Intermittent Hypoxia Alleviates ß-Aminopropionitrile Monofumarate Induced Thoracic Aortic Dissection in C57BL/6 Mice.

OBJECTIVE: Thoracic aortic dissection (TAD) has a high mortality rate. Intermittent hypoxia (IH) triggers both harmful and beneficial effects in numerous physiological systems. The effects of IH on TAD development were explored in a mouse model. METHODS: ß-Aminopropionitrile monofumarate (BAPN) was used to induce TAD in C57BL/6 mice. Three week old male mice were treated with 1 g/kg/day BAPN in drinking water for four weeks and simultaneously subjected to IH (n = 30) (21%-5% O2, 90 s/cycle, 10 h/day, IH + BAPN group) or normoxia (n = 30) (21% O2, 24 h/day, BAPN group). Human VSMCs (HUASMCs) exposed to IH (30 min, 5% O2)/re-oxygenation (30 min, 21% O2) cycles with a maximum of 60 min/cycle to detect the effect of IH on HIF-1α and LOX via HIF-1α-siRNA. RESULTS: It was found that BAPN administration significantly increased the lumen size and wall thickness of aortas compared with the normal group, but was significantly reversed by IH exposure. Additionally, IH exposure significantly increased the survival rate of BAPN induced TAD (70% vs. 40%). Furthermore, IH exposure reduced BAPN induced elastin breaks and apoptosis of vascular smooth muscle cells. IH exposure also reversed BAPN induced upregulation of inflammation and extracellular matrix (ECM) degradation. Real time polymerase chain reaction (RT-PCR) confirmed that IH inhibited inflammation and ECM degradation related genes interleukin (IL)-1ß, IL-6, cathepsin S (Cat S), and matrix metalloproteinase 9 (MMP-9), but upregulated the ECM synthesis related genes lysyl oxidase (LOX) and collagen type I alpha2 (Col1a2) compared with the BAPN group. In vitro results suggest that IH promotes the expression of LOX via HIF-1α. CONCLUSION: The results suggest that IH alleviates BAPN induced TAD in C57BL/6 mice.

Effects of continuous positive airway pressure on cardiovascular biomarkers in patients with obstructive sleep apnea: a meta-analysis of randomized controlled trials.

PURPOSE: Obstructive sleep apnea (OSA) is associated with increased levels of systemic inflammatory markers, increased arterial stiffness, and endothelial dysfunction, which may lead to increased cardiovascular risk. We aimed to quantify the effects of continuous positive airway pressure (CPAP) on cardiovascular biomarkers and to establish predictors of response to CPAP. METHODS: We searched PubMed and the Cochrane Library from inception to May 31, 2017. Randomized controlled trials (RCTs) assessing the efficacy of CPAP on high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumor necrosis factor- alpha (TNF-α), augmentation index (AIx), pulse wave velocity (PWV), and flow-mediated dilatation (FMD) in patients with OSA were selected by consensus. RESULTS: We included 15 RCTs comprising 1090 patients in the meta-analysis. The pooled standard mean difference (SMD) of effect of CPAP on hs-CRP was - 0.64 (95% confidence interval (CI) - 1.19 to - 0.09; P = 0.02). CPAP was associated with a reduction in AIx of 1.53% (95% CI, 0.80 to 2.26%; P < 0.001) and a significant increase in FMD of 3.96% (95% CI 1.34 to 6.59%; P = 0.003). Subgroup analyses found CPAP was likely to be more effective in improving FMD levels in severe OSA patients or patients with effective CPAP use ≥ 4 h/night. CONCLUSIONS: Among patients with OSA, CPAP improves inflammatory marker hs-CRP, arterial stiffness marker AIx, and endothelial function marker FMD. These biomarkers may provide information related to response to treatment. Future studies will need to clarify the efficacy of these biomarkers in assessing cardiovascular risk reduction among OSA treated with CPAP.

