Prolonged cord separation in a newborn: a rare case of an unusual epithelialised umbilical cord.

A female full-term neonate, accompanied by her parents, was referred to the paediatric surgery department on the day of after birth. She presented with a 9 cm length pathological umbilical cord, of which the first 7 cm was red and wet, with ulceration, necrosis and healing areas. The patient never had a fever. Abdominal palpation showed no umbilical hernia and abdominal Doppler ultrasound was normal. After several days of disinfection, by biseptine antiseptic solution, and a monthly follow-up, most of the umbilical cord fell out. It only remained a 4 cm length navel consisting of 2 cm of excessive skin and 2 cm of mucous tissue. The lesion was surgically excised at 6 months old. The patient was discharged on postoperative day 1. The results of the histology confirmed the diagnosis of an epithelialised umbilical cord. The 1-month follow-up was uneventful.

Initial experience of the treatment of large glioma with microwave ablation-assisted surgical resection.

Aim: This study aimed to investigate the preliminary clinical outcomes of microwave ablation (MWA)-assisted surgical treatment for large glioma. Materials and Methods: In total, six cases of large glioma (diameter >4 cm) were described. All cases were treated with MWA-assisted surgical resection, which was performed using ultrasound to guide the accurate placement of the antenna in the central region of the tumor. The MWA power was 40-45 W, and 6 min was applied. Changes in the ablation area were observed using intraoperative Doppler ultrasound and contrast-enhanced ultrasound (CEUS). Ten patients treated with surgical resection alone were included in the control group. Data on surgical times (i.e., the time from the incision of the dura to the removal of the tumor), intraoperative blood loss, and complications were recorded. Results: The median patient age was 45 years (range: 36.5-60.3 years). The median lesion diameter was 4.9 cm (range: 4.3-5.8). The microwave power was 40-45 W, and the median ablation time was 240 s (range: 208-297 s). The intra-tumoral vascular flow was significantly reduced after MWA. The median surgical time was shorter (38.5 min [range: 34.3-42.8 min]) and the median intraoperative blood loss was less (400 mL, [range: 400-450 mL]) in the combination treatment group than in the surgery-alone group. During the ablation process, no obvious additional neurological deficits were detected; however, a tube-shaped carbonide was found after the operation. Conclusion: MWA may be a useful complement to conventional techniques for the surgical resection of large glioma.

Deep learning and ultrasound feature fusion model predicts the malignancy of complex cystic and solid breast nodules with color Doppler images.

This study aimed to evaluate the performance of traditional-deep learning combination model based on Doppler ultrasound for diagnosing malignant complex cystic and solid breast nodules. A conventional statistical prediction model based on the ultrasound features and basic clinical information was established. A deep learning prediction model was used to train the training group images and derive the deep learning prediction model. The two models were validated, and their accuracy rates were compared using the data and images of the test group, respectively. A logistic regression method was used to combine the two models to derive a combination diagnostic model and validate it in the test group. The diagnostic performance of each model was represented by the receiver operating characteristic curve and the area under the curve. In the test cohort, the diagnostic efficacy of the deep learning model was better than traditional statistical model, and the combined diagnostic model was better and outperformed the other two models (combination model vs traditional statistical model: AUC: 0.95 > 0.70, P = 0.001; combination model vs deep learning model: AUC: 0.95 > 0.87, P = 0.04). A combination model based on deep learning and ultrasound features has good diagnostic value.

Skeletal muscle derived Musclin protects the heart during pathological overload.

Cachexia is associated with poor prognosis in chronic heart failure patients, but the underlying mechanisms of cachexia triggered disease progression remain poorly understood. Here, we investigate whether the dysregulation of myokine expression from wasting skeletal muscle exaggerates heart failure. RNA sequencing from wasting skeletal muscles of mice with heart failure reveals a reduced expression of Ostn, which encodes the secreted myokine Musclin, previously implicated in the enhancement of natriuretic peptide signaling. By generating skeletal muscle specific Ostn knock-out and overexpressing mice, we demonstrate that reduced skeletal muscle Musclin levels exaggerate, while its overexpression in muscle attenuates cardiac dysfunction and myocardial fibrosis during pressure overload. Mechanistically, Musclin enhances the abundance of C-type natriuretic peptide (CNP), thereby promoting cardiomyocyte contractility through protein kinase A and inhibiting fibroblast activation through protein kinase G signaling. Because we also find reduced OSTN expression in skeletal muscle of heart failure patients, augmentation of Musclin might serve as therapeutic strategy.

