[Systematic review and Meta-analysis of Gusongbao preparation in treatment of primary osteoporosis].

This study aims to provide evidence for clinical practice by systematically reviewing the efficacy and safety of Gusongbao preparation in the treatment of primary osteoporosis(POP). The relevant papers were retrieved from four Chinese academic journal databases and four English academic journal databases(from inception to May 31, 2022). The randomized controlled trial(RCT) of Gusongbao preparation in the treatment of POP was included after screening according to the inclusion and exclusion criteria. The quality of articles was evaluated using risk assessment tools, and the extracted data were subjected to Meta-analysis in RevMan 5.3. A total of 657 articles were retrieved, in which 15 articles were included in this study, which involved 16 RCTs. A total of 3 292 patients(1 071 in the observation group and 2 221 in the control group) were included in this study. In the treatment of POP, Gusongbao preparation+conventional treatment was superior to conventional treatment alone in terms of increasing lumbar spine(L2-L4) bone mineral density(MD=0.03, 95%CI[0.02, 0.04], P<0.000 01) and femoral neck bone mineral density, reducing low back pain(MD=-1.69, 95%CI[-2.46,-0.92], P<0.000 1) and improving clinical efficacy(RR=1.36, 95%CI[1.21, 1.53], P<0.000 01). Gusongbao preparation was comparable to similar Chinese patent medicines in terms of improving clinical efficacy(RR=0.95, 95%CI[0.86, 1.04], P=0.23). Gusongbao preparation was inferior to similar Chinese patent medicines in reducing traditional Chinese medicine syndrome scores(MD=1.08, 95%CI[0.44, 1.71], P=0.000 9) and improving Chinese medicine syndrome efficacy(RR=0.89, 95%CI[0.83, 0.95], P=0.000 4). The incidence of adverse reactions of Gusongbao preparation alone or combined with conventio-nal treatment was comparable to that of similar Chinese patent medicines(RR=0.98, 95%CI[0.57, 1.69], P=0.94) or conventio-nal treatment(RR=0.73, 95%CI[0.38, 1.42], P=0.35), and the adverse reactions were mainly gastrointestinal discomforts. According to the available data, Gusongbao preparation combined with conventional treatment is more effective than conventional treatment alone in increasing lumbar spine(L2-L4) bone mineral density and femoral neck bone mineral density, reducing low back pain, and improving clinical efficacy. The adverse reactions of Gusongbao preparation were mainly gastrointestinal discomforts, which were mild.

Evaluation of longitudinal trajectory of functional tricuspid regurgitation on the risk of right ventricular dysfunction after mitral valve replacement.

OBJECTIVE: Functional tricuspid regurgitation (FTR) levels can vary over time and its longitudinal changing patterns may predict right ventricular dysfunction (RVD) risk. We aim to identify different trajectories of FTR in those who received mitral valve replacement (MVR) and investigate the association between longitudinal trajectory groups and RVD risk in a cohort study. METHODS AND RESULTS: A prospective cohort study, reported usual FTR levels at baseline in 2005-2015 and the participants of MVR have been followed up for 5-6 years, approximately every 1 year, and so far, the data have been collected across five subsequent phases. Five-year longitudinal trajectories of FTR were identified using group-based trajectory modeling (GBTM). We identified 3 distinct trajectories using a GBTM, labeled by initial value and changing pattern: stable group (258/378, 68.2%), increasing-slow group (67/378, 17.6%) and increasing-fast group (53/378, 14.2%). Treating the stable group as the reference, the age- and sex-adjusted odds ratio (OR) was 25.84 (95% confidence interval [CI]: 11.78-56.65) for the increasing-slow group and 139.94 (95% CI: 45.47-430.68) for the increasing-fast group by logistic regression model. After adjustment for every potential confounding factors, the OR is 14.21 (95% CI: 4.36-46.33) and 49.34 (95% CI: 8.88-273.87), respectively. CONCLUSIONS: The longitudinal trajectories of worsening FTR were mostly associated with increased risk of RVD outcomes, which is independent of other factors including FTR levels. These findings have implications for intervention and prevention of RVD among individuals who received MVR.

Establishment and Validation of a Predictive Model for Long-Term Severe Functional Tricuspid Regurgitation after Mitral Valve Replacement.

