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The current study was to report our initial experiences of fetal pulmonary valvuloplasty (FPV) for fetuses with pulmonary atresia with intact ventricular septum (PA/IVS) and critical pulmonary stenosis (CPS), including case selection, technical feasibility, and the effects of FPV on utero and postnatal outcome. Two fetuses with PA/IVS and three fetuses with CPS were enrolled between September 2016 and April 2018. All fetuses were with concomitant severe right ventricular dysplasia and growth arrest. Parameters of right cardiac development and hemodynamics, including tricuspid/mitral annulus ratio (TV/MV), right ventricle/left ventricle long-axis ratio (RV/LV), tricuspid valve inflow duration/cardiac cycle ratio (TVI/CC), degree of tricuspid regurgitation (TR), and blood flow direction of arterial duct and ductus venosus, were evaluated using echocardiogram. FPV was performed trans-abdominally under ultrasound guidance. Echocardiogram was performed post-FPV and every 2–4 weeks thereafter until delivery. The median gestational age at the time of FPV was 28 weeks. From technical perspective, pulmonary balloon valvuloplasty was successfully performed and the opening of pulmonary valve was improved in all fetuses in 2–4 weeks. However, progressive restenosis was observed in four fetuses with gestation advancing, and re-atresia occurred in two PA/IVS fetuses at 36th and 37th weeks' gestation, respectively. The growth trajectories of TV/MV, RV/LV, and TVI/CC were improved in the 1st week after FPV and then slowed down along with pulmonary valve restenosis. All fetuses were born alive and underwent postnatal interventions, including pulmonary balloon valvuloplasty in three fetuses and surgical procedures in two fetuses. During follow-up, three fetuses turned to be biventricular, one became one and a half ventricular at 1-year old, and one died of neonatal infection. Although pulmonary valve restenosis might occur as gestation advancing, FPV seems to be a safe and feasible procedure to improve the growth trajectories of right heart for fetuses with PA/IVS and CPS. [ABSTRACT FROM AUTHOR]

It is a consensus in the international manned space field that factors such as microgravity during the space flight can cause anxiety, depression and other important brain function abnormalities in astronauts. However, the neural mechanism at the molecular level is still unclear. Due to the limitations of research conditions, studies of biological changes in the primate brain have been comparatively few. We took advantage of -6° head-down bed rest (HDBR), one of the most implemented space analogues on the ground, to investigate the effects of simulated weightlessness on non-human primate brain metabolites. The Rhesus Macaque monkeys in the experiment were divided into three groups: the control group, the 42-day simulated weightlessness group with HDBR, and the recovery group, which had 28 days of free activity in the home cage after the HDBR. Liquid chromatography-mass spectrometry (LC-MS) was used to perform metabolomics analysis on specific brain areas of the monkeys under three experimental conditions. Our results show that simulated weightlessness can cause neurotransmitter imbalances, the amino acid and energy metabolism disorders, and hormone disturbances. But these metabolomics changes are reversible after recovery. Our study suggests that long-term brain damage in space flight might be reversible at the metabolic level. This lays a technical foundation for ensuring brain health and enhancing the brain function in future space studies. [ABSTRACT FROM AUTHOR]

