Improved therapeutic effects on vascular intimal hyperplasia by mesenchymal stem cells expressing MIR155HG that function as a ceRNA for microRNA-205.

Coronary artery bypass grafting (CABG) is an effective treatment for coronary heart disease, with vascular transplantation as the key procedure. Intimal hyperplasia (IH) gradually leads to vascular stenosis, seriously affecting the curative effect of CABG. Mesenchymal stem cells (MSCs) were used to alleviate IH, but the effect was not satisfactory. This work aimed to investigate whether lncRNA MIR155HG could improve the efficacy of MSCs in the treatment of IH and to elucidate the role of the competing endogenous RNA (ceRNA). The effect of MIR155HG on MSCs function was investigated, while the proteins involved were assessed. IH was detected by HE and Van Gieson staining. miRNAs as the target of lncRNA were selected by bioinformatics analysis. qRT-PCR and dual-luciferase reporter assay were performed to verify the binding sites of lncRNA-miRNA. The apoptosis, Elisa and tube formation assay revealed the effect of ceRNA on the endothelial protection of MIR155HG-MSCs. We observed that MIR155HG improved the effect of MSCs on IH by promoting viability and migration. MIR155HG worked as a sponge for miR-205. MIR155HG/miR-205 significantly improved the function of MSCs, avoiding apoptosis and inducing angiogenesis. The improved therapeutic effects of MSCs on IH might be due to the ceRNA role of MIR155HG/miR-205.

Bioaccessibility of lead and cadmium in soils around typical lead-acid power plants and their effect on gut microorganisms.

Potentially toxic elements (Pb and Cd) contamination of soil can adversely affect human health. Moreover, these metal ions interact with the gut microbiota after entering the human digestive system. Based on the physiologically based extraction test and the simulator of human intestinal microbial ecosystem, the bioaccessibility of Pb and Cd in soils contaminated with lead-acid power plants was assessed. The gastric stage exhibited the greatest average bioaccessibility of lead and cadmium (63.39% and 57.22%), followed by the small intestinal stage (6.86% and 36.29%); due to gut microorganisms, the bioaccessibility of lead and cadmium was further reduced in the colon stage (1.86% and 4.22%). Furthermore, to investigate soil contamination's effects on gut microbes, 16S rRNA high-throughput sequencing was used to identify the gut microbial species after the colon period. Due to Pb and Cd exposure, the relative abundance of Firmicutes and unidentified_Bacteria decreased, while the relative abundance of Proteobacteria, Synergistota, and Bacteroidota increased. The relationship between environmental factors and the number of microbial species in the gut was also examined using Spearman correlation analysis. Pb and Cd exposure has been found to affect the composition and structure of the gut microbiota.

Safety and efficacy of the Amplatzer Amulet and Watchman 2.5 for left atrial appendage occlusion: A systematic review and meta-analysis.

BACKGROUND: Left atrial appendage occlusion (LAAO) is an alternative to oral anticoagulation (OAC) to decrease the risk of stroke in patients with nonvalvular atrial fibrillation (NVAF); however, certain complications remain a concern. Amplatzer Amulet and Watchman are the two most popular used devices for preventing stroke in patients with NVAF. We assessed the safety and efficacy of LAAO using the Amplatzer Amulet and Watchman. METHODS: A meta-analysis was conducted to compare the safety and efficacy outcomes associated with the use of the Amplatzer Amulet and Watchman 2.5. The Newcastle-Ottawa Scale has been utilized to assess the quality of study. RESULTS: The meta-analysis includes seven studies involving 2926 patients (1418 patients with an amulet and 1508 with a Watchman 2.5). Generally, adverse event rates for both systems were minimal. No significant differences between the two devices were found in safety (pericardial effusion, device embolization, and cardiac tamponade) or efficacy outcomes (death, TIA, stroke, major/minor bleeding, device leak, and thromboembolic events). CONCLUSIONS: The data suggest LAAO is a safe procedure, regardless of which device was used. LAAO devices generally have low complication rates. Outcomes were comparable between the two groups with no significant differences in their safety or efficacy.

A rare case on anomalous pulmonary venous drainage in congenital cardiovascular disease.

