Adenocarcinoma of esophagogastric junction (AEG) was initially proposed in 1999 by Siewert. During recent decades, the incidence and prevalence of AEG were arising globally whereas the incidence of gastric cancer is gradually declining. Complete blood counting and liver function tests, as the routine examination of immune and nutritional status, were reported to be the predictors of overall survival (OS) in some tumors. However, little is known about the prognostic significance of these indexes in AEG patients. The purpose of this study was to assess the prediction of preoperative pre-albumin, hemoglobin, and prognostic nutritional index (PNI) for survival outcomes in AEG patients.
A retrospective cohort of 101 AEG patients followed by radical surgery was recruited between January and July 2010. Clinical and laboratory data were obtained and used to evaluate the predictive value through survival analysis. Receiver operating characteristic (ROC) curve analysis determined 200 mg/L, 120 g/L, 5 cm, and 51 as the cutoff values of pre-albumin, hemoglobin, tumor size, and PNI, respectively.
Univariate analysis revealed that AEG patients with hemoglobin ≥120 g/L, albumin ≥40 g/L, pre-albumin ≥200 g/L, PNI ≥51, and tumor size <5 cm had longer OS (P < 0.05). Additionally, pre-albumin, tumor size, and TNM stage were demonstrated to be independent prognostic indicators by multivariate analysis with Cox regression, and the performance of pre-albumin for predicting OS in AEG patients was further identified by ROC curves (P = 0.006).
Preoperative pre-albumin was an independent prognostic factor, and a high level of pre-albumin predicted longer OS in AEG patients.
AEG; Gastric cancer; Pre-albumin; PNI; OS
In the study, we evaluated chemical composition and antimicrobial, antibiofilm, and antitumor activities of essential oils from dried leaf essential oil of leaf and flower of Agastache rugosa for the first time. Essential oil of leaf and flower was evaluated with GC and GC–MS methods, and the essential oil of flower revealed the presence of 21 components, whose major compounds were pulegone (34.1%), estragole (29.5%), and p-Menthan-3-one (19.2%). 26 components from essential oil of leaf were identified, the major compounds were p-Menthan-3-one (48.8%) and estragole (20.8%). At the same time, essential oil of leaf, there is a very effective antimicrobial activity with MIC ranging from 9.4 to 42 μg ml−1 and potential antibiofilm, antitumor activities for essential oils of flower and leaf essential oil of leaf. The study highlighted the diversity in two different parts of A. rugosa grown in Xinjiang region and other places, which have different active constituents. Our results showed that this native plant may be a good candidate for further biological and pharmacological investigations.
Essential oil; Agastache rugosa; GC–MS; Biological; Pharmacological; China
Corticotropin releasing factor (CRF), a peptide hormone involved in the stress response, holds a key position in cardiovascular regulation. Here, we report that the central effect of CRF on cardiovascular activities is mediated by the posterior hypothalamic nucleus (PH), an important structure responsible for stress-induced cardiovascular changes. Our present results demonstrate that CRF directly excites PH neurons via two CRF receptors, CRFR1 and CRFR2, and consequently increases heart rate (HR) rather than the mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). Bilateral vagotomy does not influence the tachycardia response to microinjection of CRF into the PH, while β adrenergic receptor antagonist propranolol almost totally abolishes the tachycardia. Furthermore, microinjecting CRF into the PH primarily increases neuronal activity of the rostral ventrolateral medulla (RVLM) and rostral ventromedial medulla (RVMM), but does not influence that of the dorsal motor nucleus of the vagus nerve (DMNV). These findings suggest that the PH is a critical target for central CRF system in regulation of cardiac activity and the PH-RVLM/RVMM-cardiac sympathetic nerve pathways, rather than PH-DMNV-vagus pathway, may contribute to the CRF-induced tachycardia.
Reduced left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI), which implies the occurrence of cardiac dysfunction, impacts cardiac prognosis, even after primary percutaneous coronary intervention (PCI). This study was designed to clarify the difference of clinical and angiographic predictors for reduced LVEF in ST-elevation myocardial infarction (STEMI) patients with left anterior descending artery (LAD) or non-LAD vessel as culprit artery.
This was a retrospective study to review a total of 553 patients of STEMI underwent primary PCI in our hospital. All patients underwent echocardiography. Univariate analysis, multivariate analysis and classification and regression tree (CART) were performed between LAD related AMI and non-LAD related STEMI. The primary outcome was the occurrence of reduced LVEF 4–6 days after PCI.