Aumento do trabalho miocárdico desperdiçado como indicador de lesão coronariana significativa / Increased wasted myocardial work as an indicator of significant coronary lesion

Introdução: A avaliação dos índices de trabalho miocárdico global em condições basais pode ser útil para a estratificação clínica de pacientes com suspeita de obstrução coronariana. Objetivo: Correlacionar o valor do índice de trabalho miocárdico global e a presença de lesões obstrutivas coronarianas significativas. Método: Estudo transversal, com pacientes encaminhados para cinecoronarioangiografia eletiva. Foi realizado ecocardiograma com obtenção das medidas para cálculo do valor do trabalho miocárdico, sendo avaliada a presença de lesões obstrutivas coronarianas significativas à cinecoronarioangiografia. Resultados: A amostra foi composta de 30 pacientes, com a idade média de 64,2±12,8 anos, sendo a maioria do sexo masculino (63,3%), dos quais 68,4% apresentaram lesões obstrutivas coronarianas significativas. O índice de trabalho miocárdico global foi de 1.876mmHg%±253,8 no grupo com lesões obstrutivas coronarianas significativas e de 2.054,2mmHg%±417,3 naqueles sem lesões significativas (p=0,089). O trabalho miocárdio construtivo global nos pacientes sem lesões obstrutivas coronarianas significativas foi maior (2.329,3mmHg%±462,9) do que naqueles com lesões obstrutivas coronarianas significativas (2.109,5mmHg%±332,3; p=0,064). O trabalho miocárdio desperdiçado global foi maior nos pacientes com lesões obstrutivas coronarianas significativas (103,7mmHg%±47,1 versus 68,3mmHg%±33,8; p=0,038). O ponto de corte de 115mmHg% foi aquele com a melhor área sob a curva (0,625), com sensibilidade de 83,3%. Conclusão: O aumento do trabalho miocárdio desperdiçado global se correlacionou com a presença de lesões obstrutivas coronarianas significativas em nossa amostra.(AU)

Introduction: The assessment of global myocardial work indices under baseline conditions may be useful for the clinical stratification of patients with suspected coronary obstruction. Objective: To correlate the value of global myocardial work indices and the presence of significant obstructive coronary lesions. Method: Cross-sectional study, with patients referred for elective coronary angiography. An echocardiogram was performed to obtain measurements to calculate the value of myocardial work and evaluated the presence or presence of significant obstructive coronary lesions at coronary angiography. Results: The sample consisted of 30 patients, with a mean age of 64.2±12.8 years, the majority being male (63.3%), of which 68.4% had significant obstructive coronary lesions. The global myocardial work indices was 1,876mmHg%±253.8 in the group with significant obstructive coronary lesions and 2,054.2mmHg%±417.3 in those without significant lesions (p=0.089). Global constructive myocardial work in patients without significant obstructive coronary lesions was higher (2,329.3mmHg%±462.9) than in those with significant obstructive coronary lesions (2,109.5mmHg%±332.3; p=0.064). Global wasted myocardial work was higher in patients with significant obstructive coronary lesions (103.7mmHg%±47.1 versus 68.3mmHg%±33.8; p=0.038). The cutoff point of 115 mmHg% was the one with the best area under the curve (0.625), with a sensitivity of 83.3%. Conclusion: The increase in global wasted myocardial work correlated with the presence of significant obstructive coronary lesions in our sample. (AU)

