BackgroundSeveral observational studies suggested an association between rheumatoid arthritis (RA) and bronchiectasis. Nevertheless, the presence of a causal relationship between these conditions is yet to be determined. This study aimed to investigate whether genetically predicted RA is associated with the risk of bronchiectasis and vice versa.MethodsWe obtained RA genome-wide association study (GWAS) data from FinnGen consortium, and bronchiectasis GWAS data from IEU Open GWAS project. Univariate Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW) estimation as the main method. Furthermore, bidirectional and replication MR analysis, multivariate MR (MVMR), Mediation analysis, and sensitivity analyses were conducted to validate the findings.ResultsIn the UVMR analysis, the IVW results revealed that RA had an increased risk of bronchiectasis (OR = 1.18, 95% CI = 1.10–1.27; p = 2.34 × 10−6). In the reverse MR analysis, no evidence of a causal effect of bronchiectasis on the risk of RA was detected. Conversely, in the replication MR analysis, RA remained associated with an increased risk of bronchiectasis. Estimates remained consistent in MVMR analyses after adjusting for the prescription of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. Immunosuppressants were found to mediate 58% of the effect of the RA on bronchiectasis. Sensitivity analyses confirmed the stability of these associations.ConclusionThis study demonstrated a positive causal relationship between RA and an increased risk of bronchiectasis, offering insights for the early prevention of bronchiectasis in RA patients and shedding new light on the potential role of immunosuppressants as mediators in promoting the effects of RA on bronchiectasis.

Previous research has shown a strong correlation between sepsis and brain structure. However, whether this relationship represents a causality remains elusive. In this study, we employed Mendelian randomization (MR) to probe the associations of genetically predicted sepsis and sepsis-related death with structural changes in specific brain regions. Genome-wide association study (GWAS) data for sepsis phenotypes (sepsis and sepsis-related death) were obtained from the IEU OpenGWAS. Correspondingly, GWAS data for brain structural traits (volume of the subcortical structure, cortical thickness, and surface area) were derived from the ENIGMA consortium. Inverse variance weighted was mainly utilized to assess the causal effects, while weighted median and MR-Egger regression served as complementary methods. Sensitivity analyses were implemented with Cochran Q test, MR-Egger regression, and MR-PRESSO. In addition, a reverse MR analysis was carried out to assess the possibility of reverse causation. We identified that genetic liability to sepsis was normally significantly associated with a reduced surface area of the postcentral gyrus (beta = -35.5280, SE = 13.7465, P = .0096). The genetic liability to sepsis-related death showed a suggestive positive correlation with the surface area of fusiform gyrus (beta = 11.0920, SE = 3.6412, P = .0023) and posterior cingulate gyrus (beta = 3.6530, SE = 1.6684, P = .0286), While it presented a suggestive negative correlation with surface area of the caudal middle frontal gyrus (beta = -11.4586, SE = 5.1501, P = .0261) and frontal pole (beta = -1.0024, SE = 0.4329, P = .0206). We also indicated a possible bidirectional causal association between genetic liability to sepsis-related death and the thickness of the transverse temporal gyrus. Sensitivity analyses verified the robustness of the above associations. These findings suggested that genetically determined liability to sepsis might influence the specific brain structure in a causal way, offering new perspectives to investigate the mechanism of sepsis-related neuropsychiatric disorders.

Background This study was performed to explore the causal association between asthma and chronic obstructive pulmonary disease(COPD). Methods We obtained summary statistics for asthma from 408,442 Europeans in an open genome-wide association study (GWAS) from the UK Biobank to select strongly associated single nucleotide polymorphisms that could serve as instrumental variables for asthma (P < 5×10−8). Additional summary statistics for COPD were obtained from 193,638 individuals of European ancestry in the GWAS published by FinnGen. Univariable Mendelian randomization(UVMR) analysis was performed using inverse variance weighted (IVW) as the primary method of analysis. The reliability of the results was verified by multivariable MR(MVMR), reverse and replication MR analysis, and sensitivity analysis. Results In the UVMR analysis, asthma increased the risk of COPD, with an odds ratio (OR) of 1.27 (95% confidence interval (CI) = 1.16–1.39, P = 5.44×10−7). Estimates were consistent in MVMR analyses by the adjustments of smoking initiation, age of smoking initiation, cigarettes per day, PM 2.5, and the combination of the above factors. In the reverse MR analysis, there was no evidence of a causal effect of COPD on asthma risk(OR = 1.02, 95% CI = 0.97–1.07, P = 0.3643). In the replication MR analysis, asthma still increased the risk of COPD. Sensitivity analyses validated the robustness of the above associations. Conclusions We found that genetically predicted asthma was positively associated with the risk of COPD. Additionally, there was no evidence that COPD increases the risk of asthma. Further clarification of this link and underlying mechanisms is needed to identify feasible measures to promote COPD prevention.

