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1.  Does recurrent laryngeal nerve lymph node metastasis really affect the prognosis in node-positive patients with squamous cell carcinoma of the middle thoracic esophagus? 
BMC Surgery  2014;14:43.
Recurrent laryngeal nerve (RLN) lymph node metastasis used to be shown a predictor for poor prognosis in esophageal squamous cell carcinoma. The purpose of this study was to evaluate the prognostic impact of RLN node metastasis and the number of metastatic lymph nodes in node-positive patients with squamous cell carcinoma of middle thoracic esophagus.
A cohort of 235 patients who underwent curative surgery for squamous cell carcinoma of middle thoracic esophagus was investigated. The prognostic impact was evaluated by univariate and multivariate analyses.
Lymph node metastasis was found in 133 patients. Among them, 81 had metastatic RLN nodes, and 52 had at least one positive node but no RLN nodal involvement. The most significant difference in survival was detected between patients with metastatic lymph nodes below and above a cutoff value of six (P < 0.001). Multivariate analysis revealed that the number of metastatic lymph nodes was a significant factor associated with overall survival (P < 0.001), but RLN lymph node metastasis was not (P = 0.865).
RLN Lymph node metastasis is not, but the number of metastatic nodes is a prognostic predictor in node-positive patients with squamous cell carcinoma of the middle thoracic esophagus.
PMCID: PMC4105105  PMID: 25016483
Esophageal cancer; Lymph node metastasis; Recurrent laryngeal nerve; Squamous cell carcinoma
2.  Association of Gln27Glu and Arg16Gly Polymorphisms in Beta2-Adrenergic Receptor Gene with Obesity Susceptibility: A Meta-Analysis 
PLoS ONE  2014;9(6):e100489.
The beta2-adrenergic receptor (ADRB2) gene polymorphism has been implicated in susceptibility to obesity, but study results are still controversial.
The present meta-analysis is performed to determine whether there are any associations between the Gln27Glu (rs1042714) or the Arg16Gly (rs1042713) polymorphisms in ADRB2 and obesity susceptibility.
The PubMed (1950–2014), Embase (1974–2014), and China National Knowledge Infrastructure (CNKI, 1994–2014) databases were searched using the search terms (“Beta2-adrenergic receptor”, “β2-adrenergic receptor” or “ADRB2”), “polymorphism,” and “obesity”. Fixed- or random-effects pooled measures were determined on the bias of heterogeneity tests across studies. Publication bias was examined by Egger's test and the modified Begg's test.
Eighteen published articles were selected for meta-analysis. Overall analyses showed that rs1042714 (Gln27Glu) was associated with significantly increased obesity risk in the heterozygote model (Gln/Glu vs. Gln/Gln: OR: 1.16, 95% CI: 1.04–1.30, I2 = 49%, P = 0.009) and the dominant model (Gln/Glu + Glu/Glu vs. Gln/Gln: OR: 1.2, 95% CI: 1.00–1.44, I2 = 55%, P = 0.04), whereas no significant association was found in the other models for rs1042714. Also, no significant association was found between the rs1042713 (Arg16Gly) gene polymorphism and the risk of obesity in all genetic models. In addition, neither rs1042713 (Arg16Gly) nor rs1042714 (Gln27Glu) showed any significant association with obesity susceptibility when the population were stratified based on gender.
Our meta-analysis revealed that the rs1042714 (Gln27Glu) polymorphism is associated with obesity susceptibility. However, our results do not support an association between rs1042713 (Arg16Gly) polymorphisms and obesity in the populations investigated. This conclusion warrants confirmation by more case-control and cohort studies.
PMCID: PMC4069060  PMID: 24960039
3.  Associations of leukocyte telomere length with body anthropometric indices and weight change in Chinese women 
Obesity (Silver Spring, Md.)  2013;21(12):10.1002/oby.20321.
Telomeres are specialized chromatin structures essential for maintenance of chromosomal integrity and stability. Obesity has been proposed to be associated with telomere shortening; however, epidemiologic evidence has been conflicting. We conducted a study to evaluate the associations of telomere length with various anthropometric indices of general and abdominal obesity, as well as weight change.
Design and Methods
The study included 2,912 Chinese women ages 40–70 years. Monochrome multiplex quantitative PCR was applied to measure relative telomere length. ANOVA and the Dunnett test were used to compare log-transformed relative telomere length. Tests for linear trend were performed by entering the ordinal exposure as continuous parameters in the models.