Anomalous pulmonary veins drain into the right side of the left atrium is an uncommon variety of anomalous pulmonary venous return. Rarely, anomalous pulmonary venous drainage combined with cor triatriatum and atrial septal defect. We presented the imaging findings of a male patient who had anomalous pulmonary venous drainage which has not previously been described.

Predictive Efficacy of the Index of Microcirculatory Resistance for Acute Allograft Rejection and Cardiac Events After Heart Transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND: In patients treated by heart transplantation, the index of microcirculatory resistance (IMR) has been found to have predictive potential for subsequent acute allograft rejection (AAR) and long-time cardiac events. When consulting related literature, the studies mostly were single-center with small sample sizes. The question of whether IMR can be utilized as a predictive biomarker is becoming increasingly contentious. To confirm the predictive efficacy of IMR, researchers did a systematic review and meta-analysis. METHOD: From inception to April 2022, PubMed, EMBASE, Cochrane Library, Web of Science, Ovid, ProQuest, and Scopus systematically were searched. The results were presented as pooled ratio rate (RR) with 95% confidence intervals (CI). Assessment of the quality, heterogeneity analyses, and publication bias analysis also were performed. RESULTS: A total of 616 patients were studied in five trials. There were significant differences in subsequent AAR (RR = 4.08; 95% CI: 2.69~6.17; P = 0.000) or long-time cardiac events (RR=2.14; 95% CI: 1.44~3.19; P = 0.000) between IMR-high and IMR-low patients in the forest plots. Patients treated with heart transplantation in the high IMR group had better predictive efficacy than the low IMR group. CONCLUSIONS: High IMR could predict the events of subsequent AAR and cardiac events after heart transplantation. This will help reduce the occurrence of adverse events and personalize treatment for patients.

Analysis of Influencing Factors of Surgical Options for Coronary Atherosclerotic Heart Disease Complicated with Moderate Ischemic Mitral Regurgitation.

BACKGROUND: There are several controversies regarding the surgical approach for patients with coronary atherosclerotic heart disease (CAHD) complicated with moderate ischemic mitral regurgitation (IMR). METHODS: A retrospective study was performed among 115 patients divided into two groups. Clinical and echocardiographic parameters, including perioperative indexes and follow ups, degree of stenosis in the coronary arteries, and cardiac function index, were analyzed. Patients who died in the hospital due to complications during the perioperative period were defined as the deterioration group (deterioration of coronary artery bypass grafting, CABG vs. deterioration of coronary artery bypass grafting combined with mitral valve surgery, CABG+MVS: N = 7, 58.3% vs. N = 5, 41.7%), whereas the remaining patients were defined as the rehabilitation group (rehabilitation of CABG vs. rehabilitation of CABG+MVS: N = 52, 50.5% vs. N = 51, 49.5%). Data were compared between the rehabilitation of the CABG and CABG+MVS groups to explore the predictors for surgical method selection. RESULTS: Postoperative patients who died during hospitalization were excluded (N = 12). At 1-year follow up, there were 52 patients in the CABG rehabilitation group and 51 in the CABG+MVS rehabilitation group. During the follow-up period, 10 patients died (rehabilitation of CABG vs. rehabilitation of CABG+MVS: N = 7, 13.7% vs. N = 3, 5.8%). Nevertheless, the difference was not statistically significant. The logistic regression analysis identified four independent factors when choosing the surgical modality: prior-myocardial infarction (prior-MI), preoperative atrial fibrillation (pre-AF), and the stenotic degree of the left circumflex (LCX) and left main (LM) arteries. CONCLUSIONS: Prior-MI, pre-AF, and the degree of stenosis in LCX and LM could influence the choice of surgical method. This study provided new insights into the treatment of CAHD with moderate IMR.

Pharmacological analysis of dexmedetomidine hydrochloride in pediatric anesthesia during magnetic resonance imaging.

