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1.  Anterior cervical discectomy and fusion versus anterior cervical corpectomy and fusion in the treatment of multilevel cervical spondylotic myelopathy: systematic review and a meta-analysis 
Background
To date, the decision to treat multilevel cervical spondylotic myelopathy (CSM) with anterior cervical discectomy and fusion (ACDF) or anterior cervical corpectomy and fusion (ACCF) remains controversial. Therefore, we conducted a meta-analysis to quantitatively determine the efficacy of ACDF and ACCF in the treatment of multilevel CSM.
Methods
We searched several databases for related research articles published in English or Chinese. We extracted and assessed the data independently. We determined the pooled data, data heterogeneity, and overall effect, respectively.
Results
We identified 15 eligible studies with 1,368 patients. We found that blood loss and numbers of complications during surgery in ACDF were significantly less that in ACCF; however, other clinical outcomes, such as operation time, bone fusion failure, post Japanese Orthopedic Association scores, recovery rates, and visual analog scale scores between ACDF and ACCF with multilevel CSM were not significantly different.
Conclusion
Our results strongly suggest that surgical treatments of multilevel CSM are similar in terms of most clinical outcomes using ACDF or ACCF.
doi:10.2147/TCRM.S72699
PMCID: PMC4321642
meta-analysis; therapy; anterior cervical discectomy and fusion; anterior cervical corpectomy and fusion; cervical spondylotic myelopathy
2.  Genomes of the rice pest brown planthopper and its endosymbionts reveal complex complementary contributions for host adaptation 
Genome Biology  2014;15(12):521.
Background
The brown planthopper, Nilaparvata lugens, the most destructive pest of rice, is a typical monophagous herbivore that feeds exclusively on rice sap, which migrates over long distances. Outbreaks of it have re-occurred approximately every three years in Asia. It has also been used as a model system for ecological studies and for developing effective pest management. To better understand how a monophagous sap-sucking arthropod herbivore has adapted to its exclusive host selection and to provide insights to improve pest control, we analyzed the genomes of the brown planthopper and its two endosymbionts.
Results
We describe the 1.14 gigabase planthopper draft genome and the genomes of two microbial endosymbionts that permit the planthopper to forage exclusively on rice fields. Only 40.8% of the 27,571 identified Nilaparvata protein coding genes have detectable shared homology with the proteomes of the other 14 arthropods included in this study, reflecting large-scale gene losses including in evolutionarily conserved gene families and biochemical pathways. These unique genomic features are functionally associated with the animal’s exclusive plant host selection. Genes missing from the insect in conserved biochemical pathways that are essential for its survival on the nutritionally imbalanced sap diet are present in the genomes of its microbial endosymbionts, which have evolved to complement the mutualistic nutritional needs of the host.
Conclusions
Our study reveals a series of complex adaptations of the brown planthopper involving a variety of biological processes, that result in its highly destructive impact on the exclusive host rice. All these findings highlight potential directions for effective pest control of the planthopper.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0521-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s13059-014-0521-0
PMCID: PMC4269174  PMID: 25609551
3.  Controlling Cyanobacterial Blooms in Hypertrophic Lake Taihu, China: Will Nitrogen Reductions Cause Replacement of Non-N2 Fixing by N2 Fixing Taxa? 
PLoS ONE  2014;9(11):e113123.
Excessive anthropogenic nitrogen (N) and phosphorus (P) inputs have caused an alarming increase in harmful cyanobacterial blooms, threatening sustainability of lakes and reservoirs worldwide. Hypertrophic Lake Taihu, China’s third largest freshwater lake, typifies this predicament, with toxic blooms of the non-N2 fixing cyanobacteria Microcystis spp. dominating from spring through fall. Previous studies indicate N and P reductions are needed to reduce bloom magnitude and duration. However, N reductions may encourage replacement of non-N2 fixing with N2 fixing cyanobacteria. This potentially counterproductive scenario was evaluated using replicate, large (1000 L), in-lake mesocosms during summer bloom periods. N+P additions led to maximum phytoplankton production. Phosphorus enrichment, which promoted N limitation, resulted in increases in N2 fixing taxa (Anabaena spp.), but it did not lead to significant replacement of non-N2 fixing with N2 fixing cyanobacteria, and N2 fixation rates remained ecologically insignificant. Furthermore, P enrichment failed to increase phytoplankton production relative to controls, indicating that N was the most limiting nutrient throughout this period. We propose that Microcystis spp. and other non-N2 fixing genera can maintain dominance in this shallow, highly turbid, nutrient-enriched lake by outcompeting N2 fixing taxa for existing sources of N and P stored and cycled in the lake. To bring Taihu and other hypertrophic systems below the bloom threshold, both N and P reductions will be needed until the legacy of high N and P loading and sediment nutrient storage in these systems is depleted. At that point, a more exclusive focus on P reductions may be feasible.
doi:10.1371/journal.pone.0113123
PMCID: PMC4236137  PMID: 25405474
4.  Brown Planthopper Nudivirus DNA Integrated in Its Host Genome 
Journal of Virology  2014;88(10):5310-5318.
