Long Noncoding RNA and mRNA Expression Profiles in Rats with LPS-induced Myocardial Dysfunction.

Background: Sepsis is an uncontrolled systemic inflammatory response. Long noncoding RNAs (lncRNAs) are involved in the pathogenesis of sepsis. However, little is known about the roles of lncRNAs in sepsis-induced myocardial dysfunction. Objective: We aimed to determine the regulatory mechanism of lncRNAs in sepsis-induced myocardial dysfunction. Methods: In this study, we analysed the lncRNA and mRNA expression profiles using microarray analysis. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, protein-protein interaction network, and gene set enrichment analysis were used to evaluate the data. We also constructed coding and noncoding coexpression and competing endogenous RNA networks to investigate the mechanisms. Results: In vivo lipopolysaccharide -induced sepsis rat model was established. A total of 387 lncRNAs and 1,952 mRNAs were identified as significantly changed in the left ventricle. Kyoto Encyclopedia of Genes and Genomes analysis of mRNAs showed that the upregulated genes were mainly enriched in the "complement and coagulation cascade pathway" and "immune-related biological processes" terms. Eight significantly changed lncRNAs detected by RT-qPCR may be responsible for these processes. A competing endogenous RNA network was generated, and the results indicated that eight lncRNAs were related to the "calcium ion binding" process. Conclusion: These results demonstrate that crosstalk between lncRNAs and mRNAs may play important roles in the development of sepsis-induced myocardial dysfunction.

Analyses of circRNA and mRNA profiles in the submandibular gland in hypertension.

The aim of this study was to elucidate the roles played by circular RNAs (circRNAs) in the mechanism underlying submandibular gland (SMG) dysfunction in hypertension. We employed RNA-seq to analyze the circRNA and mRNA expression profiles of SMGs. Seventy-five differentially expressed (DE) circRNAs and 691 DE mRNAs were determined to be significantly altered in spontaneously hypertensive rats. Altered mRNAs were primarily related to the immune system and immune response. Eight circRNAs were selected for further analysis. Cell adhesion molecules were determined to be the most strongly enriched pathway through analysis of DE mRNAs, the coding noncoding gene co-expression (CNC) network and the competitive endogenous RNA (ceRNA) network. The salivary secretion pathway was observed to be notably enriched through analysis of the ceRNA network. These results suggest that the crosstalk among circRNAs may play a crucial role in the development of SMG dysfunction in hypertension.

Efficacy of adaptive servo-ventilation and continuous positive airway pressure treatment in chronic heart failure with sleep-disordered breathing: a systematic review and meta-analysis.

Noninvasive positive-pressure ventilation (NPPV) is recognized as an effective adjuvant therapy for sleep-disordered breathing (SDB) in heart failure patients with reduced ejection fraction (HFrEF + SDB). In recent years, some studies have found that adaptive servo-ventilation (ASV) has a negative impact on survival, especially among patients with central sleep apnea (CSA), the use of which is controversial. This study aims to explore the effects of NPPV on cardiac function and survival in patients with sleep-disordered breathing and chronic congestive heart failure. This meta-analysis was based on literature searches of publications published before August 31, 2019, in the PubMed, EMBASE, Cochrane Library, and Web of Science databases. A total of 88 independent studies were summarized and compared, comprising a sampling of 19,259 subjects. Compared with the nontreatment group, treatment with ASV had no effect on all-cause mortality in patients with HFrEF + CSA (hazard ratio (HR) = 1.13 [0.84, 1.51]). Short-term treatment with ASV, e.g., 3-6 months, was significantly beneficial regarding event-free survival in patients with HFrEF + CSA (HR = 0.13 [0.04, 0.45]). Periodic short-term (e.g., 3-6 months) positive-pressure ventilation can significantly improve cardiac function, which is beneficial for the survival of patients with HFrEF + CSA. Attention should be paid to the length and period of treatment, as prolonged treatment may have negative effects.

A clinical strategy to improve the diagnostic accuracy of 1.5-T non-contrast MR coronary angiography for detection of coronary artery disease: combination of whole-heart and volume-targeted imaging.