Dexmendetomidine hydrochloride (DEX) is a new common adrenergic receptor agonist, which not only keeps children calm but also has analgesic effect. Dexmedetomidine hydrochloride will enable children to maintain the natural non-REM sleep, which can be stimulated sedation or language arousal. The aim of this study is to observe the sedative effect and adverse drug reactions of dexmedetomidine hydrochloride injection and propofol injection in MRI examination. In this study, no children in the experimental group were required to add sedative drugs, and 2 cases in the control group were treated with sedative drugs. In experimental group, it used dexmedetomidine hydrochloride as (1.64±0.91) g/kg; in control group, dosage of narcotic drugs as (5.26±1.82) g/kg, and the total complication rate of the children in the experimental group was lower than that of the control group (P<0.05). After returning to the ward, the doses of phenobarbital sedation were dexmedetomidine group (4.28±1.53) mg/kg and propofol group (6.40±1.71) mg/kg. There was significant difference between the two groups. The total complication rate in the experimental group was lower than that in the control group (P<0.05). The quality of MRI in the test group was significantly higher than that in the control group, which showed that dexmedetomidine hydrochloride could provide a satisfactory sedative effect in the MRI examination of children. To sum up, dexmedetomidine hydrochloride is a wide range of clinical applications. It is an effective drug for the maintenance of sedation in clinical disease treatment. It is flexible in the way of administration and with less adverse reactions. It is suitable for popularization and application in clinical practice.

TNF-α promotes survival and migration of MSCs under oxidative stress via NF-κB pathway to attenuate intimal hyperplasia in vein grafts.

The oxidative stress caused by endothelial injury is involved in intimal hyperplasia (IH) in vein grafts. Mesenchymal stem cells (MSCs) can home to injured intima and promote endothelial repair. However, MSC apoptosis is increased accompanied by decreased functional activity under oxidative stress. Thus, we investigate whether tumour necrosis factor-α (TNF-α) can promote the survival and activity of MSCs under oxidative stress to reduce IH more effectively, and establish what role the NF-κB pathway plays in this. In this study, we preconditioned MSCs with TNF-α (TNF-α-PC MSCs) for 24 hrs and measured the activation of the IKK/NF-κB pathway. EdU and transwell assays were performed to assess proliferation and migration of TNF-α-PC MSCs. Apoptosis and migration of TNF-α-PC MSCs were evaluated in conditions of oxidative stress by analysis of the expression of Bcl-2 and CXCR4 proteins. TNF-α-PC MSCs were transplanted into a vein graft model, so that cell homing could be tracked, and endothelial apoptosis and IH of vein grafts were measured. The results demonstrated that TNF-α promotes proliferation and migration of MSCs. Furthermore, survival and migration of TNF-α-PC MSCs under oxidative stress were both enhanced. A greater number of MSCs migrated to the intima of vein grafts after preconditioning with TNF-α, and the formation of neointima was significantly reduced. These effects could be partially abolished by IKK XII (NF-κB inhibitor). All these results indicate that preconditioning with TNF-α can promote survival and migration of MSCs under oxidative stress via the NF-κB pathway and thus attenuate IH of vein grafts.

Effects of Ulinastatin on Perioperative Inflammatory Response and Pulmonary Function in Cardiopulmonary Bypass Patients.

The aim of this study was to investigate whether ulinastatin (UTL) has protective effects on perioperative proinflammatory cytokines and lung injury in cardiopulmonary bypass (CPB) patients. The study included 60 patients undergoing CPB who were randomly divided into a UTL group and a control group. Blood routine examination and inflammatory cytokines concentrations were detected after anesthetic induction (T1), immediately after aortic valve opening (T2), and 4 (T3) and 24 (T4) hours after weaning from CPB. Flow cytometry was used to detect TLR4 and HSP70 expressions. Arterial blood gas and respiratory function were analyzed at the same time points. Compared with the control group, the levels of IL-2, IL-8, TNF-α, NE, TLR4, PA - aDO2, and RI at T2 were significantly lower, whereas HSP70, PaO2, OI, Cd, and Cs were higher in the UTL group (all P < 0.05). Relative to the control group at T3, white blood cell count, TLR4, IL-2, IL-6, IL-8, TNF-α, NE, and RI decreased significantly, whereas IL-10, HSP70, PaO2, OI, and Cs increased in the UTL group (all P < 0.05). At T4, IL-2, IL-6, IL-8, TNF-α, TLR4, and PaCO2 in the UTL group were significantly lower, and PaO2, IL-10, HSP70, and Cs were higher than in the control group (all P < 0.05). Our data show strong evidence that UTL suppresses proinflammatory cytokine elevation and upregulates release of anti-inflammatory mediators, reducing pulmonary injury and improving pulmonary function after CPB.

Combined low-dose aspirin and warfarin anticoagulant therapy of postoperative atrial fibrillation following mechanical heart valve replacement.