[Effects of thyroid hormone on macrophage dysfunction induced by oxidized low-density lipoprotein].

It has been recognized that patients with hypothyroidism have higher risks of atherosclerosis and coronary heart disease, however, the mechanisms are largely unknown. Considering that macrophage dysfunction plays an important role in the formation and development of atherosclerosis plaques, this study aimed to investigate the direct effects of thyroid hormone on macrophage functions and to provide new insight for the mechanism of hypothyroid atherosclerosis. RAW264.7 cells (mouse leukaemic monocyte macrophage cell line) were incubated with oxidized low-density lipoprotein (oxLDL) to establish macrophage foam cells model in vitro, and the protective effects of different concentration of thyroxine (T4) on the macrophage foam cells function were explored. The proliferation, migration and cell aging of macrophages were detected by MTT method, scratch test and ß-galactosidase staining respectively. The ELISA method was used to detect the secretion of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-1ß (IL-1ß). Western blot analysis was applied to measure the phosphorylation of focal adhesion kinase (FAK), which was required for the process of proliferation and migration of macrophages. The results showed that oxLDL significantly inhibited the macrophage proliferation and migration, induced cell senescence, and promoted the secretion of TNF-α, MCP-1, and IL-1ß; while T4 reversed those effects of oxLDL on macrophage in a concentration-dependent manner. Moreover, oxLDL increased the phosphorylation of FAK in macrophage, while T4 concentration-dependently reversed the effect. These results suggest that T4 modulates macrophage proliferation, migration, senescence, and secretion of inflammation factors in a concentration-dependent way.

Apolipoprotein A-I Mimetic Peptide D-4F Reduces Cardiac Hypertrophy and Improves Apolipoprotein A-I-Mediated Reverse Cholesterol Transport From Cardiac Tissue in LDL Receptor-null Mice Fed a Western Diet.

Epidemiological studies have suggested that hypercholesterolemia is an independent determinant of increased left ventricular (LV) mass. Because high-density lipoprotein and its major protein apolipoprotein A-I (apoA-I) mediate reverse cholesterol transport (RCT) and have cardiac protective effects, we hypothesized that the apoA-I mimetic peptide D-4F could promote RCT in cardiac tissue and decrease cardiac hypertrophy induced by hypercholesterolemia. Low-density lipoprotein receptor-null mice were fed by a Western diet for 18 weeks and then randomized to receive water, or D-4F 0.3 mg/mL, or D-4F 0.5 mg/mL added to drinking water for 6 weeks. After D-4F administration, an increase in high-density lipoprotein cholesterol and a decrease in low-density lipoprotein cholesterol, total cholesterol, and triglyceride in a trend toward dose-responsivity were found in cardiac tissue. Ultrasound biomicroscopy revealed a reduction in LV posterior wall end-diastolic dimension, and an increase in mitral valve E/A ratio and LV ejection fraction. Hematoxylin-eosin staining showed reduced LV wall thickness and myocardial cell diameter. The protein levels of ABCA1 and LXRα were elevated in cardiac tissue of D-4F treated mice compared with the controls (P < 0.05). These results demonstrated that D-4F treatment reduced cardiac hypertrophy, and improved cardiac performance in low-density lipoprotein receptor-null mice fed a Western diet, presumably through the LXRα-ABCA1 pathway associated with enhanced myocardial RCT.

Mechanical stretch-induced endoplasmic reticulum stress, apoptosis and inflammation contribute to thoracic aortic aneurysm and dissection.

