects. Product specific modulations in circulating interleukin-6 levels and in the composition of the gut microbiota were also detected. Together, these data suggest a role for probiotic supplementation to exert beneficial effects on the gastrointestinal functioning of healthy subjects and highlight the need for further longer-term studies in healthy populations to gain a greater understanding of the impact of probiotics.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"183-195"},"PeriodicalIF":3.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9263723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F Raya Tonetti, M Tomokiyo, K Fukuyama, M Elean, R Ortiz Moyano, H Yamamuro, R Shibata, S Quilodran-Vega, S Kurata, J Villena, H Kitazawa
{"title":"Post-immunobiotics increase resistance to primary respiratory syncytial virus infection and secondary pneumococcal pneumonia.","authors":"F Raya Tonetti, M Tomokiyo, K Fukuyama, M Elean, R Ortiz Moyano, H Yamamuro, R Shibata, S Quilodran-Vega, S Kurata, J Villena, H Kitazawa","doi":"10.3920/BM2022.0118","DOIUrl":"10.3920/BM2022.0118","url":null,"abstract":"<p><p>Previously, we demonstrated that post-immunobiotics derived from Lactobacillus gasseri TMT36, TMT39, and TMT40 strains (HK36, HK39 and HK40, respectively) differentially regulated Toll-like receptor 3 (TLR3)-mediated antiviral respiratory immunity in infant mice. In this work, we investigated whether the HK36, HK39 and HK40 nasal treatments were able to improve the resistance against primary respiratory syncytial virus (RSV) infection and secondary pneumococcal pneumonia. Our results demonstrated that the three treatments increased the resistance to primary viral infection by reducing variations in body weight, RSV titers and lung damage of infected infant mice. Post-immunobiotics significantly enhanced the expressions of interferon (IFN)-λ, IFN-β, IFN-γ, interleukin(IL) - 1β, IL-6, IL-27, Mx1, RNAseL and 2'-5'-oligoadenylate synthetase 1 (OAS1) genes and decreased tumour necrosis factor (TNF)-α in alveolar macrophages of RSV-challenged mice. In addition, the studies in the model of RSV-Streptococcus pneumoniae superinfection showed that the HK39 and HK40 treatments were capable of reducing lung damage, lung bacterial cell counts, and the dissemination of S. pneumoniae into the blood of infant mice. The protective effect was associated with increases in IFN-β, IFN-γ, IL-10, and IL-27 in the respiratory tract. This study demonstrates that the nasal application of the post-immunobiotics HK39 and HK40 stimulates innate respiratory immunity and enhances the defences against primary RSV infection and secondary pneumococcal pneumonia offering an alternative to combat respiratory superinfections in children, which can be fatal.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"209-221"},"PeriodicalIF":3.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9400112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S Lacroix, N Leblanc, A Abolghasemi, S Paris-Robidas, C Martin, M Frappier, N Flamand, C Silvestri, F Raymond, M Millette, V Di Marzo, A Veilleux
{"title":"Probiotic interventions promote metabolic health in high fat-fed hamsters in association with gut microbiota and endocannabinoidome alterations.","authors":"S Lacroix, N Leblanc, A Abolghasemi, S Paris-Robidas, C Martin, M Frappier, N Flamand, C Silvestri, F Raymond, M Millette, V Di Marzo, A Veilleux","doi":"10.3920/BM2022.0080","DOIUrl":"10.3920/BM2022.0080","url":null,"abstract":"<p><p>Probiotics represent a promising tool to improve metabolic health, including lipid profiles and cholesterol levels. Modulation of the gut microbiome and the endocannabinoidome - two interrelated systems involved in several metabolic processes influenced by probiotics - has been proposed as a potential mechanism of action. This study establishes the impact of probiotics on metabolic health, gut microbiota composition and endocannabinoidome mediators in an animal model of hypercholesterolaemia. Syrian hamsters were fed either a low-fat low-cholesterol or high-fat high-cholesterol (HFHC) diet to induce hypercholesterolaemia and gavaged for 6 weeks with either Lactobacillus acidophilus CL1285, Lactiplantibacillus plantarum CHOL-200 or a combination of the two. Globally, probiotic