Early postoperative constrictive pericarditis in China: a single-center retrospective observational study.

Background: The diagnosis, treatment, and prognosis of early postoperative constrictive pericarditis (EPCP) have not been discussed in depth. The objective of this study was to devise and propose a management strategy for EPCP. Methods: In this study, constrictive pericarditis (CP) within 6 months after cardiac surgery was defined as EPCP, and patients were divided into two groups based on intraoperative findings: a parietal thickening group and a visceral thickening group. Results: A total of 20 patients were included in this study, and the incidence rate of recurrent pericardiectomy was 0.32% among all patients undergoing cardiovascular surgery. EPCP after valve surgery occurred in 85.0% of patients. Pleural effusion was the most common preoperative symptom, occurring in 90% of patients. Pericardial thickening occurred in the visceral layer in seven cases and in the parietal layer in 13 cases. There were no differences in comorbidities, C-reactive protein (CRP) level, or erythrocyte sedimentation rate (ESR) between the two groups. Most patients with visceral thickening (83.3%) needed cardiopulmonary bypass (CPB) assistance during surgery and had a longer hospital stay than those with parietal thickening (52.8±21.8 vs. 34.9±13.8 days, P=0.049). Central venous pressure (CVP) was decreased in all patients after pericardiectomy (24.9±6.96 vs. 8.9±2.92 cmH2O, P<0.001), and the cardiac function improved significantly in patients with parietal thickening [New York Heart Association (NYHA) grade ≥ III accounted for 28.6% of patients]. The long-term survival rate of patients with parietal thickening was 92.3% and that of patients with visceral thickening was 57.1%, and there was no significant difference between them (P=0.056). Conclusions: Recurrent episodes of chest tightness, pleural effusion, and elevated CVP within 6 months after cardiac surgery should be considered highly suggestive of EPCP. There are few points of difference between pericarditis with thickening of the parietal and visceral layers. After failure of conservative medical treatment, pericardiectomy results in significant improvements in cardiac function and quality of life, especially in patients with thickening of the parietal layer.

Inhibition of valve mesenchymal stromal cell calcium deposition by bFGF through alternative polyadenylation regulation of the CAT gene.

OBJECTIVE: Calcific aortic valve disease (CAVD) is the leading cause of angina, heart failure, and death from aortic stenosis. However, the molecular mechanisms of its progression, especially the complex disease-related transcriptional regulatory mechanisms, remain to be further elucidated. METHODS: This study used porcine valvular interstitial cells (PVIC) as a model. We used osteogenic induced medium (OIM) to induce calcium deposition in PVICs to calcify them, followed by basic fibroblast growth factor (bFGF) treatment to inhibit calcium deposition. Transcriptome sequencing was used to study the mRNA expression profile of PVICs and its related transcriptional regulation. We used DaPars to further examine alternative polyadenylation (APA) between different treatment groups. RESULTS: We successfully induced calcium deposition of PVICs through OIM. Subsequently, mRNA-seq was used to identify differentially expressed mRNAs for three different treatments: control, OIM-induced and OIM-induced bFGF treatment. Global APA events were identified in the OIM and bFGF treatment groups by bioinformatics analysis. Finally, it was discovered and proven that catalase (CAT) is one of the potential targets of bFGF-induced APA regulation. CONCLUSION: We described a global APA change in a calcium deposition model related to CAVD. We revealed that transcriptional regulation of the CAT gene may contribute to bFGF-induced calcium deposition inhibition.

An improved nomogram including elastography for the prediction of non-sentinel lymph node metastasis in breast cancer patients with 1 or 2 sentinel lymph node metastases.