Energetic Basis for Exercise-Induced Pulmonary Congestion in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Transient pulmonary congestion during exercise is emerging as an important determinant of reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF). We sought to determine whether an abnormal cardiac energetic state underpins this process. METHODS: We recruited patients across the spectrum of diastolic dysfunction and HFpEF (controls, n=11; type 2 diabetes, n=9; HFpEF, n=14; and severe diastolic dysfunction attributable to cardiac amyloidosis, n=9). Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to ATP ratio. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging and echocardiography and lung water using magnetic resonance proton density mapping. Studies were performed at rest and during submaximal exercise using a magnetic resonance imaging ergometer. RESULTS: Paralleling the stepwise decline in diastolic function across the groups (E/e' ratio; P<0.001) was an increase in NT-proBNP (N-terminal pro-brain natriuretic peptide; P<0.001) and a reduction in phosphocreatine/ATP ratio (control, 2.15 [2.09, 2.29]; type 2 diabetes, 1.71 [1.61, 1.91]; HFpEF, 1.66 [1.44, 1.89]; cardiac amyloidosis, 1.30 [1.16, 1.53]; P<0.001). During 20-W exercise, lower left ventricular diastolic filling rates (r=0.58; P<0.001), lower left ventricular diastolic reserve (r=0.55; P<0.001), left atrial dilatation (r=-0.52; P<0.001), lower right ventricular contractile reserve (right ventricular ejection fraction change, r=0.57; P<0.001), and right atrial dilation (r=-0.71; P<0.001) were all linked to lower phosphocreatine/ATP ratio. Along with these changes, pulmonary proton density mapping revealed transient pulmonary congestion in patients with HFpEF (+4.4% [0.5, 6.4]; P=0.002) and cardiac amyloidosis (+6.4% [3.3, 10.0]; P=0.004), which was not seen in healthy controls (-0.1% [-1.9, 2.1]; P=0.89) or type 2 diabetes without HFpEF (+0.8% [-1.7, 1.9]; P=0.82). The development of exercise-induced pulmonary congestion was associated with lower phosphocreatine/ATP ratio (r=-0.43; P=0.004). CONCLUSIONS: A gradient of myocardial energetic deficit exists across the spectrum of HFpEF. Even at low workload, this energetic deficit is related to markedly abnormal exercise responses in all 4 cardiac chambers, which is associated with detectable pulmonary congestion. The findings support an energetic basis for transient pulmonary congestion in HFpEF.

Protective Mechanism of Trimetazidine in Myocardial Cells in Myocardial Infarction Rats through ERK Signaling Pathway.

OBJECTIVE: To study the protective effect of trimetazidine on myocardial cells in rats with myocardial infarction and explore its effect on ERK signaling pathway. METHODS: 40 SD rats were randomly divided into the sham operation group, model group, low-dose group, and high-dose group (intra-abdominal injection of trimetazidine 5 mg/kg and 10 mg/kg, respectively), construction of rat myocardial infarction model by coronary artery left anterior descending artery ligation. 7 days after surgery, the survival rate and cardiac function of each group of rats were recorded. The myocardial infarct size was detected by TTC staining. The apoptosis level of rat cardiomyocytes was detected by TUNEL staining. The content of ROS in rat cardiomyocytes was detected by DCFH-DA. Western-blot was used to detection of Caspase-3, Bcl-2/Bax, and ERK signaling pathway-related proteins in myocardial tissue. RESULTS: Compared with the model group, the survival rate of the rats in the low-dose group and the high-dose group was significantly increased (P < 0.01), the cardiac function was significantly improved (P < 0.01), the myocardial infarct size was significantly decreased (P < 0.01), the level of apoptosis was significantly decreased (P < 0.01), the content of ROS in cardiomyocytes was significantly decreased (P < 0.01), the protein expression of Caspase-3 and NF-κB in cardiomyocytes was significantly decreased (P < 0.01), and the expression of Bcl-2/Bax and p-ERK were significantly increased (P < 0.01). CONCLUSION: Trimetazidine can activate ERK signaling pathway in cardiomyocytes of rats with myocardial infarction, increase the expression of p-ERK, decrease the content of ROS in cardiomyocytes, decrease the expression of apoptotic proteins, reduce myocardial infarct size, improve cardiac function, and increase myocardial function.

Loss of Mitochondrial Ca2+ Uniporter Limits Inotropic Reserve and Provides Trigger and Substrate for Arrhythmias in Barth Syndrome Cardiomyopathy.

