Calycosin protects against oxidative stress-induced cardiomyocyte apoptosis by activating aldehyde dehydrogenase 2.

Myocardial infarction (MI) is the leading cause of death worldwide, and oxidative stress is part of the process that causes MI. Calycosin, a naturally occurring substance with cardioprotective properties, is one of the major active constituents in Radix Astragali. In this study, effect of Calycosin was investigated in vivo and in vitro to determine whether it could alleviate oxidative stress and oxidative stress-induced cardiac apoptosis in neonatal cardiomyocytes (NCMs) via activation of aldehyde dehydrogenase 2 (ALDH2). Calycosin protected against oxidative stress and oxidative stress-induced apoptosis in NCMs. Molecular docking revealed that the ALDH2-Calycosin complex had a binding energy of -9.885 kcal/mol. In addition, molecular docking simulations demonstrated that the ALDH2-Calycosin complex was stable. Using BLI assays, we confirmed that Calycosin could interact with ALDH2 (KD  = 1.9 × 10-4 M). Furthermore, an ALDH2 kinase activity test revealed that Calycosin increased ALDH2 activity, exhibiting an EC50 of 91.79 µM. Pre-incubation with ALDH2 inhibitor (CVT-10216 or disulfiram) reduced the cardio-protective properties Calycosin. In mice with MI, Calycosin therapy substantially reduced myocardial apoptosis, oxidative stress, and activated ALDH2. Collectively, our findings clearly suggest that Calycosin reduces oxidative stress and oxidative stress-induced apoptosis via the regulation of ALDH2 signaling, which supports potential therapeutic use in MI.

Dauricine inhibits proliferation and promotes death of melanoma cells via inhibition of Src/STAT3 signaling.

Melanoma is the most common type of skin cancer. Signal transducer and activator of transcription 3 (STAT3) signaling has been demonstrated to be a therapeutic target for melanoma. Dauricine (Dau), an alkaloid compound isolated from the root of Menispermum dauricum DC., has shown tumor-suppressing effects in multiple human cancers, but its potential in melanoma remains unexplored. In this study, we demonstrated that Dau significantly inhibited the viability and proliferation of A375 and A2058 melanoma cells. Death of melanoma cells was also markedly promoted by Dau. Moreover, Dau inhibited phosphorylation-mediated activation of STAT3 and Src in a dose-dependent manner. Notably, constitutive activation of Src partially abolished the antiproliferative and cytotoxic activities of Dau on melanoma cells. Molecular docking showed that Dau could dock on the kinase domain of Src with a binding energy of -10.42 kcal/mol. Molecular dynamics simulations showed that Src-Dau binding was stable. Surface plasmon resonance imaging analysis also showed that Dau has a strong binding affinity to Src. In addition, Dau suppressed the growth of melanoma cells and downregulated the activation of Src/STAT3 in a xenograft model in vivo. These data demonstrated that Dau inhibits proliferation and promotes cell death in melanoma cells by inhibiting the Src/STAT3 pathways.

Incidence of Deep Sternal Wound Infection in Diabetic Patients Undergoing Off-Pump Skeletonized Internal Thoracic Artery Grafting.

OBJECTIVES: To evaluate the impact of skeletonized bilateral or single internal thoracic artery (ITA) grafting on the risk of deep sternal wound infection (DSWI) in diabetic patients undergoing off-pump coronary artery bypass grafting (OPCAB). MATERIALS AND METHODS: A total of 803 diabetic patients undergoing OPCAB surgery from January 2010 to December 2014 were enrolled into this study and assigned to the pSITA group (patients undergoing pedicled single ITA grafting, n = 362), the sSITA group (skeletonized single ITA grafting, n = 295), or the sBITA group (skeletonized bilateral ITA grafting, n = 146). The primary end point was the diagnosis of a DSWI. RESULTS: Eighteen patients developed postoperative DSWI, with an incidence of 2.2%. Patients in the sSITA group had a significantly lower incidence of DSWI than those in the pSITA group (1.0 vs. 3.6%, p = 0.0408). In multivariate logistic regression analysis, the risk of DSWI in the sSITA group was 0.41 times that in the pSITA group. CONCLUSIONS: sSITA grafting lowered the risk of DSWI in diabetic patients undergoing OPCAB surgery compared to pSITA grafting. Multicenter clinical trials involving larger sample sizes are needed to determine the merit of pSITA grafting in reducing the risk of DSWI following OPCAB surgery.

