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1.  Abnormal Expression of Serum Soluble E-Cadherin is Correlated with Clinicopathological Features and Prognosis of Breast Cancer 
Background
Increased amounts of soluble E-cadherin (E-cad) have been found in the serum in various cancers, but the role of serum soluble E-cad in the prognosis of breast cancer patients has not been explored in Asian populations.
Material/Method
Blood samples from 111 consecutive patients diagnosed with breast cancer and 55 healthy controls were investigated. Serum soluble E-cad expression levels were measured by enzyme-linked immunosorbent assay (ELISA) with an immunoassay kit according to the manufacturer’s directions. Kaplan-Meier analyses were used to evaluate the association between serum soluble E-cad expression level and survival. All statistical tests were 2-sided.
Results
The serum levels of soluble E-cad in breast cancer patients were significantly higher than those of the control group (2218.9±319.6 ng/ml vs. 742.8±91.7 ng/ml, p<0.001). Serum levels of soluble E-cad correlated significantly with TNM stage (P=0.007), tumor grade (P=0.03), and lymph node metastasis (P<0.001). Kaplan-Meier analysis with the log-rank test indicated that high serum levels of soluble E-cad had a significant impact on overall survival (55.4% vs. 81.4%; P=0.032) and disease-free survival (36.8% vs. 67.8%; P=0.002) in breast cancer. Multivariate analysis revealed that serum levels of soluble E-cad were independently associated with overall survival and disease-free survival in breast cancer patients.
Conclusions
Serum soluble E-cad level is an independent prognostic factor in Asian breast cancer patients.
doi:10.12659/MSM.892049
PMCID: PMC4280058  PMID: 25553984
Biological Markers; Breast Neoplasms; Cadherins; Prognosis
2.  Osteoblast inhibition by chemokine cytokine ligand3 in myeloma-induced bone disease 
Cancer Cell International  2014;14(1):132.
Background
Multiple myeloma is a hematologic malignancy characterized by the accumulation of monoclonal plasma cells in the bone marrow. A common manifestation of the disease is myeloma bone disease (MBD), which is caused by increased osteoclastic bone resorption and decreased bone formation. The chemokine cytokine ligand 3 (CCL3) is a pro-inflammatory protein and chemokine that stimulates osteoclasts in MBD. However, little is known about the effect of CCL3 on osteoblasts (OB).
Methods
The OBs are induced from patients with MBD and healthy donors, cultured in vitro, and identified by histochemistry. The effects of CCL3 and CCL3 antibody on the OBs in vitro are observed. The CCL3 receptor (CCR1), osteocalcin (OCN), runt-related transcription factor 2 (Runx2), and osterix (Osx) are detected using flow cytometry, enzyme-linked immunosorbent assay, and real-time PCR.
Results
Proliferation and osteogenic potential of the OB in patients with MBD are suppressed. Moreover, the CCR1 expression is significantly higher in patients with MBD than in normal controls. The OCN level, quantity of calcium nodules, and Runx2 and Osx levels decrease after CCL3 stimulation, which indicates that CCL3 inhibits OB function. Furthermore, CCL3 antibody partially restores OB activity through the upregulation of the OCN, Runx2, and Osx.
Conclusions
CCL3 contributes to the OB/OC imbalance by inhibiting OB differentiation and function in MBD.
doi:10.1186/s12935-014-0132-6
PMCID: PMC4268854  PMID: 25520585
Chemokine cytokine ligand 3; Myeloma bone disease; Osteoblast; Runx2; Osterix
3.  EPR and Mössbauer Spectroscopy Show Inequivalent Hemes in Tryptophan Dioxygenase 
Tryptophan 2,3-dioxygenase (TDO) is an essential enzyme in the pathway of NAD biosynthesis and important for all living organisms. TDO catalyzes oxidative cleavage of the indole ring of L-tryptophan (L-Trp), converting it to N-formylkynurenine (NFK). The crystal structure of TDO shows a dimer of dimer quaternary structure of the homotetrameric protein. The four catalytic sites of the protein, one per subunit, contain a heme that catalyzes the activation and insertion of dioxygen into L-Trp. Because of the α4 structure and because only one type of heme center has been identified in previous spectroscopic studies, the four hemes sites have been presumed to be equivalent. The present work demonstrates that the heme sites of TDO are not equivalent. Quantitative interpretation of EPR and Mössbauer spectroscopic data indicates the presence of two dominant inequivalent heme species in reduced and oxidized states of the enzyme, which is consistent with a dimer of dimer protein quaternary structure that now extends to the electronic properties of the hemes. The electronic properties of the hemes in the reduced state of TDO change significantly upon L-Trp addition, which is attributed to a change in the protonation state of the proximal histidine to the hemes. The binding of O2 surrogates NO or CO shows two inequivalent heme sites. The heme–NO complexes are 5- and 6-coordinate without L-Trp, and both 6-coordinate with L-Trp. NO can be selectively photodissociated from only one of the heme–NO sites and only in the presence of L-Trp. Cryoreduction of TDO produces a novel diamagnetic heme species, tentatively assigned as a reduced heme-OH complex. This work presents a new description of the heme interactions with the protein, and with the proximal His, which must be considered during the general interpretation of physical data as it relates to kinetics, mechanism, and function of TDO.
doi:10.1021/ja908851e
PMCID: PMC4251817  PMID: 20047315
4.  Primary mediastinal sarcoma: surgical outcomes of 21 cases 
OBJECTIVES
Primary sarcomas of the mediastinum are relatively rare. This article reviews the surgical outcomes of 21 cases diagnosed with localized mediastinal sarcomas receiving multidisciplinary treatment modalities in Sichuan province, China, from January 1996 to January 2011.
