Treatment of upper tract urothelial carcinoma with ureteroscopy and thulium laser: a retrospective single center study.

BACKGROUND: Treatment with the combination of ureteroscopy and thulium laser ablation may provide an alternative to radical nephroureterectomy (RNU) for patients with upper tract urothelial carcinoma (UTUC). The purpose of this study was to investigate the efficacy and safety of this technique. METHODS: We performed a retrospective review of the data for patients who were treated surgically for upper tract urothelial carcinoma in a single center. It included 32 patients treated by endoscopic thulium laser resection and 107 patients treated by radical nephroureterectomy (RNU). We compared the data of patient sex, age at diagnosis, location of carcinoma, length of hospitalization, tumor site, size, grade, recurrence, preoperative creatinine and postoperative creatinine in two groups. Patients were examined by ureteroscopy every 3 months during the first year after surgery, then every 6 months each year. RESULTS: All 32 patients were treated successfully, among which 6 were operated by a flexible ureteroscope. The average tumor size was 13 ± 7 mm in diameter. The tumor was rated as low grade in 27 patients and high grade in 5 patients. Ureteral stricture developed in 4 patients 3 months later after surgery, but the stricture was succesfully treated through endoscopic dilation. Seven patients had tumor recurrence, 3 of which underwent nephroureterectomy during the follow-up. Postoperative creatinine levels (umol/L) were respectively 89 ± 7.5 in laser group and 123 ± 15.4 in RNU group (p < 0.01). Length of hospitalization was respectively 3.6 ± 1.9 and 8.6 ± 2.4 days (p < 0.01). Local or bladder recurrence rate of thulium laser group and RNU group was respectively 21.9 and 13.1% (p < 0.01). CONCLUSIONS: Thulium laser group is associated with a less loss of renal function, a shorter length of hospitalization, but a higher rate of tumor recurrence. Thulium laser therapy combined with ureteroscopic treatment can be considered as an acceptable treatment for selected cases of UTUC. Lifetime intensive surveillance is necessary.

Dietary fat alters the response of hypothalamic neuropeptide Y to subsequent energy intake in broiler chickens.

Dietary fat affects appetite and appetite-related peptides in birds and mammals; however, the effect of dietary fat on appetite is still unclear in chickens faced with different energy statuses. Two experiments were conducted to investigate the effects of dietary fat on food intake and hypothalamic neuropeptides in chickens subjected to two feeding states or two diets. In Experiment 1, chickens were fed a high-fat (HF) or low-fat (LF) diet for 35 days, and then subjected to fed (HF-fed, LF-fed) or fasted (HF-fasted, LF-fasted) conditions for 24 h. In Experiment 2, chickens that were fed a HF or LF diet for 35 days were fasted for 24 h and then re-fed with HF (HF-RHF, LF-RHF) or LF (HF-RLF, LF-RLF) diet for 3 h. The results showed that chickens fed a HF diet for 35 days had increased body fat deposition despite decreasing food intake even when the diet was altered during the re-feeding period (P<0.05). LF diet (35 days) promoted agouti-related peptide (AgRP) expression compared with HF diet (P<0.05) under both fed and fasted conditions. LF-RHF chickens had lower neuropeptide Y (NPY) expression compared with LF-RLF chickens; conversely, HF-RHF chickens had higher NPY expression than HF-RLF chickens (P<0.05). These results demonstrate: (1) that HF diet decreases food intake even when the subsequent diet is altered; (2) the orexigenic effect of hypothalamic AgRP; and (3) that dietary fat alters the response of hypothalamic NPY to subsequent energy intake. These findings provide a novel view of the metabolic perturbations associated with long-term dietary fat over-ingestion in chickens.

Intracoronary infusion of Wharton's jelly-derived mesenchymal stem cells in acute myocardial infarction: double-blind, randomized controlled trial.