Direct observation of turbulent magnetic fields in hot, dense laser produced plasmas.

Turbulence in fluids is a ubiquitous, fascinating, and complex natural phenomenon that is not yet fully understood. Unraveling turbulence in high density, high temperature plasmas is an even bigger challenge because of the importance of electromagnetic forces and the typically violent environments. Fascinating and novel behavior of hot dense matter has so far been only indirectly inferred because of the enormous difficulties of making observations on such matter. Here, we present direct evidence of turbulence in giant magnetic fields created in an overdense, hot plasma by relativistic intensity (10(18) W/cm(2)) femtosecond laser pulses. We have obtained magneto-optic polarigrams at femtosecond time intervals, simultaneously with micrometer spatial resolution. The spatial profiles of the magnetic field show randomness and their k spectra exhibit a power law along with certain well defined peaks at scales shorter than skin depth. Detailed two-dimensional particle-in-cell simulations delineate the underlying interaction between forward currents of relativistic energy "hot" electrons created by the laser pulse and "cold" return currents of thermal electrons induced in the target. Our results are not only fundamentally interesting but should also arouse interest on the role of magnetic turbulence induced resistivity in the context of fast ignition of laser fusion, and the possibility of experimentally simulating such structures with respect to the sun and other stellar environments.

Application of Dynamic Contrast-Enhanced Ultrasound in Evaluation the Activity of Crohn's Disease.

BACKGROUND AND OBJECTIVE: The dynamic assessment of disease activity during the follow-up of patients with Crohn's disease (CD) remains a significant challenge. In this study, we aimed to identify the role of dynamic contrast-enhanced ultrasound (DCE-US) in the evaluation of activity of CD. METHODS: In the retrospective study, patients diagnosed with CD in our hospital were included. All the diagnoses were confirmed by clinical symptoms and ileocolonoscopical results. All patients underwent intestinal ultrasound and contrast-enhanced ultrasound (CEUS) examinations within 1 week of the ileocolonoscopy examinations. Acuson Sequoia (Siemens Healthineers, Mountain View, CA, USA) and Resona R9 Elite (Mindray Medical Systems, China) with curved array and Line array transducers were used. The CEUS examination was performed with SonoVue (Bracco SpA, Milan, Italy). DCE-US analysis was performed by UltraOffice (version: 0.3-2010, Mindray Medical Systems, China) software. Two regions of interest (ROIs) were set in the anterior section of the infected bowel wall and its surrounding normal bowel wall 2 cm distant from the inflamed area. Time-intensity curves (TICs) were generated and quantitative perfusion parameters were obtained after curve fittings. The Simple Endoscopic Score for Crohn's disease (SES-CD) was regarded as the reference standard to evaluate the activity of CD. The receiver operating characteristic curve (ROC) analyses were used to determine the diagnostic efficiency of DCE-US quantitative parameters. RESULTS: From March 2023 to November 2023, 52 CD patients were included. According to SES-CD score, all patients were divided into active group with the SES-CD score > 5 (n = 39) and inactive group SES-CD score < 5 (n = 13). Most of the active CD patients showed bowel wall thickness (BWT) > 4.2 mm (97.4%, 38/39) or mesenteric fat hypertrophy (MFH) on intestinal ultrasound (US) scan (69.2%, 27/39). Color Doppler signal of the bowel wall mostly showed spotty or short striped blood flow signal in active CD patients (56.4%, 22/39). According to CEUS enhancement patterns, most active CD patients showed a complete hyperenhancement of the entire intestinal wall (61.5%, 24/39). The TICs of active CD showed an earlier enhancement, higher peak intensity, and faster decline. Among all CEUS quantitative parameters, amplitude-derived parameters peak enhancement (PE), wash-in area under the curve (WiAUC), wash-in rate (WiR), wash-in perfusion index (WiPI), and wash-out rate (WoR) were significantly higher in active CD than in inactive CD (p < 0.05). The combined AUROC of intestinal ultrasound features and DCE-US quantitative perfusion parameters in the diagnosis of active CD was 0.987, with 97.4% sensitivity, 100% specificity, and 98.1% accuracy. CONCLUSIONS: DCE-US with quantitative perfusion parameters is a potential useful noninvasive imaging method to evaluate the activity of Crohn's disease.

[Risk factors for failure of continuous veno-venous hemodialysis in the treatment of acute kidney injury following cardiac surgery].

