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1.  A medical costs study of older patients with acute myocardial infarction and metabolic syndrome in hospital 
Background
Older patients with acute myocardial infarction (AMI) usually have a poor prognosis, but whether this poor prognosis leads to high hospital costs remains unclear. This study investigated the clinical outcomes of and costs incurred by older patients with AMI and metabolic syndrome (MS) in hospital.
Methods and results
Patients with AMI seen at Qilu Hospital of Shandong University between January 2011 and May 2013 were separated into four groups: young non-MS patients (n=282), older non-MS patients (n=324), young MS patients (n=217), and older MS patients (n=174). We found that advanced age was significantly associated with worse clinical outcomes, and that the clinical outcomes in patients with AMI and MS are also worsened. At the same cost (RMB¥10,000), older patients with and without MS had a markedly increased number of cardiovascular incidences compared with younger patients without MS. In a comparison of the incremental cost-effectiveness ratio (ICER) of percutaneous coronary intervention, older patients without MS had a lower ICER for cardiovascular incidences and a higher ICER for cardiac event-free survival rate when compared with young patients without MS, but a lower ICER for cardiovascular incidences and a higher ICER for cardiac event-free survival rate when compared with older MS patients.
Conclusion
Older AMI patients have poor clinical outcomes and their treatment is not cost-effective; however, the results are worse in patients with AMI and MS. Percutaneous coronary intervention is a cost-effective therapy in older patients with AMI, but its cost-effectiveness decreases in patients with AMI and MS.
doi:10.2147/CIA.S70372
PMCID: PMC4315548
metabolic syndrome; aging; vascular; acute myocardial infarction; cost-effectiveness
2.  Time-dependent changes of plasma inflammatory biomarkers in type A aortic dissection patients without optimal medical management 
Objectives
To investigate the time-dependent changes in plasma levels of interleukin-6, C-reactive protein, and tumor necrosis factor-α in patients with type A aortic dissection (TAAD) who received unoptimal medical management since the onset of dissections.
Design and methods
Plasma levels of interleukin-6, C-reactive protein, and tumor necrosis factor-α were detected by ELISA and immuno-turbidimetric assay in 92 TAAD patients at hospital admission. Blood samples from 78 patients with uncontrolled hypertension and 82 healthy volunteers were also analyzed as controls. The occurrence of TAAD-related complication and its relationship with the plasma levels of these inflammatory biomarkers was also investigated.
Results
The concentrations of inflammatory mediators were significant higher in TAAD than those in the uncontrolled hypertension and the healthy group. The time to peak plasma level of IL-6.and TNF-α was shorter than that of CRP in TAAD group. In the TAAD group, 51 patients suffered TAAD-related complications, and their plasma level of CRP was significantly higher than that in patients without TAAD-related complications (94.5 ± 58.8 mg/L versus 47.4 ± 47.8 mg/L, p < 0.001). Also, CRP levels strongly correlated with the value of PaO2/FiO2 ratio (r = −0.69, p < 0.001) and creatinine (r = 0.60, p < 0.001). The time to the peak level of CRP was shorter and the duration of persistently high CRP level was longer in the complication group than those in the complication-free group.
Conclusions
Elevated and persistently high levels of plasma CRP, IL-6 and TNF-α were associated with progressively development of the TAAD. The changing pattern of CRP might be a marker for diagnosis and prophylactic treatment of complications. Our findings suggested a critical role of the inflammation in the progression of dissection and TAAD-related complications.
doi:10.1186/s13019-014-0199-0
PMCID: PMC4302155  PMID: 25592634
Type A aortic dissection; Inflammatory mediator; Interleukin-6; C-reactive protein; Tumor necrosis factor-α; Complication
3.  Identification of PLXDC1 and PLXDC2 as the transmembrane receptors for the multifunctional factor PEDF 
eLife  null;3:e05401.
Pigment Epithelium Derived Factor (PEDF) is a secreted factor that has broad biological activities. It was first identified as a neurotrophic factor and later as the most potent natural antiangiogenic factor, a stem cell niche factor, and an inhibitor of cancer cell growth. Numerous animal models demonstrated its therapeutic value in treating blinding diseases and diverse cancer types. A long-standing challenge is to reveal how PEDF acts on its target cells and the identities of the cell-surface receptors responsible for its activities. Here we report the identification of transmembrane proteins PLXDC1 and PLXDC2 as cell-surface receptors for PEDF. Using distinct cellular models, we demonstrate their cell type-specific receptor activities through loss of function and gain of function studies. Our experiments suggest that PEDF receptors form homooligomers under basal conditions, and PEDF dissociates the homooligomer to activate the receptors. Mutations in the intracellular domain can have profound effects on receptor activities.