OBJECTIVES: To evaluate the diagnostic performance of 1.5-T non-contrast MR coronary angiography (MRCA) for detection of coronary artery disease (CAD) using whole-heart imaging combined with volume-targeted imaging. METHODS: Forty-five patients scheduled for conventional coronary angiography (CAG) underwent 1.5-T free-breathing non-contrast steady-state free-precession MRCA, including whole-heart and subsequent three-vessel volume-targeted imaging. Coronary stenosis was evaluated as follows: (1) by whole-heart MRCA alone; (2) by combined MRCA (whole-heart plus volume-targeted images). The diagnostic performance for significant stenosis (≥ 50% diameter reduction) was evaluated and compared using CAG as a reference standard. RESULTS: Combined MRCA was completed in all 45 patients with a total acquisition time of 16.6 ± 3.3 min. The sensitivity, specificity, and accuracy of combined MRCA per patient were 97% (95% confidence interval 84-100%), 83% (52-98%), and 93% (82-98%), respectively. The areas under the receiver operating characteristic curve of combined MRCA were significantly higher than those of whole-heart MRCA on a per patient (0.97 versus 0.85, p = 0.0078) and per vessel (0.96 versus 0.86, p < 0.0001) basis. Compared with whole-heart MRCA, combined MRCA showed equally high sensitivity but significantly improved specificity on a per patient (83% versus 25%, p = 0.016) and per vessel (85% versus 50%, p < 0.0001) basis. CONCLUSIONS: 1.5-T non-contrast MRCA combining whole-heart and volume-targeted imaging can detect significant CAD with high sensitivity and moderate specificity. Combined MRCA significantly improves specificity compared with whole-heart imaging alone. KEY POINTS: • 1.5-T non-contrast MRCA with combined whole-heart and volume-targeted imaging can detect CAD with high sensitivity and moderate specificity comparable with coronary CTA. • Compared with whole-heart imaging alone, combined imaging provides improved diagnostic accuracy, especially specificity.

Low-dose CT perfusion with combined use of CTP and CTP-derived coronary CT angiography at 70 kVp: validation with invasive fractional flow reserve.

OBJECTIVES: To investigate the diagnostic performance of 70-kVp stress dynamic myocardial CT perfusion (CTP) as a low-dose, one-stop cardiac CT examination in clinical application. MATERIALS AND METHODS: Consecutive symptomatic patients were prospectively recruited and scanned with stress dynamic myocardial CTP. The CTP phase with the best enhancement of the coronary arteries was selected and extracted as the CTP-derived single-phase coronary CT angiography (SP-CTA). The diagnostic performance of CTP and CTP+SP-CTA for functionally significant CAD was assessed. Invasive coronary angiography and fractional flow reserve were used as the reference standard for the myocardial ischemia evaluation. RESULTS: In total, 71 patients (43 men and 28 women; 63.6 ± 8.8 years old) underwent the stress dynamic myocardial CTP; 63 vessels (36.2%) from 42 of the patients (59.2%) were identified as causing ischemia. On a per-vessel basis, the sensitivity, specificity, PPV, NPV, and diagnostic accuracy for CTP and CTP+SP-CTA were 77.8%, 93.7%, 87.5%, 88.1%, and 87.9% and 84.1%, 93.7%, 88.3%, 91.2%, and 90.2%, respectively. The area under the curve (AUC) of CTP+SP-CTA (AUC = 0.963; 95%CI, 0.938-0.989) was significantly superior to that of CTP (AUC = 0.922; 95%CI, 0.880-0.964) and that of SP-CTA (AUC = 0.833; 95%CI, 0.765-0.900) alone (all p < 0.01). The mean radiation dose of the CTP examination was 3.8 ± 1.4 mSv. CONCLUSION: CTP-derived SP-CTA improved the diagnostic value of CTP. With a promising performance of myocardial ischemia detection and low radiation dose, the innovative low-dose, one-stop CTP examination is clinically feasible for patients who need to receive a myocardial perfusion assessment. KEY POINTS: • Myocardial CTP performed well in the evaluation of hemodynamically significant CAD. • CTP-derived single-phase CCTA improved the diagnostic value of CTP. • The combined use of low-dose CTP and CTP-derived CCTA at 70 kVp is clinically feasible for CAD patients who need to receive a myocardial perfusion assessment.

[Clinical Value of 1.5-T Non-contrast Whole-heart Magnetic Resonance Coronary Angiography in Evaluating the Severity of Coronary Stenosis].

