Relationship between carotid intima-media thickness and aspirin resistance in patients with stable coronary artery disease / 西安交通大学学报(医学版)

Objective: To explore the relationship between carotid intima-media thickness (IMT) and aspirin resistance (AR) in patients with stable coronary artery disease (SCAD). Methods: A total of 316 SCAD patients were enrolled and divided into 3 groups according to IMT measured by carotid artery ultrasound: normal group (n=80), atherosclerosis group (n=102), and plaque group (n=134). Thrombelastogram instrument (TEG) was used to detect platelet aggregation rate (PAG) according to the level of PAG induced by adenosine diphosphate (ADP) to determination AR. The correlation between PAG level (ADP-PAG) and various factors was analyzed, and Logistic regression was used to analyze the risk factors for AR in SCAD patients. Results: The ADP-PAG level was higher in plaque group than in atherosclerosis group and normal group (59.12±11.44 vs. 53.34±10.78 vs. 49.58±11.62, P<0.01); the incidences of AR and aspirin semi-resistance were both higher than those in the other two groups. After adjustment for age and other factors, Logistic regression analysis showed that age (OR=4.08), female (OR=5.06), carotid atherosclerosis (OR=3.57) and carotid plaque (OR=6.35) were independent risk factors for predicting AR in SACD patients (P<0.05). ROC curve analysis revealed that the optimal cutoff of IMT to predict AR in SCAD patients was 1.95 mm, the sensitivity was 86.3%, the specificity was 62.9%, and the area under curve was 0.762 (95% CI: 0.670-0.853, P<0.01). Conclusion: Carotid atherosclerosis is closely related to aspirin resistance in patients with SCAD, and it is an independent risk factor for AR.

Mass Spectrometry-based Proteomics in Acute Respiratory Distress Syndrome: A Powerful Modality for Pulmonary Precision Medicine / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Acute respiratory distress syndrome (ARDS) is an acute and lethal clinical syndrome that is characterized by hypoxemic respiratory failure and diffuse alveolar inflammatory damage. This review aimed to search and discuss the mass spectrometry (MS)-based proteomic studies on different subsets of ARDS patients.</p><p><b>DATA SOURCES</b>Original research articles were collected from the PubMed database published in English up to December 2015.</p><p><b>STUDY SELECTION</b>The literature search was done using the term "(acute lung injury OR acute respiratory distress syndrome) AND (proteomics OR proteome OR mass spectrum OR differential in-gel electrophoresis OR two-dimensional polyacrylamide gel electrophoresis)". Related original research articles were included and were carefully analyzed.</p><p><b>RESULTS</b>Eight original proteomic researches on ARDS patients were found. The common proteomic modalities were two-dimensional (2D) high-performance liquid chromatography-based electronic spray ion-MS/MS and 2D-polyacrylamide gel electrophoresis/differential in-gel electrophoresis-based matrix-assisted laser desorption ionization-time of flight/MS. They compared the proteome between ARDS patients and normal controls and analyzed the dynamic changes of proteome at different ARDS stages or severity. The disturbed proteome in ARDS patients includes plasma acute-phase proteins, inflammatory/immune-associated proteins, and coagulation proteins.</p><p><b>CONCLUSIONS</b>Although several previous studies have provided some useful information about the lung proteome in ARDS patients and gained several interesting disease-associated biomarkers, clinical proteomic studies in ARDS patients are still in the initial stage. An increased cooperation is still needed to establish a global and faithful database containing disease-specific proteome from the largest ARDS subsets.</p>

