Interpreting polygenic score effects in sibling analysis.

Researchers often claim that sibling analysis can be used to separate causal genetic effects from the assortment of biases that contaminate most downstream genetic studies (e.g. polygenic score predictors). Indeed, typical results from sibling analysis show large (>50%) attenuations in the associations between polygenic scores and phenotypes compared to non-sibling analysis, consistent with researchers' expectations about bias reduction. This paper explores these expectations by using family (quad) data and simulations that include indirect genetic effect processes and evaluates the ability of sibling analysis to uncover direct genetic effects of polygenic scores. We find that sibling analysis, in general, fail to uncover direct genetic effects; indeed, these models have both upward and downward biases that are difficult to sign in typical data. When genetic nurture effects exist, sibling analysis creates "measurement error" that attenuates associations between polygenic scores and phenotypes. As the correlation between direct and indirect effect changes, this bias can increase or decrease. Our findings suggest that interpreting results from sibling analysis aimed at uncovering direct genetic effects should be treated with caution.

Diagnostic accuracy of CT-FFR with a new coarse-to-fine subpixel algorithm in detecting lesion-specific ischemia: a prospective multicenter study.

INTRODUCTION AND OBJECTIVES: A new computed tomography-derived fractional flow reserve (CT-FFR) technique with a "coarse-to-fine subpixel" algorithm has been developed to generate precise lumen contours. The aim of this study was to assess the diagnostic performance of this new CT-FFR algorithm for discriminating lesion-specific ischemia using wire-based FFR ≤ 0.80 as the reference standard in patients with coronary artery disease. METHODS: This prospective, multicenter study screened 330 patients undergoing coronary CT angiography (CCTA) and invasive FFR (median interval 2 days) from 6 tertiary hospitals. CT-FFR was evaluated in a blinded fashion with a "coarse-to-fine subpixel" algorithm for lumen contour. RESULTS: Between March 2019 and May 2020, we included 316 patients with 324 vessels. There was a good correlation between CT-FFR and invasive FFR (r=0.76, P<.001). The diagnostic sensitivity, specificity, and accuracy on a per-vessel level were 95.3%, 89.8%, and 92.0% for CT-FFR, and 96.4%, 26.4%, and 53.1% for CCTA>50% stenosis, respectively. CT-FFR showed improved discrimination of ischemia compared with CCTA alone overall (AUC, 0.95 vs 0.74, P<.001) and in intermediate (AUC, 0.96 vs 0.62, P<.001) and "gray zone" lesions (AUC, 0.88 vs 0.61, P<.001). The diagnostic specificity, accuracy, and AUC for CT-FFR (71.9%, 82.8%, and 0.84) outperformed CCTA (9.4%, 48.3%, and 0.66) in patients or in vessels with severe calcification (all P<.05). CONCLUSIONS: CT-FFR with a new "coarse-to-fine subpixel" algorithm showed high performance in identifying hemodynamically significant stenosis. The diagnostic performance of CT-FFR was superior to that of CCTA in intermediate lesions, "gray zone" lesions, and severely calcified lesions. Clinical Trial Register: NCT04731285.

Association between bullying victimization and post-traumatic stress disorders among Chinese adolescents: a multiple mediation model.