OBJECTIVE: To evaluate the independent risk factors for failure of continuous veno-venous hemodialysis (CVVHD) in the treatment of acute kidney injury (AKI) following cardiac surgery. METHODS: Adult patients without any prior pre-operative history of chronic renal disease suffering AKI following cardiac surgery and undergoing CVVHD at our center from January 2005 to December 2012 were recruited and divided into either a success group or a failure group. All pre-, intra- and post-operative data were collected and retrospectively analyzed. RESULTS: Ninety-three adult patients were enrolled. Among them, sixty-three patients survived with a failure rate of 32.2% and a mortality rate of 19.4%. Through univariate analysis and multivariate Logistic regression, independent risk factors for failure of CVVHD in the treatment of post-operative AKI included pre-operative LVEF (OR = 0.61, 95%CI 0.42-0.85) and duration of oliguria until dialysis (OR = 2.76, 95%CI 1.51-5.83). CONCLUSION: Pre-operative impaired left ventricular function is an important risk factor for failure of CVVHD in the treatment of AKI after cardiac surgery. The sooner the implementation of CVVHD, the better prognosis.

Inhibition of STAT3 signaling contributes to the anti-melanoma effects of chrysoeriol.

BACKGROUND: Melanoma is an aggressive malignancy with a high mortality rate. Signal transducer and activator of transcription 3 (STAT3), an oncoprotein, is considered as an effective target for treating melanoma. Chrysoeriol is a flavonoid compound, and possesses anti-tumor activity in lung cancer, breast cancer and multiple myeloma; while whether it has anti-melanoma effects is still not known. Chrysoeriol has been shown to restrain STAT3 signaling in an inflammation mouse model. PURPOSE: In this study, the anti-melanoma effects of chrysoeriol and the involvement of STAT3 signaling in these effects were investigated. STUDY DESIGN AND METHODS: CCK8 assays, 5-ethynyl-2'-deoxyuridine (EdU) staining, Annexin V-FITC/PI staining, Western blot analyses of cleaved caspase-9 and wound healing assays were used to study the anti-melanoma effects of chrysoeriol in cell models. A B16F10 melanoma bearing mouse model was used to evaluate the in vivo anti-melanoma effects of chrysoeriol. Indicators of cell proliferation, cell apoptosis and angiogeneis in melanoma tissues were detected by immunohistochemistry (IHC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Immune cells in melanoma tissues were analyzed by flow cytometry. STAT3-overactivated cell models were used to investigate the involvement of STAT3 signaling in the anti-melanoma effects of chrysoeriol. Molecular dynamics (MD) simulations and surface plasmon resonance (SPR) assays were conducted to determine whether chrysoeriol binds to Src, an upstream kinase of STAT3. RESULTS: The results of cell experiments showed that chrysoeriol dose-dependently inhibited viability, proliferation and migration of, and induced apoptosis in, A375 and B16F10 melanoma cells. Chrysoeriol inhibited the phosphorylation of STAT3, and downregulated the expression of STAT3-target genes involved in melanoma growth and metastasis. Mouse studies showed that chrysoeriol restrained melanoma growth and tumor-related angiogenesis, and altered compositions of immune cells in melanoma microenvironment. Chrysoeriol also inhibited STAT3 signaling in B16F10 allografts. Chrysoeriol's viability-inhibiting effects were attenuated by over-activating STAT3 in A375 cells. Furthermore, chrysoeriol bound to the protein kinase domain of Src, and suppressed Src phosphorylation in melanoma cells and tissues. CONCLUSION: This study, for the first time, demonstrates that chrysoeriol has anti-melanoma effects, and these effects are partially due to inhibiting STAT3 signaling. Our findings indicate that chrysoeriol has the potential to be developed into an anti-melanoma agent.