ABSTRACT
The brown planthopper (BPH), Nilaparvata lugens (Hemiptera:Delphacidae), is one of the most destructive insect pests of rice crops in Asia. Nudivirus-like sequences were identified during the whole-genome sequencing of BPH. PCR examination showed that the virus sequences were present in all of the 22 BPH populations collected from East, Southeast, and South Asia. Thirty-two of the 33 nudivirus core genes were identified, including 20 homologues of baculovirus core genes. In addition, several gene clusters that were arranged collinearly with those of other nudiviruses were found in the partial virus genome. In a phylogenetic tree constructed using the supermatrix method, the original virus was grouped with other nudiviruses and was closely related to polydnavirus. Taken together, these data indicated that the virus sequences belong to a new member of the family Nudiviridae. More specifically, the virus sequences were integrated into the chromosome of its insect host during coevolution. This study is the first report of a large double-stranded circular DNA virus genome in a sap-sucking hemipteran insect.
IMPORTANCE This is the first report of a large double-stranded DNA virus integrated genome in the planthopper, a plant sap-sucking hemipteran insect. It is an exciting addition to the evolutionary story of bracoviruses (polydnaviruses), nudiviruses, and baculoviruses. The results on the virus sequences integrated in the chromosomes of its insect host also represent a story of successful coevolution of an invertebrate virus and a plant sap-sucking insect.
doi:10.1128/JVI.03166-13
PMCID: PMC4019104  PMID: 24574410
5.  Vitreoscilla hemoglobin promotes Salecan production by Agrobacterium sp. ZX09*  
Salecan is a novel exopolysaccharide produced by the strain Agrobacterium sp. ZX09, and it is composed of only glucose monomers. The unique chemical composition and excellent physicochemical properties make Salecan a promising material for applications in coagulation, lubrication, protection against acute liver injury, and alleviating constipation. In this study, we cloned the Vitreoscilla hemoglobin gene into a broad-host-range plasmid pCM158. Without antibiotic selection, there was negligible loss of the plasmid in the host Agrobacterium sp. ZX09 after one passage of cultivation. The expression of Vitreoscilla hemoglobin was demonstrated by carbon monoxide (CO) difference spectrum. The engineered strain Agrobacterium sp. ZX09 increased Salecan yield by 30%. The other physiological changes included its elevated respiration rate and cellular invertase activity.
doi:10.1631/jzus.B1400123
PMCID: PMC4228510  PMID: 25367790
Salecan; Vitreoscilla hemoglobin; Agrobacterium sp. ZX09; Invertase; Respiration rate
6.  Association between cardiothoracic ratio, left ventricular size and systolic function in patients undergoing computed tomography coronary angiography 
The present study aimed to investigate the association between cardiothoracic ratio (CTR) and left ventricular (LV) systolic function parameters in patients with or without preserved LV ejection fraction (LVEF). A total of 203 subjects suspected with coronary artery disease underwent chest radiography and dual source computed tomography coronary angiography (DSCT-CA). The LV systolic function parameters: LV end-diastolic volume index (LVEDVI), LV end-systolic volume index (LVESVI), and LVEF were measured from the DSCT-CA. The association between CTR and LV systolic function parameters was analyzed according to LVEF value (<55%, depressed LVEF group; versus ≥55%, preserved LVEF group) and CTR value (<0.5, normal range CTR group; versus ≥0.5, larger CTR group). The LVEDVI and LVESVI were higher in the depressed LVEF group compared with the preserved LVEF group (108.56±57.15 vs. 67.52±14.56 ml/m2, P<0.001; and 64.07±37.81 vs. 20.23±7.23 ml/m2, P<0.001, respectively) and lower in the normal range CTR group compared with the larger CTR group (67.10±15.00 vs. 77.30±34.32 ml/m2, P=0.009 and 21.94±8.96 vs. 28.97±26.54 ml/m2, P=0.017, respectively). Significant correlations were found between CTR and LVEDVI, and LVESVI and LVEF in the depressed LVEF group (r=0.66, P<0.001; r=0.65, P<0.001; and r=−0.46, P=0.018, respectively). However, there was no significant association detected between CTR and LV systolic function parameters in the other subgroups. The LVEDVI and LVESVI showed an inverse correlation with the LVEF in each group. Although the CTR was not a reliable indicator of LV size and systolic function in patients with preserved LVEF, it was correlated with LV size and LVEF in patients with depressed LVEF.