BACKGROUND: Barth syndrome (BTHS) is caused by mutations of the gene encoding tafazzin, which catalyzes maturation of mitochondrial cardiolipin and often manifests with systolic dysfunction during early infancy. Beyond the first months of life, BTHS cardiomyopathy typically transitions to a phenotype of diastolic dysfunction with preserved ejection fraction, blunted contractile reserve during exercise, and arrhythmic vulnerability. Previous studies traced BTHS cardiomyopathy to mitochondrial formation of reactive oxygen species (ROS). Because mitochondrial function and ROS formation are regulated by excitation-contraction coupling, integrated analysis of mechano-energetic coupling is required to delineate the pathomechanisms of BTHS cardiomyopathy. METHODS: We analyzed cardiac function and structure in a mouse model with global knockdown of tafazzin (Taz-KD) compared with wild-type littermates. Respiratory chain assembly and function, ROS emission, and Ca2+ uptake were determined in isolated mitochondria. Excitation-contraction coupling was integrated with mitochondrial redox state, ROS, and Ca2+ uptake in isolated, unloaded or preloaded cardiac myocytes, and cardiac hemodynamics analyzed in vivo. RESULTS: Taz-KD mice develop heart failure with preserved ejection fraction (>50%) and age-dependent progression of diastolic dysfunction in the absence of fibrosis. Increased myofilament Ca2+ affinity and slowed cross-bridge cycling caused diastolic dysfunction, in part, compensated by accelerated diastolic Ca2+ decay through preactivated sarcoplasmic reticulum Ca2+-ATPase. Taz deficiency provoked heart-specific loss of mitochondrial Ca2+ uniporter protein that prevented Ca2+-induced activation of the Krebs cycle during ß-adrenergic stimulation, oxidizing pyridine nucleotides and triggering arrhythmias in cardiac myocytes. In vivo, Taz-KD mice displayed prolonged QRS duration as a substrate for arrhythmias, and a lack of inotropic response to ß-adrenergic stimulation. Cellular arrhythmias and QRS prolongation, but not the defective inotropic reserve, were restored by inhibiting Ca2+ export through the mitochondrial Na+/Ca2+ exchanger. All alterations occurred in the absence of excess mitochondrial ROS in vitro or in vivo. CONCLUSIONS: Downregulation of mitochondrial Ca2+ uniporter, increased myofilament Ca2+ affinity, and preactivated sarcoplasmic reticulum Ca2+-ATPase provoke mechano-energetic uncoupling that explains diastolic dysfunction and the lack of inotropic reserve in BTHS cardiomyopathy. Furthermore, defective mitochondrial Ca2+ uptake provides a trigger and a substrate for ventricular arrhythmias. These insights can guide the ongoing search for a cure of this orphaned disease.

Downregulation of p300/CBP-associated factor inhibits cardiomyocyte apoptosis via suppression of NF-κB pathway in ischaemia/reperfusion injury rats.

Cardiomyocyte apoptosis is the main reason of cardiac injury after myocardial ischaemia-reperfusion (I/R) injury (MIRI), but the role of p300/CBP-associated factor (PCAF) on myocardial apoptosis in MIRI is unknown. The aim of this study was to investigate the main mechanism of PCAF modulating cardiomyocyte apoptosis in MIRI. The MIRI model was constructed by ligation of the rat left anterior descending coronary vessel for 30 min and reperfusion for 24 h in vivo. H9c2 cells were harvested after induced by hypoxia for 6 h and then reoxygenation for 24 h (H/R) in vitro. The RNA interference PCAF expression adenovirus was transfected into rat myocardium and H9c2 cells. The area of myocardial infarction, cardiac function, myocardial injury marker levels, apoptosis, inflammation and oxidative stress were detected respectively. Both I/R and H/R remarkably upregulated the expression of PCAF, and downregulation of PCAF significantly attenuated myocardial apoptosis, inflammation and oxidative stress caused by I/R and H/R. In addition, downregulation of PCAF inhibited the activation of NF-κB signalling pathway in cardiomyocytes undergoing H/R. Pretreatment of lipopolysaccharide, a NF-κB pathway activator, could blunt these protective effects of PCAF downregulation on myocardial apoptosis in MIRI. These results highlight that downregulation of PCAF could reduce cardiomyocyte apoptosis by inhibiting the NF-κB pathway, thereby providing protection for MIRI. Therefore, PCAF might be a promising target for protecting against cardiac dysfunction induced by MIRI.

Interrogating the haemodynamic effects of haemodialysis arteriovenous fistula on cardiac structure and function.