Background: Acute type A aortic dissection (ATAAD) is a cardiovascular emergency and has high mortality and morbidity. We retrospectively compared the effects on outcomes of single arterial cannulation via axillary artery (AAC) with double arterial cannulation via axillary and femoral artery (DAC) in patients who underwent cardiopulmonary bypass (CPB) for ATAAD. Methods: Between January 2017 and May 2021, four hundred 29 patients who underwent aortic arch repair with circulatory arrest for ATAAD were divided into AAC group (n = 283) and DAC group (n = 146). The propensity score-matched (PSM) analysis were performed to compare the characteristics and outcomes of the groups. Results: After PSM (n = 137 in each), the DAC group had a longer duration of CPB (229 vs 244, p = 0.011), aortic cross-clamp time (121 vs 149, p < 0.001), durations of Intensive Care Unit (ICU) stay (7 vs 8, p = 0.014) and hospital stay (19 vs 25, p < 0.001) compared with AAC group. The incidences of dialysis (21% vs. 31%, p = 0.073), postoperative stroke (9% vs 15%, p = 0.143), ECMO support (2% vs 7%, p = 0.077), in-hospital mortality (7% vs 14%, p = 0.071) and follow-up mortality (10% vs 19%, p = 0.059) showed no significant difference between two groups. Multivariate logistic regression analysis showed postoperative ECMO (OR: 16.69, 95% CI: 1.78–156.29; p = 0.014) or stroke (OR: 11.34, 95% CI: 2.64–48.72; p < 0.001) were associated with in-hospital mortality. Univariate Cox regression results showed stroke history (OR: 4.61, 95% CI: 1.90–11.16; p = 0.001), aortic valvuloplasty (OR: 0.21, 95% CI: 0.07–0.59; p = 0.003), postoperative ALT day1 (OR: 1.00, 95% CI: 1.00–1.00; p = 0.008), ECMO (OR: 16.30, 95% CI: 4.78–55.61; p < 0.001), tracheotomy (OR: 3.78, 95% CI: 1.08–13.20; p = 0.037), postoperative stroke (OR: 4.61, 95% CI: 1.90–11.16; p < 0.001) and re-exploration for bleeding (OR: 3.52, 95% CI: 1.01–12.27; p = 0.048) were associated to follow-up mortality. Conclusions: For surgical treatment of ATAAD with CPB when compared to double axillary and femoral artery, single axillary cannulation was associated with shorter durations of CPB and ACC as well as ICU and hospital stays but no with significant difference in mortality. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the epidemiological characteristics and trends in death after thoracotomy in children with congenital heart disease (CHD). Methods: The clinical data of children with CHD aged 0–14 years who died after thoracotomy in our hospital from January 1, 2005, to December 31, 2020, were retrospectively collected to analyze the characteristics of and trends in postoperative death. Results: A total of 502 patients (365 males; 72.7%) died from January 1, 2005, to December 31, 2020, with an average of 31 deaths per year. For these patients, the median age was 2.0 months, the median length of hospital stay was 16.0 days, the median postoperative time to death was 5.0 days, and the median risk adjustment in congenital heart surgery-1 (RACHS-1) score was 3.0. 29.5% underwent emergency surgery, 16.9% had postoperative ECMO support, and 15.9% received postoperative blood purification treatment. In the past 16 years, the deaths of children with CHD under 1 year old accounted for 80.5% of all deaths among children with CHD aged 0–14 years, and deaths (349 cases) under 6 kg accounted for 69.5% of all deaths. Age at death, weight, and disease type were characterized by annual changes. Conclusions: The postoperative deaths of children with CHD mainly occurred in infants and toddlers who weighed less than 6.0 kg, and TGA and PA were the most lethal CHDs. The proportion of deaths has been increasing across the years among patients who are young, have a low body weight, and have complex cyanotic CHD. [ABSTRACT FROM AUTHOR]

Objectives: To compare the safety and efficacy of del-Nido cardioplegia (DNC) with traditional 4:1 cold blood cardioplegia (CBC) in coronary artery bypass grafting and/or valve surgeries in elderly patients. Methods: The present study is a retrospective case-series study that included 302 consecutive patients aged 70 years and over who underwent on-pump valve surgery and/or coronary artery bypass graft (CABG). DNC was administered to 90 patients and CBC to 212 patients. After propensity-score matching, 89 pairs were compared. The safety and efficacy were analyzed between the two groups. Results: The DNC group had a similar mortality (3.4% vs. 5.6%, OR = 0.79, P = 0.720) and extracorporeal membrane oxygenation (ECMO) implantation rate (1.1% vs. 2.2%, OR = 0.75, P = 1.000) to the CBC group, a lower incidence of postoperative intra-aortic balloon pump (IABP) implantation (1.1% vs. 9.0%, OR = 