scholarly journals Circulating Exosomal circRNAs Contribute to Potential Diagnostic Value of Large Artery Atherosclerotic Stroke

2022 ◽  
Vol 12 ◽  
Author(s):  
Qi Xiao ◽  
Rongyao Hou ◽  
Hong Li ◽  
Shuai Zhang ◽  
Fuzhi Zhang ◽  
...  

Large artery atherosclerotic (LAA) stroke is closely associated with atherosclerosis, characterized by the accumulation of immune cells. Early recognition of LAA stroke is crucial. Circulating exosomal circRNAs profiling represents a promising, noninvasive approach for the detection of LAA stroke. Exosomal circRNA sequencing was used to identify differentially expressed circRNAs between LAA stroke and normal controls. From a further validation stage, the results were validated using RT-qPCR. We then built logistic regression models of exosomal circRNAs based on a large replication stage, and receiver operating characteristic (ROC) curves were constructed to assess the diagnostic efficacy. Using exosomal circRNA sequencing, large sample validation, and diagnostic model construction revealed that exosomal circ_0043837 and circ_ 0001801were independent predictive factors for LAA stroke, and had better diagnostic efficacy than plasma circRNAs. In the atherosclerotic group (AS), we developed a nomogram for clinical use that integrated the two-circRNA-based risk factors to predict which patients might have the risk of plaque rupture. Circulating exosomal circRNAs profiling identifies novel predictive biomarkers for the LAA stroke and plaque rupture, with superior diagnostic value than plasma circRNAs. It might facilitate the prevention and better management of this disease.

2021 ◽  
Author(s):  
Jianhong Yu ◽  
Qirui Cai

Abstract Objective This study aimed to establish a predictive model based on the clinical manifestations and laboratory findings in pleural fluid of patients with pleural effusion for the differential diagnosis of malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE). Methods Clinical data and laboratory indices of pleural fluid were collected from patients with malignant pleural effusion and tuberculous pleural effusion in Zigong First People's Hospital between January 2019 and June 2020,and were compared between the two groups. Independent risk factors or Independent protective factors for malignant pleural effusion were investigated using multivariable logistic regression analysis. Receiver operating characteristic curve (ROC) analysis was performed to assess the diagnostic performance of factors with independent effects, and combined diagnostic models were established based on two or more factors with independence effect. ROC curve was used to evaluate the diagnostic ability of each model, and the fit of the eath model was measured using Hosmer-Lemeshow goodness-of-fit test. Results Patients with MPE were older than those with TPE, the rate of fever of patients with MPE was lower than that of patients with TPE, and these differences were statistically significant (p < 0.05). Carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin-19 fragment antigen (CYFRA21-1), cancer antigen 125 (CA125), and glucose (GLU) levels in the pleural fluid were higher, but total protein (TP), albumin (ALB) and Adenosine deaminase (ADA) levels in the pleural fluid were lower in MPE patients than in TPE patients, and the differences were statistically significant (P<0.05). In multivariate logistic regression analysis, CEA and NSE levels in the pleural fluid were independent risk factors for MPE, whereas ADA levels in pleural fluid and fever were independent protective factors for MPE. The differential diagnostic value of pleural fluid CEA and pleural fluid ADA for MPE and TPE were higher than that of pleural fluid NSE(p<0.05) and the area under the ROC curve was 0.901, 0.892, and 0.601, respectively. Four different binary logistic diagnostic models were established based on pleural fluid CEA combined with pleural fluid NSE, pleural fluid ADA or ( and ) fever. Among them, the model established with the combination of pleural fluid CEA and pleural fluid ADA (logit (P) = 0.513 + 0.457*CEA-0.101*ADA) had the highest diagnostic value for malignant pleural effusion, and its predictive accuracy was high with an area under the ROC curve of 0.968 [95% confidence interval (0.947, 0.988)]. But the diagnostic efficacy of the diagnostic model could not be improved by adding pleural fluid NSE and fever. Conclusion The model established with the combination of CEA and ADA in the pleural fluid has a high differential diagnostic value for malignant pleural effusion and tuberculous pleural effusion, and NSE in the pleural fluid and fever cannot improve the diagnostic efficacy of the diagnostic model.


2021 ◽  
Author(s):  
Kaiping Jiang ◽  
Lei Zhang ◽  
Jianhong Li ◽  
Hongtao Hu ◽  
Qinghua Huang ◽  
...  