Thoracic aortic aneurysm/dissection (TAAD) is characterized by excessive smooth muscle cell (SMC) loss, extracellular matrix (ECM) degradation and inflammation. In response to certain stimuli, endoplasmic reticulum (ER) stress is activated and regulates apoptosis and inflammation. Excessive apoptosis promotes aortic inflammation and degeneration, leading to TAAD. Therefore, we studied the role of ER stress in TAAD formation. A lysyl oxidase inhibitor, 3-aminopropionitrile fumarate (BAPN), was administrated to induce TAAD formation in mice, which showed significant SMC loss (α-SMA level). Excessive apoptosis (TUNEL staining) and ER stress (ATF4 and CHOP), along with inflammation, were present in TAAD samples from both mouse and human. Transcriptional profiling of SMCs after mechanical stress demonstrated the expression of genes for ER stress and inflammation. To explore the causal role of ER stress in initiating degenerative signalling events and TAAD, we treated wild-type (CHOP(+/+)) or CHOP(-/-) mice with BAPN and found that CHOP deficiency protected against TAAD formation and rupture, as well as reduction in α-SMA level. Both SMC apoptosis and inflammation were significantly reduced in CHOP(-/-) mice. Moreover, SMCs isolated from CHOP(-/-) mice were resistant to mechanical stress-induced apoptosis. Taken together, our results demonstrated that mechanical stress-induced ER stress promotes SMCs apoptosis, inflammation and degeneration, providing insight into TAAD formation and progression.

Long Noncoding RNA Expression Signatures of Abdominal Aortic Aneurysm Revealed by Microarray.

OBJECTIVE: This study is aimed at observing the role of long noncoding RNAs (lncRNAs) in the pathogenesis of abdominal aortic aneurysm (AAA). METHODS: LncRNA and mRNA expression signatures of AAA tissues and normal abdominal aortic tissues (NT) were analyzed by microarray and further verified by Real-time quantitative reverse-transcription PCR (qRT-PCR). The lncRNAs-mRNAs targeting relationships were identified using computational analysis. The effect of lnc-ARG on 5-lipoxygenase (ALOX5) expression was tested in HeLa cells. RESULTS: Differential expressions of 3,688 lncRNAs and 3,007 mRNAs were identified between AAA and NT tissues. Moreover, 1,284 differentially expressed long intergenic noncoding RNAs and 206 differentially expressed enhancer-like lncRNAs adjacent to protein-coding genes were discerned by bioinformatics analysis. Some differentially expressed lncRNAs and mRNAs between AAA and normal tissue samples were further verified using qRT-PCR. A co-expression network of coding and noncoding genes was constructed based on the correlation analysis between the differentially expressed lncRNAs and mRNAs. In addition, the lnc-ARG located within the upstream of ALOX5 was sorted as a noncoding transcript by analyzing the protein-coding potential using computational analysis. Furthermore, we found that lnc-ARG can decrease the mRNA level of ALOX5 and reactive oxygen species production in HeLa cells. CONCLUSION: This study revealed new lncRNA candidates are related to the pathogenesis of AAA.

Association of the polymorphisms of MMP-9 and TIMP-3 genes with thoracic aortic dissection in Chinese Han population.

AIM: Thoracic aortic dissection (TAD) is the most common life-threatening disorder, and a shifted balance of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is involved in TAD pathogenesis. The aim of this study was to evaluate the association of 4 single-nucleotide polymorphisms (SNPs) in MMP-9 and TIMP-3 genes with TAD risk in Chinese Han population. METHODS: A total of 206 Chinese patients with TAD and 180 controls were included in this study. Four SNPs (rs3918249, rs2274756, rs9609643 and rs8136803) were genotyped using high-throughput MALDI-TOF mass spectrometry. Allele and genotype association analyses were conducted using PLINK. RESULTS: All the 4 SNPs resulted in Hardy-Weinberg equilibrium in patients and controls. The G allele frequency for the MMP-9 SNP rs2274756 was significantly higher in female TAD patients than in female controls (P=0.0099). Moreover, after adjusting for traditional cardiovascular risk factors (sex, age, hypertension, dyslipidemia, diabetes and smoking habit), the rs2274756 polymorphism (odds ratio: 0.30; 95% confidence interval: 0.11 to 0.79, P=0.015) resulted in an independent susceptibility factor for TAD in females. No associations were found between the other SNPs and TAD. CONCLUSION: The results provide strong evidence for an association between MMP-9 SNP rs2274756 and female TAD risk in Chinese Han population.

