MicroRNAs (miRNAs) packaged into exosomes mediate cell communication and contribute to the pathogenesis of acute type A aortic dissection (ATAAD) with acute lung injury (ALI). The expression profile of plasma exosomal miRNAs in ATAAD patients with ALI hasn’t been identified. We performed a miRNA-sequencing to analyze the differentially expressed miRNAs (DE-miRNAs) of circulating exosomes in ATAAD patients with ALI compared to patients without ALI, founding 283 specific miRNAs in two groups. We respectively selected the top 10 downregulated and upregulated DE-miRNAs for further studies. The predicted transcription factors (TFs) of these DE-miRNAs were SMAD2, SRSF1, USF1, etc. The Gene Ontology (GO) and Kyoto Encyclopedia Genes and Genomes (KEGG) analysis predicted their target genes mainly involved acute inflammatory response, cell junction, cytoskeleton, NF-κB signaling pathway, etc. Construction and analysis of the PPI network revealed that RHOA and INSR were considered hub genes with the highest connectivity degrees. Moreover, we confirmed two exosomal miRNAs (hsa-miR-485-5p and hsa-miR-206) by real-time quantitative polymerase chain reaction (RT-qPCR) in a validation cohort. Our study identified a plasma exosomal miRNAs signature related to ATAAD with ALI. Certain DE-miRNAs may contribute to the progression of this disease, which help us better understand the pathogenesis of ATAAD with ALI.
1 August 2021 in International Journal of General Medicine
Objective: Serum bicarbonate (HCO3−) level is strongly related to multiple cardiovascular complications. Currently, there is no study evaluating the prognostic ability of serum HCO3− level in intensive care unit (ICU) patients with acute aortic dissection (AAD). Hence, this study was to assess the relationship between admission serum HCO3− level and clinical outcomes in patients with AAD. Design, Settings and Participants: Clinical data were extracted from the MIMIC-III database. Cox proportional hazards models and Kaplan–Meier (KM) survival curve were used to evaluate the association between serum HCO3− levels and short- and long-term mortality in ICU patients with AAD. The subgroup analysis and the receiver operating characteristic (ROC) curve analysis and further KM survival curve based on best cut-off value were applied to assessment of the performance of HCO3− in predicting the mortality in each period (30 days, 90 days, 1 year and 5 years). Main Results: Firstly, 336 eligible patients were trisected to low-HCO3− level group (< 22 mmol/L), mid-HCO3− level group (22– 24 mmol/L) and high-HCO3− level group (> 24 mmol/L). Then, in multivariate analysis, the serum HCO3− of low levels (< 22 mmol/L) was a significant risk predictor of all-cause mortality in 30 days, 90 days, 1 year and 5 years. Subgroup analyses indicated that there is no interaction in most strata. Finally, areas under ROC curve ranged from 0.60 to 0.69. Conclusion: The low HCO3− serum level measured at ICU admission significantly predicts short-term and long-term mortality in AAD patients.
Background: Inflammation underlies both the pathogenesis and prognosis in patients with acute aortic dissection (AAD). This study aimed to assess the association of ICU admission of white blood cell count (WBCc) with post-discharge mortality in these patients. Methods: Clinical data were extracted from the MIMIC-III V1.4 database. After adjusted to covariables, Cox regression analysis and Kaplan–Meier survival curve were performed to determine the relationship between WBCc on admission and post-discharge mortality (30-day, 90-day, 1-year and 5-year) in AAD patients. Subgroup analysis and receiver operating characteristic (ROC) curve analysis were used to test the performance of WBCc in predicting mortality in AAD patients. Results: A total of 325 eligible patients were divided into 2 groups: normal-WBCc group (≤ 11 k/uL) and high-WBCc group (> 11 K/uL). In univariate Cox regression analysis, high WBCc was significant risk predictor of 30-day, 90-day, 1-year and 5-year mortality [hazard ratio (HR), 95% CI, P 2.58 1.36–4.91 0.004; 3.16 1.76–5.70 0.000; 2.74 1.57–4.79 0.000; 2.10 1.23–3.54 0.006]. After adjusting for age and other risks, high WBCc remained a significant predictor of 30-day, 90-day and 1-year mortality in AAD patients (HR, 95% CI, P 1.994 1.058–3.76 0.033; 2.118 1.175–3.819 0.013; 2.37 1.343–4.181 0.003). The area under ROC curve of WBCc for predicting 30-day, 90-day, 1-year and 5-year mortality were 0.69, 0.70, 0.66 and 0.61, respectively. The results from subgroups analysis showed that there was no interaction in most strata and patients who were younger than 69 years of age or had history of respiratory disease with an elevated WBCc had an excess risk of 30-day mortality (HR, 95% CI, P 3.18 1.41–7.14 0.005; 3.84 1.05–14.13 0.043). Conclusions: Higher than normal WBCc on admission may predict post-discharge mortality in patients with AAD.