DOI: http://dx.doi.org/10.7554/eLife.05401.001
eLife digest
Many cells in our body release signals that trigger responses in other cells. A protein called PEDF is a signal released from a variety of cells that can prevent the formation of new blood vessels, protect cells in the retina and brain from damage and stop cancer cells from growing. Experiments using model animals have also demonstrated that PEDF could be used to treat a variety of eye diseases that lead to blindness and many types of cancer.
PEDF is found in tissues including the brain, eye, liver, heart and lung, but it was not known how cells sense this signal. Cells are expected to have specific proteins called receptors on the cell surface membrane to detect PEDF and transmit the signal into the cell; however, the identity of these receptors has remained a long-standing unsolved puzzle.
Cheng, Zhong, Kawaguchi et al. have now identified two human proteins that act as receptors for PEDF. These proteins—known as PLXDC1 and PLXDC2—span the cell surface membrane, and bind to PEDF on the outside of the cell. PLXDC1 and PLXDC2 are expressed on different types of cells that respond to PEDF. Furthermore, PEDF was unable to act upon cells that had been engineered to make less of these two receptors.
This study also revealed that each receptor can play different roles in different cell types. For example, exposing one type of cell from blood vessels to PEDF would normally kill them, but cells without PLXDC2 (but not those without PLXDC1) could survive PEDF treatment. Furthermore, PEDF treatment protects a type of neuron against environmental damage, and this activity depends on PLXDC1, but not PLXDC2.
How do the receptors transmit the PEDF signal from the outside of the cell to the inside of the cell? Cheng, Zhong, Kawaguchi et al. found that when PEDF is not present, both PLXDC1 and PLXDC2 form complexes containing more than one copy of either receptor. When PEDF binds to the receptors, it causes these complexes to disassemble and this activates further downstream signaling events inside the cell.
Understanding PEDF receptors and their mechanisms will open the way to developing new drugs that target these receptors to treat human diseases.
DOI: http://dx.doi.org/10.7554/eLife.05401.002
doi:10.7554/eLife.05401
PMCID: PMC4303762  PMID: 25535841
membrane receptors; signal transduction; human disease; none
4.  High levels of SIRT1 expression enhance tumorigenesis and associate with a poor prognosis of colorectal carcinoma patients 
Scientific Reports  2014;4:7481.
SIRT1, a NAD+ dependent class III deacetylase, takes part in many important biological processes. Previous studies show that SIRT1 is overexpressed in some cancers and plays an essential role in tumorigenesis. However, the association between SIRT1 and colorectal cancer (CRC) is still unclear. We found that many CRC specimens had strong SIRT1 expression, which had an obvious correlation with poor prognosis of CRC patients. Meanwhile, SIRT1 expression had a co-localization with CD133, a current universal marker to characterize colorectal cancer stem cells (CSCs). In vitro studies also revealed that SIRT1 was overexpressed in colorectal CSC-like cells. Moreover, SIRT1 deficiency decreased percentage of CD133+ cells, attenuated the abilities of colony and sphere formation, and inhibited tumorigenicity in vivo in CRC cells. Further study demonstrated that the expressions of several stemness-associated genes, including Oct4, Nanog, Cripto, Tert and Lin28, were reduced by SIRT1 knockdown in CRC cells. Taken together, our findings suggest that SIRT1 plays a crucial role in keeping the characteristics of CSCs cells. SIRT1 is a potential independent prognostic factor of CRC patients after tumor resection with curative intent, and will contribute to providing a promising new approach to target at CSCs in CRC treatment.
doi:10.1038/srep07481
PMCID: PMC4265776  PMID: 25500546
6.  Apo-RBP, Holo-RBP, and Insulin Resistance 
Molecular and Cellular Biology  2014;34(11):2105-2106.
doi:10.1128/MCB.01425-12
PMCID: PMC4019056  PMID: 24803600
7.  Neurogenesis in Adult Human Brain after Traumatic Brain Injury 
Journal of Neurotrauma  2013;30(22):1872-1880.
Abstract
While much work has been conducted regarding the neurogenesis response to traumatic brain injury (TBI) in rodents, it remains largely unknown whether neurogenesis in adult human brain also responds to TBI in a similar manner. Here, we performed immunocytochemistry on 11 brain specimens from patients with traumatic brain injury, who underwent surgical intervention. We found that expression of neural stem/progenitor cell (NSC) protein markers, including DCX, TUC4, PSA-NCAM, SOX2 and NeuroD, was increased in the perilesional cortex of human brain after TBI compared to that of normal brain. Confocal images showed that these NSC proteins were expressed in one single cell. We also found that proliferative markers were expressed in NSC protein-positive cells after TBI, and the number of proliferative NSCs was significantly increased after TBI. Our data suggest that TBI may also induce neurogenesis in human brain.
doi:10.1089/neu.2010.1579
PMCID: PMC3815038  PMID: 21275797
brain trauma; human; injury; neurogenesis; stem cells
8.  Notch4 is Activated in Endothelial and Smooth Muscle Cells in Human Brain Arteriovenous Malformations 
Journal of cellular and molecular medicine  2013;17(11):10.1111/jcmm.12115.