Radix Glycyrrhizae extract and licochalcone a exert an anti-inflammatory action by direct suppression of toll like receptor 4.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Glycyrrhizae (GL), a herbal medicine that is widely available, has shown advantages for a variety of inflammatory diseases. Toll like receptor 4 (TLR4) pathway has been shown to play a key role in the progression of inflammation. AIM OF THE STUDY: The purpose of this study was to investigate the involvement of TLR4 in the anti-inflammatory mechanism of GL extract and its active constituent on acute lung injury (ALI). MATERIALS AND METHODS: A model of inflammation produced by lipopolysaccharide (LPS) was established in C57BL/6 mice and macrophages derived from THP-1. To screen the active components of GL, molecular docking was used. Molecular dynamics and surface plasmon resonance imaging (SPRi) were used to study the interaction of a specific drug with the TLR4-MD2 complex. TLR4 was overexpressed by adenovirus to confirm TLR4 involvement in the anti-inflammatory activities of GL and the chosen chemical. RESULTS: We observed that GL extract significantly reduced both LPS-induced ALI and the production of pro-inflammatory factors including TNF-α, IL-6 and IL-1ß. Additionally, GL inhibited the binding of Alexa 488-labeled LPS (LPS-488) to the membrane of THP-1 derived macrophages. GL drastically reduce on the expression of TLR4 and the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-B (NF-κB). Furthermore, molecular docking revealed that Licochalcone A (LicoA) docked into the LPS binding site of TLR4-MD2 complex. MD2-LicoA binding conformation was found to be stable using molecular dynamic simulations. SPRi indicated that LicoA bound to TLR4-MD2 recombinant protein with a KD of 3.87 × 10-7 M. LicoA dose-dependently reduced LPS-488 binding to the cell membrane. LicoA was found to significantly inhibit LPS-induced lung damage and inflammation. Furthermore, LicoA inhibited TLR4 expression, MAPK and NF-κB activation in a dose-dependent manner. The inhibitory effects of GL and LicoA on LPS-induced inflammation and TLR4 signaling activation were partly eliminated by TLR4 overexpression. CONCLUSION: Our findings imply that GL and LicoA exert inhibitory effects on inflammation by targeting the TLR4 directly.

Ethyl ferulate suppresses post-myocardial infarction myocardial fibrosis by inhibiting transforming growth factor receptor 1.

BACKGROUND: With an increasing number of myocardial infarction (MI) patients, myocardial fibrosis is becoming a widespread health concern. It's becoming more and more urgent to conduct additional research and investigations into efficient treatments. Ethyl ferulate (EF) is a naturally occurring substance with cardioprotective properties. However, the extent of its impact and the underlying mechanism of its treatment for myocardial fibrosis after MI remain unknown. PURPOSE: The goal of this study was to look into how EF affected the signaling of the TGF-receptor 1 (TGFBR1) in myocardial fibrosis after MI. METHODS: Echocardiography, hematoxylin-eosin (HE) and Masson trichrome staining were employed to assess the impact of EF on heart structure and function in MI-affected mice in vivo. Cell proliferation assay (MTS), 5-Ethynyl-2'-deoxyuridine (EdU), and western blot techniques were employed to examine the influence of EF on native cardiac fibroblast (CFs) proliferation and collagen deposition. Molecular simulation and surface plasmon resonance imaging (SPRi) were utilized to explore TGFBR1 and EF interaction. Cardiac-specific Tgfbr1 knockout mice (Tgfbr1ΔMCK) were utilized to testify to the impact of EF. RESULTS: In vivo experiments revealed that EF alleviated myocardial fibrosis, improved cardiac dysfunction after MI and downregulated the TGFBR1 signaling in a dose-dependent manner. Moreover, in vitro experiments revealed that EF significantly inhibited CFs proliferation, collagen deposition and TGFBR1 signaling followed by TGF-ß1 stimulation. More specifically, molecular simulation, molecular dynamics, and SPRi collectively showed that EF directly targeted TGFBR1. Lastly, knocking down of Tgfbr1 partially reversed the inhibitory activity of EF on myocardial fibrosis in MI mice. CONCLUSION: EF attenuated myocardial fibrosis post-MI by directly suppressing TGFBR1 and its downstream signaling pathway.

10-Gingerol, a natural AMPK agonist, suppresses neointimal hyperplasia and inhibits vascular smooth muscle cell proliferation.