BACKGROUND: Research that focused on the mechanisms underlying the relation between school bullying victimization and PTSD ignored the simultaneous effect of emotional and cognitive factors, which may limit our comprehensive understanding of their roles. Besides, most researchers included non-bullying victims in data analysis, and this may mask the true effect among bullying victims. The present study aimed to explore the relation between bullying victimization and PTSD, and the mediating roles of social anxiety, loneliness, and rumination, after filtering out non-bullying victims. MATERIALS AND METHODS: In April 2019, we used convenience sampling to recruit 5013 students from Grade 10 and 11 in two high schools in Anhui Province, China. The mean age of these students was 16.77 (SD = 0.92) years. They completed five self-report questionnaires including the Delaware Bullying Victimization Scale-Student Chinese Revision (DBVS-S), the modified PTSD Checklist, the Social Anxiety Scale, the Adolescent Loneliness Scale, and the Rumination Scale. Further, a total of 443 bullying victims were screened out for this study according to the critical score of the DBVS-S. RESULTS: The results showed that bullying victimization had a direct and positive association with PTSD among adolescents (ß = 0.16, 95%CI: 0.046-0.252). Bullying victimization was positively associated with PTSD through increasing adolescents' social anxiety (ß = 0.06, 95%CI: 0.017-0.105), as well as through increasing their loneliness (ß = 0.16, 95%CI: 0.109-0.215). In addition, bullying victimization was positively associated with PTSD through social anxiety via loneliness (ß = 0.04, 95%CI: 0.013-0.067), as well as through loneliness via rumination (ß = 0.02, 95%CI: 0.003-0.033). Bullying victimization was also positively associated with PTSD through a three-step path from social anxiety to rumination via loneliness (ß = 0.004, 95%CI: 0.001-0.009). CONCLUSIONS: Social anxiety, loneliness, and rumination have important mediating effects in the relation between bullying victimization and adolescents' PTSD, in which emotional factors (e.g., social anxiety, loneliness) are more crucial than cognitive factors (e.g., rumination). Intervention should pay more attention to timely alleviate victims' emotional problems to reduce the risk of developing PTSD.

Comparison between a dedicated stent positioning system and conventional stenting of aorto-ostial lesions: a prospective, multi-center, randomized controlled study.

Background: The accurate placement of stents for treatment of coronary aorto-ostial lesions (AOLs) is technically challenging. The purpose of this study was to evaluate the efficacy and safety of a stent positioning system with a dedicated nitinol device and compare them with those of the conventional approach for stenting of coronary AOLs. Methods: In this prospective, multi-center, open-label, randomized study, conducted from November 2015 to April 2019, patients with coronary AOLs that underwent percutaneous coronary intervention (PCI) were randomly allocated (allocation ratio 1:1) using block randomization method to either a stent positioning system group or a conventional technique group. The primary endpoint was the range of stent slippage when positioning. The following secondary endpoints were applied: (I) the extent of swing of the guiding catheters during stent positioning; (II) the rate of accurate stent placement; (III) the procedure time; and (IV) the incidence of major adverse cardiovascular events (MACEs) including cardiac death, myocardial infarction, target lesion revascularization, and stent thrombosis. Results: During the study period, 139 patients with aorto-ostial coronary artery stenosis were included at 5 centers. A total of 69 patients were allocated to the stent positioning system group and 70 patients to the conventional technique group. Angiographic and clinical success were achieved in 100% of the patients included in both groups. The range of stent slippage was significantly shorter in the stent positioning system group than it was in the conventional technique group [0.64 (0.22; 1.35) vs. 1.11 (0.48; 1.72) mm, P=0.01]. The rate of accurate placement of stents was higher in the stent positioning system group than it was in the conventional technique group (74.6% vs. 57.1%, P=0.03). The extent of guiding catheter swing during the stent positioning [0.24 (0.19; 0.53) vs. 0.23 (0.19; 0.53) mm; P=0.95] and the MACEs rates (1.4% vs. 2.9%, P>0.99) were similar between the 2 groups. The procedural time of the stent positioning system was longer than that of the conventional approach [1.00 (0.50; 1.50) vs. 0.80 (0.50; 1.50) min, P=0.09]. Conclusions: The dedicated stent positioning system was is safer and provides more accurate placement of stents for coronary AOLs than the conventional approach, and the associated prolongation of procedure time is insignificant. Trial Registration: Chinese Clinical Trial Registry (ChiCTR), Unique identifier: ChiCTR2100053869. URL: https://www.chictr.org.cn/showproj.html?proj=133280.

CHA2DS2-VASc score as a prognostic indicator in patients with atrial fibrillation undergoing coronary stenting.

