ABSTRACT
Objective: The objective of this study is to investigate the causal relationship between gut microbiota and juvenile idiopathic arthritis, and to identify and quantify the potential role of plasma metabolites as mediators. Methods: Using summary-level data from genome-wide association studies, a two-sample Mendelian randomization was conducted involving 131 gut microbiota genus, 1,400 plasma metabolites, and juvenile idiopathic arthritis. Additionally, a two-step approach was employed to quantify the proportion of the effect of gut microbiota on juvenile idiopathic arthritis mediated by plasma metabolites. Effect estimation primarily utilized Inverse Variance Weighting, with further validation using Bayesian weighted Mendelian randomization. Results: In our MR analysis, a positive correlation was observed between Rikenellaceae and the risk of juvenile idiopathic arthritis, while Dorea showed a negative correlation with juvenile idiopathic arthritis risk. Mediation analysis indicated that Furaneol sulfate levels acted as a mediator between Dorea and juvenile idiopathic arthritis, with an indirect effect proportion of 19.94, 95% CI [8.86-31.03%]. Conclusion: Our study confirms a causal relationship between specific microbial genus and juvenile idiopathic arthritis, and computes the proportion of the effect mediated by plasma metabolites, offering novel insights for clinical interventions in juvenile idiopathic arthritis.
ABSTRACT
Objective: Investigating the causal relationship between Lachnospiraceae and Appendicular lean mass (ALM) and identifying and quantifying the role of Aminopeptidase O Protein (AOPEP) as a potential mediator. Methods: The summary statistics data of gut microbiota composition from the largest available genome-wide association study (GWAS) meta-analysis conducted by the MiBioGen Consortium (n = 13,266). Appendicular lean mass data were obtained from the UK-Biobank (n = 450,243). We conducted bidirectional two-sample Mendelian randomization (MR) analysis using summary-level data from GWAS to investigate the causal relationship between Lachnospiraceae and ALM. Additionally, we employed a drug-targeted MR approach to assess the causal relationship between AOPEP and ALM. Finally, a two-step MR was employed to quantitatively estimate the proportion of the effect of Lachnospiraceae on ALM that is mediated by AOPEP. Cochran's Q statistic was used to quantify heterogeneity among instrumental variable estimates. Results: In the MR analysis, it was found that an increase in genetically predicted Lachnospiraceae [OR = 1.031, 95% CI (1.011-1.051), P = 0.002] is associated with an increase in ALM. There is no strong evidence to suggest that genetically predicted ALM has an impact on Lachnospiraceae genus [OR = 1.437, 95% CI (0.785-2.269), P = 0.239]. The proportion of genetically predicted Lachnospiraceae mediated by AOPEP was 34.2% [95% CI (1.3%-67.1%)]. Conclusion: Our research reveals that increasing Lachnospiraceae abundance in the gut can directly enhance limb muscle mass and concurrently suppress AOPEP, consequently mitigating limb muscle loss. This supports the potential therapeutic modulation of gut microbiota for sarcopenia. Interventions such as drug treatments or microbiota transplantation, aimed at elevating Lachnospiraceae abundance and AOPEP inhibition, synergistically improve sarcopenia in the elderly, thereby enhancing the overall quality of life for older individuals.
ABSTRACT
BACKGROUND: Paediatric orthopaedics is a significant and difficult for undergraduate students to master. During the COVID-19 pandemic, we used the WeChat platform to combine the advantages offered by problem-based learning (PBL), case-based learning (CBL) and paper review teaching methods to establish a new blended online teaching model and demonstrated its feasibility and effectiveness. OBJECTIVE: This study aims to demonstrate the feasibility and effectiveness of a new blended pedagogical method that uses the WeChat platform and combines PBL, CBL and paper review. METHODS: We enrolled 22 students participating in the Department of Paediatric Orthopaedics. They participated in the WeChat blended pedagogy mode. Their departmental rotation examination scores were compared with those of 23 students who participated in the traditional teaching method. Moreover, an anonymous questionnaire was used to evaluate students' perceptions and experiences. RESULTS: The total average scores of students who participated in the WeChat blended pedagogy mode and the traditional teaching method were 47.27 and 44.52, respectively. There were no statistically significant differences between the online teaching mode and the traditional teaching method in terms of possessing professional accomplishment, gaining knowledge and promoting interpersonal skills (P = 0.07, P = 0.12 and P = 0.65, respectively). In terms of independent clinical thinking, self-improving capability and improving clinical skills, the scores associated with the WeChat blended pedagogy mode were 8.00, 8.00 and 6.00, whereas those associated with the traditional teaching method were 6.70, 6.87 and 7.48. The overall satisfaction with the WeChat blended pedagogy mode reached 100%. A total of 64%, 86%, 68%, 64% and 59% of students chose very large or large in response to the items concerning professional accomplishment, knowledge absorption, independent clinical thinking skills, English reading and literature exploring capacity, as well as interpersonal skills, respectively. Fifteen participants claimed that the WeChat blended pedagogy mode was less helpful to them with regard to promoting the improvement of their clinical skills. Nine students claimed that the WeChat blended pedagogy mode was time-consuming. CONCLUSIONS: Our study verified the feasibility and effectiveness of the WeChat blended pedagogy mode for undergraduate paediatric orthopaedics internships. TRIAL REGISTRATION: Retrospectively registered.
