Anzhen Risk Evaluation System for Acute Aortic Syndrome (AZSCORE-AAS): protocol for a multicentre prospective cohort study in northern China.

INTRODUCTION: Acute aortic syndrome (AAS) is a group of acute and critical conditions, including acute aortic dissection (AAD), acute intramural haematoma and penetrating aortic ulcer. High mortality and morbidity rates result in a poor patient prognosis. Prompt diagnoses and timely interventions are paramount for saving patients' lives. In recent years, risk models for AAD have been established worldwide; however, a risk evaluation system for AAS is still lacking in China. Therefore, this study aims to develop an early warning and risk scoring system in combination with the novel potential biomarker soluble ST2 (sST2) for AAS. METHODS AND ANALYSIS: This multicentre, prospective, observational study will recruit patients diagnosed with AAS at three tertiary referral centres from 1 January 2020 to 31 December 2023. We will analyse the discrepancies in sST2 levels in patients with different AAS types and explore the accuracy of sST2 in distinguishing between them. We will also incorporate potential risk factors and sST2 into a logistic regression model to establish a logistic risk scoring system for predicting postoperative death and prolonged intensive care unit stay in patients with AAS. ETHICS AND DISSEMINATION: This study was registered on the Chinese Clinical Trial Registry website (http://www. chictr. org. cn/). Ethical approval was obtained from the human research ethics committees of Beijing Anzhen Hospital (KS2019016). The ethics review board of each participating hospital agreed to participate. The final risk prediction model will be published in an appropriate journal and disseminated as a mobile application for clinical use. Approval and anonymised data will be shared. TRIAL REGISTRATION NUMBER: ChiCTR1900027763.

Outcome for concomitant mitral regurgitation after surgery for aortic insufficiency.

BACKGROUND: Moderate/severe aortic regurgitation (AR) with concomitant mitral regurgitation (MR) is a common multiple valve disease for which treatment strategies are controversial. The current study explored long-term outcomes of concomitant MR after AR surgery and the effect of combined mitral valvuloplasty. METHODS: A total of 506 patients with moderate/severe AR and concomitant MR undergoing aortic valve surgery between January 2013 and December 2021 in our cardiac center were enrolled. Risk factors for early mortality, late mortality and persistent MR were identified by logistic regression and generalized linear mixed model. RESULTS: At least one follow-up record was available for 96.3% patients up to May 2022 and 264 (66.8%) patients had no or trivial MR, 112 (28.4%) had mild MR, 16 (4.1%) had moderate MR and 3 (0.8%) patients had severe MR. Persistent MR was recorded for 92 (23.3%) patients during follow-up. Combined mitral valvuloplasty (odds ratio: 0.23; 95% confidential interval: 0.08-0.64; p = 0.005) and better left ventricular reverse remodeling (odds ratio: 0.99; 95% confidential interval: 0.986-0.996); p < 0.001) were found likely to reduce the possibility of persistent MR during follow-up. CONCLUSIONS: Most patients with moderate/severe AR and concomitant MR had a good long-term post-surgical outcome for MR. However, a few had persistent MR during follow-up. Combined mitral valvuloplasty and better left ventricular reverse remodeling reduced the possibility of long-term persistent MR.

2022 CMICS Expert Consensus on the Management of Isolated Tricuspid Regurgitation after Left-Sided Valve Surgery.

Tricuspid regurgitation (TR) may occur late after left-sided valve surgery (LSVS). Isolated tricuspid regurgitation after left-sided valve surgery (iTR-LSVS) refers to isolated TR without significant lesions in the mitral and/or aortic position late after mitral and/or aortic replacement or repair. Severe TR has a negative impact on long-term prognosis and requires surgical or transcatheter treatment. However, there is no clear recommendation on when and how intervention should be performed for patients with iTR-LSVS in the current guidelines for the management of valvular heart disease. The historically high operative mortality may be reduced by current minimally invasive techniques and transcatheter therapy. To further understand iTR-LSVS, standardize the treatment, improve the prognosis, and promote the collaboration, the Chinese Minimally Invasive Cardiovascular Surgery Committee (CMICS) wrote this expert consensus on the management of iTR-LSVS from the aspects of etiology, preoperative evaluation, indications for intervention, surgical treatment, transcatheter therapy, and postoperative management.