Upregulation of Notch4 was observed in the endothelial cells in the arteriovenous malformations (AVMs) in mice. However, whether Notch4 is also involved in brain AVMs in humans remains unclear. Here, we performed immunohistochemistry on normal brain vascular tissue and surgically-resection brain AVMs and found that Notch4 was upregulated in the subset of abnormal vessels of the brain AVM nidus, compared with control brain vascular tissue. Two-photon confocal images show that Notch4 was expressed not only in the endothelial but also in the smooth muscle cells of the vascular wall in brain AVMs. Western blotting shows that Notch 4 was activated in brain AVMs, but not in middle cerebral artery of normal human brain, which was confirmed by immunostaining. Our findings suggest a possible contribution of Notch4 signaling to the development of brain AVMs in human.
doi:10.1111/jcmm.12115
PMCID: PMC3877925  PMID: 24373503
Notch4; AVM; human; brain; signaling
9.  Decreased expression of interleukin-36α predicts poor prognosis in colorectal cancer patients 
Interleukin-36α (IL-36α), previously designated as IL-1F6, has been found to have a pathogenic role in psoriasis. However, possible functions of IL-36α in cancer remain unclear. In present study, we investigate the possible role of interleukin-36α involved in the pathogenesis of colorectal cancer. IL-36α expression was detected in 345 colorectal cancer tissue samples by immunohistochemical staining, and its relation with clinicopathologic parameters and prognosis of colorectal cancer patients were analyzed. IL-36α was highly expressed in nearly half of all tested colorectal cancer patients. However, low expression level of IL-36α significantly correlated with larger tumor size and advanced TNM stage. Kaplan-Meier survival analysis showed that low expression level of IL-36α resulted in a remarkably poor prognosis of colorectal cancer patients. Multivariate Cox’s analysis revealed that the IL-36α expression level was a significant and independent prognostic factor for overall survival rate of colorectal cancer patients. Thus, our study may provide insight into the application of IL-36α as a novel predictor of prognosis and a potential therapeutic drug for colorectal cancer.
PMCID: PMC4270616  PMID: 25550854
Interleukin-36α; colorectal cancer; prognosis; therapy
10.  Natakalim improves post-infarction left ventricular remodeling by restoring the coordinated balance between endothelial function and cardiac hypertrophy 
Endothelial dysfunction can lead to congestive heart failure and the activation of endothelial ATP-sensitive potassium (KATP) channels may contribute to endothelial protection. Therefore, the present study was carried out to investigate the hypothesis that natakalim, a novel KATP channel opener, ameliorates post-infarction left ventricular remodeling and failure by correcting endothelial dysfunction. The effects of myocardial infarction were assessed 8 weeks following left anterior descending coronary artery occlusion in male Wistar rats. Depressed blood pressure, cardiac dysfunction, evidence of left ventricular remodeling and congestive heart failure were observed in the rats with myocardial infarction. Treatment with natakalim at daily oral doses of 1, 3 or 9 mg/kg/day for 8 weeks prevented these changes. Natakalim also prevented the progression to cardiac failure, which was demonstrated by the increase in right ventricular weight/body weight (RVW/BW) and relative lung weight, signs of cardiac dysfunction, as well as the overexpression of atrial and brain natriuretic peptide mRNAs. Our results also demonstrated that natakalim enhanced the downregulation of endothelium-derived nitric oxide, attenuated the upregulation of inducible nitric oxide synthase-derived nitric oxide (NO), inhibited the upregulated endothelin system and corrected the imbalance between prostacyclin and thromboxane A2. Overall, our findings suggest that natakalim prevents post-infarction hypertrophy and cardiac failure by restoring the coordinated balance between endothelial function and cardiac hypertrophy.
doi:10.3892/ijmm.2014.1931
PMCID: PMC4199399  PMID: 25215478
natakalim; myocardial infarction; left ventricular remodeling; cardiac hypertrophy; congestive heart failure; endothelial function
11.  Control of Dendritic Cell Migration, T Cell-Dependent Immunity, and Autoimmunity by Protein Tyrosine Phosphatase PTPN12 Expressed in Dendritic Cells 
Molecular and Cellular Biology  2014;34(5):888-899.