BACKGROUND: The use of adult stem cells is limited by the quality and quantity of host stem cells. It has been demonstrated that Wharton's jelly-derived mesenchymal stem cells (WJMSCs), a primitive stromal population, could integrate into ischemic cardiac tissues and significantly improve heart function. In this randomized, controlled trial, our aim was to assess the safety and efficacy of intracoronary WJMSCs in patients with ST-elevation acute myocardial infarction (AMI). METHODS: In a multicenter trial, 116 patients with acute ST-elevation MI were randomly assigned to receive an intracoronary infusion of WJMSCs or placebo into the infarct artery at five to seven days after successful reperfusion therapy. The primary endpoint of safety: the incidence of adverse events (AEs) within 18 months, was monitored and quantified. The endpoint of efficacy: the absolute changes in myocardial viability and perfusion of the infarcted region from baseline to four months, global left ventricular ejection fraction (LVEF) from baseline to 18 months were measured using F-18-fluorodeoxyglucose positron emission computed tomography (F-18-FDG-PET) and 99mTc-sestamibi single-photon emission computed tomography (99mTc-SPECT), and two-dimensional echocardiography, respectively. RESULTS: During 18 months follow-up, AEs rates and laboratory tests including tumor, immune, and hematologic indexes were not different between the two groups. The absolute increase in the myocardial viability (PET) and perfusion within the infarcted territory (SPECT) was significantly greater in the WJMSC group [6.9 ± 0.6 % (95 %CI, 5.7 to 8.2)] and [7.1 ± 0.8 % (95 %CI, 5.4 to 8.8) than in the placebo group [3.3 ± 0.7 % (95 %CI, 1.8 to 4.7), P <0.0001] and 3.9 ± 0.6(95 %CI, 2.8 to 5.0), P = 0.002] at four months. The absolute increase in the LVEF at 18 months in the WJMSC group was significantly greater than that in the placebo group [7.8 ± 0.9 (6.0 to approximately 9.7) vs. 2.8 ± 1.2 (0.4 to approximately 5.1), P = 0.001]. Concomitantly, the absolute decreases in LV end-systolic volumes and end-diastolic volumes at 18 months in the WJMSC group were significantly greater than those in the placebo group (P = 0.0004, P = 0.004, respectively). CONCLUSIONS: Intracoronary infusion of WJMSCs is safe and effective in patients with AMI, providing clinically relevant therapy within a favorable time window. This study encourages additional clinical trials to determine whether WJMSCs may serve as a novel alternative to BMSCs for cardiac stem cell-based therapy. TRIAL REGISTRATION: Clinical Trials NCT01291329 (02/05/2011).

Effect of biological behavior and clinical significance of maspin gene on cervical squamous carcinoma SiHa cell.

OBJECTIVE: This study was performed to evaluate the effect of mammary serine protease inhibitor (maspin) overexpression on human cervical squamous carcinoma (SCC) SiHa cell proliferation and apoptosis in vitro. MATERIAL AND METHODS: Recombinant plasmid pcDNA3-maspin was stably transfected into human cervical SCC SiHa cell. Maspin mRNA was determined by RT-PCR, whereas maspin protein was detected by Western blot analysis and immunocytochemistry (IHC). Cell proliferation activity was measured by MTT method. Apoptosis rate and cell cycle distribution were detected by flow cytometry to understand the changes in the cell biological characteristics. RESULTS: The strengthened expression of the maspin gene in the SiHa cell was confirmed by RT-PCR, Western blot, and immunocytochemistry (IHC) (p < 0.05). Suppressed proliferation activity and increased apoptosis rate of SiHa-m (maspin stable transfected) versus SiHa and SiHa-vector cell (SiHa-pc3) were shown by MTT and flow cytometry (p < 0.05). SiHa and SiHa-pc3-had no statistical significance (p > 0.05). CONCLUSION: The results showed that maspin gene can significantly inhibit human cervical SCC SiHa cell proliferation and effectively slow cancer growth. Maspin may be a new molecular target in the gene therapy of human cervical SCC.

miR146a impairs the IFN-induced anti-HBV immune response by downregulating STAT1 in hepatocytes.

