Beneficial microbes最新文献

{"title":"Postbiotics: what are they?","authors":"M L Chikindas, L S Sichel, I V Popov, J R Tagg, X Lu, O V Mitrokhin, S D Todorov","doi":"10.1163/18762891-bja00103","DOIUrl":"https://doi.org/10.1163/18762891-bja00103","url":null,"abstract":"<p><p>Although several internationally recognised scientific groups and non-governmental organisations have attempted to define 'postbiotics,' there remains no consensus. Leading experts have highlighted persistent problems of terminological inconsistency, lack of standardisation, and unclear boundaries between related concepts. What is needed is a comprehensive analysis that integrates existing definitions with considerations of manufacturing processes, mechanisms of action, and clinical applications. Ultimately, progress requires harmonisation of terminology to ensure comparability across studies and to provide a solid foundation for both academic and industry development.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"1-8"},"PeriodicalIF":3.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224768","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":"A multicenter real-world, open-label study assessing the impact of a probiotic mixture on symptoms of irritable bowel syndrome in adults.","authors":"L Drago, V D Corleto, G Ciprandi, V F Brindicci, V N Dargenio, F Cristofori, F Schettini, A Mauro, V P Di Marino, G la Grasta, G Marseglia, R Francavilla","doi":"10.1163/18762891-bja00097","DOIUrl":"https://doi.org/10.1163/18762891-bja00097","url":null,"abstract":"<p><p>Irritable bowel syndrome (IBS) is faced by gastroenterologists daily, and probiotics are a potential therapeutic tool; however, there are no strain recommendations. This multicenter, real-world, single-arm, open-label study aims to assess a novel probiotic mixture's effectiveness, safety, and patient satisfaction in patients with IBS. This study was conducted by 52 Italian gastroenterologists across 16 of the 21 Italian regions who enrolled patients with IBS (n = 1,098). Throughout the 8-week treatment (T1) period with a probiotic mixture (Lactobacillus paracasei 101/37 LMG P-17504, Lactobacillus plantarum 14D CECT 4528, Bifidobacterium breve Bbr8 LMG P-17501, Bifidobacterium breve BL10 LMG P-17500, and Bifidobacterium animalis ssp. lactis Bi1 LMG P-17502), participants completed a questionnaire to evaluate IBS symptoms at baseline, at the end of treatment, and after one-month follow-up (T2). The primary outcome was the progress of abdominal pain and bloating according with a 5-point Likert scale, (0 absence and 5 highly intense symptoms) and treatment success was defined as a change towards categories of lower IBS severity for abdominal pain and/or bloating. Treatment success for abdominal pain and bloating was achieved in 73% and 81.9% at T1 and 68% and 73.1% at T2, respectively. The probiotic was associated with significantly reducing abdominal pain and bloating at T1 and T2 (P < 0.001). Patients with regular bowel movements increased to 68.5% at T1 and 68.7% at T2, respectively (P < 0.001). Patients reporting that IBS did not affect their daily life increased from 1.8% at entry to 22.7% at T1 and 41.6% at T2 (P < 0.001). This real-world, single-arm, open-label study showed that an 8-week treatment with a novel probiotic mixture is effective, safe, well tolerated, and can improve patients' social lives during and after treatment. Future randomised placebo-controlled studies are necessary to validate these findings. The trial is registered at www.ClinicalTrials.gov (NCT06610149).</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"1-12"},"PeriodicalIF":3.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129964","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":"Development of a combination of probiotics and plant extracts targeting adherent-invasive Escherichia coli associated with Crohn's disease.","authors":"F De Clercq, N Boisseau, C Leclaire, J Denizot, S Holowacz, N Barnich, A Sivignon","doi":"10.1163/18762891-bja00095","DOIUrl":"https://doi.org/10.1163/18762891-bja00095","url":null,"abstract":"<p><p>Abnormal colonisation of the ileal mucosa by adherent-invasive Escherichia coli (AIEC) is a key feature of Crohn's disease. To date, no curative treatment for this disease exists, highlighting the need to develop new therapies targeting the origin of the inflammation, in particular the intestinal microbiota and more specifically AIEC. This study investigated the anti-virulence properties of 17 bacterial strains (lactobacilli and bifidobacteria) and three plant extracts (walnut and green tea leaves and liquorice roots) against AIEC. In vitro, six lactobacilli strains and one bifidobacterium strain reduced AIEC LF82 adhesion to Caco-2/TC7 cells and/or suppressed IL-8 secretion induced by AIEC. Although plant extracts did not prevent adhesion or inflammation, they inhibited AIEC growth. In a murine model of dextran sulfate sodium-induced colitis exacerbated by LF82 infection, two Lacticaseibacillus strains, one Bifidobacterium strain, and walnut and green tea extracts efficiently alleviated colitis and reduced faecal lipocalin-2 levels. For the green tea extract and one Lacticaseibacillus strain, beneficial effects were correlated with a decreased number of AIEC associated with the colonic mucosa. Building on these findings, bacteria and plant extract combinations were tested in the same model. A formulation combining two Lacticaseibacillus strains (Lbs. casei and Lbs. rhamnosus) with the walnut extract demonstrated the greatest efficacy, markedly reducing colitis score and preserving intestinal mucosa integrity. While untreated mice remained heavily colonised, the combination promoted AIEC elimination from the gut of half the mice, contributing to the alleviation of colitis symptoms. These results highlight the ability of combinations of specific bacteria/plant extracts to limit the presence of AIEC in the ileal mucosa of Crohn's disease patients, presenting a promising approach for disease management.