Incidence and clinical characteristics of pulmonary hypertension in patients with idiopathic pulmonary fibrosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pulmonary hypertension (PH) frequently complicates the course of idiopathic pulmonary fibrosis (IPF) patients and is associated with significantly worse outcomes. The aim of the present study was to investigate the incidence of PH in IPF patients and evaluate the correlation between clinical parameters and systolic pulmonary artery pressure (sPAP).</p><p><b>METHODS</b>Hospitalized patients with IPF, who were evaluated for sPAP by Doppler echocardiography from January 2004 to December 2011, were enrolled in our study. Patients were defined as PH by an estimated sPAP > 50 mmHg and graded as PH likely, PH possible and PH unlikely, based on the 2009 European Society of Cardiology/European Respiratory Society PH Guidelines. The correlations between clinical parameters and sPAP were analyzed by multiple linear regression.</p><p><b>RESULTS</b>Totally, 119 IPF patients were enrolled in our study and 28 (23.5%), 20 (16.8%) and 71 (59.7%) patients were PH likely, PH possible and PH unlikely, respectively. Borg dyspnea score was positively correlated with sPAP, r = 0.467, P < 0.001. Oxygen saturation was negatively correlated with sPAP, r = -0.416, P < 0.001. Diffusing capacity of the lung for carbon monoxide percentage predicted was negatively correlated with sPAP, r = -0.424, P = 0.003. N-terminal fragment of pro-brain natriuretic peptide and pulmonary artery width was positively correlated with sPAP, r = 0.452, P = 0.011 and r = 0.513, P < 0.001, respectively.</p><p><b>CONCLUSIONS</b>The incidence of PH in IPF patients was 23.5% in a single center of China. PH may worsen the dyspnea, right heart dysfunction and decrease the life quality of the patients with IPF.</p>

Relationship between expression of endothelial nitric oxide synthase and NADPH oxidase in lungs of mice exposed to chronic hypoxia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the relationship between the expression of endothelial nitric oxide synthase (eNOS) and NADPH oxidase (NOX) in the lungs of mice treated by chronic hypoxic exposure.</p><p><b>METHODS</b>Thirty male wild-type (WT) C57Bl/6 mice and thirty male eNOS-knockout (KO) C57BL/6 mice were randomly divided into normoxic groups (exposed to normoxia for 7 days or 21 days), hypoxic groups (exposed to 10% oxygen for 7 days or 21 days), and treatment groups (exposed to 10% oxygen and orally administrated 10 mmol/L 4-hydroxy TEMPO in drinking water for 7 days or 21 days) (n=6 in each group). The remodeling of the small pulmonary arteries was evaluated by the percentage of media wall thickness (MT%). The weight ratio of right ventricle to left ventricle plus septum (RV/[LV+S]) was calculated to evaluate the hypertrophy of right ventricle. Real-time PCR was used to measure the mRNA expression of NOX2, NOX4, and eNOS in mouse lungs. ELISA was used to determine the concentration of reactive oxygen species (ROS) in mouse lungs.</p><p><b>RESULTS</b>In WT mice and KO mice, the hypoxic groups had significantly increased pulmonary vascular remodeling and RV/[LV+S] compared with the normoxic and treatment groups (P<0.05), but there were no significant differences between the normoxic and treatment groups (P>0.05). In WT mice, the hypoxic and treatment groups had significantly lower ROS concentrations than the normoxic group (P<0.05), but there were no significant differences between the hypoxic and treatment groups (P>0.05). In WT mice, the mRNA expression of eNOS, NOX2, and NOX4 was significantly higher in the hypoxic group than in the normoxic group (P<0.05), and 4-hydroxy TEMPO reversed their over-expression. In the normoxic group, the KO mice had significantly higher NOX2 and NOX4 mRNA expression than the WT mice (P<0.05); in KO mice, the hypoxic group showed no significant changes in NOX4 mRNA expression (P>0.05), but had significantly reduced NOX2 mRNA expression (P<0.05), as compared with the normoxic group; the treatment group had reduced expression of NOX2 mRNA expression and increased NOX4 mRNA expression (P<0.05), as compared with the hypoxic group.</p><p><b>CONCLUSIONS</b>eNOS plays a key role in the regulation of expression of NOX2 and NOX4 in the lungs exposed to hypoxia. It suggests that NOX and eNOS may physically interact with one another in pulmonary vascular remodeling induced by chronic hypoxia.</p>