interventions ameliorated, at least partially, lipid metabolism in HFHC-fed hamsters. The interventions, especially those including L. acidophilus, modified the gut microbiota composition of the small intestine and caecum in ways suggesting reversal of HFHC-induced dysbiosis. Several associations were observed between changes in gut microbiota composition and endocannabinoidome mediators following probiotic interventions and both systems were also associated with improved metabolic health parameters. For instance, potential connexions between the Eubacteriaceae and Deferribacteraceae families, levels of 2‑palmitoylglycerol, 2‑oleoylglycerol, 2‑linoleoylglycerol or 2‑eicosapentaenoylglycerol and improved lipid profiles were found. Altogether, our results suggest a potential crosstalk between gut microbiota and the endocannabinoidome in driving metabolic benefits associated with probiotics, especially those including L. acidophilus, in an animal model of hypercholesterolaemia.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"223-237"},"PeriodicalIF":3.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9942149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Opportunities for growth in the growing field of psychobiotics.","authors":"E Wissel, L Leon, L Tipton","doi":"10.3920/BM2022.0051","DOIUrl":"https://doi.org/10.3920/BM2022.0051","url":null,"abstract":"<p><p>There is growing interest in the field of psychobiotics, which are probiotics that confer a mental health benefit when ingested. As this field grows, it should pay particular attention to three areas within psychobiotics research that are currently under-studied - sex (and gender) representation, fungi and the mycobiome, and vagus nerve activity. Giving these three domains more attention is currently feasible without significant increased investment of time or money. We discuss these three domains briefly, why they are of particular relevance for psychobiotics research, and how psychobiotics research can easily integrate their perspectives. Our recommendations are summarised in the conclusion, but include equal sex representation at all phases of research (human and animal studies), investigating the relationship between psychobiotics and commensal fungi, and measuring the activity of the vagus nerve in psychobiotics studies.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":"13 6","pages":"445-452"},"PeriodicalIF":5.4,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10444861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R Amamoto, K Shimamoto, T Suwa, S Park, H Matsumoto, K Shimizu, M Katto, H Makino, S Matsubara, Y Aoyagi
{"title":"Relationships between dietary diversity and gut microbial diversity in the elderly.","authors":"R Amamoto, K Shimamoto, T Suwa, S Park, H Matsumoto, K Shimizu, M Katto, H Makino, S Matsubara, Y Aoyagi","doi":"10.3920/BM2022.0054","DOIUrl":"https://doi.org/10.3920/BM2022.0054","url":null,"abstract":"<p><p>Diet is considered as a major driver of gut microbiota composition. However, little is known about the relationship between overall dietary balance and gut microbiota, especially in the elderly. Here, using the Quantitative Index for Dietary Diversity (QUANTIDD), we analysed the relationships between dietary diversity and gut microbiota diversity in 445 Japanese subjects aged 65-90 years. We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). QUANTIDD showed significant positive relationships with Pielou's evenness and Shannon indices, two α-diversity indices related to the uniformity of species distribution. This suggests that a more diverse diet is associated with a more uniform abundance of various bacterial groups, rather than a greater variety of gut bacteria. QUANTIDD also showed significant positive associations with the abundance of <i>Anaerostipes</i>, <i>Eubacterium eligens</i> group, and <i>Eubacterium ventriosum</i> group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. Negative association was found with the abundance of <i>Ruminococcus gnavus</i> group, which produces inflammatory polysaccharides. Positive associations between QUANTIDD and α-diversity indices or the abundance of specific bacterial groups were identified among all subjects and in the <75 years group, but not in the ≥75 years group. Our results suggest that dietary diversity contributes to the diversity of the gut microbiota and increases the abundance of SCFAs-producing bacteria, but only up to a certain age. These findings help to understand the complex relationship between diet and gut microbiota, and provide hints for specific dietary interventions to promote beneficial gut microbiota in the elderly.