Background: The rate of breast-conserving surgery is very low in China, compared with that in developed countries; most breast cancer patients receive mastectomy. It is great important to explore the possibility of omitting axillary lymph node dissection (ALND) in early-stage breast cancer patients with 1 or 2 positive sentinel lymph nodes (SLNs) in China. The aim of this study was to develop a nomogram based on elastography for the prediction of the risk of non-SLN (NSLN) metastasis in early-stage breast cancer patients with 1 or 2 positive SLNs. Methods: A total of 601 breast cancer patients were initially recruited. According to the inclusion and exclusion criteria, 118 early-stage breast cancer patients with 1 or 2 positive SLNs were finally enrolled and were assigned to the training cohort (n=82) and the validation cohort (n=36), respectively. In the training cohort, the independent predictors were screened by logistic regression analysis and then were used to conducted the nomogram for the prediction of NSLN metastasis in early-stage breast cancer patients with 1 or 2 positive SLNs. The calibration curves, concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and Decision curve analysis (DCA) were used to verified the performance of the nomogram. Results: The multivariable analysis showed that the enrolled patients with positive HER2 expression (OR=6.179, P=0.013), Ki67≥14% (OR=8.976, P=0.015), larger lesion size (OR=1.038, P=0.045), and higher Emean (OR=2.237, P=0.006) were observed to be the independent factors of NSLN metastasis. Based on the above four independent predictors, a nomogram was conducted to predict the risk of the NSLN metastasis in early-stage breast cancer patients with 1 or 2 positive SLNs. The nomogram showed good discrimination in the prediction of NSLN metastasis, with bias-corrected C-index of 0.855 (95% CI, 0.754-0.956) and 0.853 (95% CI, 0.724-0.983) in the training and validation cohorts, respectively. Furthermore, the AUC was 0.877 (95%CI: 0.776- 0.978) and 0.861 (95%CI: 0.732-0.991), respectively, indicating a good performance of the nomogram. The calibration curve suggested a satisfactory agreement between the predictive and actual risk in both the training (χ2 = 11.484, P=0.176, HL test) and validation (χ2 = 6.247, p = 0.620, HL test) cohorts, and the obvious clinical nets were revealed by DCA. Conclusions: We conducted a satisfactory nomogram model to evaluate the risk of NSLN metastasis in early-stage breast cancer patients with 1 or 2 SLN metastases. This model could be considered as an ancillary tool to help such patients to be selectively exempted from ALND.

Effect of preoperative pulmonary artery pressure on the prognosis of end-stage heart failure patients after heart transplantation.

OBJECTIVE: To evaluate the effect of preoperative pulmonary artery pressure on perioperative outcome of end-stage heart failure patients undergoing heart transplantation. METHODS: Retrospective analysis was undertaken on the clinical data of patients receiving heart transplantation in the Department of Cardiovascular Surgery of our hospital from March 2017 to March 2022. A ROC curve analysis was developed between mean pulmonary artery pressure (mPAP) and postoperative mortality using mPAP as diagnostic criteria. Patients were divided into groups based on this threshold to determine the best mPAP threshold value for predicting postoperative nosocomial mortality, and the differences in preoperative and intraoperative data, postoperative complications, and clinical prognosis of patients in the two groups were compared. Patients were followed up to draw the survival curve of patients in the two groups. RESULTS: The study enlisted the participation of 105 patients. ROC curve research revealed that preoperative pulmonary artery pressure was substantially linked with death following heart transplantation, with mPAP = 30.5mmHg being the best threshold. The group with mPAP ≥ 30.5mmHg had a greater incidence of postoperative ECMO support (28.2% vs. 10.6%, P = 0.021) and a higher incidence of in-hospital mortality (15.4% vs. 1.5%, P = 0.019) than the group with mPAP < 30.5mmHg. The postoperative survival rates of 105 patients were 91.3%, 88.7%, 81.6%, and 77.5% at 1, 2, 3, and 4 years, respectively, however, there was no significant difference between the two groups of patients in the postoperative intermediate-far survival rate (P = 0.431). CONCLUSIONS: Preoperative pulmonary artery pressure in patients with end-stage heart failure is intimately correlated with perioperative prognosis of heart transplant recipients. The optimal cut-off mPAP value in predicting perioperative prognosis of heart transplant recipients is 30.5mmHg. In the high mPAP group, perioperative ECMO support rate and perioperative mortality rate are high, which do not affect the medium and long-term prognosis of the recipients undergoing heart transplantation.

Tetraphenylethene-Based cis/trans Isomers for Targeted Fluorescence Sensing and Biomedical Applications.