Polymorphism analysis of the ABCA3 gene: association with neonatal respiratory distress syndrome in preterm infants / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous reports indicated that mutations in the adenosine triphosphate (ATP)-binding cassette transporter A3 (ABCA3) cause fatal respiratory failure in term infants, and common ABCA3 gene polymorphisms have been characterized at the population level in Caucasians. But the role of ABCA3 in relation to respiratory distress syndrome (RDS) in newborns has not been evaluated within a Chinese population. The aim of this study was to analyze eight single-nucleotide polymorphisms (SNPs) of the ABCA3 gene, and to assess the ABCA3 gene as a candidate gene for susceptibility to RDS in newborns.</p><p><b>METHODS</b>Eight SNPs were selected and genotyped in 203 newborns. The data analysis and statistical tests were used for allele frequencies, haplotype and Hardy-Weinberg equilibrium pairwise linkage disequilibrium measures.</p><p><b>RESULTS</b>There was a haplotype association with SNP rs313909 and SNP rs170447, but no haplotype association was observed among the newborns with and without RDS (P > 0.05). The minor allele frequency (G) of the coding SNP (cSNP) rs323043 (P585P) was significantly increased in preterm infants with RDS.</p><p><b>CONCLUSION</b>There is an association between a synonymous cSNP rs323043 and the development of RDS.</p>

Type 2 epithelial mesenchymal transition in vivo: truth or pitfalls? / 中华医学杂志(英文版)

Epithelial-mesenchymal transition (EMT) is a process by which fully differentiated epithelial cells undergo a phenotypic conversion and assume a mesenchymal cell phenotype, including elongated morphology, enhanced migratory and invasiveness capacity, and greatly increased production of extracellular matrix (ECM) components. The EMTs associated with wound healing, tissue regeneration, and organ fibrosis are termed as type 2 EMT. Over the past two decades, emerging evidence suggested that injured epithelial cells, via type 2 EMT, may serve as important sources of fibroblasts and contribute to organ fibrosis, such as kidney, liver, lung and eyes. There is perhaps no doubt that adult epithelial cells can undergo EMT in vitro in response to transforming growth factor (TGF)-β1 and other inflammatory or pro-fibrotic stimuli. However, whether type 2 EMT really occurs in vivo, whethers it is actually a source of functional and activated interstitial fibroblasts and whether it contributes to tissue fibrosis have already been the subjects of heated debate. In this review, we will describe the main features of EMT, the major findings of type 2 EMT in vitro, the evidences for and against type 2 EMT in vivo and discuss the heterogeneity and pitfalls of the techniques used to detect EMT during fibrotic diseases. We suggest that in order to ascertain the existence of type 2 EMT in vivo, different proper phenotype markers of epithelial and mesenchymal cells should be jointly used and cell lineage tracking techniques should be standardized and avoid false positives. Finally, we believe that if EMT really occurs and contributes to tissue fibrosis, efforts should be made to block or reverse EMT to attenuate fibrotic process.

Epigenetics in neonatal diseases / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To review the role of epigenetic regulation in neonatal diseases and better understand Barker's "fetal origins of adult disease hypothesis".</p><p><b>DATA SOURCES</b>The data cited in this review were mainly obtained from the articles published in Medline/PubMed between January 1953 and December 2009.</p><p><b>STUDY SELECTION</b>Articles associated with epigenetics and neonatal diseases were selected.</p><p><b>RESULTS</b>There is a wealth of epidemiological evidence that lower birth weight is strongly correlated with an increased risk of adult diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular disease. This phenomenon of fetal origins of adult disease is strongly associated with fetal insults to epigenetic modifications of genes. A potential role of epigenetic modifications in congenital disorders, transient neonatal diabetes mellitus (TNDM), intrauterine growth retardation (IUGR), and persistent pulmonary hypertension of the newborn (PPHN) have been studied.</p><p><b>CONCLUSIONS</b>Acknowledgment of the role of these epigenetic modifications in neonatal diseases would be conducive to better understanding the pathogenesis of these diseases, and provide new insight for improved treatment and prevention of later adult diseases.</p>

