Publications by authors named "Lu Hou"

33 Publications

Recent developments on PET radiotracers for TSPO and their applications in neuroimaging.

Acta Pharm Sin B 2021 Feb 25;11(2):373-393. Epub 2020 Aug 25.

Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA.

The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.
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http://dx.doi.org/10.1016/j.apsb.2020.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893127PMC
February 2021

Sex and gender differences in presentation, treatment and outcomes in acute coronary syndrome, a 10 year study from a multi-ethnic Asian population: The Malaysian National Cardiovascular Disease Database-Acute Coronary Syndrome (NCVD-ACS) registry.

PLoS One 2021 8;16(2):e0246474. Epub 2021 Feb 8.

University Malaya Medical Centre, Kuala Lumpur, Malaysia.

Background: Sex and gender differences in acute coronary syndrome (ACS) have been well studied in the western population. However, limited studies have examined the trends of these differences in a multi-ethnic Asian population.

Objectives: To study the trends in sex and gender differences in ACS using the Malaysian NCVD-ACS Registry.

Methods: Data from 24 hospitals involving 35,232 ACS patients (79.44% men and 20.56% women) from 1st. Jan 2012 to 31st. Dec 2016 were analysed. Data were collected on demographic characteristics, coronary risk factors, anthropometrics, treatments and outcomes. Analyses were done for ACS as a whole and separately for ST-segment elevation myocardial infarction (STEMI), Non-STEMI and unstable angina. These were then compared to published data from March 2006 to February 2010 which included 13,591 ACS patients (75.8% men and 24.2% women).

Results: Women were older and more likely to have diabetes mellitus, hypertension, dyslipidemia, previous heart failure and renal failure than men. Women remained less likely to receive aspirin, beta-blocker, angiotensin-converting enzyme inhibitor (ACE-I) and statin. Women were less likely to undergo angiography and percutaneous coronary intervention (PCI) despite an overall increase. In the STEMI cohort, despite a marked increase in presentation with Killip class IV, women were less likely to received primary PCI or fibrinolysis and had longer median door-to-needle and door-to-balloon time compared to men, although these had improved. Women had higher unadjusted in-hospital, 30-Day and 1-year mortality rates compared to men for the STEMI and NSTEMI cohorts. After multivariate adjustments, 1-year mortality remained significantly higher for women with STEMI (adjusted OR: 1.31 (1.09-1.57), p<0.003) but were no longer significant for NSTEMI cohort.

Conclusion: Women continued to have longer system delays, receive less aggressive pharmacotherapies and invasive treatments with poorer outcome. There is an urgent need for increased effort from all stakeholders if we are to narrow this gap.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246474PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869989PMC
February 2021

Positron Emission Tomography Imaging of the Endocannabinoid System: Opportunities and Challenges in Radiotracer Development.

J Med Chem 2021 01 30;64(1):123-149. Epub 2020 Dec 30.

Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, and Department of Radiology, Harvard Medical School, Boston, Massachusetts 02114, United States.

The endocannabinoid system (ECS) is involved in a wide range of biological functions and comprises cannabinoid receptors and enzymes responsible for endocannabinoid synthesis and degradation. Over the past 2 decades, significant advances toward developing drugs and positron emission tomography (PET) tracers targeting different components of the ECS have been made. Herein, we summarized the recent development of PET tracers for imaging cannabinoid receptors 1 (CB1R) and 2 (CB2R) as well as the key enzymes monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), particularly focusing on PET neuroimaging applications. State-of-the-art PET tracers for the ECS will be reviewed including their chemical design, pharmacological properties, radiolabeling, as well as preclinical and human PET imaging. In addition, this review addresses the current challenges for ECS PET biomarker development and highlights the important role of PET ligands to study disease pathophysiology as well as to facilitate drug discovery.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877880PMC
January 2021

Genome-wide association studies of fruit quality traits in jujube germplasm collections using genotyping-by-sequencing.

Plant Genome 2020 11 7;13(3):e20036. Epub 2020 Aug 7.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, National Engineering Laboratory for Tree Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083, China.

Chinese jujube (Ziziphus jujuba Mill.) is an important fruit crop and harbors many highly diverse traits of potential economic importance. Fruit size, stone size, and fruit cracking have an important influence on the commercial value of jujube. This study is the first to conduct a genome-wide association study (GWAS) on 180 accessions of jujube and focuses on locating single-nucleotide polymorphisms (SNPs) associated with nine important fruit quality traits. Genotyping was performed using genotyping-by-sequencing and 4651 high-quality SNPs were identified. A genetic diversity analysis revealed the presence of three distinct groups, and rapid linkage disequilibrium decay was observed in this jujube population. Using a mixed linear model, a total of 45 significant SNP-trait associations were detected, among which 33 SNPs had associations with fruit size-related traits, nine were associated with stone size-related traits, and three with fruit cracking-related traits. In total, 21 candidate genes involved in cell expansion, abiotic stress responses, hormone signaling, and growth development were identified from the genome sequences of jujube. These results are useful as basic data for GWAS of other jujube traits, and these significant SNP loci and candidate genes should aid marker-assisted breeding and genomic selection of improved jujube cultivars.
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http://dx.doi.org/10.1002/tpg2.20036DOI Listing
November 2020

Synthesis and preliminary evaluation of a novel positron emission tomography (PET) ligand for imaging fatty acid amide hydrolase (FAAH).

Bioorg Med Chem Lett 2020 11 27;30(21):127513. Epub 2020 Aug 27.

Center of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China. Electronic address:

Fatty acid amide hydrolase (FAAH) exerts its main function in the catabolism of the endogenous chemical messenger anandamide (AEA), thus modulating the endocannabinoid (eCB) pathway. Inhibition of FAAH may serve as an effective strategy to relieve anxiety and possibly other central nervous system (CNS)-related disorders. Positron emission tomography (PET) would facilitate us to better understand the relationship between FAAH in certain disease conditions, and accelerate clinical translation of FAAH inhibitors by providing in vivo quantitative information. So far, most PET tracers show irreversible binding patterns with FAAH, which would result in complicated quantitative processes. Herein, we have identified a new FAAH inhibitor (1-((1-methyl-1H-indol-2-yl)methyl)piperidin-4-yl)(oxazol-2-yl)methanone (8) which inhibits the hydrolysis of AEA in the brain with high potency (IC value 11 nM at a substrate concentration of 0.5 µM), and without showing time-dependency. The PET tracer [C]8 (also called [C]FAAH-1906) was successfully radiolabeled with [C]MeI in 17 ± 6% decay-corrected radiochemical yield (n = 7) with >74.0 GBq/μmol (2 Ci/μmol) molar activity and >99% radiochemical purity. Ex vivo biodistribution and blocking studies of [C]8 in normal mice were also conducted, indicating good brain penetration, high brain target selectivity, and modest to excellent target selectivity in peripheral tissues. Thus, [C]8 is a potentially useful PET ligand with enzyme inhibitory and target binding properties consistent with a reversible mode of action.
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http://dx.doi.org/10.1016/j.bmcl.2020.127513DOI Listing
November 2020

Synthesis of monodisperse water-stable surface Pb-rich CsPbCl nanocrystals for efficient photocatalytic CO reduction.