[Application of amplitutude integrated electroencephalography for early diagnosis of brain injury in premature infants].

OBJECTIVE: To study the characteristics of amplitude integrated electroencephalography (aEEG) in preterm infants with brain injury. METHODS: This study included 62 cerebral damage infants with 28-36 weeks gestational age (GA), and another 51 normal infants in control group, aEEG recording was performed to each infant during the first 48 h of life, the duration of each recording was at least 2 h. The features of aEEG, such as continuity(Co), sleep-wake cycling (Cy) and amplitude of the lower border (LB), were evaluated by semiquantitative analysis and compared between the two groups. RESULTS: All the aEEG features were found having significantly lower values in brain injuries group (P < 0.05). Logistic regression of aEEG features to the presence of brain injury revealed that only Cy was significantly correlated to the outcome (OR = 0.217, P < 0.05). ROC curve demonstrated Cy of the best sensitivity and specificity with 0.769 AUC. Co, LB yielded 0.677, 0.602 AUC respectively. Correlation analysis of GA to Co, Cy, LB and total score showed significantly correlated, the correlation coefficient for Co, Cy, LB and total scores were 0.546, 0.488, 0.536, 0.588 respectively (P < 0.05). CONCLUSION: The Cy in the initial aEEG is predictive for brain injury in premature infants with 28-36 weeks GA. The older the GA at birth, the more mature the aEEG pattern in premature neonates.

Angiopoietin-like protein 8 deficiency attenuates thoracic aortic aneurysm/dissection development in ß-aminopropionitrile monofumarate-induced model mice.

Thoracic aortic aneurysm/dissection (TAAD) is a life-threatening cardiovascular disorder. Endoplasmic reticulum stress (ERS) and vascular smooth muscle cell (VSMC) apoptosis are involved in TAAD progression. The Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) pathway is associated with VSMC apoptosis. Serum Angiopoietin-Like Protein 8 (ANGPTL8) levels are associated with aortic diameter and rupture rate of TAAD. However, a direct role of ANGPTL8 in TAAD has not been determined. ß-Aminopropionitrile monofumarate (BAPN) was used to induce TAAD in C57BL/6 mice. ANGPTL8 knockout mice were used to detect the effects of ANGPTL8 on TAAD development. ANGPTL8knockdown in vitro was used to analyze the role of ANGPTL8 in VSMCs and ERS. In addition, over-expression of ANGPTL8 in VSMCs and a PERK inhibitor were used to assess the effect of ANGPTL8 on the PERK pathway. ANGPTL8 levels were increased in the aortic wall and VSMCs of BAPN-induced TAAD mice. Compared with BAPN-treated wild-type mice, ANGPTL8 knockout significantly reduced the rupture rate of TAAD to 0 %. In addition, the protein levels of proinflammatory cytokines and matrix metalloproteinase 9 (MMP9) and ERS proteins were decreased in the aorta wall. Angptl8 shRNA decreased MMP9 and ERS protein levels in VSMCs in vitro. Overexpression of ANGPTL8 significantly increased the levels of ERS proteins and MMPs, while a PERK inhibitor significantly decreased the effects of ANGPTL8 in VSMCs. ANGPTL8 contributed to TAAD development by inducing ERS activation and degradation of extracellular matrix in the aorta wall. Inhibition of ANGPTL8 may therefore represent a new strategy for TAAD therapy.

Osteopontin stimulates autophagy via integrin/CD44 and p38 MAPK signaling pathways in vascular smooth muscle cells.