Epidemiology of respiratory distress and the illness severity in late preterm or term infants: a prospective multi-center study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The severity of respiratory distress was associated with neonatal prognosis. This study aimed to explore the clinical characteristics, therapeutic interventions and short-term outcomes of late preterm or term infants who required respiratory support, and compare the usage of different illness severity assessment tools.</p><p><b>METHODS</b>Seven neonatal intensive care units in tertiary hospitals were recruited. From November 2008 to October 2009, neonates born at ≥ 34 weeks' gestational age, admitted at < 72 hours of age, requiring continuous positive airway pressure (CPAP) or mechanical ventilation for respiratory support were enrolled. Clinical data including demographic variables, underlying disease, complications, therapeutic interventions and short-term outcomes were collected. All infants were divided into three groups by Acute care of at-risk newborns (ACoRN) Respiratory Score < 5, 5 - 8, and > 8.</p><p><b>RESULTS</b>During the study period, 503 newborn late preterm or term infants required respiratory support. The mean gestational age was (36.8 ± 2.2) weeks, mean birth weight was (2734.5 ± 603.5) g. The majority of the neonates were male (69.4%), late preterm (63.3%), delivered by cesarean section (74.8%), admitted in the first day of life (89.3%) and outborn (born at other hospitals, 76.9%). Of the cesarean section, 51.1% were performed electively. Infants in the severe group were more mature, had the highest rate of elective cesarean section, Apgar score < 7 at 5 minutes and resuscitated with intubation, the in-hospital mortality increased significantly. In total, 58.1% of the patients were supported with mechanical ventilation and 17.3% received high frequency oscillation. Adjunctive therapies were commonly needed. Higher rate of infants in severe group needed mechanical ventilation or high frequency oscillation, volume expansion, bicarbonate infusion or vasopressors therapy (P < 0.05). The incidence of complications was also increased significantly in severe group (P < 0.05). The in-hospital mortality in the severe group was significantly higher than other two groups (P < 0.05). ACoRN Respiratory Score was correlated with Score for Neonatal Acute Physiology-Version II (SNAP-II) (P < 0.01). High gestational age, high SNAP-II score and oxygenation index (OI), and Apgar score at 5 minutes < 5 were independent risks for death.</p><p><b>CONCLUSIONS</b>Neonatal respiratory distress is still a common cause of hospitalization in China. Illness severity assessment is important for the management. ACoRN Respiratory Score which correlated with SNAP-II score is easy to use and may be helpful in facilitating the caregivers in local hospital to identify the early signs and make the transfer decision promptly.</p>

Modulation of leak K(+) channel in hypoglossal motoneurons of rats by serotonin and/or variation of pH value / 生理学报

The cloned TWIK-related acid-sensitive K(+) channel (TASK-1) is sensitive to the pH changes within physiological pH range (pK~7.4). Recently, the native TASK-1-like channel was suggested to be the main contributor to the background (or leak) K(+) conductance in the motoneurons of the brain stem. Serotonin (5-HT) and variation of pH value in perfused solution could modulate these currents. Here we aimed to examine the properties and modulation of the currents by serotonin or variation of pH value in hypoglossal motoneurons of rats. Transverse slices were prepared from the brainstem of neonatal Sprague-Dawley rats (postnatal days 7-8). Hypoglossal motoneurons were used for the study. The leak K(+) current (TASK-1-like current) and hyperpolarization-activated cationic current (I(h)) were recorded with the whole-cell patch-clamp technique. The results showed that these currents were inhibited by acidified artificial cerebrospinal fluid (ACSF, pH 6.0) and activated by alkalized ACSF (pH 8.5). 5-HT (10 mumol/L) significantly inhibited both leak K(+) current and I(h) with depolarization of membrane potential and the occurrence of oscillation and/or spikes. Bath application of Ketanserine, an antagonist of 5-HT₂ receptor, reversed or reduced the inhibitory effect of acidified solution on leak K(+) current and I(h). The results suggest that 5-HT₂ receptors mediate the effects of acidified media on leak K(+) current and I(h) in hypoglossal motoneurons.

Morphogenesis in formative process in vitro from Rehmannia glutinosa / 中国中药杂志

<p><b>OBJECTIVE</b>To study the morphogenesis in formative process of tuberous root in vitro from Rehmannia glutinosa and compare the anatomical shape of tuberous root with nature term R. glutinosa.</p><p><b>METHOD</b>Tuberous roots of different vegetal phase were cut and dyed, then made into paraffin cuts and observed microscope.</p><p><b>RESULT AND CONCLUSION</b>In anatomical shape, nature R. glutinosa and tuberous root were the same, which showed that no structural variation occurred in tuberous root induced process.</p>