doi:10.3892/etm.2014.2016
PMCID: PMC4217771  PMID: 25371728
dual source computed tomography; chest radiography; cardiothoracic ratio; left ventricular systolic function; left ventricular volume index
7.  Substrate-Based Fragment Identification for the Development of Selective, Nonpeptidic Inhibitors of Striatal-Enriched Protein Tyrosine Phosphatase 
Journal of medicinal chemistry  2013;56(19):10.1021/jm401037h.
High levels of striatal-enriched protein tyrosine phosphatase (STEP) activity are observed in a number of neuropsychiatric disorders such as Alzheimer’s disease. Over-expression of STEP results in the dephosphorylation and inactivation of many key neuronal signaling molecules, including ionotropic glutamate receptors. Moreover, genetically reducing STEP levels in AD mouse models significantly reversed cognitive deficits and decreased glutamate receptor internalization. These results support STEP as a potential target for drug discovery for the treatment of Alzheimer’s disease. Herein, a substrate-based approach for the discovery and optimization of fragments called substrate activity screening (SAS) has been applied to the development of low molecular weight (<450 Da) and non-peptidic, single-digit micromolar mechanism-based STEP inhibitors with greater than 20-fold selectivity across multiple tyrosine and dual specificity phosphatases. Significant levels of STEP inhibition in rat cortical neurons are also observed.
doi:10.1021/jm401037h
PMCID: PMC3875168  PMID: 24083656
8.  Multivariate Dimensionality Reduction Approaches to Identify Gene-Gene and Gene-Environment Interactions Underlying Multiple Complex Traits 
PLoS ONE  2014;9(9):e108103.
The elusive but ubiquitous multifactor interactions represent a stumbling block that urgently needs to be removed in searching for determinants involved in human complex diseases. The dimensionality reduction approaches are a promising tool for this task. Many complex diseases exhibit composite syndromes required to be measured in a cluster of clinical traits with varying correlations and/or are inherently longitudinal in nature (changing over time and measured dynamically at multiple time points). A multivariate approach for detecting interactions is thus greatly needed on the purposes of handling a multifaceted phenotype and longitudinal data, as well as improving statistical power for multiple significance testing via a two-stage testing procedure that involves a multivariate analysis for grouped phenotypes followed by univariate analysis for the phenotypes in the significant group(s). In this article, we propose a multivariate extension of generalized multifactor dimensionality reduction (GMDR) based on multivariate generalized linear, multivariate quasi-likelihood and generalized estimating equations models. Simulations and real data analysis for the cohort from the Study of Addiction: Genetics and Environment are performed to investigate the properties and performance of the proposed method, as compared with the univariate method. The results suggest that the proposed multivariate GMDR substantially boosts statistical power.
doi:10.1371/journal.pone.0108103
PMCID: PMC4178067  PMID: 25259584
9.  Feasibility of fine-needle aspiration biopsy and its applications in superficial cervical lesion biopsies 
The aim of the study was to investigate the feasibility and value of clinical application of fine-needle aspiration histological biopsy via ultrasound-guided thyroid nodule and enlarged cervical lymph node fine-needle aspiration histological biopsy. Fine-needle aspiration cytological and histological biopsies and surgical treatments were performed on 982 patients with thyroid nodule and 1435 patients with enlarged cervical lymph nodes. A comparative study of the histological and cytological examination results and post-surgical etiology results was subsequently conducted. Among the 982 thyroid nodule patients, the acquisition rates were 89.8% (882/982) for fine-needle aspiration histological biopsy and 96.2% (945/982) for cytological biopsy, while among the 1435 patients with enlarged cervical lymph nodes, the acquisition rate for fine-needle aspiration cytological biopsy was slightly higher than that for histological biopsy, with values of 95.7% (1374/1435) and 91.4% (1312/1435), respectively. For the thyroid nodule patients, when the acquired histological and cytological biopsy results were compared with the post-surgical etiology results, the sensitivity, specificity, and accuracy of the histological results were 98.5%, 100%, and 98.9%, respectively, whereas those of the cytological results were 86.8%, 82.9%, and 85.6%, respectively; the differences between the 2 biopsy methods were statistically significant (P < 0.05). For the patients with enlarged cervical lymph nodes, when the acquired histological and cytological biopsy results were compared with the post-surgical etiology results, the sensitivity, specificity, and accuracy of the histological results were 96.3%, 99.8%, and 97.6%, respectively, whereas the those of the cytological results were 76.8%, 92.1%, and 82.2%, respectively; again, the differences between the 2 methods were statistically significant (P < 0.05). In conclusion, Fine-needle aspiration histological biopsy is a reliable and highly accurate examination method. It is simple and feasible, thus facilitating the discrimination of malignant and benign thyroid nodules and enlarged cervical lymph nodes and playing an important role in the establishment of reasonable clinical therapeutic regimens.