SHP-1/STAT3 Interaction Is Related to Luteolin-Induced Myocardial Ischemia Protection.

Prevention and management of myocardial ischemia/reperfusion (I/R) injury is a key step in coronary heart disease surgery. Luteolin is a falconoid compound that has an antioxidant effect, but its mechanism in I/R injury in vivo and in vitro is still under explored. This study attempted to reveal the role of luteolin (Lut) in I/R through mediation of the Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1)/Signal transducer and activator of transcription 3 (STAT3) pathway. To establish I/R rat models, the left anterior descending artery (LAD) was ligated for 30 min and re-perfused for 1 h in Lut-pretreated or nude rats. Comparisons between infarct area, cardiac dysfunction, and myocardial cell death and inflammatory reaction were performed in I/R-induced rats. Hypoxia/reoxygenation (H/R) cell models were established by stimulating H9c2 cells with 95% nitrogen and 5% carbon dioxide. Simultaneously, H/R-related cell death and inflammatory reactions were investigated following Lut treatment. The target protein of Lut was identified using western blotting. Pro-inflammatory cytokines were also measured in serum or Lut-pretreated cell culture medium. The results revealed that compared with the I/R group, Lut treatment could significantly decrease myocardial infarction (MI) area, increase left ventricular ejection fraction (LVEF), and decrease cell death and pro-inflammatory cytokines in the serum. Decreased apoptosis and inflammatory cytokines were also observed in H/R cells after Lut treatment. Lut treatment downregulated SHP-1 expression and subsequently upregulated STAT3 phosphorylation in both I/R rat heart tissue and H9c2 cells. The findings of the current study suggest that Lut can protect the heart and reduce MI area, cell apoptosis rate, and inflammatory level in I/R models.

The fate of concomitant mild mitral regurgitation in aortic insufficiency: A neglected subject.

Objectives: Mitral regurgitation (MR) is commonly experienced by patients with aortic insufficiency (AI), and in its mild form, it is considered benign. However, the progression of concomitant mild regurgitation after the aortic valve surgery (AVS) for AI is poorly characterized. The current study aimed to define the long-term outcomes of MR after surgery and identify the risk factors involved in deterioration. Methods: Patients presenting with moderate/severe AI and concomitant mild MR (n = 347) between January 2013 and December 2021 were enrolled. MR grade was assessed by transthoracic echocardiography during the follow-up, and deterioration is defined as an increase in grade to moderate or severe MR from the previous follow-up echocardiography. Analysis of risk factors for early mortality, MR deterioration, and long-term mortality was performed. Results: A total of 278 patients (84.8%) among 328 survivors had at least one follow-up echocardiography, and complete follow-up occurred for 316 patients (96.3%). Mild MR improved to trivial or none in 194 patients (69.8%), progressed to persistent mild MR for 74 patients (26.6%), and deteriorated for 10 patients (3.6%). Preoperative atrial fibrillation [odds ratio (OR), 23.09; 95% confidence interval (CI), 4.35-122.54] and rheumatic AI (OR, 11.61; 95% CI, 1.26-106.85) were shown to be independent risk factors for MR deterioration by generalized linear mixed analysis. Conclusion: Progression of concomitant mild MR is rare in patients with AI after AVS. However, rheumatic AI and preoperative atrial fibrillation increase the probability of MR deterioration. Careful follow-up for this cohort of patients is recommended.

Current Surgical Management of Acute Type A Aortic Dissection in China: A Multicenter Registry Study.