The safety and efficacy of combined low dose aspirin and warfarin therapy in patients with atrial fibrillation after mechanical heart valve replacement were evaluated. A total of 1016 patients (620 females, mean age of 36.8±7.7 years) admitted for cardiac valve replacement and complicated with atrial fibrillation after surgery were randomly divided into study (warfarin plus 75-100 mg aspirin) or control (warfarin only) groups. International normalized ratio (INR) and prothrombin time were maintained at 1.8-2.5 and 1.5-2.0 times the normal values, respectively. Thromboembolic events and major bleedings were registered during the follow-up period. Patients were followed up for 24±9 months. The average dose of warfarin in the study and control groups was 2.91±0.83 mg and 2.88±0.76 mg, respectively (P>0.05). The incidence of overall thromboembolic events in study group was lower than that in control group (2.16% vs. 4.35%, P=0.049). No statistically significant differences were found in hemorrhage events (3.53% vs. 3.95%, P=0.722) or mortality (0.20% vs. 0.40%, P=0.559) between the two groups. Combined low dose aspirin and warfarin therapy in the patients with atrial fibrillation following mechanical heart valve replacement significantly decreased thromboembolic events as compared with warfarin therapy alone. This combined treatment was not associated with an increase in the risk of major bleeding or mortality.

The metabolic role of the CD73/adenosine signaling pathway in HTR-8/SVneo cells: A Double-Edged Sword?

The ecto-5'-nucleotidase (CD73)/adenosine signaling pathway has been reported to regulate tumor epithelial-mesenchymal transition (EMT), migration and proliferation. However, little is known about the metabolic mechanisms underlying its role in trophoblast proliferation and migration. In this study, we aimed to investigate the metabolic role of the CD73/adenosine signaling pathway on the proliferation and migration of trophoblast. We found that CD73 levels were upregulated in preeclamptic placentas compared with the placentas of normotensive pregnant women. EMT and migration of HTR-8/SVneo cells were enhanced when treated with a CD73 inhibitor (100 µM) in vitro. Conversely, excessive adenosine (25 or 50 µM) suppressed trophoblast cell EMT, migration and proliferation. RNA-seq, metabolomics and seahorse findings showed that adenosine treatment resulted in increased expression of PDK1, suppression of aerobic respiration, glycolysis and amino acids synthesis, as well as increased utilization of short-chain fatty acids (SCFAs). Furthermore, the 13C-adenosine isotope tracking experiment demonstrated that adenosine served as a carbon source for the tricarboxylic acid (TCA) cycle. Our results reveal the role of adenosine in regulating trophoblast energy metabolism is like a double-edged sword - either inhibiting aerobic respiration or supplementing carbon sources into metabolic flux. CD73/adenosine signaling regulated trophoblast EMT, migration, and proliferation by modulating energy metabolism. This study indicates that CD73/adenosine signaling potentially plays a role in the occurrence of placenta-derived diseases, including preeclampsia.

Study on arsenic speciation, bioaccessibility, and gut microbiota in realgar-containing medicines by DGT technique and artificial gastrointestinal extraction (PBET) combine with simulated human intestinal microbial ecosystem (SHIME).

It is well-known that several Chinese patent medicines use realgar as a specific component. People are more aware of the health dangers associated with realgar since it includes arsenic. Previous research overstated the arsenic toxicity of realgar-containing Chinese prescription medications because little thought was given to the influence of arsenic bioaccessibility by gut microbiota. In light of this, this study examined the total content, bioaccessibility and speciation of targeted medications while also examining intestinal epithelial transit utilizing the diffusive gradients in thin-films (DGT). All samples contained arsenic, and the bioaccessibilities of the colon, intestine and gastric regions ranged from 0.19% to 1.73%, 0.25-1.88% and 0.21-1.70% respectively. The range of DGT-bioaccessibility is 0.01-0.0018%. Three steps of analysis were conducted on inorganic As(III) and As(V). In health risk assessment, the ADDs and HQs of DGT-bioaccessibility were below the threshold levels when compared to computing average daily intake dose (ADD) and hazard quotient (HQ) by bioaccessibility of gastric, intestinal and colon. Additionally, Proteobacteria and Firmicutes were discovered to be the two predominant kinds of gut microbes in this study. Under arsenic exposure, the abundance of Christensenellaceae, Desulfovibrionaceae and Akkermansiaceae increased, but the quantity of Rikenellaceae decreased. These findings revealed that alterations in gut microbiota had an impact on host metabolism.

