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Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients

  • Guan Wang , Chun Wang , Zhengyi Huang , Shuai Sun and Yanjun Chen EMAIL logo
Published/Copyright: October 11, 2023
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Open Medicine
From the journal Open Medicine Volume 18 Issue 1

Abstract

This study attempted to identify exosomal circular RNAs (circRNAs) as diagnostic and prognostic biomarkers for patients with ST-segment elevation myocardial infarction (STEMI). The differentially expressed exosomal circRNAs (DEECs) were screened from microarray dataset (GSE160717 and GSE197137) and RNA-Seq dataset (GSE208194), and the expression levels of DEECs in patients with STEMI were validated using reverse transcription and quantitative real-time PCR. The diagnostic value of DEECs was assessed using receiver operating characteristic curves. The major adverse cardiovascular event (MACE)-free 1-year survival rate was evaluated using the Kaplan–Meier method, and the factors affecting prognosis were determined using Cox regression model analysis. Results showed that four DEECs were screened including exo-circ-0001490, exo-circ-0020887, exo-circ-0009590, and exo-circ-0055440, and only upregulated exo-circ-0020887 and exo-circ-0009590 expression was validated in patients with STEMI. The exo-circ-0020887 and exo-circ-0009590 expression was positively correlated with hs-CRP, LDL-C, cTnI, and CK-MB. The exo-circ-0020887 and exo-circ-0009590 showed good diagnostic efficacy to distinguish STEMI patients from healthy controls (area under the curves: 0.85 and 0.80). STEMI patients with high levels of exo-circ-0020887 and exo-circ-0009590 had lower MACE-free 1-year survival rate, and exo-circ-0020887 and exo-circ-0009590 expression was independent risk factors for adverse prognosis. In summary, upregulation of plasma exo-circ-0020887 and exo-circ-0009590 might act as potential biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in patients with STEMI.

Keywords: STEMI; exo-circ-0020887; exo-circ-0009590; MACE-free 1-year survival rate; biomarkers

1 Introduction

ST-segment elevation myocardial infarction (STEMI) is a serious form of acute coronary syndrome, which mainly caused by acute thrombotic coronary artery occlusion at the site of a ruptured pre-existing atherosclerotic plaque [1]. At present, STEMI remains a significant contributor to the high rate of morbidity and mortality worldwide [2]. Over the past few decades, several conventional biomarkers including lactate dehydrogenase, cardiac troponin I (cTnI), creatine kinase isoenzymes (CK-MB), and myoglobin have been used as diagnostic biomarkers for STEMI [3]. However, the application of these biomarkers in the early stage of STEMI onset is limited due to low sensitivity, and there is a lack of prognostic biomarkers for STEMI. Therefore, identification of novel biomarkers with high specificity and sensitivity for STEMI is urgently needed.

Exosomes are first reported by Trams EG team in 1981, which are small extracellular vesicles at 40–150 nm in diameter and contain a specific cargo of proteins, mRNAs, and non-coding RNAs (ncRNAs) [4]. Exosomes are secreted by a wide variety of eukaryotic cells and are existed in nearly all body fluids, including plasma, serum, sweat, tears, saliva, urine, breast milk, gastric juice, and cerebrospinal fluid [5,6]. Recently, exosomes are found to functionally modulate the activities of neighboring and distant recipient cells and participate in the regulation of various pathological states in human diseases [7,8]. Circular RNAs (circRNAs) are a special type of endogenous ncRNAs, which characterized by covalently closed loop structures and highly resistant to Ribonuclease R (RNase R) activity [9]. It has been suggested that circRNAs are enriched and stable in exosomes. Currently, with the development of gene microarray and sequencing, a large number of dysregulated exosomal circRNAs have been found in serum and plasma [10]. Accumulating evidence has indicated that circRNA can be encapsulated in exosomes and participate in the pathological process of various diseases [11].

Recent studies have shown that exosomal circRNAs have potential applications as disease biomarkers and novel therapeutic targets [12]. Comparatively, there have been few studies on the correlations between exosomal circRNAs and STEMI. Our study is based on the hypothesis that exosomal circRNAs can be used as potential biomarkers for STEMI. In the present study, we aim to identify differentially expressed exosomal circRNAs (DEECs) from microarray dataset (GSE160717 and GSE197137) and RNA-Seq dataset (GSE208194). The correlations between the expression levels of DEECs and clinicopathological features were analyzed, and the diagnostic and prognostic values of DEECs were evaluated. This approach may provide novel potential diagnostic and prognostic biomarkers for patients with STEMI.

2 Methods

2.1 Patients and plasma samples

The sample size of this study was calculated according to diagnostic accuracy studies [13,14]. A total of 128 participants aged from 18 to 75 years [64 STEMI patients (33 males and 31 females; average age of 48.60 ± 11.92 years) and 64 age- and gender-matched healthy controls (39 males and 25 females; average age of 50.14 ± 9.25 years)] were retrospective collected from Peking University Shenzhen Hospital (Shenzhen, China) between May 2017 and April 2019. The STEMI patients was defined according to the European Society of Cardiology guidelines [15], and the inclusion criteria were as follows: (1) patients with acute chest pain, chest tightness, and shortness of breath exceeded 30 min; (2) abnormal electrocardiogram with significant ST-segment elevation in at least two contiguous leads; (3) elevation of cTnI and CK-MB exceeded the upper 99th percentile of the reference values and exhibited dynamic evolution; and (4) the diagnostic coronary angiography confirmed coronary artery stenosis of more than 30%. The exclusion criteria were as follows: (1) patients with a previous history of cardiac diseases (myocardial infarction, valve abnormalities, cardiomyopathy, arrhythmia, and heart failure); (2) patients received percutaneous coronary intervention (PCI), venous thrombolytic injection, and anticoagulant within the past 6 months; (3) significant hepatic, renal, and respiratory failure, coagulation disorders, thyroid dysfunction, acute and chronic infection, immune system abnormalities, and malignant tumors; (4) pregnant women and patients with mental illnesses; and (5) patients with failed follow-up. The healthy controls with no clinical signs of acute chest pain, chest tightness and shortness of breath, and normal coronary arteries.