BACKGROUND: Patients with atrial fibrillation (AF) and coronary stenting had a poor prognosis. This study aimed to assess the accuracy of CHA2DS2-VASc score for predicting and grading adverse clinical outcomes in this population. METHODS: We reviewed the clinical data of all patients with previously documented nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. The study population was divided into three groups: 1) Low CHA2DS2-VASc score, ≦ 2 points, 2) Intermediate score, 3-4 points, and 3) High score, ≧ 5 points. Major adverse cardiac/cerebrovascular events (MACCE) were defined as a composite of all-cause death, nonfatal myocardial infarction, repeat revascularization and ischemic stroke/systemic thromboembolism (IS/SE). RESULTS: A total of 2394 patients (men: 72.3% vs. women: 27.7%, median age: 67 years) were included, with the CHA2 DS2-VASc score of 3.6 ± 1.6. The median follow-up duration was 36.2 months. All-cause mortality increased 3 folds from the low score (4.8%) to the high score group (15.8%). The high score group had more IS/SE (7.4%) and MACCE (26.3%). The CHA2 DS2-VASc score ≧ 5 points was independently associated with all-cause death (hazard ratio [HR]: 2.303, 95% confidence interval [CI]: 1.492- 3.555), IS/SE (HR: 4.169, 95% CI: 2.216-7.845) and MACCE (HR: 1.468, 95% CI: 1.113-1.936) on multivariate Cox proportional hazards regression. The area under the receiver operating characteristic curve of the CHA2DS2-VASc score was 0.644 (95% CI: 0.624-0.663) for all-cause death, 0.647 (95% CI: 0.627-0.666) for IS/SE, and 0.592 (95% CI: 0.572-0.611) for MACCE. DISCUSSION: CHA2DS2-VASc score was a reliable prognostic indicator in patients with AF and coronary stenting.

Long-term outcomes of high-risk percutaneous coronary interventions under extracorporeal membrane oxygenation support: An observational study.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) offers hemodynamic support for patients undergoing high-risk percutaneous coronary interventions (PCIs). However, long-term outcomes associated with VA-ECMO have not previously been studied. AIM: To explore long-term outcomes in high-risk cases undergoing PCI supported by VA-ECMO. METHODS: In the present observational cohort study, 61 patients who received VA-ECMO-supported high-risk PCI between April 2012 and January 2020 at the Sixth Medical Center of Chinese People's Liberation Army General Hospital were enrolled. The endpoint characteristics such as all-cause mortality, repeated cardiovascular diseases, and cardiac death were examined. RESULTS: Among 61 patients, three failed stent implantation due to chronic total occlusions with severely calcified lesions. One patient showed VA-ECMO intolerance because of high left ventricular afterload. PCI was successfully performed in 57 patients (93.4%). The in-hospital mortality was 23.0%, and the overall survival was 45.9%, with a median follow-up period of 38.6 (8.6-62.1) mo. CONCLUSION: VA-ECMO can be used as a support in patients undergoing high-risk PCI as it is associated with favorable long-term patient survival.

Development and Validation of a Nomogram for Predicting Mortality in Patients with Atrial Fibrillation and Acute Coronary Syndrome Who Underwent Percutaneous Coronary Intervention in a Chinese Multicenter Cohort.

Background: This study is aimed at to establish an effective prognostic nomogram for patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) underwent percutaneous coronary intervention (PCI). Methods: The nomogram was based on a retrospective study of 977 patients with AF and ACS who underwent PCI who were admitted to any of the 11 tertiary hospitals in the Beijing area between 2009 and 2015. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index) and calibration curve and were compared using current risk scores such as GRACE, CRUSADE, CHA2DS2-VASc, and HAS-BLED. The results were validated using bootstrap resampling and a retrospective cohort study of 409 patients enrolled in Fuwai Hospital at the same institution. Results: Independent factors derived from multivariable analysis of the primary cohort to predict all-cause mortality were age, pattern of ACS, red blood cell distribution width, N-terminal proBNP, and serum creatinine, all of which were assembled into the nomogram. The calibration curve for the probability of recurrence showed that the nomogram-based predictions were in good agreement with actual observations. The C-index of the nomogram for predicting mortality was 0.764 (95% CI, 0.718-0.810), which was statistically higher than the C-index values for the current risk scores (from 0.573 to 0.681). In the validation cohort, the C-index of the nomogram for predicting all-cause death was 0.706 (95% CI 0.601-0.811), with no significant differences compared with GRACE and CRUSADE, but better than that of CHA2DS2-VASc and HAS-BLED. Conclusions: The nomogram has good prognostic prediction for patients with AF and ACS who underwent PCI.