Dendritic cells (DCs) capture and process antigens in peripheral tissues, migrate to lymphoid tissues, and present the antigens to T cells. PTPN12, also known as PTP-PEST, is an intracellular protein tyrosine phosphatase (PTP) involved in cell-cell and cell-substratum interactions. Herein, we examined the role of PTPN12 in DCs, using a genetically engineered mouse lacking PTPN12 in DCs. Our data indicated that PTPN12 was not necessary for DC differentiation, DC maturation, or cytokine production in response to inflammatory stimuli. However, it was needed for full induction of T cell-dependent immune responses in vivo. This function largely correlated with the need of PTPN12 for DC migration from peripheral sites to secondary lymphoid tissues. Loss of PTPN12 in DCs resulted in hyperphosphorylation of the protein tyrosine kinase Pyk2 and its substrate, the adaptor paxillin. Pharmacological inhibition of Pyk2 or downregulation of Pyk2 expression also compromised DC migration, suggesting that Pyk2 deregulation played a pivotal role in the migration defect caused by PTPN12 deficiency. Together, these findings identified PTPN12 as a key regulator in the ability of DCs to induce antigen-induced T cell responses. This is due primarily to the role of PTPN12 in DC migration from peripheral sites to secondary lymphoid organs through regulation of Pyk2.
doi:10.1128/MCB.01369-13
PMCID: PMC4023833  PMID: 24366546
12.  Multicenter phase ii study of a combination of cyclosporine a, methotrexate and mycophenolate mofetil for GVHD prophylaxis: results of the Chinese Bone Marrow Transplant Cooperative Group (CBMTCG) 
Background
Improvement of current GVHD prophylactic therapies remains an important goal in the allo-HSCT. We have described a novel prophylaxis regimen in a single institution trial. The Chinese Bone Marrow Transplant Cooperative Group (CBMTCG) initiated a phase II multicenter study.
Methods
The study was designed as a prospective, single arm phase II open-label, multicenter clinical trial. The primary endpoint was improvement of aGVHD by 25% over historical control (40%) in Chinese patients. 508 patients were enrolled. All of the patients received cyclosporine A (CsA), methotrexate (MTX) and mycophenolate mofetil (MMF) (0.5-1.0 g daily for 30 days) as GVHD prophylaxis regimen.
Results
The primary endpoint was met with cumulative incidences of grades 2 to 4 and grades 3 to 4 aGVHD of 23.2% and 10.3%, respectively. Incidence for cGVHD was 67.4%. The non-relapse mortality (NRM) rate was 18.4% at 2 years. The probabilities of leukemia free survival (LFS) for non-advanced stage and advanced stage patients at 2 years were 69.7% and 44.8% respectively (p = 0.000). Recipient age ≥ 40 years, advanced stage and Busulfan-Fludarabine(BuFlu) conditioning regimen were identified as major risk factors for aGVHD. Recipient age ≥ 40 years, BuFlu conditioning regimens, female donor/male recipient and prior aGVHD were associated with cGVHD. Despite lower RM (relapse mortality), patients with grade 2–4 aGVHD had higher NRM and worse OS and LFS compared to patients with grade 0–1 aGVHD. In contrast, patients with cGVHD had better OS and LFS and lower RM compared to patients without cGVHD.
Conclusion
The novel GVHD regimen decreased the risk for aGVHD by 42% without improving the risk for cGVHD compared to historical controls. Development of aGVHD was associated with worse OS and LFS as well as higher NRM. In contrast, cGVHD was associated with improved OS and LFS likely attributed to a GVL effect.
doi:10.1186/s13045-014-0059-3
PMCID: PMC4237802  PMID: 25139202
Allogeneic hematopoietic stem cell transplantation (allo-HSCT); Graft-versus-host disease (GVHD) prophylaxis; Mycophenolate mofetil (MMF)
13.  Antisense knockdown of pyruvate dehydrogenase kinase promotes the neutral lipid accumulation in the diatom Phaeodactylum tricornutum 
Microbial Cell Factories  2014;13(1):100.
Background
Microalgae have been an emerging biofuel resource; however, the germplasm improvement has been slow due to the lack of molecular tools. Pyruvate dehydrogenase kinase (PDK) deactivates the pyruvate dehydrogenase complex (PDC) which catalyzes the oxidative decarboxylation of pyruvate. Acetyl-CoA production via PDC is important in plant tissues that are active in fatty acid synthesis.
Results
A 1261-bp cDNA of a putative PDK gene (PtPDK) was cloned from a diatom Phaeodactylum tricornutum, and PtPDK antisense knockdown transgenic diatoms were generated. Both PtPDK transcript abundance and enzyme activity were reduced significantly due to antisense knockdown of PtPDK. Neutral lipid content of transgenic diatom cells increased up to 82% as determined by Nile red staining, and fatty acid composition was not altered. Transgenic cells showed slightly lower growth rate but similar cell size with the wild type, hence retaining similar biomass productivity.
