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Background: Persistent infection with the high-risk of human papillomavirus (HR-HPVs) is the primary etiological factor of cervical cancer; HR-HPVs express oncoproteins E6 and E7, both of which play key roles in the progression of cervical carcinogenesis. Zinc Finger Nucleases (ZFNs) targeting HPV E7 induce specific shear of the E7 gene, weakening the malignant biological effects, hence showing great potential for clinical transformation. Objective: Our aim was to develop a new comprehensive therapy for better clinical application of ZFNs. We here explored the anti-cancer efficiency of HPV targeted ZFNs combined with a platinum-based antineoplastic drug Cisplatin (DDP) and an HDAC inhibitor Trichostatin A (TSA). Methods: SiHa and HeLa cells were exposed to different concentrations of DDP and TSA; the appropriate concentrations for the following experiments were screened according to cell apoptosis. Then cells were grouped for combined or separate treatments; apoptosis, cell viability and proliferation ability were measured by flow cytometry detection, CCK-8 assays and colony formation assays. The xenograft experiments were also performed to determine the anti-cancer effects of the combined therapy. In addition, the HPV E7 and RB1 expressions were measured by western blot analysis. Results: Results showed that the combined therapy induced about two times more apoptosis than that of ZFNs alone in SiHa and HeLa cells, and much more inhibition of cell viability than either of the separate treatment. The colony formation ability was inhibited more than 80% by the co-treatment, the protein expression of HPV16/18E7 was down regulated and that of RB1 was elevated. In addition, the xenografts experiment showed a synergistic effect between DDP and TSA together with ZFNs. Conclusion: Our results demonstrated that ZFNs combined with DDP or TSA functioned effectively in cervical cancer cells, and it provided novel ideas for the prevention and treatment of HPV-related cervical malignancies.

Persistent high-risk HPV infection is the main cause of cervical cancer. The HPV oncogene E7 plays an important role in HPV carcinogenesis. Currently, HPV vaccines do not offer an effective treatment for women who already present with cervical disease, and recommended periodical cervical screenings are difficult to perform in countries and areas lacking medical resources. Our aim was to develop nanoparticles (NPs) based on poly (β-amino ester) (PBAE) and HPV16 E7-targeting CRISPR/short hairpin RNA (shRNA) to reduce the levels of HPV16 E7 as a preliminary form of a drug to treat HPV infection and its related cervical malignancy. Our NPs showed low toxicity in cells and mouse organs. By reducing the expression of HPV16 E7, our NPs could inhibit the growth of cervical cancer cells and xenograft tumors in nude mice, and they could reverse the malignant cervical epithelium phenotype in HPV16 transgenic mice. The performance of NPs containing shRNA is better than that of NPs containing CRISPR. HPV-targeting NPs consisting of PBAE and CRISPR/shRNA could potentially be developed as drugs to treat HPV infection and HPV-related cervical malignancy.

BACKGROUND This study aimed to evaluate the factors associated with a survival benefit for patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib, with and without cytoreductive nephrectomy (CN). MATERIAL AND METHODS This retrospective clinical study included 118 patients with mRCC who were treated with CN and sunitinib (CN-sunitinib) (N=70) and with sunitinib-alone (N=48). Categorical clinicopathological variables were compared with hypothesis tests using contingency tables and a chi-squared test. Independent indicators for progression-free survival (PFS) and overall survival (OS) were analyzed with univariate and multivariate Cox regression models. The Kaplan-Meier method and log-rank test were used to evaluate patient survival. RESULTS The median PFS and OS for the 118 patients were 8.38 and 15.48 months, respectively. There were no significant differences between the CN-sunitinib group and the sunitinib-alone group for either PFS (7.2 months vs. 11.6 months; P=0.525) or OS (16.7 months vs. 15.2 months; P=0.839). Stratification of patients based on clinicopathological characteristics showed that CN was significantly associated with reduced PFS and OS for patients with lymph node metastasis (PFS, P

Background: The oral administration of anticoagulants is an effective means of preventing thromboembolic complications in patients implanted with mechanical valves. This treatment strategy, however, entails a dose-dependent in the risk of hemorrhage that is a cause for concern in China. As such, in this study, we sought to better determine what the ideal oral anticoagulant therapy intensity is in a Chinese population of patients implanted with mechanical valves. Methods: In the present observational cohort study, we observed the outcomes of eligible enrolled patients that had been implanted with St. Jude Medical prosthetic valves and who had been treated at our institution from 2013 onwards. All enrolled patients were followed for between 1 and 6 years through outpatient visits or telephone interviews following discharge. Study endpoints included instances of thromboembolism and major hemorrhage. We calculated the international normalized ratio (INR)-specific incidence of such adverse events as a means of determining optimal anticoagulant therapeutic intensity in patients with these bileaflet mechanical valve prostheses. Results: In total this study enrolled 3176 patients, of whom 3017 were followed for 12,746.08 total person-years (4.22 mean years per patient), while the remaining 159 patients (5%) were lost during follow-up. A total of 182 patients suffered from adverse events, with a roughly 1.43% annual incidence rate of such adverse events (95% confidence interval [CI], 1.22–1.64). Of these, 54 patients suffered from episodes of major bleeding (0.42% per patient-year, 95% CI, 0.31–0.53), while 131 suffered from thromboembolism (1.03% per patient-year, 95% CI, 0.85–1.21). Based on these analyses, we determined that the ideal low-intensity anticoagulant treatment regimen for patients with bileaflet mechanical heart valve prostheses was an INR between 1.5 and 2.5. In those patients that had undergone aortic valve replacement (AVR), the optimal INR was between 1.5 and 2.0 regardless of any thromboembolism risk factors in these patients. In contrast, in patients that had undergone mitral valve replacement (MVR) who were not at risk for thromboembolism, the optimal INR was between 1.5 and 2.0, whereas in those at risk of thromboembolism the optimal INR was between 2.0 and 2.5. The ideal anticoagulant intensity in patients undergoing both AVR and MVR (DVR) was the same as in patients undergoing MVR alone. Conclusions: In order to achieve optimal outcomes by maintaining effective anticoagulant dosing while entailing minimal risk in Chinese patients that have undergone a bileaflet mechanical valve replacement, the target INR range should be between 1.5 and 2.5, with the final intensity of this anticoagulant regimen being determined based on a given patient's risk of thromboembolism.

Cervical cancer is a serious threat to women's health and is the third most common malignancy in women worldwide. Recent studies indicate that the long non-coding RNA CCAT1 plays a role in the malignant behavior of many tumors. However, the role of CCAT1 in cervical cancer is still unknown. Our aim is to evaluate the expression and investigate the regulatory role and potential mechanism of CCAT1 in cervical cancer. CCAT1 expression was measured by qRT-PCR. In addition, CCK-8 assays, colony formation assays, qRT-PCR assays, Transwell assays and xenograft experiments were performed to determine the role of CCAT1 in the proliferation and invasion in cervical cancer cells. The expression of CCAT1 in the cervical cancer tissues was higher than in the adjacent normal tissues. Overexpressing CCAT1 promoted cervical cancer cell proliferation, colony formation, and invasion in vitro. Elevated CCAT1 suppressed miR-181a expression, which was accompanied by an increased expression of MMP14 and HB-EGF. In contrast, knocking down CCAT1 resulted in increased expression of miR-181a, along with decreased expression of MMP14 and HB-EGF. Thus, CCAT1 is a key oncogenic lncRNA associated with cervical cancer and plays a role in promoting cervical cancer cell proliferation and invasion by regulating the miR-181a-5p/MMP14 axis.