Objective To evaluate the diagnostic performance of 1.5-T non-contrast free-breathing whole-heart magnetic resonance coronary angiography(MRCA)for≥50% and≥70% coronary artery stenosis in coronary artery disease(CAD).Methods Forty-one patients clinically scheduled for invasive coronary angiography(ICA)underwent 1.5-T non-contrast free-breathing whole-heart MRCA.The diagnostic performance for≥50% and≥70% stenosis was evaluated and compared using ICA as a reference standard.Results MRCA was completed in all the 41 patients with the total acquisition time of(10.1 ± 2.2)min.The sensitivity,specificity,and accuracy of MRCA for≥50% and≥70% stenosis were 100%(95% CI:89%-100%)and 82%(95%CI:63%-94%),38%(95%CI:9%-76%)and 54%(95%CI:25%-81%),and 88%(95%CI:73%-95%)and 73%(95%CI:57%-85%)on a per-patient basis,respectively;they were 95%(95%CI:87%-99%)and 86%(95%CI:73%-95%),58%(95%CI:45%-71%)and 76%(95%CI:65%-85%),and 78%(95%CI:69%-84%)and 80%(95%CI:71%-86%)on a per-vessel basis,respectively.The sensitivity of MRCA for≥50% stenosis was higher than that for≥70% stenosis(97%vs.88%,χ 2=5.73,P=0.017),and the specificity showed an opposite trend(86% vs. 94%,χ 2=14.12,P<0.001)on a per-segment basis.Conclusions The 1.5-T non-contrast whole-heart MRCA can detect both≥50% and≥70% coronary artery stenosis with high sensitivity and accuracy.MRCA showed lower sensitivity while higher specificity for≥70% stenosis than for≥50% stenosis on a per-segment basis.

Identification of circRNA and mRNA expression profiles and functional networks of vascular tissue in lipopolysaccharide-induced sepsis.

Sepsis is the most common cause of death in intensive care units. This study investigated the circular RNA (circRNA) and mRNA expression profiles and functional networks of the aortic tissue in sepsis. We established a lipopolysaccharide (LPS)-induced rat sepsis model. High-throughput sequencing was performed on the aorta tissue to identify differentially expressed (DE) circRNAs and mRNAs, which were validated by real-time quantitative polymerase chain reaction (RT-qPCR). Bioinformatic analysis was carried out and coding and non-coding co-expression (CNC) and competing endogenous RNA (ceRNA) regulatory networks were constructed to investigate the mechanisms. In total, 373 up-regulated and 428 down-regulated circRNAs and 2063 up-regulated and 2903 down-regulated mRNAs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of mRNAs showed that the down-regulated genes were mainly enriched in the process of energy generation. CNC and ceRNA regulatory networks were constructed with seven DE circRNAs. The results of functional enrichment analysis of CNC target genes revealed the important role of circRNAs in inflammatory response. The ceRNA network also highlighted the significant enrichment in calcium signalling pathway. Significant alterations in circRNAs and mRNAs were observed in the aortic tissue of septic rats. In addition, CNC and ceRNA networks were established.

Association Between Oxidative Stress and Peripheral Leukocyte Telomere Length in Patients with Premature Coronary Artery Disease.

BACKGROUND Leukocyte telomere length (LTL) is regarded as a potential marker of biological aging. Oxidative stress plays a major role in the rate of telomeric DNA loss. The aim of this study was to explore whether the LTL was shorter in Chinese patients with premature coronary artery disease (PCAD) than in non-CAD controls and to determine the relationship between oxidative stress and LTL shortening in this population. MATERIAL AND METHODS Patients for coronary angiography were recruited. In total, 128 patients with PCAD and 128 non-CAD controls were enrolled. Samples of circulating leukocytes and plasma were collected. The mean LTL was measured using a polymerase chain reaction-based assay and expressed as the ratio of telomere repeat copies to single-copy gene (SCG) copies (T/S ratio). Reactive oxygen species (ROS) levels and total antioxidant capacity (T-AOC) were determined in plasma. RESULTS Both the T/S ratio (0.88±0.86 vs. 1.10±0.57, P=0.015) and telomere base pairs (4.97±1.37 kb vs. 5.32±0.91 kb, P=0.015) were significantly shorter in the PCAD group than in non-CAD controls. The T-AOC levels of the PCAD group were significantly lower than those of the non-CAD controls (0.482 mM [0.279, 0.603 mM]) vs. 0.778 mM [0.421, 0.924 mM], P=0.000). The ratio of T-AOC to ROS in the PCAD patients was significantly decreased compared to that of the non-CAD controls (0.1026±0. 1587 [Mm*ml/ng] vs. 0.1435±0.1946 [Mm*ml/ng], P=0.013). CONCLUSIONS The results point to a potential link between reduced LTLs in patients with PCAD and early onset of atherosclerosis. The decline in antioxidant capacity may play an important role in accelerating the attrition of telomeres in PCAD patients.