Osteopontin (OPN) exerts pro-inflammatory effect and is associated with the development of abdominal aortic aneurysm (AAA). However, the molecular mechanism underlying this association remains obscure. In the present study, we compared gene expression profiles of AAA tissues using microarray assay, and found that OPN was the highest expressed gene (>125-fold). Furthermore, the expression of LC3 protein and autophagy-related genes including Atg4b, Beclin1/Atg6, Bnip3, and Vps34 was markedly upregulated in AAA tissues. To investigate the ability of OPN to stimulate autophagy as a potential mechanism involved in the pathogenesis of this disease, we treated vascular smooth muscle cells (SMCs) with OPN, and found that OPN significantly increased the formation of autophagosomes, expression of autophagy-related genes and cell death, whereas blocking the signal by anti-OPN antibody markedly inhibited OPN-induced autophagy and SMC death. Furthermore, inhibition of integrin/CD44 and p38 MAPK signaling pathways markedly abrogated the biological effects of OPN on SMCs. These data for the first time demonstrate that OPN sitmulates autophagy directly through integrin/CD44 and p38 MAPK-mediated pathways in SMCs. Thus, inhibition of OPN-induced autophagy might be a potential therapeutic target in the treatment of AAA disease. J. Cell. Physiol. 227: 127-135, 2012. © 2011 Wiley Periodicals, Inc.

Angiopoietin-like proteins 8 knockout reduces intermittent hypoxia-induced vascular remodeling in a murine model of obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) is a major risk factor for cardiovascular mortality. Apnea-induced chronic intermittent hypoxia (CIH) is a primary pathophysiological manifestation of OSA that promotes various cardiovascular alterations, such as aortic vascular remodeling. In this study, we investigated the association between angiopoietin-like proteins 8 (ANGPTL8) and CIH-induced aortic vascular remodeling in mice. METHODS: C57BL/6J male mice were divided into four groups: Normoxia group, ANGPTL8-/- group, CIH group, CIH + ANGPTL8-/- group. Mice in the normoxia group and ANGPTL8-/- group received no treatment, while mice in the CIH and CIH + ANGPTL8-/- group were subjected to CIH (21%-5% O2, 180 s/cycle, 10 h/day) for 6 weeks. At the end of the experiments, intima-media thickness (IMT), elastin disorganization, and aortic wall collagen abundance were assessed in vivo. Immunohistochemistry and Western-blot were used to detect endoplasmic reticulum stress (ERS) and aortic vascular smooth muscle cell proliferation. ANGPTL8 shRNA and ANGPL8 overexpression were used in aortic vascular smooth muscle cells to investigate the mechanism of ANGPTL8 in CIH. RESULTS: Compared to the control group, CIH exposure significantly increased intima-media thickness (IMT), elastic fibers disorganization, and aortic wall collagen abundance. CIH also significantly increased blood pressure, induced hyperlipidemia, as well as the expression of ERS protein activating transcription factor-6 (ATF6) and aortic vascular smooth muscle cell proliferation. Contrary, ANGPTL8-/- significantly mitigated the CIH-induced vascular remodeling; ANGPTL8-/- decreased CIH-induced hypertension and hyperlipidemia, inhibited the protein expression of ATF6, and aortic vascular smooth muscle cell proliferation. Moreover, our in vitro study suggested that CIH could induce ANGPTL8 expression via hypoxia-inducible factor (HIF-1α); ANGPTL8 induced proliferation of aortic vascular smooth muscle cells via the ERS pathway. CONCLUSION: ANGPTL8-/- can prevent CIH-induced aortic vascular remodeling, probably through the inhibition of the ERS pathway. Therefore, ANGPTL8 might be a potential target in CIH-induced aortic vascular remodeling.

Simvastatin inhibited cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice fed a "Western-style diet" by increasing PPAR α and γ expression and reducing TC, MMP-9, and Cat S levels.