Arteriovenous fistula (AVF) is the preferred type of vascular access for maintenance haemodialysis but it may contribute to maladaptive cardiovascular remodelling. We studied the effect of AVF creation on cardiac structure and function in patients with chronic kidney disease (CKD). In this prospective cohort study patients with CKD listed for first AVF creation underwent cardiac magnetic resonance (CMR) imaging at baseline and at 6 weeks. All participants had ultrasound measurements of fistula blood flow at 6 weeks. The primary outcome was the change in left ventricular (LV) mass. Secondary outcomes included changes in LV volumes, LV ejection fraction, cardiac output, LV global longitudinal strain and N-terminal-pro B-type natriuretic peptide (NT-proBNP). A total of 55 participants were enrolled, of whom 40 (mean age 59 years) had AVF creation and completed both scans. On the second CMR scan, a mean increase of 7.4 g (95% CI 1.1-13.7, p = 0.02) was observed in LV mass. Significant increases in LV end-diastolic volumes (p = 0.04) and cardiac output (p = 0.02) were also seen after AVF creation. No significant changes were observed in LV end-systolic volumes, LV ejection fraction, NT-proBNP and LV global longitudinal strain. In participants with fistula blood flows ≥ 600 mL/min (n = 22) the mean increase in LV mass was 15.5 g (95% CI 7.3-23.8) compared with a small decrease of 2.5 g (95% CI - 10.6 to 5.6) in participants with blood flows < 600 mL/min (n = 18). Creation of AVF for haemodialysis resulted in a significant increase of LV myocardial mass within weeks after surgery, which was proportional to the fistula flow.

Interleukin-7 aggravates myocardial ischaemia/reperfusion injury by regulating macrophage infiltration and polarization.

Interleukin (IL)-7 is known to enhance the macrophages cytotoxic activity and that macrophages play a pivotal role in the development and progression of myocardial ischaemia/reperfusion (I/R) injury. However, the effects of IL-7 on macrophages infiltration and polarization in myocardial I/R injury are currently unclear. This study aimed to evaluate the effects of the IL-7 expression on myocardial I/R injury and their relationship with macrophages. The data showed that IL-7 expression in mouse heart tissue increases following I/R injury and that IL-7 knockout or anti-IL-7 antibody treatment significantly improve I/R injury, including reduction in myocardial infarction area, a serum troponin T level decreases and an improvement in cardiac function. On the other hand, recombinant IL-7 (rIL-7) supplementation induces opposite effects and the anti-IL-7 antibody significantly reduces the cardiomyocyte apoptosis and macrophage infiltration. rIL-7 cannot directly cause apoptosis, but it can induce cardiomyocyte apoptosis through macrophages, in addition to increase the macrophages migration in vitro. Anti-IL-7 antibody affects the cytokine production in T helper (Th) 1 and Th2 cells and also promotes the macrophages differentiation to M2 macrophages. However, anti-IL-7 antibody does not reduce the M1 macrophage number, and it only increases the ratio of M2/M1 macrophages in mice heart tissues after I/R injury. Taking together, these data reveal that IL-7 plays an intensifying role in myocardial I/R injury by promoting cardiomyocyte apoptosis through the regulation of macrophage infiltration and polarization.

Cardiopulmonary function findings of pediatric patients with patent ductus arteriosus.

ABSTRACT: Transcatheter occlusion and surgical ligation are the treatments of choice for most patent ductus arteriosus (PDA) in children. Fifty-five children who had PDA completed a pulmonary function test and a symptom-limited treadmill exercise test from 2016 to 2018 at 1 medical center in southern Taiwan. The study group was divided into surgical ligation and catheterization groups, which were compared to a healthy control group matched for age, sex, and body mass index. Data about the performance on the exercise test, including metabolic equivalent at anaerobic threshold and peak, were analyzed. No differences in the pulmonary function and ventilatory parameters were observed between the surgery, catheterization, and control groups. Heart rate at peak and at anaerobic threshold significantly differed in the investigated groups. The post hoc analysis showed that the surgery group had a lower heart rate at peak and threshold compared to the catheterization and control groups (P = .02, P < .001, respectively). No significant difference was found between the catheterization group and the control group. A larger and younger group of patients were recruited, allowing for newer data about the cardiopulmonary function to be obtained. The findings suggest that patients with PDA could undergo physical training after intervention. The imposition of restrictions to limit sports activities should be avoided.