Nanoscale 2020 Jun;12(22):11842-11846

Key Laboratory for Ultrafine Materials of Ministry of Education; Shanghai Engineering Research Center of Hierarchical Nanomaterials; School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China and School of Chemical Engineering, East China University of Science and Technology, Shanghai 200237, China.

Surface Pb-rich lead halide (CsPbCl3) perovskite nanocrystals (NCs) with high stability and monodispersity in water have been synthesized using a general and convenient liquid-solid interpenetration (LSI) method. In this process, water molecules permeate into the solid CsPbCl3 NC layers and slowly dissolve the Cs+ and Cl- ions on the surface of CsPbCl3 NCs. The Cs+ and Cl- ions in water inhibit the decomposition rate of CsPbCl3 NCs, inducing surface Pb-rich layers. The surface Pb-rich structure increases the photoluminescence (PL) lifetimes and improves the photocatalytic performances of lead halide perovskite NCs. Under simulated solar irradiation, the largest rate of CO2 photoreduction from surface Pb-rich Ni-doped CsPbCl3 NCs reaches up to 169.37 μmol g-1 h-1. This study provides an effective general strategy to design stable lead halide perovskite quantum dots (QDs) for their wide applications.
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http://dx.doi.org/10.1039/d0nr02917cDOI Listing
June 2020

A Group of Complexes Based on PAMAM and Quantum Dots Used in Clinical Immunoassays.

Nanoscale Res Lett 2020 Apr 3;15(1):71. Epub 2020 Apr 3.

Key Laboratory for Molecular Enzymology & Engineering, the Ministry of Education, Jilin University, Changchun, 130012, Jilin, China.

We report a group of complexes used in clinical immunoassays. The complexes include a PAMAM-conjugated goat anti-rabbit IgG and a QDs-conjugated goat anti-mouse IgG. When rabbit anti-antigen and mouse anti-antigen are added, the corresponding antigen will be detected. The experiment, using the complexes, is simple, convenient, short in time, and short in steps. It is also applicable to different experiment methods, like to be used with FCM (flow cytometry), ICC (immunocytochemistry), and IHC (immunohistochemistry) to detect many kinds of antigens.
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http://dx.doi.org/10.1186/s11671-020-3291-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125291PMC
April 2020

Folate-Mediated Targeted Delivery of siPLK1 by Leucine-Bearing Polyethylenimine.

Int J Nanomedicine 2020 2;15:1397-1408. Epub 2020 Mar 2.

College of Life Science, Jilin University, Changchun, Jilin 130012, People's Republic of China.

Background: siRNA-mediated polo-like kinase 1 (PLK1) silencing has been proposed as a promising therapeutic method for multiple cancers. However, the clinic application of this method is still hindered by the low specific delivery of siPLK1 to desired tumor lesions. Herein, folate (FA)-modified and leucine-bearing polyethylenimine was successfully synthesized and showed excellent targeted silencing to folate receptor overexpressed cells.

Materials And Methods: The condensation of siPLK1 by FA-N-Ac-L-Leu-PEI (NPF) was detected by the gel retardation assay. The targeted and silencing efficiency was evaluated by flow cytometry and confocal laser scanning microscope. The PLK1 expressions at gene or protein levels were detected by quantitative real-time PCR and Western blotting assay. Further impacts of the PLK1 silencing on cell viability, cell cycle, migration, and invasion were studied by MTT, colony formation, wound healing and transwell assays.

Results: The NPF and siPLK1 could efficiently assemble to stable nanoparticles at a weight ratio of 3.0 and showed excellent condensation and protection effect. Owing to the FA-mediated targeted delivery, the uptake and silencing efficiency of NPF/siPLK1 to SGC-7901 cells was higher than that without FA modification. Moreover, NPF-mediated PLK1 silencing showed significant antitumor activity in vitro. The anti-proliferation effect of PLK1 silencing was induced via the mitochondrial-dependent apoptosis pathway with the cell cycle arrest of 45% at G2 phase and the apoptotic ratio of 28.3%.

Conclusion: FA-N-Ac-L-Leu-PEI (NPF) could generate targeted delivery siPLK1 to FA receptor overexpressed cells and dramatically downregulate the expression of PLK1 expression.
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http://dx.doi.org/10.2147/IJN.S227289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060029PMC
June 2020

Interfering cellular lactate homeostasis overcomes Taxol resistance of breast cancer cells through the microRNA-124-mediated lactate transporter (MCT1) inhibition.

Cancer Cell Int 2019 24;19:193. Epub 2019 Jul 24.

The 1st Breast Surgical Department, Affiliated Shengjing Hospital of China Medical University, Shenyang, 110004 Liaoning China.

Background: Breast cancer, the most common invasive cancer of women, is a malignant neoplasm and the second main cause of cancer death. Resistance to paclitaxel (Taxol), one of the frequently used chemotherapy agents for breast cancer, presents a major clinical challenge. Recent studies revealed that metabolic alterations of cancer cells play important roles in chemo-resistance.

Materials And Methods: In this study, Human breast cancer cells, BT474, SKBR3 and MCF7 were used to study the causal relationship between the lactate exporter, MCT1 (SLC16A1)-modulated glucose metabolism and Taxol resistance of breast cancer cells. Taxol resistant breast cancer cells were established. The intracellular lactate and extracellular lactate levels as well glucose uptake and oxygen consumption were measured. MicroRNA-124 expressions were detected by qRT-PCR from both breast cancer patient samples and breast cancer cells. Target of miR-124 was predicted and verified by Western blot and luciferase assay. An xenograft mice model was established and evaluated for the in vivo tumor therapeutic effects of MCT1 inhibitor plus microRNA-124 treatments.

Results: Low toxic Taxol treatments promoted cellular glucose metabolism and intracellular lactate accumulation with upregulated lactate dehydrogenase-A (LDHA) and MCT1 expressions. By establishing Taxol resistant breast cancer cell line, we found Taxol resistant cells exhibit upregulated LDHA and MCT1 expressions. Furthermore, glucose consumption, lactate production and intracellular ATP were elevated in Taxol resistant MCF7 cells compared with their parental cells. The miR-124, a tumor suppressive miRNA, was significantly downregulated in Taxol resistant cells. Luciferase assay and q-RT-PCR showed MCT1 is a direct target of miR-124 in both breast cancer cell lines and patient specimens. Moreover, co-treatment of breast cancer cells with either MCT1 inhibitor or miR-124 plus Taxol led to synergistically cytotoxic effects. Importantly, based on in vitro and in vivo results, inhibition of MCT1 significantly sensitized Taxol resistant cells. Finally, rescue experiments showed restoration of MCT1 in miR-124 overexpressing cells promoted Taxol resistance.