Molecular probes which can be modulated, functionalized and used to visualize the processes are highly desirable for understanding and manipulating biological systems. Geometric cis and trans isomers of tetraphenylethene (TPE) emerge as attractive candidates to fulfill these tasks thanks to the unique aggregation-induced emission properties, tailorable structures, and responsiveness to external stimuli. This minireview focuses on cis and trans isomers of TPE derivatives that are functionalized with molecular recognition units for fluorescence detection, bioimaging and cancer therapy. The effects of molecular geometry on fluorescence property, target binding ability and biological activity are summarized. The feasibility to in vitro and in vivo switch molecular configuration and thus bio-activity is discussed. Finally, the future development and challenges are discussed in view of TPE-based stereoisomers for targeted sensing and imaging-guided modulation of biological processes.

NDRG1 Signaling Is Essential for Endothelial Inflammation and Vascular Remodeling.

BACKGROUND: NDRG-1 (N-myc downstream-regulated gene 1) is a member of NDRG family that plays essential roles in cell differentiation, proliferation, and stress responses. Although the expression of NDRG1 is regulated by fluid shear stress, its roles in vascular biology remain poorly understood. The purpose of the study is to determine the functional significance of NDRG1 in vascular inflammation and remodeling. METHODS AND RESULTS: By using quantitative polymerase chain reaction, western blot, and immunohistochemistry, we demonstrate that the expression of NDRG1 is markedly increased in cytokine-stimulated endothelial cells and in human and mouse atherosclerotic lesions. To determine the role of NDRG1 in endothelial activation, we performed loss-of-function studies using NDRG1 short hairpin RNA. Our results demonstrate that NDRG1 knockdown by lentivirus bearing NDRG1 short hairpin RNA substantially attenuates both IL-1ß (interleukin-1ß) and TNF-α (tumor necrosis factor-α)-induced expression of cytokines/chemokines and adhesion molecules. Intriguingly, inhibition of NDRG1 also significantly attenuates the expression of procoagulant molecules, such as PAI-1 (plasminogen activator inhibitor type 1) and TF (tissue factor), and increases the expression of TM (thrombomodulin) and t-PA (tissue-type plasminogen activator), thus exerting potent antithrombotic effects in endothelial cells. Mechanistically, we showed that NDRG1 interacts with orphan Nur77 (nuclear receptor) and functionally inhibits the transcriptional activity of Nur77 and NF-κB (nuclear factor Kappa B) in endothelial cells. Moreover, in NDRG1 knockdown cells, both cytokine-induced mitogen-activated protein kinase activation, c-Jun phosphorylation, and AP-1 (activator protein 1) transcriptional activity are substantially inhibited. Neointima and atherosclerosis formation induced by carotid artery ligation and arterial thrombosis were markedly attenuated in endothelial cell-specific NDRG1 knockout mice compared with their wild-type littermates. CONCLUSIONS: Our results for the first time identify NDRG1 as a critical mediator implicated in regulating endothelial inflammation, thrombotic responses, and vascular remodeling, and suggest that inhibition of NDRG1 may represent a novel therapeutic strategy for inflammatory vascular diseases, such as atherothrombosis and restenosis.

An Analysis of Total Arch Re-Replacement After Proximal Aortic Surgery.

BACKGROUND: After proximal aortic surgery, total arch replacement (TAR) may again be needed because of recurrent dissection or aneurysm. This paper analyzed the relevant data of this technology with hopes of improving cognition and treatment. METHODS: There were a total of 60 eligible cases of secondary TAR after proximal aortic surgery in our center from 2010 to 2020. The primary surgical procedures included aortic valve replacement (AVR), ascending aortic replacement, Bentall, hemi-arch replacement, and thoracic endovascular aortic repair (TEVAR). The data were analyzed using the IBM SPSS Statistics 23.0 for Windows™ and presented as the mean ± standard deviations and direct frequencies, as appropriate. RESULTS: The interval between two operations was 44.8±53.6 months, 24 cases (40%) underwent emergency operation, the recurrence of type A dissection included 51 cases, accounting for 85% of the causes of total arch re-replacement. In the second surgical procedures, the ascending + TAR + stented elephant trunk (SET) implantation accounted for 75.0%. The overall surgical success rate was 98.3%. Postoperative respiratory complications were the most common, including infection, pneumothorax and hemothorax in 21 cases (35.6%). The second most common complication was acute kidney injury (AKI) in six cases (10.2%), and neurological complications took place in three cases (5.1%). The 30-day mortality rate was 15.3% and the 1-, 3- and 5-year survival rates were 96.0%, 84.0%, and 76.0%, respectively. CONCLUSIONS: The recurrence of dissection is the main cause of TAR after proximal aortic surgery, followed by aneurysm and the resurgical criteria for aneurysm needs to be unified. In addition to TAR, SET also is widely used. Despite high early mortality, its long-term prognosis is acceptable.

