Coronary artery disease (CAD) and associated comorbidities such as heart failure (HF) remain the leading cause of morbidity and mortality worldwide attributed to, at least partially, the lack of biomarkers for efficient disease diagnosis. Here, we evaluated the diagnostic potential of serum peptidoglycan recognition protein 1 (PGLYRP1), an important component of the innate immunity and inflammation system, for both CAD and HF. A machine-learning method (random forest) was used to evaluate the clinical utility of circulating PGLYRP1 for diagnosis of CAD and HF in a total of 370 individuals. Causal links of chronic serum PGLYRP1 elevation to both diseases were further explored in ApoE-/- mice. The serum levels of PGLYRP1 were significantly higher in individuals with either chronic CAD or acute coronary syndrome than those in those without coronary artery stenosis (the control group) and even more pronounced in CAD individuals with concomitant HF. Our random forest classifier revealed that this protein performed better than other recommended clinical indicators in distinguishing the CAD from the control individuals. In addition, this protein associates more with the biomarkers of HF including left ventricular ejection fraction than inflammation. Notably, our mice experiment indicated that long-term treatment with recombinant PGLYRP1 could significantly impair the cardiovascular system as reflected from both increased atherogenic lesions and reduced fractional shortening of the left ventricle. Our findings, therefore, supported the circulating levels of PGLYRP1 as a valuable biomarker for both CAD and HF.
Objective
For chronic heart failure(CHF)patients with cardiac resynchronization therapy(CRT), optimized interventricular(VV)interval can help to enhance ventricular activation synchrony and improve left ventricular function.The present study used real-time multichannel electrocardiogram(ECG)recording to optimize the VV interval during the CRT implantation, and evaluated the effects of this optimization technique on the changes of cardiac remodeling.
Methods
A total of 84 CHF patients with CRT were enrolled and divided into two groups(optimized group, n=37; non-optimized group, n=47). In optimized group, real-time QRS duration in different VV interval were measured on Bard multichannel recorder(speed, 100mm/s and accuracy 2 ms). The VV interval with the narrowest QRS duration was selected and applied to CRT.Patients in non-optimized group were not performed VV interval optimization during procedure.Echocardiography was performed at baseline, one week and one year after CRT implantation, and left ventricular ejection fraction(LVEF), left ventricular diameter and volume were analyzed were analyzed.
Results
Compared to baseline, echocardiography parameters were not changed in either optimized or non-optimized group at acute after the procedure.The percentage of responders of optimized group was 0.76 if the responder was defined as LVEF improvement more than 0.10 at one year after the procedure.The percentage of responders in non-optimized group was 0.53(P<0.05). LVEDD, LVESD, LVEDV, LVESV in optimized group at one year follow-up were all significantly decreased when compared to baseline.But these parameters of one-year after the procedure in non-optimzied group were not significantly changed when compared with baseline.
Conclusion
The real-time optimizing VV interval measured by QRS duration with multichannel recording during the procedure is feasible and effective.CRT with optimized VV interval can effectively promote percentage of responders and improve cardiac structural remodeling in patients with CHF.
Key words:
Cardiac resynchronization therapy; Interventricular optimization; Heart failure
Objective
Cryoballoon-based ablation(CBA)and remote magnetic navigation-guided(RMN)ablation are two novel means to treat paroxysmal atrial fibrillation(PAF), however, no controlled data have been reported in China.This prospective, controlled study was to assess the safety and efficacy of these two techniques and compare the procedure-related outcome.
Methods
A total of 60 patients with PAF were enrolled and divided into two groups(CBA group, n=30; RMN group, n=30). The primary endpoint was acute success of complete pulmonary vein isolation(PVI). The secondary endpoints were procedural parameters including complications, procedure time, ablation time, and fluoroscopy time.Freedom from atrial fibrillation(AF)recurrence was evaluated at 3 months follow-up.
Results
Complete PVI were achieved during the first ablation procedure in CBA group.Acute success rate of PVI was 97% of patients in RMN group.No major complication including cardiac temponade and atrial-esophageal fistulae occurred in RMN group.Phrenic nerve palsy occurred in one patient of CBA group.The complication rate was not different.Compared to RMN group, procedure time of CBA group was significantly reduced [(142±36) min vs.(108±30) min, P<0.01]; However, fluoroscopy time was increased by 10 min[(6.5±2.8) min vs.(16.4±4.8) min, P<0.001]. AF recurrence was similar between these two groups(RMN vs. CBA: 16.7% vs. 23.0%, P=0.75)within 3 months(blanking period).
Conclusion
Both CBA and RMN are safe and effective to complete PVI in patients with PAF.Our data indicated that RMN-guided PAf ablation can markedly reduce the fluoroscopy time, and CBA can shorten the procedure time.