AngioJet rheolytic thrombectomy in patients with thrombolysis in myocardial infarction thrombus grade 5: an observational study.

The aim of this study was to evaluate the effectiveness and safety of AngioJet rheolytic thrombectomy among patients with high thrombus burden. Routine manual thrombus aspiration in patients with ST-segment elevation myocardial infarction (STEMI) does not improve clinical outcomes and was associated with an increased rate of stroke. However, the safety of mechanical thrombus aspiration is still unknown. This was a retrospective, single-center study involving 621 patients with Thrombolysis In Myocardial Infarction thrombus grade 5. The primary outcome was the composite of major adverse cardiovascular events (MACE) within 12 months. The safety outcome was stroke within 1-year. Propensity matching score was calculated due to the significant baseline differences between the AngioJet rhelytic thrombectomy group and the routine treatment group. AngioJet rheolytic thrombectomy was performed in 117 patients. After propensity-score matching, there was no significant difference both in the incidence of MACE (11.1% vs 17.9%, hazard ratio, 1.641; 95% confidence interval [CI] 0.822 to 3.277, p = 0.161) and the incidences of stroke (1.7% vs 2.6%, hazard ratio 1.522; 95% confidence interval [CI] 0.254 to 9.107, p = 0.646) between two groups at 1-year follow-up. In patients with Thrombolysis In Myocardial Infarction thrombus grade 5, AngioJet rheolytic thrombectomy did not improve clinical outcomes at 1 year. However, AngioJet rheolytic thrombectomy did not increase the risk of stroke in patients with high thrombus burden.

Predictive models for adverse clinical outcomes in Chinese patients with atrial fibrillation undergoing percutaneous coronary intervention with stenting.

OBJECTIVE: This study aimed to evaluate predictors for adverse cardiovascular outcomes in patients with atrial fibrillation (AF) undergoing coronary stenting. METHODS: We retrospectively recruited consecutive patients with previously documented non-valvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. Major adverse cardiac/cerebrovascular events (MACCE) were a composite of all-cause death, non-fatal myocardial infarction, repeat revascularization, and ischaemic stroke/systemic thromboembolism (IS/STE). Major bleeding referred to grade 2 or higher of Bleeding Academic Research Consortium criteria. RESULTS: A total of 2394 patients (men: 72.3% vs. women: 27.7%, median age: 67 years) were included. The CHA2DS2-VASc and HAS-BLED were 3.6 ± 1.6 and 1.9 ± 0.7, respectively. The median follow-up duration was 36.2 months. There were 230 (9.6%) deaths, 96 (4.0%) IS/STE, 426 (17.8%) MACCE, and 72 (3.0%) major bleeding. Multivariate Cox regression yielded predictive models for (1) all-cause death: diabetes, prior myocardial infarction, chronic kidney disease (CKD), ST-segment elevation myocardial infarction (STEMI) at presentation, heart failure, no use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and statins; (2) IS/STE: advanced age, prior history of ischaemic stroke and intracranial haemorrhage; (3) MACCE: prior history of myocardial infarction and ischaemic stroke, CKD, STEMI, heart failure, and no statin use; (4) major bleeding: prior major bleeding, prior myocardial infarction, CKD and use of oral anticoagulants. CONCLUSION: Chinese patients with AF and coronary stenting had high mortality and incidence of MACCE. We compiled separate predictive models for all-cause death, IS/STE, MACCE, and major bleeding.

Anticoagulation for atrial fibrillation patients with the CHA2DS2-VASc score =1 (beyond sex).

