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Objective. Significant aortic regurgitation is a common complication following left ventricular assist device (LVAD) intervention, and existing studies have not attempted to monitor regurgitation signals and undertake preventive measures during full support. Regurgitation is an adverse event that can lead to inadequate left ventricular unloading, insufficient peripheral perfusion, and repeated episodes of heart failure. Moreover, regurgitation occurring during full support due to pump position offset cannot be directly controlled through control algorithms. Therefore, accurate estimation of regurgitation during percutaneous left ventricular assist device (PLVAD) full support is critical for clinical management and patient safety. Approach. An estimation system based on the regurgitation model is built in this paper, and the unscented Kalman filter estimator (UKF) is introduced as an estimation approach. Three offset degrees and three heart failure states are considered in the investigation. Using the mock circulatory loop experimental platform, compare the regurgitation estimated by the UKF algorithm with the actual measured regurgitation; the errors are analyzed using standard confidence intervals of ±2 SDs, and the effectiveness of the mentioned algorithms is thus assessed. The generalization ability of the proposed algorithm is verified by setting different heart failure conditions and different rotational speeds. The root mean square error and correlation coefficient between the estimated and actual values are quantified and the statistical significance of accuracy differences in estimation is illustrated using one-way analysis of variance (One-Way ANOVA), which in turn assessed the accuracy and stability of the UKF algorithm. Main results. The research findings demonstrate that the regurgitation estimation system based on the regurgitation model and UKF can relatively accurately estimate the regurgitation status of patients during PLVAD full support, but the effect of myocardial contractility on the estimation accuracy still needs to be taken into account. Significance. The proposed estimation method in this study provides essential reference information for clinical practitioners, enabling them to promptly manage potential complications arising from regurgitation. By sensitively detecting LVAD adverse events, valuable insights into the performance and reliability of the LVAD device can be obtained, offering crucial feedback and data support for device improvement and optimization., (© 2024 Institute of Physics and Engineering in Medicine.)

As a non-invasive assisted circulation therapy, enhanced external counterpulsation (EECP) has demonstrated potential in treatment of lower-extremity arterial disease (LEAD). However, the underlying hemodynamic mechanism remains unclear. This study aimed to conduct the first prospective investigation of the EECP-induced responses of blood flow behavior and wall shear stress (WSS) metrics in the femoral artery. Twelve healthy male volunteers were enrolled. A Doppler ultrasound-basedapproach was introduced for the in vivo determination of blood flow in the common femoral artery (CFA) and superficial femoral artery (SFA) during EECP intervention, with incremental treatment pressures ranging from 10 to 40 kPa. Three-dimensional subject-specific numerical models were developed in 6 subjects to quantitatively assess variations in WSS-derived hemodynamic metrics in the femoral bifurcation. A mesh-independence analysis was performed. Our results indicated that, compared to the pre-EECP condition, both the antegrade and retrograde blood flow volumes in the CFA and SFA were significantly augmented during EECP intervention, while the heart rate remained constant. The time average shear stress (TAWSS) over the entire femoral bifurcation increased by 32.41%, 121.30%, 178.24%, and 214.81% during EECP with treatment pressures of 10 kPa, 20 kPa, 30 kPa, and 40 kPa, respectively. The mean relative resident time (RRT) decreased by 24.53%, 61.01%, 69.81%, and 77.99%, respectively. The percentage of area with low TAWSS in the femoral artery dropped to nearly zero during EECP with a treatment pressure greater than or equal to 30 kPa. We suggest that EECP is an effective and non-invasive approach for regulating blood flow and WSS in lower extremity arteries., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective. A percutaneous left ventricular assist device (PLVAD) can be used as a bridge to heart transplantation or as a temporary support for end-stage heart failure. Transvalvularly placed PLVADs may result in aortic regurgitation due to unstable pump position during fully supported operation, which may diminish the pumping effect of forward flow and predispose to complications. Therefore, accurate characterization of aortic regurgitation is essential for proper modeling of heart-pump interactions and validation of control strategies. Approach. In the present study, an improved aortic valve model was used to analyze the severity of regurgitation produced by different pump position offsets. The link between pump position offset degree and regurgitation is validated in the fixed speed mode, and the influence of pump speed on regurgitation is verified in the variable speed mode, using the mock circulatory loop (MCL) experimental platform. Main results. The greater the pump offset and the more severe the regurgitation, the more carefully the pump speed needs to be managed. To avoid over-pumping, the recommended pump speed in this study should not exceed 30 000 rpm. Significance. The modeling approach provide in this study not only makes it easier to comprehend the impact of regurgitation events on the entire interactive system during mechanical assistance, but it also aids in providing timely alerts and suitable management measures., (© 2023 Institute of Physics and Engineering in Medicine.)