BACKGROUND: The objective was to develop and validate an individualized nomogram to predict severe functional tricuspid regurgitation (S-FTR) after mitral valve replacement (MVR) via retrospective analysis of rheumatic heart disease (RHD) patients' pre-clinical characteristics. METHODS: Between 2001-2015, 442 MVR patients of RHD were examined. Transthoracic echocardiography detected S-FTR, and logistic regression model analyzed its independent predictors. R software established a nomogram prediction model, and Bootstrap determined its theoretical probability, which subsequently was compared with the actual patient probability to calculate the area under the curve (AUC) and calibration plots. Decision curve analysis (DCA) identified its clinical utility. RESULTS: Ninety-six patients developed S-FTR during the follow-up period. Both uni- and multivariate analyses found significant correlations between S-FTR occurrence with gender, age, atrial fibrillation (AF), pulmonary arterial hypertension (PH), left atrial diameter (LAD), and tricuspid regurgitation area (TRA). The individualized nomogram model had the AUC of 0.99 in internal verification. Calibration test indicated high agreement of predicted and actual S-FTR onset. DCA also showed that utilization of those six aforementioned factors was clinically useful. CONCLUSION: The nomogram for the patient characteristics of age, gender, AF, PH, LAD, and TRA found that they were highly predictive for future S-FTR onset within 5 years. This predictive ability therefore allows clinicians to optimize postoperative patient care and avoid unnecessary tricuspid valve surgeries.

An ultrasound observation study on the levator hiatus with or without diastasis recti abdominis in postpartum women.

INTRODUCTION AND HYPOTHESIS: We hypothesized that differences in post-partum levator hiatus (LH) measurements, as well as the area of urethra and bladder (AUB), viewed under ultrasound, correlate with diastasis rectus abdominis (DRA) occurrence. The primary objective of this study is to determine ultrasound parameters available for diagnosing DRA in post-partum women. We compared LH and AUB measurements under ultrasound in primiparous women, with and without DRA, at 24-26 weeks postpartum. METHODS: One hundred ninety-four women underwent routine examination, including a self-made clinical symptoms questionnaire, DRA evaluation, and LH and AUB measurements. Independent samples t- and chi-squared tests were used to compare the differences between women with and without DRA. RESULTS: DRA incidence was significantly higher among those who underwent cesarean section (CS) than for vaginal delivery (VD) (P = 0.038). DRA patients could potentially have urinary urgency, frequency, pain, dysuria, and perineal tears. Additionally, statistically significant differences were found between VD patients, with or without DRA, in the resting LH transverse diameter (TrD) (P = 0.032) and the area of the levator hiatus (ALH) (P = 0.048) as well as AUB at Valsalva (P = 0.049). No differences, however, were found between the DRA and no DRA groups for all those measurements among women who had cesarean deliveries. CONCLUSIONS: DRA was more likely in post-CS women. Furthermore, the results showed a plausible association between DRA occurrence and LH expansion, especially in women with VD under rest and Valsalva. This could be useful for developing therapeutic plans based on these parameters for post-partum rehabilitation of women with DRA to avoid long-term complications.

Melatonin attenuates doxorubicin-induced cardiotoxicity through preservation of YAP expression.

There are increasing concerns related to the cardiotoxicity of doxorubicin in the clinical setting. Recently, melatonin has been shown to exert a cardioprotective effect in various cardiovascular diseases, including cardiotoxic conditions. In this study, we examined the possible protective effects of melatonin on doxorubicin-induced cardiotoxicity and explored the underlying mechanisms related to this process. We found that in vitro doxorubicin treatment significantly decreased H9c2 cell viability and induced apoptosis as manifested by increased TUNEL-positive cells, down-regulation of anti-apoptotic protein Bcl-2, as well as up-regulation of pro-apoptotic protein Bax. This was associated with increased reactive oxygen species (ROS) levels and decreased mitochondrial membrane potentials (MMP). In vivo, five weeks of doxorubicin treatment significantly decreased cardiac function, as evaluated by echocardiography. TUNEL staining results confirmed the increased apoptosis caused by doxorubicin. On the other hand, combinational treatment of doxorubicin with melatonin decreased cardiomyocyte ROS and apoptosis levels, along with increasing MMP. Such doxorubicin-melatonin co-treatment alleviated in vivo doxorubicin-induced cardiac injury. Western Blots, along with in vitro immunofluorescence and in vivo immunohistochemical staining confirmed that doxorubicin treatment significantly down-regulated Yes-associated protein (YAP) expression, while YAP levels were maintained under co-treatment of doxorubicin and melatonin. YAP inhibition by siRNA abolished the protective effects of melatonin on doxorubicin-treated cardiomyocytes, with reversed ROS level and apoptosis. Our findings suggested that melatonin treatment attenuated doxorubicin-induced cardiotoxicity through preserving YAP levels, which in turn decreases oxidative stress and apoptosis.