METHODS
Twenty-one cases of histologically diagnosed primary mediastinal sarcoma undergoing surgical treatment were reviewed retrospectively. Disease-free survival (DFS) and overall survival (OS) were statistically analysed. All the patients presented with localized tumours consisting of 5 females and 16 males with a median age of 41.0 years (range: 9.0–68.0 years). Among all cases, 17 (81.0%) had an Eastern Cooperative Oncology Group performance status score of ≤1 at diagnosis. Eight (38.1%) underwent macroscopically complete resection (R0–R1) and 13 (61.9%) had incomplete resection (R2). Ten (47.6%) received postoperative radiotherapy and 7 (33.3%) postoperative chemotherapy.
RESULTS
The median DFS was 17 months (range: 0.4–79.8 months) and the median OS was 27.2 months (range: 0.4–79.8 months). Patients receiving complete resection showed significantly improved DFS (P = 0.031) and OS (P = 0.035) compared with those with incomplete resection. Neither postoperative radiotherapy nor chemotherapy significantly improved DFS (P = 0.770, P = 0.756) or OS (P = 0.905, P = 0.738). However, 7 patients (R2) and 2 (R0–R1 and grade 3) had improved local control with a local recurrence-free survival of 28.9 months (range: 7.6–73.2 months).
CONCLUSIONS
Complete resection should be preferentially attempted compared with incomplete resection and postoperative radiotherapy might yield good local control.
doi:10.1093/icvts/ivt354
PMCID: PMC3829490  PMID: 24027167
Mediastinum; Sarcoma; Surgery; Radiotherapy; Chemotherapy
5.  Study of Sequential Dexter Energy Transfer in High Efficient Phosphorescent White Organic Light-Emitting Diodes with Single Emissive Layer 
Scientific Reports  2014;4:7009.
In this study, we report our effort to realize high performance single emissive layer three color white phosphorescent organic light emitting diodes (PHOLEDs) through sequential Dexter energy transfer of blue, green and red dopants. The PHOLEDs had a structure of; ITO(1500 Å)/NPB(700 Å)/mCP:Firpic-x%:Ir(ppy)3-0.5%:Ir(piq)3-y%(300 Å)/TPBi(300 Å)/Liq(20 Å)/Al(1200 Å). The dopant concentrations of FIrpic, Ir(ppy)3 and Ir(piq)3 were adjusted and optimized to facilitate the preferred energy transfer processes attaining both the best luminous efficiency and CIE color coordinates. The presence of a deep trapping center for charge carriers in the emissive layer was confirmed by the observed red shift in electroluminescent spectra. White PHOLEDs, with phosphorescent dopant concentrations of FIrpic-8.0%:Ir(ppy)3-0.5%:Ir(piq)3-0.5% in the mCP host of the single emissive layer, had a maximum luminescence of 37,810 cd/m2 at 11 V and a luminous efficiency of 48.10 cd/A at 5 V with CIE color coordinates of (0.35, 0.41).
doi:10.1038/srep07009
PMCID: PMC4228348  PMID: 25388087
6.  Phenotypic Variation Among Seven Members of One Family with Deficiency of Hypoxanthine-Guanine Phosphoribosyltransferase 
Molecular genetics and metabolism  2013;110(3):10.1016/j.ymgme.2013.08.016.
We describe a family of seven boys affected by Lesch-Nyhan disease with various phenotypes. Further investigations revealed a mutation c.203T>C in the gene encoding HGprt of all members, with substitution of leucine to proline at residue 68 (p.Leu68Pro). Thus patients from this family display a wide variety of symptoms although sharing the same mutation. Mutant HGprt enzyme was prepared by site-directed mutagenesis and the kinetics of the enzyme revealed that the catalytic activity of the mutant was reduced, in association with marked reductions in the affinity towards phosphoribosylpyrophosphate (PRPP). Its Km for PRPP was increased 215-fold with hypoxanthine as substrate and 40-fold with guanine as substrate with associated reduced catalytic potential. Molecular modeling confirmed that the most prominent defect was the dramatically reduced affinity towards PRPP. Our studies suggest that the p.Leu68Pro mutation has a strong impact on PRPP binding and on stability of the active conformation. This suggests that factors other than HGprt activity per se may influence the phenotype of Lesch-Nyhan patients.
doi:10.1016/j.ymgme.2013.08.016
PMCID: PMC3830450  PMID: 24075303
Lesch-Nyhan disease; variants; PRPP; phenotype-genotype; HGprt; molecular modeling
7.  The Effects of Tai Chi on the Renal and Cardiac Functions of Patients with Chronic Kidney and Cardiovascular Diseases 
Journal of Physical Therapy Science  2014;26(11):1733-1736.