AIM: The examine the cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice (ApoE-/- mice) fed a "Western-style diet" and the effect of simvastatin intervention. METHODS: Male ApoE-/- mice (n=36) were fed a "Western-style diet" from the age of 8 weeks. After 16 weeks, they were randomly given either simvastatin (25 mg·kg⁻¹·d⁻¹) or normal saline (control group) by gavage for 8, 16, or 24 weeks. The left ventricular (LV) wall thickness and diameter of the myocardial cells were determined with Hematoxylin-Eosin stain, and the level of fibrosis of the myocardial matrix was assessed with Masson stain. Real-time quantitative polymerase chain reaction and Western blotting analysis were used to determine the mRNA and protein expression of matrix metalloproteinase-9 (MMP-9), Cathepsin S (Cat S), and the peroxisome proliferator-activated receptors (PPARs) in the myocardium of ApoE-/- mice. RESULTS: ApoE-/- mice fed a "Western-style diet" showed an significant age-dependent increase in total cholesterol (TC), LV wall thickness, myocardial cell diameter and LV collagen content (P<0.05). The simvastatin treatment group showed significantly reduced LV wall thickness, myocardial cell diameters and LV collagen content at 40 weeks when compared with the control group (P<0.05). Furthermore, treatment with simvastatin also significantly inhibited the mRNA and protein expressions of MMP-9 and Cat S as well as increased the mRNA and protein expressions of PPAR alpha and PPAR gamma at 32 and 40 weeks compared with the control group (P<0.05). CONCLUSION: ApoE-/- mice fed a "Western-style diet" had cardiac hypertrophy and fibrosis, which worsened with age. Simvastatin treatment inhibits the development of cardiac hypertrophy and fibrosis, and this effect may be mediated through increased levels of PPAR alpha and PPAR gamma and reduced levels of TC, MMP-9, and Cat S.

The association between circulating APRIL levels and severity of obstructive sleep apnea in Chinese adults.

BACKGROUND: Obstructive sleep apnea (OSA) is the most common type of sleep breathing disorder and is characterized by chronic intermittent hypoxia, which could cause inflammation and nuclear factor kappa B (NF-KB)-dependent inflammatory pathways activation. Circulating APRIL (a proliferation-inducing ligand) play an important role in promoting inflammation and NF-KB-dependent inflammatory pathways activation. We explored the role of APRIL as a potential mechanism of inflammation in OSA patients. METHODS: After detailed sleep evaluated, venous blood and demographic data were collected from 155 subjects with varying severity of OSA and 52 control subjects. Plasma levels of APRIL were measured by human Magnetic Luminex assay. RESULTS: Plasma APRIL levels were significantly higher in OSA subjects compared with control subjects. Categorization of the OSA subjects into mild, moderate, and severe OSA subgroups found that plasma levels of APRIL increased with the severity of OSA. After adjusting confounding factors, found that increased plasma APRIL levels were conferred a higher odds ratio of OSA. Moreover, plasma APRIL levels were positively associated with the apnea-hypopnea index, which represents the severity of OSA. Furthermore, plasma APRIL showed higher discriminatory accuracy in predicting the presence of OSA. CONCLUSIONS: Plasma APRIL levels were significantly associated with the occurrence of OSA and its severity. APRIL could be a plasma biomarker with a positive diagnostic value for inflammation and NF-KB-dependent inflammatory pathways activation in subjects with OSA. TRIAL REGISTRATION: The project was approved by the Chinese Clinical Trial Registry (No. ChiCTRROC-17011027).

[Analysis of Transport and Transformation Characteristics Between Dissolved Phosphorus and Particulate Phosphorus in Water of the Three Gorges Reservoir].