Key words:
Atrial fibrillation; Pulmonary vein isolation; Cryoballoon ablation; Remote magnetic navigation
Background Few reports have addressed the mechanism by which microRNA miR‐10b‐5p regulates post–myocardial infarction (post‐ MI ) cardiomyocyte apoptosis under hypoxic conditions. Methods and Results C57 BL /6 mice underwent surgical ligation of the left anterior descending artery to create an MI or ischemia/reperfusion animal model. The expression of miR‐10b‐5p, PTEN (phosphatase and tensin homolog), and HIF‐1α (hypoxia‐inducible factor 1α) was detected in infarct border zone tissues at various time points. After precordial injections of the negative control or miR‐10b‐5p, overexpression lentiviruses were made in the areas surrounding the MI sites at 1 week, and myocardial infarct size, cardiac function, and cardiomyocyte apoptosis were examined. A miR‐10b‐5p mimic was transfected into primary mouse cardiomyocytes to analyze its effects on cardiomyocyte apoptosis and PTEN expression. Meanwhile, PTEN as a target of miR‐10b‐5p was verified via luciferase reporter gene assays. Cotransfection of miR‐10b‐5 and PTEN verified the relationship between miR‐10b‐5 and PTEN . Under hypoxic stress, the expression of HIF ‐1α and miR‐10b‐5p was examined. The results showed that miR‐10b‐5p expression was markedly reduced in the infarct border zone. Overexpression of miR‐10b‐5p in the murine model of MI significantly reduced MI size, improved cardiac function, and inhibited apoptosis. Overexpression of miR‐10b‐5p in vitro antagonized hypoxia‐induced cardiomyocyte apoptosis and specifically inhibited the expression of the apoptosis‐related gene PTEN , but overexpression of PTEN weakened these effects. We also found that hypoxia‐induced accumulation of HIF ‐1α resulted in decreased expression of miR‐10b‐5p. Interfering with the activation of the HIF ‐1α signaling pathway promoted Pri‐miR‐10b and miR‐10b‐5p expression and inhibited PTEN expression. Conclusions MicroRNA miR‐10b‐5p antagonizes hypoxia‐induced cardiomyocyte apoptosis, indicating that miR‐10b‐5p may serve as a potential future clinical target for the treatment of MI .
CO 2 is the determining factor of global warming, affecting the intensity and rate of global warming. Although the outbreak of COVID-19 deeply affected the emission of global carbon, the impact on the temporal variation and spatial distribution of CO 2 emission rate (E CO 2 ) is not yet conclusive. This study systematically analyzed the spatial-temporal distribution of E C0 2 from 2019 to 2021 based on one latest near real-time CO 2 dataset named GRACED. Studies show that COVID-19 has no significant impact on the spatial distribution of CO 2 in the world, but significantly reduce the values. From the perspective of the seasonal cycle, the outbreak of COVID-19 caused a shift in the minimum E CO 2 in 2020 from the Northern Hemisphere summer (JJA) to the Northern Hemisphere winter (MAM), reflecting the impact of the COVID-19 outbreak on global E CO 2 . As for the temporal variation, the impact of the COVID-19 outbreak on the monthly cycle mainly occurred in 2020, especially from March to June of that year. By 2021, the global mean values of E-C02 had largely recovered to 2019 levels as the impact of COVID-19 faded.
The objective of this study was to detect differences in the distribution of the left and right ventricle (LV & RV) activation rate (AR) during short-duration ventricular fibrillation (SDVF, <1 min) and long-duration ventricular fibrillation VF (LDVF, >1 min) in normal and heart failure (HF) canine hearts. Ventricular fibrillation (VF) was electrically induced in six healthy dogs (control group) and six dogs with right ventricular pacing-induced congestive HF (HF group). Two 64-electrode basket catheters deployed in the LV and RV were used for global endocardium electrical mapping. The AR of VF was estimated by fast Fourier transform analysis from each electrode. In the control group, the LV was activated faster than the RV in the first 20 s, after which there was no detectable difference in the AR between them. When analyzing the distribution of the AR within the bi-ventricles at 3 min of LDVF, the posterior LV was activated fastest, while the anterior was slowest. In the HF group, a detectable AR gradient existed between the two ventricles within 3 min of VF, with the LV activating more quickly than the RV. When analyzing the distribution of the AR within the bi-ventricles at 3 min of LDVF, the septum of the LV was activated fastest, while the anterior was activated slowest. A global bi-ventricular endocardial AR gradient existed within the first 20 s of VF but disappeared in the LDVF in healthy hearts. However, the AR gradient was always observed in both SDVF and LDVF in HF hearts. The findings of this study suggest that LDVF in HF hearts can be maintained differently from normal hearts, which accordingly should lead to the development of different management strategies for LDVF resuscitation.
Purpose: We have previously reported that PRDX2 plays an oncogenic role in colon cancer. In this study, the mRNA expression profile of PRDX2 in HCT116 cells was investigated. Furthermore, we selected Dynamin 3 (DNM3), which is up-regulated by siPRDX2, to investigate its expression pattern and functions in colon cancer. Patients and methods: PRDX2 siRNA was transfected into HCT116 cells and the mRNA profile was tested by RNA-Sequencing. The expression of interest proteins was determined by Western blot. DNM3 expression in colon cancer tissues and para-carcinoma tissues was evaluated by Western blot and immunohistochemistry assays. Full-length cDNA of DNM3 was cloned into pcDNA3.1 and introduced into HCT116 and HT29 cells. Cell proliferation was tested by CCK-8 and colony formation assays. Cell invasion and migration were tested by transwell assays. Gelatin zymography was utilized for detection of MMP9 activity. Cell apoptosis was investigated with Annexin V/PI staining and flow cytometry and visualized with Hoechst/PI staining assay. All statistical analysis was performed with SPSS 17.0 software. Results: PRDX2 knockdown led to 210 up-regulated genes and 16 down-regulated genes in HCT116 cells. We also found that DNM3 expression was up-regulated following PRDX2 silencing in HCT116 and HT29 cells. In colon cancer patients, DNM3 was down-regulated and showed a significant association with pathologic grading. DNM3 overexpression inhibited cell proliferation and induced apoptosis in HCT116 and HT29 cells. Cell migration and invasion were also down-regulated in DNM3 overexpressing colon cancer cells, which might be due to the inhibition of MMP9 proteolytic activities. After thorough investigation of the potential mechanism involved, we hypothesized that DNM3 overexpression induced activation of the mitochondrial apoptosis pathway and inhibition of the AKT pathway. Conclusion: These data suggest that DNM3 is down-regulated in colon cancer, serving as a tumor suppressor. Our study provides new sights into the prognostic value and therapeutic application of DNM3 in colon cancer.
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