Knock-out of MicroRNA 145 impairs cardiac fibroblast function and wound healing post-myocardial infarction.

Prevention of infarct scar thinning and dilatation and stimulation of scar contracture can prevent progressive heart failure. Since microRNA 145 (miR-145) plays an important role in cardiac fibroblast response to wound healing and cardiac repair after an myocardial infarction (MI), using a miR-145 knock-out (KO) mouse model, we evaluated contribution of down-regulation of miR-145 to cardiac fibroblast and myofibroblast function during adverse cardiac remodelling. Cardiac function decreased more and the infarct size was larger in miR-145 KO than that in WT mice after MI and this phenomenon was accompanied by a decrease in cardiac fibroblast-to-myofibroblast differentiation. Quantification of collagen I and α-SMA protein levels as well as wound contraction revealed that transdifferentiation of cardiac fibroblasts into myofibroblasts was lower in KO than WT mice. In vitro restoration of miR-145 induced more differentiation of fibroblasts to myofibroblasts and this effect involved the target genes Klf4 and myocardin. MiR-145 contributes to infarct scar contraction in the heart and the absence of miR-145 contributes to dysfunction of cardiac fibroblast, resulting in greater infarct thinning and dilatation. Augmentation of miR-145 could be an attractive target to prevent adverse cardiac remodelling after MI by enhancing the phenotypic switch of cardiac fibroblasts to myofibroblasts.

Evidence for the existence of CD34+ angiogenic stem cells in human first-trimester decidua and their therapeutic for ischaemic heart disease.

Stem cell transplantation is nearly available for clinical application in the treatment of ischaemic heart disease (IHD), where it may be joined traditional methods (intervention and surgery). The angiogenic ability of seed cells is essential for this applicability. The aim of this study was to reveal the presence of CD34+ angiogenic stem cells in human decidua at the first trimester and to use their strong angiogenic capacity in the treatment of IHD. In vitro, human decidual CD34+ (dCD34+ ) cells from the first trimester have strong proliferation and clonality abilities. After ruling out the possibility that they were vascular endothelial cells and mesenchymal stem cells (MSCs), dCD34+ cells were found to be able to form tube structures after differentiation. Their angiogenic capacity was obviously superior to that of bone marrow mesenchymal stem cells (BMSCs). At the same time, these cells had immunogenicity similar to that of BMSCs. Following induction of myocardial infarction (MI) in adult rats, infarct size decreased and cardiac function was significantly enhanced after dCD34+ cell transplantation. The survival rate of cells increased, and more neovasculature was found following dCD34+ cell transplantation. Therefore, this study confirms the existence of CD34+ stem cells with strong angiogenic ability in human decidua from the first trimester, which can provide a new option for cell-based therapies for ischaemic diseases, especially IHD.

Sirtuin3 protects aged human mesenchymal stem cells against oxidative stress and enhances efficacy of cell therapy for ischaemic heart diseases.

Sirtuin3 (SIRT3) is associated with oxidative stress and lifespan. However, the possible mechanisms underlying its influence are unknown. We hypothesized that SIRT3 increases the antioxidant capacity of aged cells and improves the efficacy of human mesenchymal stem cell (hMSC) therapy for ischaemic heart diseases in aged patients. In vitro, the antioxidant capacity of old hMSCs (O-hMSCs) was increased after SIRT3 overexpression using a gene transfection technique, while the antioxidant capacity of young hMSCs (Y-hMSCs) was decreased by SIRT3 silencing. The levels of forkhead box O3a (FoxO3a) in the nucleus, and antioxidant enzymes Mn-superoxide dismutase (MnSOD) and catalase (CAT) increased in SIRT3-overexpressed O-hMSCs while they decreased in SIRT3-silenced Y-hMSCs after oxidative stress. Following myocardial infarction in adult rats in vivo, infarct size decreased and cardiac function was significantly enhanced after cell transplantation with SIRT3 overexpressed O-hMSCs. The number of apoptotic cells decreased and the survival rate of transplanted cells increased following SIRT3 overexpression in O-hMSCs. SIRT3 protects aged hMSCs against oxidative stress by positively regulating antioxidant enzymes (MnSOD and CAT) via increasing the expression of FoxO3a in the nucleus. The efficacy of aged hMSC transplantation therapy for ischaemic heart diseases can be improved by SIRT3 overexpression.