The patients were admitted to our hospital within 4 h after onset of clinical symptoms, and venous blood samples (5 mL) were collected before any medical treatment was implemented. The plasma was separated from venous blood after centrifuged at 3,000 rpm for 10 min at 4°C and was then stored at −80°C until exosomes isolation was performed. The research was approved by the Ethics Committee of Peking University Shenzhen Hospital. Written informed content was obtained from all participants.

2.2 Clinical indicators

The baseline data of STEMI patients and healthy controls were registered after admission, including age, gender, body mass index (BMI), and medical history (diabetes mellitus and hypertension). The laboratory indicators, including white blood cells (WBC), hemoglobin, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), creatinine (CR), uric acid (UA), high sensitivity C-reactive protein (hs-CRP), lipoprotein a [LP(a)], cTnI, CK-MB, and N-terminal probrain natriuretic peptide (NT-proBNP), were detected by routine methods according to the manufacturer’s protocols.

The cardiovascular outcomes of STEMI patients were evaluated using major adverse cardiovascular events (MACEs), including angina, heart failure, malignant arrhythmias, cardiac death, and rehospitalization, due to STEMI recurrence. The MACE-free survival rate in STEMI patients up to 1 year after discharge was obtained from follow-up outpatient review and phone communication.

2.3 Screening of DEECs in patients with myocardial infarction from GEO database

The microarray and RNA-Seq data were obtained from GEO database (http://www.ncbi.nlm.nih.gov/gds/). The microarray dataset (GSE160717 and GSE197137) and the RNA-Seq dataset (GSE208194) were selected for screening DEECs in patients with myocardial infarction. R version 3.6.2 software (https://www.r-project.org/) was used for further analysis, and “|Log2 (fold change)| >  1 and P-value  <  0.05” were defined as the criteria for screening.

2.4 Exosomes isolation

For each sample, 500 µL of plasma was independently filtered with a 0.22 µm filter (Corning Incorporated, Corning, USA) and then exosomes were isolated using a UR52136 Exosome Isolation and Purification Kit (Umibio, Shanghai, China), according to the manufacturer’s protocol. After that, one of the exosomes was used for characteristic analysis via a transmission electron microscope (FEI Tecnai G2 T20; Thermo Fischer Scientific, Waltham, USA) operated at 120 kV, and the other was used for RNA extraction.

2.5 Exosomal RNA extraction and RNase R treatment

Total RNA of the acquired exosomes in each sample was extracted using a RNeasy mini kit (QIAGEN, Hilden, Germany), according to the manufacturer’s protocol. The concentrations of total RNA more than 100 ng/µL and absorbance ratio more than 2.0 at A260/280 and A260/230 were defined as having sufficient quality and quantity for further experiments. After that, 5 μg of total RNA was incubated with 15 U of RNase R (Epicenter Biotechnologies, Shanghai, China) treatment at 37°C for 20 min to remove the linear RNA.

2.6 Reverse transcription and quantitative real-time PCR (qRT-PCR)

1 μg of digested RNA was reverse transcribed into complementary DNA with random primers using a GoScript™ Reverse Transcription System (Promega Corporation, Madison, USA), according to the manufacturer’s protocol. Then, qRT-PCR procedure was performed using a GoTaq® 2-Step RT-qPCR System (Promega Corporation) on a Applied Biosystems 7500 Real-Time PCR instrument (Thermo Fisher Scientific). The reaction was designed as follows: 95°C for 10 min, followed by 40 cycles of 95°C for 10 s and 59°C for 45 s. The glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene was used as an internal control. The sequences of the primers are shown in Table A1. The relative expression level of each gene was calculated using the 2−ΔΔCT method.

2.7 Statistical analysis

The data of statistical analysis were conducted using SPSS software 28.0 (SPSS, Chicago, USA) and GraphPad Prism software 6.0 (GraphPad Prism Software Inc, San Diego, USA). Each independent experiment was repeated 3 times, and data were expressed as the percentages or the mean ± standard deviation. Significance between two groups was analyzed using an independent sample t-test (two tailed). The correlations between the levels of the DEECs and clinical characteristics in STEMI patients were assessed by Spearman’s correlation test. The area under the curves (AUC), sensitivity, and specificity for the DEECs, cTnI, and CK-MB were determined using receiver operating characteristic (ROC) curves analysis to assess its diagnostic efficiency in differentiating STEMI patients from healthy controls. Kaplan–Meier method and log-rank test were used to compare the MACE-free 1-year survival rate in different groups based on the levels of the DEECs. The univariate and multivariate Cox regression model analyses were performed to confirm independent factors for prognosis. P values less than 0.05 were considered statistically significant.