The effect of lncRNA MIR155HG-modified MSCs and exosome delivery to synergistically attenuate vein graft intimal hyperplasia.

BACKGROUND: The mesenchymal stem cells (MSCs) were used to repair tissue injury. However, the treatment effect was not satisfactory. We investigated whether lncRNA MIR155HG could promote survival and migration of MSCs under oxidative stress, which mimics in vivo environments. Furthermore, we studied the protective effect of exosomes secreted by MSCs transfected with MIR155HG on endothelial cells. This study aimed to determine whether exploiting MSCs and exosomes modified with lncRNA MIR155HG would exert synergistic therapeutic effect to attenuate vein graft intimal hyperplasia more effectively. METHODS: Lentivirus containing lncRNA MIR155HG overexpressing vector was packaged and used to infect MSCs. Then, CCK-8 assay, flow cytometry, Transwell assay, and Elisa assay were used to assess the functional changes of MSCs with overexpressed MIR155HG (OE-MSCs). Furthermore, the associated pathways were screened by Western blot. MIR155HG-MSCs-derived exosomes (OE-exo) were collected and co-cultured with human umbilicus vein endothelial cell (HUVEC). We validated the protective effect of OE-exo on HUVEC. In vivo, both MSCs and exosomes modified with MIR155HG were injected into a vein graft rat model via tail vein. We observed MSCs homing and intimal hyperplasia of vein graft using a fluorescent microscope and histological stain. RESULTS: Our study found that lncRNA MIR155HG promoted proliferation, migration, and anti-apoptosis of MSCs. NF-κB pathway took part in the regulation process induced by MIR155HG. OE-exo could enhance the activity and healing ability of HUVEC and reduce apoptosis. In vivo, OE-MSCs had a higher rate of homing to vascular endothelium. The combined treatment with OE-MSCs and OE-exo protected vascular endothelial integrity, reduced inflammatory cell proliferation, and significantly attenuated intimal hyperplasia of vein graft. CONCLUSION: LncRNA MIR155HG could promote the survival and activity of MSCs, and reduce the apoptosis of HUVECs using exosome delivery. Exploiting MSCs and exosomes modified with MIR155HG could attenuate vein graft intimal hyperplasia more effectively and maximize the surgical effect.

CD39/CD73 Dysregulation of Adenosine Metabolism Increases Decidual Natural Killer Cell Cytotoxicity: Implications in Unexplained Recurrent Spontaneous Abortion.

Unexplained recurrent spontaneous abortion (URSA) is believed to be associated with impaired immunosuppression at the maternal-fetal interface, but the detailed molecular mechanism remains unclear. The ATP-adenosine metabolic pathway regulated by CD39/CD73 has recently been recognized to be important in immunosuppression. This study aimed to investigate the regulation of decidual natural killer (dNK) cells and fetal extravillous trophoblast (EVT) cells by CD39 and CD73 in URSA, as well as the possible regulatory mechanism of CD39/CD73 via the TGF-ß-mTOR-HIF-1α pathway using clinical samples and cell models. Fewer CD39+ and CD73+ cells were found in the URSA decidual and villous tissue, respectively. Inhibition of CD39 on dNK cells transformed the cells to an activated state with increased toxicity and decreased apoptosis, and changed their cytokine secretion, leading to impaired invasion and proliferation of the co-cultured HTR8/SVneo cells. Similarly, inhibition of CD73 on HTR8/SVneo cells decreased the adenosine concentration in the cell culture media, increased the proportion of CD107a+ dNK cells, and decreased the invasion and proliferation capabilities of the HTR8/SVneo cells. In addition, transforming growth factor-ß (TGF-ß) triggered phosphorylation of mammalian target of rapamycin (mTOR) and Smad2/Smad3, which subsequently activated hypoxia-inducible factor-1α (HIF-1α) to induce the CD73 expression on the HTR8/SVneo cells. In summary, reduced numbers of CD39+ and CD73+ cells at the maternal-fetal interface, which may be due to downregulated TGF-ß-mTOR-HIF-1α pathway, results in reduced ATP-adenosine metabolism and increased dNK cytotoxicity, and potentially contributes to URSA occurrences.