Background: Abnormal proliferation of vascular smooth muscle cells (VSMCs) in the intimal region is a key event in the development of neointimal hyperplasia. 10-G, a bioactive compound found in ginger, exerted inhibitory effects on the proliferation of several cancer cells. However, the effect and mechanism of 10-G on neointimal hyperplasia are not clear. Purpose: To explore the suppressive effects of 10-G on the proliferation and migration of VSMCs, and investigate the underlying mechanisms. Methods: In vivo, a left common carotid artery ligation mouse model was used to observe the effects of neointimal formation through immunohistochemistry and hematoxylin-eosin staining. In vitro, the cell proliferation and migration of HASMCs and A7r5 cells were detected by MTS assay, EdU staining, wound healing assay, Transwell assay, and western blotting as well. Molecular docking, molecular dynamics simulations and surface plasmon resonance imaging were collectively used to evaluate the interaction of 10-G with AMP-activated protein kinase (AMPK). Compound C and si-AMPK were used to inhibit the expression of AMPK. Results: Treatment with 10-G significantly reduced neointimal hyperplasia in the left common carotid artery ligation mouse model. MST and EdU staining showed that 10-G inhibited the proliferation of VSMC cells A7r5 and HASMC. We also found that 10-G altered the expression of proliferation-related proteins, including CyclinD1, CyclinD2, CyclinD3, and CDK4. Molecular docking revealed that the binding energy between AMPK and 10-G is -7.4 kcal mol-1. Molecular simulations suggested that the binding between 10-G and AMPK is stable. Surface plasmon resonance imaging analysis also showed that 10-G has a strong binding affinity to AMPK (KD = 6.81 × 10-8 M). 10-G promoted AMPKα phosphorylation both in vivo and in vitro. Blocking AMPK by an siRNA or AMPK inhibitor pathway partly abolished the anti-proliferation effects of 10-G on VSMCs. Conclusion: These data showed that 10-G might inhibit neointimal hyperplasia and suppress VSMC proliferation by the activation of AMPK as a natural AMPK agonist.

Dihydrotanshinone I inhibits the growth of hepatoma cells by direct inhibition of Src.

BACKGROUND: Liver cancer is one of the leading causes of cancer-related death worldwide. Dihydrotanshinone I (DHI) was shown to inhibit the growth of several types of cancer. However, research related to hepatoma treatment using DHI is limited. PURPOSE: Here, we explored the inhibitory effect of DHI on the growth of hepatoma cells, and investigated the underlying molecular mechanisms. METHODS: The proliferation of Hep3B, SMCC-7721 and SK-Hep1 hepatoma cells was evaluated using the MTS and Edu staining assay. Hepatoma cell death was analyzed with a LIVE/DEAD Cell Imaging Kit. The relative expression and phosphorylation of proto-oncogene tyrosine-protein kinase Src (Src) and signal transducer and activator of transcription-3 (STAT3) proteins in hepatoma cells, as well as the expression of other protein components, were measured by western blotting. The structural interaction of DHI with Src proteins was evaluated by molecular docking, molecular dynamics simulation, surface plasmon resonance imaging and Src kinase inhibition assay. Src overexpression was achieved by infection with an adenovirus vector encoding human Src. Subsequently, the effects of DHI on tumor growth inhibition were further validated using mouse xenograft models of hepatoma. RESULTS: In vitro studies showed that treatment with DHI inhibited the proliferation and promoted cell death of Hep3B, SMCC-7721 and SK-Hep1 hepatoma cells. We further identified and verified Src as a direct target of DHI by using molecular stimulation, surface plasmon resonance image and Src kinase inhibition assay. Treatment with DHI reduced the in vitro phosphorylation levels of Src and STAT3, a transcription factor regulated by Src. In the xenograft mouse models, DHI dose-dependently suppressed tumor growth and Src and STAT3 phosphorylation. Moreover, Src overexpression partly abrogated the inhibitory effects of DHI on the proliferation and cell death in hepatoma cells. CONCLUSION: Our results suggest that DHI inhibits the growth of hepatoma cells by direct inhibition of Src.

Mini-invasive surgical instruments in transaortic myectomy for hypertrophic obstructive cardiomyopathy: a single-center experience with 168 cases.

BACKGROUND: Although septal myectomy is a standard strategy for managing patients with hypertrophic obstructive cardiomyopathy (HOCM) and drug-refractory symptoms, so far, only a few experienced myectomy centers exist globally. Mainly, this can be explained by the many technical challenges presented by myectomy. From our clinical experience, applying the mini-invasive surgical instruments during myectomy potentially reduces the technical difficulty. This study reports the preliminary experience regarding transaortic septal myectomy using mini-invasive surgical instruments for managing patients with HOCM and drug-refractory symptoms; also, we evaluate the early results following myectomy. METHODS: Between March 2016 and March 2019, consecutive HOCM patients who underwent isolated transaortic septal myectomy using the mini-invasive surgical instruments were enrolled in this analysis. Intraoperative, in-hospital and follow-up results were analyzed. RESULTS: We included 168 eligible patients (83 males, mean 56.8 ± 12.3 years). The midventricular obstruction was recorded in 7 (4.2%) patients. All patients underwent transaortic septal myectomy with a mean aortic cross-clamping time of 36.0 ± 8.1 min. During myectomy, 9 (5.4%) patients received repeat aortic cross-clamping. Surgical mortality was 0.6%. Notably, 5 (3.0%) patients developed complete atrioventricular block, they needed permanent pacemaker implantation. The median follow-up time was 6 months; however, no follow-up deaths occurred with a significant improvement in New York Heart Association functional status. We reported a sharp decrease in the maximum gradients from the preoperative value (11.6 ± 7.4 mmHg vs. 94.4 ± 22.6 mmHg, p < 0.001). The median degree of mitral regurgitation fell to 1.0 (vs. 3.0 preoperatively, p < 0.001) with a significant reduction in the proportion of moderate or more regurgitation (1.2% vs. 57.7%, p < 0.001). CONCLUSIONS: Mini-invasive surgical instruments may be beneficial in reducing the technical challenges of transaortic septal myectomy procedure. Of note, transaortic septal myectomy using the mini-invasive surgical instruments may present with favorable results.