Conclusions
This work first obtained a successful engineered diatom regulating a key gene involved in lipid metabolism. Our findings also provide powerful indications in enhancing microalgal lipid production by metabolic engineering for biofuel industry.
doi:10.1186/s12934-014-0100-9
PMCID: PMC4251698  PMID: 25106441
Microalga; Pyruvate dehydrogenase kinase; Antisense; Lipid; Biofuel
14.  Differential and Isomer-Specific Modulation of Vitamin A Transport and the Catalytic Activities of the RBP Receptor by Retinoids 
The Journal of membrane biology  2013;246(8):647-660.
Retinoids are vitamin A derivatives with diverse biological functions. Both natural and artificial retinoids have been used as therapeutic reagents to treat human diseases, but not all retinoid actions are understood mechanistically. Plasma retinol binding protein (RBP) is the principal and specific carrier of vitamin A in the blood. STRA6 is the membrane receptor for RBP that mediates cellular vitamin A uptake. The effects of retinoids or related compounds on the receptor’s vitamin A uptake activity and its catalytic activities are not well understood. In this study, we dissected the membrane receptor-mediated vitamin A uptake mechanism using various retinoids. We show that a subset of retinoids strongly stimulates STRA6-mediated vitamin A release from holo-RBP. STRA6 also catalyzes the exchange of retinol in RBP with certain retinoids. The effect of retinoids on STRA6 is highly isomer-specific. This study provides unique insights into the RBP receptor’s mechanism and reveals that the vitamin A transport machinery can be a target of retinoid-based drugs.
doi:10.1007/s00232-013-9578-z
PMCID: PMC3777752  PMID: 23811822
Membrane receptor; Membrane transport; Vitamin A transport; Retinoid
15.  Role of the C-Terminus of the Photoreceptor ABCA4 Transporter in Protein Folding, Function and Retinal Degenerative Diseases* 
The Journal of biological chemistry  2008;284(6):3640-3649.
ABCA4 is an ATP binding cassette (ABC) transporter that is expressed in rod and cone photoreceptor cells and implicated in the removal of retinal derivatives from outer segments following photoexcitation. Mutations in the ABCA4 gene are responsible for a number of related retinal degenerative diseases including Stargardt macular degeneration, cone-rod dystrophy, retinitis pigmentosa, and age-related macular degeneration. In order to determine the role of the C-terminus of ABCA4 in protein structure and function and understand mechanisms by which C-terminal mutations cause retinal degenerative diseases, we have expressed and purified a series of deletion and substitution mutants of ABCA4 and ABCA1 in HEK 293T cells for analysis of their cellular localization and biochemical properties. Removal of the C-terminal 30 amino acids of ABCA4 including a conserved VFVNFA motif resulted in the loss in N-retinylidene-phosphatidylethanolamine substrate binding, ATP photoaffinity labeling, and retinal stimulated ATPase activity. This mutant was also retained in the endoplasmic reticulum (ER) of cells. Replacement of the VFVNFA motif with alanine residues also resulted in loss in function and cellular mislocalization. In contrast C-terminal deletion mutants that retain the VFVNFA motif were functionally active and localized to intracellular vesicles similar to wild-type ABCA4. Our studies indicated that the VFVNFA motif is required for the proper folding of ABCA4 into a functionally active protein. This motif also contributes to the efficient folding of ABCA1 into an active protein. Our results provide a molecular based rationale for the disease phenotype displayed by individuals with mutations in the C-terminus of ABCA4.
doi:10.1074/jbc.M806580200
PMCID: PMC4090197  PMID: 19056738 CAMSID: cams4543
16.  Epidermal Growth Factor-Like Domain-Containing Protein 7 (EGFL7) Enhances EGF Receptor−AKT Signaling, Epithelial−Mesenchymal Transition, and Metastasis of Gastric Cancer Cells 
PLoS ONE  2014;9(6):e99922.
Epidermal growth factor-like domain-containing protein 7 (EGFL7) is upregulated in human epithelial tumors and so is a potential biomarker for malignancy. Indeed, previous studies have shown that high EGFL7 expression promotes infiltration and metastasis of gastric carcinoma. The epithelial–mesenchymal transition (EMT) initiates the metastatic cascade and endows cancer cells with invasive and migratory capacity; however, it is not known if EGFL7 promotes metastasis by triggering EMT. We found that EGFL7 was overexpressed in multiple human gastric cancer (GC) cell lines and that overexpression promoted cell invasion and migration as revealed by scratch wound and transwell migration assays. Conversely, shRNA-mediated EGFL7 knockdown reduced invasion and migration. Furthermore, EGFL7-overexpressing cells grew into larger tumors and were more likely to metastasize to the liver compared to underexpressing CG cells following subcutaneous injection in mice. EGFL7 overexpression protected GC cell lines against anoikis, providing a plausible mechanism for this enhanced metastatic capacity. In excised human gastric tumors, expression of EGFL7 was positively correlated with expression levels of the mesenchymal marker vimentin and the EMT-associated transcription repressor Snail, and negatively correlated with expression of the epithelial cell marker E-cadherin. In GC cell lines, EGFL7 knockdown reversed morphological signs of EMT and decreased both vimentin and Snail expression. In addition, EGFL7 overexpression promoted EGF receptor (EGFR) and protein kinase B (AKT) phospho-activation, effects markedly suppressed by the EGFR tyrosine kinase inhibitor AG1478. Moreover, AG1478 also reduced the elevated invasive and migratory capacity of GC cell lines overexpressing EGFL7. Collectively, these results strongly suggest that EGFL7 promotes metastasis by activating EMT through an EGFR−AKT−Snail signaling pathway. Disruption of EGFL7−EGFR−AKT−Snail signaling may a promising therapeutic strategy for gastric cancer.