Gene therapy targeted human papillomavirus (HPV) is a promising treatment for cervical cancer, and the key for clinical application depends on an effective gene delivery method. Our aim was to formulate a new pharmaceutical formula for appropriate gene delivery intravaginally. For the first time, we here developed a new polyethylenimine (PEI) based vaginal suppository. The sectional immunofluorescence results confirmed the delivery efficacy both in vivo and in vitro. The quenching fluorescence and decreased gene expression in topical epithelium of green fluorescence protein (GFP) transgenic mice demonstrated the efficient targeting potential of the suppository. The other aim of this study was to evaluate the biocompatibility of the PEI based transfer. To our knowledge, this was also the first study to explore the toxicity in vivo systematically and comprehensively. Our study provided novel ideas for the translational application of PEI based suppository to the prevention and treatment of cervical cancer.

Transcatheter aortic valve implantation (TAVI) is an established treatment for high surgical risk aortic stenosis patients; in recent years, it has also been used in patients with pure/dominant aortic regurgitation (AR). This study aimed to determine the impact of transapical TAVI on left ventricle myocardial mechanics in AR patients. Thirty AR patients (70% men; mean age, 72.8 ± 4.3 years) were enrolled. Conventional echocardiography was performed on all patients before and 12 months after TAVI. Three-dimensional speckle tracking was accomplished in 20 AR patients for the evaluation of global longitudinal strain, global circumferential strain, twist, torsion, apical rotation and basal rotation. Preoperative left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), global circumferential strain (GCS), twist, torsion and apical rotation were impaired in AR patients compared with controls. Mean left ventricular (LV) end-diastolic diameter (from 62.9 ± 7.3 to 52.0 ± 6.8 mm, p

Human papillomavirus (HPV) integration is a key genetic event in cervical carcinogenesis. By conducting whole-genome sequencing and high-throughput viral integration detection, we identified 3,667 HPV integration breakpoints in 26 cervical intraepithelial neoplasias, 104 cervical carcinomas and five cell lines. Beyond recalculating frequencies for the previously reported frequent integration sites POU5F1B (9.7%), FHIT (8.7%), KLF12 (7.8%), KLF5 (6.8%), LRP1B (5.8%) and LEPREL1 (4.9%), we discovered new hot spots HMGA2 (7.8%), DLG2 (4.9%) and SEMA3D (4.9%). Protein expression from FHIT and LRP1B was downregulated when HPV integrated in their introns. Protein expression from MYC and HMGA2 was elevated when HPV integrated into flanking regions. Moreover, microhomologous sequence between the human and HPV genomes was significantly enriched near integration breakpoints, indicating that fusion between viral and human DNA may have occurred by microhomology-mediated DNA repair pathways. Our data provide insights into HPV integration-driven cervical carcinogenesis.

Persistent HPV infection is recognized as the main etiologic factor for cervical cancer. HPV expresses the oncoproteins E6 and E7, both of which play key roles in maintaining viral infection and promoting carcinogenesis. While siRNA-mediated targeting of E6 and E7 transcripts temporarily induces apoptosis in HPV-positive cells, it does not eliminate viral DNA within the host genome, which can harbor escape mutants. Here, we demonstrated that specifically targeting E6 and E7 within host DNA with transcription activator–like effector nucleases (TALENs) induces apoptosis, inhibits growth, and reduces tumorigenicity in HPV-positive cell lines. TALEN treatment efficiently disrupted E6 and E7 oncogenes, leading to the restoration of host tumor suppressors p53 and retinoblastoma 1 (RB1), which are targeted by E6 and E7, respectively. In the K14-HPV16 transgenic mouse model of HPV-driven neoplasms, direct cervical application of HPV16-E7–targeted TALENs effectively mutated the E7 oncogene, reduced viral DNA load, and restored RB1 function and downstream targets transcription factor E2F1 and cycling-dependent kinase 2 (CDK2), thereby reversing the malignant phenotype. Together, the results from our study suggest that TALENs have potential as a therapeutic strategy for HPV infection and related cervical malignancy.

Purpose: Cervical cancer is mainly caused by infections of high-risk human papillomavirus (HR-HPV). Persistent expression of HR-HPV oncogenes E6 and E7 is implicated in malignant transformation. The aim was to provide proof-of-concept data to support use of zinc finger nucleases (ZFN) targeting HPV E7 to treat HPV-related cervical cancer. Experimental Design: We designed and constructed ZFNs that could specifically recognize and cleave HPV16/18 E7 DNA. We tested the cleavage efficiency of selected ZFN16-E7-S2 and ZFN18-E7-S2 by using single-strand annealing (SSA) assay. Cell viability and colony formation assays were used to estimate the inhibition of cell growth that received treatments of ZFNs. Gene disruption of HPV E7 and downstream genes were examined by Western blotting. Cell apoptosis assay was used to test the specificity and efficiency of induction of HPV type-specific apoptosis. We also introduced xenograft formation assays to estimate the potential of inhibition of HPV-related disease. Results: We found ZFN16-E7-S2 and ZFN18-E7-S2 disrupted HPV E7 oncogenes in HPV16/18–positive cervical cancer cells. Both ZFNs effectively led to inhibition of type-specific cervical cancer cell growth, and specifically induced apoptosis of corresponding HPV16- and HPV18-positive cervical cancer cell lines. ZFN16-E7-S2 and ZFN18-E7-S2 also repressed xenograft formation in vivo. Conclusion: ZFNs targeting HPV16/18 E7 could effectively induce disruption of E7 oncogenes and lead to type-specific and efficient growth inhibition and apoptosis of HPV-positive cells. ZFNs targeting HPV16/18 E7 oncogenes could be used as novel therapeutic agents for the treatment of HPV-related cervical cancer. Clin Cancer Res; 20(24); 6495–503. ©2014 AACR.