To detect the expression of inflammatory factors such as interleukin-1 β (IL-1 β ), interleukin-6 (IL-6), transforming growth factor (TGF- β ), and tumor necrosis factor (TNF- α ) in the tumor tissue of ventricular septal defect (VSD) in congenital heart disease and to explore the role of inflammatory response in the formation of aneurysmal perimembranous VSD(APVSD). Children with APVSD of congenital heart disease treated by surgery were selected and divided into true aneurysmal perimembranous group (TAP group) and pseudoaneurysmal perimembranous group (PAP group) according to echocardiography and surgical findings. There were 15 children in the TAP group and 31 in the PAP group. The aneurysmal perimembranous tissue of the two groups of children was collected during the operation. IL-1 β , IL-6, TGF- β , and TNF- α were positively expressed in the aneurysmal perimembranous tissue of the two groups, and the expression levels of all inflammatory factors in the PAP group were higher than those in the TAP group, and the difference was statistically significant ( P < 0.05). The expression levels of IL-1 β , IL-6, TGF- β , and TNF- α in the aneurysmal perimembranous tissue of the two groups were negatively correlated with the width of the APVSD breach. IL-1 β , IL-6, TGF- β , and TNF- α may be involved in the occurrence and development of APVSD through inflammatory mechanism., Competing Interests: The authors declare that they have no competing interest., (Copyright © 2022 Jin Zhou et al.)

Sepsis-associated encephalopathy (SAE) is a common complication of sepsis that may seriously affect the prognosis and quality of life of patients with sepsis. Microglial activation is vital to the neuroinflammation and the pathology of SAE. In the present study, in vitro cultured BV-2 microglial cells stimulated with lipopolysaccharide (LPS) were employed as a model of microglia activation. The altered profiles of long noncoding (lnc)RNAs, circular (circ)RNAs and mRNAs in BV-2 cells after 4 h of LPS exposure were arrayed by using the Agilent competing endogenous (ce)RNA Microarray Chip. Using fold change >2 and P<0.05 as the cutoff criteria, 1,135 mRNAs and 2,488 lncRNAs were determined to be upregulated and 630 mRNAs and 744 lncRNAs to be downregulated. The number of differentially expressed circRNAs was lower, with 140 upregulated and 123 downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of DE mRNAs suggested that inflammatory responses, as well as lipid metabolism, were involved in microglial activation. Furthermore, analyses of ceRNA networks of the lncRNA-miRNA-mRNA or circRNA-miRNA-mRNA interrelations were performed. The present study revealed a multitude of novel candidate mRNAs, lncRNAs and circRNAs involved in microglial activation, which may improve the current knowledge on neuroinflammation and provide potential therapeutic targets for SAE., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Wen et al.)

Objective . Impedance cardiography (ICG) is a noninvasive and continuous method for evaluating stroke volume and cardiac output. However, the ICG measurement is easily interfered due to respiration and body movements. Taking into consideration about the spectral correlations between the simultaneously collected ICG, electrocardiogram (ECG), and acceleration signals, this paper introduces a two-step spectrum denoising method to remove motion artifacts of ICG measurements in both resting and exercising scenarios. Approach . First, the major motion artifacts of ECG and ICG are separately suppressed by the spectral subtraction with respect to acceleration signals. The obtained ECG and ICG are further decomposed into two sets of intrinsic mode functions (IMFs) through the ensemble empirical mode decomposition. We then extract the shared spectral information between the two sets of IMFs using the canonical correlation analysis in a spectral domain. Finally, the ICG signal is reconstructed using those canonical variates with largest spectral correlations with ECG IMFs. Main results . The denoising method was evaluated for 30 subjects under both resting and cycling scenarios. Experimental results show that the beat contribution factor of ICG signals increases from its original 80.1%-97.4% after removing the motion artifacts. Significance . The proposed denoising scheme effectively improves the reliability of diagnosis and analysis on cardiovascular diseases relying on ICG signals., (© 2021 Institute of Physics and Engineering in Medicine.)

Heart auscultation is a convenient tool for early diagnosis of heart diseases and is being developed to be an intelligent tool used in online medicine. Currently, there are few studies on intelligent diagnosis of pediatric murmurs due to congenital heart disease (CHD). The purpose of the study was to develop a method of intelligent diagnosis of pediatric CHD murmurs. Phonocardiogram (PCG) signals of 86 children were recorded with 24 children having normal heart sounds and 62 children having CHD murmurs. A segmentation method based on the discrete wavelet transform combined with Hadamard product was implemented to locate the first and the second heart sounds from the PCG signal. Ten features specific to CHD murmurs were extracted as the input of classifier after segmentation. Eighty-six artificial neural network classifiers were composed into a classification system to identify CHD murmurs. The accuracy, sensitivity, and specificity of diagnosis for heart murmurs were 93%, 93.5%, and 91.7%, respectively. In conclusion, a method of intelligent diagnosis of pediatric CHD murmurs is developed successfully and can be used for online screening of CHD in children., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Jiaming Wang et al.)