OBJECTIVE: We investigated the risk of ischaemic stroke in patients with 1 another stroke risk factor (i.e. CHA2DS2-VASc score =1 [males] or 2 [females]) and the impact of different component risk factors. METHODS: Database were collected from two hospitals in the city of Hohhot in china. Among 3148 Nonvalvular AF patients not on antiplatelet or anticoagulant therapy, we evaluated males with a CHA2DS2-VASc score of 1 and females with a CHA2DS2-VASc score of 2. The clinical endpoint was the occurrence of ischaemic stroke. RESULTS: Among 546 AF male patients with a CHA2DS2-VASc score of 1, there were 44 patients (8.06%) who experienced ischaemic stroke during follow-up (3.4 ± 2.1 years) with an annual stroke rate of 2.62%. The risk of ischaemic stroke ranged from 1.86%/year for patients with vascular diseases to 3.33%/year for those age 65-74 years of age. For the female patients with 653 AF, 54 (8.27%) experienced ischaemic stroke during follow-up (3.4 ± 2.1 years) , for an annual stroke rate of 2.76%. The risk of ischaemic stroke increased from 1.96%/year for patients with vascular diseases to 3.38%/year for those 65-74 years of age. CONCLUTIONS: The risk of each factor is not equal in CHA2DS2-VASc score, with age 65-74 years associated with the highest stroke rate. Oral anticoagulation should be considered for AF patients with 1 another stroke risk factor given their high risk of ischaemic stroke.Article summary:The risk of each factor is not equal in CHA2DS2-VASc score.Atrial fibrillation is a risk factor of ischaemic stroke.Oral anticoagulation should be considered for AF patients with 1 another stroke risk factor given their high risk of ischaemic stroke.It is the retrospective nature of the study.We were not able to clearly confirm the cause of ischaemic stroke because it can be due to AF-related thromboembolism or atherosclerosis and thrombosis of the cerebral artery.

Sex difference in clinical outcomes of Chinese patients with atrial fibrillation and coronary stenting according to age.

OBJECTIVE: Sex differences in the clinical outcomes of patients with atrial fibrillation (AF) and coronary stenting should be assessed according to age. METHODS: We analyzed the clinical data of all patients with nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. RESULTS: A total of 2,146 patients (71.8% men and 28.2% women) were included in the study. The mean age of the patients was 66.6±9.4 years. Women in this study were older and had higher prevalence of hypertension, diabetes, chronic kidney disease (CKD), and anemia. Smoking history was found to be higher in men, and women were less likely to be current smokers. The mean follow-up duration was 39.7 months. Women younger than 65 years had a remarkably higher mortality (11.2% vs. 5.3%, p=0.012) and a significantly lower rate of repeat revascularization (1.6% vs. 6.3%, p=0.034) than men. Female gender remained an independent predictor for all-cause mortality [hazard ratio (HR)=2.03, 95% confidence interval (CI): 1.09-3.79, p=0.025], along with heart failure (HR=3.64, 95% CI: 2.02-6.57, p<0.001) and CKD (HR=2.46, 95% CI: 1.09-5.57, p=0.031) after multivariate regression analysis. No significant difference was noted between men and women with regard to mortality, ischemic events, and major bleeding in elderly patients. CONCLUSION: In Chinese patients younger than 65 years with AF and coronary stenting, female gender was independently associated with increased mortality; men were more likely to receive repeat revascularization possibly due to the current smoking. Whether it was a biological difference or a recognition disparity of the disease between men and women warrants further investigation.

Thrombus straddling a patent foramen ovale and pulmonary embolism: A case report.