Objective: This study aims to present the graft pathology at the time of harvest and its impact on long-term survival. Methods: The remnants of the bypass grafts from 66 consecutive patients with coronary artery disease receiving a coronary artery bypass grafting were investigated pathologically, and pertinent predictive risk factors and survival were analyzed. Results: Medial degenerative changes with or without intimal proliferation were present in 36.8%, 37.8% and 35.6% of left internal mammary artery (IMA), radial artery and saphenous vein grafts. There were 2 (3.0%) hospital deaths and 9 (14.1%) late deaths. Multinomial logistic regression revealed left IMA pathological changes, dyslipidemia, history of percutaneous transluminal coronary angioplasty/stent deployment and Y-graft were significant predictive risk factors negatively influencing the patients’ long-term survival. Kaplan-Meier survival analysis revealed that the long-term survival of patients with left IMA pathological changes were significantly reduced compared with those without (74.1% vs. 91.4%, P=0.002); whereas no differences were noted in long-term survivals between patients with and without pathological changes of the radial arterial or saphenous vein grafts. Conclusion: Pathological changes may be seen in the bypass graft at the time of harvest. The subtle ultrastructural modifications and the expressions of vascular tone regulators might be responsible for late graft patency. The pathological changes of the left IMA at the time of harvest rather than those of the radial artery or saphenous vein graft affect significantly longterm survival. Non-traumatic maneuver of left IMA harvest, well-controlled dyslipidemia and avoidance of using composite grafts can be helpful in maintaining the architecture of the grafts. Objetivo: Este estudo tem como objetivo apresentar a patologia do enxerto no momento da coleta e do impacto na sobrevida a longo prazo. Métodos: Os remanescentes de pontes de safena de 66 pacientes consecutivos com doença arterial coronária que receberam uma cirurgia de revascularização coronariana foram investigados patologicamente, e os fatores de risco preditivos e a sobrevivência foram analisados. Resultados: Alterações degenerativas da artéria medial, com ou sem proliferação da íntima estavam presentes em 36,8%, 37,8% e 35,6% de pontes da artéria torácica interna esquerda (ATIE), artéria radial e veia safena. Houve dois (3,0%) óbitos hospitalares e nove (14,1%) óbitos tardios. A regressão logística multinomial revelou que alterações patológicas na ATIE, dislipidemia, história de angioplastia/stent implantação coronariana transluminal percutânea e Y-enxerto foram significativos fatores de risco preditivos que influenciam negativamente a sobrevivência a longo prazo dos pacientes. Análise de sobrevida de Kaplan- Meier revelou que a sobrevivência a longo prazo de pacientes com alterações patológicas da ATIE foi significativamente reduzida em comparação com aqueles sem (74,1% vs. 91,4%, P=0,002), considerando que não foram observadas diferenças na sobrevivência de longo prazo entre pacientes com e sem alterações patológicas dos enxertos da artéria radial ou de veia safena. Conclusão: As alterações patológicas podem se desenvolver na revascularização no momento da coleta. As modificações ultraestruturais sutis e as expressões de reguladores do tônus vascular podem ser responsáveis pela patência tardia do enxerto. As alterações patológicas da ATIE no momento da coleta, em vez do enxerto da artéria radial ou da veia safena, podem afetar significativamente a sobrevida de longo prazo. Manobra não traumática da ATIE na coleta, bom controle da dislipidemia e para evitar uso de enxertos compostos pode ser útil na manutenção da arquitetura dos enxertos.

Cervical cancer is the second most common cancer and the third leading cause of cancer death in females worldwide, especially in developing countries. High risk human papillomavirus (HR-HPV) infection causes cervical cancer and precancerous cervical intraepithelial neoplasia (CIN). Integration of the HR-HPV genome into the host chromatin is an important step in cervical carcinogenesis. The detection of integrated papillomavirus sequences-PCR (DIPS-PCR) allowed us to explore HPV integration in the human genome and to determine the pattern of this integration. We performed DIPS-PCR for 4 cell lines including 3 cervical cancer cell lines and 40 tissue samples. Overall, 32 HR-HPV integration loci were detected in the clinical samples and the HeLa and SiHa cell lines. Among all the integration loci, we identified three recurrent integration loci: 3p14.2 (3 samples), 13q22.1 (2 samples and a SiHa cell line) and 8q24 (1 sample and a HeLa cell line). To further explore the effect of HR-HPV integration in the 3p14.2 locus, we used fluorescence in situ hybridization (FISH) to determine the copy number of the 3p14.2 locus and immunohistochemistry (IHC) to determine the protein expression levels of the related FHIT gene in the clinical samples. Both the 3p14.2 locus copy number and FHIT protein expression levels showed significant decreases when CIN transitioned to cervical cancer. HPV copy number was also evaluated in these clinical samples, and the copy number of HPV increased significantly between CIN and cervical cancer samples. Finally, we employed receiver operating characteristic curve (ROC curve) analysis to evaluate the potential of all these indexes in distinguishing CIN and cervical cancer, and the HPV copy number, FHIT copy number and FHIT protein expression levels have good diagnostic efficiencies.

To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) for high-risk patients with aortic stenosis using the J-Valve system.30 high-risk patients with severe AS underwent TAVI procedure were enrolled with mean age 74.5±4.5 years and mean logistic Euro-SCORE-I of 28.4±9.6%. All patients were followed up for 6 months. Outcomes were analysed in accordance with the updated standardised endpoints defined by the Valve Academic Research Consortium -2 (VRAC-2) criteria.VARC-2 defined device success was obtained in 93% (28 of 30 patients). No operative mortality was noted. No major complications such as third-degree AV-block, myocardium infraction or cerebrovascular events were noted during procedure and follow-up. Transvalvular PG was decreased at 6 months compared with preoperative state (PG mean: 55.4±14.9 vs 14.6±6.9mmHg p0.01). No moderate or above degree paravalvular leakage (PVL) was noted. All patients with successful valve implantation were alive with improved exercise tolerance.Our initial result has demonstrated that the J-Valve system has the potential to become a feasible treatment option for high-risk patients with severe AS.

// Wei-na Zhang 1, 2, * , Wei Li 1, * , Xiao-li Wang 1 , Zheng Hu 1 , Da Zhu 1 , Wen-cheng Ding 1 , Dan Liu 1 , Ke-zhen Li 1 , Ding Ma 1 , Hui Wang 1 1 Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China 2 Department of Gynecology, Qingdao Municipal Hospital, Qingdao, Shandong 266000, P.R. China * These authors have contributed equally to this work Correspondence to: Ding Ma, email: dma@tjh.tjmu.edu.cn Hui Wang, email: huit71@sohu.com Keywords: cervical cancer, CLDN1, array CGH, EMT Received: August 29, 2016 Accepted: November 07, 2016 Published: December 10, 2016 ABSTRACT Even though infection with human papillomaviruses (HPV) is very important, it is not the sole cause of cervical cancer. Because it is known that genetic variations that result from HPV infection are probably the most important causes of cervical cancer, we used human whole genome array comparative genomic hybridization to detect the copy number variations of genes in cervical squamous cell carcinoma. The results of the array were validated by PCR, FISH and immunohistochemistry. We find that the copy number and protein expression of claudin-1 (CLDN1) increase with the progression of cervical cancer. The strong positive staining of CLDN1 in the cervical lymph node metastasis group received a significantly higher score than the staining in the group with no lymph node metastasis of cervical cancer tissues. The overexpression of CLDN1 in SiHa cells can increase anti-apoptosis ability and promote invasive ability of these cells accompanied by a decrease in expression of the epithelial marker E-cadherin as well as an increase in the expression of the mesenchymal marker vimentin. CLDN1 induces the epithelial-mesenchymal transition (EMT) through its interaction with SNAI1. Furthermore, we demonstrate that CLDN1 overexpression has significant effects on the growth and metastasis of xenografted tumors in athymic mice. These data suggest that CLDN1 promotes invasion and metastasis in cervical cancer cells via the expression of EMT/invasion-related genes. Therefore, CLDN1 could be a potential therapeutic target for the treatment of cervical cancer.