Prostaglandin E1 reduces apoptosis and improves the homing of mesenchymal stem cells in pulmonary arterial hypertension by regulating hypoxia-inducible factor 1 alpha.

BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with oxidative stress and affects the survival and homing of transplanted mesenchymal stem cells (MSCs) as well as cytokine secretion by the MSCs, thereby altering their therapeutic potential. In this study, we preconditioned the MSCs with prostaglandin E1 (PGE1) and performed in vitro and in vivo cell experiments to evaluate the therapeutic effects of MSCs in rats with PAH. METHODS: We studied the relationship between PGE1 and vascular endothelial growth factor (VEGF) secretion, B-cell lymphoma 2 (Bcl-2) expression, and C-X-C chemokine receptor 4 (CXCR4) expression in MSCs and MSC apoptosis as well as migration through the hypoxia-inducible factor (HIF) pathway in vitro. The experimental rats were randomly divided into five groups: (I) control group, (II) monocrotaline (MCT) group, (III) MCT + non-preconditioned (Non-PC) MSC group, (IV) MCT + PGE1-preconditioned (PGE1-PC) MSC group, and (V) MCT+PGE1+YC-1-PCMSC group. We studied methane dicarboxylic aldehyde (MDA) levels, MSC homing to rat lungs, mean pulmonary artery pressure, pulmonary artery systolic pressure, right ventricular hypertrophy index, wall thickness index (%WT), and relative wall area index (%WA) of rat pulmonary arterioles. RESULTS: Preconditioning with PGE1 increased the protein levels of HIF-1 alpha (HIF-1α) in MSCs, which can reduce MSC apoptosis and increase the protein levels of CXCR4, MSC migration, and vascular endothelial growth factor secretion. Upon injection with PGE1-PCMSCs, the pulmonary artery systolic pressure, mean pulmonary artery pressure, right ventricular hypertrophy index, %WT, and %WA decreased in rats with PAH. PGE1-PCMSCs exhibited better therapeutic effects than non-PCMSCs. Interestingly, lificiguat (YC-1), an inhibitor of the HIF pathway, blocked the effects of PGE1 preconditioning. CONCLUSIONS: Our findings indicate that PGE1 modulates the properties of MSCs by regulating the HIF pathway, providing insights into the mechanism by which PGE1 preconditioning can be used to improve the therapeutic potential of MSCs in PAH.

Mesenchymal stem cells transfected with anti-miRNA-204-3p inhibit acute rejection after heart transplantation by targeting C-X-C motif chemokine receptor 4 (CXCR4) in vitro.

BACKGROUND: Mesenchymal stem cells (MSCs) are a promising treatment for acute rejection (AR) after heart transplantation (HTx) owing to their immunomodulatory functions by promoting the transformation of macrophages from the M0 to M2 phenotype. However, it is undetermined whether surface expression of C-X-C motif chemokine receptor 4 (CXCR4) by MSCs influences macrophage polarization. In this study, we investigated the effects of MSCs on macrophages caused by CXCR4, and detected the underlying mechanism, which may contribute to improving HTx outcomes. METHODS: The MSCs were extracted from rat bone marrow and identified using flow cytometry. We subsequently observed the effects of CXCR4 and anti-miRNA-204-3p on cell proliferation and migration, and the effects on macrophage polarization. Dual luciferase reporter assay was used to explore whether miRNA-204-3p was an upstream microRNA (miRNA) of CXCR4. A series of rescue experiments were performed to further confirm the inhibitory effect of miRNA-204-3p on CXCR4. RESULTS: The results showed that CXCR4 could promote the proliferation and migration of MSCs. Furthermore, it facilitated MSC-mediated macrophage transformation from the M0 to M2 phenotype. In addition, miRNA-204-3p inhibited the function of CXCR4 of MSCs. CONCLUSIONS: Regulated by miRNA-204-3p, CXCR4 could inhibit the progression of AR after HTx. This study provides a new insight of the treatment of AR after HTx.

Predicting the Risk of Adverse Events in Pregnant Women With Congenital Heart Disease.

