RNA methylation patterns, immune characteristics, and autophagy-related mechanisms mediated by N6-methyladenosine (m6A) regulatory factors in venous thromboembolism.

Recent studies have found a link between deep vein thrombosis and inflammatory reactions. N6-methyladenosine (m6A), a crucial element in immunological regulation, is believed to contribute to the pathophysiology of venous thromboembolism (VTE). However, how the m6A-modified immune microenvironment is involved in VTE remains unclear. In the present study, we identified a relationship between VTE and the expression of several m6A regulatory elements by analyzing peripheral blood samples from 177 patients with VTE and 88 healthy controls from public GEO databases GSE19151 and GSE48000. We used machine learning to identify essential genes and constructed a diagnostic model for VTE using multivariate logistic regression. Unsupervised cluster analysis revealed a marked difference between m6A modification patterns in terms of immune cell infiltration, inflammatory reactivity, and autophagy. We identified two m6A-related autophagy genes (i.e., CHMP2B and SIRT1) and the crucial m6A regulator YTHDF3 using bioinformatics. We also examined two potential mechanisms through which YTHDF3 may affect VTE. m6A modification, immunity, and autophagy are closely linked in VTE, offering novel mechanistic and therapeutic insights.

Noninvasive evaluation of pulmonary hypertension using the second heart sound parameters collected by a mobile cardiac acoustic monitoring system.

Background: Pulmonary hypertension (PH) is linked to higher rates of morbidity and mortality worldwide. Early diagnosis of PH is important for clinical treatment. The estimated pulmonary artery systolic pressure (ePASP ≥ 35 mmHg) measured by echocardiography helps screen PH patients. In this paper, we report a novel PH screening method through a mobile cardiac acoustic monitoring system. Methods: In the retrospective study, patients admitted to our hospital between January 2022 and April 2023 were classified into PH and control groups using ePASP and compared with acoustic cardiographic parameters. According to ePASP, PH severity was classified as mild, moderate, and severe. We analyzed the first and second heart sound (S1, S2) characteristics, including amplitude (S1A, S2A), energy (S1E, S2E), and frequency (S1F, S2F). Results: The study included 209 subjects, divided into PH (n = 121) and control (n = 88) groups. Pearson correlation analysis confirmed the positive correlation between S2F and ePASP. The diagnostic performance of S2F as assessed by the area under the ROC curve was 0.775 for PH. The sensitivity and specificity of diagnosing ePASP ≥ 35 mmHg when S2F ≥ 36 Hz were found to be 79.34% and 67.05%, respectively, according to ROC analysis. Severity classification was performed using S2F, the area under the ROC curve was 0.712-0.838 for mild PH, 0.774-0.888 for moderate PH, and 0.826-0.940 for severe PH. Conclusions: S2F collected by the mobile cardiac acoustic monitoring system offers a convenient method for remote PH screening, potentially improving PH management and outcomes.

Diagnostic performance of a wearing dynamic ECG recorder for atrial fibrillation screening: the HUAMI heart study.

BACKGROUND: Atrial fibrillation (AF) is the most prevalent cardiac dysrhythmia with high morbidity and mortality rate. Evidence shows that in every three patients with AF, one is asymptomatic. The asymptomatic and paroxysmal nature of AF is the reason for unsatisfactory and delayed detection using traditional instruments. Research indicates that wearing a dynamic electrocardiogram (ECG) recorder can guide accurate and safe analysis, interpretation, and distinction of AF from normal sinus rhythm. This is also achievable in an upright position and after exercises, assisted by an artificial intelligence (AI) algorithm. METHODS: This study enrolled 114 participants from the outpatient registry of our institution from June 24, 2020 to July 24, 2020. Participants were tested with a wearable dynamic ECG recorder and 12-lead ECG in a supine, an upright position and after exercises for 60 s. RESULTS: Of the 114 subjects enrolled in the study, 61 had normal sinus rhythm and 53 had AF. The number of cases that could not be determined by the wristband of dynamic ECG recorder was two, one and one respectively. Case results that were not clinically objective were defined as false-negative or false-positive. Results for diagnostic accuracy, sensitivity, and specificity tested by wearable dynamic ECG recorders in a supine position were 94.74% (95% CI% 88.76-97.80%), 88.68% (95% CI 77.06-95.07%), and 100% (95% CI 92.91-100%), respectively. Meanwhile, the diagnostic accuracy, sensitivity and specificity in an upright position were 97.37% (95% CI 92.21-99.44%), 94.34% (95% CI 84.03-98.65%), and 100% (95% CI 92.91-100%), respectively. Similar results as those of the upright position were obtained after exercise. CONCLUSION: The widely accessible wearable dynamic ECG recorder integrated with an AI algorithm can efficiently detect AF in different postures and after exercises. As such, this tool holds great promise as a useful and user-friendly screening method for timely AF diagnosis in at-risk individuals.