PMCID: PMC4152081  PMID: 25197391
Thyroid nodule; cervical lymph node; fine-needle aspiration histology; fine-needle aspiration cytology
10.  Multi-Walled Carbon Nanotubes Impair Kv4.2/4.3 Channel Activities, Delay Membrane Repolarization and Induce Bradyarrhythmias in the Rat 
PLoS ONE  2014;9(7):e101545.
Purpose
The potential hazardous effects of multi-walled carbon nanotubes (MWCNTs) on cardiac electrophysiology are seldom evaluated. This study aimed to investigate the impacts of MWCNTs on the Kv4/Ito channel, action potential and heart rhythm and the underlying mechanisms.
Methods
HEK293 cells were engineered to express Kv4.2 or Kv4.3 with or without KChIP2 expression. A series of approaches were introduced to analyze the effects of MWCNTs on Kv4/Ito channel kinetics, current densities, expression and trafficking. Transmission electron microscopy was performed to observe the internalization of MWCNTs in HEK293 cells and rat cardiomyocytes. Current clamp was employed to record the action potentials of isolated rat cardiomyocytes. Surface ECG and epicardial monophasic action potentials were recorded to monitor heart rhythm in rats in vivo. Vagal nerve discharge monitoring and H&E staining were also performed.
Results
Induction of MWCNTs into the cytosole through pipette solution soon accelerated the decay of IKv4 in HEK293 cells expressing Kv4.2/4.3 and KChIP2, and promoted the recovery from inactivation when Kv4.2 or Kv4.3 was expressed alone. Longer exposure (6 h) to MWCNTs decreased the IKv4.2 density, Kv4.2/Kv4.3 (but not KChIP2) expression and trafficking towards the plasma membrane in HEK293 cells. In acutely isolated rat ventricular myocytes, pipette MWCNTs also quickly accelerated the decay of IKv4 and prolonged the action potential duration (APD). Intravenous infusion of MWCNTs (2 mg/rat) induced atrioventricular (AV) block and even cardiac asystole. No tachyarrhythmia was observed after MWCNTs administration. MWCNTs did not cause coronary clot but induced myocardial inflammation and increased vagus discharge.
Conclusions
MWCNTs suppress Kv4/Ito channel activities likely at the intracellular side of plasma membrane, delay membrane repolarization and induce bradyarrhythmia. The delayed repolarization, increased vagus output and focal myocardial inflammation may partially underlie the occurrence of bradyarrhythmias induced by MWCNTs. The study warns that MWCNTs are hazardous to cardiac electrophysiology.
doi:10.1371/journal.pone.0101545
PMCID: PMC4081717  PMID: 24992664
11.  Statistical Modeling Reveals the Effect of Absolute Humidity on Dengue in Singapore 
Weather factors are widely studied for their effects on indicating dengue incidence trends. However, these studies have been limited due to the complex epidemiology of dengue, which involves dynamic interplay of multiple factors such as herd immunity within a population, distinct serotypes of the virus, environmental factors and intervention programs. In this study, we investigate the impact of weather factors on dengue in Singapore, considering the disease epidemiology and profile of virus serotypes. A Poisson regression combined with Distributed Lag Non-linear Model (DLNM) was used to evaluate and compare the impact of weekly Absolute Humidity (AH) and other weather factors (mean temperature, minimum temperature, maximum temperature, rainfall, relative humidity and wind speed) on dengue incidence from 2001 to 2009. The same analysis was also performed on three sub-periods, defined by predominant circulating serotypes. The performance of DLNM regression models were then evaluated through the Akaike's Information Criterion. From the correlation and DLNM regression modeling analyses of the studied period, AH was found to be a better predictor for modeling dengue incidence than the other unique weather variables. Whilst mean temperature (MeanT) also showed significant correlation with dengue incidence, the relationship between AH or MeanT and dengue incidence, however, varied in the three sub-periods. Our results showed that AH had a more stable impact on dengue incidence than temperature when virological factors were taken into consideration. AH appeared to be the most consistent factor in modeling dengue incidence in Singapore. Considering the changes in dominant serotypes, the improvements in vector control programs and the inconsistent weather patterns observed in the sub-periods, the impact of weather on dengue is modulated by these other factors. Future studies on the impact of climate change on dengue need to take all the other contributing factors into consideration in order to make meaningful public policy recommendations.