LncRNA-mRNA expression profile and functional network of vascular dysfunction in septic rats.

BACKGROUND: We used microarrays to analyse the changes in long non-coding RNAs (lncRNAs) and mRNAs in aorta tissue in model rats with lipopolysaccharide-induced sepsis and determined the lncRNA-mRNA and lncRNA-miRNA-mRNA functional networks. METHODS: Wistar rats were intraperitoneally injected with lipopolysaccharide, and the lncRNA and mRNA expression profiles in the aorta were evaluated using microarrays. The functions of the differentially expressed mRNAs were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. We then constructed coding/non-coding co-expression and competing endogenous RNA networks to study the mechanisms related to sepsis in rats. RESULTS: We identified 503 differentially expressed lncRNAs and 2479 differentially expressed mRNAs in the model rats with lipopolysaccharide-induced sepsis. Mitochondrial fission process 1 (MTFP1) was the most significantly down-regulated mRNA. Bioinformatics analysis showed that the significantly down-regulated mRNAs in the sepsis models were in pathways related to mitochondrial structure, function, and energy metabolism. Coding/non-coding co-expression and competing endogenous RNA analyses were conducted using 12 validated lncRNAs in combination with all mRNAs. The coding/non-coding co-expression analysis showed that the 12 validated lncRNAs were mainly regulatory factors for abnormal energy metabolism, including mitochondrial structure damage and aberrant mitochondrial dynamics. The competing endogenous RNA analysis revealed that the potential functions of these 12 lncRNAs might be related to the inflammatory response. CONCLUSION: We determined the differentially expressed lncRNAs and mRNAs in the aorta of septic rats using microarrays. Further studies on these lncRNAs will help elucidate the mechanism of sepsis at the genetic level and may identify potential therapeutic targets.

Diagnosis, Genetics, and Management of 24 Patients With Cardiac Paragangliomas: Experience From a Single Center.

Context: Paragangliomas located within the pericardium represent a rare yet challenging clinical situation. Objective: The current analysis aimed to describe the clinical characteristics of cardiac paragangliomas, with emphasis on the diagnostic approach, genetic background, and multidisciplinary management. Methods: Twenty-four patients diagnosed with cardiac paraganglioma (PGL) in Peking Union Medical College Hospital, Beijing, China, between 2003 and 2021 were identified. Clinical data was collected from medical record. Genetic screening and succinate dehydrogenase subunit B immunohistochemistry were performed in 22 patients. Results: The median age at diagnosis was 38 years (range 11-51 years), 8 patients (33%) were females, and 4 (17%) had familial history. Hypertension and/or symptoms related to catecholamine secretion were present in 22 (92%) patients. Excess levels of catecholamines and/or metanephrines were detected in 22 (96%) of the 23 patients who have completed biochemical testing. Cardiac PGLs were localized with 131I-metaiodobenzylguanidine scintigraphy in 11/22 (50%), and 99mTc-hydrazinonicotinyl-tyr3-octreotide scintigraphy in 24/24 (100%) patients. Genetic testing identified germline SDHx mutations in 13/22 (59%) patients, while immunohistochemistry revealed succinate dehydrogenase (SDH) deficiency in tumors from 17/22 (77%) patients. All patients were managed by a multidisciplinary team through medical preparation, surgery, and follow-up. Twenty-three patients received surgical treatment and perioperative death occurred in 2 cases. Overall, 21 patients were alive at follow-up (median 7.0 years, range 0.6-18 years). Local recurrence or metastasis developed in 3 patients, all of whom had SDH-deficient tumors. Conclusion: Cardiac PGLs can be diagnosed based on clinical manifestations, biochemical tests, and appropriate imaging studies. Genetic screening, multidisciplinary approach, and long-term follow-up are crucial in the management of this disease.

[Clinical and coronary features of systemic lupus erythematosus patients with coronary artery disease].

OBJECTIVES: To observe the clinical and coronary features of patients with systemic lupus erythematosus (SLE) and coronary artery disease (CAD). METHODS: Among 2877 SLE inpatients (age ≥ 18 years, male 363, female 2514) admitted in the Peking Union Medical College Hospital between January 1999 to October 2009, 33 patients [mean age (50.7 ± 12.8) years] were diagnosed with CAD and coronary angiogram was available in 20 out of these 33 patients. Clinical and coronary features of these patients were retrospectively reviewed. RESULTS: The incidence of CAD was significantly higher in male SLE patients than in female patients [2.48% (9/363) vs. 0.95% (24/2514), P = 0.022]. Patients with secondary antiphospholipid syndrome were more likely to suffer from CAD [5.76% (8/139) vs. 0.91% (25/2738), P < 0.001]. Myocardial infarction was the major form of CAD (24/33). Coronary artery angiographic changes included coronary stenosis and occlusions, coronary aneurysms and acute thrombosis and multi-vessel lesions was found in 75.0% (15/20) patients with SLE and CAD. CONCLUSIONS: Male SLE patients and patients with secondary antiphospholipid syndrome are at higher risk for CAD. Myocardial infarction and multi-vessel lesions are common in SLE patients with CAD.