Background: Many countries and regions have established multicenter registration studies to improve the outcomes of acute type A aortic dissection (ATAAD). Objectives: The aims of this study were to report actual preoperative management, surgery type, and early outcomes of surgical treatment for ATAAD in China. Methods: This cohort study uses data from the China Registry of Type A Aortic Dissection, a national clinical registry to investigate management of patients with Stanford type A aortic dissection. The data, including surgical management and outcomes of patients with ATAAD, were analyzed from January 2018 to December 2021. Results: A total of 1,058 patients with ATAAD were enrolled in this study between January 2018 and December 2021. The mean age of all patients was 51.6 ±11.7 years. The median interval from onset to hospital was 10.65 hours (IQR: 6-24 hours), and the median interval from entering the emergency room to starting operation was 13 hours (IQR: 4.08-28.7 hours). Total arch repair was performed in 938 patients (88.7%), and frozen elephant trunk repair was performed in 800 patients (75.6%). The incidence of early mortality was 7.6%. Conclusions: The population of patients with ATAAD in China experienced a longer interval from onset to arrival at the hospital, received more extensive aortic arch repair, and showed a relatively lower early mortality. These findings suggest that there may be a huge survivor bias in patients with ATAAD in China, more efforts should be made to promote prehospital emergency care and preoperative management of Chinese ATAAD patients. (A multicenter registration study of aortic dissection in China; ChiCTR1800015338).

Intrinsic left ventricular impairment in Marfan syndrome: A systematic review and meta-analysis.

BACKGROUND: Intrinsic cardiac impairment in Marfan syndrome (MFS) has been explored in many clinical studies; however, their results have been inconsistent. This meta-analysis aimed to assess the difference in cardiac structure and function between Marfan patients and healthy individuals, and to verify the hypothesis of intrinsic cardiac impairment in MFS. METHODS: Electronic searches for studies were performed in the PubMed, Embase, and Cochrane Library databases. Nine studies with 490 patients with MFS and 478 controls were included in the analysis. Age and sex were strictly matched between Marfan patients and healthy controls in every study. RESULTS: There was no difference in the left ventricular end systolic diameter index (mean difference [MD]: 0.33; 95% confidence interval [CI]: (-0.24, 0.89); p = 0.26) and left ventricular end diastolic diameter index (MD: 0.18; 95% CI: [-0.47, 0.83]; p = 0.58) between Marfan patients and controls. Marfan patients showed larger left ventricular end systolic volume index (MD: 2.62; 95% CI: [0.27, 4.97]; p = 0.03) and left ventricular end diastolic volume index (MD: 4.16; 95% CI: [2.70, 5.63]; p < 0.01) than the control group. Furthermore, Marfan patients showed a lower left ventricular ejection fraction than healthy people (MD: -2.59%; 95% CI: [-4.64%, -0.54%]; p = 0.01). CONCLUSIONS: Intrinsic cardiac impairment was observed in MFS. MFS patients showed the larger left ventricular volume and poorer left ventricular function than matched controls. Considering the potentially adverse impact on cardiac function, intrinsic cardiac impairment in MFS should be considered during the cardiac surgery.

Short-term outcomes of acute coronary involvement in type A aortic dissection without myocardial ischemia: a multiple center retrospective cohort study.

BACKGROUND: To evaluate the early prognosis and management of acute coronary involvement (ACI) in type A aortic dissection (ATAAD) patients without myocardial ischemia (MI). METHODS: We conducted a retrospective cohort study on a multicenter database. A total of 931 ATAAD patients without MI underwent thoracic aortic surgery between 2018 and 2019 in the Acute Aortic Syndrome Cooperation Network (AASCN) and were enrolled in our study. Patients were divided into two groups: ACI group and non-ACI group. RESULTS: There were 139 ACI patients (14.9%) and 792 non-ACI patients (85.1%) in our cohort. ACI group had higher 30-day mortality after surgery than non-ACI group (log-rank test: P = 0.028,Cox regression: hazard ratio [HR], 2.3; 95% confidence interval [95% CI], 1.1-5.39; P = 0.047), especially in sub-group of advanced age (53-80 years; HR, 4.0; 95% CI, 1.3-12.8; P = 0.017), low diastolic blood pressure (29-69 mmHg, HR, 3.8; 95% CI, 1.3-11.2; P = 0.018), low systolic blood pressure (51-119 mmHg, HR, 3.6; 95% CI, 1.1-12.4; P = 0.040), high body mass index (BMI;27.25-47.52 kg/m2; HR, 3.7; 95% CI, 1.3-10.7; P = 0.015) and high hemoglobin (>145 g/L; HR, 4.3; 95% CI, 1.2-16.0; P = 0.030). Acute renal failure was significant more in ACI group than non-ACI group (24.5% vs. 15.9%; P = 0.014). CONCLUSIONS: ACI increases the short-term postoperative mortality and acute renal failure in ATAAD patients without MI. ATAAD patients with ACI may need a narrower control range of blood pressure even if without myocardial ischemia. TRIAL REGISTRATION: ChiCTR1900022637 . Retrospectively registered 19 April 2019.