Abstract Background: Noninvasive diagnostic technologies that can dynamically monitor changes in liver inflammation are highly important for the management of chronic hepatitis B (CHB) patients and thus warrant further exploration. This study assessed the diagnostic efficacy of FibroScan for liver inflammation in CHB patients.Methods: A total of 1185 patients were selected, and ultrasound-guided liver biopsy was performed within one month after the FibroScan test. The liver stiffness measurement (LSM), the reliability criteria (IQR/M) of LSM, the quality of liver biopsy (complete portal area, PA), and the liver inflammation grades were the main observation items of this study. With liver biopsy as the control, the diagnostic efficacy of FibroScan for liver inflammation in CHB patients was evaluated by receiver operating characteristic (ROC) curve analysis.Results: Significant differences in the LSM of FibroScan were observed among different grades of liver inflammation (P<0.0001). Liver biopsy (PA>10) served as the control, and the cutoff point and the area under ROC curves (AUCs) of the LSMs for different inflammation grades were as follows: G2, 8.6 kPa, 0.775; G3 9.8 kPa, 0.818; and G4, 11.0 kPa; 0.832. With LSM cutoff values of 8.6 kPa, 9.8 kPa and 11.0 kPa, FibroScan showed certain diagnostic value for CHB patients with G2, G3 and G4 liver inflammation, especially those with G4 inflammation. Conclusions: The results of this study preliminarily showed that, in addition to liver fibrosis, FibroScan could evaluate liver inflammation in CHB patients in a noninvasive manner.


2022 ◽  
Vol 12 ◽  
Author(s):  
Xiuqi Chen ◽  
Danhong Wu

Background: Acute ischemic stroke (AIS) is the second leading cause of death and the third leading cause of disability worldwide. Long noncoding RNAs (lncRNAs) are promising biomarkers for the early diagnosis of AIS and closely participate in the mechanism of stroke onset. However, studies focusing on lncRNAs functioning as microRNA (miRNA) sponges to regulate the mRNA expression are rare and superficial.Methods: In this study, we systematically analyzed the expression profiles of lncRNA, mRNA (GSE58294), and miRNA (GSE110993) from the GEO database. Gene ontology (GO) analysis was performed to reveal the functions of differentially expressed genes (DEGs), and we used weighted gene co-expression network analysis (WGCNA) to investigate the relationships between clinical features and expression profiles and the co-expression of miRNA and lncRNA. Finally, we constructed a lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) network with selected DEGs using bioinformatics methods and obtained ROC curves to assess the diagnostic efficacy of differentially expressed lncRNAs (DElncRNAs) and differentially expressed mRNAs (DEmRNAs) in our network. The GSE22255 dataset was used to confirm the diagnostic value of candidate genes.Results: In total, 199 DElncRNAs, 2068 DEmRNAs, and 96 differentially expressed miRNAs were detected. The GO analysis revealed that DEmRNAs primarily participate in neutrophil activation, neutrophil degranulation, vacuolar transport, and lysosomal transport. WGCNA screened out 16 lncRNAs and 195 mRNAs from DEGs, and only eight DElncRNAs maintained an area under the curve higher than 0.9. By investigating the relationships between lncRNAs and mRNAs, a ceRNA network containing three lncRNAs, three miRNAs, and seven mRNAs was constructed. GSE22255 confirmed that RP1-193H18.2 is more advantageous for diagnosing stroke, whereas no mRNA showed realistic diagnostic efficacy.Conclusion: The ceRNA network may broaden our understanding of AIS pathology, and the candidate lncRNA from the ceRNA network is assumed to be a promising therapeutic target and diagnostic biomarker for AIS.


2019 ◽  
Vol 8 (12) ◽  
pp. 2029 ◽  
Author(s):  
Rapado-González ◽  
Majem ◽  
Álvarez-Castro ◽  
Díaz-Peña ◽  
Abalo ◽  
...  