There is an inverse association between telomere length and body mass index (BMI) (Ptrend = 0.005), waist circumference (Ptrend = 0.004), waist-to-height ratio (WHtR) (Ptrend = 0.004), weight (Ptrend = 0.010), and hip circumference (Ptrend = 0.026), but not waist-to-hip ratio (WHR) (Ptrend = 0.116) or height (Ptrend = 0.675). Weight change since age 50 was further evaluated among women over age 55. Women who maintained their weight within ±5% since age 50, particularly within a normal range (BMI = 18.5–24.9 kg/m2), or reduced their weight from overweight (BMI = 25–29.9 kg/m2) or obesity (BMI ≥30 kg/m2) to normal range, had a longer mean of current telomere length than women who gained weight since age 50 (Ptrend = 0.025), particularly those who stayed in obesity or gained weight from normal range or overweight to obesity (P = 0.023).
Our findings provide strong evidence supporting the hypothesis that telomere shortening is associated with obesity and that maintaining body weight within a normal range helps maintain telomere length.
PMCID: PMC3676725  PMID: 23408544
6.  LRIG2 expression and prognosis in non-small cell lung cancer 
Oncology Letters  2014;8(2):667-672.
The human leucine-rich repeats and immunoglobulin-like domains 2 (LRIG2) protein has been shown to be of prognostic value in several types of human cancer, however, the expression profiles of LRIG2 have not been described in non-small cell lung cancer (NSCLC). The present study evaluated the mRNA expression of LRIG2 in tumor specimens obtained from 39 NSCLC patients by SYBR Green quantitative polymerase chain reaction and the protein expression of LRIG2 in formalin-fixed paraffin sections obtained from 116 NSCLC patients by immunohistochemistry. The correlations between LRIG2 expression and clinicopathological data were analyzed. The patient survival data were collected retrospectively and the possible prognostic value of LRIG2 protein expression was investigated. The results showed that the mRNA expression of LRIG2 was decreased in NSCLC cancer tissues, which was associated with histological subtypes and tumor differentiation status. The protein expression of LRIG2 was only observed in the cytoplasm of the tumor tissue, which conformed to the mRNA expression results. Furthermore, the patients with high LRIG2 cytoplasmic expression showed poor survival times, and the five-year survival rate for patients with high LRIG2 expression was 27.8%, compared with 38.8% for patients with low expression (P=0.034), indicating that LRIG2 expression levels may have a potential role in the pathogenesis of NSCLC, and also a significant prognostic value. Further studies are required to fully elucidate the exact function of LRIG2 in NSCLC.
PMCID: PMC4081377  PMID: 25013483
non-small cell lung cancer; immunohistochemistry; leucine-rich repeats and immunoglobulin-like domains 2; real-time polymerase chain reaction
7.  Corneal ulcer caused by nocardia brasiliensis in a patient with diabetes 
PMCID: PMC4003100  PMID: 24790888
8.  Association of Leukocyte Telomere Length With Breast Cancer Risk: Nested Case-Control Findings From the Shanghai Women's Health Study 
American Journal of Epidemiology  2013;177(7):617-624.
Telomeres are specialized chromatin structures essential for the maintenance of chromosomal integrity and stability. Telomere shortening has been linked to multiple aging-related diseases, including cancer. Evidence associating telomere length with breast cancer risk—most of which has been from retrospective case-control studies—is conflicting. We conducted a nested case-control study based on the Shanghai Women's Health Study (1997–2009) in which we evaluated the association of telomere length and breast cancer risk using peripheral blood samples collected before cancer diagnosis (601 cases and 695 controls). We used monochrome multiplex quantitative polymerase chain reaction to measure relative telomere length. Multiple logistic regressions were used to derive adjusted odds ratios with 95% confidence intervals as the measure of association. Telomere length was inversely correlated with age (r = −0.22). Women with moderately long telomeres (those in the fourth quintile) had the lowest breast cancer risk. Risk increased in a dose-response manner with decreasing quintile of telomere length; odds ratios were 1.39 (95% confidence interval (CI): 0.95, 2.04), 1.79 (95% CI: 1.17, 2.75), and 2.39 (95% CI: 1.45, 3.92), respectively, for the third, second, and first quintiles compared with the fourth quintile. A slightly elevated risk of breast cancer (odds ratio = 1.35, 95% CI: 0.90, 2.04), although one that was not statistically significant, was found in the top quintile (longest telomeres). Our results support the hypothesis that telomere shortening is associated with increased risk of breast cancer and suggest a possible elevated risk associated with long telomeres.