doi:10.1371/journal.pone.0099922
PMCID: PMC4063792  PMID: 24945379
17.  Primary neuroendocrine small cell carcinoma of the parotid gland: A case report and review of the literature 
Oncology Letters  2014;8(3):1275-1278.
Small cell carcinoma (SCC) is a malignant epithelial tumor that predominantly arises in the lungs. Primary SCC of the parotid gland is rare and difficult to diagnose by analysis of frozen sections obtained during surgery. Due to the aggressive nature of SCC and the frequent occurrence of distant metastases, identification of the disease is important. The current study reports the case of a male patient who presented with a right parotid gland mass. The tumor was resected and evaluated by light microscopy and immunohistochemical analysis. Immunohistochemically, the tumor was positive for cytokeratin, epithelial membrane antigen, cluster of differentiation 117, synaptophysin and thyroid transcription factor-1, which indicated that the tumor was a SCC of the parotid gland. An extended resection of the right parotid gland mass and dissection of the facial nerve were performed. Following discharge from the hospital, the patient received radiation therapy postoperatively. The patient has remained disease free during five months of follow-up.
doi:10.3892/ol.2014.2258
PMCID: PMC4114714  PMID: 25120705
neuroendocrine small cell carcinoma; immunohistochemistry; parotid gland
18.  Gene expression analysis of potential genes and pathways involved in the pathogenic mechanisms of parvovirus B19 in human colorectal cancer 
Oncology Letters  2014;8(2):523-532.
In order to investigate the pathogenic mechanisms of parvovirus B19 in human colorectal cancer, plasmids containing the VP1 or VP2 viral capsid proteins or the NS1 non-structural proteins of parvovirus B19 were constructed and transfected into primary human colorectal epithelial cells and LoVo cells. Differential gene expression was detected using a human genome expression array. Functional gene annotation analyses were performed using Database for Annotation, Visualization and Integrated Discovery v6.7 software. Gene ontology (GO) analyses revealed that VP1-related functions included the immune response, immune system process, defense response and the response to stimulus, while NS1-associated functions were found to include organelle fission, nuclear division, mitosis, the M-phase of the mitotic cell cycle, the mitotic cell cycle, M-phase, cell cycle phase, cell cycle process and cell division. Pathway expression analysis revealed that VP1-associated pathways included cell adhesion molecules, antigen processing and presentation, cytokines and the inflammatory response. Moreover, NS1-associated pathways included the cell cycle, pathways in cancer, colorectal cancer, the wnt signaling pathway and focal adhesion. Among the differential genes detected in the present study, 12 genes were found to participate in general cancer pathways and six genes were observed to participate in colorectal cancer pathways. NS1 is a key molecule in the pathogenic mechanism of parvovirus B19 in colorectal cancer. Several GO categories, pathways and genes were selected and may be the key targets through which parvovirus B19 participates in colorectal cancer pathogenesis.
doi:10.3892/ol.2014.2151
PMCID: PMC4081382  PMID: 25013465
colorectal cancer; parvovirus B19; pathogenesis; microarray; human
19.  Impact of type 2 diabetes mellitus on hospitalization costs in older patients with acute myocardial infarction 
Background
The purpose of this study was to evaluate the impact of type 2 diabetes mellitus on hospitalization costs in older patients with acute myocardial infarction (MI).
Methods
Retrospective analysis of data from the case retrieval system of Qilu Hospital of Shandong University located in Jinan city of Shandong Province was done for patients with acute MI from January 1, 2011 to December 31, 2012.
Results
Stenting was an important factor affecting older patients’ total hospitalization costs (β=0.685, P=0.000) and treatment costs during the follow-up period (duration of hospital stay only, β=0.508, P=0.000). Stenting was also a protective factor in the prevention of acute heart failure (HF) in older patients with acute MI during the follow-up period (odds ratio 0.189, 95% confidence interval 0.059–0.602, P=0.005). Implementation of percutaneous coronary intervention reduced the incidence of acute HF in older inpatients with acute MI (27.8% versus 4.3%, P=0.001) and without diabetes (18.2% versus 3.8%, P=0.001). Moreover, among the elderly, the incremental cost-effectiveness ratio estimate for implementing percutaneous coronary intervention in diabetic patients was higher than in nondiabetic patients.