To understand the difference between transport coefficients of water runoff, sand discharge, and phosphorus flux in each subsection of a river, a judgement method for analyzing the characteristics of phosphorus transport and transformation in water of rivers was established in this study. Based on the measured data of water runoff, sand discharge, and phosphorus fraction concentrations in the water of the Three Gorges Reservoir (TGR) in January and July 2015, characteristics of phosphorus transport and transformation in the water were analyzed by using the conceptual method. The results showed that the predominant phosphorus fraction in water of the TGR was total dissolved phosphorus (TDP), which accounted for 51%-96% of total phosphorus in water. The TDP flux relative to runoff in the TGR decreased in January 2015 That was caused by the adsorption of TDP by suspended particles in the dry season. In contrast, TDP flux showed additive effect relative to water runoff in July 2015 due to exogenous water inputs with high TDP concentrations in the wet season. Both sand and total particulate phosphorus (TPP) presence in the water showed obvious sediment and retention characteristics during the two periods. The TPP flux presented an additive effect relative to sand discharge, meaning that the major transformation direction of phosphorus fractions was from TDP to TPP. The subsection between Qingxichang and Wanzhou was the main retention area of water, sand, and phosphorus in the TGR, which can be associated with the enhancement of phosphorus adsorption capacity caused by particle size reduction of suspended particles in the subsection.

TNFRSF11B: A potential plasma biomarker for diagnosis of obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) was characterized by chronic intermittent hypoxia, which was an independent risk factor for endothelial dysfunction. Circulating TNFRSF11B might play an important role in promoting endothelial cells dysfunction. We explored the role of plasma TNFRSF11B as a potential mechanism of endothelial dysfunction in OSA patients. METHODS: The study population consisted of 120 patients with varying severity of OSA and 40 control subjects. Plasma TNFRSF11B levels were measured using human Magnetic Luminex assay. RESULTS: Our data showed that plasma TNFRSF11B levels were significantly higher in patients with OSA. After adjusting confounding factors, plasma TNFRSF11B levels were independently associated with the presence of OSA (Beta:0.434, 95% CI: 664.096 to 1076.247; P < 0.001) and plasma TNFRSF11B levels were positively associated with the apnea-hypopnea index (Beta:0.486, 95% CI: 0.007 to 0.017; P < 0.001). Furthermore, plasma TNFRSF11B showed higher discriminatory accuracy in predicting the presence of OSA (AUC:0.964). CONCLUSIONS: Plasma TNFRSF11B levels were significantly associated with the presence of OSA and its severity. TNFRSF11B could be a plasma biomarker with a positive diagnostic value for premature vascular endothelial dysfunction in patients with OSA.

Rare Mutations in AHDC1 in Patients with Obstructive Sleep Apnea.

OBJECTIVES: Obstructive sleep apnea (OSA) is a common disorder influenced by genetic and environmental factors. Mutations of AT-hook DNA-binding motif containing 1 (AHDC1) gene have been implicated which could cause rare syndromes presenting OSA. This study aims to investigate some rare mutations of AHDC1 in Chinese Han individuals with OSA. PATIENTS AND METHODS: Three hundred and seventy-five patients with OSA and one hundred and nine control individuals underwent polysomnography. A targeted sequencing experiment was taken in 100 patients with moderate-to-severe OSA, and genotyping was taken in 157 moderate-to-severe OSA and 100 control individuals. The effect of mutations was validated by the luciferase reporter assay. RESULTS: One rare missense mutation (AHDC1: p.G1484D) and two mutations (c.-88C>T; c.-781C>G) in 5'-untranslated region (UTR) of AHDC1 were identified. The rare mutation (c.-781C>G) in 5'-UTR that was identified in several patients presenting more severe clinical manifestations affects expression of AHDC1. Conclusions. Our results revealed three rare mutations of AHDC1 in patients with OSA in Chinese Hanindividuals.

[Distribution of Phosphorus Fractions in Surface Sediments of Minjiang Mainstreams].