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"1-17"},"PeriodicalIF":3.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130014","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":"The impact of three distinct probiotic supplements on the gut microbiota and its metabolites in healthy adults.","authors":"D R Michael, D A John, N Coates, I Guschina, J A K McDonald, N P Danckert, M A Valdivia-Garcı́a, G Ramanathan, S F Plummer, D Wang, J R Marchesi, B H Mullish","doi":"10.1163/18762891-bja00096","DOIUrl":"https://doi.org/10.1163/18762891-bja00096","url":null,"abstract":"<p><p>The effects of probiotics on the gut microbiota and microbial metabolites in healthy individuals are not well understood. Faecal and serum samples were collected at the start and end of a 3-month, double-blind, placebo-controlled, randomised study with three different probiotic formulations in free-living, healthy adults. The composition of the faecal microbiota and levels of faecal and/or serum short-chain fatty acids (SCFA) and bile acids (BA) were measured and the probiotic formulations were found to impart differing effects including shifts in the composition and structure of the faecal microbiota, enhanced levels of circulating short chain fatty acids such as butyrate and propionate, and elevated levels of sulphated bile acids in faeces. This was in contrast to the outcomes for the placebo population where very little change occurred over the study. These findings demonstrate that probiotic supplementation elicits formulation specific effects and that there are potential benefits for healthy individuals.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"1-14"},"PeriodicalIF":3.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129997","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":"Phenotypic differences between equol-producing and non-equol-producing intestinal microbiota.","authors":"J A Curiel, S Langa, A Ruiz de la Bastida, Á Peirotén, I Álvarez, J M Landete","doi":"10.1163/18762891-bja00094","DOIUrl":"https://doi.org/10.1163/18762891-bja00094","url":null,"abstract":"<p><p>Equol is an isoflavone produced by intestinal microbiota from daidzein. It has been assumed that individuals with equol-producing microbiota are those who mainly benefit from isoflavone consumption. However, no obvious genotypic differences can be found between the microbiota of equol-producing individuals and non-equol-producing individuals. The aim of this work was to find phenotypic differences in isoflavone metabolism between equol-producing and non-equol-producing intestinal microbiota. Of the 17 faecal samples used in this work, six produced equol from both daidzein and dihydrodaidzein (DHD); however, only equol-producing faecal samples produced 5-hydroxy-equol from genistein and dihydrogenistein (DHG). The equol producing microbiota metabolised most of daidzein, genistein, DHD and DHG present in the medium, while the metabolism of daidzein and genistein by non-equol producing microbiota is much lower, and they do not metabolise DHD and DHG. Moreover, equol-producing faecal samples produced lower concentrations of O-DMA than the non-equol-producing faecal samples. In addition, we demonstrated that most of the O-DMA is produced from daidzein. Therefore, there are important phenotypic differences between equol-producing and non-equol-producing intestinal microbiota, and these differences explain the differentiation between equol-producing and non-equol-producing individuals, and help to understand the metabolism of isoflavones by microbiota and how intestinal microbiota is responsible for the benefits of isoflavone intake.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"1-11"},"PeriodicalIF":3.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940684","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":"Characterisation of the cell envelope and adhesive properties of Lactobacillus johnsonii CRL1647, a probiotic from the honeybee gut.","authors":"M Novicov-Fanciotti, S Dentice Maidana, M Elean, J Villena, M C Audisio","doi":"10.1163/18762891-bja00087","DOIUrl":"https://doi.org/10.1163/18762891-bja00087","url":null,"abstract":"<p><p>Lactobacillus johnsonii CRL1647 has been studied due to its beneficial effects on Apis mellifera L. bee colonies. In this work, we analyzed the characteristics of its cell envelope and the relationship of this bacterial structure with adhesion. The study revealed that CRL1647 cells did not harbor S-layer proteins, whereas L. acidophilus ATCC4356, used as a positive control, showed a typical