[Purpose] To assess the effects of Tai Chi on the renal and cardiac functions of patients with chronic kidney disease (CKD) and cardiovascular disease (CVD). [Subjects and Methods] Twenty-one patients with CKD and CVD were randomly divided into control and exercise groups. The exercise group performed Tai Chi training for 30 minutes three to five times a week for 12 weeks, while the control group did not. All patients’ renal and cardiac functions and blood lipid parameters were measured at baseline and after 12 weeks. [Results] The 12 weeks Tai Chi intervention improved the estimated glomerular filtration rate (eGFR), left ventricular ejection fraction (LVEF), and the high density lipoprotein (HDL) level, and decreased the serum creatintine (Scr) level, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and the total cholesterol (CH), triglyceride (TG) and low density lipoprotein (LDL) levels. The change in eGFR correlated negatively with the changes in CH, TG and LDL, and positively with the change in HDL. In addition, the change in SBP correlated positively with the changes in CH, TG and LDL, and negatively with the change in HDL. [Conclusion] Tai Chi training might improve the renal and cardiac functions of CKD and CVD patients via improved regulation of lipid metabolism.
doi:10.1589/jpts.26.1733
PMCID: PMC4242943  PMID: 25435688
Tai Chi; Renal function; Lipid metabolism
8.  TGM2 inhibition attenuates ID1 expression in CD44-high glioma-initiating cells 
Neuro-Oncology  2013;15(10):1353-1365.
Background
CD44 is a molecular marker associated with cancer stem cell populations and treatment resistance in glioma. More effective therapies will result from approaches aimed at targeting glioma cells high in CD44.
Methods
Glioma-initiating cell lines were derived from fresh surgical glioblastoma samples. Expression of tissue transglutaminase 2 (TGM2) was attenuated through lentivirus-mediated short hairpin RNA knockdown. MTT assay [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] was used to evaluate the growth inhibition induced by TGM2 inhibitor. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling was used to evaluate cell apoptosis following TGM2 inhibition. CD44+ glioma stem cells were sorted by flow cytometry. A nude mice orthotopic xenograft model was used to evaluate the in vivo effect of TGM2 inhibitor.
Results
TGM2 was highly expressed in CD44-high glioblastoma tissues and tumor-derived glioma-initiating cell lines. TGM2 knockdown impaired cell proliferation and induced apoptosis in CD44-high glioma-initiating cell lines. Further studies indicated that expression of inhibitor of DNA binding 1 protein (ID1) is regulated by TGM2 and might be an important mediator for TGM2-regulated cell proliferation in CD44-high glioma-initiating cell lines. TGM2 inhibitor reduces ID1 expression, suppresses cell proliferation, and induces apoptosis in CD44-high glioma-initiating cell lines. Furthermore, TGM2 is highly expressed in CD44+ glioma stem cells, while pharmacological inhibition of TGM2 activity preferentially eliminates CD44+ glioma stem cells. Consistently, TGM2 inhibitor treatment reduced ID1 expression and induced apoptosis in our orthotopic mice xenograft model, which can be translated into prolonged median survival in tumor-bearing mice.
Conclusions
TGM2 regulates ID1 expression in glioma-initiating cell lines high in CD44. Targeting TGM2 could be an effective strategy to treat gliomas with high CD44 expression.
doi:10.1093/neuonc/not079
PMCID: PMC3779037  PMID: 23877317
apoptosis; cell proliferation; glioma; tissue transglutaminase; tumor initiating cells
9.  Circulating Levels of 25-hydroxyvitamin D and Prostate Cancer Prognosis 
Cancer epidemiology  2013;37(5):10.1016/j.canep.2013.07.005.
Objectives
Ecological, in vitro, and in vivo studies demonstrate a link between vitamin D and prostate tumor growth and aggressiveness. The goal of this study was to investigate whether plasma concentration of vitamin D is associated with survivorship and disease progression in men diagnosed with prostate cancer.
Methods and Materials
We conducted a population-based cohort study of 1,476 prostate cancer patients to assess disease recurrence/progression and prostate cancer-specific mortality (PCSM) risks associated with serum levels of 25(OH) vitamin D [25(OH)D].
Results
There were 325 recurrence/progression and 95 PCSM events during an average of 10.8 years of follow-up. Serum levels of 25(OH)D were not associated with risk of recurrence/ progression or mortality. Clinically deficient vitamin D levels were associated with an increased risk of death from other causes.
Conclusions
We did not find evidence that serum vitamin D levels measured after diagnosis affect prostate cancer prognosis. Lower levels of vitamin D were associated with risk of non-prostate cancer mortality.
doi:10.1016/j.canep.2013.07.005
PMCID: PMC3864767  PMID: 23972671
Prostatic Neoplasms; Mortality; Prognosis; Vitamin D/blood*; Cohort Studies; Epidemiologic Studies; Humans; Male
10.  Comprehensive Assessment of the Association of WNK4 Polymorphisms with Hypertension: Evidence from a Meta-Analysis 
Scientific Reports  2014;4:6507.