3 Results

3.1 Comparison of clinical characteristics in STEMI patients and healthy controls

The clinical characteristics of STEMI patients and healthy controls are shown in Table 1. The prevalence of hypertension and the LDL-C, hs-CRP, cTnI, CK-MB, and NT-proBNP levels were higher in STEMI patients than that in healthy controls. The level of HDL-C in STEMI patients was lower compared with healthy controls. However, no significant differences were observed in age, gender, BMI, prevalence of diabetes mellitus, WBC, hemoglobin, TC, TG, CR, UA, and LP(a) levels in the two groups.

Table 1

The clinical characteristics of STEMI patients and healthy controls

Characteristics Healthy controls (n = 64) STEMI patients (n = 64) P value
Age (years) 50.14 ± 9.25 48.60 ± 11.92 0.122
Gender (man/female) 39/25 33/31 0.285
BMI (kg/m2) 24.18 ± 1.30 23.59 ± 1.47 0.592
Hypertension (n, %) 12 (18.75) 39 (60.94) <0.001
Diabetes mellitus (n, %) 15 (23.44) 20 (31.25) 0.321
WBC (×109/L) 7.51 ± 3.09 7.23 ± 4.40 0.308
Hemoglobin (g/L) 116.44 ± 17.85 123.15 ± 18.38 0.173
TC (mmol/L) 4.37 ± 0.92 4.96 ± 1.13 0.061
TG (mmol/L) 1.18 ± 0.45 1.32 ± 0.66 0.115
LDL-C (mmol/L) 2.49 ± 0.73 3.88 ± 0.91 0.007
HDL-C (mmol/L) 1.27 ± 0.30 0.95 ± 0.28 0.029
CR (μmol/L) 70.46 ± 42.56 68.31 ± 40.50 0.518
UA (μmol/L) 278.22 ± 126.18 247.17 ± 106.35 0.052
hs-CRP (mg/L) 6.74 ± 2.08 52.81 ± 43.95 <0.001
LP(a) (mg/L) 183.46 ± 112.70 192.11 ± 120.62 0.106
cTnI (ng/L) 20.97 ± 12.14 454.96 ± 421.87 <0.001
CK-MB (ng/mL) 3.06 ± 1.79 44.23 ± 40.85 <0.001
NT-proBNP (pg/mL) 350.03 ± 149.26 1731.59 ± 1334.27 <0.001

STEMI: ST-segment elevation myocardial infarction; BMI: body mass index; WBC: white blood cells; TC: total cholesterol; TG: triglyceride; LDL-C: low density lipoprotein cholesterol; HDL-C: high density lipoprotein cholesterol; CR: creatinine; UA: uric acid; hs-CRP: high sensitivity C-reactive protein; LP(a): lipoprotein a; cTnI: cardiac troponin I; CK-MB: creatine kinase isoenzymes; NT-proBNP: N-terminal probrain natriuretic peptide.

3.2 Identification and characterization of 4 DEECs in patients with myocardial infarction from GEO database

A total of 287, 224, and 428 DEECs were identified in the microarray dataset (GSE160717 and GSE197137) and the RNA-Seq dataset (GSE208194), respectively. Furthermore, four DEECs were screened from the three cohorts, including exo-circ-0001490, exo-circ-0020887, exo-circ-0009590, and exo-circ-0055440 (Figure 1a).

Figure 1 Identification and characterization 4 DEECs in patients with myocardial infarction from GEO database. (a) The microarray dataset (GSE160717 and GSE197137) and the RNA-Seq dataset (GSE208194) were downloaded for integrated analyses of DEECs, and venn diagram showed the intersection of DEECs. (b–e) The genomic loci and splicing schematic diagram of exo-circ-0001490, exo-circ-0020887, exo-circ-0009590, and exo-circ-0055440. (f) The stability of exo-circ-0001490, exo-circ-0020887, exo-circ-0009590, exo-circ-0055440, KIF2A, NUP98, RERE, and USP39 mRNA was detected by RNase R degradation assay. DEECs: differentially expressed exosomal circRNAs; KIF2A: kinesin heavy chain member 2A; NUP98: nucleoporin 98 and 96 precursor; RERE: arginine-glutamic acid dipeptide repeats; USP39: ubiquitin-specific peptidase 39; RNase R: Ribonuclease R. Data were expressed as mean ± standard deviation from three independent experiments. ns P > 0.05, ***P < 0.001.
Figure 1

Identification and characterization 4 DEECs in patients with myocardial infarction from GEO database. (a) The microarray dataset (GSE160717 and GSE197137) and the RNA-Seq dataset (GSE208194) were downloaded for integrated analyses of DEECs, and venn diagram showed the intersection of DEECs. (b–e) The genomic loci and splicing schematic diagram of exo-circ-0001490, exo-circ-0020887, exo-circ-0009590, and exo-circ-0055440. (f) The stability of exo-circ-0001490, exo-circ-0020887, exo-circ-0009590, exo-circ-0055440, KIF2A, NUP98, RERE, and USP39 mRNA was detected by RNase R degradation assay. DEECs: differentially expressed exosomal circRNAs; KIF2A: kinesin heavy chain member 2A; NUP98: nucleoporin 98 and 96 precursor; RERE: arginine-glutamic acid dipeptide repeats; USP39: ubiquitin-specific peptidase 39; RNase R: Ribonuclease R. Data were expressed as mean ± standard deviation from three independent experiments. ns P > 0.05, ***P < 0.001.