S-layer protein band. L. johnsonii CRL1647 hemagglutinated with sheep erythrocytes. Interestingly, the hemagglutination abilities of L. johnsonii CRL1647 were affected by the treatments with proteinase K and sodium metaperiodate. Transmission electron microscopy (TEM) analysis confirmed that L. acidophilus ATCC4356 has S-layer and revealed that the L. johnsonii CRL1647 cell surface was full of prolongations like 'hairs'. These ultra-structures completely disappeared after the treatment with proteinase K. The CRL1647 strain was able to efficiently adhere to intestinal epithelial cells and was phagocyted by macrophages. Both, adhesion and phagocytosis were significantly diminished when CRL1647 cells were pretreated with proteinase K. From these results, it can be inferred that the principal molecules involved in the adherence of L. johnsonii CRL1647 have a glycoprotein structure, differing them from S-layer proteins.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"1-11"},"PeriodicalIF":3.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764461","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":"Dysosmobacter welbionis J115T reduces stress-like phenotype in high-fat diet-induced obese female mice.","authors":"G C Wong, N M Delzenne, M Van Hul, P D Cani","doi":"10.1163/18762891-bja00091","DOIUrl":"https://doi.org/10.1163/18762891-bja00091","url":null,"abstract":"<p><p>This study investigated the effects of Dysosmobacter welbionis J115T on stress- and anxiety-related behaviours, inflammation, and neurobiological markers under different dietary conditions in female mice. Daily oral gavage with D. welbionis J115T for six weeks did not significantly impact body weight or fat mass, regardless of dietary treatment. Notably, high-fat diet (HFD)-fed female mice displayed increased body weight and adipose tissue accumulation compared to control diet (CTD) counterparts; however, this was not significantly altered by D. welbionis J115T administration. Behavioural testing revealed that HFD-fed female mice exhibited a mild stress/anxiety-like phenotype, especially in the elevated plus maze (EPM) and forced swim test (FST), which was attenuated by D. welbionis J115T treatment. These mice showed increased exploratory behaviour in the light-dark test (LDT), reduced time spent in closed arms of the EPM, and longer cumulative time in a highly active state in the FST. Plasma corticosterone levels, elevated post-behavioural testing in all female groups, increased less in HFD-fed D. welbionis-treated mice, suggesting a blunted stress response. These findings highlight sex-specific behavioural and molecular responses to dietary and probiotic interventions and suggest that D. welbionis J115T may modulate stress-related behaviours in female mice via the gut-brain axis.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"1-12"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752227","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":"Safety evaluation of Lactiplantibacillus plantarum N13: genomic, phenotypic, and toxicological assessment for probiotic applications.","authors":"Y Qi, W Si, Y Fan, Y Dong, Z Gai, Y Zhang","doi":"10.1163/18762891-bja00093","DOIUrl":"10.1163/18762891-bja00093","url":null,"abstract":"<p><p>Probiotics offer numerous health benefits and are increasingly incorporated into dietary supplements and food products. Rigorous safety evaluations are essential to ensure their suitability for human consumption. This study evaluates the safety profile of Lactiplantibacillus plantarum N13, isolated from traditional fermented dairy products, through genomic and phenotypic analyses. Whole-genome sequencing confirmed general length of strain N13 (containing three plasmids) is about 3,318,516 bp, GC content is 44.4% and the absence of antibiotic resistance and virulence genes. Antibiotic susceptibility tests demonstrated that N13 is sensitive to ampicillin (1 μg/ml), gentamycin (4 μg/ml), kanamycin (32 μg/ml), erythromycin (0.5 μg/ml), clindamycin (0.25 μg/ml), tetracycline (32 μg/ml), and chloramphenicol (8 μg/ml), meeting the European Food Safety Authority (EFSA) guidelines. Additionally, genome analysis confirmed that N13 lacks genes related to biogenic amine biosynthesis, indicating its low risk of biogenic amine production. Scanning electron microscopy confirmed that N13 cells exhibited typical L. plantarum morphology. Phenotypic assays demonstrated that N13 is non-hemolytic and lacks harmful enzyme activity, including α-galactosidase, β-glucuronidase, and α-mannosidase. Acute and 28-day oral toxicity tests demonstrated that N13 was well tolerated in both Immunocompetent Research mice and Sprague Dawley rats, with no observable toxic effects or adverse changes even at high doses. At the recommended dose (0.5 × 1010 CFU/kg), N13 exhibited good oral safety. These findings establish L. plantarum N13 as a safe and promising probiotic strain, paving the way for its further application in dietary and functional food products.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"1-20"},"PeriodicalIF":3.