[Effect of left ventricular ejection fraction on clinical long-term follow-up outcomes in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention].

OBJECTIVE: To evaluate the effect of left ventricular ejection fraction (LVEF) on clinical outcomes in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS: A total of 158 patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention between January 2005 to December 2007 were enrolled. They were divided into three groups: LVEF≤40% (n=14), LVEF 41%-55% (n=46) and LVEF>55% group (n=98). The clinical follow-up end-point was major adverse cardiac event (MACE) including death, acute myocardial infarction, stent thrombosis and stent restenosis. The clinical follow-up duration was 43.1±15.2 months. MACE occurred in 15 patients. RESULTS: The rates of infarction site, infarction relative artery, 1-vessel disease, 2-vessel disease, hypertension, diabetes, hyperlipidemia, smoking, obesity and aspirin use were not different in three groups (P>0.05). Average CTnI, CK, CK-MB and duration of clopidogrel use were not different in three groups (P>0.05). The rate of 3-vessel disease was significantly higher in the LVEF≤40% group than that in the LVEF 41%-55% and LVEF>55% groups (P=0.0036). The rates of TIMI flow grades (Grade III) and complete revascularization were significantly higher in the LVEF 41%-55% and LVEF>55% groups than that in the LVEF≤40% group (P=0.0099, P=0.0010). The rates of Killip classification (classes II, III, IV) and average symptom-onset-to balloon-time (SOTB) were significantly lower in the LVEF 41%-55% and LVEF>55% groups than that in the LVEF≤40% group (P=0.0100, P=0.0087). The rate of drug-eluting stents was significantly lower in the LVEF≤40% group and LVEF 41%-55% group than that in LVEF>55% group (P=0.0242). Logistic regression analysis showed that LVEF was independent predictor for MACE in the follow-up period (P=0.0029). With LVEF decrease, incidence of MACE in the follow-up period significantly increased in LVEF>55% group, LVEF 41%-55% group and LVEF≤40% group (6.12% vs 8.7% vs 35.71%, P=0.0019). Incidence of total death and cardiac death in the follow-up period significantly increased in LVEF>55% group, LVEF 41%-55% group and LVEF≤40% group (1.02% vs 4.35% vs 21.43%, P=0.0090; 1.02% vs 2.17 vs 14.29%, P=0.0060). CONCLUSION: In patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, LVEF was independent predictor for MACE in the follow-up period. With LVEF decrease, incidence of MACE in the follow-up period significantly increased.

[Effects of hemoglobin levels on long-term prognosis in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention].

OBJECTIVE: To evaluate the effects of hemoglobin (Hb) levels on long-term prognosis in the patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS: A total of 150 patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention between January 2005 to December 2007 were enrolled. They were divided into 2 groups: Hb < 120 g/L group (n = 21) and Hb ≥ 120 g/L group (n = 129). The mean clinical follow-up period was 3 years (range: 41.4 ± 16.1 months). The differences of major adverse cardiac events (MACE), including death, acute myocardial infarction, stent thrombosis & stent restenosis), were observed between two groups. RESULTS: The parameters of infarction site, infarction relative artery, 2-vessel disease, 3-vessel disease, Killip class ≥ II, drug-eluting stent, TIMI grade 3 flow, hypertension, hyperlipidemia, smoking, obesity, aspirin and clopidogrel use were not different between two groups (all P > 0.05). The rate of diabetes was significantly higher in Hb < 120 g/L group than that in Hb ≥ 120 g/L group (47.62% vs 18.60%, P = 0.0032). The mean age and symptom-onset-to balloon-time (SOTB) were significantly higher in Hb < 120 g/L group than that in Hb ≥ 120 g/L group (68.5 ± 9.2 vs 61.2 ± 12.2 years, P < 0.0001; 8.8 ± 10.5 vs 6.3 ± 5.0 h, P < 0.0001). The mean LVEF (left ventricular ejection fraction)(%) and rate of complete revascularization were significantly lower in Hb < 120 g/L group than that in Hb ≥ 120 g/L group (51.25 ± 11.34 vs 58.79 ± 10.38, P < 0.0001; 61.9% vs 86.8%, P = 0.0045). Logistic regression analysis showed that LVEF was an independent predictor of MACE during the follow-up period (P = 0.0140). During a 3-year follow-up, MACE occurred in 16 patients. The incidence of MACE was significantly higher in Hb < 120 g/L group than that in Hb ≥ 120 g/L group (33.33% vs 6.98%, P = 0.0003); Moreover the all-cause mortality and cardiac mortality were significantly higher in Hb < 120 g/L group than those in Hb ≥ 120 g/L group (28.57% vs 3.10%, P < 0.0001; 23.81% vs 2.33%, P < 0.0001). CONCLUSION: In the patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, hemoglobin level < 120 g/L at baseline is markedly associated with adverse outcomes and an elevated incidence of MACE and mortality during the follow-up period.