BACKGROUND & AIMS: Previous studies have shown that hepatitis B virus (HBV) interferes with host antiviral immunity via multiple pathways. In clinical practice, interferon resistance is a serious issue for treatment of HBV infection. Now, miRNAs have been reported to be widely involved in antiviral immunity and have become a novel tool to study virus-host interaction. We question whether miRNAs play a role in HBV-induced interferon resistance in hepatocytes. METHODS: MiRNAs levels in HepG2 and HepG2.2.15 cells were compared by qRT-PCR. The effects of miR146a on HBV infection were characterized by interference miR146a level, followed by the quantification of HBV mRNA, DNA and antigens. We employed qRT-PCR and western blot to study the effects of miR146a on the IFN-α signalling pathway. The miR146a promoter activity was validated by a luciferase reporter assay. RESULTS: HBV infection impaired IFN-α signalling pathway in hepatocytes. MiR146a was upregulated in HBV+ HepG2.2.15 cells, and the transcriptional activity of miR146a in HepG2.2.15 cells was increased compared with HepG2 cells. HBV infection, especially the introduction of HBx, induced miR146a expression in vitro. Moreover, miR146a attenuated the production of type I interferon-induced antiviral factors. Low STAT1 levels were noticed in HBV+ HCC cells, and the luciferase reporter assay showed that STAT1 was post-transcriptionally downregulated by miR146a. Furthermore, the silencing of miR146a by antisense inhibitors enhanced IFN-α-mediated anti-HBV efficiency. CONCLUSIONS: Our findings demonstrate that HBV infection promotes miR146a transcription, which represses STAT1 and results in interferon resistance. These observations reveal a novel role for miR146a in HBV immunopathogenesis, and provide a potential target for the therapeutic recovery of IFN-α-induced anti-HBV effects.

Vibro-acoustic analysis of a rectangular cavity bounded by a flexible panel with elastically restrained edges.

A coupled system consisting of an acoustic cavity and an elastic panel is a classical problem in structural acoustics and is typically analyzed using modal approaches based on in vacuo structural modes and the rigidly walled acoustic modes which are pre-determined based on separate component models. Such modeling techniques, however, tend to suffer the following drawbacks or limitations: (a) a panel is only subjected to ideal boundary conditions such as the simply supported, (b) the coupling between the cavity and panel is considered weak, and (c) the particle velocity cannot be correctly predicted from the pressure gradient on the contacting interface, to name a few. Motivated by removing these restrictions, this paper presents a general method for the vibro-acoustic analysis of a three-dimensional (3D) acoustic cavity bounded by a flexible panel with general elastically restrained boundary conditions. The displacement of the plate and the sound pressure in the cavity are constructed in the forms of standard two-dimensional and 3D Fourier cosine series supplemented by several terms introduced to ensure and accelerate the convergence of the series expansions. The unknown expansions coefficients are treated as the generalized coordinates and determined using the Rayleigh-Ritz procedure based on the energy expressions for the coupled structural acoustic system. The accuracy and effectiveness of the proposed method are demonstrated through numerical examples and comparisons with the results available in the literature.

Cytotoxic constituents of Viscum coloratum.

Phytochemical studies on Viscum coloratum have resulted in the isolation of nineteen compounds. The structures of the isolated compounds were identified on the basis of 1D, 2D NMR and HR-ESI-Q-TOF-MS. Pachypodol (4) and ombuine (6) were characterized in the family Loranthaceae for the first time. 1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one (8) and 5-hydroxy-3,7,3'-trimethoxyflavone-4'-O-beta-D-glucoside (13) were two new natural compounds, which exhibited cytotoxic activities against four human tumour cell lines (HeLa, SGC-7901, MCF-7, and U251).

Aggressive Angiomyxoma in the Scrotum: A Case Series and Literature Review.