The four DEECs were all exonic circRNAs, according to the annotation of circBank (http://www.circbank.cn/index.html) and circBase (http://www.circbase.org/). The genomic loci and splicing schematic diagram of exo-circ-0001490, exo-circ-0020887, exo-circ-0009590, and exo-circ-0055440 are shown in Figure 1b–e.

To further verify the circular characteristics of exo-circ-0001490, exo-circ-0020887, exo-circ-0009590, and exo-circ-0055440, we added RNase R to total RNA from plasma of STEMI patients, which can degrade linear RNAs characterized by a free 3′-terminus but have no influence on circRNAs. Results found that RNase R reduced the mRNA expression levels of kinesin heavy chain member 2A (KIF2A), nucleoporin 98 and 96 precursor (NUP98), arginine-glutamic acid dipeptide repeats (RERE), and ubiquitin-specific peptidase 39 (USP39), but have no significant effect on the expression levels of exo-circ-0001490, exo-circ-0020887, exo-circ-0009590, and exo-circ-0055440 (Figure 1f). The resistance to digestion via RNase R indicated that exo-circ-0001490, exo-circ-0020887, exo-circ-0009590, and exo-circ-0055440 have circular RNA structures.

3.3 Upregulated expression of exo-circ-0020887 and exo-circ-0009590 in plasma from STEMI patients

The expression levels of exo-circ-0001490, exo-circ-0020887, exo-circ-0009590, and exo-circ-0055440 in STEMI patients were assessed using qRT-PCR. Among these circRNAs, there was no significant difference of exo-circ-0001490 and exo-circ-0055440 levels between the plasma from healthy controls and the plasma from STEMI patients (Figure 2a and b). Furthermore, exo-circ-0020887 expression in plasma of STEMI patients was upregulated than that in plasma of healthy controls (Figure 2c). Similarly, Figure 2d reveals that plasma from STEMI patients had higher exo-circ-0009590 levels when compared with that in plasma from healthy controls. Therefore, exo-circ-0020887 and exo-circ-0009590 were selected for subsequent investigation.

Figure 2 Upregulated expression of exo-circ-0020887 and exo-circ-0009590 in plasma from STEMI patients. (a and b) qRT-PCR analysis of exo-circ-0001490 and exo-circ-0055440 expression levels (normalized to GAPDH) in plasma from 64 STEMI patients and 64 healthy controls. (c and d) The expression levels of plasma exo-circ-0020887 and exo-circ-0009590 were increased in STEMI patients that in plasma of healthy controls. STEMI: ST-segment elevation myocardial infarction; qRT-PCR: quantitative real-time PCR. Data were expressed as mean ± standard deviation from three independent experiments. ns P > 0.05, ***P < 0.001.
Figure 2

Upregulated expression of exo-circ-0020887 and exo-circ-0009590 in plasma from STEMI patients. (a and b) qRT-PCR analysis of exo-circ-0001490 and exo-circ-0055440 expression levels (normalized to GAPDH) in plasma from 64 STEMI patients and 64 healthy controls. (c and d) The expression levels of plasma exo-circ-0020887 and exo-circ-0009590 were increased in STEMI patients that in plasma of healthy controls. STEMI: ST-segment elevation myocardial infarction; qRT-PCR: quantitative real-time PCR. Data were expressed as mean ± standard deviation from three independent experiments. ns P > 0.05, ***P < 0.001.

3.4 Correlations between plasma exo-circ-0020887 and exo-circ-0009590 levels and the clinical characteristics of STEMI patients

As shown in Table 2 and Table A2, the increased exo-circ-0020887 and exo-circ-0009590 expression was positively correlated with the levels of hs-CRP, LDL-C, cTnI, and CK-MB but was negatively correlated with LP(a) level. However, no associations were found between exo-circ-0020887 and exo-circ-0009590 levels with other clinicopathological features, including age, gender, BMI, diabetes mellitus and hypertension, WBC, hemoglobin, TC, TG, CR, UA, HDL-C, and NT-proBNP levels. These results suggested that upregulation of plasma exo-circ-0020887 and exo-circ-0009590 is associated with adverse clinical characteristics in STEMI patients.

Table 2

The correlations between the levels of exo-circ-0020887 and exo-circ-0009590 and clinical characteristics in 64 STEMI patients

