COVID-19 vaccination and the risk of autoimmune diseases: a Mendelian randomization study.

Background: In recent times, reports have emerged suggesting that a variety of autoimmune disorders may arise after the coronavirus disease 2019 (COVID-19) vaccination. However, causality and underlying mechanisms remain unclear. Methods: We collected summary statistics of COVID-19 vaccination and 31 autoimmune diseases from genome-wide association studies (GWAS) as exposure and outcome, respectively. Random-effects inverse variance weighting (IVW), MR Egger, weighted median, simple mode, and weighted mode were used as analytical methods through Mendelian randomization (MR), and heterogeneity and sensitivity analysis were performed. Results: We selected 72 instrumental variables for exposure (p < 5 × 10-6; r2 < 0.001, genetic distance = 10,000 kb), and MR analyses showed that COVID-19 vaccination was causally associated with an increased risk of multiple sclerosis (MS) (IVW, OR: 1.53, 95% CI: 1.065-2.197, p = 0.026) and ulcerative colitis (UC) (IVW, OR: 1.00, 95% CI: 1.000-1.003, p = 0.039). If exposure was refined (p < 5 × 10-8; r2 < 0.001, genetic distance = 10,000 kb), the associations became negative. No causality was found for the remaining outcomes. These results were robust to sensitivity and heterogeneity analyses. Conclusion: Our study provided potential evidence for the impact of COVID-19 vaccination on the risk of MS and UC occurrence, but it lacks sufficient robustness, which could provide a new idea for public health policy.

Risk factors for acute kidney injury in pediatric patients after hematopoietic stem cell transplantation: a systematic review and meta-analysis.

BACKGROUND: Risk factors for acute kidney injury (AKI) in pediatric patients after hematopoietic stem cell transplantation (HSCT) remain controversial. OBJECTIVES: This study aimed to identify risk factors for AKI following HSCT in the pediatric population. DATA SOURCES: PubMed, Embase, Web of Science, Cochrane Library, and Scopus databases were searched from inception to February 8, 2023. STUDY ELIGIBILITY CRITERIA: Studies meeting the following criteria were included: (1) The study was a case-control, cohort study, or cross-sectional design, (2) the study was performed among pediatric and young patients aged 21 years or younger undergoing HSCT, (3) the study measured at least one related factor for AKI after pediatric HSCT, (4) the study included a sample of at least ten patients, and (5) original articles published in English in peer-reviewed scientific journals. PARTICIPANTS AND INTERVENTIONS: Children who were undergoing pediatric HSCT. STUDY APPRAISAL AND SYNTHESIS METHODS: We assessed the quality of the included studies and analyzed them with a random-effect model. RESULTS: Fifteen studies with a total of 2,093 patients were included. All were cohort studies of high quality. The overall pooled incidence of AKI was 47.4% (95%CI 0.35, 0.60). We found significant associations between post-transplant AKI in pediatric patients and unrelated donor [odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.09-2.79], cord blood stem cell transplantation (OR = 3.14, 95%CI 2.14-4.60), and veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) (OR = 6.02, 95%CI 1.40-25.88). Other controversial factors such as myeloablative conditioning (MAC), acute graft vs. host disease (aGVHD), and the use of calcineurin inhibitors (CNI) were not found to be related to AKI after pediatric HSCT. LIMITATIONS: Results were limited mainly by heterogeneity in the characteristics of patients and transplantation. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Posttransplant AKI in children is a common complication. Unrelated donors, cord blood stem cell transplantation, and VOD/SOS might be risk factors for AKI after pediatric HSCT. Further large-scale studies are still needed to draw firm conclusions. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42022382361 A higher resolution version of the Graphical abstract is available as Supplementary information.

Immune Cell-Related Genes in Juvenile Idiopathic Arthritis Identified Using Transcriptomic and Single-Cell Sequencing Data.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. The heterogeneity of the disease can be investigated via single-cell RNA sequencing (scRNA-seq) for its gap in the literature. Firstly, five types of immune cells (plasma cells, naive CD4 T cells, memory-activated CD4 T cells, eosinophils, and neutrophils) were significantly different between normal control (NC) and JIA samples. WGCNA was performed to identify genes that exhibited the highest correlation to differential immune cells. Then, 168 differentially expressed immune cell-related genes (DE-ICRGs) were identified by overlapping 13,706 genes identified by WGCNA and 286 differentially expressed genes (DEGs) between JIA and NC specimens. Next, four key genes, namely SOCS3, JUN, CLEC4C, and NFKBIA, were identified by a protein-protein interaction (PPI) network and three machine learning algorithms. The results of functional enrichment revealed that SOCS3, JUN, and NFKBIA were all associated with hallmark TNF-α signaling via NF-κB. In addition, cells in JIA samples were clustered into four groups (B cell, monocyte, NK cell, and T cell groups) by single-cell data analysis. CLEC4C and JUN exhibited the highest level of expression in B cells; NFKBIA and SOCS3 exhibited the highest level of expression in monocytes. Finally, real-time quantitative PCR (RT-qPCR) revealed that the expression of three key genes was consistent with that determined by differential analysis. Our study revealed four key genes with prognostic value for JIA. Our findings could have potential implications for JIA treatment and investigation.

Qiweibaizhu Decoction Treats Diarrheal Juvenile Rats by Modulating the Gut Microbiota, Short-Chain Fatty Acids, and the Mucus Barrier.

BACKGROUND: Qiweibaizhu decoction (QBD), a classic Chinese herbal formula, has been widely used for treating diarrhea in infants and children with spleen deficiency syndrome for centuries, but its mechanism of action remains unclear. The gut microbiota, short-chain fatty acids (SCFAs), and intestinal mucus are closely associated with diarrhea. METHODS: In this study, the composition of the gut microbiota in diarrheal rats was analyzed by 16S rDNA amplicon sequencing. The concentrations of colon SCFAs were determined using gas chromatography-mass spectrometry (GC-MS). The expression of mucin 2 (MUC2) in the colon was detected by immunofluorescence. RESULTS: Diarrhea significantly changed the diversity and structure of the gut microbiota and disrupted the mucus barrier in juvenile rats. QBD did not significantly change the diversity and structure of the intestinal flora, but it enhanced the increasing tendencies of Verrucomicrobia and Akkermansia and decreased the abundance of Turicibacter (P=0.037) and Flavonifractor (P=0.043). QBD tends to repair the mucus layer and promote MUC2 expression in juvenile rats with diarrhea. Moreover, S. boulardii significantly increased the abundance of Parasutterella (P=0.043). In addition, QBD treatment tends to increase the propionic acid concentration during diarrhea, but its levels of acetic acid, propionic acid, butyric acid, and total SCFAs were lower than those in the S. boulardii group. CONCLUSION: S. boulardii significantly increased the abundance of Parasutterella, leading to increased production of acetic acid, propionic acid, and butyric acid, consequently leading to alleviation of diarrhea. In comparison, QBD affected diarrhea via regulation of the intestinal flora, especially by increasing the abundance of Verrucomicrobia and Akkermansia, resulting in mucus barrier repair, protection of the intestines, and treatment of diarrhea.