Markers of Myocardial Damage Predict Mortality in Patients With Aortic Stenosis.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined. OBJECTIVES: Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality. METHODS: Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years' follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome. RESULTS: There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m2) and small (LVEDVi ≤55 mL/m2) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort. CONCLUSIONS: Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR.

Doxorubicin induces wide-spread transcriptional changes in the myocardium of hearts distinguishing between mice with preserved and impaired cardiac function.

AIMS: Doxorubicin (DOX) is an important drug for the treatment of various tumor entities. However, the occurrence of heart failure limits its application. This study investigated differential gene expression profiles in the left and right ventricles of DOX treated mice with either preserved or impaired myocardial function. We provide new mechanistic insights into the pathophysiology of DOX-induced heart failure and have discovered pathways that counteract DOX-induced cardiotoxicity. MAIN METHODS: We used in total 48 male mice and applied a chronic low dose DOX administration (5 mg/kg per injection, in total 20 mg/kg over 4 weeks) to induce heart failure. Echocardiographic parameters were evaluated one week after the final dose and mice were separated according to functional parameters into doxorubicin responding and non-responding animals. Post mortem, measurements of reactive oxygen species (ROS) and gene expression profiling was performed in separated right and left hearts. KEY FINDINGS: We detected significant ROS production in the left heart of the mice in response to DOX treatment, although interestingly, not in the right heart. We found that transcriptional changes differ between right and left heart correlating with the occurrence of myocardial dysfunction. SIGNIFICANCE: Doxorubicin induces changes in gene expression in the entire heart of animals without necessarily impairing cardiac function. We identified a set of transcripts that are associated with DOX cardiotoxicity. These might represent promising targets to ameliorate DOX-induced heart failure. Moreover, our results emphasize that parameters of left and right heart function should be evaluated during standardized echocardiography in patients undergoing DOX therapy.

Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis.

BACKGROUND: It is known that increased gastrin concentration is negatively correlated with cardiovascular mortality, and plasma gastrin levels are increased in patients after myocardial infarction (MI). However, whether gastrin can play a protective role in MI remains unknown. METHODS: Adult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery (LAD) and subcutaneous infusion of gastrin (120 µg/Kg body weight/day, 100 µL in the pump) for 28 days after MI. Plasma gastrin concentrations were measured through an ELISA detection kit. Mice were analyzed by echocardiography after surgery. CD31 and VEGF expression were quantified using immunofluorescence staining or/and western blot to assess the angiogenesis in peri-infarct myocardium. Capillary-like tube formation and cell migration assays were performed to detect gastrin-induced angiogenesis. RESULTS: We found that gastrin administration significantly ameliorated MI-induced cardiac dysfunction and reduced fibrosis at 28 days in post-MI hearts. Additionally, gastrin treatment significantly decreased cardiomyocyte apoptosis and increased angiogenesis in the infarct border zone without influencing cardiomyocyte proliferation. In vitro results revealed that gastrin up-regulated the PI3K/Akt/vascular endothelial growth factor (VEGF) signaling pathway and promoted migration and tube formation of human coronary artery endothelial cells (HCAECs). Cholecystokinin 2 receptor (CCK2R) mediated the protective effect of gastrin since the CCK2R blocker CI988 attenuated the gastrin-mediated angiogenesis and cardiac function protection. CONCLUSION: Our data revealed that gastrin promoted angiogenesis and improved cardiac function in post-MI mice, highlighting its potential as a therapeutic target candidate.