Conclusions: This study reveals a possible role of miRNA-214-mediated Taxol resistance, contributing to identify novel therapeutic targets against chemoresistant breast cancers.
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http://dx.doi.org/10.1186/s12935-019-0904-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657142PMC
July 2019

Zymolytic Grain Extract (ZGE) Significantly Extends the Lifespan and Enhances the Environmental Stress Resistance of .

Int J Mol Sci 2019 Jul 16;20(14). Epub 2019 Jul 16.

School of Life Science, Jilin University, Changchun 130012, China.

Many reports have shown that grains play an important role in our daily lives and can provide energy and nutrients to protect us from various diseases, and they are considered to be indispensable parts of our lives. It has been reported that some constituents in grains could exert functional effects against HIV infections and multiple cancers. Zymolytic grain can produce some new useful molecules and thus support the cell nutrients in the human body. In this study, the effects of zymolytic grain extract (ZGE) supernatants on the changes of nematode indicators were investigated, including lifespan, self-brood size, and body length in environmental conditions (temperature, ultraviolet radiation or 5-fluoro-2'-deoxyuridine (FUDR) stimuli). We found that, compared to the control group, the ZGE supernatant-feeding group could prolong the lifespan of nematodes under normal conditions. More importantly, ZGE supernatants could improve the ability of nematodes to resist stress. When the concentration of FUDR was 400 or 50 μM, the ZGE supernatant-feeding group could prolong lifespan by an average of 38.4% compared to the control group, and the eggs of the ZGE supernatant-feeding group could hatch and develop into adults. These results indicated that ZGE could protect from external stress and thus prolong their lifespan and improve the physiological state of nematodes. Therefore, ZGE supernatant has potential to be used as a nutritional product in antioxidant and anti-aging research.
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http://dx.doi.org/10.3390/ijms20143489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678847PMC
July 2019

Postinfarction exercise training alleviates cardiac dysfunction and adverse remodeling via mitochondrial biogenesis and SIRT1/PGC-1α/PI3K/Akt signaling.

J Cell Physiol 2019 12 11;234(12):23705-23718. Epub 2019 Jun 11.

Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, Shaanxi, China.

Exercise training mitigates cardiac pathological remodeling and dysfunction caused by myocardial infarction (MI), but its underlying cellular and molecular mechanisms remain elusive. Our present study in an in vivo rat model of MI determined the impact of post-MI exercise training on myocardial fibrosis, mitochondrial biogenesis, antioxidant capacity, and ventricular function. Adult male rats were randomized into: (a) Sedentary control group; (b) 4-week treadmill exercise training group; (c) Sham surgery group; (d) MI group with permanent ligation of left anterior descending coronary artery and kept sedentary during post-MI period; and (e) post-MI 4-week exercise training group. Results indicated that exercise training significantly improved post-MI left ventricular function and reduced markers of cardiac fibrosis. Exercise training also significantly attenuated MI-induced mitochondrial damage and oxidative stress, which were associated with enhanced antioxidant enzyme expression and/or activity and total antioxidant capacity in the heart. Interestingly, the adaptive activation of the SIRT1/PGC-1α/PI3K/Akt signaling following MI was further enhanced by post-MI exercise training, which is likely responsible for exercise-induced cardioprotection and mitochondrial biogenesis. In conclusion, this study has provided novel evidence on the activation of SIRT1/PGC-1α/PI3K/Akt pathway, which may mediate exercise-induced cardioprotection through reduction of cardiac fibrosis and oxidative stress, as well as improvement of mitochondrial integrity and biogenesis in post-MI myocardium.
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http://dx.doi.org/10.1002/jcp.28939DOI Listing
December 2019

Genome-wide identification, characterization, and expression analysis of the expansin gene family in Chinese jujube (Ziziphus jujuba Mill.).

Planta 2019 Mar 8;249(3):815-829. Epub 2018 Nov 8.

National Engineering Laboratory for Tree Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083, China.

Main conclusion 30 expansin genes were identified in the jujube genome. Phylogenetic analysis classified expansins into 17 subgroups. Closely related expansins share a conserved gene structure. ZjEXPs had different expression patterns in different tissues. Plant-specific expansins were first discovered as pH-dependent cell-wall-loosening proteins involved in diverse physiological processes. No comprehensive analysis of the expansin gene family has yet been carried out at the whole genome level in Chinese jujube (Ziziphus jujuba Mill.). In this study, 30 expansin genes were identified in the jujube genome. These genes, which were distributed with varying densities across 10 of the 12 jujube chromosomes, could be divided into four subfamilies: 19 ZjEXPAs, 3 ZjEXPBs, 1 ZjEXLA, and 7 ZjEXLBs. Phylogenetic analysis of expansin genes in Arabidopsis, rice, apple, grape, and jujube classified these genes into 17 subgroups. Members of the same subfamily and subgroup shared conserved gene structure and motif compositions. Homology analysis identified 20 homologous gene pairs between jujube and Arabidopsis. Further analysis of ZjEXP gene promoter regions uncovered various growth, development and stress-responsive cis-acting elements. Expression analysis and transcript profiling revealed that ZjEXPs had different expression patterns in different tissues at various developmental stages. ZjEXPA4 and ZjEXPA6 were highly expressed in young fruits, ZjEXPA3 and ZjEXPA5 were significantly expressed in flowers, and ZjEXPA7 was specifically expressed in young leaves. The results of this study, the first systematic analysis of the jujube expansin gene family, can serve as a strong foundation for further elucidation of the physiological functions and biological roles of jujube expansin genes.
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http://dx.doi.org/10.1007/s00425-018-3020-9DOI Listing
March 2019

De Novo Transcriptome Assembly and Population Genetic Analyses for an Endangered Chinese Endemic (Aceraceae).

Genes (Basel) 2018 Jul 27;9(8). Epub 2018 Jul 27.

National Engineering Laboratory for Tree Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China.