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":"13 6","pages":"453-464"},"PeriodicalIF":5.4,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10404559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Beneficial microbesPub Date : 2022-12-07Epub Date: 2022-10-20DOI: 10.3920/BM2021.0046
M Ma, J Su, Y Wang, L Wang, Y Li, G Ding, Z Ma, M P Peppelenbosch
{"title":"Association of body mass index and intestinal (faecal) <i>Streptococcus</i> in adults in Xining city, China P.R.","authors":"M Ma, J Su, Y Wang, L Wang, Y Li, G Ding, Z Ma, M P Peppelenbosch","doi":"10.3920/BM2021.0046","DOIUrl":"10.3920/BM2021.0046","url":null,"abstract":"<p><p>Body mass index (BMI) and gut microbiota show significant interaction, but most studies on the relationship between BMI and gut microbiota have been done in Western countries. Relationships that are also identified in other cultural backgrounds are likely to have functional importance. Hence here we explore gut microbiota in adults living in Xining city (China P.R.) and relate results to subject BMI. Analysis of bacterial 16s rRNA gene was performed on faecal samples from participants with normal-weight (n=24), overweight (n=24), obesity (n=11) and type 2 diabetes (T2D) (n=8). The results show that unweighted but not weighted Unifrac distance was significantly different when gut microbiota composition was compared between the groups. Importantly, the genus <i>Streptococcus</i> was remarkably decreased in both obese subjects and subjects suffering from T2D, as compared to normal-weight subjects. Accordingly, strong association was identified between the genus <i>Streptococcus</i> and BMI and especially <i>Streptococcus salivarius</i> subsp. <i>thermophiles</i> was a major contributor in this respect. As previous studies have shown that <i>Streptococcus salivarius</i> subsp. <i>thermophiles</i> is also negatively associated with obesity in Western cohorts, our results suggest that this species is a potential probiotic for the prevention of obesity and related disorders.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":"13 6","pages":"465-472"},"PeriodicalIF":5.4,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10341452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K Gao, C-L Chen, X-Q Ke, Y-X Yu, S Chen, G-C Liu, H-F Wang, Y-J Li
{"title":"Ingestion of <i>Lactobacillus helveticus</i> WHH1889 improves depressive and anxiety symptoms induced by chronic unpredictable mild stress in mice.","authors":"K Gao, C-L Chen, X-Q Ke, Y-X Yu, S Chen, G-C Liu, H-F Wang, Y-J Li","doi":"10.3920/BM2022.0052","DOIUrl":"https://doi.org/10.3920/BM2022.0052","url":null,"abstract":"<p><p>Emerging evidence indicates that the alterations in the gut microbiota-brain axis (GBA), which is the bilateral connection between the gut microbial communities and brain function, are involved in several mental illnesses, including depression. Certain probiotic strains have been revealed to improve depressive behaviours and the dysregulation of 5-hydroxytryptamine (5-HT) metabolism in depression. Here we evaluated the potential antidepressant effects of <i>Lactobacillus helveticus</i> strains using an <i>in vitro</i> enterochromaffin cell model (RIN14B). The <i>L. helveticus</i> strain WHH1889 was shown to significantly promote the level of 5-hydroxytryptamine (5-HTP, 5-HT precursor) and the gene expression of tryptophan hydroxylase 1 (<i>Tph1</i>), which is the key synthetase in the 5-HT biosynthesis in RIN14B cells. Ingestion of 0.2 ml WHH1889 (1´10<sup>9</sup> cfu/ml) in a chronic unpredictable mild stress (CUMS) mouse model of depression for five weeks normalised depressive and anxiety-like behaviours in the forced swim test, tail suspension test, sucrose preference test, and open field test. Meanwhile, the CUMS-induced elevated level of serum corticosterone and declined levels of hippocampal 5-HT and 5-HTP were reversed by WHH1889. Furthermore, the disturbances of the gut microbiome composition with reduced microbial diversity were also improved by WHH1889, accompanied by the increased colonic 5-HTP level and <i>Tph1</i> gene expression. In summary, these findings indicate that WHH1889 exerts antidepressant-like effects on CUMS mice, which is associated with the modulations of the 5-HT/5-HTP metabolism and gut microbiome composition. Therefore, ingestion of the <i>L. helveticus</i> strain WHH1889 with antidepressant potentials may become an encouraging therapeutic option in the treatment of depression.