A detection system of exercise electrocardiogram / Um sistema de detecção de eletrocardiograma de exercício / Un sistema de detección de electrocardiograma de ejercicio

ABSTRACT Introduction: A new exercise electrocardiogram (ECG) detection system was investigated in this study to diagnose and analyze cardiopulmonary function and related diseases in a comprehensive and timely manner and improve the accuracy of diagnosis. Besides, its reliability and clinical applicability were judged. Objective: A new type of exercise ECG detection system was constructed by adding parameters such as respiratory mechanics, carbon dioxide, and oxygen concentration monitoring based on the traditional ECG detection system. Methods: The new system constructed in this study carried out the ECG signal detection, ECG acquisition module, blood pressure and respiratory mechanics detection and conducted a standard conformance test. Results: The heart rate accuracy detected by the exercise ECG system was greatly higher than that of the doctor's manual detection (P < 0.05). The accuracy of the new exercise ECG detection system increased obviously in contrast to that of the manual detection result (P < 0.05). The key technical index input noise and input impedance test results (24.5 μV and 12.4 MΩ) of the exercise ECG detection system conformed to the standard (< 30 μV and > 2.5 MΩ). The common-mode rejection and sampling rate test results (103.5 dB and 515 Hz) of key technical indicators in the exercise ECG detection system were all in line with the standards (≥89 dB and ≥500 Hz). Conclusion: The complete exercise ECG detection system was constructed through the ECG acquisition module, blood pressure detection, and respiratory mechanics detection module. In addition, this system could be applied to detect ECG monitoring indicators with high accuracy and reliability, which could also be extensively adopted in clinical diagnosis. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: Um novo sistema de detecção de eletrocardiograma de exercício (ECG) foi investigado neste estudo para diagnosticar e analisar a função cardiopulmonar e doenças relacionadas de maneira abrangente e oportuna e melhorar a precisão do diagnóstico. Além disso, sua confiabilidade e aplicabilidade clínica foram julgadas. Objetivo: Um novo tipo de sistema de detecção de ECG de esforço foi construído adicionando parâmetros como mecânica respiratória, dióxido de carbono e monitoramento da concentração de oxigênio com base no sistema de detecção de ECG tradicional. Métodos: O novo sistema construído neste estudo realizou a detecção do sinal de ECG, módulo de aquisição de ECG e detecção de pressão arterial e mecânica respiratória, e conduziu um teste de conformidade padrão. Resultados: A precisão da frequência cardíaca detectada pelo sistema de ECG de esforço foi muito maior do que a detecção manual do médico (P <0,05). A precisão do novo sistema de detecção de ECG de esforço aumentou obviamente em contraste com o resultado da detecção manual (P <0,05). O ruído de entrada do índice técnico principal e os resultados do teste de impedância de entrada (24,5 μV e 12,4 MΩ) do sistema de detecção de ECG de esforço estão em conformidade com o padrão (<30 μV e> 2,5 MΩ). A rejeição do modo comum e os resultados do teste de taxa de amostragem (103,5 dB e 515 Hz) dos indicadores técnicos principais no sistema de detecção de ECG de esforço estavam todos alinhados com os padrões (≥89 dB e ≥500 Hz). Conclusão: O sistema completo de detecção de ECG de esforço foi construído através da combinação de módulo de aquisição de ECG, detecção de pressão arterial e módulo de detecção de mecânica respiratória. Além disso, esse sistema poderia ser aplicado à detecção de indicadores de monitoramento de ECG com alta precisão e confiabilidade, o que poderia ser amplamente adotado no diagnóstico clínico. Nível de evidência II; Estudos terapêuticos- investigação dos resultados do tratamento.

RESUMEN Introducción: En este estudio se investigó un nuevo sistema de detección de electrocardiograma de esfuerzo (ECG) para diagnosticar y analizar la función cardiopulmonar y enfermedades relacionadas de manera integral y oportuna, y mejorar la precisión del diagnóstico. Además, se evaluó su confiabilidad y aplicabilidad clínica. Objetivo: Se construyó un nuevo tipo de sistema de detección de ECG de ejercicio agregando parámetros como la mecánica respiratoria, el dióxido de carbono y el monitoreo de la concentración de oxígeno sobre la base del sistema de detección de ECG tradicional. Métodos: El nuevo sistema construido en este estudio llevó a cabo la detección de la señal de ECG, el módulo de adquisición de ECG y la detección de la presión arterial y la mecánica respiratoria, y realizó una prueba de conformidad estándar. Resultados: la precisión de la frecuencia cardíaca detectada por el sistema de ECG de ejercicio fue mucho mayor que la de la detección manual del médico (P <0,05). La precisión del nuevo sistema de detección de ECG de esfuerzo aumentó obviamente en contraste con el resultado de la detección manual (P <0.05). Los resultados de la prueba de impedancia de entrada y ruido de entrada de índice técnico clave (24,5 μV y 12,4 MΩ) del sistema de detección de ECG de esfuerzo cumplieron con el estándar (<30 μV y> 2,5 MΩ). Los resultados de la prueba de frecuencia de muestreo y rechazo en modo común (103,5 dB y 515 Hz) de los indicadores técnicos clave en el sistema de detección de ECG de esfuerzo estaban en línea con los estándares (≥89 dB y ≥500 Hz). Conclusión: El sistema completo de detección de ECG de ejercicio se construyó mediante la combinación del módulo de adquisición de ECG, la detección de la presión arterial y el módulo de detección de la mecánica respiratoria. Además, este sistema podría aplicarse a la detección de indicadores de monitoreo de ECG con alta precisión y confiabilidad, que también podría adoptarse ampliamente en el diagnóstico clínico. Nivel de evidencia II; Estudios terapéuticos- investigación de los resultados del tratamiento.