In this study, culprit arteries of STEMI were 315 in LAD system (6 in left main artery, 309 in LAD) and 238 in non-LAD system (63 in left circumflex and 175 in right coronary artery). Compared with non-LAD group, post-MI LVEF was significantly reduced in LAD related STEMI group (52.4 ± 9.3 % vs. 57.1 ± 7.8 %, P < 0.01). Multivariate analysis indicated that elder (>65 years), time to hospital and proximal occlusion were associated with reduced LVEF (<55 %) in LAD related STEMI patients. However, in non-LAD patients, time to hospital, multivessel stenosis and post-PCI blood pressure predicted the occurrence of reduced LVEF. Furthermore, CART analysis also obtained similar findings.
Patients with LAD or non-LAD related STEMI could suffer reduced LVEF, while the clinical and angiographic predictors for the occurrence were different.
ST-elevation myocardial infarction; Left ventricular ejection fraction; Primary percutaneous coronary intervention; Predictors
Previous diffusion tensor imaging tractography studies have demonstrated exponential patterns of developmental changes for diffusion parameters such as fractional anisotropy (FA) and mean diffusivity (MD) averaged over all voxels in major white matter (WM) tracts of the human brain. However, this assumes that the entire tract is changing in unison, which may not be the case. In this study, a surface model based tract-specific analysis was applied to a cross-sectional cohort of 178 healthy subjects (83 males/95 females) aged from 6 to 30 years to spatially characterize the age-related changes of FA and MD along the trajectory of seven major WM tracts – corpus callosum (CC) and six bilateral tracts. There were unique patterns of regions that showed different exponential and linear rates of increasing FA or decreasing MD and age at which FA or MD levels off along each tract. Faster change rate of FA was observed in genu of CC and frontal-parietal part of superior longitudinal fasciculus (SLF). Inferior corticospinal tract (CST), posterior regions of association tracts such as inferior longitudinal fasciculus, inferior frontal occipital fasciculus and uncinate fasciculus also displayed earlier changing patterns for FA. MD decreases with age also exhibited this posterior-to-anterior WM maturation pattern for most tracts in females. Both males and females displayed similar FA/MD patterns of change with age along most large tracts; however, males had overall reached the FA maxima or MD minima later compared with females in most tracts with the greater differences occurring in the CST and frontal-parietal part of SLF for MD. Therefore, brain WM development has spatially varying trajectories along tracts that depend on sex and the tract.
neurodevelopment; diffusion tensor imaging; fractional anisotropy; mean diffusivity; tractography
Tumor necrosis factor-α (TNF-α) plays an important role in progressive contractile dysfunction in several cardiac diseases. The cytotoxic effects of TNF-α are suggested to be partly mediated by reactive oxygen species (ROS)- and mitochondria-dependent apoptosis. Glucagon-like peptide-1 (GLP-1) or its analogue exhibits protective effects on the cardiovascular system. The objective of the study was to assess the effects of exenatide, a GLP-1 analogue, on oxidative stress, and apoptosis in TNF-α-treated cardiomyocytes in vitro.
Isolated neonatal rat cardiomyocytes were divided into three groups: Control group, with cells cultured in normal conditions without intervention; TNF-α group, with cells incubated with TNF-α (40 ng/ml) for 6, 12, or 24 h without pretreatment with exenatide; and exenatide group, with cells pretreated with exenatide (100 nmol/L) 30 mins before TNF-α (40 ng/ml) stimulation. We evaluated apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry, measured ROS production and mitochondrial membrane potential (MMP) by specific the fluorescent probes, and assessed the levels of proteins by Western blotting for all the groups.
Exenatide pretreatment significantly reduced cardiomyocyte apoptosis as measured by flow cytometry and TUNEL assay at 12 h and 24 h. Also, exenatide inhibited excessive ROS production and maintained MMP. Furthermore, declined cytochrome-c release and cleaved caspase-3 expression and increased bcl-2 expression with concomitantly decreased Bax activation were observed in exenatide-pretreated cultures.
These results suggested that exenatide exerts a protective effect on cardiomyocytes, preventing TNF-α-induced apoptosis; the anti-apoptotic effects may be associated with protection of mitochondrial function.
Cell Apoptosis; Glucagon-like Peptide-1; Mitochondrial Function; Oxidative Stress; Tumor Necrosis Factor-α
The deterministic bridge deterioration model updating problem is well established in bridge management, while the traditional methods and approaches for this problem require manual intervention. An artificial-intelligence-based approach was presented to self-updated parameters of the bridge deterioration model in this paper. When new information and data are collected, a posterior distribution was constructed to describe the integrated result of historical information and the new gained information according to Bayesian theorem, which was used to update model parameters. This AI-based approach is applied to the case of updating parameters of bridge deterioration model, which is the data collected from bridges of 12 districts in Shanghai from 2004 to 2013, and the results showed that it is an accurate, effective, and satisfactory approach to deal with the problem of the parameter updating without manual intervention.