The relationship between with-no-lysine [K] kinase 4 (WNK4) gene polymorphisms and hypertension has been widely investigated, However, the studies yielded contradictory results. To evaluate these inconclusive findings comprehensively, we therefore performed a meta-analysis. Ten articles encompassing 16 independent case-control studies with 6089 hypertensive cases and 4881 normotensive controls were selected for this meta-analysis. Four WNK4 gene polymorphisms were identified (G1155942T, G1156666A, T1155547C, and C6749T). The results showed statistically significant associations of G1155942T polymorphism (allelic genetic model: odds ration or OR = 1.62, 95% confidence interval or CI: 1.11–2.38, P = 0.01; dominant model: OR = 1.85, 95% CI: 1.07–3.19, P = 0.03) and C6749T polymorphism (allele contrast: OR = 2.04, 95% CI: 1.60–2.59, P<0.01; dominant model: OR = 2.04, 95%CI: 1.59–2.62, P<0.01; and homozygous model: OR = 5.01, 95% CI: 1.29–19.54, P = 0.02) with hypertension risk. However, neither C1155547T nor G1156666A was associated significantly with hypertension susceptibility. In conclusion, this meta-analysis suggested that WNK4 G1155942T and C6749T gene polymorphisms may contribute to the susceptibility and development of hypertension. Further well-designed studies with larger sample size are required to elucidate the association of WNK4 gene multiple polymorphisms with hypertension risk.
doi:10.1038/srep06507
PMCID: PMC4195396  PMID: 25266424
11.  Trend of Urban-Rural Disparities in Hospital Admissions and Medical Expenditure in China from 2003 to 2011 
PLoS ONE  2014;9(9):e108571.
Objectives
To assess the trend of urban-rural disparities in hospital admissions and medical expenditure between 2003 and 2011 in the context of Chinese health-care system reform.
Methods
The data were from three different national surveys: the Third National Health Services Survey in 2003, the Fourth National Health Services Survey in 2008 and the national health-care reform phased assessment survey in 2011. There were 151421, 143380 and 48356 respondents aged 15 years or older in 2003, 2008 and 2011, respectively.
Results
The health insurance coverage expanded considerably from 27.7% in 2003 to 96.4% in 2011 among respondents aged 15 years or older. Hospitalization rate increased rapidly from 4.1% in 2003 to 9.6% in 2011. Urban respondents had higher hospital admissions than rural respondents, and the RR (95% CI) of hospitalization was 1.23 (1.17–1.30), 1.06 (1.02–1.10) and 1.16 (1.10–1.23) in 2003, 2008 and 2011, respectively. The urban-rural disparity in hospital admissions significantly narrowed over time. Urban respondents had a higher admission rate if insured and a lower admission if not insured than their rural counterparts. Of the six medical expenditure measures, the disparities in reimbursement rate and the proportion of hospitalization direct cost to the total consumer spending significantly narrowed.
Conclusions
The health insurance coverage has been continually expanding and health service utilization has been substantially improved. Urban-rural disparities have been narrowed but still exist. Therefore, policy-makers should focus on increasing investment and reimbursement levels, developing a uniform standard health insurance system for urban and rural residents and improving the medical assistance system.
doi:10.1371/journal.pone.0108571
PMCID: PMC4177550  PMID: 25251367
12.  MiR-181b sensitizes glioma cells to teniposide by targeting MDM2 
BMC Cancer  2014;14(1):611.
Background
Although the incidence of glioma is relatively low, it is the most malignant tumor of the central nervous system. The prognosis of high-grade glioma patient is very poor due to the difficulties in complete resection and resistance to radio-/chemotherapy. Therefore, it is worth investigating the molecular mechanisms involved in glioma drug resistance. MicroRNAs have been found to play important roles in tumor progression and drug resistance. Our previous work showed that miR-181b is involved in the regulation of temozolomide resistance. In the current study, we investigated whether miR-181b also plays a role in antagonizing the effect of teniposide.
Methods
MiR-181b expression was measured in 90 glioma patient tissues and its relationship to prognosis of these patients was analyzed. Cell sensitivity to teniposide was tested in 48 primary cultured glioma samples. Then miR-181b stably overexpressed U87 cells were generated. The candidate genes of miR-181b from our previous study were reanalyzed, and the interaction between miR-181b and target gene MDM2 was confirmed by dual luciferase assay. Cell sensitivity to teniposide was detected on miR-181b over expressed and MDM2 down regulated cells.
Results
Our data confirmed the low expression levels of miR-181b in high-grade glioma tissues, which is related to teniposide resistance in primary cultured glioma cells. Overexpression of miR-181b increased glioma cell sensitivity to teniposide. Through target gene prediction, we found that MDM2 is a candidate target of miR-181b. MDM2 knockdown mimicked the sensitization effect of miR-181b. Further study revealed that miR-181b binds to the 3’-UTR region of MDM2 leading to the decrease in MDM2 levels and subsequent increase in teniposide sensitivity. Partial restoration of MDM2 attenuated the sensitivity enhancement by miR-181b.