PMCID: PMC3657533  PMID: 23444102
breast cancer; biomarkers; epidemiology; genetic factors; telomere
9.  Role of Investment Heterogeneity in the Cooperation on Spatial Public Goods Game 
PLoS ONE  2014;9(3):e91012.
Public cooperation plays a significant role in the survival and maintenance of biological species, to elucidate its origin thus becomes an interesting question from various disciplines. Through long-term development, the public goods game has proven to be a useful tool, where cooperator making contribution can beat again the free-rides. Differentiating from the traditional homogeneous investment, individual trend of making contribution is more likely affected by the investment level of his neighborhood. Based on this fact, we here investigate the impact of heterogeneous investment on public cooperation, where the investment sum is mapped to the proportion of cooperators determined by parameter . Interestingly, we find, irrespective of interaction networks, that the increment of (increment of heterogeneous investment) is beneficial for promoting cooperation and even guarantees the complete cooperation dominance under weak replication factor. While this promotion effect can be attributed to the formation of more robust cooperator clusters and shortening END period. Moreover, we find that this simple mechanism can change the potential interaction network, which results in the change of phase diagrams. We hope that our work may shed light on the understanding of the cooperative behavior in other social dilemmas.
PMCID: PMC3954582  PMID: 24632779
10.  Ratiometric electrochemical proximity assay for sensitive one-step protein detection 
Scientific Reports  2014;4:4360.
This work proposes the concept of ratiometric electrochemical proximity assay (REPA), which can be used for one-step, highly sensitive and selective detection of protein. The assay strategy was achieved on a sensing interface that was formed by hybridization of methylene blue (MB)-labeled antibody-DNA probe (MB-DNA1-Ab1) with ferrocene (Fc)-labeled DNA capture probe (Fc-P) modified gold electrode. On the interface the target protein could trigger the formation of immunocomplex between MB-DNA1-Ab1 and detection antibody-DNA probe (Ab2-DNA2) and subsequently the proximity hybridization of DNA1-DNA2, which led to the departure of MB-DNA1-Ab1 from the interface. The remained Fc-P could form a hairpin structure to take Fc group to electrode surface. Therefore, the recognition of target protein to Ab1 and Ab2 resulted in both the “signal-off” of MB and the “signal-on” of Fc for dual-signal electrochemical ratiometric readout. The proposed REPA could be carried out in one-step with 40-min duration and showed a wide detection range from 0.05 to 100 ng/mL with pg/mL limit of detection, displaying great potential for convenient point-of-care testing and commercial application.
PMCID: PMC3950580  PMID: 24618513
11.  Association of gyrA/B mutations and resistance levels to fluoroquinolones in clinical isolates of Mycobacterium tuberculosis 
To evaluate the association between mutations in the genes gyrA/B and resistance levels to fluoroquinolones in clinical isolates of Mycobacterium tuberculosis, a total of 80 ofloxacin-resistant isolates collected in 2009 by the Shanghai Municipal Centers for Disease Control and Prevention were studied. The minimum inhibitory concentration (MIC) of ofloxacin, moxifloxacin and gatifloxacin for each isolate was determined using the microscopic observation drug susceptibility assay. Sequencing was used to identify mutations in the quinolone resistance-determining region (QRDR) of the gyrA and gyrB genes. In total, 68 isolates had mutations in gyrA, three isolates had mutations in gyrB, six isolates had mutations in both gyrA and gyrB, and three isolates had no mutations. Two common mutations in gyrA, the D94G and D94N mutations, were associated with higher-level resistance to all three fluoroquinolones than two other common mutations (A90V and D94A). Understanding the relationship between MICs and mutations in ofloxacin-resistant isolates will facilitate the optimization of the use of new-generation fluoroquinolones to treat patients with ofloxacin-resistant tuberculosis (TB).
PMCID: PMC3974338
fluoroquinolones; MICs; M. tuberculosis; mutations
12.  2-{(E)-[4-(Di­phenyl­amino)­phen­yl]imino­meth­yl}phenol 
The asymmetric unit of the title Schiff base molecule, C25H20N2O, contains two independent mol­ecules. In each mol­ecule, the C=N bond is in an E conformation. The most significant difference between the two mol­ecules is seen for the dihedral angles between the meth­oxy-substituted benzene ring and the two phenyl rings, which are 85.5 (1) and 82.3 (1)° in the first mol­ecule, and 49.0 (1) and 40.4 (1)° in the second. This conformational difference is reflected in the central C=N—C C torsion angle, which is 28.7 (2)° in the first mol­ecule and −29.8 (3)° in the other. In each mol­ecule, there is an intra­molecular O—H⋯N hydrogen bond.