Particulate matter exposure exacerbates susceptibility to SARS-CoV-2 infection in humanized ACE2 mice.

The global outbreak of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as of 8 May 2021, has surpassed 150 700 000 infections and 3 279 000 deaths worldwide. Evidence indicates that SARS-CoV-2 RNA can be detected on particulate matter (PM), and COVID-19 cases are correlated with levels of air pollutants. However, the mechanisms of PM involvement in the spread of SARS-CoV-2 remain poorly understood. Here, we found that PM exposure increased the expression level of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in several epithelial cells and increased the adsorption of the SARS-CoV-2 spike protein. Instillation of PM in a hACE2 mouse model significantly increased the expression of ACE2 and Tmprss2 and viral replication in the lungs. Furthermore, PM exacerbated the pulmonary lesions caused by SARS-CoV-2 infection in the hACE2 mice. In conclusion, our study demonstrated that PM is an epidemiological factor of COVID-19, emphasizing the necessity of wearing anti-PM masks to cope with this global pandemic.

Pokemon Inhibits Transforming Growth Factor ß-Smad4-Related Cell Proliferation Arrest in Breast Cancer through Specificity Protein 1.

PURPOSE: Pokemon, also known as ZBTB7A, belongs to the POZ and Krüppel (POK) family of transcription repressors and is implicated in tumor progression as a key proto-oncogene. This present study aimed at determining the mechanism by which Pokemon inhibits transforming growth factor ß (TGFß)-Smad4 pathway-dependent proliferation arrest of breast cancer cells via specificity protein 1 (SP1). METHODS: Over-expressing plasmid or small interfering RNA (siRNA) transfection was used to regulate Pokemon levels. The EdU incorporation assay, MTS assay, and clone formation were used to identify the inhibitory effect of Pokemon siRNA on cell proliferation. Quantitative real-time polymerase chain reaction assay confirmed that Pokemon deletion inhibited the expression of proliferation-associated genes. The dual-luciferase reporter assay, electrophoretic mobility shift assay, and co-immunoprecipitation assay were used to analyze binding between Pokemon, Smad4, and SP1. RESULTS: Pokemon deletion induced proliferation arrest of breast cancer cells and inhibited the expression of proliferation-associated genes, especially Smad4. Pokemon bound with SP1 to interdict Smad4 promoter activity. Information on clinical samples was obtained from The Cancer Genome Atlas data, in which the Pokemon mRNA levels showed a negative correlation with Smad4 levels in different subtypes of breast cancer in two independent datasets. CONCLUSION: We demonstrated that Pokemon binds to SP1 to down-regulate Smad4 expression, thereby promoting proliferation of breast cancer cells. This suggests that Pokemon is a potential TGFß-signaling participant in breast cancer progression.

Patients over 70 years of age with moderate ischemic mitral regurgitation undergoing surgical revascularization plus mitral valve repair: insights from a single-center study of propensity-matched data.