BACKGROUND: Venous thromboembolism is a common vascular syndrome presenting as deep vein thrombosis and/or pulmonary embolism. Thrombus has the possibility of migrating into the left circulation via patent foramen ovale in certain extreme circumstances. Thrombus straddling a patent foramen ovale is a direct evidence of this scenario. However, the confirmed cases of thrombus in transit are still rare. CASE SUMMARY: A 32-year-old man suffered from recurrent syncope and intermittent dyspnea for 1 wk. Transthoracic echocardiography confirmed a thrombus straddling the patent foramen ovale, and thrombi were also found in the bilateral pulmonary artery by computed tomography. The man underwent inferior vena cava filter placement and thrombolysis with alteplase. Echocardiography showed the absence of thrombi in both the right atrium and left atrium 2 d after hospitalization. The man was discharged to home on warfarin without any complications 2 wk later. CONCLUSION: Scrutinizing intracardiac thrombi provides measurable value in pulmonary embolism as closure of patent foramen ovale may be considered in certain patients. Early intervention plays a critical role in thrombus straddling a patent foramen ovale. A sedentary lifestyle may predispose young adults to thromboembolism, even if there are no other risk factors.

Xinyue Capsule in patients with stable coronary artery disease after percutaneous coronary intervention: a multicenter, randomized, placebo-controlled trial.

BACKGROUND: Xinyue capsule, a patented Chinese herbal medicine, has been used to manage coronary artery disease (CAD) for over a decade in China, but whether it can further reduce risk of cardiovascular events beyond conventional treatment is unknown. METHODS: In this multicenter, randomized, placebo-controlled trial, we randomly assigned patients with stable CAD who underwent percutaneous coronary intervention (PCI) within the preceding 3-12 months to receive Xinyue capsule (100 mg panax quinquefolius saponins, three times a day) or placebo for 24 weeks in addition to conventional treatment. The primary endpoint was a composite that included cardiac death, nonfatal myocardial infarction and urgent revascularization with either PCI or coronary artery bypass grafting. The secondary composite endpoints included stroke, re-hospitalization due to acute coronary syndrome (ACS), pulmonary embolism, peripheral vascular events and all-cause mortality. Quality of life was assessed using a 36-item Short-Form Health Survey (SF-36). RESULTS: A total of 1054 participants were included in the analyses. The median follow up was 1 year. The primary endpoint events occurred in 16 patients (3.02%) in the Xinyue group and 34 patients (6.49%) in the placebo group (hazard ratio [HR] 0.455, 95% confidence interval [CI] 0.25 to 0.825; P = 0.009). Secondary end-point events occurred in 5.47% of patients in the Xinyue group and 10.31% in the placebo group (HR 0.515, 95% CI 0.328 to 0.809; P = 0.004). SF-36 subscale scores at 12 months were significantly higher in the Xinyue group than placebo group for general health (P = 0.048) and vitality (P = 0.008). CONCLUSIONS: In patients with stable CAD after PCI within the preceding 3 to 12 months, Xinyue capsule added on conventional treatment reduced the incidence of primary composite endpoint (cardiac death, nonfatal myocardial infarction and urgent revascularization).

Protective effects of Ulinastatin on oxidative stress and inflammation of rat-derived cardiomyocytes H9c2.

Ischemic heart disease (IHD) is a common clinical disease and has a younger tendency in recent years. This study focused on the role of Ulinastatin (UTI) in the anti-oxidative stress and anti-inflammatory response of cardiomyocytes. H9c2 cells were divided into control group, ischemia-anoxic group (ischemic hypoxia group) and ischemia-anoxia + UTI group (UTI group). Cell morphology was observed by light microscopy, Cell staining, Western blotting, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were conducted to research the effect of UTI on the nuclear factor-κB (NF-κB) signaling pathway. H9c2 cells in the ischemic hypoxia group showed hypertrophy and irregular shape, while the cell morphology of the UTI group was close to the fusiform shape. The cell hypertrophy was lighter, and the number of irregular morphological cells decreased in UTI group than ischemic hypoxia group. The content of interleukin-1ß (IL-1ß) in the ischemic hypoxic group was significantly higher than that in the control group. In the UTI group, IL-1ß was significantly lowly expressed than the ischemia hypoxia group. In addition, the expressions of SOD1, SOD2, GPX1, GPX3, Bcl-2 and Sirt1 in UTI group were higher than ischemic hypoxia group (P<0.05). The expressions of p65, Iκk-α kinase, Caspase3 and Bax in UTI group were lower than ischemic hypoxia group (P<0.05). UTI protects H9c2 cells from ischemia and hypoxia injuries by inhibiting the NF-κB pathway, thereby reducing inflammation, resisting oxidative stress, inhibiting apoptosis, and delaying cell senescence.