Salivary microRNAs (miRNAs) are of high interest as diagnostic biomarkers for non-oral cancer. However, little is known about their value for colorectal cancer (CRC) detection. Our study aims to characterize salivary miRNAs in order to identify non-invasive markers for CRC diagnosis. The screening of 754 miRNAs was performed in saliva samples from 14 CRC and 10 healthy controls. The differential expressed miRNAs were validated by RT-qPCR in 51 CRC, 19 adenomas and 37 healthy controls. Receiver operating characteristic (ROC) curves and logistic regression models were performed to analyze the clinical value of these miRNAs. Twenty-two salivary miRNAs were significantly deregulated in CRC patients vs. healthy individuals (P < 0.05) in the discovery phase. From those, five upregulated miRNAs (miR-186-5p, miR-29a-3p, miR-29c-3p, miR-766-3p, and miR-491-5p) were confirmed to be significantly higher in the CRC vs. healthy group (P < 0.05). This five-miRNA signature showed diagnostic value (72% sensitivity, 66.67% specificity, AUC = 0.754) to detect CRC, which was even higher in combination with carcinoembryonic antigen (CEA) levels. Overall, after the first global characterization of salivary miRNAs in CRC, a five-miRNA panel was identified as a promising tool to diagnose this malignancy, representing a novel approach to detect cancer-associated epigenetic alterations using a non-invasive strategy.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qiao Xiang ◽  
Tao Chen ◽  
Kai Yu ◽  
Yuanmei Li ◽  
Qianrui Li ◽  
...  

ObjectiveThe result interpretation of the captopril challenge test (CCT) for the diagnosis of primary aldosteronism (PA) is not standardized. Superiorities of different indexes in the CCT have not been fully investigated. We aimed to comprehensively evaluate the value and influence factors of different CCT-associated indexes in the diagnosis of PA.MethodsWe enrolled 312, 85, 179 and 97 patients in the groups of PA, essential hypertension (EH), unilateral PA (UPA) and bilateral PA (BPA), respectively. For each single index investigated, we computed diagnostic estimates including the area under the receiver operating characteristic curve (AUC). We performed pre-specified subgroup analyses to explore influence factors. We assessed the diagnostic value of combined indexes in binary logistic regression models.ResultsPost-CCT aldosterone to renin ratio (ARR) (AUC = 0.8771) and plasma aldosterone concentration (PAC) (AUC = 0.8769) showed high value in distinguishing PA from EH, and their combination (AUC = 0.937) was even superior to either alone. The diagnostic efficacy was moderately high for post-CCT aldosterone to angiotensin II ratio (AA2R) (AUC = 0.834) or plasma renin activity (PRA) (AUC = 0.795) but low for the suppression percentage of PAC (AUC = 0.679). Post-CCT PAC had a significantly higher AUC in the UPA than BPA subgroup (AUC = 0.914 vs 0.827, P&lt;0.05).ConclusionWe can take post-CCT ARR and PAC altogether into account to distinguish PA from EH, while caution should be taken to interpret CCT results with the suppression percentage of PAC. Post-CCT PAC may perform better to identify the unilateral than bilateral form of PA.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Liang-Yuan Li ◽  
Tian-Sheng Yan ◽  
Jing Yang ◽  
Yu-Qi Li ◽  
Lin-Xi Fu ◽  
...  

Abstract Background Subjects with chronic respiratory symptoms and preserved pulmonary function (PPF) may have small airway dysfunction (SAD). As the most common means to detect SAD, spirometry needs good cooperation and its reliability is controversial. Impulse oscillometry (IOS) may complete the deficiency of spirometry and have higher sensitivity. We aimed to explore the diagnostic value of IOS to detect SAD in symptomatic subjects with PPF. Methods The evaluation of symptoms, spirometry and IOS results in 209 subjects with chronic respiratory symptoms and PPF were assessed. ROC curves of IOS to detect SAD were analyzed. Results 209 subjects with chronic respiratory symptoms and PPF were included. Subjects who reported sputum had higher R5–R20 and Fres than those who didn’t. Subjects with dyspnea had higher R5, R5–R20 and AX than those without. CAT and mMRC scores correlated better with IOS parameters than with spirometry. R5, R5–R20, AX and Fres in subjects with SAD (n = 42) significantly increased compared to those without. Cutoff values for IOS parameters to detect SAD were 0.30 kPa/L s for R5, 0.015 kPa/L s for R5–R20, 0.30 kPa/L for AX and 11.23 Hz for Fres. Fres has the largest AUC (0.665, P = 0.001) among these parameters. Compared with spirometry, prevalence of SAD was higher when measured with IOS. R5 could detect the most SAD subjects with a prevalence of 60.77% and a sensitivity of 81% (AUC = 0.659, P = 0.002). Conclusion IOS is more sensitive to detect SAD than spirometry in subjects with chronic respiratory symptoms and PPF, and it correlates better with symptoms. IOS could be an additional method for SAD detection in the early stage of diseases.


Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 419
Author(s):  
Fares Qeadan ◽  
Benjamin Tingey ◽  
Lily Y. Gu ◽  
Ashley Hafen Packard ◽  
Esther Erdei ◽  
...  

Cytokine storm syndrome in patients with COVID-19 is mediated by pro-inflammatory cytokines resulting in acute lung injury and multiorgan failure. Elevation in serum ferritin and D-dimer is observed in COVID-19 patients. To determine prognostic values of optimal serum cutoff with trajectory plots for both serum ferritin and D-dimer in COVID-19 patients with invasive ventilator dependence and in-hospital mortality. We used retrospective longitudinal data from the Cerner COVID-19 de-identified cohort. COVID-19 infected patients with valid repeated values of serum ferritin and D-dimer during hospitalization were used in mixed-effects logistic-regression models. Among 52,411 patients, 28.5% (14,958) had valid serum ferritin and 28.6% (15,005) D-dimer laboratory results. Optimal cutoffs of ferritin (714 ng/mL) and D-dimer (2.1 mg/L) revealed AUCs ≥ 0.99 for in-hospital mortality. Optimal cutoffs for ferritin (502 ng/mL) and D-dimer (2.0 mg/L) revealed AUCs ≥ 0.99 for invasive ventilator dependence. Optimal cutoffs for in-house mortality, among females, were lower in serum ferritin (433 ng/mL) and D-dimer (1.9 mg/L) compared to males (740 ng/mL and 2.5 mg/L, respectively). Optimal cutoffs for invasive ventilator dependence, among females, were lower in ferritin (270 ng/mL) and D-dimer (1.3 mg/L) compared to males (860 ng/mL and 2.3 mg/L, respectively). Optimal prognostic cutoffs for serum ferritin and D-dimer require considering the entire trajectory of laboratory values during the disease course. Females have an overall lower optimal cutoff for both serum ferritin and D-dimer. The presented research allows health professionals to predict clinical outcomes and appropriate allocation of resources during the COVID-19 pandemic, especially early recognition of COVID-19 patients needing higher levels of care.


2021 ◽  
Vol 22 (15) ◽  
pp. 7913
Author(s):  
Julia Oto ◽  
Raquel Herranz ◽  
Emma Plana ◽  
José Vicente Sánchez-González ◽  
Javier Pérez-Ardavín ◽  
...  

Renal cell carcinoma (RCC) is the third most frequent urinary malignancy and one of the most lethal. Current diagnostic and follow-up techniques are harmful and unspecific in low-grade tumors. Novel minimally invasive markers such as urine microRNAs (miRNAs) are under study. However, discrepancies arise among studies in part due to lack of consent regarding normalization. We aimed to identify the best miRNA normalizer for RCC studies performed in urine samples together with a miRNA profile with diagnostic value and another for follow-up. We evaluated the performance of 120 candidate miRNAs in the urine of 16 RCC patients and 16 healthy controls by RT-qPCR followed by a stability analysis with RefFinder. In this screening stage, miR-20a-5p arose as the most stably expressed miRNA in RCC and controls, with a good expression level. Its stability was validated in an independent cohort of 51 RCC patients and 32 controls. Using miR-20a-5p as normalizer, we adjusted and validated a diagnostic model for RCC with three miRNAs (miR-200a-3p, miR-34a-5p and miR-365a-3p) (AUC = 0.65; Confidence Interval 95% [0.51, 0.79], p = 0.043). let-7d-5p and miR-205-5p were also upregulated in patients compared to controls. Comparing RCC samples before surgery and fourteen weeks after, we identified let-7d-5p, miR-152-3p, miR-30c-5p, miR-362-3p and miR-30e-3p as potential follow-up profile for RCC. We identified validated targets of most miRNAs in the renal cell carcinoma pathway. This is the first study that identifies a robust normalizer for urine RCC miRNA studies, miR-20a-5p, which may allow the comparison of future studies among laboratories. Once confirmed in a larger independent cohort, the miRNAs profiles identified may improve the non-invasive diagnosis and follow-up of RCC.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fei Ye ◽  
Tianzhu Wang ◽  
Xiaoxin Wu ◽  
Jie Liang ◽  
Jiaoxing Li ◽  
...  