In recent years, the total phosphorus pollution in Minjiang River was serious, and the surface sediments of the Minjiang River also threatened water quality. To study the spatial distributions of phosphorus in the surface sediments of the Minjiang River, samples of surface sediments were collected upstream (Aba District) and downstream (Yibin District) of the Minjiang River in December, 2016. The sediments were analyzed with the modified sequential extraction method (SEDEX) to obtain six forms of phosphorus, including exchangeable phosphorus (Ex-P), exchangeable organic phosphorus (Org-P), iron-bound phosphorus (Fe-P), authigenic phosphorus (Ca-P), detrital phosphorus (De-P), and refractory phosphorus (Res-P). The results indicated that the contents of total phosphorus (TP) in surface sediments ranged from 522.17 µg ·g-1 to 979.22 µg ·g-1, which were far more than the soil phosphorus background values (700 µg ·g-1). The spatial distribution characteristics of the TP of surface sediments indicated that the TP concentrations in sediments at the Meishan sections (the middle reach of the Minjiang River) were higher than those in the other sections. This was related to the smaller particle size and higher OM contents in sediments in the Meishan sections. The main phosphorus forms in the sediments in the Minjiang River were Ca-P and De-P, with their concentrations accounting for 75% of TP in the sediments. The bio-available phosphorus, which included Ex-P, Org-P, and Fe-P, accounted for 0.31%-29.62% of TP in the sediments of the Minjiang River. The concentrations of bio-available phosphorus in sediments at the Meishan sections and Leshan sections (the middle reach) were highest, indicating that bio-available phosphorus in the surface sediments was high, and its potential environmental impact risks were higher.

[Effect of PMTG on atherosclerotic lesion formation and expression of ICAM-1 and VCAM-1 in ApoE-deficient mice].

OBJECTIVE: To study the protecting effect of polygoni multiflori total glycosides (PMTG) on the atherosclerotic lesion formation and the expression of ICAM-1, VCAM-1 in aolipoprotein (apo) E-deficient transgenic mice. METHOD: Thirty-two female apoE-deficienct mice were randomized into four groups: PMTG high dose group (150 mg x kg x d), low dose group (25 mg x kg x d), atorvastatin positive control group (5 mg x kg x d), and model group. At the end of the tenth week, all mice were killed. The serum levels of Total cholesterol (TC), Triglyceride (TG), High-density lipoprotein-cholesterol (LDL-C) were measured by enzyme dynamics method. Transmission electron microscopy (TEM) were used to observe the morphologic changes of aortic endothelia cell. The expressions of NF-kappaB were studied by SABC immunohistochemistry. RESULT: As compared with the model control group. (1) PMTG could reduce the levels of serum TC, TG significantly (P < 0.01), and LDL-C level significantly (P < 0.01). (2) It could increase the levels of serum NO and the anti-oxidation capacities significantly (P < 0.01), but reduce the levels of serum MDA significantly (P < 0.01). (3) PMTG could keep the normal morphology of aortic endothelial cell. (4) PMTG could deregulated the expression of NF-kappaB in aortic wall. CONCLUSION: PMTG could inhibit the occurrence and development of atherosclerotic lesions by its anti-oxidation abilities, which reduce LDL-C level. The low LDL-C level could deregulated the of expression of NF-kappaB, which could deregulated ICAM-1 and VCAM-1 in AopE-/-mice in aortic wall through.

Heavy metal pollution in tidal zones of Bohai Bay using the dated sediment cores.

Three sediment cores were collected in November 2003 from Dagu estuary to Qikou estuary. The main polluted heavy metals in the sediment of tidal zones for the Bohai Bay have been found by analyzing the relationship among the contents of heavy metals, the contents of geochemical elements (Fe, Al and Mn) and the size of grain. The dominating contaminative elements in tidal sediments of Bohai Bay are Pb, Zn and Cd. Their contents are higher than the corresponding upper limit of environmental background values and they have very faint correlation with the corresponding contents of geochemical elements and the size of grain, indicating the anthropogenic enrichment. Especially, the preliminary study on the pollution sources and the history of heavy metals in the Dagu estuary has been done using the dated results. The contamination by Zn and Cd also started in the middle 1950s, while the contamination by Pb appeared in the early 1940s. The pollution by Zn and Cd mainly originate from sewage discharge, while the pollution by Pb has many sources, like atmosphere deposition and industrial discharge.