Ripk3 mediates cardiomyocyte necrosis through targeting mitochondria and the JNK-Bnip3 pathway under hypoxia-reoxygenation injury.

Context: Cardiomyocyte necrosis following myocardial infarction drastically the progression of heart failure.Objective: In the current study, we explored the upstream mediator for cardiomyocytes necrosis induced by hypoxia-reoxygenation (HR) injury with a focus on mitochondrial function and JNK-Bnip3 pathway.Materials and methods: Cell necrosis was determined via MTT assay, TUNEL staining and PI staining. siRNA transfection was performed to inhibit Ripk3 activation in response to HR injury. Pathway blocker was applied to prevent JNK activation.Results: Ripk3 was rapidly increased in HR-treated cardiomyocytes and correlated with the necrosis of cardiomyocytes. Interestingly, silencing of Ripk3 attenuated HR-mediated cardiomyocytes necrosis. At the molecular levels, Ripk3 deletion sustained mitochondrial bioenergetics and stabilized mitochondrial glucose metabolism. Besides, Ripk3 deletion also reduced mitochondrial oxidative stress and inhibited mPTP opening. To the end, we found Ripk3 activation was along with JNK pathway activation and Bnip3 upregulation. Interestingly, blockade of JNK pathway abolished the harmful effects of HR injury on mitochondrial function, energy metabolism and redox balance. Moreover, overexpression of Bnip3 abrogated the protection action played by Ripk3 deletion on cardiomyocytes survival.Conclusions: Taken together, these data may identify Ripk3 upregulation, mitochondrial dysfunction and JNK-Bnip3 axis activation as the novel mechanisms underlying cardiomyocytes necrosis achieved by HR injury. Thereby, approaches targeted to the Ripk3-JNK-Bnip3-mitochondria cascade have the potential to ameliorate the progression of HR-related cardiomyocytes necrosis in the clinical practice.

Antiplatelet Effect of Different Loading Doses of Ticagrelor in Patients With Non-ST-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: The APELOT Trial.

BACKGROUND: We hypothesized that a high ticagrelor loading dose (LD) may improve platelet inhibition in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). METHODS: This interventional multicentre open-label trial randomized 278 patients with NSTE-ACS to a high (360 mg) or conventional (180 mg) ticagrelor LD. The primary outcome was the platelet reactivity index (PRI) 1 hour after administration of the LD. Secondary outcomes included PRI at 0.5 hour, 1 hour, 8 hours, and 24 hours; periprocedural myocardial infarction (PMI); major cardiac adverse events; and bleeding events. RESULTS: Two hundred sixty-two patients completed the major end points. PRI was lower in the high-LD group than in the conventional-LD group at any time point (all, P < 0.05), including at 1 hour (12.2% vs 16.7%; P = 0.023). At 0.5 hour, the high-LD group showed a lower high-platelet reactivity rate (49.6% vs 60.2%; P = 0.013) and a higher low-platelet reactivity rate (24.8% vs 12.8%; P = 0.017) than did the conventional LD group. No significant differences in the bleeding rates were found between the 2 groups (14% vs 14.3%). Four cases of PMI and 1 death in each group, as well as 1 acute myocardial infarction in the conventional LD group, occurred. There was no stroke, target lesion revascularization, or target vessel revascularization. CONCLUSIONS: Doubling the ticagrelor LD achieved faster onset and greater platelet inhibition without an increase in adverse events in patients with NSTE-ACS undergoing PCI.

Prevalence and composition of CHD at different altitudes in Tibet: a cross-sectional study.