Conclusions
MiR-181b is an important positive regulator on glioma cell sensitivity to teniposide. It confers glioma cell sensitivity to teniposide through binding to the 3’-UTR region of MDM2 leading to its reduced expression. Our findings not only reveal the novel mechanism involved in teniposide resistance, but also shed light on the optimization of glioma treatment in the future.
doi:10.1186/1471-2407-14-611
PMCID: PMC4155117  PMID: 25151861
miR-181b; Teniposide; Glioma; Mouse double minute 2 homolog (MDM2)
13.  The Effects of the Context-Dependent Codon Usage Bias on the Structure of the nsp1α of Porcine Reproductive and Respiratory Syndrome Virus 
BioMed Research International  2014;2014:765320.
The information about the crystal structure of porcine reproductive and respiratory syndrome virus (PRRSV) leader protease nsp1α is available to analyze the roles of tRNA abundance of pigs and codon usage of the nsp1α gene in the formation of this protease. The effects of tRNA abundance of the pigs and the synonymous codon usage and the context-dependent codon bias (CDCB) of the nsp1α on shaping the specific folding units (α-helix, β-strand, and the coil) in the nsp1α were analyzed based on the structural information about this protease from protein data bank (PDB: 3IFU) and the nsp1α of the 191 PRRSV strains. By mapping the overall tRNA abundance along the nsp1α, we found that there is no link between the fluctuation of the overall tRNA abundance and the specific folding units in the nsp1α, and the low translation speed of ribosome caused by the tRNA abundance exists in the nsp1α. The strong correlation between some synonymous codon usage and the specific folding units in the nsp1α was found, and the phenomenon of CDCB exists in the specific folding units of the nsp1α. These findings provide an insight into the roles of the synonymous codon usage and CDCB in the formation of PRRSV nsp1α structure.
doi:10.1155/2014/765320
PMCID: PMC4137607  PMID: 25162025
14.  Zymomonas mobilis: a novel platform for future biorefineries 
Biosynthesis of liquid fuels and biomass-based building block chemicals from microorganisms have been regarded as a competitive alternative route to traditional. Zymomonas mobilis possesses a number of desirable characteristics for its special Entner-Doudoroff pathway, which makes it an ideal platform for both metabolic engineering and commercial-scale production of desirable bio-products as the same as Escherichia coli and Saccharomyces cerevisiae based on consideration of future biomass biorefinery. Z. mobilis has been studied extensively on both fundamental and applied level, which will provide a basis for industrial biotechnology in the future. Furthermore, metabolic engineering of Z. mobilis for enhancing bio-ethanol production from biomass resources has been significantly promoted by different methods (i.e. mutagenesis, adaptive laboratory evolution, specific gene knock-out, and metabolic engineering). In addition, the feasibility of representative metabolites, i.e. sorbitol, bionic acid, levan, succinic acid, isobutanol, and isobutanol produced by Z. mobilis and the strategies for strain improvements are also discussed or highlighted in this paper. Moreover, this review will present some guidelines for future developments in the bio-based chemical production using Z. mobilis as a novel industrial platform for future biofineries.
doi:10.1186/1754-6834-7-101
PMCID: PMC4094786  PMID: 25024744
Zymomonas mobilis; platform; biorefinery; biofuel; building block chemical
15.  Efficacy Trial of a DNA/rAd5 HIV-1 Preventive Vaccine 
The New England journal of medicine  2013;369(22):2083-2092.
Background
A safe and effective vaccine for the prevention of human immunodeficiency virus type 1 (HIV-1) infection is a global priority. We tested the efficacy of a DNA prime–recombinant adenovirus type 5 boost (DNA/rAd5) vaccine regimen in persons at increased risk for HIV-1 infection in the United States.
Methods
At 21 sites, we randomly assigned 2504 men or transgender women who have sex with men to receive the DNA/rAd5 vaccine (1253 participants) or placebo (1251 participants). We assessed HIV-1 acquisition from week 28 through month 24 (termed week 28+ infection), viral-load set point (mean plasma HIV-1 RNA level 10 to 20 weeks after diagnosis), and safety. The 6-plasmid DNA vaccine (expressing clade B Gag, Pol, and Nef and Env proteins from clades A, B, and C) was administered at weeks 0, 4, and 8. The rAd5 vector boost (expressing clade B Gag-Pol fusion protein and Env glycoproteins from clades A, B, and C) was administered at week 24.
Results
In April 2013, the data and safety monitoring board recommended halting vaccinations for lack of efficacy. The primary analysis showed that week 28+ infection had been diagnosed in 27 participants in the vaccine group and 21 in the placebo group (vaccine efficacy, −25.0%; 95% confidence interval, −121.2 to 29.3; P = 0.44), with mean viral-load set points of 4.46 and 4.47 HIV-1 RNA log10 copies per milliliter, respectively. Analysis of all infections during the study period (41 in the vaccine group and 31 in the placebo group) also showed lack of vaccine efficacy (P = 0.28). The vaccine regimen had an acceptable side-effect profile.
