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Abstract Connective tissue disorders such as Marfan- and Loeys-Dietz syndrome (LDS) can lead to aortic aneurysms and aortic dissections in children. Patients with LDS often necessitating multiple aortic surgeries throughout their lives to extend their lifespan. A boy with LDS underwent Bentall procedure at the age of three for aortic aneurysm. At the age of six, this boy was referred to the hospital again due to severe abdominal pain. Computed tomographic angiography (CTA)indicates aortic dissection (DeBakey Type III, Stanford Type B). After a multidisciplinary team discussion, a successful thoracoabdominal aortic replacement was performed.

Damaged skin cannot prevent harmful bacteria from invading tissues, causing infected wounds or even severe tissue damage. In this study, we developed a controlled-release antibacterial composite hydrogel system that can promote wound angiogenesis and inhibit inflammation by sustained releasing Cu-Epigallocatechin-3-gallate (Cu-EGCG) nano-capsules. The prepared SilMA/HAMA/Cu-EGCG hydrogel showed an obvious inhibitory effect on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). It could also promote the proliferation and migration of L929 fibroblasts. In vivo full-thickness infected wound healing experiments confirmed the angiogenesis and inflammation regulating effect. Accelerate collagen deposition and wound healing speed were also observed in the SilMA/HAMA/Cu-EGCG hydrogel treated group. The findings of this study show the great potential of this controlled-release antibacterial composite hydrogel in the application of chronic wound healing.

Abstract Senescence of vascular smooth muscle cells (VSMCs) contributes to the formation of abdominal aortic aneurysm (AAA). Although mesenchymal stem cell exosomes (MSC-EXO) have been confirmed to restrict the development of AAA, their biological activity depends largely on the physiological state of the MSCs. This study aimed to compare the effects of adipose-derived MSC-EXO from healthy donors (HMEXO) and AAA patients (AMEXO) on senescence of VSMCs in AAA and explore the underlying mechanisms. An ApoE-/- mouse model of AAA was used to investigate the therapeutic effects of HMEXO, AMEXO or miR-19b-3p-AMEXO on AAA development. This in vitro model of AAA was established by treating VSMCs with Ang II (Angiotensin II). The senescence of VSMCs was determined by senescence-associated β-galactosidase (SA-β-gal) staining. The morphology of mitochondria in VSMCs was examined by MitoTracker staining. HMEXO exhibited superior capacity compared with AMEXO to inhibit VSMC senescence and attenuate AAA formation in Ang II–treated ApoE-/- mice. In vitro, both AMEXO and HMEXO inhibited Ang II-induced VSMC senescence via downregulation of mitochondrial fission. Notably, compared with HMEXO, the ability of AMEXO to inhibit VSMC senescence was significantly decreased. miRNA sequencing and the expression of miR-19b-3p was significantly decreased in AMEXO compared with HMEXO. Luciferase assay suggested that MST4 (Mammalian sterile-20-like kinase 4) is a potential target of miR-19b-3p. Mechanistically, miR-19b-3p in HMEXO ameliorated VSMC senescence by inhibiting mitochondrial fission via regulation of the MST4/ERK/Drp1 signaling pathway. Overexpression of miR-19b-3p in AMEXO improved their beneficial effect on AAA formation. Our study reveals that MSC-exosomal miR-19b-3p exerts protective effects against Ang II-induced AAA and VSMC senescence via regulation of the MST4/ERK/Drp1 pathway. The pathological state of AAA patients alters the miRNA components of AMEXO and impairs their therapeutic benefits.