Conclusion
Stenting was a protective factor for preventing acute HF in the elderly during the follow-up period. From the perspective of reducing the incidence of acute HF in inpatients, implementation of percutaneous coronary intervention after an acute MI is more cost-effective in older patients with diabetes mellitus than in those without it.
doi:10.2147/CIA.S59802
PMCID: PMC4008285  PMID: 24812498
diabetes; aging; myocardial infarction; hospitalization costs; vascular
20.  A Multicenter prospective study of poor-grade aneurysmal subarachnoid hemorrhage (AMPAS): observational registry study 
BMC Neurology  2014;14:86.
Background
Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with very high mortality and morbidity. Our limited knowledge on predictors of long-term outcome in poor-grade patients with aSAH definitively managed comes from retrospective and prospective studies of small case series of patients in single center. The purpose of the AMPAS is to determine the long-term outcomes in poor-grade patients with different managements within different time after aSAH, and identify the independent predictors of the outcome that help guide the decision on definitive management.
Methods/design
The AMPAS study is a prospective, multicenter, observational registry of consecutive hospitalized patients with poor grade aSAH (WFNS grade IV and V). The aim is to enroll at least 226 poor-grade patients in 11 high-volume medical centers (eg, >150 aSAH cases per year) affiliated to different universities in China. This study will describe poor grade patients and aneurysm characteristics, treatment strategies (modality and time of definitive management), hospitalization complications and outcomes evolve over time. The definitive management is ruptured aneurysm treatment. Outcomes at 3, 6, 12 months after the management were measured using the Glasgow Outcome Scale and the Modified Rankin Scale.
Discussion
The AMPAS is the first prospective, multicenter, observational registry of poor grade aSAH with any management. This study will contribute to a better understanding of significant predictors of outcome in poor grade patients and help guide future treatment of the worst patients after aSAH.
Trial registration
Chinese Clinical Trial Registry: ChiCTR-TNRC-10001041.
doi:10.1186/1471-2377-14-86
PMCID: PMC3997185  PMID: 24742248
Aneurysmal subarachnoid hemorrhage; Poor-grade; Definitive management; Outcome; Predicators
21.  Micro-ribonucleic acid expression profiling and bioinformatic target gene analyses in laryngeal carcinoma 
OncoTargets and therapy  2014;7:525-533.
Abnormal expression of micro-ribonucleic acid (miRNA) might be clinically valuable as a biomarker or treatment target in the early diagnosis, treatment, and prognosis of tumors. However, little is known concerning abnormal miRNA expression of laryngeal carcinoma, one of the most commonly encountered head and neck tumors. Microarray analysis was used to obtain miRNA-expression profiles of ten pairs of freshly frozen laryngeal carcinoma tissue and surrounding normal tissue specimens. Characteristic miRNAs that were significantly related to laryngeal carcinoma were identified. Verification was performed using an additional 32 pairs of samples. The expression of two miRNAs (miR-21-3p and miR-106b-3p) was upregulated in both microarray and quantitative real-time polymerase chain-reaction analyses, whereas the expression of six miRNAs (let-7f-5p, miR-10a-5p, miR-125a-5p, miR-144-3p, miR-195-5p, and miR-203) was downregulated. The decreased expression of let-7f-5p and miR-195-5p is a novel finding in head and neck cancer. The target genes of these miRNAs were also predicted through multiple software programs. The differential expression of miRNAs might be related to the early onset and development of laryngeal carcinoma, and may be exploited as new biomarkers and therapeutic targets in the treatment of laryngeal carcinoma.
doi:10.2147/OTT.S59871
PMCID: PMC3983076  PMID: 24741319
microRNA; laryngeal carcinoma; expression profiling; bioinformatics; target prediction
22.  Overexpression of STAMP2 suppresses atherosclerosis and stabilizes plaques in diabetic mice 
Our research aims to evaluate the function of the STAMP2 gene, an important trigger in insulin resistance (IR), and explore its role in macrophage apoptosis in diabetic atherosclerotic vulnerable plaques. The characteristics of diabetic mice were measured by serial metabolite and pathology tests. The level of STAMP2 was measured by RT-PCR and Western blot. The plaque area, lipid and collagen content of brachiocephalic artery plaques were measured by histopathological analyses, and the macrophage apoptosis was measured by TUNEL. Correlation of STAMP2/Akt signaling pathway and macrophage apoptosis was validated by Ad-STAMP2 transfection and STAMP2 siRNA inhibition. The diabetic mice showed typical features of IR, hyperglycaemia. Overexpression of STAMP2 ameliorated IR and decreased serum glucose level. In brachiocephalic lesions, lipid content, macrophage quantity and the vulnerability index were significantly decreased by overexpression of STAMP2. Moreover, the numbers of apoptotic cells and macrophages in lesions were both significantly decreased. In vitro, both mRNA and protein expressions of STAMP2 were increased under high glucose treatment. P-Akt was highly expressed and caspase-3 was decreased after overexpression of STAMP2. However, expression of p-Akt protein was decreased and caspase-3 was increased when STAMP2 was inhibited by siRNA. STAMP2 overexpression could exert a protective effect on diabetic atherosclerosis by reducing IR and diminishing macrophage apoptosis.
