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1.  Effect of Abnormal Fasting Plasma Glucose Level on All-Cause Mortality in Older Patients With Acute Myocardial Infarction: Results From the Beijing Elderly Acute Myocardial Infarction Study (BEAMIS) 
Mayo Clinic Proceedings  2011;86(2):94-104.
OBJECTIVE: To assess whether the relationship between abnormal fasting plasma glucose (FPG) levels and patient outcomes holds for both older men and older women with acute myocardial infarction (AMI).
PATIENTS AND METHODS: From April 1, 2004, to October 31, 2006, a total of 2016 consecutive older patients (age ≥65 years) presenting with AMI were screened. Of these patients, 1854 were consecutively enrolled in the study. Patients were categorized into 4 groups: the hypoglycemic group (FPG, ≤90.0 mg/dL [to convert to mmol/L, multiply by 0.0555]; n=443, 23.9%), the euglycemic group (FPG, 90.1-126.0 mg/dL; n=812, 43.8%), the mildly hyperglycemic group (FPG, 126.1-162.0 mg/dL; n=308, 16.6%), and the severely hyperglycemic group (FPG, ≥162.1 mg/dL; n=291, 15.7%). The primary outcomes were rates of in-hospital and 3-year mortality.
RESULTS: Female patients were older and had a higher incidence of diabetes mellitus but lower rates of smoking and use of invasive therapy. Men tended to have a higher frequency of hypoglycemia, whereas women tended to have a higher frequency of hyperglycemia. No significant difference was found in in-hospital (10.9% vs 9.1%; P=.36) or 3-year (24.5% vs 24.5%; P=.99) mortality between male and female patients, and FPG-associated mortality did not vary significantly by sex.
CONCLUSION: An increased FPG level was associated with a relatively higher risk of in-hospital mortality in men but not in women. Nonetheless, increased and decreased FPG levels at admission could predict higher mortality rates regardless of sex. There was a striking U-shaped relationship between FPG levels and in-hospital and 3-year mortality. The effect of abnormal FPG level on outcomes among older patients with AMI did not vary significantly by sex.
An increased fasting plasma glucose level was associated with a relatively higher risk of in-hospital mortality in men but not in women. Nonetheless, increased and decreased fasting plasma glucose levels at admission could predict higher mortality rates regardless of sex.
doi:10.4065/mcp.2010.0473
PMCID: PMC3031433  PMID: 21282483
2.  Left Ventricular Function during Acute High-Altitude Exposure in a Large Group of Healthy Young Chinese Men 
PLoS ONE  2015;10(1):e0116936.
Objective
The purpose of this study was to observe left ventricular function during acute high-altitude exposure in a large group of healthy young males.
Methods
A prospective trial was conducted in Szechwan and Tibet from June to August, 2012. By Doppler echocardiography, left ventricular function was examined in 139 healthy young Chinese men at sea level; within 24 hours after arrival in Lhasa, Tibet, at 3700 m; and on day 7 following an ascent to Yangbajing at 4400 m after 7 days of acclimatization at 3700 m. The resting oxygen saturation (SaO2), heart rate (HR) and blood pressure (BP) were also measured at the above mentioned three time points.
Results
Within 24 hours of arrival at 3700 m, the HR, ejection fraction (EF), fractional shortening (FS), stroke volume (SV), cardiac output (CO), and left ventricular (LV) Tei index were significantly increased, but the LV end-systolic dimension (ESD), end-systolic volume (ESV), SaO2, E/A ratio, and ejection time (ET) were significantly decreased compared to the baseline levels in all subjects. On day 7 at 4400 m, the SV and CO were significantly decreased; the EF and FS Tei were not decreased compared with the values at 3700 m; the HR was further elevated; and the SaO2, ESV, ESD, and ET were further reduced. Additionally, the E/A ratio was significantly increased on day 7 but was still lower than it was at low altitude.