Targeted myocardial delivery of GDF11 gene rejuvenates the aged mouse heart and enhances myocardial regeneration after ischemia-reperfusion injury.

Ischemic cardiac injury is the main contributor to heart failure, and the regenerative capacity of intrinsic stem cells plays an important role in tissue repair after injury. However, stem cells in aged individuals have reduced regenerative potential and aged tissues lack the capacity to renew. Growth differentiation factor 11 (GDF11), from the activin-transforming growth factor ß superfamily, has been shown to promote stem cell activity and rejuvenation. We carried out non-invasive targeted delivery of the GDF11 gene to the heart using ultrasound-targeted microbubble destruction (UTMD) and cationic microbubble (CMB) to investigate the ability of GDF11 to rejuvenate the aged heart and improve tissue regeneration after injury. Young (3 months) and old (21 months) mice were used to evaluate the expression of GDF11 mRNA in the myocardium at baseline and after ischemia/reperfusion (I/R) and myocardial infarction. GDF11 expression decreased with age and following myocardial injury. UTMD-mediated delivery of the GDF11 plasmid to the aged heart after I/R injury effectively and selectively increased GDF11 expression in the heart, and improved cardiac function and reduced infarct size. Over-expression of GDF11 decreased senescence markers, p16 and p53, as well as the number of p16+ cells in old mouse hearts. Furthermore, increased proliferation of cardiac stem cell antigen 1 (Sca-1+) cells and increased homing of endothelial progenitor cells and angiogenesis in old ischemic hearts occurred after GDF11 over-expression. Repetitive targeted delivery of the GDF11 gene via UTMD can rejuvenate the aged mouse heart and protect it from I/R injury.

Three-Dimensional Speckle-Tracking Echocardiographic Monitoring of Acute Rejection in Heart Transplant Recipients.

OBJECTIVES: This study assessed the use of 3-dimensional (3D) speckle-tracking echocardiography for noninvasive monitoring and diagnosis of acute rejection in heart transplant recipients. METHODS: Fifteen heart transplant recipients underwent 32 endomyocardial biopsies; echocardiography was performed within 3 hours before biopsy. Twenty-four biopsies (acute rejection-negative group) showed grade 0 or 1A rejection, and 8 biopsies (acute rejection-positive group) showed grade 1B or higher rejection (based on the International Society for Heart and Lung Transplantation criteria). Two-dimensional, M-mode, pulsed Doppler, and tissue Doppler echocardiography were performed to assess conventional heart structure and function, and 3D full-volume echocardiography was recorded and analyzed. RESULTS: Global peak longitudinal strain was significantly lower in the acute rejection-negative group compared to the positive group (mean ± SD, -7.38% ± 1.34% versus -10.88% ± 3.81%; P = .017). Differences in left ventricular global peak radial strain (28.79% ± 10.79% versus 24.32% ± 5.24%; P= .272), global peak circumferential strain (-12.16% ± 4.87% versus -12.61% ± 2.38%; P = .806), and ejection fraction (49.42% ± 12.17% versus 50.68% ± 7.26%; P = .824) between the negative and positive groups were not significant. Significant correlations were observed between the left ventricular ejection fraction and global peak longitudinal, global peak radial, and global peak circumferential (r = -0.72; P < .001; r = 0.60; P < 0.001; and r = -0.69; P < 0.001, respectively). Receiver operating characteristic curve analysis showed that a global peak longitudinal strain cutoff value of less than -9.55% could predict grade 1B or higher rejection with sensitivity of 87.50% and specificity of 54.17%. CONCLUSIONS: Three-dimensional speckle-tracking echocardiography-derived global peak longitudinal strain is a useful parameter for detecting acute rejection; thus, 3D speckle-tracking echocardiography can monitor dynamic and acute rejection (≥1B) in heart transplant recipients.