Purpose: Aggressive angiomyxoma (AAM) was identified as a distinct clinicopathological entity in 1983. Since then, a few cases of its occurrence in the scrotum have been reported. This case series was performed to increase clinicians' understanding of the clinical features and treatment of AAM in the scrotum. Methods: We evaluated the clinical presentations, treatments, and follow-up of two patients with AAM in the scrotum in our hospital and 34 cases reported in the literature. Results: Among the 36 patients, the average age was 48.3 ± 20.6 years old (range from 1 to 81); the average maximum diameter of the tumor was 8.36 cm (1.6-25 cm); the site of one (2.78%) patient was located in the epididymis, two (5.56%) in the testes, five (13.89%) in the spermatic cord, and 28 (77.77%) in the scrotum. The clinical symptoms were generally non-specific and 20 patients inadvertently discovered their slow-growing painless masses. The treatments for all these patients were surgical excision once the tumor had been found and one case underwent excision followed by radiotherapy. The median follow-up time for the remaining 32 cases was 24.5 months (1 to 84 months). Recurrence occurred in three cases (9.09%) at the primary sites and no cases of distant metastasis. Conclusion: AAM of the scrotum can occur in middle-aged and elderly men. The clinical manifestation generally involves a long history of asymptomatic masses or swelling in the scrotum. Ultrasound is the most commonly used diagnostic technique but magnetic resonance imaging may be more effective. The mainly treatment is surgical excision and postoperative histopathological examination is still the gold standard for its diagnosis. Although it is locally aggressive, metastasis is extremely rare in males.

Convolutional neural network assistance significantly improves dermatologists' diagnosis of cutaneous tumours using clinical images.

BACKGROUND: Convolutional neural networks (CNNs) have demonstrated expert-level performance in cutaneous tumour classification using clinical images, but most previous studies have focused on dermatologist-versus-CNN comparisons rather than their combination. The objective of our study was to evaluate the potential impact of CNN assistance on dermatologists for clinical image interpretation. METHODS: A multi-class CNN was trained and validated using a dataset of 25,773 clinical images comprising 10 categories of cutaneous tumours. The CNN's performance was tested on an independent dataset of 2107 images. A total of 400 images (40 per category) were randomly selected from the test dataset. A fully crossed, self-control, multi-reader multi-case (MRMC) study was conducted to compare the performance of 18 board-certified dermatologists (experience: 13/18 ≤ 10 years; 5/18＞10 years) in interpreting the 400 clinical images with or without CNN assistance. RESULTS: The CNN achieved an overall accuracy of 78.45% and kappa of 0.73 in the classification of 10 types of cutaneous tumours on 2107 images. CNN-assisted dermatologists achieved a higher accuracy (76.60% vs. 62.78%, P < 0.001) and kappa (0.74 vs. 0.59, P < 0.001) than unassisted dermatologists in interpreting the 400 clinical images. Dermatologists with less experience benefited more from CNN assistance. At the binary classification level (malignant or benign), the sensitivity (89.56% vs. 83.21%, P < 0.001) and specificity (87.90% vs. 80.92%, P < 0.001) of dermatologists with CNN assistance were also significantly improved than those without. CONCLUSIONS: CNN assistance improved dermatologist accuracy in interpreting cutaneous tumours and could further boost the acceptance of this new technique.

Acoustic analysis of a rectangular cavity with general impedance boundary conditions.

A Fourier series method is proposed for the acoustic analysis of a rectangular cavity with impedance boundary conditions arbitrarily specified on any of the walls. The sound pressure is expressed as the combination of a three-dimensional Fourier cosine series and six supplementary two-dimensional expansions introduced to ensure (accelerate) the uniform and absolute convergence (rate) of the series representation in the cavity including the boundary surfaces. The expansion coefficients are determined using the Rayleigh-Ritz method. Since the pressure field is constructed adequately smooth throughout the entire solution domain, the Rayleigh-Ritz solution is mathematically equivalent to what is obtained from a strong formulation based on directly solving the governing equations and the boundary conditions. To unify the treatments of arbitrary nonuniform impedance boundary conditions, the impedance distribution function on each specified surface is invariantly expressed as a double Fourier series expansion so that all the relevant integrals can be calculated analytically. The modal parameters for the acoustic cavity can be simultaneously obtained from solving a standard matrix eigenvalue problem instead of iteratively solving a nonlinear transcendental equation as in the existing methods. Several numerical examples are presented to demonstrate the effectiveness and reliability of the current method for various impedance boundary conditions, including nonuniform impedance distributions.