Conclusions
The DNA/rAd5 vaccine regimen did not reduce either the rate of HIV-1 acquisition or the viral-load set point in the population studied. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00865566.)
doi:10.1056/NEJMoa1310566
PMCID: PMC4030634  PMID: 24099601
16.  The Clinical and Immune Characteristics of Patients with Hepatitis-Associated Aplastic Anemia in China 
PLoS ONE  2014;9(5):e98142.
Hepatitis-associated aplastic anemia (HAAA) is a variant of severe aplastic anemia (SAA) in which bone marrow failure follows an acute attack of hepatitis. Its pathogenesis is poorly understood. We investigated the prevalence of HAAA among cases of newly diagnosed SAA presenting to our hospital between January 1998 and February 2013, and analyzed the clinical and immune characteristics of HAAA and non-hepatitis-associated SAA (non-HASAA) patients. The prevalence of HAAA among cases of SAA was 3.8% (36/949), and the majority of patients (33/36) were seronegative for a known hepatitis virus. Compared with non-HASAA patients, HAAA patients had a larger proportion of CD8+ T cells, a lower ratio of CD4+/CD8+ T cells, and a smaller proportion of CD4+CD25+ regulatory T cells. There was no significant difference in peripheral blood count, bone marrow cellularity, or the number of blood transfusions received between HAAA and non-HASAA patients. HAAA patients had a higher early infection rate and more infection-related mortality in the first 2 years after diagnosis than non-HASAA patients, and their 2-year survival rate was lower. The results demonstrate that HAAA patients have a more severe T cell imbalance and a poorer prognosis than non-HASAA patients.
doi:10.1371/journal.pone.0098142
PMCID: PMC4028298  PMID: 24845454
17.  Expression of Shelterin Component POT1 Is Associated with Decreased Telomere Length and Immunity Condition in Humans with Severe Aplastic Anemia 
Journal of Immunology Research  2014;2014:439530.
Abnormal telomere attrition has been found to be closely related to patients with SAA in recent years. To identify the incidence of telomere attrition in SAA patients and investigate the relationship of telomere length with clinical parameters, SAA patients (n = 27) and healthy controls (n = 15) were enrolled in this study. Telomere length of PWBCs was significantly shorter in SAA patients than in controls. Analysis of gene expression of Shelterin complex revealed markedly low levels of POT1 expression in SAA groups relative to controls. No differences in the gene expression of the other Shelterin components—TRF1, TRF2, TIN2, TPP1, and RAP1—were identified. Addition of IFN-γ to culture media induced a similar fall in POT1 expression in bone marrow cells to that observed in cells cultured in the presence of SAA serum, suggesting IFN-γ is the agent responsible for this effect of SAA serum. Furthermore, ATR, phosphorylated ATR, and phosphorylated ATM/ATR substrate were all found similarly increased in bone marrow cells exposed to SAA serum, TNF-α, or IFN-γ. In summary, SAA patients have short telomeres and decreased POT1 expression. TNF-α and IFN-γ are found at high concentrations in SAA patients and may be the effectors that trigger apoptosis through POT1 and ATR.
doi:10.1155/2014/439530
PMCID: PMC4033360  PMID: 24892036
18.  Variation in selenoenzyme genes and prostate cancer risk and survival 
The Prostate  2012;73(7):10.1002/pros.22617.
Background
While several studies showed that selenium may prevent prostate cancer (PCa), few studies have evaluated variation in selenoenzyme genes in relation to PCa risk and survival.
Methods
We studied common variants in seven selenoenzymes genes in relation to risk of PCa and PCa-specific mortality (PCSM). In a population-based case-control study of men of European ancestry (1,309 cases, 1,266 controls), we evaluated 35 common, tagging single nucleotide polymorphisms (SNPs) in GPX1 (n = 2), GPX2 (n = 4), GPX3 (n = 6), GPX4 (n = 6), SEP15 (n = 4), SEPP1 (n = 6), and TXNRD1 (n = 7) in relation to PCa risk, and among cases, associations between these variants and risk of PCSM. We used logistic regression and Cox proportional hazards regression to estimate the relative risk of PCa and PCSM, respectively.
Results
Of the SNPs examined, only GPX1 rs3448 was associated with overall PCa risk with an odds ratio of 0.62 for TT versus CC (95% confidence interval, 0.44–0.88). SNPs in GPX2, GPX3, GPX4, SEP15, and SEPP1 had different risk estimates for PCa in subgroups based on stage and grade. We observed associations between SNPs in GPX4 and TXNRD1 and risk of PCSM. None of these associations, however, remained significant after adjustment for multiple comparisons.
Conclusions
We found evidence that genetic variation in a subset of selenoenzyme genes may alter risk of PCa and PCSM. These results need validation in additional subsets.
doi:10.1002/pros.22617
PMCID: PMC3859305  PMID: 23143801
prostate cancer; risk; mortality; selenoenzyme genes; genetic variation
19.  Highly efficient blue organic light-emitting diodes using quantum well-like multiple emissive layer structure 
Nanoscale Research Letters  2014;9(1):191.