Long noncoding RNA PR11-387H17.6 as a potential novel diagnostic biomarker of atherosclerotic renal artery stenosis.

BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is frequently related to ischemic nephropathy, secondary hypertension, and end-stage renal failure. Thus, this study aimed to explore whether certain circulating long noncoding RNAs (lncRNAs) may be used as potential specific ARAS biomarkers. METHODS: In the present study, a microarray analysis was performed to screen for lncRNAs in renal artery tissue from four ARAS patients and four non-ARAS individuals. To identify specific lncRNAs as candidate potential biomarkers of ARAS, we used the following criteria: the fold change was set to >3.0 (compared with non-ARAS tissues), and p value cutoff was set at .05. According to these criteria, six lncRNAs were identified from 1150 lncRNAs. After validation by quantitative PCR (qPCR), these lncRNAs were independently validated in blood from groups of 18 ARAS patients, 18 non-ARAS individuals, and 18 healthy volunteers, furthermore, the predictive value of lncRNA PR11-387H17.6 was further assessed using blood from groups of 99 ARAS patients, 49 non-ARAS individuals, and 50 healthy volunteers. A receiver operating characteristic (ROC) curve analysis was performed to assess the performance of these lncRNAs as biomarkers. RESULTS: In the ROC analysis, the area under the curve (AUC) of PR11-387H17.6 was 0.733, with 52.5% sensitivity and 84.8% specificity in predicting the occurrence of ARAS. After considering the risk factors, the AUC of PR11-387H17.6 was 0.844, and the optimal sensitivity increased from 52.5% to 74.5%, although the specificity decreased from 84.8% to 81.9%. In the multivariable logistic analysis, PR11-387H17.6 was an independent predictor of major adverse events (OR: 3.039; 95% CI: 1.388-6.654; p= .006). CONCLUSIONS: PR11-387H17.6 is a potential diagnostic biomarker of ARAS. The lncRNA levels in blood cells are regulated in ARAS. Thus, further investigations of the role of lncRNAs in ARAS are warranted.

Sex-Related Differences in Short- and Long-Term Outcome among Young and Middle-Aged Patients for ST-Segment Elevation Myocardial Infarction Underwent Percutaneous Coronary Intervention.