Development of a droplet digital PCR for detection and quantification of porcine epidemic diarrhea virus.

Porcine epidemic diarrhea, a disease caused by porcine epidemic diarrhea virus (PEDV), results in large economic losses to the global swine industry. To manage this disease effectively, it is essential to detect PEDV early and accurately. We developed a sensitive and accurate droplet digital PCR (ddPCR) assay to detect PEDV. The optimal primer-to-probe concentration and melting temperature were identified as 300:200 nM and 59.2°C, respectively. The specificity of the ddPCR assay was confirmed by negative test results for common swine pathogens. The detection limit for the ddPCR was 0.26 copies/µL, which is a 5.7-fold increase in sensitivity compared to that of real-time PCR (rtPCR). Both ddPCR and rtPCR assays exhibited good linearity, although ddPCR provided higher sensitivity for clinical detection compared to that of rtPCR. Our ddPCR methodology provides a promising tool for evaluating the PEDV viral load when used for clinical testing, particularly for detecting samples with low-copy viral loads.

Myosin light chain kinase binding to a unique site on F-actin revealed by three-dimensional image reconstruction.

Ca2+-calmodulin-dependent phosphorylation of myosin regulatory light chains by the catalytic COOH-terminal half of myosin light chain kinase (MLCK) activates myosin II in smooth and nonmuscle cells. In addition, MLCK binds to thin filaments in situ and F-actin in vitro via a specific repeat motif in its NH2 terminus at a stoichiometry of one MLCK per three actin monomers. We have investigated the structural basis of MLCK-actin interactions by negative staining and helical reconstruction. F-actin was decorated with a peptide containing the NH2-terminal 147 residues of MLCK (MLCK-147) that binds to F-actin with high affinity. MLCK-147 caused formation of F-actin rafts, and single filaments within rafts were used for structural analysis. Three-dimensional reconstructions showed MLCK density on the extreme periphery of subdomain-1 of each actin monomer forming a bridge to the periphery of subdomain-4 of the azimuthally adjacent actin. Fitting the reconstruction to the atomic model of F-actin revealed interaction of MLCK-147 close to the COOH terminus of the first actin and near residues 228-232 of the second. This unique location enables MLCK to bind to actin without interfering with the binding of any other key actin-binding proteins, including myosin, tropomyosin, caldesmon, and calponin.

Hydrogen Sulfide Alleviates Aluminum Toxicity via Decreasing Apoplast and Symplast Al Contents in Rice.

Hydrogen sulfide (H2S) plays a vital role in Al3+ stress resistance in plants, but the underlying mechanism is unclear. In the present study, pretreatment with 2 µM of the H2S donor NaHS significantly alleviated the inhibition of root elongation caused by Al toxicity in rice roots, which was accompanied by a decrease in Al contents in root tips under 50 µM Al3+ treatment. NaHS pretreatment decreased the negative charge in cell walls by reducing the activity of pectin methylesterase and decreasing the pectin and hemicellulose contents in rice roots. This treatment also masked Al-binding sites in the cell wall by upregulating the expression of OsSATR1 and OsSTAR2 in roots and reduced Al binding in the cell wall by stimulating the expression of the citrate acid exudation gene OsFRDL4 and increasing the secretion of citrate acid. In addition, NaHS pretreatment decreased the symplasmic Al content by downregulating the expression of OsNRAT1, and increasing the translocation of cytoplasmic Al to the vacuole via upregulating the expression of OsALS1. The increment of antioxidant enzyme [superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), and peroxidase (POD)] activity with NaHS pretreatment significantly decreased the MDA and H2O2 content in rice roots, thereby reducing the damage of Al3+ toxicity on membrane integrity in rice. H2S exhibits crosstalk with nitric oxide (NO) in response to Al toxicity, and through reducing NO content in root tips to alleviate Al toxicity. Together, this study establishes that H2S alleviates Al toxicity by decreasing the Al content in the apoplast and symplast of rice roots.

miR-141 Inhibits Proliferation and Migration of Colorectal Cancer SW480 Cells.