Tuning Proapoptotic Activity of a Phosphoric-Acid-Tethered Tetraphenylethene by Visible-Light-Triggered Isomerization and Switchable Protein Interactions for Cancer Therapy.

We herein report a phosphoric-acid-substituted tetraphenylethene (T-P) capable of adapting its geometric configuration and biological activity to the microenvironment upon light irradiation for apoptosis modulation. Different from most ultraviolet-responsive isomerization, T-P undergoes cis-trans isomerization under visible light irradiation, which is biocompatible and thus photo-modulation is possible in living biosystems. By using alkaline phosphatase (ALP) and albumin as dual targets, T-P isomers display different protein binding selectivity, cancer-cell internalization efficiency and apoptosis-inducing ability. The proapoptotic activity was found to be kinetically controlled by the enzymatic reaction with ALP and regulated by co-existing albumin. Motivated by these findings, two-way modulation of proapoptotic effect and on-demand boosting anticancer efficacy were realized in vitro and in vivo using light and endogenous proteins as multiple non-invasive switching stimuli.

Photosensitizer with High Efficiency Generated in Cells via Light-Induced Self-Oligomerization of 4,6-Dibromothieno[3,4-b]thiophene Compound Entailing a Triphenyl Phosphonium Group.

Photodynamic therapy (PDT) has emerged as an attractive alternative in cancer therapy, but therapeutic effects suffer from low photosensitizing efficiency and poor retention of photosensitizes in cancer cells. This paper reports the photosensitizers which show absorption and emission in the long-wavelength region and high photosensitizing efficiency can be formed in situ in cells from 4,6-dibromothieno[3,4-b]thiophene derivative (TT-5-P) after white light irradiation. The self-oligomerization of TT-5-P is uptaken in cells upon light irradiation-induced cell apoptosis simultaneously and efficiently. In addition, the formation of oligomers (TT-5-Ps) enhances the retention time in cells remarkably, which is advantageous for boosting the photodynamic therapy efficiency. Moreover, the selectivity toward tumor cells of TT-5-P can be improved obviously via the formation of complex of TT-5-P with albumin. This in situ photoinduced self-oligomerization strategy can be utilized to design effective biomaterials for long-term imaging and improved therapy.

A Systematic Strategy of Combinational Blow for Overcoming Cascade Drug Resistance via NIR-Light-Triggered Hyperthermia.

A systematic combination strategy is proposed for overcoming cisplatin resistance using near-infrared (NIR)-light-triggered hyperthermia. A new photothermal polymer DAP-F is complexed with a reduction-sensitive amphiphilic polymer P1 to form F-NPs with photothermal effect. Subsequently, to build the final nanosystem F-Pt-NPs, F-NPs are combined with Pt-NPs, which are obtained by encapsulating a Pt(IV) prodrug with P1. Mild hyperthermia (43 °C), generated from F-Pt-NPs induced by an 808 nm NIR laser, have various effects such as: i) enhancing the cellular membrane permeability to promote the uptake of drugs; ii) activating cisplatin by accelerating the glutathione consumption; iii) increasing the Pt-DNA adducts formation and possibly the formation of a portion of irreparable Pt-DNA interstrand crosslinks, thereby inhibiting the repair of DNA. In vitro, it is found that even on cisplatin-resistant A549DDP cells, the IC50 of F-Pt-NPs (43 °C) is only 7.0 × 10-6 m Pt mL-1 . In vivo, on a patient-derived xenograft model of multidrug resistant lung cancer, the efficacy of the F-Pt-NPs (43 °C) treatment group shows a tumor inhibition rate of 94%. Taken together, here, an important perspective of resolving cascade drug resistance with the assistance of mild hyperthermia triggered by NIR light is presented, which can be of great significance for clinic translation.

