BACKGROUND Incomplete right bundle branch block (ICRBBB) is commonly associated with atrial septal defect (ASD), but lacks sufficient diagnostic test characteristics. An abnormal T wave is also often observed in ASD, with horizontal or inverted displacement of the proximal T wave limb in the right precordial leads, termed "defective T wave"(DTW). METHODS We examined the diagnostic test characteristics of combining ICRBBB with DTW as a new index to diagnose ASD. A total of 132 consecutive patients with ASD and 132 cases of age/gender-matched controls without ASD were enrolled. RESULTS Sensitivities of DTW, ICRBBB, and both were 87.1%- 87.9%. Specificities were 97.0%, 96.2%, and 100%, respectively. Positive predictive values were 1.3%, 1.1%, and 100.0% respectively, while negative predictive values were 99.9% for each. CONCLUSION Combining ICRBBB with DTW in electrocardiogram (ECG) as a new index significantly increased the specificity and positive predictive values while maintaining a high sensitivity in diagnosing ASD.

Women with polycystic ovary syndrome (PCOS) have increased risks of developing metabolic abnormalities compared with the women without PCOS. Hyperandrogenemia is one of the most important characteristics of PCOS. However, the correlations between hyperandrogenemia and metabolic disorders are uncertain.To elucidate the relationship between androgen indices and metabolic abnormalities in Chinese women with PCOS.A retrospective analysis of the anthropometric and biochemical records of 408 women with PCOS.The prevalence of metabolic syndrome (MetS) was 15.7% in women with PCOS. No association existed between total testosterone (TT) and metabolic profile. Free testosterone (FT) correlated with most of the metabolic variables by unadjusted correlation analyses. The women with elevated FT levels exhibited more unfavorable metabolic profiles compared with the women with normal FT levels. After adjusting for the confounding factors by multivariate logistic regression analysis, the women with elevated FT levels had higher prevalence of central obesity than the women with normal FT levels (odds ratio [OR] 2.346, p=0.042). Women with reduced sex hormone-binding globulin levels were more likely to have central obesity, overweight, raised fasting glucose, insulin resistance, and raised diastolic blood pressure. Raised dehydroepiandrosterone sulfate (DHEAS) level was associated with a lower probability of having central obesity (OR 0.293, p=0.001) and overweight (OR 0.47, p=0.023).FT has closer association with metabolic parameters than TT. FT can involve in the development of metabolic disorders dependent on central obesity. Raised DHEAS level can reduce the risks of central obesity and overweight.

BACKGROUND 3, 3'diindolylmethane (DIM), a natural phytochemical, has shown inhibitory effects on the growth and migration of a variety of cancer cells; however, whether DIM has similar effects on vascular smooth muscle cells (VSMCs) remains unknown. The purpose of this study was to assess the effects of DIM on the proliferation and migration of cultured VSMCs and neointima formation in a carotid injury model, as well as the related cell signaling mechanisms. METHODOLOGY/PRINCIPAL FINDINGS DIM dose-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of VSMCs without cell cytotoxicity. This inhibition was caused by a G0/G1 phase cell cycle arrest demonstrated by fluorescence-activated cell-sorting analysis. We also showed that DIM-induced growth inhibition was associated with the inhibition of the expression of cyclin D1 and cyclin-dependent kinase (CDK) 4/6 as well as an increase in p27(Kip1) levels in PDGF-stimulated VSMCs. Moreover, DIM was also found to modulate migration of VSMCs and smooth muscle-specific contractile marker expression. Mechanistically, DIM negatively modulated PDGF-BB-induced phosphorylation of PDGF-recptorβ (PDGF-Rβ) and the activities of downstream signaling molecules including Akt/glycogen synthase kinase(GSK)3β, extracellular signal-regulated kinase1/2 (ERK1/2), and signal transducers and activators of transcription 3 (STAT3). Our in vivo studies using a mouse carotid arterial injury model revealed that treatment with 150 mg/kg DIM resulted in significant reduction of the neointima/media ratio and proliferating cell nuclear antigen (PCNA)-positive cells, without affecting apoptosis of vascular cells and reendothelialization. Infiltration of inflammatory cells was also inhibited by DIM administration. CONCLUSION These results demonstrate that DIM can suppress the phenotypic modulation of VSMCs and neointima hyperplasia after vascular injury. These beneficial effects on VSMCs were at least partly mediated by the inhibition of PDGF-Rβ and the activities of downstream signaling pathways. The results suggest that DIM has the potential to be a candidate for the prevention of restenosis.