BACKGROUND: This study was designed to determine the molecular function of miR-141 and the underlying mechanisms in colorectal cancer (CRC). MATERIALS AND METHODS: SW480 cells in which miR-141 was up- or down-regulated were established. Reverse transcription, quantitative polymerase chain reaction and Western blotting were used to examine the microRNA and protein expression. Cell-cycle progression was analyzed by flow cytometry. Proliferation marker Ki-67 was evaluated by immunofluorescence. Transwell assay was conducted to determine the migration rates of cells. Subcutaneous xenograft models were used to examine the effect of miR-141 on tumorigenicity. Human mitogen-activated protein kinase (MAPK) and receptor tyrosine kinase (RTK) pathway phosphorylation array assays were used to interrogate MAPK and RTK pathway activation. RESULTS: miR-141 directly targeted zinc finger E-box-binding homeobox 1/2 (ZEB1/2). We first determined the expression levels of ZEB1 and ZEB2 in miR-141-expressing cells and miR-141-knockdown cells and found that inhibition of miR-141 significantly increased the expression of ZEB2. In vitro study revealed that miR-141 overexpression inhibited the expression of Ki-67. Furthermore, overexpression of miR-141 led to a significant reduction in the proliferation of SW480 cells via induction of cell-cycle arrest at the G1 stage. In contrast, inhibition of miR-141 markedly promoted the proliferation of SW480 cells by promoting cell-cycle progression. Moreover, overexpression of miR-141 significantly inhibited SW480 cell migration in vitro. In addition, overexpression of miR-141 significantly reduced tumor size and weight, and inhibited the growth of SW480 cell-derived tumor in nude mice. Notably, overexpression of miR-141 also suppressed the liver metastasis of SW480 cells in nude mice. Using RTK and MAPK arrays, we found increased phosphorylation of hepatocyte growth factor receptor (HGFR/c-MET) following inhibition of miR-141, but phosphorylation of P53, AKT, ERK1/2, P38 and mTOR, etc., in SW480 cells was not affected by miR-141. CONCLUSION: Our results suggest that miR-141 functions as a tumor suppressor through ZEB2 and HGFR in CRC cells.

µSR investigation of a new diluted magnetic semiconductor Li(Zn,Mn,Cu)As with Mn and Cu codoping at the same Zn sites.

We report the successful synthesis and characterization of a new type I-II-V bulk form diluted magnetic semiconductor (DMS) Li(Zn,Mn,Cu)As, in which charge and spin doping are decoupled via (Cu,Zn) and (Mn,Zn) substitution at the same Zn sites. Ferromagnetic transition temperature up to ∼33 K has been observed with a coercive field ∼40 Oe for the 12.5% doping level. µSR measurements confirmed that the magnetic volume fraction reaches nearly 100% at 2 K, and the mechanism responsible for the ferromagnetic interaction in this system is the same as other bulk form DMSs.

Leucine alleviates dexamethasone-induced suppression of muscle protein synthesis via synergy involvement of mTOR and AMPK pathways.