AIM: To investigate alternative splicing in vascular endothelial growth factor A (VEGFA), amyloid beta precursor protein (APP), and Numb homolog (NUMB) in colorectal cancer (CRC).
METHODS: Real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and PCR-restriction fragment length polymorphism analyses were performed to detect the expression of VEGFA, APP, and NUMB mRNA in 20 CRC tissues and matched adjacent normal tissues, as well as their alternative splicing variants.
RESULTS: qRT-PCR analysis revealed that the expression of APP, NUMB, and VEGFA165b mRNA were significantly downregulated, while VEGFA mRNA was upregulated, in CRC tissues (all P < 0.05). PCR-restriction fragment length polymorphism analysis revealed that the expression of VEGFA165a/b in CRC tissues was significantly higher than in adjacent normal tissues (P < 0.05). Compared with adjacent normal tissues, the expression of NUMB-PRRS in CRC tissues was significantly decreased (P < 0.05), and the expression of NUMB-PRRL was increased (P < 0.05).
CONCLUSION: Alternative splicing of VEGFA, APP, and NUMB may regulate the development of CRC, and represent new targets for its diagnosis, prognosis, and treatment.
Alternative splicing; Amyloid beta precursor protein; Colorectal cancer; Numb homolog; Vascular endothelial growth factor A
Tricuspid regurgitation (TR) is frequently associated with severe mitral stenosis (MS), the importance of significant TR was often neglected. However, TR influences the outcome of patients. The aim of this study was to investigate the efficacy and safety of percutaneous balloon mitral valvuloplasty (PBMV) procedure in rheumatic heart disease patients with mitral valve (MV) stenosis and tricuspid valve regurgitation.
Two hundred and twenty patients were enrolled in this study due to rheumatic heart disease with MS combined with TR. Mitral balloon catheter made in China was used to expand MV. The following parameters were measured before and after PBMV: MV area (MVA), TR area (TRA), atrial pressure and diameter, and pulmonary artery pressure (PAP). The patients were followed for 6 months to 9 years.
After PBMV, the MVAs increased significantly (1.7 ± 0.3 cm2 vs. 0.9 ± 0.3 cm2, P < 0.01); TRA significantly decreased (6.3 ± 1.7 cm2 vs. 14.2 ± 6.5 cm2, P < 0.01), right atrial area (RAA) decreased significantly (21.5 ± 4.5 cm2 vs. 25.4 ± 4.3 cm2, P < 0.05), TRA/RAA (%) decreased significantly (29.3 ± 3.2% vs. 44.2 ± 3.6%, P < 0.01). TR velocity (TRV) and TR continue time (TRT) as well as TRV × TRT decreased significantly (183.4 ± 9.4 cm/s vs. 254.5 ± 10.7 cm/s, P < 0.01; 185.7 ± 13.6 ms vs. 238.6 ± 11.3 ms, P < 0.01; 34.2 ± 5.6 cm vs. 60.7 ± 8.5 cm, P < 0.01, respectively). The postoperative left atrial diameter (LAD) significantly reduced (41.3 ± 6.2 mm vs. 49.8 ± 6.8 mm, P < 0.01) and the postoperative right atrial diameter (RAD) significantly reduced (28.7 ± 5.6 mm vs. 46.5 ± 6.3 mm, P < 0.01); the postoperative left atrium pressure significantly reduced (15.6 ± 6.1 mmHg vs. 26.5 ± 6.6 mmHg, P < 0.01), the postoperative right atrial pressure decreased significantly (13.2 ± 2.4 mmHg vs. 18.5 ± 4.3 mmHg, P < 0.01). The pulmonary arterial pressure decreased significantly after PBMV (48.2 ± 10.3 mmHg vs. 60.6 ± 15.5 mmHg, P < 0.01). The symptom of chest tightness and short of breath obviously alleviated. All cases followed-up for 6 months to 9 years (average 75 ± 32 months), 2 patients with severe regurgitation died (1 case of massive cerebral infarction, and 1 case of heart failure after 6 years and 8 years, respectively), 2 cases lost access. At the end of follow-up, MVA has been reduced compared with the postoperative (1.4 ± 0.4 cm2 vs. 1.7 ± 0.3 cm2, P < 0.05); LAD slightly increased compared with the postoperative (45.2 ± 5.7 mm vs. 41.4 ± 6.3 mm, P < 0.05), RAD slightly also increased compared with the postoperative (36.1 ± 6.3 mm vs. 28.6 ± 5.5 mm, P < 0.05), but did not recover to the preoperative level. TRA slightly increased compared with the postoperative, but the difference was not statistically significant (P > 0.05). The PAP and left ventricular ejection fraction appeared no statistical difference compared with the postoperative (P > 0.05), the remaining patients without serious complications.