Author Summary
As dengue virus transmission is through a human-to-mosquito-to-human cycle, the influence of meteorological factors on dengue is likely to be associated with their impact on mosquito populations and behavior. Other than the influence of weather factors, the shift of dominant serotypes and pre-emptive measures taken against dengue vectors may possibly affect the dengue transmission trend. In this study, we investigate the impact of weather factors on dengue in tropical Singapore, taking into consideration the disease epidemiology and profile of virus serotypes. We found that absolute humidity, as a composite index of mean temperature and relative humidity, is a more stable and better predictor for modeling dengue incidence than the other unique weather variables when virological factors are taken into consideration. This research suggests that absolute humidity needs to be considered together with all the other contributing factors in order to make meaningful public policy recommendations for dengue control.
doi:10.1371/journal.pntd.0002805
PMCID: PMC4006725  PMID: 24786517
13.  Relationship between P53 Status and Response to Chemotherapy in Patients with Gastric Cancer: A Meta-Analysis 
PLoS ONE  2014;9(4):e95371.
Background
Previous studies have yielded conflicting results regarding the relationship between p53 status and response to chemotherapy in patients with gastric cancer. We therefore performed a meta-analysis to expound the relationship between p53 status and response to chemotherapy.
Methods/Findings
Thirteen previously published eligible studies, including 564 cases, were identified and included in this meta-analysis. p53 positive status (high expression of p53 protein and/or a mutant p53 gene) was associated with improved response in gastric cancer patients who received chemotherapy (good response: risk ratio [RR]  = 0.704; 95% confidence intervals [CI]  = 0.550–0.903; P = 0.006). In further stratified analyses, association with a good response remained in the East Asian population (RR = 0.657; 95% CI = 0.488–0.884; P = 0.005), while in the European subgroup, patients with p53 positive status tended to have a good response to chemotherapy, although this did not reach statistical significance (RR = 0.828, 95% CI = 0.525–1.305; P = 0.417). As five studies used neoadjuvant chemotherapy (NCT) and one used neoadjuvant chemoradiotherapy (NCRT), we also analyzed these data, and found that p53 positive status was associated with a good response in gastric cancer patients who received chemotherapy-based neoadjuvant treatment (RR = 0.675, 95% CI = 0.463–0.985; P = 0.042).
Conclusion
This meta-analysis indicated that p53 status may be a useful predictive biomarker for response to chemotherapy in gastric cancer. Further prospective studies with larger sample sizes and better study designs are required to confirm our findings.
doi:10.1371/journal.pone.0095371
PMCID: PMC3989310  PMID: 24740294
14.  Highly Selective Domino Multi-Cyclizations for Forming Polycyclic Fused Acridines and Azaheterocyclic Skeletons 
Organic letters  2013;15(7):1540-1543.
Highly selective four-component domino multi-cyclizations for the synthesis of new fused acridines and azaheterocyclic skeletons have been established by mixing common reactants in isobutyric acid under microwave irradiation. The reactions proceeded at fast rates, and were conducted to completion within 20–30 min. Up to seven new chemical bonds, four rings and four stereocenters were assembled in a convenient one-pot operation. The resulting hexacyclic and pentacyclic fused acridines and their stereochemistry have been fully characterized and determined by X-ray structural analysis.
doi:10.1021/ol400322v
PMCID: PMC3635953  PMID: 23506186
15.  Intramolecular Anodic Olefin Coupling Reactions and the Synthesis of Cyclic Amines 
Anodic olefin coupling reactions using a tosylamine trapping group have been studied. The cyclizations are favored by the use of a less-polar radical cation and more basic reaction conditions. The most significant factor for obtaining good yields of cyclic product is the use of the more basic reaction conditions. However, a number of factors including the nature of both the solvent and the electrolyte used can influence the yield of the cyclizations. The cyclizations allow for the rapid synthesis of both substituted proline and pipecolic acid type derivatives.
doi:10.1021/ja910586v
PMCID: PMC3950632  PMID: 20131795
16.  Intramolecular Anodic Olefin Coupling Reactions: Using Competition Studies to Probe the Mechanism of Oxidative Cyclization Reactions 
Organic letters  2010;12(8):1720-1723.