AimsUnderstanding the cellular mechanisms underlying early allograft rejection is crucial for the development of effective immunosuppressant strategies. This study aims to investigate the cellular composition of graft-infiltrating cells during the early rejection stage at a single-cell level and identify potential therapeutic targets.MethodsA heterotopic heart transplant model was established using enhanced green fluorescent protein (eGFP)-expressing mice as recipients of allogeneic or syngeneic grafts. At 3 days post-transplant, eGFP-positive cells infiltrating the grafts were sorted and subjected to single-cell RNA-seq analysis. Potential molecular targets were evaluated by assessing graft survival and functions following administration of various pharmacological inhibitors.ResultsA total of 27,053 cells recovered from syngrafts and allografts were classified into 20 clusters based on expression profiles and annotated with a reference dataset. Innate immune cells, including monocytes, macrophages, neutrophils, and dendritic cells, constituted the major infiltrating cell types (>90%) in the grafts. Lymphocytes, fibroblasts, and endothelial cells represented a smaller population. Allografts exhibited significantly increased proportions of monocyte-derived cells involved in antigen processing and presentation, as well as activated lymphocytes, as compared to syngrafts. Differential expression analysis revealed upregulation of interferon activation-related genes in the innate immune cells infiltrating allografts. Pro-inflammatory polarization gene signatures were also enriched in these infiltrating cells of allografts. Gene profiling and intercellular communication analysis identified natural killer cells as the primary source of interferon-γ signaling, activating inflammatory monocytes that displayed strong signals of major histocompatibility complexes and co-stimulatory molecules. The inflammatory response was also associated with promoted T cell proliferation and activation in allografts during the early transplant stages. Notably, caspase-1 exhibited specific upregulation in inflammatory monocytes in response to interferon signaling. The regulon analysis also revealed a significant enrichment of interferon-related motifs within the transcriptional regulatory network of downstream inflammatory genes including caspase-1. Remarkably, pharmacological inhibition of caspase-1 was shown to reduce immune infiltration, prevent acute graft rejection, and improve cardiac contractile function.ConclusionThe single-cell transcriptional profile highlighted the crucial role of caspase-1 in interferon-mediated inflammatory monocytes infiltrating heart transplants, suggesting its potential as a therapeutic target for attenuating rejection.

BackgroundWe studied acute lung injury (ALI) in thoracic aortic disease (TAD) patients and investigated the predictive effect of interleukin-6 (IL-6) in acute lung injury after thoracic aortic disease.MethodsData on 188 TAD patients, who underwent surgery between January 2016 to December 2021 at our hospital, were enrolled in. We analyzed acute lung injury using two patient groups. Patients with No-ALI were 65 and those with ALI were 123. Univariate logistic, LASSO binary logistic regression model and multivariable logistic regression analysis were performed for acute lung injury.ResultsPreoperative IL-6 level was lower (15.80[3.10,43.30] vs. 47.70[21.40,91.60] pg/ml, p 18 pg/ml (area under the curve: AUC = 0.727). Univariate logistic regression analysis showed 19 features for TAD appeared to be early postoperative risk factors of acute lung injury. Using LASSO binary logistic regression, 19 features were reduced to 9 potential predictors (i.e., Scrpost + PLTpost + CPB > 182 min + D-dimerpost + D-dimerpre + Hypertension + Age > 58 years + IL6 > 18 pg/ml + IL6). Multivariable logistic regression analysis showed that Postoperative creatinine, CPB > 182 min and IL-6 > 18 pg/ml were early postoperative risk factors for ALI after TAD, and the odds ratios (ORs) of postoperative creatinine, CPB > 182 min and IL-6 > 18 pg/ml were 1.006 (1.002–1.01), 4.717 (1.306–19.294) and 2.96 (1.184–7.497), respectively. When postoperative creatinine, CPB > 182 min and IL-6 > 18 pg/ml (AUC = 0.819), the 95% confidence interval [CI] was 0.741 to 0.898. Correction curves were nearly diagonal, suggesting that the nomogram fit well. The DCA curve was then drawn to demonstrate clinical applicability. The DCA curve showed that the threshold probability of a patient is in the range of 30% to 90%.ConclusionsThe inclusion of interleukin-6 demonstrated good performance in predicting ALI after TAD surgery.