PBMV is a safe and effective procedure for MS combined with TR in patients of rheumatic heart disease. It can alleviate the symptoms and reduce the size of TR. It can also improve the quality-of-life and prognosis. Its recent and mid-term efficacy is certain. While its long-term efficacy remains to be observed.
Apply Value; Mitral Stenosis with Tricuspid Valve Regurgitation; Percutaneous Balloon Mitral Valvuloplasty; Rheumatic Heart Disease
Recently, we identified a novel breast cancer (BC) susceptibility locus at 6q22.33 following a genome-wide association study (GWAS) in the Ashkenazi Jewish (AJ) genetic isolate. To replicate these findings, we performed case-control association analysis on 6q22.33 (rs2180341) in additional 487 AJ BC cases and in an independent non-Jewish (non-AJ), predominantly European-American (EU-Am), populations of 1,466 BC cases and 1,467 controls. We have confirmed the 6q22.33 association with BC risk in the replication cohorts (per-allele OR=1.18, 95%CI 1.04–1.33, p=0.0083) with the strongest effect in the aggregate meta-analysis of 3,039 BC cases and 2,616 AJ and non-AJ controls (per-allele OR=1.24, 95%CI 1.13–1.36, P=3.85×10−7).
We have also shown that the association was slightly stronger with ER positive tumors (per-allele OR=1.35, 95%CI 1.20–1.51, p=2.2×10−5) compared to ER negative tumors (per-allele OR=1.19, 95%CI 0.97–1.47, p=0.1). Furthermore, this study provides a novel insight into the functional significance of 6q22.33 in BC susceptibility. Due to stronger association of 6q22.33 with ER-positive BC we examined the effect of candidate genes on ER response elements (ERE). Upon transfection of overexpressed RNF146 in the MCF-7 BC cell line, we observed diminished expression of an ERE reporter construct. This study confirms the association of 6q22.33 with BC, with slightly stronger effect in ER positive tumors. Further functional studies of candidate genes are in progress and a large replication analysis is being completed as part of an international consortium.
Ashkenazi Jews; Breast Cancer; Genome-wide association studies; SNPs; estrogen receptor
This experimental study was designed to clarify the relationship between cardiomyocyte apoptosis and tumour necrosis factor-alpha (TNF-α) expression, and confirm the effect of TNF-α on cardiac dysfunction after coronary microembolization (CME) in mini-pigs. Nineteen mini-pigs were divided into three groups: sham-operation group (n = 5), CME group (n = 7) and adalimumab pre-treatment group (n = 7; TNF-α antibody, 2 mg/kg intracoronary injection before CME). Magnetic resonance imaging (3.0-T) was performed at baseline, 6th hour and 1 week after procedure. Cardiomyocyte apoptosis was detected by cardiac-TUNEL staining, and caspase-3 and caspase-8 were detected by RT-PCR and immunohistochemistry. Furthermore, serum TNF-α, IL-6 and troponin T were analysed, while myocardial expressions of TNF-α and IL-6 were detected. Both TNF-α expression (serum level and myocardial expression) and average number of apoptotic cardiomyocyte nuclei were significantly increased in CME group compared with the sham-operation group. Six hours after CME, left ventricular end-systolic volume (LVESV) was increased and the left ventricular ejection fraction (LVEF) was decreased in CME group. Pre-treatment with adalimumab not only significantly improved LVEF after CME (6th hour: 54.9 ± 2.3% versus 50.4 ± 3.9%, P = 0.036; 1 week: 56.7 ± 4.2% versus 52.7 ± 2.9%, P = 0.041), but also suppressed cardiomyocyte apoptosis and the expression of caspase-3 and caspase-8. Meanwhile, the average number of apoptotic cardiomyocytes nuclei was inversely correlated with LVEF (r = −0.535, P = 0.022). TNF-α-induced cardiomyocyte apoptosis is likely involved in cardiac dysfunction after CME. TNF-α antibody therapy suppresses cardiomyocyte apoptosis and improves early cardiac function after CME.