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":"13 6","pages":"473-488"},"PeriodicalIF":5.4,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10692932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Beneficial microbesPub Date : 2022-12-07Epub Date: 2022-11-15DOI: 10.3920/BM2022.0009
Y S Xu, Y H Wang, Y Liu, X Sun, J S Xu, Y Song, X Jiang, Z F Xiong, Z B Tian, C P Zhang
{"title":"Alteration of the faecal microbiota composition in patients with constipation: evidence of American Gut Project.","authors":"Y S Xu, Y H Wang, Y Liu, X Sun, J S Xu, Y Song, X Jiang, Z F Xiong, Z B Tian, C P Zhang","doi":"10.3920/BM2022.0009","DOIUrl":"10.3920/BM2022.0009","url":null,"abstract":"<p><p>There is limited information is known about the composition difference of the gut microbiota in patients with constipation and healthy controls. Here, the faecal 16S rRNA fastq sequence data of microbiota from the publicly available American Gut Project (AGP) were analysed. The tendency score matching (PSM) method was used to match in a 1:1 manner to control for confounding factors age, gender, body mass index (BMI), and country. A total of 524 participants including 262 patients with constipation and 262 healthy controls were included in this analysis. The richness and evenness of the gut microbiota in the constipation group were significantly lower than those in the control group. The dominant genera in the constipation group include <i>Escherichia_Shigella</i>, <i>Pseudomonas,</i> and <i>Citrobacter.</i> The dominant genera in the control group include <i>Faecalibacterium, Prevotella, Roseburia, Clostridium_XlVa,</i> and <i>Blautia</i>. The abundance of three butyrate production-related pathways were significantly higher in the constipation group than in the control groups. There was no significant difference in the diversity and gut microbiota composition in patients with constipation at different ages. In conclusion, patients with constipation showed gut microbiota and butyrate metabolism dysbiosis. This dysbiosis might provide a reference for the diagnosis and clinical therapy of diseases.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":"13 6","pages":"427-436"},"PeriodicalIF":5.4,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10404558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Beneficial microbesPub Date : 2022-12-07Epub Date: 2022-11-15DOI: 10.3920/BM2022.0006
C Marín-Tello, P Jintaridth, F Sanchez, C González, L Zelada-Castillo, A Vásquez-Arqueros, A Guevara-Vásquez, A Vieira
{"title":"Epigenetic regulation by metabolites from the gut microbiome.","authors":"C Marín-Tello, P Jintaridth, F Sanchez, C González, L Zelada-Castillo, A Vásquez-Arqueros, A Guevara-Vásquez, A Vieira","doi":"10.3920/BM2022.0006","DOIUrl":"10.3920/BM2022.0006","url":null,"abstract":"<p><p>The gut microbiome can metabolise food components, such as dietary fibres and various phytochemicals; and the microbiome can also synthesise some nutrients, for example B vitamins. The metabolites produced by bacteria and other micro-organisms in the colon can have implications for health and disease risk. Some of these metabolites are epigenetically active, and can contribute to changes in the chemical modification and structure of chromatin by affecting the activity and expression of epigenetically-active enzymes, for example histone deacetylases and DNA methyltransferases. The epigenetic activity of such gut microbiome metabolites is reviewed herein.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":"13 6","pages":"437-444"},"PeriodicalIF":5.4,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10692933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}