PMCID: PMC3998446  PMID: 24765015
13.  Correction: Network Evolution Induced by Asynchronous Stimuli through Spike-Timing-Dependent Plasticity 
PLoS ONE  2014;9(1):10.1371/annotation/417c1eb3-1de1-4d04-8c1d-3f73ffc57f26.
PMCID: PMC3905992
14.  Growth Arrest Specific 2 Is Up-Regulated in Chronic Myeloid Leukemia Cells and Required for Their Growth 
PLoS ONE  2014;9(1):e86195.
Although the generation of BCR-ABL is the molecular hallmark of chronic myeloid leukemia (CML), the comprehensive molecular mechanisms of the disease remain unclear yet. Growth arrest specific 2 (GAS2) regulates multiple cellular functions including cell cycle, apoptosis and calpain activities. In the present study, we found GAS2 was up-regulated in CML cells including CD34+ progenitor cells compared to their normal counterparts. We utilized RNAi and the expression of dominant negative form of GAS2 (GAS2DN) to target GAS2, which resulted in calpain activity enhancement and growth inhibition of both K562 and MEG-01 cells. Targeting GAS2 also sensitized K562 cells to Imatinib mesylate (IM). GAS2DN suppressed the tumorigenic ability of MEG-01 cells and impaired the tumour growth as well. Moreover, the CD34+ cells from CML patients and healthy donors were transduced with control and GAS2DN lentiviral vectors, and the CD34+ transduced (YFP+) progeny cells (CD34+YFP+) were plated for colony-forming cell (CFC) assay. The results showed that GAS2DN inhibited the CFC production of CML cells by 57±3% (n = 3), while affected those of normal hematopoietic cells by 31±1% (n = 2). Next, we found the inhibition of CML cells by GAS2DN was dependent on calpain activity but not the degradation of beta-catenin. Lastly, we generated microarray data to identify the differentially expressed genes upon GAS2DN and validated that the expression of HNRPDL, PTK7 and UCHL5 was suppressed by GAS2DN. These 3 genes were up-regulated in CML cells compared to normal control cells and the growth of K562 cells was inhibited upon HNRPDL silence. Taken together, we have demonstrated that GAS2 is up-regulated in CML cells and the inhibition of GAS2 impairs the growth of CML cells, which indicates GAS2 is a novel regulator of CML cells and a potential therapeutic target of this disease.
PMCID: PMC3897655  PMID: 24465953
15.  Correlates of 25-Hydroxyvitamin D among Chinese Breast Cancer Patients 
PLoS ONE  2014;9(1):e86467.
Few studies have investigated vitamin D status in association with modifiable lifestyle factors and clinical characteristics among breast cancer patients, with no studies among Chinese women, who may be at higher risk of vitamin D deficiency. We aimed to evaluate circulating 25-hydroxyvitamin D (25(OH)D) levels in association with clinical and lifestyle factors among 1,940 Chinese breast cancer patients.
Participants included breast cancer cases aged 22–77 from a population-based case-control study conducted in Shanghai, China during 1996–1998 (n = 1,044) and 2002–2005 (n = 896). Circulating 25(OH)D levels were measured in plasma samples (95% collected ≤6 months post-diagnosis). Prevalence ORs and 95% CIs were derived from multinomial logistic regression models, adjusting for age, season, and other factors.
About 23% and 48% of women were vitamin D deficient (<30 nmol/L) or insufficient (30–50 nmol/L), respectively. Tumor characteristics were not associated with vitamin D status. Higher BMI was associated with increased odds of vitamin D deficiency (ORs (95% CIs): 1 (reference), 1.12 (0.85,1.47), and 1.57 (1.02,2.42), for <23, 23–<27.5, and ≥27.5 kg/m2, respectively, Ptrend <0.06). Total physical activity was associated with reduced odds of vitamin D deficiency (ORs (95% CIs):1 (reference), 0.84 (0.59,1.20), 0.65 (0.45,0.93), and 0.69 (0.48,1.00), for <7.65, 7.65–<10.6, 10.6–<13.5, ≥13.5 MET-hours/day, respectively, Ptrend <0.02). Smoking was associated with vitamin D insufficiency and deficiency (ORs (95% CIs): 2.50 (1.07,5.84) and 2.78 (1.11,6.95), respectively).