coronary microembolization; apoptosis; tumour necrosis factor-alpha
Recent findings from developmental neuroimaging studies suggest that the enhancement of cognitive processes during development may be the result of a fine-tuning of the structural and functional organization of brain with maturation. However, the details regarding the developmental trajectory of large-scale structural brain networks are not yet understood. Here, we used graph theory to examine developmental changes in the organization of structural brain networks in 203 normally growing children and adolescents. Structural brain networks were constructed using interregional correlations in cortical thickness for 4 age groups (early childhood: 4.8–8.4 year; late childhood: 8.5–11.3 year; early adolescence: 11.4–14.7 year; late adolescence: 14.8–18.3 year). Late childhood showed prominent changes in topological properties, specifically a significant reduction in local efficiency, modularity, and increased global efficiency, suggesting a shift of topological organization toward a more random configuration. An increase in number and span of distribution of connector hubs was found in this age group. Finally, inter-regional connectivity analysis and graph-theoretic measures indicated early maturation of primary sensorimotor regions and protracted development of higher order association and paralimbic regions. Our finding reveals a time window of plasticity occurring during late childhood which may accommodate crucial changes during puberty and the new developmental tasks that an adolescent faces.
adolescence; connectivity; connector hub; cortical thickness; maturation
Background and Objective
A number of studies have assessed the relationship between beta-2 adrenergic receptor (ADRB2) gene polymorphisms and asthma risk. However, the results are inconsistent. A meta-analysis that focused on the association between asthma and all ADRB2 polymorphisms with at least three case-control studies was thus performed.
A literature search of the PubMed, Embase, Web of Science, CNKI, and Wangfang databases was conducted. Odds ratios with 95% confidence intervals were used to assess the strength of associations.
Arg16Gly, Gln27Glu, Thr164Ile, and Arg19Cys single nucleotide polymorphisms (SNPs) were identified in 46 case-control studies. The results showed that not all of the SNPs were associated with asthma in the overall population. Significant associations were found for the Arg16Gly polymorphism in the South American population via dominant model comparison (OR = 1.754, 95% CI = 1.179–2.609, I2 = 16.9%, studies = 2, case = 314, control = 237) in an analysis stratified by ethnicity. For the Gln27Glu polymorphism, a protective association was found in children via recessive model comparison (OR = 0.566, 95% CI = 0.417–0.769, I2 = 0.0%, studies = 11, case = 1693, control = 502) and homozygote genotype comparison (OR = 0.610, 95% CI = 0.434–0.856, I2 = 0.0%, studies = 11, case = 1693, control = 1502), and in adults via dominant model comparison (OR = 0.864, 95% CI = 0.768–0.971, I2 = 46.9%, n = 18, case = 3160, control = 3433).
None of the ADRB2 gene polymorphisms were reproducibly associated with a risk of asthma across ethnic groups in the general population.
This study aimed to investigate the expression and clinical significance of enoyl coenzyme A hydratase, short chain, 1 (ECHS1), in patients with colorectal cancer (CRC). The ECHS1 protein expression as detected by immunohistochemistry in 148 CRC specimens was evaluated and compared by clinical pathology and prognosis; 38 specimens from proximal non-cancerous colorectal tissues were included as controls. The ECHS1 protein expression was also measured by western blot analysis in 46 fresh CRC tissue specimens and 22 normal colorectal tissue specimens. The rate of positive ECHS1 expression differed significantly between the CRC tissues (56.76%, 84/148) and the proximal non-cancerous colorectal tissues (5.26%, 2/38) (P<0.001). The ECHS1 protein expression was confirmed not to be associated with gender or age. However, the positive expression of ECHS1 tended to be positively associated with clinical TNM stage (P=0.015), lymph node metastasis (P=0.011) and histological differentiation (P=0.028). The expression of the ECHS1 protein on western blot analysis was significantly increased in CRC vs. normal tissues. In addition, the overall survival curves estimated with the Kaplan-Meier method demonstrated that CRC patients exhibiting low ECHS1 expression survived significantly longer compared to patients with high ECHS1 levels (P=0.039). Our data suggested that ECHS1 protein expression may contribute to the occurrence, progression and metastasis of CRC, is closely associated with prognosis and may provide useful information for CRC molecular-targeted therapy.