(P. C. Tsoong) is a rare and highly endangered plant in China. Because of the lack of genomic information and the limited number of available molecular markers, there are insufficient tools to determine the genetic diversity of this species. Here, 93,305 unigenes were obtained by multiple assembled contigs with a transcriptome sequencing program. Furthermore, 12,819 expressed sequence tag-derived simple sequence repeat (EST-SSR) markers were generated, 300 were randomly selected and synthesized, 19 primer pairs were identified as highly polymorphic (average number of alleles (N) = 8, expected heterozygosity (H) = 0.635, polymorphism information content (PIC) = 0.604) and were further used for population genetic analysis. All 261 samples were grouped into two genetic clusters by UPGMA, a principal component analyses and a STRUCTURE analyses. A moderate level of genetic differentiation (genetic differentiation index (F) = 0.059⁻0.116, gene flow = 1.904⁻3.993) among the populations and the major genetic variance (81.01%) within populations were revealed by the AMOVA. Based on the results, scientific conservation strategies should be established using in situ and ex situ conservation strategies. The study provides useful genetic information for the protection of precious wild resources and for further research on the origin and evolution of this endangered plant and its related species.
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http://dx.doi.org/10.3390/genes9080378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115825PMC
July 2018

Inspiratory muscle training is associated with decreased postoperative pulmonary complications: Evidence from randomized trials.

J Thorac Cardiovasc Surg 2018 09 7;156(3):1290-1300.e5. Epub 2018 Apr 7.

Department of Cardiac Surgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

Objective: To determine whether preoperative inspiratory muscle training was associated with a significant difference in the rate of postoperative pulmonary adverse outcomes in patients undergoing cardiothoracic or upper abdominal surgery using trial sequential analysis to correct for the risk of random errors.

Methods: We systematically reviewed the Excerpta Medica database, PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials for randomized controlled trials evaluating inspiratory muscle training before cardiothoracic or upper abdominal surgery. Outcome measures included postoperative pulmonary complications, length of hospital stay, maximum inspiratory pressure, and quality of life. A random-effects model was used to estimate relative risks with 95% confidence intervals (CIs). We used trial sequential analysis to calculate a diversity-adjusted required information size for meta-analysis.

Results: Thirteen randomized controlled trials were included in the meta-analysis for a total of 784 patients. Compared with the standard care group, the inspiratory muscle training group exhibited significantly decreased postoperative pulmonary complications (risk ratio, 0.59; 95% CI, 0.47-0.74). Trial sequential analysis indicated that the cumulative Z curve crossed both the conventional boundary and the trial sequential monitoring boundary for benefit. The length of hospital stay was reduced in the inspiratory muscle training group (mean difference, -1.15 days; 95% CI, -2.10 to 0.20), and the maximum inspiratory pressure was significantly improved at the end of the preoperative training (mean difference, 13.66; 95% CI, 3.88-23.44). The quality of life outcome was unavailable in most of the studies.

Conclusions: Preoperative inspiratory muscle training resulted in significantly improved maximum inspiratory pressure and was associated with decreased postoperative pulmonary complications.
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http://dx.doi.org/10.1016/j.jtcvs.2018.02.105DOI Listing
September 2018

Genetic Evaluation of Natural Populations of the Endangered Conifer Using Microsatellite Markers by Restriction-Associated DNA Sequencing.

Genes (Basel) 2018 Apr 17;9(4). Epub 2018 Apr 17.

National Engineering Laboratory for Tree Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China.

Nakai is an endangered conifer of high economic and ecological value in Jilin Province, China. However, studies on its population structure and conservation genetics have been limited by the lack of genomic data. Here, 37,761 microsatellites (simple sequence repeat, SSR) were detected based on 875,792 de novo-assembled contigs using a restriction-associated DNA (RAD) approach. Among these SSRs, 300 were randomly selected to test for polymorphisms and 96 obtained loci were able to amplify a fragment of expected size. Twelve polymorphic SSR markers were developed to analyze the genetic diversity and population structure of three natural populations. High genetic diversity (mean = 5.481, = 0.548) and moderate population differentiation (pairwise = 0.048–0.078, = 2.940–4.958) were found in this species. Molecular variance analysis suggested that most of the variation (83%) existed within populations. Combining the results of STRUCTURE, principal coordinate, and neighbor-joining analysis, the 232 individuals were divided into three genetic clusters that generally correlated with their geographical distributions. Finally, appropriate conservation strategies were proposed to protect this species. This study provides genetic information for the natural resource conservation and utilization of . and will facilitate further studies of the evolution and phylogeography of the species.
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http://dx.doi.org/10.3390/genes9040218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924560PMC
April 2018

A Case of Constrictive Pericarditis Associated with Melioidosis in an Immunocompetent Patient Treated by Pericardiectomy.

Am J Case Rep 2018 Mar 19;19:314-319. Epub 2018 Mar 19.

Clinical School Johor Bahru, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Johor Bahru, Johor, Malaysia.

BACKGROUND Melioidosis is a rare tropical bacterial infection caused by the Gram-negative soil saprophyte, Burkholderia pseudomallei. Melioidosis can mimic a variety of diseases due to its varied presentation, and unless it is treated rapidly, it can be fatal.  A rare case of melioidosis, with pericarditis and pericardial effusion, is described, which demonstrates the value of early diagnosis with echocardiography and pericardiocentesis. CASE REPORT A 38-year-old native (Iban) East Malaysian man presented with shortness of breath and tachycardia. Transthoracic echocardiography (TTE) showed cardiac tamponade. Urgent pericardiocentesis drained a large amount of purulent pericardial fluid that grew Burkholderia pseudomallei. Despite appropriate dose and duration of intravenous treatment with ceftazidime followed by meropenem, the patient developed recurrent pericardial effusion and right heart failure due to constrictive pericarditis. The diagnosis of constrictive pericarditis was confirmed by computed tomography (CT) and surgical exploration. Following pericardiectomy, his symptoms resolved, but patient follow-up was recommended for possible sequelae of constrictive pericarditis. CONCLUSIONS After the onset of melioidosis pericarditis, the authors recommend follow-up and surveillance for possible complication of constrictive pericarditis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873330PMC
http://dx.doi.org/10.12659/ajcr.908310DOI Listing
March 2018

No significant association between PIK3CA mutation and survival of esophageal squamous cell carcinoma: A meta-analysis.

J Huazhong Univ Sci Technolog Med Sci 2017 Jun 6;37(3):462-468. Epub 2017 Jun 6.

Department of Cardiac Surgery, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, China.

The prognostic value of phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) in patients with esophageal squamous cell carcinoma (ESCC) is controversial. We aimed to investigate the prognostic significance of PIK3CA mutation in patients with ESCC. EMBASE, PubMed, and Web of Science databases were systematically searched from inception through Oct. 3, 2016. The hazard ratios (HRs) and 95% confidence intervals (CI) were calculated using a random effects model for overall survival (OS) and disease-free survival (DFS). Seven studies enrolling 1505 patients were eligible for inclusion of the current meta-analysis. Results revealed that PIK3CA mutation was not significantly associated with OS (HR: 0.90, 95% CI: 0.63-1.30, P=0.591), with a significant heterogeneity (I =65.7%, P=0.012). Additionally, subgroup analyses were further conducted according to various variables, such as types of specimen, the sample size, technique and statistical methodology. All results suggested that no significant relationship was found between PIK3CA mutation and OS in patients with ESCC. For DFS, there was no significant association between PIK3CA mutation and DFS in patients with ESCC (HR: 1.00, 95% CI=0.47-2.11, P=0.993, I =73.7%). Publication bias was not present and the results of sensitivity analysis were very stable in the current meta-analysis. Our findings suggest that PIK3CA mutation has no significant effects on OS and DFS in ESCC patients. More well-designed prospective studies with better methodology for PIK3CA assessment are required to clarify the prognostic significance of PIK3CA mutation in ESCC patients.
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http://dx.doi.org/10.1007/s11596-017-1758-0DOI Listing
June 2017

Genetic Diversity, Population Structure, and Linkage Disequilibrium of a Core Collection of Assessed with Genome-wide SNPs Developed by Genotyping-by-sequencing and SSR Markers.