Umbilical cord mesenchymal stem cells (UCMSCs) transplantation has been proposed as a promising treatment modality for myocardial infarction (MI), but the low retention rate remains a considerable challenge. Injectable natural polymer hydrogels with conductivity ability are highly desirable as cell delivery vehicles to repair infarct myocardium and restore the cardiac function. In this work, we developed a hydrogel system based on gelatin methacrylate (GelMA) and oxidized dextran (ODEX) as cell delivery vehicles for MI. And dopamine could be used as a reductant of graphene oxide (GO) to form reductive GO (rGO). By adjusting the amount of rGO, the conductivity of hydrogels with 0.5 mg/mL rGO concentration (≈10−4 S/cm) was similar to that of natural heart tissue. In vitro cell experiments showed that the prepared hydrogels had excellent biocompatibility and cell delivery ability of UCMSCs. More importantly, GelMA-O5/rGO hydrogel could promote UCMSCs growth and proliferation, improve the myocardial differentiation ability of UCMSCs, and up-regulate the expression of cTnI and Cx43. Further in vivo experiments demonstrated that GelMA-O5/rGO/UCMSCs Hydrogel could significantly improve the ejection fraction (EF) of rats and significantly reduce myocardial infarct area compared to PBS group, promote the survival of UCMSCs, enhance the expression level of cTnI and Cx43, and decrease the expression level of caspase-3. The findings of this study suggested that the injectable conductive GelMA-O5/rGO hydrogel encapsulating UCMSCs could improve damaged myocardial tissue and reconstruct myocardial function, which will be a promising therapeutic strategy for cardiac repair.

Pregnant women with aortic dissection are hemodynamically outmost complex patients. The two major diagnoses that should be considered in pregnant patients with congenital heart disease (CHD) and acute type A aortic dissection presenting with postoperative right ventricular dysfunction are pulmonary thromboembolism and right ventricular infarction. We present a rare case of postoperative right ventricular dysfunction in pregnant women with CHD and acute aortic dissection, which was diagnosed by pulmonary computed tomography angiography and treated by percutaneous coronary intervention.

ObjectivesIsolated abdominal aortic dissection (IAAD) is extremely rare, with its optimal treatment and intervention timing remaining poorly understood. We aimed to study the natural history of IAAD and facilitate better clinical decision.MethodsConsecutive patients admitted to our institution from January 2016 to April 2021 were enrolled and followed up prospectively. All-cause death was taken as the primary endpoint.ResultsA total of 68 patients with IAAD were included. The mean age at presentation was 61.2 ± 14.8 (Range: 26.0, 93.0) years and 55 (80.9%) were male. A total of 38 (55.9%) patients were treated conservatively, 27 (39.7%) received endovascular aneurysm repair (EVAR), and 3 (4.4%) underwent open surgery. After a mean follow-up of 2.4 years (Range: 0.1, 5.5), 9 (13.2%) patients died, 8 of whom (21.0%) were treated conservatively and 1 EVAR (3.7%). Compared with EVAR/open surgery, patient treated conservatively had a much worse survival (p = 0.043). There was no significant difference between different IAAD aortic sizes regarding mortality (p = 0.220). Patients with completely thrombosed false lumen fared improved survival rate, followed by partial thrombosis and patency, respectively, although not significantly (p = 0.190). No significant difference was observed between male and female concerning survival rate (p = 0.970). Patients without symptoms had a significantly improved survival (p = 0.048).ConclusionOn the basis of patients’ preference and surgeons’ experience, a more aggressive treatment regimen for IAAD should be considered, with EVAR being the first choice, especially for those with persistent symptoms and patent false lumen, regardless of sex, age, or aortic size.

ObjectivesWe evaluated the feasibility, effectiveness, and safety of valve-sparing aortic root reconstruction with a bovine pericardium patch for patients with acute type A aortic dissection (ATAAD).MethodsFrom January 2016 to January 2021, 895 consecutive patients with ATAAD received surgical treatment at our hospital. After applying our exclusion criteria, 508 patients were included in this research. Based on the attending surgeon's judgment and preference, 192 patients underwent our novel surgical novel surgical technique of valve-sparing aortic root reconstruction (repair group [RG]) and 316 patients underwent the Bentall procedure (Bentall group [BG]).ResultsIn the RG, the early mortality rate was 4.2% (8/192). In the BG, the early mortality rate was 5.1% (16/316). There were no significant differences between groups. The incidence of postoperative renal failure in the BG was significantly higher than that in the RG. The mean follow-up time was 2.93 years (standard deviation, ±1.38 years). There were no significant differences between groups regarding ATAAD-related mortality and reoperation. In the RG, the rate of freedom from aortic root reoperation at 5 years was 98.2%, and the grade of aortic regurgitation 6 months later was significant less than that before surgery, and it did not worsen during later follow-up.ConclusionsValve-sparing aortic root reconstruction with a bovine pericardium patch can be successfully performed for selected patients with ATAAD and is associated with low in-hospital and late mortality rates and low root reoperation rates during early and midterm follow-up.