This study was to investigate whether polymerized human placenta hemoglobin (PolyPHb) given before ischemia protects in vivo rat heart function against ischemia/reperfusion (I/R) injury. Forty-five male Sprague-Dawley rats were randomly divided (n = 15 per group) into a sham group, control group (pretreatment with Lactated Ringer's solution), or PolyPHb group (pretreatment with 0.1 gHb/kg PolyPHb). Rat hearts were subjected to 30-min ischemia by occlusion of left anterior descending, followed by 2-hr reperfusion. As compared to the control group, PolyPHb preserved cardiac function and reduced cardiac troponin-I release and histopathological changes. Therefore, PolyPHb pretreatment provided a profound cardioprotective effect on the in vivo rat heart.

Objective: We introduced a new atrial septum remodeling technique and further investigated the feasibility of this method in facilitating the intra-operative device closure (IODC) of multiple atrial septal defects (ASDs). Methods: Adult patients with multiple nearby ASDs, which were not eligible for transcatheter closure, were enrolled in this study. Transesophageal echocardiogram (TEE) was applied for intra-operative evaluation. The multiple ASDs were divided into three different types according to its morphology. Based on the concept of breaking the rim between multiple ASDs and making it feasible for single device closure, atrial septum remodeling procedure was carried out via pre-atrial approach using special clamp under the guidance of TEE. IODC was then attempted for reshaped ASD. Successful rate and perioperative complications were then noted. Results: Eleven patients were enrolled in this study, with mean age being 23.4 5.3 years and mean weight 51.6 8.0 kg. Among them, seven patients have double ASDs and four have triple ASDs. Mean diameter of isolated ASD was 10.4 3.8 mm with a mean distance of 3.2 1.2 mm between each other. Atrial septum remodeling procedure was successfully done in all patients. One device was then used for each patient. Mean ASD diameter after remodeling procedure was 20.6 3.9 mm with mean device size 23.5 4.0 mm. Complete closure of multiple ASDs was achieved in nine patients immediately after the procedure; two patients had trivial grade shunt after device deployment that resolved within the 3-month follow-up. No severe complications were noticed during the perioperative period and the 3-month follow-up. Conclusions: Atrial septum remodeling technique seems to be a safe and effective method that could largely facilitate the successful IODC of multiple ASDs. # 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Cardiac myxoma arising form right ventricular outflow tract (RVOT) is extremely rare, but could cause major clinical sequelae and pose considerable diagnostic and therapeutic challenges. Here, we report the intraoperative application of real time three-dimensional transesophageal echocardiography (RT3DTEE) in the assessment of a patient with a RVOT myxoma. RT3DTEE clearly assess the characteristics of the mass, such as the size, shape, attachment points, and composition. With the intraoperative guidance of RT3DTEE, the patient underwent successful removal of the mass.

Transcatheter aortic valve implantation (TAVI) procedure is truly challenging in patients with pure aortic regurgitation (AR). The J-Valve TAVI device (JC Medical Inc., Burlingame, California) is characterized by a U-shaped anatomically orientating device—the “clasper” [(1)][1]. This design

We used oxidative isotope-coded affinity tags (OxICAT) to investigate the global redox status of proteins in human papillomavirus (HPV)-related cervical cancer cells, in order to identify a potential target for gene therapy. Voltage-dependent anion channel 1 (VDAC1) was found to be highly oxidized in HPV-positive cervical cancer cells. VDAC1 expression correlated significantly with the invasion of cervical cancer, the grade of cervical intraepithelial neoplasia (CIN) and the expression of HPV16 E7 in CIN. Knockdown of VDAC1 in cell lines increased the rate of apoptosis, while overexpression of the VDAC1 (respectively) partly reversed the effect. Thus, VDAC1 may promote the malignant progression of HPV-related disease, and treatments designed to suppress VDAC1 could prevent the progression of HPV-induced cervical disease.

The aim of this study was to provide a histopathological validation of cardiac late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) for the assessment of left atrial (LA) substrate remodeling (SRM) in patients with rheumatic mitral valve disease and persistent atrial fibrillation (AF).Adult patients with rheumatic mitral valve disease and persistent AF undergoing open-heart surgery for mitral valve replacement were enrolled. Both two-dimensional (2D) sections and 3-dimensional (3D) full-volume LGE-MRI with different signal intensities were performed preoperatively to determine the extent of LA-SRM. Tissue samples were obtained intraoperatively from the LA roof and posterior lateral wall for pathological validation with Masson trichrome staining and immunostaining for collagen type I/III deposition. A linear regression model was used to determine the relationship between MRI-derived LA-SRM parameters and pathological results.Between February 2013 and March 2014, we successfully acquired LA tissue samples from 22 patients (13 men), with a mean age of 47 ± 8 years. All patients had rheumatic mitral valve stenosis, with a mean effective orifice area of 0.9 ± 0.2 cm(2) on echocardiography and a mean LA volume of 235 ± 85 mL on 3D-MRI. Multiple moderate linear associations were noted between the pathological results and LGE-MRI-derived LA-SRM parameters, with correlation indices (r(2)) of 0.194-0.385.LA-SRM measured by LGE-MRI showed moderate agreement with LA pathology in patients with rheumatic valve disease and persistent AF.

Background To evaluate the long-term safety and efficacy of using perventricular device closure in treating selected patient with doubly committed sub-arterial ventricular septal defect (VSD) Methods During July 2007 and April 2011, 86 patients with doubly committed subarterial VSD who met the inclusion criteria were enrolled in this study. Perventricular closure was attempted using a unique design eccentric device under the guidance of transesophageal echocardiography. Complications such as residual shunt, arrhythmia, valve regurgitation were all recorded in postoperative period and during follow-up. Multiple logistic regression analysis was performed to study risk factors for procedure failure and complications. Result Perventricular device closure was successfully done in 75 patients (87.2 %) with mean age 7.0 ± 7.0 years old, VSD size 4.8 ± 1.5 mm and device size 6.7 ± 1.7 mm. Complete closure rate was achieved in 94.7 % at discharge and 96 % during follow-up. No severe complications such as device embolism, significant arrhythmia, left ventricular outflow tract obstruction as well as obvious valve regurgitation were noted during follow-up (Mean 4.5 ± 1.5 years). Procedure induced trivial-mild grade aortic valve regurgitation (AR) was noted in 16 (21.3 %) patients at discharge while 8 of them resolved during follow-up. Multivariable analysis revealed that procedure-induced AR was associated device diameter to patients’ weight (OR = 12.3 95 % CI 1.5- 99.2). Perventricular device closure was failed in 11 patients, preoperative aortic valve prolapse was the major risk factor for failure of the procedure (OR = 65 95 % CI 7.5- 564.1). Conclusion Perventricular closure of doubly committed subarterial VSDs appears to be a safe and effective minimally invasive treatment option in selected patients with good long-term outcomes. Clinical trial registration Unique Identifier: ChiCTR-TNC-00000203.