In this study, the properties of blue organic light-emitting diodes (OLEDs), employing quantum well-like structure (QWS) that includes four different blue emissive materials of 4,4′-bis(2,2′-diphenylyinyl)-1,1′-biphenyl (DPVBi), 9,10-di(naphth-2-yl)anthracene (ADN), 2-(N,N-diphenyl-amino)-6-[4-(N,N-diphenyl amine)styryl]naphthalene (DPASN), and bis(2-methyl-8-quinolinolate)-4-(phenyl phenolato) aluminum (BAlq), were investigated. Conventional QWS blue OLEDs composed of multiple emissive layers and charge blocking layer with lower highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy level, and devices with triple emissive layers for more significant hole-electron recombination and a wider region for exciton generation were designed. The properties of triple emissive layered blue OLEDs with the structure of indium tin oxide (ITO) /N,N′-diphenyl-N,N′-bis(1-naphthyl-phenyl)-(1,1′-biphenyl)-4,4′-diamine (NPB) (700 Ǻ)/X (100 Ǻ)/BAlq (100 Ǻ)/X (100 Ǻ)/4,7-diphenyl-1,10-phenanthroline (Bphen) (300 Ǻ)/lithium quinolate (Liq) (20 Ǻ)/aluminum (Al) (1,200 Ǻ) (X = DPVBi, ADN, DPASN) were examined. HOMO-LUMO energy levels of DPVBi, ADN, DPASN, and BAlq are 2.8 to 5.9, 2.6 to 5.6, 2.3 to 5.2, and 2.9 to 5.9 eV, respectively. The OLEDs with DPASN/BAlq/DPASN QWS with maximum luminous efficiency of 5.32 cd/A was achieved at 3.5 V.
doi:10.1186/1556-276X-9-191
PMCID: PMC4036430  PMID: 24940170
Blue organic light-emitting diodes; HOMO-LUMO; QWS
20.  Erythroblastic Islands in the Bone Marrow of Patients with Immune-Related Pancytopenia 
PLoS ONE  2014;9(4):e95143.
Background
Immune-related pancytopenia (IRP) is characterized by pancytopenia caused by autoantibody-mediated bone marrow destruction or suppression. The bone marrows of IRP patients have remarkably increased erythroblastic islands (EIs).
Methodology and Principal Findings
We determined the immunoglobulin G (IgG) autoantibodies in some parts of EIs of IRP patients using immunofluorescence to investigate the biological function of EIs with IgG in the pathophysiology of IRP. The dominant class of autoantibodies detected in mononuclear cells was IgG (CD34 IgG, CD15 IgG, and GlycoA IgG), specifically IgG on GlycoA-positive cells (GlycoA IgG). Results show that extravascular hemolysis occurred in IRP through IgG autoantibodies in the EIs. These data included a high percentage of reticulocytes in the peripheral blood, hypererythrocytosis in the bone marrow, and high serum bilirubin. Furthermore, we examined the macrophages in the bone marrow of IRP patients. The results show that the number of activated macrophages relatively increased, and the phagocytic activity of macrophages significantly increased.
Conclusions and Significance
Increased EIs with IgG were the sites of erythroblast phagocytosis by the activated macrophages, rather than erythropoietic niches. The IgG autoantibodies in the EIs possibly functioned as adhesion molecules for a ring of erythroblasts around the macrophages, thereby forming morphologic EIs.
doi:10.1371/journal.pone.0095143
PMCID: PMC3989288  PMID: 24740145
21.  The Immunoregulation Effect of Alpha 1-Antitrypsin Prolong β-Cell Survival after Transplantation 
PLoS ONE  2014;9(4):e94548.
Islet transplantation has considerable potential as a cure for diabetes. However, the difficulties that arise from inflammation and the immunological rejection of transplants must be addressed for islet transplantation to be successful. Alpha 1-antitrypsin (AAT) inhibits the damage on β cells caused by inflammatory reactions and promotes β-cell survival and proliferation. This protein also induces specific immune tolerance to transplanted β cells. However, whether the expression of AAT in β cells themselves could eliminate or decrease immunological rejection of transplants is not clear. Therefore, we established a β cell line (NIT-hAAT) that stably expresses human AAT. Interestingly, in a cytotoxic T lymphocyte (CTL)-killing assay, we found that hAAT reduced apoptosis and inflammatory cytokine production in NIT-1 cells and regulated the Th1/Th2 cytokine balance in vitro. In vivo transplantation of NIT-hAAT cells into mice with diabetes showed hAAT inhibited immunological rejection for a short period of time and increased the survival of transplanted β cells. This study demonstrated that hAAT generated remarkable immunoprotective and immunoregulation effects in a model of β cell islet transplantation for diabetes model.
doi:10.1371/journal.pone.0094548
PMCID: PMC3983209  PMID: 24722487
22.  Losartan Inhibits Nuclear Factor-κB Activation Induced by Small, Dense LDL Cholesterol Particles in Human Umbilical Vein Endothelial Cells☆ 
Objective
We aimed to investigate how losartan exerts protective effects on human umbilical vein endothelial cell injury induced by small, dense, LDL (sLDL) cholesterol particles.