ObjectiveThe aim of the study was to investigate surgical modalities and outcomes in patients with type A aortic dissection involving arch anomalies.MethodPatients with type A aortic dissection who underwent surgical treatment at our center between January 2017 and 31 December 2020 were selected for this retrospective analysis. Data including computed tomography (CT), surgical records, and cardiopulmonary bypass records were analyzed. Perioperatively survived patients were followed up, and long-term mortality and aortic re-interventions were recorded.ResultA total of 81 patients with arch anomalies were included, 35 with “bovine” anomalies, 23 with an aberrant right subclavian artery, 22 with an isolated left vertebral artery, and one with a right-sided arch + aberrant left subclavian artery. The strategies of arch management and cannulation differed according to the anatomic variation of the aortic arch. In total, seven patients (9%) died after surgery. Patients with “bovine” anomalies had a higher perioperative mortality rate (14%) and incidence of neurological complications (16%). Overall, four patients died during the follow-up period, with a 6-year survival rate of 94.6% (70/74). A total of four patients underwent aortic re-intervention during the follow-up period; before the re-intervention, three received the en bloc technique (13.6% 3/22) and one received hybrid therapy (11.1% 1/9).ConclusionWith complete preservation and reconstruction of the supra-arch vessels, patients with type A aortic dissection combining arch anomalies can achieve a favorable perioperative prognostic outcome. Patients who received the en bloc technique are more likely to require aortic re-intervention than patients who underwent total arch replacement with a four-branched graft vessel. Cannulation strategies should be tailored according to the variation of anatomy, but routine cannulation with the right axillary artery can still be performed in most patients with arch anomalies, even for patients with an aberrant right subclavian artery.

Abstract Objectives The proper therapeutic management for acute type A aortic intramural hematoma (IMH) is still controversial. The purpose of this study was to compare the outcomes following emergency surgery or conservative treatment for patients with this disease. Methods From January 2015 to December 2018, 124 consecutive patients were diagnosed with an acute type A aortic IMH and were included in this study. According to our surgical indications, they were divided into two groups: an operation group (OG) and a conservative treatment group (CG). Results Of 124 patients, 83 (66.9%) patients accepted emergency surgery and 41 (33.1%) patients accepted strict conservative treatment. There were no differences between these two groups in early mortality and complications. However, the late mortality of patients in the CG was significantly higher than for patients in the OG. A maximum aortic diameter in the ascending aorta and aortic arch ≥ 45 mm and maximum thickness of IMH in the same section ≥ 8 mm were risk factors for IMH related death in patients undergoing conservative treatment. Conclusions The mortality associated with emergency surgery for patients with acute type A aortic IMH was satisfactory. In clinical centers with well-established surgical techniques and postoperative management, emergency surgical treatment may provide a better outcome than medical treatment for patients with acute type A aortic IMH.

BackgroundThe management of malperfusion is vital to improve the outcomes of surgery for acute type A acute aortic dissection (ATAAD). Open arch repair under hypothermic circulatory arrest with selective antegrade cerebral perfusion (HCA/sACP) is safe and efficient but associated with inevitable hypothermia and ischemia-reperfusion injury. The aortic balloon occlusion (ABO) technique is shown to be organ protective by allowing higher temperature and shorter circulatory arrest time. In this study, we aimed to evaluate the safety and efficacy of this new technique for ATAAD patients with lower body malperfusion.MethodsBetween January 2013 and November 2020, 355 ATAAD patients with lower body malperfusion who underwent arch repair in our institute were enrolled. The patients were divided into 2 groups: ABO group (n = 85) and HCA/sACP group (n = 271). Propensity score matching was performed to correct baseline differences.ResultsUsing the propensity score matching, 85 pairs were generated. Circulatory arrest time was significantly lower in the ABO group compared with the HCA/sACP group (median, 8 vs. 22 min; p < 0.001). The incidence of in-hospital mortality (10.6 vs. 12.9%; p = 0.812), stroke (7.1 vs. 7.1%; p = 1.000), dialysis (25.9 vs. 32.9%; p = 0.183), hepatic dysfunction (52.9 vs. 57.6%; p = 0.537), tracheostomy (4.7 vs. 2.4%; p = 0.682), paraplegia (1.2 vs. 4.7%; p = 0.368) were comparable between ABO and HCA/sACP groups. Other outcomes and major adverse events were comparable. The multivariable logistic analysis did not recognize ABO technique protective against any major adverse outcomes.ConclusionsFor ATAAD patients with lower body malperfusion, the ABO technique allows the performance of arch repair with frozen elephant trunk (FET) under higher temperature and shorter circulatory arrest time. However, ABO technique did not improve perioperative outcomes. Future studies are warranted to evaluate the efficacy of this technique.