[Clinical and coronary angiographic features of patients with systemic vasculitis and coronary artery disease].

OBJECTIVE: To evaluate the clinical and coronary angiographic features of patients with systemic vasculitis and coronary artery disease. METHOD: Fifteen patients (11 male) with systemic vasculitis and coronary artery diseases admitted to our hospital from January 1999 to October 2009 were reviewed. RESULTS: There were 6 patients with Behcet's disease, 3 patients with Churg-Strauss syndrome, 2 patients with Takayasu arteritis, 1 patient with polyarteritis nodosa, 1 patient with microscopic polyangiitis, 1 patient with Wegner's granulomatosis and 1 patient with Kawasaki disease. Mean age of this cohort was (39.3 ± 11.9) years. Adverse coronary events occurred in 4 patients during the inactive phase of systemic vasculitis and in 9 patients during the active phase of systemic vasculitis. Twelve patients were hospitalized with acute myocardial infarction, 2 with angina pectoris and 1 with cardiac tamponade. There were 3 patients with acute left ventricular dysfunction and 3 patients with severe arrhythmias. Compared to patients in the inactive phase, patients in the active phase were younger [(32.4 ± 8.1) years vs. (47.0 ± 10.2) years], had less risk factors for atherosclerosis (1.2 ± 1.5 to 2.8 ± 1.7) and the time intervals between coronary artery disease and systemic vasculitis was shorter [0 - 7 years (average 1.6 years) to 3 - 30 years (average 17.7 years)]. Coronary angiography evidenced coronary stenosis or occlusions in 11 patients, coronary aneurysm and acute thrombosis in 1 patient, coronary aneurysms and occlusions in 1 patient and coronary spasm in 2 patients. LVEF measured by echocardiography was less than 50% in 8 patients. CONCLUSION: Patients with various systemic vasculitis could develop severe coronary artery disease due to coronary stenosis/occlusion, aneurysma, thrombosis and coronary spasm.

[Long-term outcome analysis of patients underwent percutaneous coronary intervention with prior ischemic stroke].

OBJECTIVE: To analyze the clinical characteristics and long-term outcomes of patients underwent percutaneous coronary intervention (PCI) with prior ischemic stroke. METHODS: A total of 2053 patients underwent PCI in Peking union medical college hospital from January 2003 to December 2007 were included in this analysis and patients were followed up to December 2009. End-point included all-cause mortality, cardiac death, stent thrombosis, target-lesion revascularization, myocardial infarction, re-cerebral infarction. Major bleeding events were recorded during follow-up. RESULTS: There are 1945 coronary heart disease patients were followed up and 222 patients with prior ischemic stroke. Compared patients without prior ischemic stroke, patients with prior ischemic stroke were older (P = 0.000), had higher hypertension morbidity (P = 0.000), higher diabetes mellitus morbidity (P = 0.005), higher incidence of multi-vessels disease (P = 0.000). During the follow-up of (35.0 ± 19.6) months, cardiac death rate (8.5% vs. 3.9%, P = 0.002) and re-cerebral infarction rate (5.8% vs. 1.4%, P = 0.000) were higher in patients with prior ischemic stroke than patients without prior ischemic stroke. Dual antiplatelet therapy treatment time [(13.77 ± 11.33) months vs. (13.94 ± 11.33) months, P = 0.986] and major bleeding events (5.8% vs. 3.6%, P = 0.100) were similar between the two groups and cerebral hemorrhage rate (1.8% vs. 0.5%, P = 0.028) were higher in patients with prior ischemic stroke than patients without prior ischemic stroke. CONCLUSION: Patients with prior ischemic stroke were associated with increased rate of risk factors, multiple coronary artery disease, cardiac death and re-cerebral infarction and higher cerebral hemorrhage rate during follow-up despite similar dual-anti platelet therapy time.