Artificial Graft Replacement for the Pulmonary Artery Aneurysm: Three Case Reports.

Pulmonary artery aneurysm (PAA) is a relatively rare disease. The symptoms are usually nonspecific and often identified due to coughing or dyspnea. Pericardial tamponade caused by the PAA dissection or rupture is the most common cause of death, so active surgical treatment is recommended. The surgical reports in the literature are handful. Here we report three cases, all of whom were admitted due to exertional dyspnea. PAAs were observed from the main to the left and/or the right pulmonary artery. All three cases received PAA resection and artificial graft replacement with good outcomes.

Machine Learning Prediction Model for Acute Renal Failure After Acute Aortic Syndrome Surgery.

BACKGROUND: Acute renal failure (ARF) is the most common major complication following cardiac surgery for acute aortic syndrome (AAS) and worsens the postoperative prognosis. Our aim was to establish a machine learning prediction model for ARF occurrence in AAS patients. METHODS: We included AAS patient data from nine medical centers (n = 1,637) and analyzed the incidence of ARF and the risk factors for postoperative ARF. We used data from six medical centers to compare the performance of four machine learning models and performed internal validation to identify AAS patients who developed postoperative ARF. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to compare the performance of the predictive models. We compared the performance of the optimal machine learning prediction model with that of traditional prediction models. Data from three medical centers were used for external validation. RESULTS: The eXtreme Gradient Boosting (XGBoost) algorithm performed best in the internal validation process (AUC = 0.82), which was better than both the logistic regression (LR) prediction model (AUC = 0.77, p < 0.001) and the traditional scoring systems. Upon external validation, the XGBoost prediction model (AUC =0.81) also performed better than both the LR prediction model (AUC = 0.75, p = 0.03) and the traditional scoring systems. We created an online application based on the XGBoost prediction model. CONCLUSIONS: We have developed a machine learning model that has better predictive performance than traditional LR prediction models as well as other existing risk scoring systems for postoperative ARF. This model can be utilized to provide early warnings when high-risk patients are found, enabling clinicians to take prompt measures.

Comparison of the efficacy and safety of thoracic endovascular aortic repair with open surgical repair and optimal medical therapy for acute type B aortic dissection: A systematic review and meta-analysis.

BACKGROUND: Current treatment approaches for acute type B aortic dissection (TBAD) are diversified. Thoracic endovascular aortic repair (TEVAR) as an effective and convenient intervention has been adopted extensively. However, the superior efficacy and safety of TEVAR have not yet been well evaluated. This meta-analysis was designed to comprehensively compare the efficacy and safety of TEVAR with open surgical repair and optimal medical therapy for acute type B aortic dissection. METHODS: A systematic search of PubMed, Embase, Cochrane Library and Web of Science up to April 1, 2020 was conducted for relevant studies that compared the efficacy of TEVAR and other conventional interventions in the treatment of TBAD. The primary outcomes were early mortality and midterm or long term survival. The secondary outcomes included early complications and other late outcomes. Two reviewers assessed trial quality and extracted the data independently. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2. RESULTS: A total of 18 studies including 12,789 patients were identified. 30-day/in-hospital mortality was significantly lower in TBAD patients with TEVAR than open surgical repair (OSR), with a pooled OR of 0.54 (95% CI 0.43-0.68; P < 0.00001). Compared with optimal medical therapy (OMT), TEVAR experienced lower incidence of long-term death (≥5-yr mortality), with a pooled OR of 0.46 (95% CI 0.24-0.86; P = 0.02). However, no significant difference between TEVAR and OSR or OMT in long-term survival was found. Compared with OSR, lower incidence of cardiac and pulmonary complications as well as shorter length of stay were observed in TEVAR. Compared with OMT, TEVAR showed higher rate of paraplegia or paraparesis, higher complete thrombosis of the false lumen, as well as longer length of ICU stay. CONCLUSIONS: Our analysis shows that TEVAR may be favorable in reducing 30-day/in-hospital mortality (than OSR) and long-term mortality (than OMT). TEVAR experienced equal efficacy with OSR and OMT in long-term survival. TEVAR showed higher rate of paraplegia or paraparesis, higher complete thrombosis of the false lumen, as well as longer length of ICU stay than OMT; and lower incidence of cardiac and pulmonary complications as well as shorter length of stay than OSR. However, TEVAR indicated similar incidence of other complications and outcomes with OSR and OMT. Further studies especially randomized clinical trials are needed to comprehensively compare the efficacy TEVAR.