In the largest study to date, the prevalence of low vitamin D status was high among Chinese breast cancer patients and associated with higher BMI, smoking, and lower physical activity. Our findings support careful monitoring of vitamin D status and recommendations for supplementation and other lifestyle modifications that may improve vitamin D status in breast cancer patients.
PMCID: PMC3897707  PMID: 24466109
16.  Systemic Spread and Propagation of a Plant-Pathogenic Virus in European Honeybees, Apis mellifera 
mBio  2014;5(1):e00898-13.
Emerging and reemerging diseases that result from pathogen host shifts are a threat to the health of humans and their domesticates. RNA viruses have extremely high mutation rates and thus represent a significant source of these infectious diseases. In the present study, we showed that a plant-pathogenic RNA virus, tobacco ringspot virus (TRSV), could replicate and produce virions in honeybees, Apis mellifera, resulting in infections that were found throughout the entire body. Additionally, we showed that TRSV-infected individuals were continually present in some monitored colonies. While intracellular life cycle, species-level genetic variation, and pathogenesis of the virus in honeybee hosts remain to be determined, the increasing prevalence of TRSV in conjunction with other bee viruses from spring toward winter in infected colonies was associated with gradual decline of host populations and winter colony collapse, suggesting the negative impact of the virus on colony survival. Furthermore, we showed that TRSV was also found in ectoparasitic Varroa mites that feed on bee hemolymph, but in those instances the virus was restricted to the gastric cecum of Varroa mites, suggesting that Varroa mites may facilitate the spread of TRSV in bees but do not experience systemic invasion. Finally, our phylogenetic analysis revealed that TRSV isolates from bees, bee pollen, and Varroa mites clustered together, forming a monophyletic clade. The tree topology indicated that the TRSVs from arthropod hosts shared a common ancestor with those from plant hosts and subsequently evolved as a distinct lineage after transkingdom host alteration. This study represents a unique example of viruses with host ranges spanning both the plant and animal kingdoms.
Pathogen host shifts represent a major source of new infectious diseases. Here we provide evidence that a pollen-borne plant virus, tobacco ringspot virus (TRSV), also replicates in honeybees and that the virus systemically invades and replicates in different body parts. In addition, the virus was detected inside the body of parasitic Varroa mites, which consume bee hemolymph, suggesting that Varroa mites may play a role in facilitating the spread of the virus in bee colonies. This study represents the first evidence that honeybees exposed to virus-contaminated pollen could also be infected and raises awareness of potential risks of new viral disease emergence due to host shift events. About 5% of known plant viruses are pollen transmitted, and these are potential sources of future host-jumping viruses. The findings from this study showcase the need for increased surveillance for potential host-jumping events as an integrated part of insect pollinator management programs.
PMCID: PMC3903276  PMID: 24449751
17.  Network Evolution Induced by Asynchronous Stimuli through Spike-Timing-Dependent Plasticity 
PLoS ONE  2013;8(12):e84644.
In sensory neural system, external asynchronous stimuli play an important role in perceptual learning, associative memory and map development. However, the organization of structure and dynamics of neural networks induced by external asynchronous stimuli are not well understood. Spike-timing-dependent plasticity (STDP) is a typical synaptic plasticity that has been extensively found in the sensory systems and that has received much theoretical attention. This synaptic plasticity is highly sensitive to correlations between pre- and postsynaptic firings. Thus, STDP is expected to play an important role in response to external asynchronous stimuli, which can induce segregative pre- and postsynaptic firings. In this paper, we study the impact of external asynchronous stimuli on the organization of structure and dynamics of neural networks through STDP. We construct a two-dimensional spatial neural network model with local connectivity and sparseness, and use external currents to stimulate alternately on different spatial layers. The adopted external currents imposed alternately on spatial layers can be here regarded as external asynchronous stimuli. Through extensive numerical simulations, we focus on the effects of stimulus number and inter-stimulus timing on synaptic connecting weights and the property of propagation dynamics in the resulting network structure. Interestingly, the resulting feedforward structure induced by stimulus-dependent asynchronous firings and its propagation dynamics reflect both the underlying property of STDP. The results imply a possible important role of STDP in generating feedforward structure and collective propagation activity required for experience-dependent map plasticity in developing in vivo sensory pathways and cortices. The relevance of the results to cue-triggered recall of learned temporal sequences, an important cognitive function, is briefly discussed as well. Furthermore, this finding suggests a potential application for examining STDP by measuring neural population activity in a cultured neural network.