Identification of apoptosis-related microRNAs and their target genes in myocardial infarction post-transplantation with skeletal myoblasts.

BACKGROUND: Skeletal myoblasts (SkMs) has provided a promising treatment for myocardial infarction (MI). Functioning as posttranscriptional regulators, microRNAs (miRNAs) play important roles in cardiac repairment and stem cell regulation. However, the correlation between miRNAs and their targeted genes in SkM cell therapy for MI was not fully understood. METHODS: We explored the cardioprotection by SkMs in infracted rats and determined cardiac functions at 4 weeks. In addition, we compared the expression profiles of miRNAs and mRNAs in post-MI rats with or without SkM cell therapy using microarray. The concordance between miRNA expression and mRNA levels of potential target genes was confirmed by quantitative real-time PCR. RESULTS: Quantitative echocardiography and histology showed improved cardiac function, attenuated heart infarcted area and inhibited cardiomyocyte apoptosis in the SkM group, compared with MI group. We identified that 160 miRNAs were differentially expressed in MI group as compared to the control group and 78 miRNAs were differentially expressed in the SkM treated group as compared to the untreated post-MI. We focused on a novel set of apoptosis-associated miRNAs and their target genes, among which 4 miRNAs (miR-30a-5p, miR-30c-5p, miR-145-5p, miR-140-3p), except one (miR-143-3p), were downregulated in the SkM treated group as compared to the untreated group. Furthermore, we found seven genes including Angptl4, Dpep1, Egr1, Eif5a, Tsc22d3, Irs2 and Cebpb that showed a linear correlation with which miRNAs. CONCLUSIONS: The downregulation of apoptosis-regulatory miRNAs and in turn upregulation of target genes may partially account for rescue effect of SKM therapy for MI.

Three-dimensional transesophageal echocardiographic study of aortic-mitral valve coupling after coronary artery bypass grafting.

AIMS: To observe the geometric changes in aortic-mitral valve coupling (AMC) on three-dimensional transesophageal echocardiography and the factors leading to decreased mitral regurgitation (MR) after coronary artery bypass grafting (CABG). METHODS AND RESULTS: This study included 23 patients undergoing CABG for coronary artery disease. Fifteen patients with moderate to severe MR were separately analyzed to determine whether the severity of MR influences the geometric change in AMC. Echocardiographic examinations were performed pre- and post-CABG, and the studied parameters were obtained using Siemens Auto Valve Analysis software. The effective mitral regurgitant orifice area, left ventricular ejection fraction (LVEF), end-diastolic volume (EDV), and end-systolic volume (ESV) were measured pre- and post-CABG using Philips QLAB software. Ischemic MR, EDV, and ESV significantly decreased (all P < 0.05) and LVEF significantly improved (P < 0.05) after CABG. There were no significant differences between the pre- and post-CABG mitral valve (MV) parameters, aortic valve parameters, aortic-mitral annular angle, or centroid distance (all P > 0.05). Patients with moderate to severe MR exhibited the same results. CONCLUSION: The results of this study show that CABG does not cause an acute change in the geometry of AMC. Improved left ventricular function might increase the closing force of the MV, leading to decreased MR after CABG alone. MR significantly improved after CABG alone without MV treatment in the present study. This result may help to guide surgeons in choosing the optimal surgical methods for individual patients.

Wave Intensity Analysis Can Identify Eccentric Cardiac Hypertrophy in Hypertensive Patients With Varied Left Ventricular Configurations.

OBJECTIVES: The primary aim of this study was to determine whether wave intensity can discriminate cases of eccentric hypertrophy in patients with essential hypertension who have varied left ventricular configurations. METHODS: A total of 155 hypertensive patients with different ventricular configurations (27 normal configuration, 42 concentric remodeling, 62 concentric hypertrophy, and 24 eccentric hypertrophy) were recruited. We performed a noninvasive wave intensity analysis of the common carotid artery and conventional echocardiography. Blood pressure and flow velocity were measured in the right carotid artery of all patients. RESULTS: The left ventricular ejection fraction (LVEF) in the eccentric hypertrophy group was significantly lower than the values in the other groups (P < .05). The R-W1 interval/W1-W2 interval ratio (where W1 indicates the first positive peak and W2 the second positive peak) in the eccentric hypertrophy group was much higher than the values in the other groups (P < .05). However, there were no significant differences in W1, W2, and negative area among these groups. Pearson correlation analysis showed that R-W1/W1-W2, R-W1, and W1-W2were correlated with the LVEF, whereas there was no correlation between W1, W2, negative area, and the reflection coefficient with the LVEF. CONCLUSIONS: We propose that by using the R-W1/W1-W2 ratio, wave intensity analysis can identify hypertensive patients with eccentric hypertrophy without the need for echocardiography.