Conclusion
Upon acute high-altitude exposure, left ventricular systolic function was elevated with increased stroke volume, but diastolic function was decreased in healthy young males. With higher altitude exposure and prolonged acclimatization, the left ventricular systolic function was preserved with reduced stroke volume and improved diastolic function.
doi:10.1371/journal.pone.0116936
PMCID: PMC4309605  PMID: 25629435
3.  Quantitative Detection of Circulating Nucleophosmin Mutations DNA in the Plasma of Patients with Acute Myeloid Leukemia 
Objective: The aim of this study was to quantify the copies of circulating nucleophosmin (NPM) mutations DNA in the plasma of patients with acute myeloid leukemia (AML) and to explore the association of circulating NPM mutation levels with clinical characteristics.
Design and Methods: The presence of NPM mutations in 100 Chinese patients newly diagnosed with AML were identified by RT-PCR and sequencing analysis. Copies of circulating NPM mutation A (NPM mut.A) DNA in the plasma of mutation-positive cases were quantified by real-time quantitative PCR (qRT-PCR). Furthermore, the association of circulating NPM mutation levels and clinical characteristics was analyzed.
Results: NPM mutations were identified in 37 of the 100 patients and all cases were NPM mut.A. The circulating NPM mut.A levels ranged from 0.35×108 copies/ml to 6.0×108 copies/ml in the 37 mutation-positive cases. The medium and quartile M (P25, P75) of the circulating NPM mut.A levels in patients classified as M2, M4 and M5 morphological subtypes were 1.35×108 (0.76×108, 1.91×108) copies/ml, 1.81×108 (1.47×108, 2.2×108) copies/ml and 2.50×108 (2.42×108, 3.05×108) copies/ml, respectively. Circulating NPM mut.A levels were significantly higher in patients with the M5 subtype of AML compared to patients with the M2 and M4 subtypes (p=0.000, p=0.046). In addition, circulating NPM mut.A copies were significantly associated with a higher white blood cell count, platelet count and bone marrow blast percentage (p<0.05).
Conclusion: Our results suggest that circulating NPM mutations DNA assay serves as a complementary to the routine investigative protocol of NPM-mutated leukemia.
doi:10.7150/ijms.10144
PMCID: PMC4278871  PMID: 25552914
nucleophosmin; mutation; acute myeloid leukemia; circulating DNA; real-time quantitative polymerase chain reaction.
4.  Intramuscular dendritic fibromyxolipoma in a 24-year-old male: A case report and review of the literature 
Oncology Letters  2014;9(2):583-586.
Dendritic fibromyxolipoma (DFML) is an uncommon, benign soft tumor that usually arises in the subcutis. To date, ~24 cases of DFML have been reported in the literature and only one of these has been in the muscle. The present study reports the case of a 24-year-old male with a slow-growing, painless mass located deep in the triceps brachii in the left shoulder region. The mass was 14.0×8.5×8.0 cm in size, with well-circumscribed margins. Microscopically, the resected mass was characterized by a proliferation of small spindle or stellate cells, prominent abundant myxoid stroma with ropey collagen bundles and admixed mature adipose tissue. Further immunohistochemical staining indicated that the spindle and stellate cells were reactive with cluster of differentiation 34, vimentin and B-cell lymphoma-2, but not with smooth muscle actin and desmin. Fluorescence in situ hybridization showed that the tumor cells did not have the DDIT3 alteration or amplification of MDM2. The tumor was confirmed to be a DFML due to the typical histological, immunophenotypic and genetic findings. To date, subsequent to 4 years of clinical follow-up, there is no sign of recurrence or metastasis. The present study reports a case of DFML in the youngest known patient, and is the second reported case of an intramuscular DFML occurring in the triceps brachii in the left shoulder region. The study discusses the clinicopathological features and the differential diagnosis of DFML, with a review of the literature.