Objective:This meta-analysis and systematic review investigated whether partial thrombosed false lumen was a predictor for adverse events in uncomplicated Type B aortic dissection (TBAD).Methods:We performed the current systematic review of the medical literature according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The Newcastle-Ottawa Scale was used to evaluate the quality of individual studies. Search terms based on the MEDLINE database included “type B aortic dissection,” “false lumen” and “thrombosis.” The primary outcomes included mortality, intervention, and aortic growth.Results:Six studies were included in this systematic review, with a total number of 692 patients, including 197 patency (28.5%), 214 partial thrombosis (30.9%), and 281 complete thrombosis (40.6%). Due to the insufficient data for quantitative analysis, we only conducted a scoping review for mortality and intervention. For aortic growth, we conducted a meta-analysis based on Standardized Mean Difference (SMD). The SMD of PT vs. P by random effect model was −0.05 (random effect model) [95% confidence interval (CI), −0.39 to 0.29]. The 95% CI crossed with the null line of 0, indicating no significant difference. The SMD was 0.37 (fixed effects model) (95% CI, 0.03–0.71) and 0.70 (fixed effects model) (95% CI, 0.37–1.04) for PT vs. CT, and P vs. CT, respectively.Conclusions:Current researches on partial thrombosis of TBAD are inconsistent. Partial thrombosis is not associated with a faster aortic growth rate. Until more solid evidence is available, we do not recommend partial thrombosis as a surgical indication or high-risk profile for TBAD.Systematic Review Registration: Unique Identifier: CRD42019121912.

As a subunit of the nucleosome remodeling and histone deacetylation (NuRD) complex, GATA zinc finger domain containing 2B (GATAD2B) plays a vital role in chromatin modification and transcriptional regulation. To further investigate the role of GATAD2B in cell fate determination of human ESCs, we generated two GATAD2B homozygous knockout human ESC lines by CRISPR/Cas9 technology. The cell line exhibits normal karyotype and typical stem cell morphology, following the high expression of pluripotent genes and differentiation potential in vitro. These cell lines will provide cell resources to investigate epigenetic regulation in extensive biological processes as menthioned above.

For patients with acute type A aortic dissection, strongly suspected of having concomitant severe coronary artery disease (CAD), preoperative or intraoperative coronary angiography has been recommended. However, conventional selective coronary angiography in this setting may extend the dissection or aortic rupture. We present the use of intraoperative open-heart coronary angiography in a patient with acute type A aortic dissection. A 50-year-old man presented with chest pain and dyspnea and was admitted to our department with acute type A aortic dissection. The patient underwent coronary artery stent implantation in the left anterior descending coronary artery (LAD) 3 years previously due to an acute myocardial infarction. This time we failed to evaluate the patency of the LAD using multidetector computed tomography. An aortic rupture occurred due to conventional coronary angiography, and open-heart coronary angiography was performed. The examination revealed no significant stenosis. A Bentall procedure and total aortic arch replacement were performed, with an intraoperative stent inserted into the descending aorta, and the patient had an uneventful postoperative course. From this case, we learn that intraoperative open-heart coronary angiography is safe and effective in patients with acute type A aortic dissection.