PMCID: PMC3877323  PMID: 24391971
18.  The High Prevalence of Vitamin D Deficiency and Its Related Maternal Factors in Pregnant Women in Beijing 
PLoS ONE  2013;8(12):e85081.
Maternal vitamin D deficiency has been suggested to influence fetal and neonatal health. Little is known about vitamin D status in Chinese pregnant women. The purpose of this study was to assess the vitamin D status of pregnant women residing in Beijing in winter and evaluate the impact of maternal factors on serum 25-hydroxyvitamin D [25(OH)D] levels. The study was conducted on 125 healthy pregnant women. For each individual, data concerning pre-pregnancy weight, educational status, use of multivitamins and behavioral factors such as daily duration of computer use, walking and sun exposure were obtained. Serum concentrations of 25(OH)D were measured by enzyme-linked immunosorbent assay. The prevalence of vitamin D deficiency (25(OH)D < 50 nmol/L) was 96.8% and almost half (44.8%) of women were severely vitamin D deficiency (25(OH)D < 25 nmol/L). The concentration of 25(OH)D was lower in women with shorter duration of sun exposure (≤ 0.5 h/day, 25.3 ± 8.9 nmol/L) than that in women with longer duration of sun exposure (> 0.5 h/day; 30.3± 9.5 nmol/L; P = 0.003). Thirty six women (28.8%) had sun exposure duration ≥ 1.5h/day. The 25(OH)D concentration in these women was 31.5 ± 9.4 nmol/L which was also much lower than the normal level. Women who reported taking a multivitamin supplement had significantly higher 25(OH)D concentrations (32.3 ± 9.5 nmol/L) when compared with non-users (24.9 ± 8.2 nmol/L; P < 0.001). Pregnant women in Beijing are at very high risk of vitamin D deficiency in winter. Duration of Sun exposure and the use of multivitamin were the most important determinants for vitamin D status. However, neither prolonging the time of sunlight exposure nor multivitamin supplements can effectively prevent pregnant women from vitamin D deficiency. Other measures might have to be taken for pregnant women to improve their vitamin D status in winter.
PMCID: PMC3873449  PMID: 24386450
19.  Rapid microsatellite development for tree peony and its implications 
BMC Genomics  2013;14:886.
Microsatellites are ubiquitous in genomes of various organisms. With the realization that they play roles in developmental and physiological processes, rather than exist as ‘junk’ DNA, microsatellites are receiving increasing attention. Next-generation sequencing allows acquisition of large-scale microsatellite information, and is especially useful for plants without reference genome sequences.
In this study, enriched DNA libraries of tree peony, a well-known ornamental woody shrub, were used for high-throughput microsatellite development by 454 GS-FLX Titanium pyrosequencing. We obtained 675,221 reads with an average length of 356 bp. The total size of examined sequences was 240,672,018 bp, from which 237,134 SSRs were identified. Of these sequences, 164,043 contained SSRs, with 27% featuring more than one SSR. Interestingly, a high proportion of SSRs (43%) were present in compound formation. SSRs with repeat motifs of 1–4 bp (mono-, di-, tri-, and tetra-nucleotide repeats) accounted for 99.8% of SSRs. Di-nucleotide repeats were the most abundant. As in most plants, the predominant motif in tree peony was (A/T)n, with (G/C)n less common. The lengths of SSRs were classified into 11 groups. The shortest SSRs (10 bp) represented 1% of the total number, whereas SSRs 21–30 and 101–110 bp long accounted for 26% and 29%, respectively, of all SSRs. Many sequences (42,111) were mapped to CDS (coding domain sequence) regions using Arabidopsis as a reference. GO annotation analysis predicted that CDSs with SSRs performed various functions associated with cellular components, molecular functions, and biological processes. Of 100 validated primer pairs, 24 were selected for polymorphism analysis among 23 genotypes; cluster analysis of the resulting data grouped genotypes according to known relationships, confirming the usefulness of the developed SSR markers.