Clinical Outcome of Reoperation for Mechanical Prosthesis at Aortic Position.

AIM: Redo aortic valve surgery is usually associated with a high risk of mortality and complications. The aim of this study was to investigate the perioperative and long-term outcomes of reoperation after prior mechanical prosthesis implantation at the aortic position. METHOD: The clinical data of 146 consecutive patients who underwent reoperation at the aortic position between 2003 and 2019 were analysed. RESULTS: Mean age was 51.5±12.7 years and 69 (47.3%) were female. The median interval from prior surgery to redo aortic valve surgery was 6 years. The aetiologies were pannus formation with prosthetic aortic stenosis in 62 cases (42.5%), prosthetic valve endocarditis (PVE) in five (3.4%), PVE with perivalvular leakage (PVL) in 16 (11.0%), PVL in 45 (30.8%), thrombosis in seven (4.8%), and aortic disease in 11 (7.5%). As for surgical procedure, aortic valve replacement was performed in 81 cases (55.5%), Bentall in 34 (23.3%), PVL repair in six (4.1%), and pannus debridement in 25 (17.1%). Fourteen (14) (9.6%) patients expired perioperatively. Prolonged ventilation time and postoperative renal failure were proved to be significant independent predictors of mortality according to multivariate analysis. Overall survival was 87.8%±7.4% and 76.4%±15.1% at 5 and 10 years, respectively. Survival was 87.7%±13.7% and 84.2%±15.6% in the pannus group, and 84.5%±12.6% and 74.6%±19.4% in the non-pannus group at 5 and 10 years, respectively (p=0.951). Survival was 87.5%±14.2% and 75.8%±22.7% in the PVL group and 84.7%±11.9% and 81.6%±13.5% in the non-PVL group at 5 and 10 years, respectively (p=0.365). CONCLUSIONS: Pannus formation and PVL are two major indications for reoperation of mechanical prosthesis at the aortic position. Redo aortic valve surgery has a satisfactory outcome but with a high risk of complications. Long-term survival of patients seems not to be related to the aetiology. Final decision-making of redo aortic valve surgery should be based on aetiology.

Risk factors of chronic left ventricular dysfunction after cardiac valve surgery.

BACKGROUND: To analyze the risk factors of chronic left ventricular dysfunction (LVD) after cardiac valve surgery. METHODS: A retrospective analysis of 860 patients who underwent heart valve surgery in our center from January 2017 to December 2018, including 650 males and 210 females, aged 58±5.8 years. Inclusion criteria: (I) the patient was clinically diagnosed with heart valve disease and met the surgical indications for mitral valve replacement (MVR), mitral valve repair (MVP), aortic valve replacement (AVR) and double valve replacement (DVR); (II) if atrial fibrillation, coronary artery disease, and tricuspid regurgitation are combined before surgery, radiofrequency ablation, coronary bypass and tricuspid angioplasty were performed contemporarily. Exclusion criteria: (I) preoperative LVEF <50%; (II) aortic dissection underwent Bentall and right heart valve replacement procedures; (III) cardiopulmonary resuscitation and death during perioperative period and 6 months after operation; (IV) postoperative CRRT, IABP, or ECMO assistance; (V) postoperative cardiac dysfunction due to valvular dysfunction, perivalvular leak, or infective endocarditis. Patients were divided into LVD group (LVEF <40%) and control group (LVEF ≥40%) based on cardiac LVEF at 6 months after surgery. Logistic regression was used to analyze the risk factors of postoperative LVD. RESULTS: There were 126 cases in LVD group and 734 cases in control group. There were significant differences in preoperative coronary artery disease, atrial fibrillation, pulmonary hypertension, NYHA classification, left ventricular end diastolic diameter (LVEDD), and left ventricular end systolic diameter (LVESD) between the two groups (P<0.05). The differences in the changes of LVEDD and LVESD before and after operation between the two groups were statistically significant (P<0.05). Logistic regression analysis showed that preoperative LVEDD >55 mm, preoperative LVESD >40 mm, preoperative combined atrial fibrillation, preoperative combined pulmonary hypertension, preoperative NYHA III-IV, and preoperative combined coronary artery disease were the risks of postoperative chronic LVD. CONCLUSIONS: The left ventricular diameter, preoperative coronary artery disease, NYHA III-IV, preoperative atrial fibrillation, and preoperative pulmonary hypertension are risk factors for chronic LVD after heart valve surgery.