A competition experiment was designed so that the relative rates of anodic cyclization reactions under various electrolysis conditions can be determined. Reactions with ketene dithioacetal and enol ether-based substrates that use lithium methoxide as a base were shown to proceed through radical cation intermediates that were trapped by a sulfonamide anion. Results for the oxidative coupling of a vinyl sulfide with a sulfonamide anion using the same conditions were consistent with the reaction proceeding through a nitrogen-radical.
doi:10.1021/ol100317t
PMCID: PMC3943423  PMID: 20302359
17.  Intramolecular Hydroamination of Dithioketene Acetals: An Easy Route To Cyclic Amino Acid Derivatives 
Organic letters  2010;12(22):5174-5177.
Catalytic intramolecular hydroamination of dithioketene acetals was developed for the synthesis of cyclic amino acid derivatives. Triggered by the addition of a catalytical amount of n-BuLi, the reaction proceeds to give proline and pipecolic acid derivatives in excellent yields and diastereoselectivity.
doi:10.1021/ol102193x
PMCID: PMC3943425  PMID: 20945849
18.  Increased Risk for Developing Major Adverse Cardiovascular Events in Stented Chinese Patients Treated with Dual Antiplatelet Therapy after Concomitant Use of the Proton Pump Inhibitor 
PLoS ONE  2014;9(1):e84985.
Background
Some clinical studies have demonstrated that the proton pump inhibitor (PPI) could decrease clopidogrel platelet response and increase major adverse cardiovascular events (MACE) in white or black subjects. However, that remains to be determined in Chinese patients. In this study, we sought to determine whether there could be an increased risk for developing MACE after concomitant use of dual antiplatelet therapy (DAT) and a PPI in Chinese patients treated with percutaneous coronary intervention (PCI) and stenting.
Methods
This study was a 5-year, single-center, retrospective cohort analysis of eligible patients (n = 6188) who received DAT and a PPI concomitantly (defined as PPI users) before discharge and/or 12-month follow-up after discharge as compared with those who received DAT alone (also defined as non-PPI users, n = 1465). The incidence of recurrent MACE, such as myocardial infarction (MI), definite stent thromboses (ST), or cardiovascular death, was compared between the PPI users and non-users.
Results
PPI users had a significantly higher incidence of the MACE than non-users (13.9% vs. 10.6%; adjusted HR: 1.33; 95% CI: 1.12 – 1.57, P = 0.007). Stratified analysis revealed that concurrent use of DAT and a PPI was associated with a significantly increased risk for developing ST compared with DAT alone (1% vs. 0.4%; adjusted HR: 2.66, 95% CI: 1.16 – 5.87, P = 0.012). However, there were no significant differences in the risk of MI, cardiovascular death and other adverse events, regardless of combination of clopidogrel and a PPI.
Conclusions
The study further suggests that concomitant use of DAT and a PPI may be associated with an increased risk for developing MACE, in particular definite ST, in Chinese PCI patients after discharge as compared with use of DAT alone.
doi:10.1371/journal.pone.0084985
PMCID: PMC3885647  PMID: 24416326
19.  Detecting genetic variations in hereditary retinal dystrophies with next-generation sequencing technology 
Molecular Vision  2014;20:553-560.
Purpose
To identify pathogenic mutations responsible for retinal dystrophies (RDs) in three unrelated Chinese families.
Methods
Three probands from unrelated families with RDs were recruited. Genomic DNA prepared from leukocytes was analyzed using gene chip–based next-generation sequencing (NGS) to capture and sequence all of the exons of 100 known RD-associated genes. Candidate variants were validated with PCR and Sanger sequencing in the respective families. Thorough ophthalmic examinations including best-corrected visual acuity, funduscopic examination, and full-field electroretinograms were performed in the affected individuals.
Results
We successfully identified causative mutations in patients from the Chinese families with RDs: the known mutation IMPDH1 c.942_944delGAA in a family with retinitis pigmentosa, the novel mutation ABCA4 c.1924T>A in a family with Stargardt disease, and the novel mutation NMNAT1 c.272A>G and known mutation NMNAT1 c.196C>T in a family with Leber congenital amaurosis. All variations segregated with the disease phenotypes in the respective families and were absent from ethnically matched control chromosomes. Prediction analysis demonstrated the two novel missense mutations might be damaging.