Cryptotanshinone is an active ingredient of Salvia miltiorrhiza that has been used in traditional Chinese medicine for treating cardiovascular disorders. Thus, we investigated the effects of cryptotanshinone on cardiac fibrosis induced by isoprenaline and examined whether cardiac matrix metalloproteinase (MMP)-2 is involved in this process. Male C57BL/6 mice received a daily injection of 0.9% saline, 3 mg/kg isoprenaline or isoprenaline plus 20 mg/kg cryptotanshinone by gastric gavage for 2 weeks. In this study we demonstrated that cryptotanshinone was able to significantly ameliorate isoprenaline-induced cardiac fibrosis, which was associated with a marked upregulation and activation of MMP-2 in the ventricular myocardium. Additionally, we demonstrated that cryptotanshinone dose-dependently upregulated and activated MMP-2 in cultured cardiac fibroblasts. Moreover, incubation with cryptotanshinone also prevented the isoprenaline-induced downregulation and inactivation of MMP-2 in cultured cardiac fibroblasts. Taken together, our data suggest that cryptotanshinone is a novel and potent antifibrotic agent. The present findings further our understanding of the role of MMP-2 in cardiac fibrosis and the antifibrotic mechanisms of cryptotanshinone.

The 5-year survival rate for gastric adenocarcinoma (GA) remains only 40% and biomarkers to identify patients at high risk of tumor recurrence are urgently needed. Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix glycoprotein that mediates cell matrix interactions, and upregulation of SPARC can promote tumor progression and metastasis. This study investigated whether single-nucleotide polymorphisms (SNPs) in SPARC impact the prognosis of GA. Blood or formalin-fixed, paraffin-embedded tissues were obtained from 137 GA patients at the University of Southern California and Memorial Sloan-Kettering Cancer Center medical facilities. DNA was isolated and five SNPs in the SPARC 3'-untranslated region (UTR) were evaluated by DNA sequencing or PCR-restriction fragment length polymorphism. Associations between SNPs and time to tumor recurrence (TTR) were analyzed using Kaplan-Meier curves, log-rank tests, and likelihood-ratio test within logistic or Cox regression model as appropriate. Patients carrying at least one G allele of the SPARC rs1059829 polymorphism (GG, AG) showed a median TTR of 3.7 years compared with 2.1 years TTR for patients with AA (hazard ratio (HR) 0.57; P=0.033). In a multivariate analysis adjusted for T and N category as covariates and stratified by race, hospital and chemotherapy, patients with at least one SPARC rs1059829 G allele (GG, AG) remained significantly associated with superior TTR than patients with AA genotype (adjusted P=0.026). In addition, patients harboring the G-A-A haplotype had the highest risk of tumor recurrence (HR 1.892; adjusted P=0.016). Our findings suggest that SPARC 3'-UTR SNPs may be useful in predicting GA patients at increased risk of recurrence.The Pharmacogenomics Journal advance online publication, 10 April 2012; doi:10.1038/tpj.2012.11.

BACKGROUND Because the Bonfils fibrescope has a semi-rigid optical stylet and is similar in shape to a lightwand, we aimed to evaluate and compare the efficacy of transillumination-assisted orotracheal intubation with the Bonfils fibrescope and the Trachlight(TM) lightwand in patients with normal airways. METHODS As a preliminary investigation to form a basis for later studies, therefore, we performed a randomized, single-blind study of 300 patients with normal airways to compare the efficiency of Trachlight and transillumination-assisted Bonfils orotracheal intubation in these patients. In both groups, orotracheal intubation was performed using a transillumination technique. The first attempt and overall success rates of tracheal intubation, the times required, and any untoward effects were recorded. RESULTS Although the overall success rates were similar for Bonfils and Trachlight intubations (97.3% and 98.7%, respectively), tracheal intubation was successful on the first attempt in 87.3% of patients with the Bonfils fibrescope compared with 95.3% of patients with the Trachlight (P < 0.05). The mean intubation time for the first attempt was 15 ± 5 s with the Bonfils fibrescope and 9 ± 2 s with the Trachlight (P < 0.001). Patients intubated using the Bonfils fibrescope also experienced significantly more sore throat and hoarseness than those intubated using the Trachlight. CONCLUSIONS For patients with normal airways, the Trachlight is superior for orotracheal intubation with respect to reliability, rapidity, and safety compared with the Bonfils fibrescope used with the transillumination technique.