Methods
sLDL cholesterol was isolated by a 2-steps method and the nuclear translocation and activation of nuclear factor-κB (NF-κB) in endothelial cells was observed by confocal microscopy and electrophoretic mobility shift assays.
Results
Losartan greatly inhibited the nuclear translocation of NF-κB induced by sLDL cholesterol in a dose-dependent manner.
Conclusions
sLDL cholesterol may be involved in endothelial dysfunction possibly through NF-κB activation; losartan protects against sLDL cholesterol-inducing endothelial cell injury by inhibiting NF-κB activation, suggesting that losartan may play a role in the prevention and treatment of cardiovascular disease.
doi:10.1016/j.curtheres.2013.11.006
PMCID: PMC3994917  PMID: 25031662
losartan; nuclear factor-κB; small, dense, LDL
23.  Serological report of pandemic (H1N1) 2009 infection among cats in Northeastern China in 2012-02 and 2013-03 
Virology Journal  2014;11:49.
Background
Influenza A virus has a wide range of hosts. It has not only infected human, but also been reported interspecies transmission from humans to other animals, such as pigs, poultry, dogs and cats. However, prevalence of A (H1N1) pdm09 influenza virus infections in cats in northeastern China is unknown. Therefore, the prevalence of A (H1N1) pdm09 influenza virus infections was performed among cats in northeastern China in this study.
Findings
Of all samples in this study, the overall seroprevalence of pandemic (H1N1) 2009 infection in cats was 21% (240/1140). It also showed a higher prevalence rate of pandemic(H1N1) 2009 infection in pet cats (30.6%) than roaming cats (11%) based on NT. In addition, the results also showed a trend of difference in term of species of cats and it was statistically significant.
Conclusions
This is the first survey on the seroprevalence of pandemic (H1N1) 2009 infection among cats in northeastern China. This study has observed a relatively high seroprevalence of pandemic (H1N1) 2009 among different cat populations in northeastern China, similar seroprevalence studies should be conducted elsewhere.
doi:10.1186/1743-422X-11-49
PMCID: PMC3995557  PMID: 24624924
Pandemic (H1N1) 2009; Cats; Serological
24.  Estrogen receptor α gene PvuII polymorphism and coronary artery disease: a meta-analysis of 21 studies*  
The association between the estrogen receptor α gene (ESR1) PvuII polymorphism (c.454-397T>C) and coronary artery disease (CAD) is controversial. Thus, we conducted a meta-analysis to evaluate the relationship. Data were collected from 21 studies encompassing 9926 CAD patients and 16 710 controls. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the relationship between PvuII polymorphism and CAD. The polymorphism in control populations in all studies followed Hardy-Weinberg equilibrium. We found a significant association between ESR1 PvuII polymorphism and CAD risk in all subjects. When the data were stratified by region, a significant association between ESR1 PvuII polymorphism and CAD risk was observed in Asian populations but not in Western populations. The current study suggests that ESR1 PvuII polymorphism has an important role in CAD susceptibility.
doi:10.1631/jzus.B1300220
PMCID: PMC3955911  PMID: 24599688
Estrogen receptor α gene; Polymorphism; Meta-analysis; Coronary artery disease (CAD)
25.  Discerning primary tumors from metastases in synchronous nasopharyngeal squamous cell carcinoma and cutaneous squamous cell carcinoma: A case report and review of the literature 
Oncology Letters  2014;7(5):1391-1394.
Nasopharyngeal carcinoma is one of the most common types of malignant tumor in Southern China and Southeast Asia, and its etiology is closely associated with Epstein-Barr virus (EBV) infection. Non-keratinizing carcinoma accounts for >95% of all nasopharyngeal carcinoma cases. In addition, metastatic nasopharyngeal carcinoma from other locations in the body is extremely rare. This study reports the case of a 53-year-old female who presented with a lesion on the left nasal alar skin that had slowly developed over a five-year period. A biopsy was obtained and the lesion was histologically diagnosed as cutaneous squamous cell carcinoma (SCC). A nasopharyngeal neoplasm was also detected by 18-fluorine-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography and nasopharyngoscopy. A biopsy of the nasopharyngeal neoplasm confirmed a diagnosis of SCC. However, a small EBV-encoded nuclear RNA (EBER) test demonstrated that the nasopharyngeal tumor cells were all negative for EBV. As the majority of nasopharyngeal carcinomas were positive for EBER, it was concluded that the nasopharyngeal carcinoma had metastasized from the cutaneous SCC. A brief review of literature is also presented, in addition to a discussion of the pathogen, epidemiology and diagnosis of cutaneous and nasopharyngeal carcinomas.
doi:10.3892/ol.2014.1915
PMCID: PMC3997691  PMID: 24765143
squamous cell carcinoma; nasopharynx; metastasis

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