Genome-wide identification of altered RNA m6A profiles in vascular tissue of septic rats.

Sepsis is the leading cause of death in hospital intensive care units. In light of recent studies showing that variations in N6-methyladenosine (m6A) levels in different RNA transcripts influence inflammatory responses, we evaluated the m6A profiles of rat aortic mRNAs and lncRNAs after lipopolysaccharide (LPS)-induced sepsis. LC-MS-based mRNA modification analysis showed that global m6A levels were significantly decreased in aortic tissue of rats injected intraperitoneally with LPS. This finding was consistent with downregulated expression of METTL3 and WTAP, two members of the m6A writer complex, in LPS-exposed aortas. Microarray analysis of m6A methylation indicated that 40 transcripts (31 mRNAs and 9 lncRNAs) were hypermethylated, while 223 transcripts (156 mRNAs and 67 lncRNAs) were hypomethylated, in aortic tissue from LPS-treated rats. On GO and KEGG analyses, 'complement and coagulation cascades', 'transient receptor potential channels', and 'organic anion transmembrane transporter activity' were the major biological processes modulated by the differentially m6A methylated mRNAs. In turn, competing endogenous RNA network analysis suggested that decreased m6A levels in lncRNA-XR_343955 may affect the inflammatory response through the cell adhesion molecule pathway. Our data suggest that therapeutic modulation of the cellular m6A machinery may be useful to preserve vascular integrity and function during sepsis.

[Effect of duration of clopidogrel use on clinical follow-up outcomes in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention].

OBJECTIVE: To evaluate effect of duration of clopidogrel use on clinical follow-up outcomes in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. METHODS: A total of 214 patients with acute myocardial infarction undergoing primary percutaneous coronary intervention between January 2005 to December 2007 were enrolled. All patients were divided into two groups by duration of clopidogrel use: <1 year group (n=59) and > or =1 years group (n=155). Baseline characteristics [age, gender, angiographic characteristics, Killip classification, LVEF (left ventricular ejection fraction) , CK (creatine kinase), CK-MB, CTnI (cardiac troponin-I), hemoglobin levels and history of hypertension, diabetes, hyperlipidemia, obesity and smoking] of two groups were collected. Clinical follow-up end-point was major adverse cardiac event (MACE) including death, acute myocardial infarction, stent thrombosis and stent restenosis. Clinical follow-up duration was 41.6 +/- 16.3 months. MACE occurred in 28 patients. RESULTS: Rates of male, infarction site, infarction relative artery, multivessel disease, Killip classification (class I), aspirin use and history of smoking, obesity, hypertension and hyperlipidemia were not different (P > 0.05) in duration of clopidogrel use <1 year group and > or =1 years group. Average LVEF, hemoglobin levels and rate of drug-eluting stents were significantly lower in duration of clopidogrel use <1 year group than that in duration of clopidogrel use > or =1 years group (P < 0.0001, P < 0.0001, P = 0.0065). Average CK, CK-MB, CTnI were significantly higher in duration of clopidogrel use > or =1 years group than that in duration of clopidogrel use <1 year group (P < 0.0001). Rate of diabetes and average age were significantly higher in duration of clopidogrel use <1 year group than that in duration of clopidogrel use > or =1 years group (P = 0.0190, P < 0.0001). Incidence of MACE in follow-up period was significantly lower in duration of clopidogrel use > or =1 years group than that in duration of clopidogrel use < 1 year group (6.45% vs. 30.51%, P < 0.01). After stopping clopidogrel use, incidence of MACE in followup period was significantly lower in duration of clopidogrel use > or =1 years group than that in duration of clopidogrel use <1 year group (2.58% vs. 20. 34%, P < 0.01). CONCLUSION: Primary percutaneous coronary intervention is an effective therapeutic method. Incidence of MACE in follow-up period was significantly lower in duration of clopidogrel use > or =1 years group than that in duration of clopidogrel use <1 year group. Duration of clopidogrel use may influence clinical outcomes in follow-up period in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

[Clinical and coronary characteristics of young patients (< 30 years old) with acute myocardial infarction].