0.54, P = 0.034) and a higher left ventricular ejection fraction (LVEF) at discharge (60 (56–64) % vs. 57 (51–62)%, P = 0.007). The estimated glomerular filtration rate (eGFR) in the DNC group was higher when the patient was transferred to the intensive care unit (79.4 (65.0-94.3) ml/min/1.73m2 vs. 77.2 (59.8–88.7) ml/min/1.73m2, P = 0.014), but no significant differences were identified after 24 h. The serum lactate values of the DNC group were significantly lower than those of the CBC group (0 h: 2.7 (2.0-3.2) vs. 3.2 (2.4–4.4), P = 0.001; 3 h: 3.2 (2.0-4.8) vs. 4.8 (2.8–6.6), P < 0.001; 6 h: 3.5 (2.2–5.4) vs. 5.8 (3.4–8.4), P < 0.001; 9 h: 3.4 (2.0–7.0) vs. 5.5 (2.9–8.3), P = 0.005). There were no differences between the two groups in respect of lactate levels at 12 h and thereafter. Postoperative creatinine kinase-MB concentrations were similar between the two groups. Conclusions: Del-Nido cardioplegia is safe and effective in elderly patients undergoing CABG and/or valve surgery. [ABSTRACT FROM AUTHOR]

Drug resistance to irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a primary factor affecting their therapeutic efficacy in human non-small cell lung cancer (NSCLC). NSCLC cells can undergo epithelial-mesenchymal transition (EMT) induced by many factors in the tumour microenvironment (TME), which plays a crucial role in tumour drug resistance. In this study, a multicellular lung-on-a-chip that can realise the cell co-culture of the human non-small cell lung cancer cell line HCC827, human foetal lung fibroblasts (HFL-1), and human umbilical vein endothelial cells (HUVECs) is prepared. The TME was simulated on the chip combined with perfusion and other factors, and the drug evaluation of osimertinib was performed to explore the drug resistance mechanism of EGFR-TKIs. In the early stages, a two-dimensional static cell co-culture was achieved by microchip, and the results showed that HFL-1 cells could be transformed into cancer-associated fibroblasts (CAFs), and HCC827 cells could undergo EMT, both of which were mediated by Interleukin-6 (IL-6). Vimentin (VIM) and Alpha Skeletal Muscle Actin (a-SMA) expression of HFL-1 was upregulated, whereas E-cadherin (E-cad) expression of HCC827 was down-regulated. Further, N-cadherin (N-cad) expression of HCC827 was upregulated. In both the static cell co-culture and multicellular lung-on-a-chip, HCC827 cells with CAFs co-culture or IL-6 treatment developed resistance to osimertinib. Further use of the IL-6 antibody inhibitor tocilizumab could reverse EGFR-TKI resistance to a certain extent. Combination therapy with tocilizumab and EGFR-TKIs may provide a novel therapeutic strategy for overcoming EGFR-TKI resistance caused by EMT in NSCLC. Furthermore, the lung-on-a-chip can simulate complex TME and can be used for evaluating tumour resistance and exploring mechanisms, with the potential to become an important tool for personalised diagnosis, treatment, and biomedical research. [Display omitted] [ABSTRACT FROM AUTHOR]

Isosteviol has been indicated as a cardiomyocyte protector. However, the underlying mechanism remains unclear. Thus, we sought to confirm the protective effect of isosteviol after myocardial infarction in a model of permanent coronary artery occlusion and investigate the potential proangiogenic activity in vitro and in vivo. A 4-week permanent coronary artery occlusion rat model was generated, and the protective effect of isosteviol was evaluated by echocardiographic imaging and hemodynamics assays. The coronary capillary density was tested by immunochemistry and micro-computed tomography (μCT) imaging. The effect of isosteviol on endothelial cells was determined in human umbilical vein endothelial cells (HUVECs) in vitro and Tg (kdrl: EGFP) zebrafish in vivo. We also examined the expression of related transcription factors by real-time polymerase chain reaction (RT-qPCR). Isosteviol increased ejection fraction (EF), fractional shortening (FS), cardiac systolic index (CI), maximum rate of increase of left ventricular pressure (Max dp/dt), and left ventricular systolic pressure (LVSP) by 32%, 40%, 25%, 26%, and 10%, respectively, in permanent coronary