BACKGROUND: Elderly patients, compared with the young, have a higher burden of surgical risk factors with reduced functional capacity and increased comorbidities conditions, and may have worse clinical outcomes. So far, few reports have focused on clinical outcomes of patients over 70 years of age with moderate chronic ischemic mitral regurgitation (IMR) undergoing mitral valve repair at the time of coronary artery bypass grafting (CABG). This single-center study of propensity-matched data attempts to answer a question: compared with patients with age of 70 or less, whether patients over 70 years of age with moderate IMR undergoing CABG plus mitral valve repair receive poor outcomes. METHODS: All eligible patients were included in this study and were entered into either an elderly group (n=142) or a control group (n=182) according to patients' age. In-hospital outcomes (consisting of surgical mortality and major postoperative morbidity) and midterm clinical outcomes (including all-cause mortality and recurrent mitral regurgitation) were compared after propensity score matching (1:1). RESULTS: Using propensity-score matching, 103 pairs of patients were successfully established in a 1:1 ratio. No significant differences between the two matched groups were found with regard to surgical mortality (5.8% vs. 3.9%, P=0.754) and major postoperative morbidity. A total of 184 patients (91 in the elderly group and 93 in the control group) received regular follow-up visit with the median duration of 38 months [interquartile range (IQR), 27-56 months]. There were not any significant differences between the two matched groups regarding overall survival and recurrent IMR-free survival (stratified log-rank P=0.185 and stratified log-rank P=0.453, respectively). The elderly group as compared to the control group did not affect midterm mortality via cox proportional hazard regression (propensity score adjusted hazard ratio, 1.143; 95% confidence interval, 0.761-1.943; P=0.285). CONCLUSIONS: Patients over 70 years of age with moderate chronic IMR undergoing combined CABG and mitral valve repair may receive favorable in-hospital and midterm clinical outcomes.

[Clinical profiles and surgical outcomes of coronary obstruction due to type A aortic dissection: a single institution experience].

OBJECTIVE: To investigate the clinical profile of myocardial infarction (MI) due to retrograde aortic dissection of aortic root and the relevant predictors of in-hospital death. METHODS: The clinical data of 207 consecutive patients with type A aortic dissection (AD), who were hospitalized and underwent operation between December 2003 and October 2007, were analyzed retrospectively. RESULTS: Eight of the 207 patients were diagnosed as with MI due to retrograde aortic dissection of aortic root, 6 males and 2 females, aged (49 +/- 14). Surgical repair of the aorta and coronary revascularization was implanted: ascending aorta replacement in 2 cases, hemi-arch replacement in 5 cases, arch replacement in 1 case; coronary artery bypass grafting in 5 cases, and coronary repair in 3 cases. In-hospital death occurred in 4 of the 8 patients (50%) who all had preoperative renal insufficiency and developed acute renal failure (ARF) after surgery. Univariate analysis identified preoperative renal insufficiency an independent predictor of in-hospital death (The preoperative serum creatinine (sCr) level of the surviving patients was (80 +/- 30) micromol/L, significantly lower than that of the deceased patients [(176 +/- 67) micromol/L, P = 0.02]. There were no significant differences in other parameters between the surviving and deceased groups. CONCLUSION: MI due to type A AD is associated with high operative mortality. Preoperative renal insufficiency attributes to development of ARF after surgery and the unfavorable outcome. Renal function before surgery is essential for risk stratification in this lethal condition.

[Artificial radial head replacement for the treatment of comminuted fractures of the radial head].

OBJECTIVE: To assess the clinical effects of artificial radial head prosthesis replacement for the treatment of comminuted fracture of the radial head. METHODS: From June 2011 to June 2015, 25 patients with radial head comminuted fracture were treated with artificial radial head replacement, including 10 males and 15 females, ranging in age form 24 to 61 years old(mean, 40 years old). The functional recovery of the patients suffering from limb and elbow in different periods, the activity degree of the elbow joint and the function of the elbow in the latest follow-up were compared. RESULTS: All the patients were followed up, and the duration ranged from 12 to 48 months, averaged 26 months. There were no complications such as infection, elbow instability, subluxation of the distal radioulnar joint, and myositis ossificans. The VAS, Broberg and Morrey elbow function score were improved 6, 9 months after operation compared with that 3 months after operation(P<0.05). There were significant differences in elbow flexion and extension, rotation activity between injured side and healthy side 3, 6, 9 months after operation(P<0.01), but no significant differences between injured side and healthy side at the latest follow-up(P>0.05). At the latest follow-up, according to Broberg and Morrey elbow function evaluation criteria, 16 cases got an excellent result, 7 good and 2 poor. CONCLUSIONS: It can maximize the recovery of elbow joint stability and quicken early functional exercise, prevent and reduce the occurrence of complications by using the artificial radial head replacement therapy to repair comminuted fracture of the radial head. The short-term curative effect is satisfactory, but the long-term effect needs further observation.

Impact of severe left ventricular dysfunction on in-hospital and mid-term outcomes of Chinese patients undergoing first isolated off-pump coronary artery bypass grafting.