Characteristics Cases (n = 64) Exo-circ-0020887 expression P value Exo-circ-0009590 expression P value
Age (years) 0.721 0.598
<50 28 10.13 ± 1.67 26.72 ± 2.34
≥50 36 9.93 ± 1.15 26.13 ± 2.16
Gender 0.474 0.091
Man 33 9.86 ± 1.25 25.90 ± 2.08
Female 31 10.19 ± 1.48 26.91 ± 1.96
BMI (kg/m2) 0.954 0.617
<24 50 10.01 ± 1.70 26.50 ± 1.95
≥24 14 10.05 ± 1.32 25.99 ± 1.82
Hypertension 0.488 0.214
No 25 10.20 ± 1.34 26.86 ± 2.17
Yes 39 9.90 ± 1.51 26.08 ± 2.05
Diabetes mellitus 0.172 0.074
No 44 9.79 ± 1.55 26.05 ± 1.98
Yes 20 10.52 ± 1.27 27.13 ± 2.34
WBC (×109/L) 0.309 0.673
<10 56 10.07 ± 1.54 26.32 ± 1.94
≥10 8 9.67 ± 1.49 26.88 ± 2.53
Hemoglobin (g/L) 0.327 0.542
<120 23 10.21 ± 1.23 25.97 ± 2.11
≥120 41 9.91 ± 1.50 26.62 ± 1.99
TC (mmol/L) 0.532 0.956
<5.69 47 9.96 ± 1.44 26.35 ± 1.92
≥5.69 17 10.18 ± 1.59 26.50 ± 2.14
TG (mmol/L) 0.475 0.125
<1.7 54 9.95 ± 1.30 26.25 ± 2.33
≥1.7 10 10.39 ± 1.43 27.13 ± 2.10
LDL-C (mmol/L) 0.006 <0.001
<3.4 22 8.81 ± 1.05 23.98 ± 1.63
≥3.4 42 10.65 ± 1.39 27.65 ± 2.29
HDL-C (mmol/L) 0.136 0.085
<1.08 30 9.77 ± 1.32 26.94 ± 2.19
≥1.08 34 10.24 ± 1.47 25.90 ± 2.26
CR (μmol/L) 0.851 0.712
<106 61 10.02 ± 1.55 26.40 ± 2.45
≥106 3 9.96 ± 1.20 26.18 ± 2.39
UA (μmol/L) 0.429 0.529
<300 49 9.90 ± 1.25 26.22 ± 2.17
≥300 15 10.41 ± 1.38 26.94 ± 1.98
hs-CRP (mg/L) 0.015 <0.001
<10 12 9.15 ± 0.95 23.52 ± 1.58
≥10 52 10.22 ± 1.63 27.05 ± 2.07
LP(a) (mg/L) <0.001 <0.001
<180 35 11.13 ± 1.05 27.24 ± 2.15
≥180 29 8.68 ± 1.21 25.36 ± 2.27
cTnI (ng/L) 0.011 0.035
<40 16 9.03 ± 1.40 25.31 ± 2.23
≥40 48 10.35 ± 1.19 26.75 ± 2.45
CK-MB (ng/mL) 0.027 0.030
<5 20 9.24 ± 1.17 25.42 ± 2.20
≥5 44 10.37 ± 1.65 26.83 ± 2.09
NT-proBNP (pg/mL) 0.473 0.971
<450 6 10.31 ± 1.38 26.33 ± 2.28
≥450 58 9.99 ± 1.26 26.39 ± 2.43

Exo-circ-0020887: exosomal circular RNA 0020887; exo-circ-0009590: exosomal circular RNA 0009590.

3.5 Diagnostic efficacy of plasma exo-circ-0020887 and exo-circ-0009590 for STEMI patients

To further verify the efficacy of exo-circ-0020887 and exo-circ-0009590 for the diagnosis of STEMI, ROC curves were plotted and compared with cTnI and CK-MB. Figure 3a reveals that plasma exo-circ-0020887 had greater AUC (0.85 vs 0.73 vs 0.69), sensitivity (84.38% vs 70.31% vs 59.38%), and specificity (70.33% vs 60.94% vs 60.70%) values than cTnI and CK-MB in diagnosing STEMI within 4 h after onset. Similarly, the diagnostic efficiency of exo-circ-0009590 for STEMI early detection was higher than cTnI and CK-MB, according to the AUC (0.80 vs 0.73 vs 0.69), sensitivity (71.88% vs 70.31% vs 59.38%), and specificity (67.19% vs 60.94% vs 60.70%) values (Figure 3b). Moreover, when exo-circ-0020887 and exo-circ-0009590 combined with cTnI and CK-MB, the diagnostic value was greatly improved compared with anyone of them (AUC: 0.93, sensitivity: 81.25%, specificity: 98.44%) (Figure 3c). Therefore, we concluded that plasma exo-circ-0020887 and exo-circ-0009590 might be used as potential biomarkers for STEMI early detection and could improve the diagnostic efficacy when in combined with cTnI and CK-MB.

Figure 3 Diagnostic efficacy of plasma exo-circ-0020887 and exo-circ-0009590 in STEMI patients. (a) ROC curves analysis of exo-circ-0020887, cTnI, and CK-MB for differentiating STEMI patients from healthy controls. (b) ROC curves analysis showed that the diagnostic power of exo-circ-0009590 for STEMI exceeded cTnI and CK-MB. (c) The exo-circ-0020887 and exo-circ-0009590 in combination with cTnI and CK-MB had the highest diagnostic accuracy. ROC: receiver operating characteristic; cTnI: cardiac troponin I; CK-MB: creatine kinase isoenzymes.
Figure 3

Diagnostic efficacy of plasma exo-circ-0020887 and exo-circ-0009590 in STEMI patients. (a) ROC curves analysis of exo-circ-0020887, cTnI, and CK-MB for differentiating STEMI patients from healthy controls. (b) ROC curves analysis showed that the diagnostic power of exo-circ-0009590 for STEMI exceeded cTnI and CK-MB. (c) The exo-circ-0020887 and exo-circ-0009590 in combination with cTnI and CK-MB had the highest diagnostic accuracy. ROC: receiver operating characteristic; cTnI: cardiac troponin I; CK-MB: creatine kinase isoenzymes.