Glucocorticoids (GCs) are negative muscle protein regulators that contribute to the whole-body catabolic state during stress. Mammalian target of rapamycin (mTOR)-signalling pathway, which acts as a central regulator of protein metabolism, can be activated by branched-chain amino acids (BCAA). In the present study, the effect of leucine on the suppression of protein synthesis induced by GCs and the pathway involved were investigated. In vitro experiments were conducted using cultured C2C12 myoblasts to study the effect of GCs on protein synthesis, and the involvement of mTOR pathway was investigated as well. After exposure to dexamethasone (DEX, 100 µmol/l) for 24 h, protein synthesis in muscle cells was significantly suppressed (P<0.05), the phosphorylations of mTOR, ribosomal protein S6 protein kinase 1 (p70s6k1) and eukaryotic initiation factor 4E binding protein 1 (4EBP1) were significantly reduced (P<0.05). Leucine supplementation (5 mmol/l, 10 mmol/l and 15 mmol/l) for 1 h alleviated the suppression of protein synthesis induced by DEX (P<0.05) and was accompanied with the increased phosphorylation of mTOR and decreased phosphorylation of AMPK (P<0.05). Branched-chain amino transferase 2 (BCAT2) mRNA level was not influenced by DEX (P>0.05) but was increased by leucine supplementation at a dose of 5 mmol/l (P<0.05).

NADPH oxidase contributes to the left ventricular dysfunction induced by sinoaortic denervation in rats.

The aim of this work was to investigate the role nicotinamide adenine dinucleotide phosphate (NADPH) oxidase on left ventricular dysfunction of rats submitted to sinoaortic denervation (SAD). Experiment 1: 8 weeks after SAD of rats, NADPH oxidase in left ventricles was assayed by Western blotting analysis. Experiment 2: Rats were subjected to SAD and received treatment with apocynin (an NADPH oxidase inhibitor, 30 mg/kg/day, intragastric administration) for 8 weeks; 8 weeks after SAD, Nox2 and Nox4 expressions and Rac1 activity of left ventricles were higher in SAD rats than those in sham-operated rats. Although treatment of SAD rats with apocynin did not affect blood pressure, blood pressure variability (BPV), and baroreflex function, it significantly attenuated left ventricular hypertrophy marked by reduced expression of atrial natriuretic factor and ß-myosin heavy chain. Treatment of SAD rats with apocynin abated oxidative stress marked by reduced malondialdehyde formation and suppressed nuclear factor-kappa B (NFκB) activation; inflammation marked by reduced monocyte chemoattractant protein-1 expression and myeloperoxidase activity; attenuated endoplasmic reticulum stress marked by reduced expression of CCAAT-enhancer-binding protein homologous protein, chaperone-glucose-regulated protein 78, and X-box protein 1; and alleviated cardiac fibrosis marked by reduced mRNA levels of collagens I and III and transforming growth factor beta. In conclusion, exaggerated BPV induces chronic myocardial oxidative stress and thereby aggravates cardiac remodeling in rats. These data suggest a potential role of NADPH oxidases in the pathogenesis of cardiac dysfunction induced by exaggerated BPV.

Incidence and natural history of left ventricular thrombus following anterior wall acute myocardial infarction.

Previous studies have reported left ventricular (LV) thrombus in 20% to 56% of patients after anterior wall acute myocardial infarction (AMI). The Healing and Early Afterload Reducing Therapy (HEART) study was a prospective study comparing effects of early (24 hours) or delayed (14 days) initiation of ramipril, an angiotensin-converting enzyme inhibitor, on LV function after anterior wall AMI. This ancillary study assessed prevalence of LV thrombus. Two-dimensional echocardiography was performed on days 1, 14, and 90 after myocardial infarction. The cohort consisted of 309 patients. Q-wave anterior wall AMI occurred in 78%; 87% received reperfusion therapy. The prevalence of LV thrombus was 2 of 309 (0.6%) at day 1, 11 of 295 (3.7%) at day 14, and 7 of 283 (2.5%) at day 90. One patient had thrombus at 2 examinations. The day 1 echocardiogram was not correlated with thrombus development. LV size increased more in patients with thrombus than in those without thrombus. Patients with thrombus had more wall motion abnormality after day 1 than patients without thrombus (p = 0.03). Thus, the current prevalence of LV thrombus in anterior wall AMI is lower than previously reported, possibly due to changes in AMI management. Preservation of LV function is likely to be an important mechanism. Most thrombi are seen by 2 weeks after AMI. Resolution documented by echocardiography is frequent.