BACKGROUND: The prevalence of CHD has been well described worldwide except in Tibet. This study aimed to illustrate the prevalence and composition of CHD in Tibetan children according to altitude. Methods and results In the first part, we prospectively recruited 7088 unselected Tibetan children (4-17 years) from south-west Tibet. The total prevalence of CHD increased from 4.6/1000 below 4200 m to 13.4/1000 above 4700 m, with a female-to-male ratio of 1.3:3.1. The total prevalence and female prevalence of patent ductus arteriosus increased more than 10-fold. Females living above 4700 m had exceptionally high prevalence of patent ductus arteriosus (14.9/1000). The prevalence of atrial septal defect was comparable among different altitudes (3.3-3.8/1000). The prevalence of ventricular septal defect was 1.3/1000 below 4700 m, and no cases were found above this altitude. In the second part, we retrospectively reviewed the clinical data of 383 CHD children in Tibet and 73 children at lower altitudes. The percentage of isolated ventricular septal defect decreased from 54.8 to 3.1%, and the percentage of isolated patent ductus arteriosus increased from 8.2 to 68.4% with elevation. Children living below 4200 m (10.4-13.7%) had a larger proportion of complex CHD than those above this altitude (2.0-3.1%). Of the 20 Tibetan children with complex CHD, 14 (70.0%) lived below 4200 m. CONCLUSIONS: A wide variation in CHD prevalence and composition existed in Tibetan children among different altitudes.

Transthoracic contrast echocardiography using vitamin B6 and sodium bicarbonate as contrast agents for the diagnosis of patent foramen ovale.

To evaluate the utility of transthoracic contrast echocardiography (cTTE) using vitamin B6 and sodium bicarbonate as contrast agents for diagnosing right-to-left shunt (RLS) caused by patent foramen ovale (PFO) compared to that of transesophageal echocardiography (TEE). We investigated 125 patients admitted to our neurology department with unexplained cerebral infarction and migraine. All patients underwent cTTE using vitamin B6 and sodium bicarbonate as contrast agents, after which they underwent transthoracic echocardiography. The Doppler signal was recorded during the Valsalva maneuver, and TEE examinations were performed. The feasibility, diagnostic sensitivity, and safety of cTTE and TEE for PFO recognition were compared. Evidence of PFO was found in 49 (39.20%) patients with cTTE, more than were detected with TEE (39, 31.20%) (χ2=5.0625, P=0.0244). cTTE had a sensitivity of 92.31% and a specificity of 84.88% for diagnosing PFO, showing high concordance with TEE for PFO recognition (κ=0.72). Further, results of a semi-quantitative evaluation of PFO-RLS by cTTE were better than those with TEE (Z=-2.011, P=0.044). No significant adverse reaction was discovered during cTTE examination. cTTE using vitamin B6 and sodium bicarbonate as contrast agents has relatively good sensitivity and specificity for diagnosing RLS caused by PFO when compared with those for TEE. Using vitamin B6 and sodium bicarbonate as contrast agents to perform cTTE is recommended for detecting and diagnosing the PFO due to its simplicity, non-invasive character, low cost, and high feasibility.

High-Performance Personalized Heartbeat Classification Model for Long-Term ECG Signal.

Long-term electrocardiogram (ECG) has become one of the important diagnostic assist methods in clinical cardiovascular domain. Long-term ECG is primarily used for the detection of various cardiovascular diseases that are caused by various cardiac arrhythmia such as myocardial infarction, cardiomyopathy, and myocarditis. In the past few years, the development of an automatic heartbeat classification method has been a challenge. With the accumulation of medical data, personalized heartbeat classification of a patient has become possible. For the long-term data accumulation method, such as the holter, it is difficult to obtain the analysis results in a short time using the original method of serial design. The pressure to develop a personalized automatic classification model is high. To solve these challenges, this paper implemented a parallel general regression neural network (GRNN) to classify the heartbeat, and achieved a 95% accuracy according to the Association for the Advancement of Medical Instrumentation. We designed an online learning program to form a personalized classification model for patients. The achieved accuracy of the model is 88% compared to the specific ECG data of the patients. The efficiency of the parallel GRNN with GTX780Ti can improve by 450 times.