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Introduction: Acute respiratory distress syndrome (ARDS) remains a major clinical challenge for patients in intensive care units. Determining the differential mechanisms underlying ARDS with different etiologies is a key goal to improve the effectiveness of ARDS therapy. Despite growing evidence that different immune cell types are involved in ARDS, the role of altered immune cell subpopulations in disease progression is unelucidated. Methods: In this study, we combined scRNA-seq and bulk-level sequencing to analyze the transcriptomes of peripheral blood mononuclear cells from healthy volunteers and patients with septic ARDS (sep-ARDS) and pneumonic ARDS (PNE-ARDS). Results: Our data revealed differential alterations at the cellular and molecular levels and within biological signaling pathways in ARDS with different etiologies. The dynamics of neutrophils, macrophages (Macs), classical dendritic cells (cDCs), myeloid-derived suppressive cells (MDSCs), and CD8+ T cells varied significantly among groups of different samples, with neutrophils and cDCs at higher, and Macs at significantly lower, amounts in the patients with sep-ARDS. Furthermore, MDSCs were highly enriched only in the sep-ARDS patients, whereas a higher abundance of CD8+ T cells was observed in patients with PNE-ARDS. In addition, these cell subpopulations were found to be significantly involved in apoptosis, inflammatory, and immune-related pathways. In particular, a significant enhancement of the oxidative stress response was observed in the neutrophil subpopulation. Conclusion: Our study shows that the composition of cells involved in the main peripheral circulation differs in patients with ARDS with different etiologies. Studying the role and mechanism of action of these cells during ARDS will provide new opportunities for the treatment of this condition.
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Vascular dementia (VD) and Alzheimer's disease (AD) are common types of dementia for which no curative therapies are known. In this study, we identified hub genes associated with AD and VD in order to explore new potential therapeutic targets. Genes differentially expressed in VD and AD in all three datasets (GSE122063, GSE132903, and GSE5281) were identified and used to construct a protein-protein interaction network. We identified 10 modules containing 427 module genes in AD and VD. Module genes showing an area under the diagnostic curve > 0.60 for AD or VD were used to construct a least absolute shrinkage and selection operator model and were entered into a support vector machine-recursive feature elimination algorithm, which identified REPS1 as a hub gene in AD and VD. Furthermore, REPS1 was associated with activation of pyruvate metabolism and inhibition of Ras signaling pathway. Module genes, together with differentially expressed microRNAs from the dataset GSE46579, were used to construct a regulatory network. REPS1 was predicted to bind to the microRNA hsa_miR_5701. Single-sample gene set enrichment analysis was used to explore immune cell infiltration, which suggested a negative correlation between REPS1 expression and infiltration by plasmacytoid dendritic cells in AD and VD. In conclusion, our results suggest core pathways involved in both AD and VD, and they identify REPS1 as a potential biomarker of both diseases. This protein may aid in early diagnosis, monitoring of treatment response, and even efforts to prevent these debilitating disorders.
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PURPOSE: Acute respiratory distress syndrome (ARDS) is a rapidly progressive diffuse lung injury that is characterized by high mortality and acute onset. The pathological mechanisms of ARDS are still unclear. But alveolar macrophages have been shown to play an important role in inflammatory responses during ARDS. We aimed to find the biomarkers for ARDS for early diagnosis, to give ARDS patients timely treatment. METHODS: Gene expression profiles were downloaded from Gene Expression Omnibus (GEO) and screened for differentially expressed genes (DEGs). The common upregulated genes in all the datasets were defined as circulating ARDS alveolar macrophage-related genes (cARDSAMGs). We performed a functional enrichment analysis to explore potential biological functions of cARDSAMGs, and we built protein-protein interaction networks. Gene set variation analysis (GSVA) was used to calculate the core gene set variation analysis (CGSVA) score for individual samples. Receiver operating characteristic (ROC) curve analysis was applied on the CGSVA score to evaluate its ability for diagnosis of ARDS. RESULTS: A total of 60 genes were upregulated in all ARDS datasets and were therefore denominated as cARDSAMGs. The cARDSAMGs were significantly involved in multiple inflammation-, immunity- and phagocytosis-related biological processes and pathways. In the protein-protein interaction network associated with host responses to ADRS, eight genes were identified as a core gene set: PTCRA, JAG1, C1QB, ADAM17, C1QA, MMP9, VSIG4 and TNFAIP3. ROC curve analysis showed that the CGSVA score may be considered as a biomarker for ARDS: it was significantly higher in patients with ARDS than those in healthy in both alveolar lavage fluid and whole blood. CONCLUSION: The ARDS alveolar macrophage-related CGSVA score may be useful as a biomarker for ARDS.
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AIM: To evaluate the diagnostic accuracy of magnetic resonance cholangiopancreatography (MRCP) in patients with choledocholithiasis. METHODS: We systematically searched MEDLINE, EMBASE, Web of Science, and Cochrane databases for studies reporting on the sensitivity, specificity and other accuracy measures of diagnostic effectiveness of MRCP for detection of common bile duct (CBD) stones. Pooled analysis was performed using random effects models, and receiver operating characteristic curves were generated to summarize overall test performance. Two reviewers independently assessed the methodological quality of studies using standards for reporting diagnostic accuracy and quality assessment for studies of diagnostic accuracy tools. RESULTS: A total of 25 studies involving 2310 patients with suspected choledocholithiasis and 738 patients with CBD stones met the inclusion criteria. The average inter-rater agreement on the methodological quality checklists was 0.96. Pooled analysis of the ability of MRCP to detect CBD stones showed the following effect estimates: sensitivity, 0.90 (95%CI: 0.88-0.92, χ (2) = 65.80; P < 0.001); specificity, 0.95 (95%CI: 0.93-1.0, χ (2) = 110.51; P < 0.001); positive likelihood ratio, 13.28 (95%CI: 8.85-19.94, χ (2) = 78.95; P < 0.001); negative likelihood ratio, 0.13 (95%CI: 0.09-0.18, χ (2) = 6.27; P < 0.001); and diagnostic odds ratio, 143.82 (95%CI: 82.42-250.95, χ (2) = 44.19; P < 0.001). The area under the receiver operating characteristic curve was 0.97. Significant publication bias was not detected (P = 0.266). CONCLUSION: MRCP has high diagnostic accuracy for the detection of choledocholithiasis. MRCP should be the method of choice for suspected cases of CBD stones.