Aggregation-Induced Emission Luminogens for Mitochondria-Targeted Cancer Therapy.

The importance of mitochondria in tumorigenesis makes these organelles an ideal target for cancer therapy. In recent years, luminogens with the aggregation-induced emission (AIE) effect have been developed for mitochondrial targeting and cancer treatment. The induction of mitochondrial dysfunction can be an effective pathway of chemotherapy, photodynamic therapy, and combination therapy against cancer. This review focuses on recent progress in the field of AIE luminogens (AIEgens) for cancer theranostics based on mitochondrial targeting and dysfunction. AIEgens for cancer treatment, including chemotherapy, photodynamic therapy, and combination therapy, are summarized herein. Molecular design efforts toward mitochondrial targeting and mitochondria-damaging mechanisms are also discussed. Finally, we discuss the challenges and future directions of development for AIEgens in mitochondria-targeted cancer treatment.

Long-term outcomes of surgical procedures for Marfan syndrome: aortic dissection versus aneurysm.

BACKGROUND: Multiple of subsequent procedures may necessary in Marfan syndrome (MFS) patients after initial surgery. The aim of this study was to investigate the full spectrum of secondary distal vascular or valvular interventions encountered after initial surgery. METHODS: Retrospective analysis of 201 consecutive MFS patients between January 2000 and March 2019 who underwent 274 distal aortic reinterventions and 5 mitral valve replacements. RESULTS: Of the enrolled 201 MFS patients (73 female, mean age 37.0±12.8 years), the surgical indication for 93 patients was aortic root aneurysm, and for another 108 patients was dissection. The mean follow-up interval was 8.4±5.5 years. Total arch replacement (TAR) was performed in 68.5% of MFS patients presenting with type A aortic dissection (TAAD) and in 2.2% of patients with aneurysm. Secondary TAR became necessary for 3.4% of patients who failed to receive TAR at initial surgery in aneurysm group during follow-up, while for 33.3% of patients in dissection group (P<0.001). Freedom from distal aortic reoperation in dissection group were 65.4%±5.2%, 49.6%±6.4%, and 38.3%±7.7% and in aneurysm group were 90.5%±3.5%, 84.2%±4.8%, and 84.2%±4.8% at 5, 10, and 15 years, respectively (P<0.001). Survival in dissection group were 94.4%±2.4%, 83.4%±5.7%, 68.4%±10.8% and in aneurysm group were 100%, 97.7%±2.3%, 97.7%±2.3% at 5, 10, and 15 years, respectively (P=0.001). Freedom from mitral valve reoperation in dissection group were 98.8%±1.2%, 98.8%±1.2%, 88.9%±9.4% at 5, 10, and 15 years, respectively. Freedom from mitral valve reoperation in aneurysm group were 97.2%±1.9%, 94.6%±3.2%, 94.6%±3.2% at 5, 10, and 15 years, respectively (P=0.775). CONCLUSIONS: TAAD at initial surgery was an independent predictor of distal aortic reoperation. Limited repair was feasible for MFS patients presenting with aneurysm at initial surgery, extended repair might be better for TAAD for its higher risk of distal reintervention. Concomitant mitral valve procedures may depend on mitral regurgitation grades.

Pyridinium-Substituted Tetraphenylethylenes Functionalized with Alkyl Chains as Autophagy Modulators for Cancer Therapy.