Objective: Thymosin alpha1 (Ta1) is widely used to treat patients with coronavirus disease 2019 (COVID-19), however, its effect remains unclear. This systematic review and meta-analysis aimed to evaluate the effect of Ta1 as a COVID-19 therapy.Methods: PubMed, EMBASE, the Cochrane library, Web of Science, and the reference lists of relevant articles were searched to identify eligible studies. Assessment of heterogeneity was done using the I-squared (I2) test and random/fixed effect analysis was done to determine the risk ratio (RR). We polled the data related to mortality mainly by using Review Manager 5.4. Predefined subgroup analyses and sensitivity analyses were also performed.Results: A total of 9 studies were included, on a total of 5352 (Ta1 symbolscript 1152, control symbolscript 4200) patient outcomes. Meta-analysis results indicated that Ta1 therapy had no statistically significant effect on mortality [RR 1.03 (0.60, 1.75), p symbolscript 0.92, I2 symbolscript 90 %]. Subgroup analyses demonstrated that the beneficial effect in mortality was associated with mean age>60 years in the T alpha 1 group [RR 0.68 (0.58, 0.78), p < 0.0000.1, I2 symbolscript 0 %], the proportion of female symbolscript 40 % in the T alpha 1 group [RR 0.67 (0.58, 0.77), p < 0.0000.1, I2 symbolscript 0 %], and severe/critical COVID-19 patients [RR 0.66 (0.57, 0.76), p < 0.0000.1, I2 symbolscript 0 %]. Sensitivity analysis further demonstrated the results to be robust.Conclusions: The results of this meta-analysis do not support the use of Ta1 in hospitalized adult COVID-19 patients.

The study aims to summarize topical and frontier issues in sepsis and exosomes and provide advice and resources for researchers working in related disciplines. Publications on exosomes in sepsis from 2004 to 2022 were extracted from the Web of Science Core Collection database. VOSviewer 1.6.18 and CiteSpace 6.1.3 were used to conduct the bibliometric analysis. The number of publications on exosomes in sepsis showed a rapidly rising trend globally. China and the United States were the most published countries. Shanghai Jiao Tong University is the most prolific institution. Frontiers in Immunology was one of the journals with the highest number of papers. Journal of Immunology was the most co-cited journal. Ping Wang was the most productive author. Clotilde Thery was the author who has been cited the most times among co-cited authors. Singer m, 2016, Jama-j am med assoc was the most co-cited reference. "Mesenchymal stem cells derived exosomes," "microRNAs," "apoptosis," and "immunomodulatory therapy" are the current research hot spots and frontiers. This study provides a comprehensive overview of the current status and trends in sepsis and exosomal research. Researchers working in this area will benefit from the hot spots and trends of exosomes in sepsis discovered through this study.

Micro RNAs (MiRNAs) act as a key regulator participating in various biological process, and the roles of that play in chronic obstructive pulmonary disease (COPD) are discovered. However, recent pharmacological treatment for COPD focus on alleviating symptoms and reducing the risk events. The heterogeneous COPD causes variable responses to pharmacological interventions. COPD treatment has gradually developed into precision medicine, integrating clinical and biomarker information to optimize personalized therapy. Thus, targeting miRNAs represents a promising strategy for COPD individual therapy. Twelve COPD patients, 7 community-acquired pneumonia and 4 normal people were recruited. Total RNAs were collected from the bronch alveolar lavage cells and peripheral blood plasma of each participant. miRNAs were profiled by microarray and systematically compared between patients with different groups. Bioinformatic analysis identified pathways relevant to the pathogenesis of COPD. Next, the target pathway networks were mapped. Compared different groups, we obtain differential expression of miRNAs (Q value (Adjusted P value) < .05 and |log2FC| >2). Gene ontology enrichment analyses showed that differentially expressed miRNAs function as regulators in different modules of cellular component, molecular function and biological process. Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that signals, such as MAPK signaling pathway, Ras signaling pathway, FoxO signaling pathway and oxidative stress may participate in the pathogenesis of COPD. In the miRNAs target pathway networks, novel-hsa-miR26-3p or hsa-miR-3529-3p/CDC42/MAPK signaling pathway may play a role in regulating COPD. Our findings demonstrate critical roles of the miRNAs in COPD molecular pathology. The data support a plausible mechanism that miRNAs may be involved in the development of COPD by affecting the inflammatory and oxidative stress. Moreover, hsa-miR-4748/CDC42/MAPK signaling pathway may contribute to the pathogenesis of COPD, providing a potential novel therapeutic strategy in COPD.