artery occlusion rats. Interestingly, it also promoted coronary capillary density by 2.5-fold. In addition, isosteviol promoted the proliferation and branching of HUVECs in vitro. It also rescued intersegmental vessel (ISV) development and improved endothelial cell proliferation by approximately fivefold (4–6) in zebrafish embryos in vivo. Isosteviol also upregulated the expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) in zebrafish by fourfold and 3.5-fold, respectively. Our findings suggest that isosteviol is a proangiogenic agent and that this activity is related to its protective effects against myocardial ischemia. After using the permanent coronary artery occlusion model, we demonstrated that isosteviol promotes angiogenesis directly and increases capillary density in myocardial ischemia rats. Isosteviol promotes angiogenesis in zebrafish in vivo and increases vascular endothelial cell proliferation in HUVECs and zebrafish. The angiogenesis activity of isosteviol may be correlated with VEGFA and HIF-1α signaling. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the efficacy of the resin hemoperfusion device (HA380 hemoperfusion cartridge) on inflammatory responses during adult cardiopulmonary bypass (CPB). Methods: Sixty patients undergoing surgical valve replacement were randomized into the HP group (n = 30) with an HA380 hemoperfusion cartridge in the CPB circuit or the control group (n = 30) with the conventional CPB circuit. The results of routine blood tests, blood biochemical indexes, and inflammatory factors were analyzed at V0 (pre-CPB), V1 (CPB 30 min), V2 (ICU 0 h), V3 (ICU 6 h), and V4 (ICU 24 h). Results: The HP group had significantly lower levels of IL-6, IL-8, and IL-10. Significant estimation of group differences in the generalized estimating equation (GEE) models was also observed in IL-6 and IL-10. The HP group had significantly lower levels of creatinine (Cr), aminotransferase (AST), and total bilirubin (TBil) compared to the control group. The estimation of differences of Cr, AST, and TBil all reached statistical significance in GEE results. The HP group had significantly less vasopressor requirement and shorter mechanical ventilation time and ICU stay time as compared to the control group. Conclusion: The HA380 hemoperfusion cartridge could effectively reduce the systemic inflammatory responses and improve postoperative recovery of patients during adult CPB. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Coronavirus disease-19 (COVID-19) is a new type of epidemic pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The population is generally susceptible to COVID-19, which mainly causes lung injury. Some cases may develop severe acute respiratory distress syndrome (ARDS). Currently, ARDS treatment is mainly mechanical ventilation, but mechanical ventilation often causes ventilator-induced lung injury (VILI) accompanied by hypercapnia in 14% of patients. Extracorporeal carbon dioxide removal (ECCO2R) can remove carbon dioxide from the blood of patients with ARDS, correct the respiratory acidosis, reduce the tidal volume and airway pressure, and reduce the incidence of VILI. CASE REPORT: Two patients with critical COVID-19 combined with multiple organ failure undertook mechanical ventilation and suffered from hypercapnia. ECCO2R, combined with continuous renal replacement therapy (CRRT), was conducted concomitantly. In both cases (No. 1 and 2), the tidal volume and positive end-expiratory pressure (PEEP) were down-regulated before the treatment and at 1.5 hours, one day, three days, five days, eight days, and ten days after the treatment, together with a noticeable decrease in PCO2 and clear increase in PO2, while FiO2 decreased to approximately 40%. In case No 2, compared with the condition before treatment, the PCO2 decreased significantly with down-regulation in the tidal volume and PEEP and improvement in the pulmonary edema and ARDS after the treatment. CONCLUSION: ECCO2R combined with continuous blood purification therapy in patients with COVID-19 who are criti-cally ill and have ARDS and hypercapnia might gain both time and opportunity in the treatment, down-regulate