Front Plant Sci 2017 18;8:575. Epub 2017 Apr 18.

National Engineering Laboratory for Tree Breeding, College of Biological Sciences and Technology, Beijing Forestry UniversityBeijing, China.

Chinese jujube ( Mill) is an economically important fruit species native to China with high nutritious and medicinal value. Genotyping-by-sequencing was used to detect and genotype single nucleotide polymorphisms (SNPs) in a core collection of 150 Chinese jujube accessions and further to characterize their genetic diversity, population structure, and linkage disequilibrium (LD). A total of 4,680 high-quality SNPs were identified, of which 38 sets of tri-allelic SNPs were detected. The average polymorphism information content (PIC) values based on bi-allelic SNPs and tri-allelic SNPs were 0.27 and 0.38, respectively. STRUCTURE and principal coordinate analyses based on SNPs revealed that the 150 accessions could be clustered into two groups. However, neighbor-joining trees indicated the accessions should be grouped into three major clusters. Our data confirm that the resolving power for genetic diversity was similar for the SSRs and SNPs. In contrast, regarding population structure, the resolving power was higher for SSRs than for SNPs. The LD pattern in Chinese jujube was investigated for the first time. We observed a relatively rapid LD decay with a short range (∼10 kb) for all pseudo-chromosomes and for individual pseudo-chromosomes. Our findings provide important information for future genome-wide association analyses and marker-assisted selective breeding of Chinese jujube.
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http://dx.doi.org/10.3389/fpls.2017.00575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394126PMC
April 2017

Beta-blocker use and risk of symptomatic bradyarrhythmias: a hospital-based case-control study.

J Geriatr Cardiol 2016 Sep;13(9):749-759

Department of Cardiology, Sultanah Aminah Hospital, Jalan Masjid Abu Bakar, Johor Bahru, Johor, Malaysia.

Objective: To investigate the risk factors of symptomatic bradyarrhythmias in relation to β-blockers use.

Methods: A hospital-based case-control study [228 patients: 108 with symptomatic bradyarrhythmias (cases) and 120 controls] was conducted in Sultanah Aminah Hospital, Malaysia between January 2011 and January 2014.

Results: The mean age was 61.1 ± 13.3 years with a majority of men (68.9%). Cases were likely than control to be older, hypertensive, lower body mass index and concomitant use of rate-controlling drugs (such as digoxin, verapamil, diltiazem, ivabradine or amiodarone). Significantly higher level of serum potassium, urea, creatinine and lower level of estimated glomerular filtration rate (eGFR) were observed among cases as compared to controls. On univariate analysis among patients on β-blockers, older age (crude OR: 1.07; 95% CI: 1.03-1.11, = 0.000), hypertension (crude OR: 5.6; 95% CI: 1.51-20.72, = 0.010), lower sodium (crude OR: 0.04; 95% CI: 0.81-0.99, = 0.036), higher potassium (crude OR: 2.36; 95% CI: 1.31-4.26, = 0.004) and higher urea (crude OR: 1.23; 95% CI: 1.11-1.38, = 0.000) were associated with increased risk of symptomatic bradyarrhythmias; eGFR was inversely and significantly associated with symptomatic bradyarrhythmias in both 'β-blockers' (crude OR: 0.97; 95% CI: 0.96-0.98, = 0.000) and 'non-β-blockers' (crude OR: 0.99; 95% CI: 0.97-0.99, = 0.023) arms. However, eGFR was not significantly associated with symptomatic bradyarrhythmias in the final model of both 'β-blockers' (adjusted OR: 0.98; 95% CI: 0.96-0.98, = 0.103) and 'non-β-blockers' (adjusted OR: 0.99; 95% CI: 0.97-1.01, = 0.328) arms. Importantly, older age was a significant predictor of symptomatic bradyarrhythmias in the 'β-blockers' as compared to the 'non-β-blockers' arms (adjusted OR: 1.09; 95% CI: 1.03-1.15, = 0.003 . adjusted OR: 1.03; 95% CI: 0.98-1.09, = 0.232, respectively).

Conclusion: Older age was a significant predictor of symptomatic bradyarrhythmias in patients on β-blockers than those without β-blockers.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2016.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122500PMC
September 2016

Pu-erh Tea Protects the Nervous System by Inhibiting the Expression of Metabotropic Glutamate Receptor 5.

Mol Neurobiol 2017 09 30;54(7):5286-5299. Epub 2016 Aug 30.

Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, Jilin University, Changchun, 130012, China.

Glutamate is one of the major excitatory neurotransmitters of the CNS and is essential for numerous key neuronal functions. However, excess glutamate causes massive neuronal death and brain damage owing to excitotoxicity via the glutamate receptors. Metabotropic glutamate receptor 5 (mGluR5) is one of the glutamate receptors and represents a promising target for studying neuroprotective agents of potential application in neurodegenerative diseases. Pu-erh tea, a fermented tea, mainly produced in Yunnan province, China, has beneficial effects, including the accommodation of the CNS. In this study, pu-erh tea markedly decreased the transcription and translation of mGluR5 compared to those by black and green teas. Pu-erh tea also inhibited the expression of Homer, one of the synaptic scaffolding proteins binding to mGluR5. Pu-erh tea protected neural cells from necrosis via blocked Ca influx and inhibited protein kinase C (PKC) activation induced by excess glutamate. Pu-erh tea relieved rat epilepsy induced by LiCl-pilocarpine in behavioural and physiological assays. Pu-erh tea also decreased the expression of mGluR5 in the hippocampus. These results show that the inhibition of mGluR5 plays a role in protecting neural cells from glutamate. The results also indicate that pu-erh tea contains biological compounds binding transcription factors and inhibiting the expression of mGluR5 and identify pu-erh tea as a novel natural neuroprotective agent.
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http://dx.doi.org/10.1007/s12035-016-0064-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533841PMC
September 2017

Biatrial thrombi resembling myxoma regressed after prolonged anticoagulation in a patient with mitral stenosis: a case report.