Introduction. Idiopathic pulmonary arterial hypertension (IPAH) is a severe cardiopulmonary disease with a relatively low survival rate. Moreover, the pathogenesis of IPAH has not been fully recognized. Thus, comprehensive analyses of miRNA‐mRNA network and potential drugs in IPAH are urgent requirements. Methods. Microarray datasets of mRNA and microRNA (miRNA) in IPAH were searched and downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMIs) were identified. Then, the DEMI‐DEG network was conducted with associated comprehensive analyses including Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein‐protein interaction (PPI) network analysis, while potential drugs targeting hub genes were investigated using L1000 platform. Results. 30 DEGs and 6 DEMIs were identified in the lung tissue of IPAH. GO and KEGG pathway analyses revealed that these DEGs were mostly enriched in antimicrobial humoral response and African trypanosomiasis, respectively. The DEMI‐DEG network was conducted subsequently with 4 DEMIs (hsa‐miR‐34b‐5p, hsa‐miR‐26b‐5p, hsa‐miR‐205‐5p, and hsa‐miR‐199a‐3p) and 16 DEGs, among which 5 DEGs (AQP9, SPP1, END1, VCAM1, and SAA1) were included in the top 10 hub genes of the PPI network. Nimodipine was identified with the highest CMap connectivity score in L1000 platform. Conclusion. Our study conducted a miRNA‐mRNA network and identified 4 miRNAs as well as 5 mRNAs which may play important roles in the pathogenesis of IPAH. Moreover, we provided a new insight for future therapies by predicting potential drugs targeting hub genes.
Objective: The study aimed to determine the relationship between body mass index (BMI) and the risk of acute aortic syndrome (AAS) with preoperative oxygenation impairment.Methods: A meta-analysis of published observational studies involving BMI and AAS with preoperative oxygenation impairment was conducted. A total of 230 patients with AAS were enrolled for retrospective analysis. All patients were divided into 2 groups (Non-oxygenation impairment group and Oxygenation impairment group). Logistic regression analysis was performed to assess the relation between BMI and the risk of preoperative oxygenation impairment after the onset of AAS. Dose-response relationship curve and subgroup analysis were conducted to test the reliability of BMI as an independent factor of it.Results: For the meta-analysis, the quantitative synthesis indicated that excessive BMI increased the risk of preoperative oxygenation impairment (OR: 1.30, 95% CI: 1.05-1.60, Pheterogeneity = 0.001). For the retrospective analysis, a significant association was observed after adjusting for a series of variables. BMI was significantly related to preoperative oxygenation impairment after the onset of AAS (OR: 1.34, 95% CI: 1.15-1.56, p <0.001), and compared with normal weight group (18.5 kg/m2 ≤ BMI < 23.0 kg/m2), the individuals with excessive BMI were at higher risk of preoperative oxygenation impairment for the obese group (BMI ≥ 25 kg/m2) (OR: 17.32, 95% CI: 4.03-74.48, p <0.001). A J-shape curve in dose-response relationship analysis further confirmed their positive correlation. Subgroup analysis showed that diastolic blood pressure (DBP) ≥ 90mmHg carried an excess risk of preoperative oxygenation impairment in obese patients.Conclusion: Excessive BMI was an independent risk factor for AAS with preoperative oxygenation impairment.
Postoperative oxygenation impairment represents a common complication in patients with the acute aortic syndrome (AAS). The study aimed to explore the relationship between inflammatory indicators and AAS patients with oxygenation impairment after operation. In this study, 330 AAS patients who underwent surgery were enrolled and divided into 2 groups based on postoperative oxygenation impairment (non-oxygenation impairment group and oxygenation impairment group). Regression analysis was performed to assess the relationship between inflammatory indicators and postoperative oxygenation impairment. A smooth curve and interaction analysis were further conducted. Stratified analysis was used according to preoperative monocyte/lymphocyte ratio (MLR) (Tertiles). Multivariate analysis showed that preoperative MLR was independently related to oxygenation impairment after surgery in AAS patients (OR, 95% CI, P: 2.77, 1.10-7.00, 0.031). The smooth curve indicated the risk of postoperative oxygenation impairment was higher with the elevated preoperative MLR. Interaction analysis revealed that patients with AAS with high preoperative MLR who had coronary artery disease (CAD) had a higher risk of oxygenation impairment after operation. Moreover, stratified analysis was performed according to baseline MLR (Tertiles), and a higher baseline MLR level in AAS patients was correlated with a lower arterial oxygen tension (PaO2) / inspiratory oxygen fraction (FiO2) ratio perioperatively. In AAS patients, preoperative MLR level was independently related to postoperative oxygenation impairment.