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752228","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":"Effects of spore-forming probiotic Bacillus subtilis HU58™ in children with antibiotic-associated diarrhoea: a randomised, double-blind, placebo-controlled trial.","authors":"K Sorensen, P Jog, S Mankar, C Holz, S Jadhav","doi":"10.1163/18762891-bja00086","DOIUrl":"https://doi.org/10.1163/18762891-bja00086","url":null,"abstract":"<p><p>Antibiotics are among the most prescribed medicines in children globally. Antibiotic-associated diarrhoea (AAD) and associated abdominal pain are common side effects, caused by alterations to the intestinal microbiota composition. Most research on probiotic interventions involves prophylactic use of Saccharomyces, lactobacilli or bifidobacteria. Less is known about spore-forming strains administered after AAD onset. Bacillus subtilis HU58™ was found to improve AAD symptoms in adults. This randomised, double-blind, placebo-controlled trial in India investigated the effects of a dietary supplement containing B. subtilis HU58 (2 × 109 cfu/day) versus placebo for seven days on diarrhoea duration (Bristol Stool Scale, BSS), abdominal pain intensity (Visual Analogue Scale, VAS), and overall gastrointestinal wellbeing (adapted Gastrointestinal Restoration Questionnaire, GIRQ; Physician Global Assessment, PGA) in 68 children (1-12 years) with AAD. Between-group comparison of data from each timepoint was conducted for the intention to treat population (Chi-squared test of independence for distribution of BSS types, Wilcoxon rank sum test for mean BSS types, mixed model for repeated measures for VAS, GIRQ and PGA scores). By day 3, 93.5% of the probiotic group had normal BSS types, versus 22.6% in the placebo group ( P < 0.001). Almost all subjects in both groups had normal stool types by day 7. Significantly greater decreases in abdominal pain VAS scores were observed among those receiving the probiotic versus placebo at day 3 (-7.4 [SE 0.5] versus -1.9 [SE 0.3], P < 0.001) and day 7 (-9.1 [SE 0.3] versus -8.5 [SE 0.2], P < 0.001). Greater improvements for both adapted GIRQ and PGA scores assessing GI wellbeing were observed in the probiotic group compared to the placebo group at days 3 and 7 (all P < 0.001). Spore-forming B. subtilis HU58 administered to children after onset of AAD may lead to faster resolution of diarrhoea and associated abdominal pain. Further research with daily clinical assessment and faecal microbiome analysis is warranted. The trial is registered at https://ctri.nic.in/Clinicaltrials (CTRI/2022/02/040138).</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"1-10"},"PeriodicalIF":3.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727161","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":"Lactobacillus helveticus-derived postbiotic and live Saccharomyces boulardii restore gut microbiota after antibiotic disturbance in an in vitro canine gut model.","authors":"C Deschamps, D Humbert, M Brun, S Denis, C Durif, E Apper, S Blanquet-Diot","doi":"10.1163/18762891-bja00088","DOIUrl":"https://doi.org/10.1163/18762891-bja00088","url":null,"abstract":"<p><p>Gut microbiota plays a central role in dog health, supporting nutritional and physiological processes. However, antibiotic treatment can disturb microbiota equilibrium, leading to a perturbated state, called dysbiosis. While probiotic and postbiotic strategies are increasingly studied, their use in dogs remains poorly documented, particularly in the context of antibiotic-induced dysbiosis. In this study, we provide novel insights by evaluating for the first time, the efficacy of two microbiota restoration strategies using a canine-specific in vitro gut model (Canine Mucosal Artificial Colon, CANIM-ARCOL): the probiotic live yeast Saccharomyces boulardii CNCM I-1079 and the postbiotic heat-inactivated Lactobacillus helveticus HA-122. Both were administered at in-field doses twice a day, during and after a 5-day antibiotic treatment (metronidazole/enrofloxacin), to assess their ability to enhance microbiota resistance and/or promote recovery in both lumen and mucus-associated microbiota. Our results demonstrated that within two days post-antibiotic treatment, both interventions significantly mitigated the bloom of Enterobacteriaceae (up to -75% relative abundance, P < 0.05), accelerated the recovery of total bacterial load (increase of ∼1.5 log 10 copies/ml), and promoted a faster restoration of bacterial diversity (Shannon index returning to baseline by day 14 vs day 16 in the control). Additionally, S. boulardii significantly reduced redox potential (+200 mV with antibiotic vs only +80 mV with yeast, P < 0.0001), while L. helveticus preserved short-chain fatty acid concentrations (>100 mM vs 80 mM under control conditions) and upregulated beneficial metabolic pathways (e.g. norspermidine biosynthesis). Moreover, both treatments reduced variability in microbiota profiles and enhanced functional resilience post-antibiotic exposure. These findings provide compelling evidence supporting the relevance of probiotic and postbiotic strategies in companion animal and highlight the potential of the CANIM-ARCOL model as an ethical and robust alternative to in vivo trials for preclinical evaluation of microbiota-targeted intervention in canine nutrition and health.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"1-21"},"PeriodicalIF":3.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727163","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}