Conclusions
The results strongly suggested these mutations were responsible for different RD phenotypes in the Chinese families. NGS technology provides an accurate and economic method for identifying causative genes for RDs.
PMCID: PMC4000715  PMID: 24791140
20.  Identification of novel CYP4V2 gene mutations in 92 Chinese families with Bietti’s crystalline corneoretinal dystrophy 
Molecular Vision  2014;20:1806-1814.
Purpose
To characterize the spectrum of CYP4V2 gene mutations in 92 unrelated Chinese probands with Bietti’s crystalline dystrophy (BCD) and to describe the molecular and clinical characteristics of four novel CYP4V2 mutations associated with BCD.
Methods
All study participants underwent a complete ophthalmological examination. Mutational screening of CYP4V2 coding regions and flanking intron sequences was examined via directional Sanger sequencing, with allele separation confirmed by screening other family members. Subsequent in silico analysis of the mutational consequence on protein function was undertaken, with the impact of the novel mutation on pre-mRNA splicing examined via RT–PCR.
Results
Fifteen disease-causing variants were identified in 92 probands with BCD, including four novel mutations and eleven previously reported mutations. The most prevalent mutation was c.802_810del17insGC, which was detected in 69 unrelated families, with an allele frequency of 52.7% (97/184). Homozygosity was revealed in 35 unrelated families, and compound heterozygosity was observed in 43 subjects. Four patients harbored four novel variants, with these mutations cosegregated within all affected individuals and were not found in unaffected family members and 100 unrelated controls. Transcriptional analysis of a novel splice mutation revealed altered RNA splicing. In silico analysis predicted that the missense variant, p.Tyr343Asp, disrupted the CYP4V2 surface electrostatic potential distribution and spatial conformation. Among the patients with four novel mutations, genotype did not always correlate with age at onset, disease course, or electroretinogram (ERG) changes, with phenotypic variations even noted within the same genotype.
Conclusions
The c.802_810del17insCG mutation was the most common mutation in the 92 Chinese probands with BCD examined. Four novel mutations were identified, contributing to the spectrum of CYP4V2 mutations associated with BCD, with no clear link established between disease phenotype and genotype.
PMCID: PMC4287718  PMID: 25593508
21.  Effects of sevoflurane and propofol on right ventricular function and pulmonary circulation in patients undergone esophagectomy 
Object: Sevoflurane and propofol are both widely used in clinical anesthesia. The aim of this study is to compare the effects of sevoflurane and propofol on right ventricular function and pulmonary circulation in patients receiving esophagectomy. Methods: Forty adult patients undergoing an elective open-chest thoracotomy for esophagectomy were randomized to receive either propofol (n=20) or sevoflurane (n=20) as the main anesthetic agent. The study was performed in Changzheng Hospital. Hemodynamic data were recorded at specific intervals: before the surgery (T0), BIS values reaching 40 after anesthesia induction (T1), two-lung ventilation (T2), ten minutes after one-lung ventilation (T3), the end of the operation (T4) using PiCCO2 and Swan-Ganz catheter. Results: CI, RVEF, RVSWI and RVEDVI were significantly smaller in propofol group than those in sevoflurane group throughout the surgery (P<0.05). However, SVRI was significantly greater in propofol group than that in sevoflurane group (P<0.05). Compared with the patients in propofol group, the patients who received sevoflurane had a greater reduction in OI and increase in Os/Ot (P<0.05). And, PVRI was significantly smaller in sevoflurane group than in propofol group (P<0.05). Conclusion: Anesthesia with sevoflurane preserved better right ventricular function than propofol in patients receiving esophagectomy. However, propofol improved oxygenation and shunt fraction during one-lung ventilation compared with sevoflurane anesthesia. To have the best effect, anesthesiologists can choose the two anesthetics flexibly according to the monitoring results.
PMCID: PMC3885482  PMID: 24427348
Sevoflurane; propofol; right ventricular function; pulmonary circulation; esophagectomy
22.  Competitive Interactions between Parasitoids Provide New Insight into Host Suppression 
PLoS ONE  2013;8(11):e82003.