Chitosan Hydrogel Enhances the Therapeutic Efficacy of Bone Marrow-Derived Mesenchymal Stem Cells for Myocardial Infarction by Alleviating Vascular Endothelial Cell Pyroptosis.

Myocardial infarction (MI) is one of the higher mortality rates, and current treatment can only delay the progression of the disease. Experiments have shown that cell therapy could improve cardiac function and mesenchymal stem cells (MSCs)-based therapies provide a great promising approach in the treatment of MI. However, low cell survival and engraftment restricts the successful application of MSCs for treating MI. Here, we explored whether co-transplantation of a chitosan (CS) thermosensitive hydrogel with bone marrow-derived MSCs (BMSCs) could optimize and maximize the therapeutic of BMSCs in a mouse model of MI. The fate of transplanted BMSCs was monitored by bioluminescence imaging, and the recovery of cardiac function was detected by echocardiogram. Our results proved that CS hydrogel enhanced the BMSCs' survival and the recovery of cardiac function by protecting the vascular endothelial cells. Further studies revealed that the increased number of vascular endothelial cells was due to the fact that transplanted BMSCs inhibited the inflammatory response and alleviated the pyroptosis of vascular endothelial cells. In conclusions, CS hydrogel improved the engraftment of transplanted BMSCs, ameliorated inflammatory responses, and further promoted functional recovery of heart by alleviating vascular endothelial cell pyroptosis.

Original Research: Adipose-derived stem cells from younger donors, but not aging donors, inspire the host self-healing capability through its secreta.

Adipose-derived stem cells demonstrate promising effects in promoting cutaneous wound healing, but the mechanisms are still not well defined and contradictory views are still debatable. In the present research, we established a mouse cutaneous wound model and investigated the effects of adipose-derived stem cells in wound healing. Adipocyte, adipose-derived stem cells, and epidermal keratinocyte stem cells were isolated from younger and aged donors according to the standard protocol. The conditioned medium either from adipose-derived stem cells or from adipocytes was used to treat epidermal keratinocyte cells. The results showed that adipocytes or adipose-derived stem cells isolated from younger donors demonstrated mild advantage over those cells isolated from aging donors. Adipose-derived stem cells showed stronger stimuli than adipocytes, and the adipose-derived stem cells or adipocytes from younger donors enabled to support higher growth rate of keratinocyte stem cells. The invasion of vasculature was observed at day 10 after posttransplantation in the mice bearing the keratinocyte stem cells or combination of keratinocyte stem cells with adipose-derived stem cells; however, simply inoculating keratinocyte stem cells from aging donors did not result in vasculature formation. Adipose-derived stem cells isolated from younger donors were able to inspire the host's self-healing capabilities, and age-associated factors should be taken into consideration when designing a feasible therapeutic treatment for skin regeneration.

Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA­21 expression, Akt and the Bcl­2/Bax pathway.