The death receptor Fas and its physiological ligand (FasL) regulate apoptosis of cancerous cells, thereby functioning as a critical component of the host cancer immunosurveillance system. To evade Fas-mediated apoptosis, cancer cells often downregulate Fas to acquire an apoptosis-resistant phenotype, which is a hallmark of metastatic human colorectal cancer. Therefore, targeting Fas resistance is of critical importance in Fas-based cancer therapy and immunotherapy. In this study, we demonstrated that epigenetic inhibitors decitabine and vorinostat cooperate to upregulate Fas expression in metastatic human colon carcinoma cells. Decitabine also upregulates BNIP3 and Bik expression, whereas vorinostat decreased Bcl-x(L) expression. Altered expression of Fas, BNIP3, Bik, and Bcl-x(L) resulted in effective sensitization of the metastatic human colon carcinoma cells to FasL-induced apoptosis. Using an experimental metastasis mouse model, we further demonstrated that decitabine and vorinostat cooperate to suppress colon carcinoma metastasis. Analysis of tumor-bearing lung tissues revealed that a large portion of tumor-infiltrating CD8(+) T cells are FasL(+), and decitabine and vorinostat-mediated tumor-suppression efficacy was significantly decreased in Fas(gld) mice compared with wild-type mice, suggesting a critical role for FasL in decitabine and vorinostat-mediated tumor suppression in vivo. Consistent with their function in apoptosis sensitization, decitabine and vorinostat significantly increased the efficacy of CTL adoptive transfer immunotherapy in an experimental metastasis mouse model. Thus, our data suggest that combined modalities of chemotherapy to sensitize the tumor cell to Fas-mediated apoptosis and CTL immunotherapy is an effective approach for the suppression of colon cancer metastasis.

ABSTRACT: A novel and convenient one-pot electrodeposition approach has been developed for precisely controlled fabrication of large-scale Bi-Ni nanowire and nanocable arrays. Using porous anodic aluminum oxide as a shape-directing template, by simply changing the electrochemical deposition mode, desired Bi-Ni hybrid nanowires and Bi-Ni core-shell nanocables have been obtained in the CV and CC modes, respectively. The structure, morphology, and composition of the as-prepared samples were characterized using X-ray powder diffraction, transmission electron microscopy, elemental mapping, and energy-dispersive X-ray spectrometry.

Immunoglobulin E (IgE) antibodies may play a role in the development of kidney diseases that are related to hypersensitivity reactions. Patients with idiopathic nephrotic syndrome often exhibit increased serum IgE levels and this may be related to sensitivity to steroid treatment. In the present study, the serum IgE levels in 120 patients with different types of primary nephrotic syndrome (PNS) were analysed and found to be significantly elevated in cases of minimal change nephrotic syndrome (MCNS) compared with membranous nephropathy or membrano-proliferative glomerulonephritis. No difference in serum IgE level was observed between cases of steroid-sensitive nephrotic syndrome (SSNS) or steroid-resistant nephrotic syndrome, although the serum IgE level was significantly elevated in SSNS patients in relapse compared with SSNS patients in remission. In MCNS patients, 73.6% exhibited SSNS regardless of their serum IgE level at diagnosis. It is concluded that elevated levels of IgE may be a feature of steroid resistance or relapse, indicating prognostic significance in adult PNS, particularly in MCNS.

The cytoplasmic male sterility (CMS) phenotype in plants can be reversed by the action of nuclear-encoded fertility restorer (Rf) genes. The molecular mechanism involved in Rf gene-mediated processing of CMS-associated transcripts is unclear, as are the identities of other proteins that may be involved in the CMS-Rf interaction. In this study, we cloned the restorer gene Rf5 for Hong-Lian CMS in rice and studied its fertility restoration mechanism with respect to the processing of the CMS-associated transcript atp6-orfH79. RF5, a pentatricopeptide repeat (PPR) protein, was unable to bind to this CMS-associated transcript; however, a partner protein of RF5 (GRP162, a Gly-rich protein encoding 162 amino acids) was identified to bind to atp6-orfH79. GRP162 was found to physically interact with RF5 and to bind to atp6-orfH79 via an RNA recognition motif. Furthermore, we found that RF5 and GRP162 are both components of a restoration of fertility complex (RFC) that is 400 to 500 kD in size and can cleave CMS-associated transcripts in vitro. Evidence that a PPR protein interacts directly with a Gly-rich protein to form a subunit of the RFC provides a new perspective on the molecular mechanisms underlying fertility restoration.