Understanding the dynamics of potential inter- and intraspecific competition in parasitoid communities is crucial in the screening of efficient parasitoid species and for utilization of the best parasitoid species combinations. In this respect, the host-parasitoid systems, Bemisia tabaci and two parasitoids, Eretmocerus hayati (exotic) and Encarsia sophia (existing) were studied under laboratory conditions to investigate whether interference competition between the exotic and existing species occurs as well as the influence of potential interference competition on the suppression of the host B. tabaci. Studies on interspecific-, intraspecific- and self-interference competition in two parasitoid species were conducted under both rich and limited host resource conditions. Results showed that (1) both parasitoid species negatively affect the progeny production of the other under both rich and limited host resource conditions; (2) both parasitoid species interfered intraspecifically on conspecific parasitized hosts when the available hosts are scarce and; 3) the mortality of B. tabaci induced by parasitoids via parasitism, host-feeding or both parasitism and host-feeding together varied among treatments under different host resource conditions, but showed promise for optimizing control strategies. As a result of our current findings, we suggest a need to investigate the interactions between the two parasitoids on continuous generations.
doi:10.1371/journal.pone.0082003
PMCID: PMC3842984  PMID: 24312394
23.  Characteristics of Clinical Shiga Toxin-Producing Escherichia coli Isolated from British Columbia 
BioMed Research International  2013;2013:878956.
Shiga toxin-producing Escherichia coli (STEC) are significant public health threats. Although STEC O157 are recognized foodborne pathogens, non-O157 STEC are also important causes of human disease. We characterized 10 O157:H7 and 15 non-O157 clinical STEC derived from British Columbia (BC). Eae, hlyA, and stx were more frequently observed in STEC O157, and 80 and 100% of isolates possessed stx1 and stx2, respectively. In contrast, stx1 and stx2 occurred in 80 and 40% of non-O157 STEC, respectively. Comparative genomic fingerprinting (CGF) revealed three distinct clusters (C). STEC O157 was identified as lineage I (LI; LSPA-6 111111) and clustered as a single group (C1). The cdi gene previously observed only in LII was seen in two LI O157 isolates. CGF C2 strains consisted of diverse non-O157 STEC while C3 included only O103:H25, O118, and O165 serogroup isolates. With the exception of O121 and O165 isolates which were similar in virulence gene complement to STEC O157, C1 O157 STEC produced more Stx2 than non-O157 STEC. Antimicrobial resistance (AMR) screening revealed resistance or reduced sensitivity in all strains, with higher levels occurring in non-O157 STEC. One STEC O157 isolate possessed a mobile blaCMY-2 gene transferrable across genre via conjugation.
doi:10.1155/2013/878956
PMCID: PMC3807556  PMID: 24199201
24.  A video-assisted thoracic surgical lobectomy for a lung tumour with a rare anomalous pulmonary artery 
A detailed knowledge of anomalies of the anatomical course of the pulmonary vessels is extremely important for video-assisted thoracic surgery (VATS). Inadvertent vascular ligation and dissection are catastrophic for patients undergoing lobectomy. We describe a case with a rare anomaly of the left pulmonary artery and highlight the importance of identifying the courses of pulmonary vessels for VATS lobectomy.
doi:10.1093/icvts/ivs290
PMCID: PMC3445375  PMID: 22815327
Video-assisted thoracic surgery; Anomaly; Pulmonary artery
25.  Phytoestrogen α-Zearalanol Attenuates Homocysteine-Induced Apoptosis in Human Umbilical Vein Endothelial Cells 
BioMed Research International  2013;2013:813450.
Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. The enhanced nitrative stress plays an important role in homocysteine-induced endothelial dysfunction. Previous studies have showed that phytoestrogen α-zearalanol alleviated endothelial injury in ovariectomized hyperhomocysteinemic rats; however, the underlying mechanism remains to be clarified. This study was to investigate the effects of α-zearalanol on homocysteine-induced endothelial apoptosis in vitro and explore the possible role of nitrative stress in these effects. Results showed that homocysteine (500 μmol/L, 24 h) induced the apoptosis of human umbilical vein endothelial cells (HUVECs) obviously, and this effect was significantly attenuated by pretreatment with α-zearalanol (10−8~10−6 mol/L). Moreover, α-zearalanol downregulated proapoptotic protein Bax, upregulated antiapoptotic proteins Bcl-2 and Bcl-XL, and decreased the expression and activity of caspase-9. These findings demonstrated that α-zearalanol could effectively alleviate homocysteine-induced endothelial apoptosis, and this antiapoptosis effect might be related to the inhibition of the intrinsic pathway. Western blot indicated an enhanced 3-nitrotyrosine expression in HUVECs when challenged with homocysteine, which was attenuated by pretreatment with α-zearalanol. This result implied that inhibition of nitrative stress might play a role in the protective effect of α-zearalanol on endothelial cells. Such discovery may shed a novel light on the antiatherogenic activities of α-zearalanol in hyperhomocysteinemia.
doi:10.1155/2013/813450
PMCID: PMC3806352  PMID: 24195080

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