Background Women with congenital heart disease are considered at high risk for adverse events. Therefore, we aim to establish 2 prediction models for mothers and their offspring, which can predict the risk of adverse events occurred in pregnant women with congenital heart disease. Methods and Results A total of 318 pregnant women with congenital heart disease were included; 213 women were divided into the development cohort, and 105 women were divided into the validation cohort. Least absolute shrinkage and selection operator was used for predictor selection. After validation, multivariate logistic regression analysis was used to develop the model. Machine learning algorithms (support vector machine, random forest, AdaBoost, decision tree, k-nearest neighbor, naïve Bayes, and multilayer perceptron) were used to further verify the predictive ability of the model. Forty-one (12.9%) women experienced adverse maternal events, and 93 (29.2%) neonates experienced adverse neonatal events. Seven high-risk factors were discovered in the maternal model, including New York Heart Association class, Eisenmenger syndrome, pulmonary hypertension, left ventricular ejection fraction, sinus tachycardia, arterial blood oxygen saturation, and pregnancy duration. The machine learning-based algorithms showed that the maternal model had an accuracy of 0.76 to 0.86 (area under the receiver operating characteristic curve=0.74-0.87) in the development cohort, and 0.72 to 0.86 (area under the receiver operating characteristic curve=0.68-0.80) in the validation cohort. Three high-risk factors were discovered in the neonatal model, including Eisenmenger syndrome, preeclampsia, and arterial blood oxygen saturation. The machine learning-based algorithms showed that the neonatal model had an accuracy of 0.75 to 0.80 (area under the receiver operating characteristic curve=0.71-0.77) in the development cohort, and 0.72 to 0.79 (area under the receiver operating characteristic curve=0.69-0.76) in the validation cohort. Conclusions Two prenatal risk assessment models for both adverse maternal and neonatal events were established, which might assist clinicians in tailoring precise management and therapy in pregnant women with congenital heart disease.

[Hemodynamic performance of newly developed composite stentless porcine aortic valve: in vitro testing and in vivo experiment with sheep].

OBJECTIVE: To investigate the effects of a newly developed composite stentless porcine aortic valve constructed from noncoronary leaflets of three porcine aortic valves. METHODS: Fresh porcine hearts with ascending aorta were obtained from a slaughterhouse. The porcine aortic roots with ascending aorta and anterior leaflet of mitral valve and partial ventricular septum were dissected out and were pressurized to maintain their natural anatomical shapes with the leaflets floating freely at zero-pressure. Three noncoronary leaflets fixed in 0.6% glutaraldehyde were carefully matched for size and symmetry to construct a novel composite stentless porcine aortic valve. The lower margin and outside of the valve was covered with a piece of bovine pericardium. The novel stentless valves were tested in vitro pulsatile flow to detect the effective orifice area (EOA) and mean pressure difference (DeltaP) of the valve compared with the stented bovine pericardial bioprostheses of the same size. Sixteen male juvenile sheep underwent implantation of the novel valves in the supra-annular position in under cardio-pulmonary bypass. The intraoperative and postoperative echocardiography and pathological specimen were given to evaluate the hemodynamic performance and observed in the respects of a long-term survival, function of valve and pathological specimen. RESULTS: Since novel valves had the unfavorable muscle-based right coronary leaflet characteristic of porcine valve removed it had larger EOA. Pulsatile flow testing indicated that the EOA of the 3 novel valves was (3.47 +/- 0.15), (3.69 +/- 0.11), and (3.92 +/- 0.18) cm2 respectively, all significantly greater than those of the stented bovine pericardial bioprosthesis [(2.00 +/- 0.16), (2.21 +/- 0.26), and (2.37 +/- 0.42) cm2 respectively] at each integral simulated cardiac output between 3 - 6 L/min (all P < 0.05), while the DeltaP levels of the novel valves were (2.35 +/- 0.41), (3.10 +/- 0.20), and (3.56 +/- 0.16) mm Hg respectively, all significantly lower than those of the stented bovine pericardial bioprosthesis [(4.98 +/- 0.46), (6.82 +/- 1.27), and (8.40 +/- 1.83) mm Hg respectively, all P < 0.05]. Twelve of the sixteen sheep survived after operation. Five of them had lived for more than 90 days, 3 more than 180 days, and 2 more than 360 days. The intra-operative echocardiographic analyses showed low DeltaP [(3.90 +/- 0.78) mm Hg] and no regurgitation in all sheep. After 15 to 360 days, all valves performed excellently. The sheep were postoperatively sacrificed in 5 d, 15 d, 45 d, 90 d, 180 d, or 300 d respectively. Necropsy revealed the valves had a low to mild level of calcification, without periprosthetic leakage and overgrowth of fibrous tissue. CONCLUSION: The newly developed composite stentless porcine aortic valves show excellent hemodynamic performance with lower transvalvular pressure gradient and are relatively easy to implant.