Development and validation of a simple model to predict functionally significant coronary artery disease in Chinese populations: A two-center retrospective study.

Objectives: This study sought to derive and validate a simple model combining traditional clinical risk factors with biomarkers and imaging indicators easily obtained from routine preoperative examinations to predict functionally significant coronary artery disease (CAD) in Chinese populations. Methods: We developed five models from a derivation cohort of 320 patients retrospective collected. In the derivation cohort, we assessed each model discrimination using the area under the receiver operating characteristic curve (AUC), reclassification using the integrated discrimination improvement (IDI) and net reclassification improvement (NRI), calibration using the Hosmer-Lemeshow test, and clinical benefit using decision curve analysis (DCA) to derive the optimal model. The optimal model was internally validated by bootstrapping, and external validation was performed in another cohort including 96 patients. Results: The optimal model including 5 predictors (age, sex, hyperlipidemia, hs-cTnI and LVEF) achieved an AUC of 0.807 with positive NRI and IDI in the derivation cohort. Moreover, the Hosmer-Lemeshow test showed a good fit, and the DCA demonstrated good clinical net benefit. The C-statistic calculated by bootstrapping internal validation was 0.798, and the calibration curve showed adequate calibration (Brier score = 0.179). In the external validation cohort, the optimal model performance was acceptable (AUC = 0.704; Brier score = 0.20). Finally, a nomogram based on this model was constructed to facilitate its use in clinical practice. Conclusions: A simple model combined clinical risk factors with hs-cTnI and LVEF improving the prediction of functionally significant CAD in Chinese populations. This attractive model may be a choice for clinicians to risk stratification for CAD.

Using an Improved Residual Network to Identify PIK3CA Mutation Status in Breast Cancer on Ultrasound Image.

Background: The detection of phosphatidylinositol-3 kinase catalytic alpha (PIK3CA) gene mutations in breast cancer is a key step to design personalizing an optimal treatment strategy. Traditional genetic testing methods are invasive and time-consuming. It is urgent to find a non-invasive method to estimate the PIK3CA mutation status. Ultrasound (US), one of the most common methods for breast cancer screening, has the advantages of being non-invasive, fast imaging, and inexpensive. In this study, we propose to develop a deep convolutional neural network (DCNN) to identify PIK3CA mutations in breast cancer based on US images. Materials and Methods: We retrospectively collected 312 patients with pathologically confirmed breast cancer who underwent genetic testing. All US images (n=800) of breast cancer patients were collected and divided into the training set (n=600) and test set (n=200). A DCNN-Improved Residual Network (ImResNet) was designed to identify the PIK3CA mutations. We also compared the ImResNet model with the original ResNet50 model, classical machine learning models, and other deep learning models. Results: The proposed ImResNet model has the ability to identify PIK3CA mutations in breast cancer based on US images. Notably, our ImResNet model outperforms the original ResNet50, DenseNet201, Xception, MobileNetv2, and two machine learning models (SVM and KNN), with an average area under the curve (AUC) of 0.775. Moreover, the overall accuracy, average precision, recall rate, and F1-score of the ImResNet model achieved 74.50%, 74.17%, 73.35%, and 73.76%, respectively. All of these measures were significantly higher than other models. Conclusion: The ImResNet model gives an encouraging performance in predicting PIK3CA mutations based on breast US images, providing a new method for noninvasive gene prediction. In addition, this model could provide the basis for clinical adjustments and precision treatment.

Melatonin alleviates arginine vasopressin-induced cardiomyocyte apoptosis via increasing Mst1-Nrf2 pathway activity to reduce oxidative stress.