3.6 Prognostic values of plasma exo-circ-0020887 and exo-circ-0009590 in STEMI patients

According to the median value (9.84) of exo-circ-0020887 expression, 64 STEMI patients were divided by high exo-circ-0020887 expression group (n = 32) and low exo-circ-0020887 expression group (n = 32). Similarly, based on the median value (26.45) of exo-circ-0009590 expression, 64 STEMI patients were classified into the high exo-circ-0009590 expression group (n = 32) and the low exo-circ-0009590 expression group (n = 32). Kaplan–Meier analysis showed that MACE-free 1-year survival rate in STEMI patients with high exo-circ-0020887 expression was lower than that in those patients with low exo-circ-0020887 expression (Figure 4a). Similar results of lower MACE-free survival rate were found in STEMI patients with high exo-circ-0009590 expression when compared with low exo-circ-0009590 expression (Figure 4b).

Figure 4 Prognostic value of plasma exo-circ-0020887 and exo-circ-0009590 in STEMI patients. (a) Kaplan–Meier survival curves analysis of the MACE-free 1-year survival rate in STEMI patients based on exo-circ-0020887 expression status. (b) The MACE-free 1-year survival rate was lower in STEMI patients with high exo-circ-0009590 expression than those patients with low exo-circ-0009590 expression. MACE: major adverse cardiovascular events.
Figure 4

Prognostic value of plasma exo-circ-0020887 and exo-circ-0009590 in STEMI patients. (a) Kaplan–Meier survival curves analysis of the MACE-free 1-year survival rate in STEMI patients based on exo-circ-0020887 expression status. (b) The MACE-free 1-year survival rate was lower in STEMI patients with high exo-circ-0009590 expression than those patients with low exo-circ-0009590 expression. MACE: major adverse cardiovascular events.

Additionally, we analyzed the correlations of the levels of LDL-C, hs-CRP, LP(a), cTnI, and CK-MB with prognosis in STEMI patients. The results revealed that high hs-CRP expression and high LDL-C expression were associated with lower MACE-free 1-year survival rate (Figure A1a and b). And no correlation of LP(a), cTnI, and CK-MB levels with MACE-free 1-year survival rate was found (Figure A1c–e). These results demonstrated that elevated plasma exo-circ-0020887, exo-circ-0009590, hs-CRP, and LDL-C predicted short-term adverse cardiovascular outcomes.

3.7 Factors affecting the short-term cardiovascular outcomes of STEMI patients

As shown in Table A3, the results from univariate Cox regression analysis regarding the clinical variables and their impact on the MACE-free 1-year survival rate of STEMI patients, indicating that hypertension, WBC, LDL-C, hs-CRP, exo-circ-0020887 and exo-circ-0009590 expression were risk factors for short-term adverse cardiovascular outcomes. In addition, multivariate Cox regression analysis showed that hypertension, hs-CRP, exo-circ-0020887, and exo-circ-0009590 expression were independent risk prognosticators. Together, elevated plasma exo-circ-0020887 and exo-circ-0009590 might used as biomarkers for short-term adverse cardiovascular outcomes of STEMI patients.

4 Discussion

The cTnI and CK-MB are the most common biomarkers for STEMI diagnosis, but their utilizing may be limited in some cases due to hysteresis, non-specificity, and other factors. Therefore, researchers are currently investigating novel promising biomarkers for STEMI diagnosis and prognosis with use in clinical practice. In consideration of their roles, steadily growing studies in life science of the expression pattern reveal that ncRNAs are dysregulated in venous blood, showing their potential as biomarkers for STEMI [16,17]. For example, Salama et al. reported that miR-208a is a good diagnostic biomarker and a predictor of no-reflow in STEMI patients undergoing primary PCI [18]. Xiao et al. indicated that miR-146a acts as a biomarker for adverse prognosis of STEMI patients [19]. In a recent study by Horváth et al. showed that miR-331 and miR-151-3p are novel biomarkers in STEMI and may be associated with plaque rupture [20]. In another study by Yang et al. suggested that lncRNA MALAT1 could serve as an effective biomarker of no-reflow phenomenon in STEMI patients receiving primary PCI [21]. In addition, highly expressed lncRNA LIPCAR in plasma serves as a warning sign for the diagnosis of STEMI [22]. In this study, we identified exo-circ-0020887 and exo-circ-0009590 in patients with myocardial infarction from GEO database. The exo-circ-0020887 and exo-circ-0009590 expression was upregulated in STEMI patients and was positively correlated with hs-CRP, LDL-C, cTnI, and CK-MB. Elevated plasma exo-circ-0020887 and exo-circ-0009590 had a good diagnostic efficacy for STEMI and predicted short-term adverse cardiovascular outcomes.

Previous studies have confirmed that circRNAs can be stably and repeatedly detected in exosomes [23]. Thus, the specific expression of exo-circRNAs could be a promising biomarker for many diseases. Regarding myocardial infarction, a study of high-throughput RNA sequencing found that 3,862 circRNAs are dysregulated in peripheral blood, and the differentially expressed circ-TMEM165, circ-UBAC2, circ-ZNF609, circ-ANKRD12, and circ-SLC8A1 are confirmed in the AC16 cell model [24]. Also, Yin et al. identified 650 circRNAs, including 115 downregulated circRNAs and 535 upregulated circRNAs, that are differentially expressed in plasma from AMI patients [25].