Objective: To investigate the N6-methyladenosine (m6A) modification and the expressions of the m6A regulatory genes in the acute aortic dissection (AD).Methods: MeRIP-seq and RNA-seq experiments of aortic media tissue samples obtained from AD (n = 4) and Controls (n = 4) were conducted. m6A methylation quantification was used to measure the total mRNA m6A level. The five m6A regulators mRNA expressions were analyzed by quantitative polymerase chain reaction (qPCR). Western blot analyses and immunofluorescence staining were used to detect the difference of METTL14 protein expression in the aortas of AD and Normal.Results: Among AD patients, we detected significantly elevated levels of m6A in total RNA. Compared with the normal group, the up methylated coding genes of AD were primarily enriched in the processes associated with extracellular fibril organization, while the genes with down methylation were enriched in the processes associated with cell death regulation. Furthermore, many differentially methylated m6A sites (DMMSs) coding proteins were mainly annotated during the extracellular matrix and inflammatory responses.Conclusions: These findings indicate that differential m6A methylation and m6A regulatory genes, including MTEEL14 and FTO, may act on functional genes through RNA modification, thereby regulating the pathogenesis of aortic dissection.

Background: Aortic aneurysms and/or dissection (AADs) in the aorta are a leading cause of human morbidity and mortality. To date, data on non-syndromic thoracic AADs (TAADs) have been mainly derived from Caucasians, and the genetic basis of TAADs remains to be elucidated. In this study, we assessed gene mutations in a Chinese population with TAADs. Methods: A cohort of 68 non-syndromic familial TAAD Chinese patients was screened for the most common TAAD-causing genes (ACTA2, MYH11, TGFBR1, TGFBR2, and SMAD3) using high-resolution melting (HRM) analysis. Thereafter, 142 unrelated non-syndromic sporadic cases were recruited and further analyzed using HRM analysis to estimate the prevalence of disease-causing mutations in these candidate genes. Results: Two novel ACTA2 mutations (N117I and L348R) were identified in each familial TAAD proband separately, and an additional novel ACTA2 mutation (Y168N) was identified in one patient with sporadic TAADs. In contrast, none of the three mutations occurred in 480 control subjects. Also, no other gene mutations were identified in this cohort of Chinese TAAD patients. Conclusions: The current study identified three novel ACTA2 mutations in Chinese TAAD patients, and these mutations represented the most predominant genes responsible for non-syndromic TAADs. In addition, HRM analysis was shown to be a sensitive and high-throughput method for screening gene mutations. [ABSTRACT FROM AUTHOR]

(J Card Surg 2010;25:742-744) [ABSTRACT FROM AUTHOR]

Background: Inhibition of chemokine receptor 5 (CCR5), a chemokine receptor expressed on activated T cells, is efficacious in modulating inflammation and immunity as well as in patients with human immunodeficiency virus infection. This study examined the effect and mechanism of CCR5 blockade in combination with cyclosporine in prolonging cardiac allograft survival in mice. Methods: Hearts from BALB/c mice were transplanted into C57BL/10 recipients. They were administrated with anti-CCR5 antibody (Ab) or control Ab and cyclosporine or phosphate-buffered (PBS) saline, respectively. To investigate the role of regulatory cells, naïve mice (secondary recipients) underwent adoptive transfer of splenocytes from anti-CCR5 Ab plus cyclosporine-treated recipients and cardiac allograft transplantation. Results: Compared with recipients treated with control Ab plus PBS, allografts treated with anti-CCR5 Ab and cyclosporine showed significantly prolonged survival (p < 0.001), markedly decreased CD4+ and CD8+ T cells (p < 0.005), and increased frequency of CD4+CD25+Foxp3+ regulatory cells (23.98% ± 1.55% vs 6.30% ± 0.57%, p < 0.005). Adoptive transfer of CD4+CD25+ splenocytes from anti-CCR5 Ab plus cyclosporine-treated recipients induced significantly prolonged survival in secondary recipients (p < 0.01 vs adoptive transfer from naïve mice and recipients depleted of CD25+ cells). Conclusions: CCR5 blockade combined with cyclosporine is effective in protecting the cardiac allograft in a robust murine model. This effect is partly mediated by regulatory cell recruitment and control of effector cell infiltration. [Copyright &y& Elsevier]