the ventilator parameters, reduce the incidence of VILI and achieve favorable therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Pulmonary stenosis (PS) is a congenital heart disease characterized by a dynamic or fixed anatomic obstruction of blood flow from the right ventricle to the pulmonary arterial vasculature. In the present study, extracellular vesicle long RNAs (EVLRs) from pregnant females who had healthy infants or PS infants were analyzed by RNA sequencing, and their diagnostic potential for PS during pregnancy was evaluated. A method for the selection of genes that could be considered as informative for the prediction PS based on extracellular vesicles (EVs) from pregnant females using long-read RNA sequencing was developed. Blood samples were collected from females carrying fetuses with PS and females carrying unaffected fetuses (n=6 in each group). Physical characterization of EVs was performed using nanoparticle tracking analysis, transmission electron microscopy and western blotting. EVLRs from plasma were profiled by RNA sequencing and mRNA co-expression modules were constructed by weighted gene co-expression network analysis (WGCNA). Gene Ontology (GO) enrichment analysis was used to predict the function of the genes in each module. Hub genes were filtered out based on WGCNA and visualized using Cytoscape. EVLRs consisted of mRNAs, microRNAs and long non-coding RNA. Overall, 26 modules were identified containing 16,394 genes. All modules were independent of each other. One particular module, referred to as the blue module, was markedly different between the two groups. A total of 735 hub genes in the blue module were identified, of which 33 were visualized, demonstrating the connection between these hub genes. GO enrichment analysis demonstrated that the analyzed hub genes were enriched in 'glucose transport', 'ATP-dependent chromatin remodeling', 'histone deacetylation', 'histone H3-K4 methylation', 'DNA methylation', 'apoptotic signaling pathway' and 'glucocorticoid receptor signaling pathway'. The hub genes identified in this module may provide a genetic framework for prenatal PS diagnosis. Furthermore, functional analysis of these associated genes may provide a theoretical basis for further research on PS pathogenesis. [ABSTRACT FROM AUTHOR]

Tobacco smoking was one of the important adverse factors for congenital heart disease. The effects of nicotine, the main component of tobacco, on human embryonic cardiogenesis and related mechanisms remain poorly understood. This work used single-cell RNA sequencing to investigate the effects of nicotine on human embryonic stem cell (hESC) line H9 and its underlying mechanisms during cardiac differentiation. H9 was cultured in feeder-free medium and differentiated in cardiac condition medium when cells reached 90% confluent. Cell viability was detected by MTT after different concentration of nicotine treatment. Different expressed genes during cardiac differentiation was analyzed by single-cell RNA sequencing (scRNA-seq). Key gene expressions were confirmed by qPCR and Western blot. Results showed that 0.1μM–10μM nicotine did not affect H9 cell proliferation. Nicotine 1 μM down-regulated cardiac progenitor cell, mesoderm cell, smooth muscle cell and neural crest cell relatively. Snail1/2 regulating endocardial cushion development were downregulated apparently at differention day 6. Nicotine didn't affect bry-1 and mesp-1 but inhibited cardiac transcript factors. Consequently, the expression of cTnI, a marker of cardiomyocytes was decreased significantly. The data suggest direct adverse effects of nicotine on heart development at the single-cell level and offer a new approach for estimate drug and environmental toxicity on the pathogenesis of the embryonic cardiovascular system development. • Nicotine affected cardiac differentiation from hESCs. • Dataset of scRNA-seq was valuable for estimate nicotine toxicity. [ABSTRACT FROM AUTHOR]