BACKGROUND: Few studies focused on evaluating the impacts of preoperative severe left ventricular dysfunction on clinical outcomes of patients undergoing off-pump coronary artery bypass grafting surgery (OPCAB). This single center retrospective study aimed to evaluate the impacts of severe left ventricular dysfunction on in-hospital and mid-term clinical outcomes of Chinese patients undergoing first, scheduled, and isolated OPCAB surgery. METHODS: From January 2010 to December 2014, 2032 eligible patients were included in this study and were divided into 3 groups: a severe group (patients with preoperative left ventricular ejection fraction (LVEF) of ≤35%, n = 128), an impaired group (patients with preoperative LVEF of 36-50%, n = 680), and a normal group (patients with preoperative LVEF of >50%, n = 1224). In-hospital and follow-up clinical outcomes were investigated and compared. RESULTS: Patients in the severe group compared to the other 2 groups had higher in-hospital mortality and higher incidences of low cardiac output and prolonged ventilation. Kaplan-Meier curves showed a similar cumulative follow-up survival between the severe group and the impaired group (χ2 = 1.980, Log-rank p = 0.159) and between the severe group and the normal group (χ2 = 2.701, Log-rank p = 0.102). Multivariate Cox regression indicated that grouping was not a significant variable related to mid-term all-cause mortality. No significant difference was found in the rate of repeat revascularization between the severe group (2.4%) and the other 2 groups. CONCLUSIONS: Patients with preoperative LVEF of ≤35% compared to preoperative LVEF of >35% increased the risk of in-hospital death and incidences of postoperative low cardiac output and prolonged ventilation, but shared similar mid-term all-cause mortality and repeat revascularization after OPCAB surgery.

Preliminary investigation on the cytotoxicity of tellurite to cultured HeLa cells.

Cytotoxicity of tellurite to cultured HeLa cells was examined by cell viability, lactate dehydrogenase (LDH) assay, and tellurite uptake. The experimental results show that the toxicity of tellurite depends on its concentrations and exposure time. HeLa cells exposed to tellurite for 2 h at 9.1 x 10(-4) to 4.5 x 10(-3) mmol/L did not exhibit cytotoxic effects as measured by cell viability. Exposure to tellurite for 24 h at the same concentrations markedly reduced the cell viability to 57% of the control during the first 5 minutes. Additionally, HeLa cells incubated at 2.7 x 10(-2) to 0.27 mmol/L of tellurite for 2 h retained 53% to 67% of cell viability. Even after 24 h exposure, the HeLa cells incubated at 9.1 x 10(-4) to 4.5 x 10(-2) mmol/L of tellurite still retained 57% to 66% of cell viability. Furthermore, tellurite toxicity was also demonstrated in supernatant of the culture at 37 degrees C by LDH assay. It was found that exposure to tellurite for 90 minutes did not stimulate LDH activity. However, tellurite uptake seems to be more sensitive than the cell viability and LDH activity release tests, as it significantly increases with the increasing of exposure time.

[Orthotopic heart transplantation: clinical experience on 56 patients].

OBJECTIVE: To summarize the clinical experience on 56 patients undergoing orthotopic heart transplantation. METHODS: Between May 2000 and December 2003 56 patients, 47 with cardiomyopathy, 2 with end-stage valvular heart disease, 2 with end-stage ischemic heart disease, 2 with primary malignant cardiac tumor, 1 with complicated congenital heart disease, 1 with muscular dystrophy cardiomyopathy, and 1 with refractory malignant ventricular arrhythmias, underwent orthotopic heart transplantation in the Transplantation Center of Fudan University. The operative procedures included 19 conventional Stanford orthotopic cardiac transplantation in 19 cases and bicaval anastomotic cardiac transplantation in 37 cases. Postoperatively, the patients were prescribed with cyclosporine A + corticosteroids + MMF or FK506 + corticosteroids + MMF as anti-rejection therapy. RESULTS: One patient undergoing his fifth operation died of bleeding 3 days after operation. All survivors were followed-up for 12.4 months on average. Five patients died within 1 year postoperatively with a one-year survival rate of 91%. One patient died of allograft vasculopathy 38 months after operation. Other patients enjoyed heart function recovering to class I-II (NYHA). CONCLUSION: With proper recipient selection, excellent donor heart conservation, bicaval anastomotic technique, and efficient postoperative surveillance and treatment, heart transplantion may produce satisfying mid-term results.