colorectal cancer; enoyl coenzyme A hydratase; short chain; 1; metastasis; prognosis
Channel estimation problem is one of the key technical issues in sparse frequency-selective fading multiple-input multiple-output (MIMO) communication systems using orthogonal frequency division multiplexing (OFDM) scheme. To estimate sparse MIMO channels, sparse invariable step-size normalized least mean square (ISS-NLMS) algorithms were applied to adaptive sparse channel estimation (ACSE). It is well known that step-size is a critical parameter which controls three aspects: algorithm stability, estimation performance, and computational cost. However, traditional methods are vulnerable to cause estimation performance loss because ISS cannot balance the three aspects simultaneously. In this paper, we propose two stable sparse variable step-size NLMS (VSS-NLMS) algorithms to improve the accuracy of MIMO channel estimators. First, ASCE is formulated in MIMO-OFDM systems. Second, different sparse penalties are introduced to VSS-NLMS algorithm for ASCE. In addition, difference between sparse ISS-NLMS algorithms and sparse VSS-NLMS ones is explained and their lower bounds are also derived. At last, to verify the effectiveness of the proposed algorithms for ASCE, several selected simulation results are shown to prove that the proposed sparse VSS-NLMS algorithms can achieve better estimation performance than the conventional methods via mean square error (MSE) and bit error rate (BER) metrics.
AIM: To investigate the protective effects of combinations of probiotic (Bifico) on interleukin (IL)-10-gene-deficient (IL-10 KO) mice and Caco-2 cell monolayers.
METHODS: IL-10 KO mice were used to assess the benefits of Bifico in vivo. IL-10 KO and control mice received approximately 1.5 × 108 cfu/d of Bifico for 4 wk. Colons were then removed and analyzed for epithelial barrier function by Ussing Chamber, while an ELISA was used to evaluate proinflammatory cytokines. The colon epithelial cell line, Caco-2, was used to test the benefit of Bifico in vitro. Enteroinvasive Escherichia coli (EIEC) and the probiotic mixture Bifico, or single probiotic strains, were applied to cultured Caco-2 monolayers. Barrier function was determined by measuring transepithelial electrical resistance and tight junction protein expression.
RESULTS: Treatment of IL-10 KO mice with Bifico partially restored body weight, colon length, and epithelial barrier integrity to wild-type levels. In addition, IL-10 KO mice receiving Bifico treatment had reduced mucosal secretion of tumor necrosis factor-α and interferon-γ, and attenuated colonic disease. Moreover, treatment of Caco-2 monolayers with Bifico or single-strain probiotics in vitro inhibited EIEC invasion and reduced the secretion of proinflammatory cytokines.
CONCLUSION: Bifico reduced colon inflammation in IL-10 KO mice, and promoted and improved epithelial-barrier function, enhanced resistance to EIEC invasion, and decreased proinflammatory cytokine secretion.
Probiotic bacteria; Intestinal barrier function; Tight junction proteins; Interleukin-10 gene-deficient mice; Caco-2 monolayers
Coronary artery disease (CAD) severity is associated with patient prognosis. However, few efficient scoring systems have been developed to screen severe CAD in patients with stable angina and suspected CAD before coronary angiography. Here, we present a novel scoring system for CAD severity before elective coronary angiography.
Five hundred fifty-one patients with stable angina who were admitted for coronary angiography were enrolled in this study. Patients were divided into training (n = 347) and validation (n = 204) cohorts. Severe CAD was defined as having a Gensini score of 20 or more. All patients underwent echocardiography (ECG) to detect ejection fraction and aortic valve calcification (AVC). Multivariable analysis was applied to determine independent risk factors and develop the scoring system.
In the training cohort, age, male sex, AVC, abnormal ECG, diabetes, hyperlipidemia, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were identified as independent factors for severe CAD by multivariable analysis, and the Severe Prediction Scoring (SPS) system was developed. C-indices of receiver operating characteristic (ROC) curves for severe CAD were 0.744 and 0.710 in the training and validation groups, respectively. The SPS system also performed well during calibration, as demonstrated by Hosmer-Lemeshow analysis in the validation group. Compared with the Diamond-Forrester score, the SPS system performed better for severe CAD prediction before elective coronary angiography.
Severe CAD prediction was achieved by analyzing age, sex, AVC, ECG, diabetes status, and lipid levels. Angina patients who achieve high scores using this predicting system should undergo early coronary angiography.
Barnacles are major sessile components of the intertidal areas worldwide, and also one of the most dominant fouling organisms in fouling communities. Larval settlement has a crucial ecological effect not only on the distribution of the barnacle population but also intertidal community structures. However, the molecular mechanisms involved in the transition process from the larval to the juvenile stage remain largely unclear. In this study, we carried out comparative proteomic profiles of stage II nauplii, stage VI nauplii, cyprids, and juveniles of the barnacle Balanus amphitrite using label-free quantitative proteomics, followed by the measurement of the gene expression levels of candidate proteins. More than 700 proteins were identified at each stage; 80 were significantly up-regulated in cyprids and 95 in juveniles vs other stages. Specifically, proteins involved in energy and metabolism, the nervous system and signal transduction were significantly up-regulated in cyprids, whereas proteins involved in cytoskeletal remodeling, transcription and translation, cell proliferation and differentiation, and biomineralization were up-regulated in juveniles, consistent with changes associated with larval metamorphosis and tissue remodeling in juveniles. These findings provided molecular evidence for the morphological, physiological and biological changes that occur during the transition process from the larval to the juvenile stages in B. amphitrite.