Background: Certain pregnant women suffer from cardiac pathology,and a few of them need cardiac operations under cardiopulmonary bypass during pregnancy. Feto-neonatal and maternal outcomes have not been sufficiently described.Methods: We conducted a retrospective review of 22 cases of women undergoing cardiac operations under cardiopulmonary bypass during pregnancy in our hospital from Jan.2014 to Mar.2019.Results: All 22 patients were alive after treatment. The types of cardiac disorders included congenital heart defects, rheumatic heart disease,infective endocarditis,aortic dissection, obstruction and/or thrombosis of a prosthetic valve. Only one case was a twin pregnancy,and the other 21 cases were singletons. Four fetuses died in the utero after surgery. Three patients chose termination of the pregnancy after the cardiac operations: one fetus was detected abnormity of the brain and the other two patients abandoned pregnancy. Fourteen fetuses were alive and born without any abnormity. Two fetuses suffered from neonatal intracranial hemorrhage and died after birth.Conclusions: Cardiac operation under cardiopulmonary bypass during pregnancy is a challenge for physicians in multidisciplinary teams. Strictly evaluating the indication is vital. On the other hand, some patients can benefit from this management. [ABSTRACT FROM AUTHOR]

Smoke exposure during pregnancy has detrimental effects upon numerous fetal and neonatal outcomes. Nicotine (the main component of tobacco) has been suggested to affect placental development. During placental development, efficient invasion by trophoblasts is required for establishment of the fetus–maternal circulation. In this study we explored the regulation of trophoblast invasion by nicotine. An immortalized first trimester extravillous trophoblast cell line (HTR-8/SVneo cells) was used for all the experiments, which were treated by nicotine, methyllycaconitine, and C-X-C motif chemokine ligand 12 (CXCL12). Total RNA and protein were used to study the expressions of nicotinic acetylcholine receptors (nAChRs), and transwell assay was used to study invasiveness. Changes of RNA expression due to nicotine treatment were detected by RNA sequence. Level of CXCL12 mRNA was verified by quantitative PCR. We showed that HTR-8/SVneo expressed subunits α2–4, α7, α9, β1, and β2 of nAChRs. Nicotine downregulated CXCL12 expression and inhibited trophoblast invasion. Methyllycaconitine, as an antagonist of the α7 homopolymer, blocked the inhibitory effect of nicotine. CXCL12 could rescue the nicotine-induced inhibitory effect on invasion of HTR-8/SVneo cells. These results suggest that the α7 subunit of the nAChR has important roles in modulating trophoblast invasion through CXCL12. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the effects of different shunt diameters and pulmonary artery (PA) stenosis grades on the hemodynamics of central shunts to determine an optimal surgical plan and improve the long-term outcomes of the operation. A 3D anatomical model was reconstructed based on the patient's clinical CT data. 3D computational fluid dynamics models were built with varying degrees of stenosis (the stenosis ratio α was represented by the ratio of blood flow through the main pulmonary artery to cardiac output, ranging from 0 to 30%; the smaller the value of α, the more severe the pulmonary artery stenosis) and varying shunt diameters (3, 3.5, 4, 4.5, and 5 mm). Our results show that the asymmetry of pulmonary artery flow increased with increasing shunt diameter and α, which will be more conducive to the development of the left pulmonary artery. Additionally, the pulmonary-to-systemic flow ratio (QP/QS) increases with the shunt diameter and α, and all the values exceed 1. When the shunt diameter is 3 mm and α = 0%, QP/QS reaches the minimum value of 1.01, and the oxygen delivery reaches the maximum value of 205.19 ml/min. However, increasing shunt diameter and α is beneficial to reduced power loss and smoother PA flow. In short, for patients with severe PA stenosis (α is small), a larger-diameter shunt may be preferred. Conversely, when the degree of PA stenosis is moderate, a smaller shunt diameter can be considered. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the influence and possible pathophysiological mechanism of pulsatile cardiopulmonary bypass (CPB) in various frequencies in pediatric patients undergoing congenital cardiac surgery.Patients and Methods: Clinical data and hemodynamic parameters were collected in 80 patients who underwent congenital cardiac surgeries and were perfused in different settings: pulsatile perfusion (PP) in frequencies of 30 beats/min, PP 60 beats/min, PP 100 beats/min and non-pulsatile perfusion (NP). Serum proteins, plasma-free hemoglobin (PFH), endothelin-1 (ET-1) and nitric oxide (NO) were collected to study possible pathophysiological changes, possible hematological injury and oxidative status under different perfusing conditions.Results: Patients in all groups had similar baseline characteristics, aortic cross-clamping time and CPB duration. More effective pulse gradient (PG), energy-equivalent pressure (EEP) and surplus hemodynamic energy (SHE) were observed in pulsatility with lower frequency setting, under which more patients achieved physiologically normal mean arterial pressure (MAP), without the support of inotropic agents during bypass. Significant between-group differences of serum proteins and PFH were absent the whole time during and after bypass, while a relatively lower percentage of perioperative requirement of diuretics was observed in the low frequency pulsatile group. A better performance to oxidative stress was seen in the low frequency group with higher levels of NO and lower concentration of ET-1, and both intergroup differences were found (P<0.01). Satisfactory clinical outcome was obtained on post procedure course in all groups.Conclusion: Pulsatile perfusion with low frequency setting in pediatric patients undergoing congenital cardiac surgery showed better hemodynamic profiles, potential protective effects on vital organs, better oxidative status and satisfactory clinical outcome. [ABSTRACT FROM AUTHOR]

Background: COVID-19 has become a major global threat. The present study aimed to develop a nomogram model to predict the survival of COVID-19 patients based on their clinical and laboratory data at admission.Methods: COVID-19 patients who were admitted at Hankou Hospital and Huoshenshan Hospital in Wuhan, China from January 12, 2020 to March 20, 2020, whose outcome during the hospitalization was known, were retrospectively reviewed. The categorical variables were compared using Pearson's χ2-test or Fisher's exact test, and continuous variables were analyzed using Student's t-test or Mann Whitney U-test, as appropriate. Then, variables with a P-value of ≤0.1 were included in the log-binomial model, and merely these independent risk factors were used to establish the nomogram model. The discrimination of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), and internally verified using the Bootstrap method.Results: A total of 262 patients (134 surviving and 128 non-surviving patients) were included in the analysis. Seven variables, which included age (relative risk [RR]: 0.905, 95% confidence interval [CI]: 0.868-0.944; P < 0.001), chronic heart disease (CHD, RR: 0.045, 95% CI: 0.0097-0.205; P < 0.001, the percentage of lymphocytes (Lym%, RR: 1.125, 95% CI: 1.041-1.216; P = 0.0029), platelets (RR: 1.008, 95% CI: 1.003-1.012; P = 0.001), C-reaction protein (RR: 0.982, 95% CI: 0.973-0.991; P < 0.001), lactate dehydrogenase (LDH, RR: 0.993, 95% CI: 0.990-0.997; P < 0.001) and D-dimer (RR: 0.734, 95% CI: 0.617-0.879; P < 0.001), were identified as the independent risk factors. The nomogram model based on these factors exhibited a good discrimination, with an AUC of 0.948 (95% CI: 0.923-0.973).Conclusions: A nomogram based on age, CHD, Lym%, platelets, C-reaction protein, LDH and D-dimer was established to accurately predict the prognosis of COVID-19 patients. This can be used as an alerting tool for clinicians to take early intervention measures, when necessary. [ABSTRACT FROM AUTHOR]