BACKGROUND: Females with ST-segment elevation myocardial infarction (STEMI) have higher in-hospital and short-term mortality rates compared with males in China, suggesting that a sex disparity exists. The age of onset of STEMI is ahead of time and tends to be younger. However, there are relatively little data on the significance of sex on prognosis for long-term outcomes for adult patients with STEMI after percutaneous coronary intervention (PCI) in China. This study sought to analyze the sex differences in 30-day, 1-year, and long-term net adverse clinical events (NACEs) in Chinese adult patients with STEMI after PCI. METHODS: This study retrospectively analyzed 1920 consecutive STEMI patients (age ≤60 years) treated with PCI from January 01, 2006, to December 31, 2012. A propensity score analysis between males and females was performed to adjust for differences in baseline characteristics and comorbidities. The primary endpoint was the incidence of 3-year NACE. Survival curves were constructed with Kaplan-Meier estimates and compared by log-rank tests between the two groups. Multivariate analysis was performed using a Cox proportional hazards model for 3-year NACE. RESULTS: Compared with males, females had higher risk profiles associated with old age, longer prehospital delay at the onset of STEMI, hypertension, diabetes mellitus, and chronic kidney disease, and a higher Killip class (≥3), with more multivessel diseases (P < 0.05). The female group had a higher levels of low-density lipoprotein (2.72 [2.27, 3.29] vs. 2.53 [2.12, 3.00], P < 0.001), high-density lipoprotein (1.43 [1.23, 1.71] vs. 1.36 [1.11, 1.63], P = 0.003), total cholesterol (4.98 ± 1.10 vs. 4.70 ± 1.15, t = -3.508, P < 0.001), and estimated glomerular filtration rate (103.12 ± 22.22 vs. 87.55 ± 18.03, t = -11.834, P < 0.001) than the male group. In the propensity-matched analysis, being female was associated with a higher risk for 3-year NACE and major adverse cardiac or cerebral events compared with males. In the multivariate model, female gender (hazard ratio [HR]: 2.557, 95% confidence interval [CI]: 1.415-4.620, P = 0.002), hypertension (HR: 2.017, 95% CI: 1.138-3.576, P = 0.016), and family history of coronary heart disease (HR: 2.256, 95% CI: 1.115-4.566, P = 0.024) were independent risk factors for NACE. The number of stents (HR: 0.625, 95% CI: 0.437-0.894, P = 0.010) was independent protective factors of NACE. CONCLUSIONS: Females with STEMI undergoing PCI have a significantly higher risk for 3-year NACE compared with males in this population. Sex differences appear to be a risk factor and present diagnostic challenges for clinicians.

Safety and Necessity of Antiplatelet Therapy on Patients Underwent Endovascular Aortic Repair with Both Stanford Type B Aortic Dissection and Coronary Heart Disease.

BACKGROUND: Acute aortic dissection is known as the most dangerous aortic disease, with management and prognosis determined as the disruption of the medial layer provoked by intramural bleeding. The objective of this study was to evaluate the safety and necessity of antiplatelet therapy on patients with Stanford Type B aortic dissection (TBAD) who underwent endovascular aortic repair (EVAR). METHODS: The present study retrospectively analyzed 388 patients with TBAD who underwent EVAR and coronary angiography. The primary outcomes were hemorrhage, death, endoleak, recurrent dissection, myocardial infarction, and cerebral infarction in patients with and without aspirin antiplatelet therapy at 1 month and 12 months. RESULTS: Of those 388 patients, 139 (35.8%) patients were treated with aspirin and 249 (64.2%) patients were not treated with aspirin. Patients in the aspirin group were elderly (57.0 ± 10.3 years vs. 52.5 ± 11.9 years, respectively, χ2 = 3.812, P < 0.001) and had more hypertension (92.1% vs. 83.9%, respectively, χ2 = 5.191, P = 0.023) and diabetes (7.2% vs. 2.8%, respectively, χ2 = 4.090, P = 0.043) than in the no-aspirin group. Twelve patients (aspirin group vs. no-aspirin group; 3.6% vs. 2.8%, respectively, χ2 = 0.184, P = 0.668) died at 1-month follow-up, while the number was 18 (4.6% vs. 5.0%, respectively, χ2 = 0.027, P = 0.870) at 12-month follow-up. Hemorrhage occurred in 1 patient (Bleeding Academic Research Consortium [BARC] Type 2) of the aspirin group, and 3 patients (1 BARC Type 2 and 2 BARC Type 5) in the no-aspirin group at 1-month follow-up (χ2 = 0.005, P = 0.944). New hemorrhage occurred in five patients in the no-aspirin group at 12-month follow-up. Three patients in the aspirin group while five patients in the no-aspirin group had recurrent dissection for endoleak at 1-month follow-up (2.3% vs. 2.2%, respectively, χ2 = 0.074, P = 0.816). Four patients had new dissection in the no-aspirin group at 12-month follow-up (2.3% vs. 3.8%, respectively, χ2 = 0.194, P = 0.660). Each group had one patient with myocardial infarction at 1-month follow-up (0.8% vs. 0.4%, respectively, χ2 = 0.102, P = 0.749) and one more patient in the no-aspirin group at 12-month follow-up. No one had cerebral infarction in both groups during the 12-month follow-up. In the percutaneous coronary intervention (PCI) subgroup, 44 (31.7%) patients had taken dual-antiplatelet therapy (DAPT, aspirin + clopidogrel) and the other 95 (68.3%) patients had taken only aspirin. There was no significant difference in hemorrhage (0% vs. 1.1%, respectively, χ2 = 0.144, P = 0.704), death (4.8% vs. 4.5%, respectively, χ2 = 0.154, P = 0.695), myocardial infarction (2.4% vs. 0%, respectively, χ2 = 0.144, P = 0.704), endoleak, and recurrent dissection (0% vs. 3.4%, respectively, χ2 = 0.344, P = 0.558) between the two groups at 12-month follow-up. CONCLUSIONS: The present study indicated that long-term oral low-dose aspirin was safe for patients with both TBAD and coronary heart disease who underwent EVAR. For the patients who underwent both EVAR and PCI, DAPT also showed no increase in hemorrhage, endoleak, recurrent dissection, death, and myocardial infarction.