doi:10.3892/ol.2014.2794
PMCID: PMC4301481  PMID: 25621027
intramuscular; dendritic fibromyxolipoma; myxoid spindle cell lipoma; solitary fibrous tumor
5.  Effects of Acarbose Addition on Ruminal Bacterial Microbiota, Lipopolysaccharide Levels and Fermentation Characteristics In vitro 
This study investigated the effects of acarbose addition on changes in ruminal fermentation characteristics and the composition of the ruminal bacterial community in vitro using batch cultures. Rumen fluid was collected from the rumens of three cannulated Holstein cattle fed forage ad libitum that was supplemented with 6 kg of concentrate. The batch cultures consisted of 8 mL of strained rumen fluid in 40 mL of an anaerobic buffer containing 0.49 g of corn grain, 0.21 g of soybean meal, 0.15 g of alfalfa and 0.15g of Leymus chinensis. Acarbose was added to incubation bottles to achieve final concentrations of 0.1, 0.2, and 0.4 mg/mL. After incubation for 24 h, the addition of acarbose linearly decreased (p<0.05) the total gas production and the concentrations of acetate, propionate, butyrate, total volatile fatty acids, lactate and lipopolysaccharide (LPS). It also linearly increased (p<0.05) the ratio of acetate to propionate, the concentrations of isovalerate, valerate and ammonia-nitrogen and the pH value compared with the control. Pyrosequencing of the 16S rRNA gene showed that the addition of acarbose decreased (p<0.05) the proportion of Firmicutes and Proteobacteria and increased (p<0.05) the percentage of Bacteroidetes, Fibrobacteres, and Synergistetes compared with the control. A principal coordinates analysis plot based on unweighted UniFrac values and molecular variance analysis revealed that the structure of the ruminal bacterial communities in the control was different to that of the ruminal microbiota in the acarbose group. In conclusion, acarbose addition can affect the composition of the ruminal microbial community and may be potentially useful for preventing the occurrence of ruminal acidosis and the accumulation of LPS in the rumen.
doi:10.5713/ajas.2014.14292
PMCID: PMC4213684  PMID: 25358366
Acarbose; Ruminal Microbiota; Pyrosequencing; In vitro Fermentation
6.  Resources and Biological Activities of Natural Polyphenols 
Nutrients  2014;6(12):6020-6047.
The oxidative stress imposed by reactive oxygen species (ROS) plays an important role in many chronic and degenerative diseases. As an important category of phytochemicals, phenolic compounds universally exist in plants, and have been considered to have high antioxidant ability and free radical scavenging capacity, with the mechanism of inhibiting the enzymes responsible for ROS production and reducing highly oxidized ROS. Therefore, phenolic compounds have attracted increasing attention as potential agents for preventing and treating many oxidative stress-related diseases, such as cardiovascular diseases, cancer, ageing, diabetes mellitus and neurodegenerative diseases. This review summarizes current knowledge of natural polyphenols, including resource, bioactivities, bioavailability and potential toxicity.
doi:10.3390/nu6126020
PMCID: PMC4277013  PMID: 25533011
polyphenols; antioxidant; cardioprotection; anticancer; anti-inflammation; antimicrobial; bioavailability
7.  Synchronous poorly-differentiated neuroendocrine carcinoma and gastrointestinal stromal tumor of the stomach: a case report with immunohistochemical and molecular genetic analyses of KIT and PDGFRA 
Although the stomach is the most common location for gastrointestinal stromal tumor (GIST) with co-primary tumors, the synchronous appearance of a poorly differentiated neuroendocrine carcinoma (NEC) and GIST in the stomach is extremely rare. To the best of our knowledge, this is the first case of gastric GIST coexisting with gastric NEC to be reported in the literature. The current study reports the case of a 71-year-old male with gastric poorly differentiated NEC and GIST discovered incidentally during surgical treatment of the NEC. Immunohistochemistry analysis showed that the NEC tumor cells were positive for CK (cytokeratin), CD57, synaptophysin, chromogranin, CD117 (KIT protein), Dog-1 (discovered on GIST-1 protein) and CD34. The synchronous GIST immunophenotype showed positivity for CD117, Dog-1 and CD34 (100%), whereas staining for CK, SMA, desmin and S100 was negative. Ki-67 labeling of proliferating cells was 90% in NEC and 1% in GIST. An accurate diagnosis was confirmed by immunohistochemical findings. Furthermore, genetic analysis using PCR direct sequencing identified no mutations in the KIT (exons 9, 11, 13 and 17) and PDGFRA (exons 12 and 18) genes. The patient developed lymph node metastases and underwent cisplatin-based chemotherapy after the operation. This is the first documented case of synchronous gastric GIST and NEC with the examination of protein expression and gene mutations in KIT and PDGFRA, which will help to further understand the etiology and pathogenesis of NEC coexisting with GIST in a gastric location.