MiR-125b inhibits cardiomyocyte apoptosis by targeting BAK1 in heart failure.

BACKGROUND: Although miR-125b plays a crucial role in many human cancers. However, its function in heart failure (HF) remains unclear. Our study aimed to investigate its involvement in heart failure. METHODS: In this study, the mouse HF model was successfully constructed through transverse aortic constriction (TAC) operation. Changes in mRNA and protein levels in isolated myocytes and heart tissues were examined using qRT-PCR, Western blot and Immunohistochemical staining and immunofluorescent staining. Changes in cardiac functions were examined using ultrasound. Interactions between miR-125b and BAK1 was analyzed using the luciferase reporter assay. Cardiomyocyte apoptosis was evaluated using the TUNEL staining. RESULTS: We found that miR-125b expression was significantly downregulated in myocardial tissues of HF mice. Moreover, miR-125b upregulation in HF mice injected with agomir-125b efficiently ameliorated cardiac function. Further, miR-125b upregulation significantly decreased the protein levels of apoptosis-related makers c-caspase 3 and Bax, while increased Bcl-2 expression. In addition, BAK1 was identified as a direct target of miR-125b. As expected, BAK1 overexpression observably reversed the effect of agomir-125b on cardiac function and on the expression of apoptosis-related makers in the heart tissues of HF mice. CONCLUSIONS: Taken together, miR-125b overexpression efficiently attenuated cardiac function injury of HF mice by targeting BAK1 through inhibiting cardiomyocyte apoptosis, suggesting that miR-125b/BAK1 axis might be a potential target for the diagnosis or treatment of HF.

Cardiac and skeletal muscle predictors of impaired cardiorespiratory fitness post-anthracycline chemotherapy for breast cancer.

This study aimed to characterize peak exercise cardiac function and thigh muscle fatty infiltration and their relationships with VO2peak among anthracycline-treated breast cancer survivors (BCS). BCS who received anthracycline chemotherapy ~ 1 year earlier (n = 16) and matched controls (matched-CON, n = 16) were enrolled. Resting and peak exercise cardiac function, myocardial T1 mapping (marker of fibrosis), and thigh muscle fat infiltration were assessed by magnetic resonance imaging, and VO2peak by cycle test. Compared to matched-CON, BCS had lower peak SV (64 ± 9 vs 57 ± 10 mL/m2, p = 0.038), GLS (- 30.4 ± 2.2 vs - 28.0 ± 2.5%, p = 0.008), and arteriovenous oxygen difference (16.4 ± 3.6 vs 15.2 ± 3.9 mL/100 mL, p = 0.054). Mediation analysis showed: (1) greater myocardial T1 time (fibrosis) is inversely related to cardiac output and end-systolic volume exercise reserve; (2) greater thigh muscle fatty infiltration is inversely related to arteriovenous oxygen difference; both of which negatively influence VO2peak. Peak SV (R2 = 65%) and thigh muscle fat fraction (R2 = 68%) were similarly strong independent predictors of VO2peak in BCS and matched-CON combined. Post-anthracyclines, myocardial fibrosis is associated with impaired cardiac reserve, and thigh muscle fatty infiltration is associated with impaired oxygen extraction, which both contribute to VO2peak.