J Med Case Rep 2016 Aug 10;10(1):221. Epub 2016 Aug 10.

Department of Cardiology, Penang General Hospital, Jalan Residensi, 10990, Georgetown, Pulau Pinang, Malaysia.

Background: Many cases of cardiac masses have been reported in the literature, but in this case report we described a rare case of biatrial cardiac mass that represented a challenge for diagnosis and therapy. The differentiation between cardiac masses such as thrombi, vegetations, myxomas and other tumors is not always straightforward and an exact diagnosis is important because of its distinct treatment strategy. Transthoracic/esophageal echocardiography and cardiac magnetic resonance play an important role in establishing the diagnosis of cardiac masses. However, no current noninvasive diagnostic tool has the ability to absolutely diagnose cardiac masses; obtaining a pathological specimen by surgical resection of cardiac masses is the only reliable method to diagnose cardiac masses accurately. Our case report is an exception in that the final diagnosis was affirmed by empirical anticoagulation therapy based on clinical judgment and noninvasive characterization of biatrial mass.

Case Presentation: We described a 54-year-old Malay man with severe mitral stenosis and atrial fibrillation who presented with a biatrial mass. Transthoracic/esophageal echocardiography and cardiac magnetic resonance detected a large, homogeneous right atrial mass typical of a thrombus, and a left atrial mass adhering to interatrial septum that mimicked atrial myxoma. The risk factors, morphology, location, and characteristics of the biatrial cardiac mass indicated a diagnosis of thrombi. However, our patient declined surgery. As a result, the nature of his cardiac masses was not specified by histology. Of note, his left atrial mass was completely regressed by long-term warfarin, leaving a residual right atrial mass. Thus, we affirmed the most probable diagnosis of cardiac thrombi. During the course of treatment, he had an episode of non-fatal ischemic stroke most probably because of a thromboembolism.

Conclusions: Noninvasive characterization of cardiac mass is essential in clarifying the diagnosis and directing treatment strategy. Anticoagulation is a feasible treatment when the clinical assessment, risk factors, and imaging findings indicate a diagnosis of thrombi. After prolonged anticoagulation therapy, complete resolution of biatrial thrombi was achievable in our case.
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http://dx.doi.org/10.1186/s13256-016-1018-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980798PMC
August 2016

An uncommon and insidious presentation of renal cell carcinoma with tumor extending into the inferior vena cava and right atrium: a case report.

J Med Case Rep 2016 May 3;10(1):109. Epub 2016 May 3.

Department of Urology, Sultanah Aminah Hospital, Jalan Abu Bakar, 80100, Johor Bahru, Johor, Malaysia.

Background: Renal cell carcinoma is a potentially lethal cancer with aggressive behavior and it tends to metastasize. Renal cell carcinoma involves the inferior vena cava in approximately 15% of cases and it rarely extends into the right atrium. A majority of renal cell carcinoma are detected as incidental findings on imaging studies obtained for unrelated reasons. At presentation, nearly 25% of patients either have distant metastases or significant local-regional disease with no symptoms that can be attributed to renal cell carcinoma.

Case Presentation: A 64-year-old Indian male with a past history of coronary artery bypass graft surgery, congestive heart failure, and diabetes mellitus complained of worsening shortness of breath for 2 weeks. Incidentally, a transthoracic echocardiography showed a "thumb-like" mass in his right atrium extending into his right ventricle through the tricuspid valve with each systole. Abdomen magnetic resonance imaging revealed a heterogenous lobulated mass in the upper and mid-pole of his right kidney with a tumor extending into his inferior vena cava and right atrium, consistent with our diagnosis of advanced renal cell carcinoma which was later confirmed by surgical excision and histology. Radical right nephrectomy, lymph nodes clearance, inferior vena cava cavatomy, and complete tumor thrombectomy were performed successfully. Perioperatively, he did not require cardiopulmonary bypass or deep hypothermic circulatory arrest. He had no recurrence during the follow-up period for more than 2 years after surgery.

Conclusions: Advanced extension of renal cell carcinoma can occur with no apparent symptoms and be detected incidentally. In rare circumstances, atypical presentation of renal cell carcinoma should be considered in a patient presenting with right atrial mass detected by echocardiography. Renal cell carcinoma with inferior vena cava and right atrium extension is a complex surgical challenge, but excellent results can be obtained with proper patient selection, meticulous surgical techniques, and close perioperative patient care.
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http://dx.doi.org/10.1186/s13256-016-0888-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855703PMC
May 2016

Mono- and tetra-substituted zinc(II) phthalocyanines containing morpholinyl moieties: Synthesis, antifungal photodynamic activities, and structure-activity relationships.

Eur J Med Chem 2016 May 3;114:380-9. Epub 2016 Mar 3.

College of Chemistry, Fuzhou University, Fuzhou 350116, China. Electronic address:

A series of zinc(II) phthalocyanines (ZnPcs) mono-substituted and tetra-substituted with morpholinyl moieties and their quaternized derivatives have been synthesized and evaluated for their antifungal photodynamic activities toward Candida albicans. The α-substituted, quaternized, and mono-substituted ZnPcs are found to have higher antifungal photoactivity than β-substituted, neutral, and tetra-substituted counterparts. The cationic α-mono-substituted ZnPc (6a) exhibits the highest photocytotoxicity. Moreover, it is more potent than axially di-substituted analogue. The different photocytotoxicities of these compounds have also been rationalized by investigating their spectroscopic and photochemical properties, aggregation trend, partition coefficients, and cellular uptake. The IC90 value of 6a against C. albicans cells is as low as 3.3 μM with a light dose of 27 J cm(-2), meaning that 6a is a promising candidate as the antifungal photosensitizer for future investigations.
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http://dx.doi.org/10.1016/j.ejmech.2016.02.066DOI Listing
May 2016

Quasi-distributed birefringence dispersion measurement for polarization maintain device with high accuracy based on white light interferometry.

Opt Express 2016 Jan;24(2):1587-97

A white light temporal interferometric technique for measurement of the quasi-distributed birefringence dispersion (BD) in a polarization maintain (PM) device with high accuracy based on weighted least square (WLS) method is presented. It is verified theoretically and experimentally that the accuracy of WLS method and the conventional ordinary least square (OLS) method both are proportional to the signal-to-noise ratio (SNR) of interferogram, whereas the WLS method holds a higher scaling factor because it is more suitable for heteroscedastic model that has unequal error variance. The experiment results show a repeatability of ~4.6 × 10(-5) ps/nm @ 1550 nm with WLS method for 100 sets of data, and ~4.3 × 10(-4) ps/nm with OLS method, for an interferogram with SNR of 30 dB. Besides, WLS method without iterative operation is carried out by using power spectrum of interferogram as weight value. The feasibility of this technique is demonstrated by distinguishing the quasi-distributed BD of every part for a packaged Y-waveguide with two 1m-long PM pigtails.
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http://dx.doi.org/10.1364/OE.24.001587DOI Listing
January 2016

Microarray analysis of potential genes in the pathogenesis of recurrent oral ulcer.