The exo-circ-0020887 and exo-circ-0009590 are two novel circRNAs, which were chose following the microarray dataset (GSE160717 and GSE197137) and the RNA-Seq dataset (GSE208194). To date, the researches about specific connections between exo-circ-0020887 and exo-circ-0009590 levels and presence of STEMI and its prognostic value are unclear. Here, we found that the expression levels of exo-circ-0020887 and exo-circ-0009590 were increased in plasma from STEMI patients. Meanwhile, a positive correlation was observed between upregulated exo-circ-0020887 and exo-circ-0009590 expression and hs-CRP, LDL-C, cTnI, and CK-MB levels. More importantly, we found that the diagnostic power of exo-circ-0020887 and exo-circ-0009590 for STEMI exceeded the common markers cTnI and CK-MB and could therefore be used as biomarkers to improve the clinical diagnosis of STEMI.

Moreover, based on the Kaplan–Meier method, we showed that STEMI patients with high levels of exo-circ-0020887 and exo-circ-0009590 had lower MACE-free survival rate than those patients with low exo-circ-0020887 and exo-circ-0009590 levels during the 1-year follow-up period. Additionally, we found that high hs-CRP expression and high LDL-C expression were associated with lower MACE-free 1-year survival rate. Hypertension is traditional risk factor for MACE-free survival rate [26]. The MACE-free survival rate of STEMI is affected by inflammation and WBC, and LDL-C plays an important role in mediating the release of inflammatory cytokines [27]. Consistent with previous studies [19,28], we found that hypertension, WBC, LDL-C, hs-CRP, exo-circ-0020887, and exo-circ-0009590 expression were risk factors for short-term adverse cardiovascular outcomes in univariate Cox regression model. Interestingly, multivariate Cox regression model showed that hypertension, hs-CRP, exo-circ-0020887, and exo-circ-0009590 expression were independent risk prognosticators. Thus, plasma increased exo-circ-0020887 and exo-circ-0009590 might prove to be useful biomarkers for the prediction of short-term adverse cardiovascular outcomes.

Growing evidence have confirmed that circRNAs performing its function by acting as a “sponging” to miRNAs [29]. We used circRNAs interactome tool (https://circinteractome.nia.nih.gov/index.html) to find that several miRNAs could be targeting by exo-circ-0020887 and exo-circ-0009590, including miR-330-3p, miR-637, miR-661, miR-1236, and miR-1299. Among these miRNAs, previous studies revealed that the biological processes of miR-637 and miR-1299 are related to vascular endothelial cell dysfunction and vascular smooth muscle cell injury, respectively [30,31]. Accordingly, we speculated that exo-circ-0020887 and exo-circ-0009590 might be involved in the development of STEMI by sponge of miR-637 and miR-1299.

The limitation of our research is that a relatively small sample size was used, and further investigation with a larger sample size with a longer follow-up study is required to obtain accurate and reproducible results. In addition, the function and molecular mechanism of exo-circ-0020887 and exo-circ-0009590 in STEMI still need further exploration.

5 Conclusion

In conclusion, our research demonstrated that the expression levels of plasma exo-circ-0020887 and exo-circ-0009590 are upregulated in STEMI patients and might serve as promising biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes of STEMI.

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Acknowledgements

Not applicable.

  1. Funding information: This work was supported by the General Program for Clinical Research at Peking University Shenzhen Hospital (No. LCYJ2021021).

  2. Author contributions: Guan Wang and Yanjun Chen conceived and designed the study. Guan Wang, Chun Wang, Zhengyi Huang and Shuai Sun collected the clinical specimens, performed the experimets and data analysis. Guan Wang drafted the manuscript. All authors read and approved the final manuscript.

  3. Conflict of interest: The authors declare no conflicts of interest.

  4. Data availability statement: The analyzed data sets generated during the study are available from the corresponding author on reasonable request.

Appendix

Table A1

Sequences of primers for qRT-PCR

Name Sequences
exo-circ-0001490 Forward 5′-CAGGAAAGAACCAAGATTGTTCTAA-3′
Reverse 5′-GTACCATCACAACATCTTTACTAGG-3′
exo-circ-0020887 Forward 5′-TGGATGATATTGTGCATATCCGGA-3′
Reverse 5′-TCTGGGTGGTTGTAGCCTG-3′
exo-circ-0009590 Forward 5′-TGTCATTACAGACCCAGTTATCA-3′
Reverse 5′-AGATGCTGTGGTGGCTGT-3′
exo-circ-0055440 Forward 5′-CTGTGTTCTATCTCCCTCTCAC-3′
Reverse 5′-TGTCCAGGTACGGGCAGT-3′
KIF2A Forward 5′-AAGGCAAAGAGATTGACCTGG-3′
Reverse 5′-GAAGCTACAGTCCGTCGATTC-3′
NUP98 Forward 5′-GGAATCCGATGTCAGACCCTAA-3′
Reverse 5′-TTGGCTGTGCCTGTTGTTTGTA-3′
RERE Forward 5′-AGGGTTTGCAGGGACGATGTTA-3′
Reverse 5′-AATGGAAGAGGTCTGATGGAGC-3′
USP39 Forward 5′-CACTTACCTGCCGGGTATTGT-3′
Reverse 5′-CCTGGAGGACGTTTGATGTTCT-3′
GAPDH Forward 5′-ATCTTCCAGGAGCGAGATCCC-3′
Reverse 5′-TGAGTCCTTCCACGATACCAA-3′

KIF2A: kinesin heavy chain member 2A; NUP98: nucleoporin 98 and 96 precursor; RERE: arginine-glutamic acid dipeptide repeats; USP39: ubiquitin specific peptidase 39; GAPDH: glyceraldehyde-3-phosphate dehydrogenase.