The results of our large-scale SSR marker development using tree peony are valuable for investigating plant genomic structural evolution and elucidating phenotypic variation in this species during its evolution and artificial selection. The newly identified SSRs should be useful for genetic linkage map construction, QTL mapping, gene location and cloning, and molecular marker-assisted breeding. In addition, the genome-wide marker resources generated in this study should aid genomic studies of tree peony and related species.
PMCID: PMC3878651  PMID: 24341681
zzzMicrosatellite; Next-generation sequencing; Tree peozzzzny; Ornamental; SSR marker
20.  Angiotensin-converting enzyme gene 2350 G/A polymorphism and susceptibility to atrial fibrillation in Han Chinese patients with essential hypertension 
Clinics  2013;68(11):1428-1432.
The angiotensin-converting enzyme gene is one of the most studied candidate genes related to atrial fibrillation. Among the polymorphisms of the angiotensin-converting enzyme gene, the 2350 G/A polymorphism (rs4343) is known to have the most significant effects on the plasma angiotensin-converting enzyme concentration. The aim of the present study was to investigate the association of the angiotensin-converting enzyme 2350 G/A polymorphism with atrial fibrillation in Han Chinese patients with essential hypertension.
A total of 169 hypertensive patients were eligible for this study. Patients with atrial fibrillation (n = 75) were allocated to the atrial fibrillation group, and 94 subjects without atrial fibrillation were allocated to the control group. The PCR-based restriction fragment length polymorphism technique was used to assess the genotype frequencies.
The distributions of the angiotensin-converting enzyme 2350 G/A genotypes (GG, GA, and AA, respectively) were 40.43%, 41.49%, and 18.08% in the controls and 18.67%, 46.67%, and 34.66% in the atrial fibrillation subjects (p = 0.037). The frequency of the A allele in the atrial fibrillation group was significantly greater than in the control group (58.00% vs. 38.83%, p = 0.0007). Compared with the wild-type GG genotype, the GA and AA genotypes had an increased risk for atrial fibrillation. Additionally, atrial fibrillation patients with the AA genotype had greater left atrial dimensions than the patients with the GG or GA genotypes (p<0.01 and p<0.05, respectively).
The results obtained in this study indicate that the angiotensin-converting enzyme 2350 G/A polymorphism is associated with atrial fibrillation and that the A allele shows an increased risk for atrial fibrillation in Han Chinese patients with essential hypertension.
PMCID: PMC3812555  PMID: 24270955
Angiotensin-converting enzyme; Genetic polymorphism; Atrial fibrillation; Essential hypertension; China
21.  JAK1 truncating mutations in gynecologic cancer define new role of cancer-associated protein tyrosine kinase aberrations 
Scientific Reports  2013;3:3042.
Cancer-associated protein tyrosine kinase (PTK) mutations usually are gain-of-function (GOF) mutations that drive tumor growth and metastasis. We have found 50 JAK1 truncating mutations in 36 of 635 gynecologic tumors in the Total Cancer Care® (TCC®) tumor bank. Among cancer cell lines containing JAK1 truncating mutations in the Cancer Cell Line Encyclopedia databank, 68% are gynecologic cancer cells. Within JAK1 the K142, P430, and K860 frame-shift mutations were identified as hot spot mutation sites. Sanger sequencing of cancer cell lines, primary tumors, and matched normal tissues confirmed the JAK1 mutations and showed that these mutations are somatic. JAK1 mediates interferon (IFN)-γ-regulated tumor immune surveillance. Functional assays show that JAK1 deficient cancer cells are defective in IFN-γ-induced LMP2 and TAP1 expression, loss of which inhibits presentation of tumor antigens. These findings identify recurrent JAK1 truncating mutations that could contribute to tumor immune evasion in gynecologic cancers, especially in endometrial cancer.
PMCID: PMC3807107  PMID: 24154688
22.  A Novel Nicotinic Mechanism Underlies β-Amyloid-Induced Neuronal Hyperexcitation 
The Journal of Neuroscience  2013;33(17):7253-7263.