[The clinical value of balloon dilatation through flexible bronchoscope in the management of tracheobronchial stenosis in 149 cases of endobronchial tuberculosis].

OBJECTIVE: To explore the clinical value of balloon dilatation through flexible bronchoscope in the management of tracheobronchial stenosis of endobronchial tuberculosis. METHODS: From January 2005 to September 2009, 149 cases of tracheobronchial stenosis caused by endobronchial tuberculosis were examined by flexible bronchoscope and treated with balloon dilatation. Changes of the clinical features, atelectasis and airway diameters were observed and evaluated before and after the last treatment and in 12 months. RESULTS: The airway diameters were immediately enlarged (100%, 149/149) after the procedure, and the clinical symptoms were relieved. The average airway diameter changed from (2.7 ± 1.4) mm before the procedure, to (6.8 ± 2.0) mm, (6.4 ± 1.7) mm and (6.3 ± 2.3) mm immediately, 3 and 12 months after the treatments. Expansion of atelectasis was seen in 92% (34/37) of the cases, and the rate of restenosis was 3.4% (5/146) 12 months after treatment. There were significant differences before and after the treatments in the airway diameters, expansion rate of atelectasis and the general outcome (t = 13.09-20.50, P < 0.01), but there were no differences among measurements immediately, 3 and 12 months after the treatments. The final effective rate was 93.3% (139/149). Severe complications (4.0%, 6/149) were rare in these patients. CONCLUSION: Balloon dilatation through flexible bronchoscope is a simple, effective and safe method for the management of tracheobronchial stenosis after endobronchial tuberculosis.

MEF2C mediates the activation induced cell death (AICD) of macrophages.

Activation-induced cell death (AICD) of immune cells is widely believed to be crucial for the regulation of immune responses. Although macrophage apoptosis has been observed under a variety of pathological conditions, questions as to whether there is AICD of macrophages and how macrophage life span is regulated have not been well addressed. AICD in macrophages requires two signals. One is cell activation triggered by LPS or other bacterial components. The other is an event that exists in AICD-susceptible (primed) but not unsusceptible (resting) macrophages. Here we show that RAW264.7 cell is susceptible to LPS stimulation when it is primed with Salmonella typhimurium, type 5 adenovirus (Ad5) or IFN-gamma. We found that the stability of the transcription factor MEF2C is increased in primed RAW264.7 cell. Transfection of a dominant negative form of MEF2C protects primed macrophage from cell death triggered by LPS. Our data demonstrate that the increase of MEF2C protein stability is a key factor in the AICD of macrophage.