Background: Some patients with sepsis are found with accompanying mild hypothermia (ACMH); however, the effects of ACMH on the patients with sepsis are poorly understood., Objective: To compare the impacts of ACMH and artificial mild hypothermia (ATMH) on mortality, systemic inflammatory reactions, and organ functions in mice with sepsis., Methods: Septic mouse models were induced and divided into ACMH, un-hypothermia, keep normothermia, and ATMH groups, according to the anal temperature and the thermic intervention strategy. The mortality rate, serum levels of tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), and interleukin (IL)-4 and liver and renal functions of the mice in each group were recorded. Liver, lung, and renal tissues of the mice were stained and examined under optic microscope., Results: The mortality rate in the ACMH group was the lowest among all the sepsis groups. Increased serum levels of TNF-α, IFN-γ, and IL-4 and impairments of the liver and renal functions were found in the septic mice. The serum levels of TNF-α, IFN-γ, and IL-4 were significantly lower and the liver and renal functions of ACMH group were not impaired significantly as compared with other sepsis groups. Pathological examinations of the lung, liver, and renal tissues showed that the ACMH group were with the lowest pathological score among all the sepsis groups., Conclusion: Accompanying mild hypothermia and ATMH could both reduce mortalities in mice with sepsis, and ACMH could reduce mortality even lower, and more alleviate systemic inflammatory responses and the damages in lung, kidney, and other organs were lighter., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To investigate the impact of mild hypothermia on the lipopolysaccharide (LPS)-induced expressions of Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB) and downstream inflammatory cytokines in BV-2 microglias., Methods: BV-2 cells cultured in vitro were divided into 33 Degrees Celsius-PBS, 33 Degrees Celsius-LPS, 37 Degrees Celsius-PBS and 37 Degrees Celsius-LPS groups. Real-time quantitative PCR was performed to detect the mRNA expressions of TLR4 and NF-κB in BV-2 cells, Western blotting was performed to detect the protein expressions of TLR4 and NF-κB in BV-2 cells, and ELISA to detect the levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) in the culture medium., Results: After LPS stimulated BV-2 cells, TLR4 pathway protein exhibited the trend of increasing firstly and decreasing afterwards, while the expression of NF-κB protein in the pathway downstream continued to increase, and the release of inflammatory cytokines TNF-α and IL-1β were significantly promoted. Mild hypothermia could significantly inhibit the transcription and expressions of TLR4 and NF-κB as well as the release of inflammatory cytokines., Conclusion: The mild hypothermia could inhibit the LPS/TLR4 pathway in BV-2 cells, and depress the expressions of TNF-α and IL-1β.

Purpose: This study aimed to investigate the influence of mild hypothermia on the number of CD11b+ Gr-1+ myeloid-derived suppressor cells (MDSCs) induced by lipopolysaccharide (LPS) injection in mice with sepsis., Methods: BALB/c mice were administered LPS to establish a mouse model of sepsis. Then, these mice were randomly divided into 3 groups: the mild hypothermia plus LPS group, the normothermia plus LPS group, and the LPS group. The normal control group was injected the same amount of 0.9% sodium chloride solution. The ratio of CD11b+ Gr-1+ MDSCs in the mouse spleen and bone marrow was determined at 6, 12, 24, 48, and 72 hours after LPS injection and after injected 0.9% sodium chloride solution., Results: Compared with the control group, the number of MDSCs in the spleen in the sepsis group increased gradually, and the difference was significant at 12 hours after injection (P<.01). Moreover, the number of MDSCs was the lowest in the mild hypothermia group, and there was a significant difference than the other 2 groups at 48 hours (P<.01). The number of MDSCs in the bone marrow increased gradually, and the difference between the sepsis and control groups was significant at 24 hours (P<.01). The number of MDSCs in the mild hypothermia group was the lowest, and there was a statistically significant difference than the other 2 groups (P<.05)., Conclusion: Mild hypothermia inhibited the production and accumulation of MDSCs induced by LPS administration in septic mice., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Intrahepatic cholestasis of pregnancy (ICP) is a common disease affecting up to 5% of pregnancies and which can cause fetal arrhythmia and sudden intrauterine death. We previously demonstrated that bile acid taurocholate (TC), which is raised in the bloodstream of ICP, can acutely alter the rate and rhythm of contraction and induce abnormal calcium destabilization in cultured neonatal rat cardiomyocytes (NRCM). Apart from their hepatic functions bile acids are ubiquitous signalling molecules with diverse systemic effects mediated by either the nuclear receptor FXR or by a recently discovered G-protein coupled receptor TGR5. We aim to investigate the mechanism of bile-acid induced arrhythmogenic effects in an in-vitro model of the fetal heart., Methods and Results: Levels of bile acid transporters and nuclear receptor FXR were studied by quantitative real time PCR, western blot and immunostaining, which showed low levels of expression. We did not observe functional involvement of the canonical receptors FXR and TGR5. Instead, we found that TC binds to the muscarinic M(2) receptor in NRCM and serves as a partial agonist of this receptor in terms of inhibitory effect on intracellular cAMP and negative chronotropic response. Pharmacological inhibition and siRNA-knockdown of the M(2) receptor completely abolished the negative effect of TC on contraction, calcium transient amplitude and synchronisation in NRCM clusters., Conclusion: We conclude that in NRCM the TC-induced arrhythmia is mediated by the partial agonism at the M(2) receptor. This mechanism might serve as a promising new therapeutic target for fetal arrhythmia.