There is a significantly elevated incidence of epilepsy in Alzheimer's disease (AD). Moreover, there is neural hyperexcitation/synchronization in transgenic mice expressing abnormal levels or forms of amyloid precursor protein and its presumed, etiopathogenic product, amyloid-β1–42 (Aβ). However, the underlying mechanisms of how Aβ causes neuronal hyperexcitation remain unclear. Here, we report that exposure to pathologically relevant levels of Aβ induces Aβ form-dependent, concentration-dependent, and time-dependent neuronal hyperexcitation in primary cultures of mouse hippocampal neurons. Similarly, Aβ exposure increases levels of nicotinic acetylcholine receptor (nAChR) α7 subunit protein on the cell surface and α7-nAChR function, but not α7 subunit mRNA, suggesting post-translational upregulation of functional α7-nAChRs. These effects are prevented upon coexposure to brefeldin A, an inhibitor of endoplasmic reticulum-to-Golgi protein transport, consistent with an effect on trafficking of α7 subunits and assembled α7-nAChRs to the cell surface. Aβ exposure-induced α7-nAChR functional upregulation occurs before there is expression of neuronal hyperexcitation. Pharmacological inhibition using an α7-nAChR antagonist or genetic deletion of nAChR α7 subunits prevents induction and expression of neuronal hyperexcitation. Collectively, these results, confirmed in studies using slice cultures, indicate that functional activity and perhaps functional upregulation of α7-nAChRs are necessary for production of Aβ-induced neuronal hyperexcitation and possibly AD pathogenesis. This novel mechanism involving α7-nAChRs in mediation of Aβ effects provides potentially new therapeutic targets for treatment of AD.
PMCID: PMC3865500  PMID: 23616534
23.  Association of leukocyte telomere length with colorectal cancer risk: nested case-control findings from the Shanghai Women's Health Study 
Telomeres are specialized chromatin structures essential for maintenance of chromosomal integrity and stability. Abnormal alteration of telomere length has been linked to several cancers; however, epidemiologic evidence regarding the association of telomere length with colorectal cancer risk has been conflicting.
We conducted a nested case-control study to evaluate the association between telomere length and colorectal cancer risk using peripheral blood samples collected prior to cancer diagnosis. The study included 441 women with incident colorectal cancer and 549 matched controls. Monochrome multiplex quantitative PCR was applied to measure relative telomere length. Multiple logistic regressions were used to derive adjusted odds ratios (OR) with 95% confidence intervals (CI) as the measure of association between telomere length and subsequent colorectal cancer risk.
A U-shaped association was observed between telomere length and colorectal cancer risk (test for nonlinearity P = 0.0112). Women with telomere length in the third quintile (40th to 60th percentiles) had the lowest risk of colorectal cancer, and the risks were elevated with a shorter or longer telomere length. This U-shaped association did not statistically differ for colon cancer and rectum cancer.
Conclusions and Impact
Our prospective study revealed a U-shaped association between telomere length in peripheral blood cells and colorectal cancer risk. Our findings provide strong evidence that both very short and very long telomeres are associated with increased risk of colorectal cancer.
PMCID: PMC3467322  PMID: 22911335
24.  Mapping Single Cell-Substrate Interactions by Surface Plasmon Resonance Microscopy 
We report on imaging of cell-substrate adhesion of a single cell with sub-cellular spatial resolution. Osmotic pressure was introduced to provide a controllable mechanical stimulation to the cell attached to a substrate, and high-resolution surface plasmon resonance microscopy was used to map the response of the cell, from which local cell-substrate adhesion was determined. In addition to high spatial resolution, the approach is non-invasive and fast, and allows for continuously mapping of cell-substrate interactions and single cell movements.
PMCID: PMC3660850  PMID: 22920036
Single cell imaging; Surface Plasmon Resonance imaging; osmotic effect; cell adhesion
25.  Selective endoscopic ligation for treatment of upper gastrointestinal protuberant lesions 
This study explored the clinical value of endoscopic ligation for the treatment of upper gastrointestinal (GI) protuberant lesions in children. According to the appearance and size of lesions, we used different ligation techniques for the treatment of the lesions. Endoscopic ultrasonography was used for preliminary characterization of the lesions. One case diagnosed with Peutz-Jeghers syndrome was successfully treated by a detachable snare. Two cases with semi-pedunculated or broad-base lesions originating from the submucosal layer of the upper GI were treated with endoscopic variceal ligation; endoscopic examination showed that one case had complete healing 11 wk after ligation, while an ulcer scar was observed at the ligation site after 6 wk in the other case. All lesions were successfully ligated at the first attempt. No significant complications occurred either during or after the procedure. Selective endoscopic ligation of upper GI lesions is an effective and safe treatment for upper GI protuberant lesions in children.
PMCID: PMC3761114  PMID: 24023504
Endoscopy; Ligation; Endoscopic ultrasonography; Protuberant lesion; Children

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