PMCID: PMC4313951
Snchronous tumor; neuroendocrine; carcinoma; GIST; gastric
8.  Role of microRNAs on therapy resistance in Non-Hodgkin’s lymphoma 
Non-Hodgkin’s lymphoma (NHL) is a heterogeneous group of malignancies that originate in lymphatic hematopoietic tissue. Chemotherapy has been used as the main therapy for NHL all the time, and local radiotherapy is also a necessary approach to supplementary treatment. However, resistance of tumor cells to chemo- and radiotherapy often prevent a successful long-term treatment of NHL. MicroRNAs (miRNAs) are a class of approximately 22-nucleotide endogenous non-coding RNAs that play an important regulatory role in gene expression, involving in the process of cell proliferation and differentiation. Alterations of miRNAs have been reported in a variety of human cancers, such as lymphomas, and will critically influence the tumor development and progression. Recently, there is increasing evidence that miRNAs could also influence sensitivity of tumor cells to chemo- and radiotherapy, revealing a crucial role of microRNAs in resistance to anticancer treatment. Therefore, understanding the role of miRNAs in chemo- and radio-resistance of tumor and targeting specific miRNAs will open novel avenues for lymphoma treatment and improve the prognosis of NHL patients. This review outlines the role of miRNAs associated with chemo-and radiotherapy resistance in NHL.
PMCID: PMC4276148  PMID: 25550890
MicroRNA; Non-Hodgkin’s lymphoma; chemoresistance; radio-resistance
9.  Chronic Glucocorticoid Exposure-Induced Epididymal Adiposity Is Associated with Mitochondrial Dysfunction in White Adipose Tissue of Male C57BL/6J Mice 
PLoS ONE  2014;9(11):e112628.
Prolonged and excessive glucocorticoids (GC) exposure resulted from Cushing's syndrome or GC therapy develops central obesity. Moreover, mitochondria are crucial in adipose energy homeostasis. Thus, we tested the hypothesis that mitochondrial dysfunction may contribute to chronic GC exposure-induced epididymal adiposity in the present study. A total of thirty-six 5-week-old male C57BL/6J mice (∼20 g) were administrated with 100 µg/ml corticosterone (CORT) or vehicle through drinking water for 4 weeks. Chronic CORT exposure mildly decreased body weight without altering food and water intake in mice. The epididymal fat accumulation was increased, but adipocyte size was decreased by CORT. CORT also increased plasma CORT, insulin, leptin, and fibroblast growth factor 21 concentrations as measured by RIA or ELISA. Interestingly, CORT increased plasma levels of triacylglycerols and nonesterified fatty acids, and up-regulated the expression of both lipolytic and lipogenic genes as determined by real-time RT-PCR. Furthermore, CORT impaired mitochondrial biogenesis and oxidative function in epididymal WAT. The reactive oxygen species production was increased and the activities of anti-oxidative enzymes were reduced by CORT treatment as well. Taken together, these findings reveal that chronic CORT administration-induced epididymal adiposity is, at least in part, associated with mitochondrial dysfunction in mouse epididymal white adipose tissue.
doi:10.1371/journal.pone.0112628
PMCID: PMC4229254  PMID: 25389775
10.  A new potential risk factor in patients with erectile dysfunction and premature ejaculation: folate deficiency 
Asian Journal of Andrology  2014;16(6):902-906.