Trimetazidine is a piperazine-derived metabolic agent, which exerts cell protective effects and has been reported to be efficient in the treatment of chronic stable angina pectoris. In addition, it has been shown to exert protection against acute myocardial infarction. The present study aimed to investigate whether trimetazidine protects against cardiac ischemia/reperfusion (I/R) injury, and to determine whether its curative effects are associated with microRNA (miRNA)­21 expression, Akt, and the B­cell lymphoma 2 (Bcl­2)/Bcl­2­associated X protein (Bax) pathway. Cardiac I/R injury was induced by ligating the left anterior descending coronary artery in adult rats. Subsequently, cardiac function was evaluated, and the expression levels of miRNA­21, Bcl­2, Bax and phosphorylated­Akt were detected using quantitative polymerase chain reaction and western blotting. The results indicated that trimetazidine was able to significantly protect cardiac function and reduce infarct size in rats following cardiac I/R injury. Furthermore, trimetazidine significantly promoted miRNA­21 expression and phosphorylated­Akt protein expression, and reduced the Bcl­2/Bax ratio in rats following cardiac I/R injury. Knockdown of miRNA­21 using anti­miR­21 plasmids was able to reverse the protective effects of trimetazidine against cardiac I/R injury. These results indicated that miRNA­21 serves a protective role in cardiac I/R injury via Akt and the Bcl­2/Bax pathway. In addition, trimetazidine exerts protective effects against cardiac I/R injury through cardiac miRNA­21 expression, Akt, and the Bcl­2/Bax pathway. Therefore, the present study provided evidence regarding the protective effects of miRNA­21 on cardiac I/R injury following treatment with trimetazidine in vivo.

[Mid-term outcome of endoscopic greater saphenous vein harvesting in coronary artery bypass grafting].

OBJECTIVE: To evaluate the mid-term clinical outcome of endoscopic greater saphenous vein harvesting (EVH) in coronary artery bypass grafting (CABG). Method A total of 205 patients receiving off-pump CABG between July, 2012 and April, 2013 at our department were enrolled in this study, including 66 patients (35 male and 31 female patients with a mean age of 60.3±7.92 years) undergoing EVH and 139 patients (109 male and 30 female patients with a mean age of 59.20±8.37 years) undergoing open greater saphenous vein harvesting (OVH). RESULTS: The surgical procedures were completed smoothly in all the cases. The perioperative mortality rates was 3.03% (2/66) in EVH group, as compared with 3.60% (5/139) in OVH group (P=1.00). Acute myocardial infarction (AMI) occurred during the perioperative period in 3 (2.16%) patients in OVH group and in 1 (1.52%) patient in EVH group. Perioperative low cardiac output syndrome was diagnosed in 4 (2.88%) patients in OVH group and in 2 (3.03%) in EVH group (P>0.05). During the follow-up, 8 (8.80%) patients in OVH group and 5 (8.06%) in EVH group had recurrent angina (P=0.93). No patients experienced AMI during the follow-up. The 2-year patency rate of the venous grafts was 83.59% in OVH group and 82.22% in EVH group (P=0.73). CONCLUSION: EVH has significant advantage in reducing the complications of the incision in the lower limbs. The mid-term patency rates of venous grafts are similar between OVH and EVH, but the long-term patency rate needs further evaluation.

The Tumor Suppressive Role of MiRNA-509-5p by Targeting FOXM1 in Non-Small Cell Lung Cancer.

BACKGROUND/AIMS: Deregulation of microRNAs (miRNAs) expression is a frequent event in cancer development and progression. Recent studies have implied that abnormal expression of miRNAs is frequently observed in non-small cell lung cancer (NSCLC). Here, we examined the levels and biological functions of miR-509-5p in NSCLC. METHODS: The levels of miR-509-5p were measured by real-time quantitative PCR (RT-PCR) in NSCLC cell lines and NSCLC tissues along with adjacent normal tissues. Cell viability was analyzed by MTT and colony formation assay. Cell migration and invasion were evaluated by transwell and wound healing assay. In addition, we predicted the putative targets of miR-509-5p by bioinformatics analyses. Moreover, by luciferase-reporter assay, we analyzed the relationship between miR-509-5p and the target in NSCLC cells. RESULTS: miR-509-5p expression was significantly reduced in NSCLC tissues compared with adjacent normal tissues. In addition, miR-509-5p decreased cell proliferation, migration and invasive capability of NSCLC cells. Moreover, we found that FOXM1 was a putative target of miR-509-5p. Enforced miR-509-5p expression in NSCLC cells reduced both mRNA and protein levels of FOXM1. Furthermore, dual-luciferase reporter assay showed miR-509-5p could bind to the 3' untranslational regions of FOXM1 mRNA. Furthermore, overexpression of FOXM1 reversed cell viability, migration, invasion and vimentin levels suppressed by miR-509-5p mimics in H1299 cells. CONCLUSIONS: miR-509-5p exerts tumor-suppressive effects by attenuating FOXM1 in NSCLC. Collectively, these findings provide further evidence that miR-509-5p may be considered as a novel and potential target for the diagnosis, prognosis and treatment of NSCLC.