BVES is a transmembrane protein, our previous work demonstrated that single nucleotide mutations of BVES in tetralogy of fallot (TOF) patients cause a downregulation of BVES transcription. However, the relationship between BVES and the pathogenesis of TOF has not been determined. Here we reported our research results about the relationship between BVES and the right ventricular outflow tract (RVOT) stenosis. BVES expression was significantly downregulated in most TOF samples compared with controls. The expression of the second heart field (SHF) regulatory network genes, including NKX2.5, GATA4 and HAND2, was also decreased in the TOF samples. In zebrafish, bves knockdown resulted in looping defects and ventricular outflow tract (VOT) stenosis, which was mostly rescued by injecting bves mRNA. bves knockdown in zebrafish also decreased the expression of SHF genes, such as nkx2.5, gata4 and hand2, consistent with the TOF samples' results. The dual-fluorescence reporter system analysis showed that BVES positively regulated the transcriptional activity of GATA4, NKX2.5 and HAND2 promoters. In zebrafish, nkx2.5 mRNA partially rescued VOT stenosis caused by bves knockdown. These results indicate that BVES downregulation may be associated with RVOT stenosis of non-syndromic TOF, and bves is probably involved in the development of VOT in zebrafish. [ABSTRACT FROM AUTHOR]

Due to an error in production, the article should have indicated that Jing Chen and Min Qiu are co-first authors, as displayed here. [ABSTRACT FROM AUTHOR]

• The hemodynamic effect of nonclosure of Patent ductus arteriosus (PDA) on modified Blalock-Taussig shunt (MBTS) was investigated numerically. • MBTS with nonclosure of PDA plays an active role in preventing early acute shunt failure and produced a better hemodynamic environment including lower blood velocity, energy loss, WSS values at MBT shunt, smaller vortex regions, higher oxygen content (Sao2) and more uniform velocity distribution in the LPA and RPA compared to MBTS with closure of PDA. However, excessive PA flow induced by nonclosure of PDA may result in a series of complication. • MBTS with nonclosure of PDA could be preferred for cases with very low PA overflow risk and maybe benefit for patients with underdeveloped myocardium due to lower energy dissipation. MBTS with closure of PDA could be preferred for cases with very high PA overflow risk. Studying the hemodynamic effects of nonclosure of patent ductus arteriosus (PDA) on the modified Blalock-Taussig shunt (MBTS) is beneficial for surgical PDA management. In the present study, the effect of PDA on MBTS was investigated numerically. A series of parameters including energy loss, wall shear stress (WSS), and left/right Pulmonary artery (LPA/RPA) flow ratio were computed from simulations to analyze the hemodynamic effects of PDA on MBTS. To ensure the universality of the research conclusions, three typical models, including models with a well-developed RPA, a symmetrically-developed pulmonary artery(PA) and a well-developed LPA, were constructed based on patient-specific pre-surgery clinical data sets. A commercial CFD solver ANSYS-Fluent software was adopted for this study. A pressure-based solver for incompressible Newtonian flows, the K-omega based shear-stress-transport model and a second-order accurate numerical discretization scheme were employed for simulation. Our results show that MBTS with nonclosure of PDA is accompanied by lower blood velocity, energy loss and WSS values at the MBT shunt; smaller vortex regions; higher oxygen content(Sao 2) and PA flow; and more uniform velocity distribution in the LPA and RPA than MBTS with closure of PDA. If the PDA was not closed when performing primary MBTS, a series of hemodynamic changes occurs during PDA closure in postoperative recovery: the energy loss, PA flow and Sao 2 decrease, while the oxygen delivery(Do2) and WSS values at the MBT shunt increase. Nonclosure of PDA could provide a better hemodynamic environment and play an active role in preventing early acute shunt failure. It could be preferred for cases with very low PA overflow risk and may benefit patients with an underdeveloped myocardium due to its lower energy dissipation than PDA closure. However, excessive PA flow induced by nonclosure of PDA may result in a series of complications. Surgeon's decision-making process with respect to PDA management should consider the individual patient to achieve optimal postoperative recovery. [ABSTRACT FROM AUTHOR]