Small cell neuroendocrine carcinoma arising in the ureter is extremely rare; only a few cases have been previously reported in the literature. The current study reports the case of a 65-year-old female who presented with right-sided back pain. A mass was identified in the right ureter, and a nephroureterectomy was performed. The microscopic examination revealed that the mass was composed of a monotonous population of small cells and that the cells of the carcinoma were positive for cluster of differentiation 56, chromogranin A and synaptophysin. The tumor was diagnosed as a ureteral neuroendocrine small cell carcinoma. The patient returned 4 months later with recurrences in the retroperitoneum. Chemotherapy was administered and following 80 mg/m2 intravenous irinotecan on days 1 and 8 and 25 mg/m2 cisplatin on days 1–3, every 21 days for 4 cycles, the tumor was considerably smaller. During the regular follow-up examinations, the tumor remained stable.
ureter; neuroendocrine carcinoma; chemotherapy
The ability to achieve energy saving in architectures and optimal solar energy utilisation affects the sustainable development of the human race. Traditional smart windows and solar cells cannot be combined into one device for energy saving and electricity generation. A VO2 film can respond to the environmental temperature to intelligently regulate infrared transmittance while maintaining visible transparency, and can be applied as a thermochromic smart window. Herein, we report for the first time a novel VO2-based smart window that partially utilises light scattering to solar cells around the glass panel for electricity generation. This smart window combines energy-saving and generation in one device, and offers potential to intelligently regulate and utilise solar radiation in an efficient manner.
Understanding the development of human brain organization is critical for gaining insight into how the enhancement of cognitive processes is related to the fine-tuning of the brain network. However, the developmental trajectory of the large-scale white matter (WM) network is not fully understood. Here, using graph theory, we examine developmental changes in the organization of WM networks in 180 typically-developing participants. WM networks were constructed using whole brain tractography and 78 cortical regions of interest were extracted from each participant. The subjects were first divided into 5 equal sample size (n = 36) groups (early childhood: 6.0–9.7 years; late childhood: 9.8–12.7 years; adolescence: 12.9–17.5 years; young adult: 17.6–21.8 years; adult: 21.9–29.6 years). Most prominent changes in the topological properties of developing brain networks occur at late childhood and adolescence. During late childhood period, the structural brain network showed significant increase in the global efficiency but decrease in modularity, suggesting a shift of topological organization toward a more randomized configuration. However, while preserving most topological features, there was a significant increase in the local efficiency at adolescence, suggesting the dynamic process of rewiring and rebalancing brain connections at different growth stages. In addition, several pivotal hubs were identified that are vital for the global coordination of information flow over the whole brain network across all age groups. Significant increases of nodal efficiency were present in several regions such as precuneus at late childhood. Finally, a stable and functionally/anatomically related modular organization was identified throughout the development of the WM network. This study used network analysis to elucidate the topological changes in brain maturation, paving the way for developing novel methods for analyzing disrupted brain connectivity in neurodevelopmental disorders.
graph theory; neurodevelopment; anatomical connectivity; modular networks; small world network
The barnacle Balanus amphitrite is a globally distributed marine crustacean and has been used as a model species for intertidal ecology and biofouling studies. Its life cycle consists of seven planktonic larval stages followed by a sessile juvenile/adult stage. The transitional processes between larval stages and juveniles are crucial for barnacle development and recruitment. Although some studies have been conducted on the neuroanatomy and neuroactive substances of the barnacle, a comprehensive understanding of neuropeptides and peptide hormones remains lacking. To better characterize barnacle neuropeptidome and its potential roles in larval settlement, an in silico identification of putative transcripts encoding neuropeptides/peptide hormones was performed, based on transcriptome of the barnacle B. amphitrite that has been recently sequenced. Potential cleavage sites andstructure of mature peptides were predicted through homology search of known arthropod peptides. In total, 16 neuropeptide families/subfamilies were predicted from the barnacle transcriptome, and 14 of them were confirmed as genuine neuropeptides by Rapid Amplification of cDNA Ends. Analysis of peptide precursor structures and mature sequences showed that some neuropeptides of B. amphitrite are novel isoforms and shared similar characteristics with their homologs from insects. The expression profiling of predicted neuropeptide genes revealed that pigment dispersing hormone, SIFamide, calcitonin, and B-type allatostatin had the highest expression level in cypris stage, while tachykinin-related peptide was down regulated in both cyprids and juveniles. Furthermore, an inhibitor of proprotein convertase related to peptide maturation effectively delayed larval metamorphosis. Combination of real-time PCR results and bioassay indicated that certain neuropeptides may play an important role in cypris settlement. Overall, new insight into neuropeptides/peptide hormones characterized in this study shall provide a platform for unraveling peptidergic control of barnacle larval behavior and settlement process.