Tuning autophagy in a controlled manner could facilitate cancer therapy but it remains challenging. Pyridinium-substituted tetraphenylethylene salts (PTPE 1-3), able to target mitochondria and disrupt autophagy after forming complexes with albumin, are reported. Mitochondrion affinity and autophagy-inducing activity are improved by prolonging the length of alkyl chains in PTPE 1-3. PTPE 1-3 demonstrate proautophagic activity and a mitophagy blockage effect. Failure of autophagosome-lysosome fusion in downstream autophagy flux results in cancer cell death. Moreover, fast formation of complexes of PTPE 1-3 with albumin in blood can facilitate biomimetic delivery and deep tumor penetration. Efficient tumor accumulation and effective tumor suppression are successfully demonstrated with in vitro and in vivo studies. PTPE 1-3 salts exhibit dual functionality: they target and image mitochondria because of aggregation-induced emission effects and they are promising for cancer therapy.

Nur77 limits endothelial barrier disruption to LPS in the mouse lung.

Nur77 is an orphan nuclear receptor implicated in the regulation of a wide range of biological processes, including the maintenance of systemic blood vessel homeostasis. Although Nur77 is known to be expressed in the lung, its role in regulating pulmonary vascular functions remains entirely unknown. In this study, we found that Nur77 is expressed at high levels in the lung, and its expression is markedly upregulated in response to LPS administration. While the pulmonary vasculature of mice that lacked Nur77 appeared to function normally under homeostatic conditions, we observed a dramatic decrease in its barrier functions after exposure to LPS, as demonstrated by an increase in serum proteins in the bronchoalveolar lavage fluid and a reduction in the expression of endothelial junctional proteins, such as vascular endothelial cadherin (VE-cadherin) and ß-catenin. Similarly, we found that siRNA knockdown of Nur77 in lung microvascular endothelial cells also reduced VE-cadherin and ß-catenin expression and increased the quantity of fluorescein isothiocyanate-labeled dextran transporting across LPS-injured endothelial monolayers. Consistent with Nur77 playing a vascular protective role, we found that adenoviral-mediated overexpression of Nur77 both enhanced expression of VE-cadherin and ß-catenin and augmented endothelial barrier protection to LPS in cultured cells. Mechanistically, Nur77 appeared to mediate its protective effects, at least in part, by binding to ß-catenin and preventing its degradation. Our findings demonstrate a key role for Nur77 in the maintenance of lung endothelial barrier protection to LPS and suggest that therapeutic strategies aimed at augmenting Nur77 levels might be effective in treating a wide variety of inflammatory vascular diseases of the lung.

Tissue kallikrein-related peptidase8 protects rat heart against acute ischemia reperfusion injury.

Tissue kallikrein-related peptidases (KLKs) play important roles in acute cardiac injury and cardiac remodeling. However, the exact cardiac actions of KLK8 have not been determined. Transgenic rat overexpressing KLK8 was established to examine the role of KLK8 in the heart. Cardiac injury was induced by ischemia/reperfusion (I/R) and examined by infarct size measurement and TUNEL staining. The molecular mechanisms were investigated in cultured neonatal rat cardiomyocytes (CMs). Western blot analysis was used to determine the protein levels. KLK8 protein level was significantly increased in the cardiac ischemic risk area. KLK8 overexpression mitigated I/R-induced cardiac injury, as evidenced by decreased infarct size and apoptosis in cardiac ischemic risk area in vivo. Via in vitro studies, it was found that KLK8 overexpression attenuated the Hypoxia/Reoxygenation (H/R) injury in CMs; both B2R and PAR2 antagonist significantly attenuated KLK8-induced protective actions under H/R injury. Moreover, KLK8 overexpressed CMs showed significant higher phosphorylation levels of Akt, ERK1/2 and PKA under H/R stimulation; B2R antagonist attenuated the phosphorylation levels of Akt and ERK1/2, while PAR2 antagonist attenuated the phosphorylation levels of PKA and ERK1/2. KLK8 protects the heart against I/R-induced cardiac injury, which may represent a new therapeutic target in cardiac medicine.