OBJECTIVE: To explore the clinical characteristics and angiographic features of acute myocardial infarction in patients aged 30 years or younger. METHODS: Data of 360 consecutive patients referred to Peking Union Medical College Hospital for evaluation of chest pain or discomfort from January 2007 to December 2009, diagnosed as acute myocardial infarction and underwent emergent coronary angiography were analyzed. Seven patients (1.9%) with age ≤ 30 years [4 male, (25 ± 5) years] were included in this study, patients were followed up for (12 ± 9) months. RESULTS: There were 6 cases of ST-segment elevated myocardial infarction and 1 non-ST-segment elevated myocardial infarction. The culprit vessels were as follows: 5 left anterior descending artery, 1 left main and 1 right coronary artery. All 3 female patients were complicated with congenital coronary malformation or autoimmune disease, including 1 coronary artery aneurismal dilation of left anterior descending, 1 Takayasu's arteritis and 1 systemic lupus erythematosus. Three of the 4 male patients were smokers. Two patients underwent percutaneous coronary intervention. There was no death or cardiovascular re-admission during the follow-up. CONCLUSIONS: The majority of acute myocardial infarction in patients aged 30 years or younger were presented with ST-segment elevated myocardial infarction and single vessel non-obstructive lesion. The most common culprit vessel was left anterior descending artery. All female patients were complicated with congenital coronary malformation or autoimmune disease. The short-term prognosis in patients of this cohort was good.

LncRNA and mRNA expression profiles and functional networks of hyposalivation of the submandibular gland in hypertension.

Hyposalivation is a complication of hypertension. However, little is known about the role of long non-coding RNAs (lncRNAs) in salivary glands in hypertension. This study aimed to compare the lncRNA and mRNA expression profiles between spontaneous hypertension rats (SHRs) and Wistar-Kyoto (WKY) rats through microarray analysis and apple bioinformatics methods to analyse their potential roles in hyposalivation. The differentially expressed (DE) lncRNAs and mRNAs were confirmed by quantitative real-time PCR (qRT-PCR). Compared with WKY rats, 225 DE lncRNAs and 473 DE mRNAs were identified in the SMG of SHRs. The pathway analyses of DE mRNAs showed that inflammatory mediator regulation of transient receptor potential channels was involved in hyposalivation in SHRs. Ten DE lncRNAs were chosen for further research. A coding-non-coding gene co-expression (CNC) network and competing endogenous RNA (ceRNA) network analysis revealed that the potential functions of these 10 DE lncRNAs were closely connected with the processes of the immune response. This study showed abundant DE lncRNAs and mRNAs in hypertensive SMGs. Furthermore, our results indicated strong associations between the immune response and hyposalivation and showed the potential of immune-related genes as novel and therapeutic targets for hyposalivation.

Myocardial blood flow analysis of stress dynamic myocardial CT perfusion for hemodynamically significant coronary artery disease diagnosis: The clinical value of relative parameter optimization.

BACKGROUND: The methods for calculating the optimal myocardial blood flow (MBF) relative parameters in stress dynamic myocardial CT perfusion (CTP) in the detection of hemodynamically significant coronary artery disease (CAD) are non-uniform and lack standards. METHODS: A total of 86 patients who were prospectively recruited underwent APT stress dynamic myocardial CTP. The relative MBF perfusion parameters were calculated as av_Ratio, Q3av_Ratio and hi_Ratio according to the three types of reference MBF values, respectively: (1) average segmental MBF value, (2) the third quartile of the average segmental MBF value, and (3) highest segmental MBF value. All the data were derived from both the endocardial and transmural layers of the myocardium. Invasive coronary angiography and fractional flow reserve (ICA/FFR) were used as the reference standards for myocardial ischemia evaluation. RESULTS: A total of 151 vessels of 60 patients (43 men and 17 women; 61.38 ±â€¯8.01 years) were enrolled in the analysis. The performance of the endocardial layer was superior to that of the transmural layer (all P < 0.05). The hi_Ratio of the endocardial myocardium (AUC = 0.906, 95% CI: 0.857-0.954), for which the highest segmental value was selected as the reference MBF, was superior to both av_Ratio and Q3av_Ratio for ischemia detection (AUC, 0.906 vs.0.879, P < 0.05; 0.906 vs.0.891, P = 0.18), and the sensitivity, specificity, PPV, NPV and diagnostic accuracy were 74.1%, 93.6%, 87.8%, 85.3% and 86.1%, respectively. The cutoff value of hi_Ratio was 0.675. CONCLUSIONS: The relative MBF parameter of the endocardial myocardium using the highest segmental MBF value as a reference provided optimal diagnostic accuracy for the detection of hemodynamically significant CAD.