Table A2

The correlation coefficient between exo-circ-0020887 and exo-circ-0009590 expression and the levels of hs-CRP, LDL-C, LP(a), cTnI, and CK-MB

Indicators exo-circ-0020887 exo-circ-0009590
r P value r P value
hs-CRP 0.386 0.025 0.622 <0.001
LDL-C 0.770 <0.001 0.403 0.027
LP(a) -0.491 0.004 -0.312 0.046
cTnI 0.516 <0.001 0.445 0.020
CK-MB 0.845 <0.001 0.757 <0.001
Table A3

Univariate and multivariate Cox regression model analysis of the factors affecting the MACE-free 1-year survival rate of STEMI patients

Characteristics Univariate HR (95% CI) P value Multivariate HR (95% CI) P value
Age (≥50 vs <50) 0.782 (0.214–2.393) 0.584 NA NA
Gender (female vs man) 1.147 (0.576–2.737) 0.162 NA NA
BMI (≥24 vs <24) 0.753 (0.145–1.329) 0.722 NA NA
Hypertension (Yes vs No) 3.018 (1.986–9.255) <0.001 2.659 (1.457–5.864) 0.002
Diabetes mellitus (Yes vs No) 1.114 (0.291–3.051) 0.214 NA NA
WBC (≥10 vs <10) 2.149 (1.264–4.831) 0.015 1.395 (0.528–2.906) 0.124
Hemoglobin (≥120 vs <120) 0.611 (0.187–1.598) 0.620 NA NA
TC (≥5.69 vs <5.69) 0.572 (0.251–1.345) 0.706 NA NA
TG (≥1.7 vs <1.7) 1.806 (0.532–4.356) 0.193 NA NA
LDL-C (≥3.4 vs <3.4) 2.520 (1.341–4.737) 0.007 2.013 (0.815–4.311) 0.059
HDL-C (≥1.08 vs <1.08) 1.701 (0.435–3.741) 0.087 NA NA
CR (≥106 vs <106) 0.965 (0.451–1.663) 0.920 NA NA
UA (≥300 vs <300) 1.593 (0.874–3.511) 0.088 NA NA
hs-CRP (≥10 vs <10) 2.673 (1.341–5.437) 0.007 2.015 (1.178–4.751) 0.038
LP(a) (≥180 vs <180) 1.364 (0.722–2.576) 0.231 NA NA
cTnI (≥40 vs <40) 1.581 (0.801–3.124) 0.150 NA NA
CK-MB (≥5 vs <5) 1.660 (0.871–3.163) 0.102 NA NA
NT-proBNP (≥450 vs <450) 1.037 (0.651–2.808) 0.469 NA NA
Exo-circ-0020887 (high vs low) 2.339 (1.235–4.427) 0.005 2.422 (1.624–4.948) <0.001
Exo-circ-0009590 (high vs low) 3.001 (1.583–5.685) <0.001 2.792 (1.549–5.273) 0.002

HR: hazard ratio; CI: confidence interval; NA: not available.

Figure A1 Correlations between the MACE-free 1-year survival rate and LDL-C, hs-CRP, LP(a), cTnI and CK-MB expression in STEMI patients. (a–e) Kaplan-Meier survival curves analysis of the MACE-free 1-year survival rate in STEMI patients based on the levels of LDL-C, hs-CRP, LP(a), cTnI and CK-MB. MACE: major adverse cardiovascular events; LDL-C: low density lipoprotein cholesterol; hs-CRP: high sensitivity C-reactive protein; LP(a): lipoprotein a; cTnI: cardiac troponin I; CK-MB: creatine kinase isoenzymes.
Figure A1

Correlations between the MACE-free 1-year survival rate and LDL-C, hs-CRP, LP(a), cTnI and CK-MB expression in STEMI patients. (a–e) Kaplan-Meier survival curves analysis of the MACE-free 1-year survival rate in STEMI patients based on the levels of LDL-C, hs-CRP, LP(a), cTnI and CK-MB. MACE: major adverse cardiovascular events; LDL-C: low density lipoprotein cholesterol; hs-CRP: high sensitivity C-reactive protein; LP(a): lipoprotein a; cTnI: cardiac troponin I; CK-MB: creatine kinase isoenzymes.

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Received: 2023-02-10
Revised: 2023-08-09
Accepted: 2023-09-01
Published Online: 2023-10-11

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
  89. miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
  90. lncRNA OIP5-AS1 attenuates the osteoarthritis progression in IL-1β-stimulated chondrocytes
  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
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  96. circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
  97. Prone position effect in intensive care patients with SARS-COV-2 pneumonia
  98. Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children
  99. Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
  101. Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
  102. Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study
  103. Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
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  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
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  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
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  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
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  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
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  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
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  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
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  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
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  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
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  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
https://doi.org/10.1515/med-2023-0807
Keywords for this article
STEMI; exo-circ-0020887; exo-circ-0009590; MACE-free 1-year survival rate; biomarkers
Creative Commons
BY 4.0

Articles in the same Issue

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  3. Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
  4. circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
  5. circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
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  9. 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
  10. Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
  11. PVT1/miR-16/CCND1 axis regulates gastric cancer progression
  12. Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
  13. Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
  14. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
  15. Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder’s lung
  16. lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
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  18. Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation
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  21. circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway
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  42. CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
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  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
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  99. Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
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  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
  109. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy
  110. A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
  115. Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
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