Background Cardiac masses are rare with high morbidity and mortality that challenging the management. The purpose of this study was to evaluate the potential role of cardiac-MRI based multi-modality imaging in the clinical decision-making for patients with cardiac mass. Methods From November 2011 to May 2014, 59 consecutive patients (33 females; mean age, 48.2±21.1 [range, 0.6–85] years) with suspected cardiac mass were enrolled in this prospective single center study, underwent MRI based multi-modality imaging and were followed up for survival status. Management strategy (surgery, chemotherapy or observation) was based on patient's clinical status and cardiac mass imaging characteristics (location, morphology, hemodynamics, embolization risk, metastasis, and resectability). Results Using cardiac MRI, 39 patients were diagnosed with intra-cardiac neoplasm (28 benign, 11 malignant) and 20 with pseudo-tumors (13 thrombi, 4 cysts and 3 fat infiltration); 34 masses (23 neoplasms, 11 pseudo-tumors) were eligible for surgical removal, and 4 underwent PET-CT scan to further delineate characteristics and metastasis. Pathological examination revealed high accuracy of cardiac MRI in differentiating benign from malignant tumors (96%), and neoplasm from pseudo-tumors (100%). As for the 16 patients with cardiac neoplasm not surgically treated, the 9 with "benign" masses as per MRI-based multimodality imaging survived during follow-up, while all 7 with "malignancy" died; the 9 with pseudo-tumors not surgically treated also survived with good condition. The median follow-up period is 2years (10days–3years). Conclusion Cardiac MRI based multimodality imaging appears useful for risk stratification and clinical decision making for patients with suspected cardiac mass.

To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) for patients with aortic stenosis (AS) or pure/dominant aortic regurgitation (AR) using the J-Valve™ system.Twenty patients with isolated aortic valve disease (11 with pure/dominant AR and 9 with AS) at high risk for open-heart surgery were enrolled in this study. The mean Logistic Euro-SCORE I was 27.2±8.2% (mean age 74.5±4.7years). Four sizes of prosthesis were used for annular size up to 21 mm (n=1), 23mm (n=2), 25mm (n=10) and 27mm (n=7). Clinical and echocardiographic evaluations were performed at baseline, post-procedure and follow-up. The primary endpoint was all-cause mortality. Secondary endpoints were procedural success, major adverse events as well as echocardiographic performance.TAVI with the J-Valve™ device was successfully performed in 19 patients (95%). Conversion to surgical valve replacement was necessary in one patient due to prosthesis embolization. No mortality occurred during 90 days follow-up. Pacemaker implantation for new onset conduction disorders was necessary in one patient (5%). For patient with severe AS, post-procedure TAVI resulted in favorable reduction of mean transvalvular gradients (55.3±8.5 vs. 16.4±13.3 mmHg, P0.01). Mean transvalvular gradient was also favorable in AR patients after valve implantation (6.9±1mmHg). The majority of patients had none or trivial paravalvular regurgitation (17/19) while none had moderate or severe paravalvular regurgitation.Trans-apical TAVI using the J-Valve™ prosthesis is potentially an effective treatment option for patients with AS or pure/dominant AR at high risk for open-heart surgery.

Introduction: Minimally invasive surgical ablation is an emerging alternative method to catheter ablation and the full surgical maze procedure for nonpharmacologic treatment of atrial fibrillation (AF). We present a totally thoracoscopic “box lesion” radiofrequency ablation procedure in patients with paroxysmal or persistent AF. Materials and Methods: From June 2011 to October 2012, 14 patients with lone paroxysmal (n = 7) or persistent AF (n = 7) were enrolled in this study. Procedures were performed through 3 5-12 mm holes on each side of the chest wall. A bipolar ablation device was used to create a box lesion in the posterior wall of the left atrium that encircled the 4 pulmonary veins (achieving bilateral pulmonary vein/posterior left atrial wall isolation). Perioperative complications were recorded for all patients. Freedom from AF was assessed by 24-hour Holter monitoring every 3 months or during symptoms of arrhythmia. Results: The ablation was successfully performed in all patients, with median operation time of 128 minutes (range, 45 to 180 minutes). No operative mortality or morbidity were noted during the study period. Freedom from AF was achieved in 12 patients (85.7%) during follow-up (median follow-up 9 months). One patient with persistent AF was shifted to paroxysmal AF. No atrial flutter or atrial tachycardia was noted during the follow-up. Conclusion: These early results show that totally thoracoscopic surgical ablation using a unique “box lesion” procedure for persistent or paroxysmal AF is a feasible and effective method with good short-term results. Further study is necessary to validate this result. Key words: Arrhythmia therapy, Flutter, Surgery, Thoracoscopy

In diabetes, intracellular accumulation of sorbitol resulting from the high extracellular levels of glucose leads to depletion of intracellular compounds including taurine. This is associated with the development of late diabetic complications such as cardiomyopathy. The development of myocyte hypertrophy has been largely attributed to angiotensin II, whose growth properties are antagonized by taurine. However, the interaction between taurine, angiotensin II type2 receptor (AT2) and cardiomyopathy related to angiotensin II is still unknown. This study investigates the roles of taurine and AT2 in rats with streptozotocin (STZ)-induced diabetic cardiomyopathy.Of 60 female 4-week-old Wistar rats, 8 were treated with common diet and the other 52 with high sugar/fat diet (during the whole experiment) to induce insulin resistance. At the 4th week, of the 52 rats, 7 treated with sodium citrate buffer (pH = 4.5) were grouped into control group1 (con1) and the other 45 were treated by intraperitoneal injection (I.P) with STZ to develop type 2 diabetes. At the 28th week, the maximal velocity decrease of pressure per second in left ventricle within the period of isovolumic relaxation (-dp/dt(max)) was detected by a cannula through right carotid artery. After the cannula operation, of the 45 rats, all the living 24 with -dp/dt(max)or = 5250 mmHg/s, who had developed diabetic cardiomyopathy, were grouped as follows: 7 treated with double distilled H2O (I.P) were grouped into control group2 (con2). 8 treated with AT2 agonist (CGP42112A) (I.P) were grouped into experimental group1 (exp1). Another 9 treated with taurine (I.P) were grouped into experimental group2 (exp2). All injections lasted 4 weeks (Q.D) and the heart weight (HW) was recorded. To examine cardiomyocyte apoptosis index (CAI), mRNA and protein of AT2 and Bcl-2 in cardiomyocytes, methods of terminal-deoxynucltidyl transferase mediated nick end labeling (TUNEL), reversal transcription polymerase chain reaction (RT-PCR) and immunoblot (Western Blot) were used, respectively.Values of -dp/dt(max) in exp1, exp2 or con2 were much less than those in con1, respectively (p0.01). CAI (= stained cell number/total cell number x 100%) and AT2 values both in mRNA and protein levels in con1 were less than those in the other three groups, respectively (p0.01). The three parameters above were more in exp1 but less in exp2 than those in con2, respectively (p0.01). The three parameters and HW in exp1 were much higher than those in exp2, respectively (p0.01). Changes of Bcl-2 were opposed to those of AT2.A high expression of AT2 may accelerate the apoptosis of cardiomyocytes in diabetic rats and play a role in precipitating diabetic cardiomyopathy; taurine may protect diabetic rats from developing cardiomyopathy also by downregulating AT2 receptors.