Heart failure patients have elevated arginine vasopressin (AVP) levels, which are involved in inducing peripheral vasoconstriction and cardiac hypertrophy. This hypertrophy, along with cardiomyocyte apoptosis, results from oxidative stress. Therefore, the antioxidant drug, melatonin (Mel), is commonly used to treat cardiac hypertrophy and apoptosis; however, whether it could alleviate AVP-induced myocardialinjury remains to be addressed. In this study, high AVP doses were found to induce H9c2 cardiomyoblast apoptosis, demonstrated by increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, pro-apoptotic B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax) up-regulation, and anti-apoptotic Bcl-2 downregulation. This AVP-induced apoptotic increase, along with lowered cell viability, was also associated with higher reactive oxygen species (ROS) levels and lowered mitochondrial membrane potentials (MMP), which were all reversed upon Mel administration. Further investigations found that apoptosis, ROS, and MMP outcomes under high AVP were associated with Mst1-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway suppression, yielding mitochondrial dysfunction, and Mel reversed them via promoting Mst1 phosphorylation, which then activated Nrf2 to increase anti-oxidative enzyme production. These findings were supported by siRNA gene suppression, where knocking down either Nrf2 or Mst1 abrogated the anti-apoptotic effects of Mel in cardiomyoblasts. Therefore, Mel could reduce cardiomyoblast apoptosis under high AVP levels, via Mst1-Nrf2 pathway re-activation, to enhance anti-oxidative responses.

LncRNA PVT1 is a novel mediator promoting the angiogenesis response associated with collateral artery formation.

AIMS: Angiogenesis plays a key role in coronary collateral circulation (CCC), the compensatory formation of new blood vessels during chronic total coronary occlusion. This study aimed to determine whether plasmacytoma variant translocation 1 (PVT1), a long non-coding (lnc) RNA involved in tumor angiogenesis, plays a role in regulating angiogenesis during chronic coronary ischemia. MAIN METHODS: Patients with coronary artery disease, and ≥ 90% stenosis, were examined and divided into "Good" and "Poor" CCC groups based on Rentrop Cohen classification. RNA samples were obtained from all patients, as well as from oxygen and glucose-deprived (OGD) HUVECs. PVT1, miR-15b-5p and AKT3 levels were measured with RT-qPCR or Western blot, while HUVEC migration and angiogenesis were detected by, respectively, wound-healing and tube formation assays. Luciferase reporter assay confirmed direct PVT1-miR-15b-5p binding. KEY FINDINGS: Increased PVT1 was found in "Good CCC" patient plasma, along with being highly expressed among OGD HUVECs; PVT1 knockdown reduced HUVEC migration, tube formation, and pro-angiogenic factor expression. Conversely, OGD HUVECs had downregulated miR-15b-5p, and miR-15b-5p overexpression significantly depressed their angiogenic capabilities. These PVT1 knockdown- or miR-15b-5p overexpression-associated reductions in angiogenic effects were reversed by AKT3 overexpression. In vivo, neovascularization and functioning in both ischemic mice hind-limbs and infarcted myocardium injected with ADV-sh-PVT1 were reduced, which were ameliorated by concurrent antagomiR-15b-5p injections. SIGNIFICANCE: Circulating PVT1 may serve as a useful biomarker to distinguish between good versus poor CCC, as it is involved in orchestrating angiogenesis via the miR-15b-5p-AKT3 axis; it thus has potential as a target for treating ischemic disease.

Melatonin activates the Mst1-Nrf2 signaling to alleviate cardiac hypertrophy in pulmonary arterial hypertension.

Among pulmonary arterial hypertension (PAH) patients, right ventricular (RV) functioning has been considered a major determining factor for cardiac capacity and survival. However, despite the recognition of the clinical importance for preserving RV functioning, no effective treatments are currently available for RV failure. This study aims to suggest one such possible treatment, through investigating the cardio-protective capabilities of the anti-oxidant, melatonin (Mel), for treating adverse RV remodeling in PAH, along with its underlying mechanisms. Arginine vasopressin induced neonatal rat cardiomyocyte hypertrophy in vitro; in vivo, PAH was induced in rats through intraperitoneal monocrotaline (MCT) injections, and Mel was administered intraperitoneally 24 h prior to MCT. Mel reduced rat cardiomyocyte hypertrophy and mitochondrial oxidative stress in vitro by activating the Mst1-Nrf2 pathway, which were all reversed upon siRNA knockdown of Mst1. Likewise, in vivo, Mel pre-treatment significantly ameliorated MCT-induced deterioration in cardiac function, RV hypertrophy, fibrosis and dilation. These beneficial effects were also associated with Mst1-Nrf2 pathway up regulation and its associated reduction in oxidative stress, as evidenced by the decrease in RV malondialdehyde content. Notably, results from Mel treatment were similar, or even superior, to those obtained from N-acetyl cysteine (NAC), which has already been-confirmed as an anti-oxidative treatment for PAH. By contrast, co-treatment with the Mst1 inhibitor XMU-MP-1 reversed all of those Mel-associated beneficial effects. Our findings thus identified Mel as a potent cardio-protective agent against the onset of maladaptive RV remodeling, through enhancement of the anti-oxidative response via Mst1-Nrf2 pathway activation.