Int J Clin Exp Pathol 2015 1;8(10):12419-27. Epub 2015 Oct 1.

Department of Orthodontics, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, Heilongjiang, China.

Recurrent oral ulcer seriously threatens patients' daily life and health. This study investigated potential genes and pathways that participate in the pathogenesis of recurrent oral ulcer by high throughput bioinformatic analysis. RT-PCR and Western blot were applied to further verify screened interleukins effect. Recurrent oral ulcer related genes were collected from websites and papers, and further found out from Human Genome 280 6.0 microarray data. Each pathway of recurrent oral ulcer related genes were got through chip hybridization. RT-PCR was applied to test four recurrent oral ulcer related genes to verify the microarray data. Data transformation, scatter plot, clustering analysis, and expression pattern analysis were used to analyze recurrent oral ulcer related gene expression changes. Recurrent oral ulcer gene microarray was successfully established. Microarray showed that 551 genes involved in recurrent oral ulcer activity and 196 genes were recurrent oral ulcer related genes. Of them, 76 genes up-regulated, 62 genes down-regulated, and 58 genes up-/down-regulated. Total expression level up-regulated 752 times (60%) and down-regulated 485 times (40%). IL-2 plays an important role in the occurrence, development and recurrence of recurrent oral ulcer on the mRNA and protein levels. Gene microarray can be used to analyze potential genes and pathways in recurrent oral ulcer. IL-2 may be involved in the pathogenesis of recurrent oral ulcer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4680373PMC
October 2016

Mapping a Large Number of QTL for Durable Resistance to Stripe Rust in Winter Wheat Druchamp Using SSR and SNP Markers.

PLoS One 2015 13;10(5):e0126794. Epub 2015 May 13.

State Key Laboratory of Crop Stress Biology in Arid Areas and College of Plant Protection, Northwest A&F University, Yangling, Shaanxi, China.

Winter wheat Druchamp has both high-temperature adult-plant (HTAP) resistance and all-stage resistance to stripe rust caused by Puccinia striiformis f. sp. tritici (Pst). The HTAP resistance in Druchamp is durable as the variety has been resistant in adult-plant stage since it was introduced from France to the United States in late 1940s. To map the quantitative trait loci (QTL) for stripe rust resistance, an F8 recombinant inbred line (RIL) population from cross Druchamp × Michigan Amber was phenotyped for stripe rust response in multiple years in fields under natural infection and with selected Pst races under controlled greenhouse conditions, and genotyped with simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers. Composite interval mapping (CIM) identified eight HTAP resistance QTL and three all-stage resistance QTL. Among the eight HTAP resistance QTL, QYrdr.wgp-1BL.2 (explaining 2.36-31.04% variation), QYrdr.wgp-2BL (2.81-15.65%), QYrdr.wgp-5AL (2.27-17.22%) and QYrdr.wgp-5BL.2 (2.42-15.13%) were significant in all tests; and QYrdr.wgp-1BL.1 (1.94-10.19%), QYrdr.wgp-1DS (2.04-27.24%), QYrdr.wgp-3AL (1.78-13.85%) and QYrdr.wgp-6BL.2 (1.69-33.71%) were significant in some of the tests. The three all-stage resistance QTL, QYrdr.wgp-5BL.1 (5.47-36.04%), QYrdr.wgp-5DL (9.27-11.94%) and QYrdr.wgp-6BL.1 (13.07-20.36%), were detected based on reactions in the seedlings tested with certain Pst races. Among the eleven QTL detected in Druchamp, at least three (QYrdr.wgp-5DL for race-specific all-stage resistance and QYrdr.wgp-3AL and QYrdr.wgp-6BL.2 for race non-specific HTAP resistance) are new. All these QTL, especially those for durable HTAP resistance, and their closely linked molecular markers could be useful for developing wheat cultivars with durable resistance to stripe rust.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0126794PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430513PMC
February 2016

Sex differences in acute coronary syndrome in a multiethnic asian population: results of the malaysian national cardiovascular disease database-acute coronary syndrome (NCVD-ACS) registry.

Glob Heart 2014 Dec;9(4):381-90

Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Kuala Lumpur, Malaysia.

Background: Sex differences in acute coronary syndrome (ACS) have been well studied in major registries and clinical trials in Western populations. Limited studies have examined the sex differences in ACS using a large number of Asian women as the subjects.

Objectives: The aim was to study the sex differences in ACS using the NCVD-ACS (National Cardiovascular Disease Database-Acute Coronary Syndrome) registry.

Methods: We analyzed 13,591 ACS patients, of which 75.8% were men and 24.2% were women, from March 2006 to February 2010. Data were collected on demographic characteristics, risk factors, anthropometrics, treatments, procedures, mortalities, and complications. The results were compared among 3 cohorts of ACS (ST-segment elevation myocardial infarction [STEMI], non-STEMI, and unstable angina).

Results: Women were older and more likely to have diabetes, hypertension, previous heart failure, and cerebral vascular accidents than men were. Women were less likely to receive in-hospital administration of aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers, and they were less likely to undergo angiography and percutaneous coronary intervention. In STEMI, a significantly lower proportion of women than men received primary percutaneous coronary intervention (6.2% vs. 6.7%, respectively, p = 0.000) and fibrinolysis (64.4% vs. 74.6%, respectively, p = 0.000). In addition, with regard to STEMI, women had a significantly higher unadjusted in-hospital mortality rate than men did (15.0% vs. 8.1%, respectively, p < 0.000). There was no statistically significant in-hospital mortality difference between sexes for non-STEMI and unstable angina. After adjustment for age and other covariates, a multivariate analysis showed no sex differences in the in-hospital mortality in all spectrums of ACS.

Conclusions: Our study showed significant sex differences in the demographic characteristics, risk factors, treatments, and outcomes of ACS. More importantly, in ACS patients, we found evidence of suboptimal treatments and interventions in women versus men. Our findings provide an opportunity to narrow the sex gap in the care of women with ACS in Malaysia.
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http://dx.doi.org/10.1016/j.gheart.2014.06.001DOI Listing
December 2014

Ethnic differences in the occurrence of acute coronary syndrome: results of the Malaysian National Cardiovascular Disease (NCVD) Database Registry (March 2006 - February 2010).

BMC Cardiovasc Disord 2013 Nov 6;13:97. Epub 2013 Nov 6.

Clinical School Johor Bahru, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Sunway campus, 8 Jalan Masjid Abu Bakar, 80100, Johor Bahru, Johor, Malaysia.