The objective of the present study was to evaluate the potential effect of environmental exposure to cadmium on pregnancy outcome and fetal growth. Normal pregnant women were selected from Da-ye city of Hubei province, a cadmium-polluted area, from November 2002 through January 2003. Whole blood of pregnant women, cord blood, and placenta were collected and cadmium levels were determined by inductively coupled plasma emission mass spectroscopy. Incidence rate of preterm labor (gestational ageor = 37 weeks) and neonatal asphyxia, neonatal birth height, and birth weight were compared between lower and higher cadmium exposure level groups. Whole blood cadmium of 44 mothers ranged from 0.80 to 25.20 microg/L. Cadmium concentration in maternal blood was significantly higher than that in cord blood (t = 11.44, P0.01). Placenta cadmium ranged from 0.084 to 3.97 microg/g dry weight. After adjustment for maternal age, history of gestation, abortion and lactation, Logistic regression analysis showed that there was no significant association between cadmium exposure levels and pregnancy outcome (premature labor or neonatal asphyxia). Multiple linear regression analysis showed that, cord blood cadmium level, but not maternal blood cadmium and placenta cadmium, was significantly negatively associated with neonatal birth height (t= -2.33, P0.05). Compared with lower cord blood cadmium level (or = 0.40 microg/L), higher level of cord blood cadmium (0.40 microg/L) was associated with 2.24cm decrease in neonatal birth height. There was no significant association between cadmium exposure and birth weight. It was concluded that environmental exposure to cadmium significantly lower neonatal birth height.

The objective of the present study was to evaluate the potential effects of zinc, copper, and selenium on placental cadmium transport. From November 2002 through January 2003, a total of 47 healthy pregnant women from Da-Ye City, Hubei Province in Central China participated in the study. Their age, parity, gestational age, pregnancy history, and lifestyle data were obtained by questionnaire interview. The placental, whole-blood, and cord blood levels of cadmium were determined by inductively coupled plasma mass spectrometer (ICP-MS), whole-blood zinc was measured by flame atomic absorption spectrometry (F-AAS), whole-blood copper by ICP-MS, and selenium was by atomic fluorescence spectrophotometry (AFS). The cord blood cadmium concentration (0.020-1.48 microg/L) was significantly lower than in maternal blood (0.80-25.20 microg/L, p

Transcatheter closure is the mainstay of treatment for patent ductus arteriosus (PDA) in the pediatric patient but it is technically challenging and does not always succeed, especially in a younger age child with a large PDA. We present a technique of using a transesophageal echocardiogram-guided minimally invasive perventricular closure for the pediatric patient with a large PDA who failed transcatheter closure.

Transcatheter aortic valve implantation (TAVI) has evolved as a routine procedure to treat selected high-risk patients with severe aortic stenosis. The new J-Valve™ prosthesis is designed for antegrade transapical implantation, it is characterized by a porcine aortic prosthesis attaching to a self-expandable Nitinol stent. The key feature of the device are three U-shape anatomically oriented devices - “graspers” which could facilitate intuitive ‘self-positioning’ valve implantation. Hereby, we report a successful case of trans-apical TAVI in an elderly high-risk patient with severe aortic stenosis using J-Valve™ system.

Circular RNAs (circRNAs) are a unique class of endogenous RNAs which could be used as potential diagnostic and prognostic biomarkers of many diseases. Our study aimed to investigate circRNA profiles in human granulosa cells (GCs) during maternal aging and to uncover age-related circRNA variations that potentially reflect decreased oocyte competence. CircRNAs in GCs from in vitro fertilization (IVF) patients with young age (YA, ≤ 30 years) and advanced age (AA, ≥ 38 years) were profiled by microarray, and validated in 20 paired samples. The correlation between circRNAs expression and clinical characteristics was analyzed in additional 80 samples. Chip-based analysis revealed 46 up-regulated and 11 down-regulated circRNAs in AA samples (fold change > 2.0). Specifically, circRNA_103829, circRNA_103827 and circRNA_104816 were validated to be up-regulated, while circRNA_101889 was down-regulated in AA samples. After adjustment for gonadotropin treatment, only circRNA_103827 and circRNA_104816 levels were positively associated with maternal age (partial r = 0.332, P = 0.045; partial r = 0.473, P = 0.003; respectively). Moreover, circRNA_103827 and circRNA_104816 expressions in GCs were negatively correlated with the number of top quality embryos (r = -0.235, P = 0.036; r = -0.221, P = 0.049; respectively). Receiver operating characteristic (ROC) curve analysis indicated that the performance of circRNA_103827 for live birth prediction reached 0.698 [0.570–0.825], with 77.2% sensitivity and 60.9% specificity (P = 0.006), and that of circRNA_104816 was 0.645 [0.507–0.783] (P = 0.043). Bioinformatics analysis revealed that both circRNAs were potentially involved in glucose metabolism, mitotic cell cycle, and ovarian steroidogenesis. Therefore, age-related up-regulation of circRNA_103827 and circRNA_104816 might be potential indicators of compromised follicular micro-environment which could be used to predict IVF prognosis, and improve female infertility management.

The surgical management of multiple muscular ventricular septal defects (mVSDs) in the infant remains a challenging problem because of the presence of residual shunts and postoperative myocardial dysfunction. We present a case of successful repair of multiple mVSDs with a unique hybrid procedure combining both the perventricular closure and open surgical repair. (J Card Surg 2011;26:237-239)

Transcatheter aortic valve implantation (TAVI) has become an effective treatment option for high-risk or inoperable patients with aortic stenosis. However, experience with TAVI for non-calcified aortic regurgitation is still limited. The new J-Valve(™) system is a new second-generation TAVI device that is designed for transapical implantation. It is characterized by three U-shaped, anatomically oriented devices-'graspers' that could facilitate intuitive 'self-positioning' valve implantation and provide extra-radial fixation by embracing the native valve leaflets. Here, we reported the initial experience of TAVI in high-risk patients with pure aortic regurgitation using the J-Valve(™) system.

Lymphatic vessels are one of the major routes for the dissemination of cancer cells. Malignant tumors release growth factors such as VEGF-C to induce lymphangiogenesis, thereby promoting lymph node metastasis. Here, we report that sine oculis homeobox homolog 1 (SIX1), expressed in tumor cells, can promote tumor lymphangiogenesis and lymph node metastasis by coordinating with TGFβ to increase the expression of VEGF-C. Lymphangiogenesis and lymph node metastasis in cervical cancer were closely correlated with higher expression of SIX1 in tumor cells. By enhancing VEGF-C expression in tumor cells, SIX1 could augment the promoting effect of tumor cells on the migration and tube formation of lymphatic endothelial cells (LEC) in vitro and lymphangiogenesis in vivo. SIX1 enhanced TGFβ-induced activation of SMAD2/3 and coordinated with the SMAD pathway to modulate VEGF-C expression. Together, SIX1 and TGFβ induced much higher expression of VEGF-C in tumor cells than each of them alone. Despite its effect in promoting VEGF-C expression, TGFβ could inhibit lymphangiogenesis by directly inhibiting tube formation by LECs. However, the increased production of VEGF-C not only directly promoted migration and tube formation of LECs but also thwarted the inhibitory effect of TGFβ on LECs. That is, tumor cells that expressed high levels of SIX1 could promote lymphangiogenesis and counteract the negative effects of TGFβ on lymphangiogenesis by increasing the expression of VEGF-C. These findings provide new insights into tumor lymphangiogenesis and the various roles of TGFβ signaling in tumor regulation. Our results also suggest that SIX1/TGFβ might be a potential therapeutic target for preventing lymph node metastasis of tumor. Cancer Res; 74(19); 5597–607. ©2014 AACR.