Abstract Background Progressive multiple sclerosis (PMS) is an uncommon and severe subtype of MS that worsens gradually and leads to irreversible disabilities in young adults. Currently, there are no applicable or reliable biomarkers to distinguish PMS from relapsing–remitting multiple sclerosis (RRMS). Previous studies have demonstrated that dysfunction of N6-methyladenosine (m6A) RNA modification is relevant to many neurological disorders. Thus, the aim of this study was to explore the diagnostic biomarkers for PMS based on m6A regulatory genes in the cerebrospinal fluid (CSF). Methods Gene expression matrices were downloaded from the ArrayExpress database. Then, we identified differentially expressed m6A regulatory genes between MS and non-MS patients. MS clusters were identified by consensus clustering analysis. Next, we analyzed the correlation between clusters and clinical characteristics. The random forest (RF) algorithm was applied to select key m6A-related genes. The support vector machine (SVM) was then used to construct a diagnostic gene signature. Receiver operating characteristic (ROC) curves were plotted to evaluate the accuracy of the diagnostic model. In addition, CSF samples from MS and non-MS patients were collected and used for external validation, as evaluated by an m6A RNA Methylation Quantification Kit and by real-time quantitative polymerase chain reaction. Results The 13 central m6A RNA methylation regulators were all upregulated in MS patients when compared with non-MS patients. Consensus clustering analysis identified two clusters, both of which were significantly associated with MS subtypes. Next, we divided 61 MS patients into a training set (n = 41) and a test set (n = 20). The RF algorithm identified eight feature genes, and the SVM method was successfully applied to construct a diagnostic model. ROC curves revealed good performance. Finally, the analysis of 11 CSF samples demonstrated that RRMS samples exhibited significantly higher levels of m6A RNA methylation and higher gene expression levels of m6A-related genes than PMS samples. Conclusions The dynamic modification of m6A RNA methylation is involved in the progression of MS and could potentially represent a novel CSF biomarker for diagnosing MS and distinguishing PMS from RRMS in the early stages of the disease.


Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 829
Author(s):  
Yana Kogan ◽  
Edmond Sabo ◽  
Majed Odeh

Objectives: The role of serum C-reactive protein (CRPs) and pleural fluid CRP (CRPpf) in discriminating uncomplicated parapneumonic effusion (UCPPE) from complicated parapneumonic effusion (CPPE) is yet to be validated since most of the previous studies were on small cohorts and with variable results. The role of CRPs and CRPpf gradient (CRPg) and of their ratio (CRPr) in this discrimination has not been previously reported. The study aims to assess the diagnostic efficacy of CRPs, CRPpf, CRPr, and CRPg in discriminating UCPPE from CPPE in a relatively large cohort. Methods: The study population included 146 patients with PPE, 86 with UCPPE and 60 with CPPE. Levels of CRPs and CRPpf were measured, and the CRPg and CRPr were calculated. The values are presented as mean ± SD. Results: Mean levels of CRPs, CRPpf, CRPg, and CRPr of the UCPPE group were 145.3 ± 67.6 mg/L, 58.5 ± 38.5 mg/L, 86.8 ± 37.3 mg/L, and 0.39 ± 0.11, respectively, and for the CPPE group were 302.2 ± 75.6 mg/L, 112 ± 65 mg/L, 188.3 ± 62.3 mg/L, and 0.36 ± 0.19, respectively. Levels of CRPs, CRPpf, and CRPg were significantly higher in the CPPE than in the UCPPE group (p < 0.0001). No significant difference was found between the two groups for levels of CRPr (p = 0.26). The best cut-off value calculated by the receiver operating characteristic (ROC) analysis for discriminating UCPPE from CPPE was for CRPs, 211.5 mg/L with area under the curve (AUC) = 94% and p < 0.0001, for CRPpf, 90.5 mg/L with AUC = 76.3% and p < 0.0001, and for CRPg, 142 mg/L with AUC = 91% and p < 0.0001. Conclusions: CRPs, CRPpf, and CRPg are strong markers for discrimination between UCPPE and CPPE, while CRPr has no role in this discrimination.


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