ATF3 Inhibits Tenascin-C-induced Foam Cell Formation in LPS-Stimulated THP-1 Macrophages by Suppressing TLR-4.

AIM: Efficiently inhibiting the formation of macrophage foam cells is indispensable for mitigating and treating atherosclerosis. Tenascin-C (TN-C) plays an important role in promoting atherosclerosis; therefore, it is essential to inhibit foam cell formation associated with TN-C for controlling atherosclerosis. Activating transcription factor 3 (ATF3) is one of the factors involved in regulating the complex process of foam cell formation. This study aimed to explore the role of TN-C and ATF3 in LPS-stimulated THP-1-derived macrophages. METHODS: RT-PCR was used for evaluating the expression of TN-C in LPS-stimulated THP-1 macrophages. Further, exogenous TN-C was introduced and incubated with cultured THP-1 macrophages to confirm the effect of TN-C on LPS-stimulated THP-1 macrophages. ATF3-modified THP-1 macrophages were constructed and verified by western blot. High performance liquid chromatography (HPLC) assay and Oil red O staining were applied for detecting cholesteryl ester/total cholesterol (CE/TC) and lipid formation in THP-1 macrophages. RESULTS: The expression of TN-C was determined to be upregulated in LPS-stimulated THP-1 macrophages in a dose- and time-dependent manner. HPLC assay and Oil red O staining confirmed that TN-C can enhance LPS-induced THP-1 macrophage foam cell formation. Moreover, ATF3 can act as a negative regulatory factor for inhibiting TN-C-induced foam cell formation by suppressing TLR-4 in LPS-stimulated THP-1 macrophages. CONCLUSION: ATF3 can inhibit TN-C-induced foam cell formation in LPS-stimulated THP-1 macrophages by suppressing TLR-4. It may be a useful molecular target to control TN-C-induced foam cell formation in atherosclerosis.

A novel, minimally invasive rat model of normothermic cardiopulmonary bypass model without blood priming.

BACKGROUND: Cardiopulmonary bypass (CPB) has been shown to be associated with systemic inflammatory response leading to postoperative organ dysfunction. Elucidating the underlying mechanisms and developing protective strategies for the pathophysiological consequences of CPB have been hampered due to the absence of a satisfactory recovery animal model. The purpose of this study was to establish a novel, minimally invasive rat model of normothermic CPB model without blood priming. METHODS: Twenty adult male Sprague-Dawley rats weighing 450-560 g were randomly divided into CPB group (n = 10) and control group (n = 10). All rats were anaesthetized and mechanically ventilated. The carotid artery and jugular vein were cannulated. The blood was drained from the right atrium via the right jugular and further transferred by a miniaturized roller pump to a hollow fiber oxygenator and back to the rat via the left carotid artery. The volume of the priming solution, composed of 6% HES 130/0.4 and 125 IU heparin, was less than 12 ml. The surface of the hollow fiber oxygenator was 0.075 m(2). CPB was conducted for 60 minutes at a flow rat of 100-120 ml × kg (-1)× min(-1) in CPB group. Oxygen flow/perfusion flow was 0.8 to 1.0, and the mean arterial pressure remained 60-80 mmHg. RESULTS: All CPB processes were successfully achieved. Blood gas analysis and hemodynamic parameters of each time point were in accordance with normal ranges. The vital signs of all rats were stable. CONCLUSIONS: The establishment of CPB without blood priming in rats can be achieved successfully. The nontransthoracic model should facilitate the investigation of pathophysiological processes concerning CPB-related multiple organ dysfunction and possible protective interventions. This novel, recovery, and reproducible minimally invasive CPB model may open the field for various studies on the pathophysiological process of CPB and systemic ischemia-reperfusion injury in vivo.