To evaluate the safety and efficiency of using hybrid perventricular closure in treating pediatric patients with the doubly committed subarterial ventricular septal defects (VSD).Ninety pediatric patients with doubly committed subarterial VSD were enrolled from October 2007 to September 2010 in this retrospective study. Among them, 41 underwent open-heart surgery (surgical group), while 49 underwent perventricular device closure (perventricular group).There was no difference in age (4.36 ± 3.21 vs. 5.82 ± 4.32 years, p 0.05) between the two groups. VSD diameter was significantly larger in the surgical group than in the perventricular group (5.03 ± 1.31 vs. 6.03 ± 1.94 mm, p 0.05). There were no major complications such as death, severe valve insufficiency, significant residual shunt, or lethal arrhythmias in two groups. The perventricular group was associated with a significant reduction of transfusion rate (18.4% vs. 97.6%, p 0.05) as well as mean intensive care unit (ICU) stay (0.97 ± 0.53 vs. 2.78 ± 3.00 days, p 0.05) in comparison with the surgical group. No difference was noted for complete closure rate between two groups at discharge (97.6% vs. 85.7%, p 0.05) as well as during follow-up (97.6% vs. 95.9%, p 0.05). Perventricular device closure was not associated with an increased risk of procedure-induced aortic insufficiency compared with the open-heart surgical group during follow-up (14.3% vs. 14.6%, p 0.05).Hybrid perventricular closure may be an alternative to open-heart surgery in selected pediatric patients with doubly committed subarterial VSD.

Ventricular septal defect (VSD) is a common congenital heart disease. Open surgical repair with cardiopulmonary bypass (CPB) and sternotomy is the classic treatment. Percutaneous device closure is a minimally invasive alternative in treating selected VSDs, but it is limited by vascular access as well as radiation exposure especially in pediatric patients. Hybrid perventricular device closure of VSDs was designed to combine the advantages of both approaches allowing direct access to the defect without CPB and has gained wider acceptance in recent years. Under transesophageal echocardiography guidance, it could effectively close muscular, perimembranous, and even doubly committed defects. It is a safe and effective option for selected patients with congenital VSDs. In this article, we reviewed the application and results of this technique.

Biopsy confirmed that cervical intraepithelial neoplasia (CIN) may naturally regress or progress. Currently, the risk assessment for CIN progression to cervical cancer is still not satisfactory in clinical practice. We investigated copy number and protein expression of TP63 and MYC and explored the possibility to use them as progression biomarkers.Copy numbers of TP63 and MYC, as well as human papilloma virus (HPV) integration status, were determined by fluorescence in situ hybridization in 39 patients with CIN and 66 patients with cervical cancer. Corresponding protein expressions were analyzed by immunohistochemistry. Receiver operating characteristic curves were used to measure the diagnostic test performance for the detection of cervical cancer from CIN. Sensitivity and specificity values of biomarkers were calculated.The average copy number and expression of TP63 and MYC, as well as the HPV integration rate, increased in the progression of CIN to cervical cancer. Receiver operating characteristic analysis for detection of cervical cancer resulted in area under the curve (AUC) values of TP63 copy number (AUC, 0.96; 95% confidence interval [CI], 0.91-1.00), MYC copy number (AUC, 0.92; 95% CI, 0.85-0.96), TP63 expression (AUC, 0.73; 95% CI, 0.61-0.85), and HPV-16 integration (AUC, 0.73; 95% CI, 0.60-0.85). MYC expression was not able to statistically distinguish cancer from CIN (P = 0.393). The combinations increased the specificity slightly but not sensitivity. Among them, TP63 amplification showed the best diagnostic performance.Amplification and overexpression of TP63 and MYC, and HPV integration rate, are associated with the transition of CIN to cervical cancer. Future studies on these biomarkers will help to assess the risk of CIN progression.

Residual muscular ventricular septal defects are surgical challenges, especially after the repair of complex congenital heart defects. We investigated perventricular device closure as a salvage technique in pediatric patients who had postoperative residual muscular ventricular septal defects. From February 2009 through June 2011, 14 pediatric patients at our hospital had residual muscular ventricular septal defects after undergoing surgical repair of complex congenital heart defects. Ten patients met our criteria for perventricular device closure of the residual defects: significant left-to-right shunting (Qp/Qs1.5) or substantial hemodynamic instability (a defect ≥2 mm in size). The patients' mean age was 20.4 ± 13.5 months, and their mean body weight was 10 ± 3.1 kg. The median diameter of the residual defects was 4.2 mm (range, 2.5-5.1 mm). We deployed a total of 11 SQFDQ-II Muscular VSD Occluders (Shanghai Shape Memory Alloy Co., Ltd.; Shanghai, China) in the 10 patients, in accord with conventional techniques of perventricular device closure. The mean procedural duration was 31.1 ±9.1 min. We recorded the closure and complication rates perioperatively and during a 12-month follow-up period. Complete closure was achieved in 8 patients; 2 patients had persistent trivial residual shunts. No deaths, conduction block, device embolism, or other complications occurred throughout the study period. We conclude that perventricular device closure is a safe, effective salvage treatment for postoperative residual muscular ventricular septal defects in pediatric patients. Long-term studies with larger cohorts might further confirm this method's feasibility.

High-risk human papillomavirus (HR-HPV) has been recognized as a major causative agent for cervical cancer. Upon HPV infection, early genes E6 and E7 play important roles in maintaining malignant phenotype of cervical cancer cells. By using clustered regularly interspaced short palindromic repeats- (CRISPR-) associated protein system (CRISPR/Cas system), a widely used genome editing tool in many organisms, to target HPV16-E7 DNA in HPV positive cell lines, we showed for the first time that the HPV16-E7 single-guide RNA (sgRNA) guided CRISPR/Cas system could disrupt HPV16-E7 DNA at specific sites, inducing apoptosis and growth inhibition in HPV positive SiHa and Caski cells, but not in HPV negative C33A and HEK293 cells. Moreover, disruption of E7 DNA directly leads to downregulation of E7 protein and upregulation of tumor suppressor protein pRb. Therefore, our results suggest that HPV16-E7 gRNA guided CRISPR/Cas system might be used as a therapeutic strategy for the treatment of cervical cancer.

The aim of this study is to review the strategy of performing aortic valve replacement (AVR) by using the St. Jude Medical (SJM) Regent valve with a continuous suture technique in patients with a small aortic root.Forty-six patients with small aortic annulus underwent AVR by using 19 or 21 mm SJM Regent valves. There were 15 males and 31 females. The mean age of the patients was 51.8 ± 12.4 years. The aortic annular diameter was 20.2 ± 0.9 mm. AVR procedures were performed with continuous suture technique using SJM Regent valves under standard cardiopulmonary bypass. Echocardiaographic data were collected before operation, at discharge, and at a follow-up time, respectively.The intraoperative course was uneventful and there was no operative mortality. The implanted SJM Regent valves consisted of 21 mm valves in 15 patients and 19 mm valves in 31 patients. Echocardiography at 5.6 ± 1.3 months after operation showed a significant increase in the mean effective orifice area index (0.97 ± 0.24 cm(2) /m(2) ), decrease in the mean and peak transvavluar pressure gradient (12.5 ± 5.9 and 22.3 ± 9.6 mmHg), and decrease in the mean left ventricular mass index (106 ± 41.3 g/m(2) ). Moderate prosthesis-patient mismatch (PPM) (effective orifice area index between 0.65 and 0.85 cm(2) /m(2) ) was present in three patients and no severe PPM (effective orifice area index0.65 cm(2) /m(2) ) occurred at discharge and during follow-up.Replacement of SJM Regent valve with a continuous suture technique maybe a good option to prevent PPM in the aortic position.