Background: The National Cardiovascular Disease (NCVD) Database Registry represents one of the first prospective, multi-center registries to treat and prevent coronary artery disease (CAD) in Malaysia. Since ethnicity is an important consideration in the occurrence of acute coronary syndrome (ACS) globally, therefore, we aimed to identify the role of ethnicity in the occurrence of ACS among high-risk groups in the Malaysian population.

Methods: The NCVD involves more than 15 Ministry of Health (MOH) hospitals nationwide, universities and the National Heart Institute and enrolls patients presenting with ACS [ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI) and unstable angina (UA)]. We analyzed ethnic differences across socio-demographic characteristics, hospital medications and invasive therapeutic procedures, treatment of STEMI and in-hospital clinical outcomes.

Results: We enrolled 13,591 patients. The distribution of the NCVD population was as follows: 49.0% Malays, 22.5% Chinese, 23.1% Indians and 5.3% Others (representing other indigenous groups and non-Malaysian nationals). The mean age (SD) of ACS patients at presentation was 59.1 (12.0) years. More than 70% were males. A higher proportion of patients within each ethnic group had more than two coronary risk factors. Malays had higher body mass index (BMI). Chinese had highest rate of hypertension and hyperlipidemia. Indians had higher rate of diabetes mellitus (DM) and family history of premature CAD. Overall, more patients had STEMI than NSTEMI or UA among all ethnic groups. The use of aspirin was more than 94% among all ethnic groups. Utilization rates for elective and emergency percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) were low among all ethnic groups. In STEMI, fibrinolysis (streptokinase) appeared to be the dominant treatment options (>70%) for all ethnic groups. In-hospital mortality rates for STEMI across ethnicity ranges from 8.1% to 10.1% (p = 0.35). Among NSTEMI/UA patients, the rate of in-hospital mortality ranges from 3.7% to 6.5% and Malays recorded the highest in-hospital mortality rate compared to other ethnic groups (p = 0.000). In binary multiple logistic regression analysis, differences across ethnicity in the age and sex-adjusted ORs for in-hospital mortality among STEMI patients was not significant; for NSTEMI/UA patients, Chinese [OR 0.71 (95% CI 0.55, 0.91)] and Indians [OR 0.57 (95% CI 0.43, 0.76)] showed significantly lower risk of in-hospital mortality compared to Malays (reference group).

Conclusions: Risk factor profiles and ACS stratum were significantly different across ethnicity. Despite disparities in risk factors, clinical presentation, medical treatment and invasive management, ethnic differences in the risk of in-hospital mortality was not significant among STEMI patients. However, Chinese and Indians showed significantly lower risk of in-hospital mortality compared to Malays among NSTEMI and UA patients.
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http://dx.doi.org/10.1186/1471-2261-13-97DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229312PMC
November 2013

Genetic and Molecular Mapping of Stripe Rust Resistance Gene in Wheat-Psathyrostachys huashanica Translocation Line H9020-1-6-8-3.

Plant Dis 2012 Oct;96(10):1482-1487

State Key Laboratory of Crop Stress Biology for Arid Areas/College of Plant Protection, Northwest A&F University, Yangling 712100, China.

Stripe rust, caused by Puccinia striiformis f. sp. tritici, is one of the most important diseases of wheat worldwide. The best strategy to control stripe rust is to grow resistant cultivars, but only a few effective genes are available. The wheat accession H9020-1-6-8-3 is a translocation line previously developed from interspecific hybridization between wheat genotype 7182 and Psathyrostachys huashanica, and is resistant to most Chinese Puccinia striiformis f. sp. tritici races. To identify the resistance genes in the translocation line, H9020-1-6-8-3 was crossed with susceptible genotype Mingxian 169, and seedlings of parents and F, F, and F progenies were tested with prevalent Chinese P. striiformis f. sp. tritici races CYR32 and CYR33 under controlled greenhouse conditions. The genetic results indicated that two single dominant genes in H9020-1-6-8-3 confer resistance to CYR32 and CYR33, respectively. The gene for resistance to CYR33 was temporarily designated as YrH9020. Six simple-sequence repeat markers were used to map the resistance gene to the short arm of wheat chromosome 2D, using 329 F plants tested with CYR33 in the greenhouse. The genetic distances of the two closest flanking markers, Xgwm261 and Xgwm455, were 4.4 and 5.8 centimorgans, respectively. Disease assessments and polymorphic tests of the flanking markers among the Psathyrostachys huashanica line and wheat lines 7182, H9020-1-6-8-3, and Mingxian169 suggested that the resistance gene YrH9020 in H9020-1-6-8-3 was originally from P. huashanica. The exotic stripe rust resistance gene and linked molecular markers should be useful for pyramiding with other genes to develop wheat cultivars with high-level and durable resistance to stripe rust.
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http://dx.doi.org/10.1094/PDIS-03-11-0204-REDOI Listing
October 2012

Functional identification and regulation of the PtDrl02 gene promoter from triploid white poplar.

Plant Cell Rep 2010 May 24;29(5):449-60. Epub 2010 Feb 24.

National Engineering Laboratory for Tree Breeding, Key Laboratory of Genetics and Breeding in Forest Trees and Ornamental Plants, Ministry of Education, Beijing Forestry University, Beijing, People's Republic of China.

The PtDrl02 gene belongs to the TIR-NBS gene family in triploid white poplar (Populus tomentosa x P. bolleana) x P. tomentosa. Its expression pattern displays tissue-specificity, and the transcript level can be induced by wounding, methyl jasmonate (MeJA), and salicylic acid (SA). To understand the regulatory mechanism controlling PtDrl02 gene expression, we functionally characterized the PtDrl02 promoter region. Using the beta-glucuronidase as a reporter, we found that the PtDrl02 promoter directed gene expression mainly in the aerial parts of the plants and was confined to the cortex tissues of leaf veins, petioles, stems, and stem piths, showing a typical tissue-specific expression pattern. Deletion analysis revealed two positive regulatory regions (-985 to -669 and -669 to -467) responsible for the basal activity of the PtDrl02 promoter. Impressively, the sequence from -669 to -467 was shown to contain cis-element (s) responding to wounding and MeJA, while the promoter region between -244 and 0 could individually display wounding-responsiveness, and the fragment from -467 to -244 was required for SA- and NaCl-inducible expression of the PtDrl02 promoter. Additionally, it was found that the -985 to -669 sequence was the ABA-responding promoter fragment. These results suggested that the PtDrl02 promoter was modulated by multiple cis-regulatory elements in distinct and complex patterns to regulate PtDrl02 gene expression. Our study also suggested that the PtDrl02 gene 5' untranslated region, as well as a Populus WRKY transcription factor, PtWRKY1, was involved in the regulation of PtDrl02 promoter activities.
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http://dx.doi.org/10.1007/s00299-010-0834-8DOI Listing
May 2010