Evaluation of different minimally invasive techniques in the surgical treatment of atrial septal defect.

OBJECTIVE: Minimally invasive cardiac surgery is becoming a safe and cosmetic alternative to standard median sternotomy (SMS). In the present retrospective study, we reviewed our results and experience with the totally thoracoscopic (TTS) and right vertical infra-axillary thoracotomy (RVIAT) techniques for atrial septal defect closure compared with SMS. METHODS: From December 2010 to February 2012, 198 patients underwent repair of atrial septal defect using the TTS technique (n = 66), RVIAT (n = 59), or SMS (n = 73). Cardiopulmonary bypass was achieved peripherally in the TTS group and directly in the RVIAT and SMS groups. RESULTS: The procedures were performed successfully in all 3 groups, and no in-hospital mortality occurred. No patient required conversion to SMS in the TTS group, although 2 patients did so in the RVIAT group. The cardiopulmonary bypass time was 87.26 ± 21 minutes in the TTS group, 41.81 ± 13.97 minutes in the RVIAT group, and 36.99 ± 10.84 minutes in the SMS group (P < .01). The crossclamp time was 32.86 ± 13.36, 22.54 ± 9.08, and 19.23 ± 6.92 minutes in the TTS, RVIAT, and SMS groups, respectively (P < .01). The total incision length in the SMS group (7.45 ± 1.54 cm) was longer than that in the other groups (TTS group, 5.21 ± 0.63 cm; RVIAT group, 6.48 ± 1.37 cm); the difference was statistically significant (P < .01). CONCLUSIONS: The TTS technique and RVIAT can both be performed with favorable cosmetic and acceptable clinical results for closing atrial septal defects. They are promising alternatives to SMS and merit additional study.

A novel, recovery, and reproducible minimally invasive cardiopulmonary bypass model with lung injury in rats.

BACKGROUND: Cardiopulmonary bypass (CPB) has been shown to be associated with a systemic inflammatory response leading to postoperative organ dysfunction. Elucidating the underlying mechanisms and developing protective strategies for the pathophysiological consequences of CPB have been hampered due to the absence of a satisfactory recovery animal model. The purpose of this study was to establish a good rat model of CPB to study the pathophysiology of potential complications. METHODS: Twenty adult male Sprague-Dawley rats weighing 450-560 g were randomly divided into a CPB group (n = 10) and a control group (n = 10). All rats were anaesthetized and mechanically ventilated. The carotid artery and jugular vein were cannulated. The blood was drained from the right atrium via the right jugular and transferred by a miniaturized roller pump to a hollow fiber oxygenator and back to the rat via the left carotid artery. Priming consisted of 8 ml of homologous blood and 8 ml of colloid. The surface of the hollow fiber oxygenator was 0.075 m(2). CPB was conducted for 60 minutes at a flow rate of 100-120 ml× kg(-1)×min(-1) in the CPB group. Oxygen flow/perfusion flow was 0.8 to 1.0, and the mean arterial pressure remained 60-80 mmHg. Blood gas analysis, hemodynamic investigations, and lung histology were subsequently examined. RESULTS: All CPB rats recovered from the operative process without incident. Normal cardiac function after successful weaning was confirmed by electrocardiography and blood pressure measurements. Mean arterial pressure remained stable. The results of blood gas analysis at different times were within the normal range. Levels of IL-1ß and TNF-α were higher in the lung tissue in the CPB group (P < 0.005). Histological examination revealed marked increases in interstitial congestion, edema, and inflammation in the CPB group. CONCLUSION: This novel, recovery, and reproducible minimally invasive CPB model may open the field for various studies on the pathophysiological process of CPB and systemic ischemia-reperfusion injury in vivo.