Left atrial strain predicts risk and prognosis in patients with acute coronary syndrome: A retrospective study with external validation.

Objectives: To explore the association between left atrial (LA) strain and the GRACE score in patients with acute coronary syndrome (ACS) and to investigate the utility of LA function in predicting short-term adverse cardiovascular events post ACS. Methods: This retrospective study included ACS patients who underwent coronary angiography (CAG) in two independent cohorts from October 2020 to July 2022. The patients were classified into low-intermediate risk group and high-risk group based on the GRACE score. All participants underwent a transthoracic echocardiogram, with LA strain analysis before CAG. Correlation analysis was used to determine the relationship between LA strain and the GRACE score. The predictive value of LA strain was examined utilizing the area under the curve (AUC). Participants were followed for 10.5 ± 2.9 months for the primary endpoint of major adverse cardiovascular events (MACE). Results: A total of 229 patients were included in this study, including 196 in the primary group and 33 in the validation group. Spearman's correlation analysis showed there was a moderate negative correlation between the GRACE and left atrial reservoir strain (LASr) in both the primary (r = -0.63, P < 0.001) and validation (r = -0.73, P < 0.001) cohorts. Receiver operator characteristic (ROC) curve analysis showed that the AUC of LASr for prediction of the high-risk group was 0.86. Taking LASr 19.6% as the cut-off value, the sensitivity and specificity were 0.71 and 0.92, respectively. The cut-off value of 19.6% remains good at identifying high-risk group in the validation group (AUC = 0.87, sensitivity: 77.8%, specificity: 95.8%). Furthermore, 49 patients reached the endpoint in the primary cohort during the follow-up. On multivariable regression analysis, LASr (P = 0.03) was the independent echocardiographic predictor for the primary endpoint, rather than left atrial volume index (LAVI). Conclusions: LASr can identify high-risk patients with ACS as defined by the GRACE score and may be superior to Max LAVI in predicting incidents of MACE in the short-term following ACS.

Automatic myocardial infarction detection in contrast echocardiography based on polar residual network.

PURPOSE: Heart disease is one of the leading causes of death. Among patients with cardiovascular diseases, myocardial infarction (MI) is the main reason. Precise and timely identification of MI is significant for early treatment. Myocardial contrast echocardiography (MCE) is widely used for the detection of MI in clinic practice. However, existing clinical exam using MCE is subjective and highly operator dependent and time-consuming. Hence an automatic computer-aided MI detection in MCE is necessary to improve the diagnosis performance and decrease the workload of clinicians. METHODS: In this study, a novel deep learning model, polar residual network (PResNet) is proposed to identify MI regions in MCE images which design a polar layer considering the ring shape of the myocardium. MCE images are fed into the PResNet and a newly defined polar layer is used to describe the myocardium with a ring shape. The whole polar images are evenly divided into several subsections and a residual network is improved to classify the subsection into normal and abnormal categories. Finally, the detection results are mapped back to the original image to illustrate the infarction regions' locations for the further process. RESULTS: To evaluate the proposed PResNet, a dataset is constructed via performing MCE on five mice, which underwent the left anterior descending artery ligation and receive erythropoietin or saline injection, and the area variation fraction is manually annotated by an experienced expert as golden standards. The results demonstrate that the proposed PResNet model accomplishes high classification precisions with 99.6% and 98.7%, and 0.999 and 0.996 of AUC (area under the receiver operator curve) values on two different testing sets, respectively. Results suggest that the proposed model could enable accurate infarct detection and diagnosis of the MCE images. CONCLUSION: Those efficiency gains highlight the powerful ability to describe and interpret the MCE images using the polar layer and residual network. The proposed PResNet might aid the clinicians in fast and accurate assessing the infarcted myocardium on MCE.