Gender-associated differences in left ventricular geometry in patients with aortic valve disease and effect of distinct overload subsets.

Gender-associated differences may play an important role in the way the left ventricle adapts to overload. The purpose of this study is to evaluate left ventricular (LV) geometry in patients referred for aortic valve replacement with distinct overload subsets. The echocardiograms of 128 patients with isolated aortic stenosis (n = 44), mixed aortic valvular disease (n = 51), and pure aortic regurgitation (n = 33) before aortic valve replacement were evaluated. Women had better LV function as measured by ejection fraction (58% vs 52%; p = 0.01) and were slightly older (67 vs 62 years, p = 0.11). LV dimensions and volumes indexes were distinctively smaller in women irrespective of the subgroups analyzed. Men had larger LV mass and LV mass index, but women had higher LV mass/volume ratio. Gender-related differences in LV mass/volume ratio were most prominent in the aortic stenosis patients (3.1 g/ml for women vs 2.3 g/ml for men; p = 0.001), tended to decrease in mixed aortic disease (2.3 g/ml for women vs 1.8 g/ml for men; p = 0.01), and were not present in patients with pure aortic regurgitation (1.7 g/ml for women vs 1.7 g/ml for men; p = 0.83). Multivariate analysis showed that gender was independently associated with LV mass/volume ratios, after adjusting for the severity of the valvular lesion, age, LV function, and concomitant coronary bypass graft surgery. Thus, in a selected population of patients with severe aortic valvular disease, there were significant gender-related differences in LV geometry, mainly in patients exposed to chronic pressure overload.

Single-nucleotide polymorphisms in the lipoprotein lipase gene associated with coronary heart disease in Chinese.

Coronary heart disease is a complex disease reflecting the interaction of multiple genes with the environment (e.g. diet, life style). Lipoprotein lipase (LPL) plays an important role in lipid metabolism and the pathogenesis of coronary atherosclerosis. Recent associations between single-nucleotide polymorphisms in the LPL gene and heart disease have been reported, but little is known in Chinese. The LPL gene spans >26 kb, with an mRNA of 3549 bp. In the present study, we screened 5155 bp (565 bp of 5' flanking region, nine exons and donor- and acceptor-splice sites, and some intronic bases) in 160 Chinese patients with confirmed coronary heart disease and 150 age- and gender-matched controls. Thirteen of the sixteen single-nucleotide polymorphisms that we found have not been previously reported. In males, significant (P<0.05) differences between the coronary heart disease patients and controls were found for five single-nucleotide polymorphisms: -421G>A (5' flanking region); +13,577C>A (intron 2); +16,052G>A, R192Q (exon 5); +16,173C>G and +16,177T>C (intron 5). In females, significant differences between the patients with coronary heart disease and controls were found for only the -421G>A and +16,052G>A (R192Q) mutations. Among the coronary heart disease males, significant (P<0.05) associations were found between the low-HDL high-triglyceride (LHDL/HTG) phenotype and the non-LHDL/HTG trait for the 5' flanking-421G, the intron 2+13,577C, and the exon 5+16,052G mutations, with odds-ratios (ORs)[confidence intervals] of 3.90[1.12-13.66], 3.38[1.22-9.40], and 3.22[1.04-10.01], respectively; no corresponding associations were found in females. There were 69, 51, 57 and 41 unphased haplotype patterns in male coronary heart disease, male control, female coronary heart disease and female control groups, respectively; the computer program PM-Plus found the heterogeneity model by far the best fit (P<0.0001 in males, >0.01 in females). These data show that some single-nucleotide polymorphisms in the LPL gene among Chinese are associated with abnormal lipid and lipoprotein profiles and predisposition to coronary heart disease, a genetically heterogeneous complex disease, and that they are gender-specific.