doi:10.1111/jcmm.12222
PMCID: PMC4000123  PMID: 24467451
STAMP2/Akt signalling pathway; apoptosis of macrophage; Type 2 diabetes mellitus; insulin resistance; vulnerable plaque; vascular
23.  Evaluation of Abbott RealTime CT/NG Assay for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae in Cervical Swabs from Female Sex Workers in China 
PLoS ONE  2014;9(3):e89658.
Background
To evaluate the performance of the Abbott RealTime CT/NG assay for detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) among female sex workers (FSWs) in China.
Methods
Cervical swabs from 997 participants were blindly detected by the Abbott RealTime CT/NG assay on the automated m2000 molecular platform and Roche Cobas Amplicor CT/NG assay. Discrepant analysis were confirmed by the Qiagen care CT PCR assay. The sample was defined as candidate nvCT-positive if it was CT positive in the Abbott m2000 assay, but CT negative in the other two assays.
Results
25 specimens that were discordant for CT and 26 specimens that were discordant for NG between the two assays were resolved by Qiagen care CT & NG PCR assays. The sensitivity and specificity, respectively, for Abbott m2000 assay were 92.59% and 100% for CT and 95.45% and 99.90% for NG. The positive predictive value (PPV) and negative predictive value (NPV) of Abbott m2000 assay were100% and 98.52% for CT and 95.5% and 99.90% for NG, respectively. No candidate new-variant CT(nvCT)specimens were identified.
Conclusion
Abbott RealTime CT/NG assay were more specify for CT and NG detection, however, its sensitivity for CT and NG were a little bit lower than Roche Cobas Amplicor CT/NG assay. Abbott RealTime CT/NG assay had higher PPV for NG detection than Roche Cobas Amplicor CT/NG assay; it would be more suitable for screening for population with low-prevalence NG. There is currently no evidence that nvCT is present in FSWs in China.
doi:10.1371/journal.pone.0089658
PMCID: PMC3943787  PMID: 24599315
24.  Real-Time Analyses of Retinol Transport by the Membrane Receptor of Plasma Retinol Binding Protein 
Vitamin A is essential for vision and the growth/differentiation of almost all human organs. Plasma retinol binding protein (RBP) is the principle and specific carrier of vitamin A in the blood. Here we describe an optimized technique to produce and purify holo-RBP and two real-time monitoring techniques to study the transport of vitamin A by the high-affinity RBP receptor STRA6. The first technique makes it possible to produce a large quantity of high quality holo-RBP (100%-loaded with retinol) for vitamin A transport assays. High quality RBP is essential for functional assays because misfolded RBP releases vitamin A readily and bacterial contamination in RBP preparation can cause artifacts. Real-time monitoring techniques like electrophysiology have made critical contributions to the studies of membrane transport. The RBP receptor-mediated retinol transport has not been analyzed in real time until recently. The second technique described here is the real-time analysis of STRA6-catalyzed retinol release or loading. The third technique is real-time analysis of STRA6-catalyzed retinol transport from holo-RBP to cellular retinol binding protein I (CRBP-I). These techniques provide high sensitivity and resolution in revealing RBP receptor’s vitamin A uptake mechanism.
doi:10.3791/50169
PMCID: PMC3582664  PMID: 23407361
Vitamin A; retinoid; membrane transport; membrane receptor; STRA6; retinol binding protein
25.  Coexisting primary central nervous system non-Hodgkin’s lymphoma and colorectal adenocarcinoma: A case report 
Oncology Letters  2014;7(4):994-996.
A 61-year-old female presented with night sweats following a resection for non-Hodgkin’s lymphoma of splenium corporis callosi. A positron emission tomography-computed tomography scan demonstrated that original lymphoma activity remained. A new ascending colon mass was identified simultaneously, which was diagnosed as an adenocarcinoma following the surgery. To the best of our knowledge, this is the first case to report a coexistence of primary central nervous system non-Hodgkin’s lymphoma and colorectal adenocarcinoma. The case poses a difficult clinical challenge.
doi:10.3892/ol.2014.1818
PMCID: PMC3961312  PMID: 24944656
primary central nervous system non-Hodgkin’s lymphoma; colorectal adenocarcinoma; synchronous carcinomas

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