Baseline and Outcome Characteristics of Multiple Valve Surgery Compared with Single Valve Procedures in Mainland China: A Multicenter Experience.

BACKGROUND: To compare baseline and outcome characteristics of multiple valve surgery with single-valve procedures in a multicenter patient population of mainland China. METHODS: From January 2008 to December 2012, data from 14,322 consecutive patients older than 16 years who underwent heart valve surgery at five cardiac surgical centers (except pulmonary valve operations) were collected. The patients were divided into seven subgroups according to the type of valve procedures, and baseline characteristics and postoperative outcomes were contrasted between all seven combinations of single-valve and multiple-valve procedures involving aortic, mitral, and tricuspid valves. Two independent logistic regression analyses were performed and multivariable risk factors for mortality were compared, with emphasis on single-valve versus multiple-valve surgery. RESULTS: Baseline characteristics for MUV procedures (n = 8945) shared many differences to those for single-valve procedures (n = 5377). Proportion of females, chronic obstructive pulmonary disease, cerebrovascular disease, renal impairment, congestive heart failure, NHYA class III-IV, atrial fibrillation, pulmonary hypertension, and decreased ejection fraction were more common in MUV subgroups, and smoker, hypertension, dyslipidemia, active infectious endocarditis, and coronary bypass graft was less frequent. In-hospital mortality was higher for MUV as compared with single-valve procedures (2.4% versus 1.6%, P = .007). Preoperative independent predictors for mortality of patients undergoing MUV procedures were age, chronic obstructive pulmonary disease, diabetes mellitus, renal dysfunction, dialysis, congestive heart failure, cardiogenic shock, NYHA class III-IV, mitral stenosis, tricuspid regurgitation, mitral valve replacement, and concomitant CABG. However, risk factors for mortality were relatively different between single-valve and MUV procedures. CONCLUSION: Baseline characteristics and epidemiology were different between MUV and single-valve procedures. The in-hospital mortality and postoperative complications for MUV procedures remained considerably higher and determinants of mortality were relatively different across procedures types. These findings serve as a benchmark for further studies, as well as suggest a continued search for explanations of MUV outcomes.

Decision-making at initial surgery for type A aortic dissection in patients with Marfan syndrome: proximal or extensive repair.

BACKGROUND: Data on outcome of Stanford type A aortic dissection (TAAD) in Marfan syndrome (MFS) patients are limited. We investigated the full spectrum of reoperation and survival after initial surgery in MFS patients who suffered TAAD. METHODS: Retrospective analysis of 85 consecutive MFS patients in one-single center during the past 15 years. RESULTS: Overall, 85 MFS patients with TAAD underwent surgical repair [74% acute dissections; 80% DeBakey type I; 91% composite valved graft; 70% total arch replacement (TAR); 68% frozen elephant trunk (FET); 7% in-hospital mortality] at Changhai hospital affiliated to the Second Military Medical University over the past 15 years. Five (20.8%) patients in non-TAR group need aortic arch reintervention with resternotomy during follow-up, which is significantly higher than that in TAR group (P=0.001). Freedom from aortic arch reoperation in non-TAR group was all 78.7%±8.5% at 5, 10, and 15 years. No patient required aortic arch reoperation in TAR group (P=0.001). On the other hand, the FET was inserted into false lumen intentionally at initial surgery in 2 cases of chronic TAAD with narrowed true lumen. Scheduled thoracoabdominal aortic replacement was performed 6 months later. Both 2 patients are with well clinical outcomes. At last, we found that Debakey type and TAR at initial surgery were irrelevant to survival and reoperation for descending aorta. CONCLUSIONS: TAR combined with FET is recommended in MFS patients when the aortic arch is dissected or enlarged. The FET could be inserted into the false lumen intentionally in selective case for scheduled 2-staged descending aortic repair.

Selectively light-up hydrogen peroxide in hypoxic cancer cells with a novel fluorescent probe.

A novel fluorescent turn-on probe (HCyHP) was developed in a simple two-step synthesis for monitoring of exogenous and endogenous H2O2 levels in biological samples and hypoxic cancer diagnosis.