Oxygenation impairment after total arch replacement with a stented elephant trunk for type-A dissection.

OBJECTIVE: To study the risk factors of oxygenation impairment in patients with type-A acute aortic dissection who underwent total arch replacement with a stented elephant trunk. METHODS: In this study, 169 consecutive patients were enrolled who were diagnosed with type-A acute aortic dissection and underwent a total arch replacement procedure at the Qilu Hospital of Shandong University between January 2015 and February 2017. Postoperative oxygenation impairment was defined as arterial oxygen partial pressure/inspired oxygen fraction ≤ 200 with positive end expiratory pressure ≥ 5 cm H2O that occurred within 72 hours of surgery. Perioperative clinical characteristics of all patients were collected and univariable analyses were performed. Risk factors associated with oxygenation impairment identified by univariable analyses were included in the multivariable regression analysis. RESULTS: The incidence of postoperative oxygenation impairment was 48.5%. Postoperative oxygenation impairment was associated with prolonged mechanical ventilation time, intensive care unit stay, and hospital stay. Multivariable regression analysis demonstrated that body mass index (odds ratio [OR], 1.204; 95% confidence interval [CI], 1.065-1.361; P = .003), preoperative oxygenation impairment (OR, 9.768; 95% CI, 4.159-22.941; P < .001), preoperative homocysteine (OR, 1.080; 95% CI, 1.006-1.158; P = .032), circulatory arrest time (OR, 1.123; 95% CI, 1.044-1.207; P = .002), and plasma transfusion (OR, 1.002; 95% CI, 1.001-1.003; P = .002) were significantly associated with postoperative oxygenation impairment. CONCLUSIONS: Postoperative oxygenation impairment is a common complication of surgery for type-A acute aortic dissection. Body mass index, preoperative oxygenation impairment, preoperative homocysteine, circulatory arrest time, and plasma transfusion were independent risk factors for oxygenation impairment after a total arch replacement procedure.

[Expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule in cardiac allografts and significance thereof: experiment with rats].

OBJECTIVE: To investigate the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in allograft with chronic rejection (CR) after heart transplantation. METHODS: Seventy-two SD rats receiving transplantation of the heats of 71 Wistar rats were divided into 4 equal groups: Group A, undergoing heterotopic cervical heart transplantation (transplanted with donor's heart subcutaneously at the neck) and receiving none intervention, and with the transplanted hearts taken out 3 d after transplantation to the end of CR; Group B, injected intravenously with the splenocytes (SPCs) of the donors on day 0, injected with cyclophomide (CP) on d2, transplanted with the donor hearts on d15, with the transplanted hearts taken out 15 - 120 days after transplantation; Group C, transplanted with the donor's heart and injected intraperitoneally with cyclosporine A (Cs A) 10 mg/kg every other day for 8 - 10 times, and with the transplanted hearts taken out 60 d after transplantation to the end of CR; and Group D, injected intravenously with the SPCs of the donors on day 0, injected with CP on d2, transplanted with the donor hearts on d15, with the transplanted hearts taken out 150 - 420 days after transplantation. Immunohistochemical method was used to detect the expression of ICAM-1 and VCAM-1 in the allografts. RESULTS: The cardiac allograft survival time of Group B was the longest. Less ICAM-1 and VCAM-1 expression and lymphocyte infiltration were observed in SPC and CP-pretreated group. Reversely, protein expression levels of ICAM-1 and VCAM-1 were both high and significant lymphocyte infiltration was seen in Groups B and D. There was no significant difference in the expression of ICAM-1 and VCAM-1 between Groups A and C (P > 0.05). CONCLUSION: The expression levels of ICAM-1 and VCAM-1 are associated with the occurrence and development of rejection and have positive correlation with the severity of graft rejection. Determination of ICAM-1 and VCAM-1 can predict the function of allograft and provide evidence for early diagnosis and prevention of CR.