AIM: To screen the differential expressed genes in colorectal cancer and polyp tissue samples.
METHODS: Tissue specimens containing 16 cases of colorectal adenocarcinoma and colorectal polyp vs normal mucosae were collected and subjected to cDNA microarray and bioinformatical analyses. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to confirm some of the cDNA microarray data.
RESULTS: The experimental data showed that eight genes were differentially expressed, most of which were upregulated in adenomatous polyp lesions. Forty-six genes expressions were altered in colorectal cancers, of which 29 were upregulated and 17 downregulated, as compared to the normal mucosae. In addition, 18 genes were similarly altered in both adenomatous polyps and colorectal cancer. qRT-PCR analyses confirmed the cDNA microarray data for four of those 18 genes: MTA1, PDCD4, TSC1 and PDGFRA.
CONCLUSION: These differentially expressed genes likely represent biomarkers for early detection of colorectal cancer and may be potential therapeutic targets after confirmed by further studies.
Colorectal polyp; Colorectal cancer; cDNA microarray; Quantitative reverse transcription-polymerase chain reaction
Barnacles are one of the most common organisms in intertidal areas. Their life cycle includes seven free-swimming larval stages and sessile juvenile and adult stages. The transition from the swimming to the sessile stages, referred to as larval settlement, is crucial for their survivor success and subsequent population distribution. In this study, we focused on the involvement of calmodulin (CaM) and its binding proteins in the larval settlement of the barnacle, Balanus ( = Amphibalanus) amphitrite. The full length of CaM gene was cloned from stage II nauplii of B. amphitrite (referred to as Ba-CaM), encoding 149 amino acid residues that share a high similarity with published CaMs in other organisms. Quantitative real-time PCR showed that Ba-CaM was highly expressed in cyprids, the stage at which swimming larvae are competent to attach and undergo metamorphosis. In situ hybridization revealed that the expressed Ba-CaM gene was localized in compound eyes, posterior ganglion and cement glands, all of which may have essential functions during larval settlement. Larval settlement assays showed that both the CaM inhibitor compound 48/80 and the CaM-dependent myosin light chain kinase (MLCK) inhibitor ML-7 effectively blocked barnacle larval settlement, whereas Ca2+/CaM-dependent kinase II (CaMKII) inhibitors did not show any clear effects. The subsequent real-time PCR assay showed a higher expression level of Ba-MLCK gene in larval stages than in adults, suggesting an important role of Ba-MLCK gene in larval development and competency. Overall, the results suggest that CaM and CaM-dependent MLCK function during larval settlement of B. amphitrite.
The barnacle Balanus amphitrite is a globally distributed biofouler and a model species in intertidal ecology and larval settlement studies. However, a lack of genomic information has hindered the comprehensive elucidation of the molecular mechanisms coordinating its larval settlement. The pyrosequencing-based transcriptomic approach is thought to be useful to identify key molecular changes during larval settlement.
Methodology and Principal Findings
Using 454 pyrosequencing, we collected totally 630,845 reads including 215,308 from the larval stages and 415,537 from the adults; 23,451 contigs were generated while 77,785 remained as singletons. We annotated 31,720 of the 92,322 predicted open reading frames, which matched hits in the NCBI NR database, and identified 7,954 putative genes that were differentially expressed between the larval and adult stages. Of these, several genes were further characterized with quantitative real-time PCR and in situ hybridization, revealing some key findings: 1) vitellogenin was uniquely expressed in late nauplius stage, suggesting it may be an energy source for the subsequent non-feeding cyprid stage; 2) the locations of mannose receptors suggested they may be involved in the sensory system of cyprids; 3) 20 kDa-cement protein homologues were expressed in the cyprid cement gland and probably function during attachment; and 4) receptor tyrosine kinases were expressed higher in cyprid stage and may be involved in signal perception during larval settlement.
Our results provide not only the basis of several new hypotheses about gene functions during larval settlement, but also the availability of this large transcriptome dataset in B. amphitrite for further exploration of larval settlement and developmental pathways in this important marine species.