To evaluate plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels as a marker of cardiac function during severe sepsis and septic shock.A prospective study was conducted, and 44 patients without history of heart diseases but suffering from severe sepsis and septic shock underwent the transesophageal echocardiography (TEE) to obtain data about left and right ventricular function on 1, 3, 7 days in intensive care unit (ICU). At the same time, blood samples were collected to measure the levels of plasma NT-proBNP, quality of creatine kinase isoenzyme (CK-MBmass), troponin T (cTnT) and lactate. The factors affecting plasma NT-proBNP levels in patients with severe sepsis and septic shock were analyzed, and correlation between NT-proBNP and cardiac function indexes were evaluated.Of 44 patient with severe sepsis and septic shock, 21 cases died in 28 days, with the mortality rate of 47.73%. The plasma NT-proBNP values on 1, 3, 7 days in ICU of 21 non-survivors were obviously higher than those of 23 survivors [10 112 (855-35 000) ng/L vs. 4 116 (185-28 437)ng/L, Z=-2.622, P=0.009; 13 811 (1 127-35 000) ng/L vs. 899 (116-35 000)ng/L, Z=-3.459, P=0.000; 6 786 (398-35 000) ng/L vs. 623 (98-4 118)ng/L, Z=-3.001, P=0.003]. Non-conditional logistic regression analysis and linear regression analysis, plasma lactate (t=2.420, P=0.020) and acute physiology and chronic health evaluation system II (APACHEII) score (t=3.482, P=0.001) on day 1, and left ventricular ejection fraction (LVEF, t=-2.326, P=0.029) on day 7 showed that they were independent affecting factors for plasma NT-proBNP levels. Patients were subdivided into two groups based on LVEF. It was found that the plasma NT-proBNP values in abnormal group (LVEF0.50, n=8) were significantly higher than those in normal group (LVEF≥0.50, n=17) on day 7 [1 231 (398-5 000) ng/L vs. 513 (98-10 047) ng/L, Z=-1.831, P=0.047].Plasma NT-proBNP levels on day 7 in ICU could reflect the left ventricular systolic dysfunction in patients with severe sepsis and septic shock.

To investigate the monitoring of renal microcirculation perfusion alteration with contrast-enhanced ultrasound (CEU) during cardiopulmonary bypass (CPB).Renal microcirculation perfusion before and during CPB was assessed by CEU. Time-intensity curve (TIC) were derived from three region of interest (ROI) using QLAB post-analysis software. Parameters such as TIC curve wash in slope (A), area under curve (AUC), peak intensity (DPI) as well as time to peak intensity (TTP) were then calculated.Contrast-enhanced ultrasound showed a significant reduction (or elongation) of perfusion parameter (A, AUC, DPI, TTP) in all three regions (superficial cortex, deep cortex and medulla) during cardiopulmonary bypass in comparison with normal cardiac cycle.Cardiopulmonary bypass (CPB) has a dramatic impact on renal microcirculation in pediatric patients which manifest as global reduction in renal perfusion as well as significant region perfusion difference. Contrast-enhanced ultrasound (CEU) could detect the renal microcirculation alteration during CPB.

We used 3-dimensional computed tomographic images to create a disease-based transesophageal echocardiographic simulation system for complex congenital heart defects. We enrolled 7 pediatric patients with complex congenital heart defects in this proof-of-concept study. Preoperative computed tomographic images and intraoperative transesophageal echocardiographic images were acquired for all patients. Two- and 3-dimensional computed tomographic cross-sectional images were created to simulate the process of transesophageal echocardiographic image acquisition. Computed tomographic images simulating the midesophageal 4- and 5-chamber views, aortic valve short-axis views, long-axis views, and ascending aortic short-axis views were created to correspond with the actual transesophageal echocardiographic images from each patient. Four reviewers then evaluated the image quality of the computed tomographic images, the agreement between the echocardiographic and tomographic images, and the ability of the 3-dimensional computed tomographic full-volume and cross-sectional images to yield the spatial and temporal congruence of transesophageal echocardiograms. In most of the patients, computed tomography yielded images of good-to-excellent quality. Strong agreement was noted between the computed tomographic and transesophageal echocardiographic images acquired in the same patients. The ability of 3-dimensional computed tomography to yield the spatial and temporal congruence of transesophageal echocardiography in selected planes was also good to excellent. We found that 3-dimensional computed tomographic images can simulate the process of transesophageal echocardiography in acquiring the echocardiographic image clearly. This imaging method has the potential to be applied successfully to a disease-based transesophageal echocardiographic simulation system.

Paradoxical embolism is a common cause of cryptogenic stroke. Cardiogenic origin is often the real culprit of unexplained stroke. We report a rare case of double atrial septum with an interatrial chamber and stenosis of the inferior vena cava orifice, which lead to recurrent paradoxical embolism, and then highlight the clinical importance of this rare type of congenital heart disease.

Meningioma is one of the most common primary tumors of the central nervous system, but there are not many detailed studies on the sex, age, subtypes and locations of large series. This study was a retrospective analysis of the characteristics of meningioma cases consecutively operated on at a single institution in China from 2001 to 2010.This study investigated the demographic background of 7084 meningioma cases, and the subtypes and locations of the tumors. Sex and age distributions were analyzed, and the pathological subtypes were classified according to the World Health Organization (WHO) classification. The location of the meningiomas was also categorized.The female:male ratio of the 7084 cases was 2.34:1. The mean age was 51.4 years (range, 11 months-86 years). The mean age of cases of WHO grade I meningioma was significantly older than that of grade II or III meningiomas (P0.001, Fisher's Least Significant Digit test). There was a significantly higher female:male ratio in WHO grade I meningiomas than in grade II or grade III meningiomas (2.57, 1.03 and 0.76, respectively; P0.001, χ(2) test). Meningothelial (n = 2061) and fibrous meningiomas (n = 3556) were the most common subtypes, comprising 79.3% of all meningiomas. All meningioma cases were classified into 23 locations in this study, with the cerebral convexity the most common site (38.33%, n = 2722). Cases with uncommon locations such as extra-cranial and sylvian fissure meningiomas were also present in this series.Female predominance was found for benign meningiomas, while malignant subtypes showed male predominance. The mean age of patients with WHO grade I meningiomas was older than that of patients with higher-grade tumors. Meningothelial and fibrous meningiomas were the most common subtypes. The cerebral convexity was the most common meningioma location.

Secretory meningioma (SM) is a rare, benign subtype of meningioma. Between January 2005 and December 2010, 70 SMs were operated on at the Department of Neurosurgery, Huashan Hospital, Fudan University. We retrospectively analyzed the clinical data, radiological and immunohistochemical findings, and patient outcome to discuss the specific features of SMs. Cranial base preference, hyper-signal in T2 weighted MR image, “xenon light” gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhancement were frequently observed in the 70 cases. Non-skull base SMs, which received more complete resection (p