We investigated serum folic acid (FA) levels in patients with erectile dysfunction (ED) and/or premature ejaculation (PE). Fasting serum samples were obtained from 42 patients with ED, 36 with PE, 25 ED patients with PE, and 30 healthy men; the mean intravaginal ejaculation latency time (IELT) was measured during a 4 weeks baseline period. Levels of sex hormones (follicle-stimulating hormone, luteinizing hormone, total testosterone), homocysteine (Hcys), and FA were measured using chemiluminescent immunoassays. The sexual functions of PE patients and normal control men were evaluated using the Chinese Index of Premature Ejaculation (CIPE). The abridged International Index of Erectile Function-5 (IIEF-5) questionnaire was used to gauge erectile quality for ED patients and for normal controls. Serum FA concentrations were lower in ED (7.61 ± 3.97 ng ml−1), PE (9.37 ± 3.40 ng ml−1), and ED/PE (8.84 ± 4.28 ng ml−1) patients than in healthy men (12.23 ± 5.76 ng ml−1, P < 0.05). No significant differences in sex hormone levels were found between patients with sexual dysfunction and healthy controls (P > 0.05). There were positive correlations between serum FA concentrations and CIPE scores (r = 0.530, P < 0.01), IIEF-5 scores (r = 0.589, P < 0.01), and IELT (r = 0.445, P < 0.01); negative correlations with Hcys concentrations (r = −0.487, P < 0.01) were found in all participants. These findings showed a strong relationship between serum FA levels and sexual dysfunction, possibly due to an effect of FA on the metabolism of nitric oxide, Hcys, and 5-hydroxytryptamine.
doi:10.4103/1008-682X.135981
PMCID: PMC4236337  PMID: 25080932
5-hydroxytryptamine; erectile dysfunction; folic acid; homocysteine; nitric oxide; premature ejaculation
11.  Preoperative Neutrophil-to-Lymphocyte Ratio Is a Predictor of Recurrence following Thermal Ablation for Recurrent Hepatocellular Carcinoma: A Retrospective Analysis 
PLoS ONE  2014;9(10):e110546.
Purpose
The aim of this study is to determine the predictive value of preoperative blood neutrophil-to-lymphocyte ratio (NLR) for recurrence in recurrent hepatocellular carcinoma (RHCC) patients following thermal ablation.
Material and Methods
This retrospective study enrolled 506 RHCC patients who underwent thermal ablation from April 2006 to April 2014. The clinicopathological parameters including NLR were evaluated to identify predictors of recurrence rate after thermal ablation. A Cox multiple regression analysis was performed to determine the parameters that predicted recurrence in RHCC patients. The best cutoff value of NLR was determined with time-dependent receiver operating characteristic (ROC) curve analysis. The recurrence-free survival (RFS) rate was determined in patients with high and low NLR.
Results
The multivariate Cox proportional hazard model analysis showed that NLR was a prognostic factor in recurrence-free survival. NLR ≥2.14 was evaluated (AUROC = 0.824; P<0.001), and 183 of 506 patients (36.2%) had a NLR of more than 2.14. During the follow-up period (12–96 months), the 1-, and 3- year recurrence rates were 20.7% and 31.6% in low NLR group, respectively. These recurrence rates were significantly less than those in the high NLR group (57.9% and 82.5%, respectively) (P<0.001). A recurrence-free survival analyses demonstrated that the RFS in the low NLR group (67.2%) was significantly higher than that in the high NLR group (13.1%) (P<0.001).
Conclusion
Our results show that preoperative NLR is a predictor for re-recurrence after thermal ablation in RHCC patients. Additionally, patients with NLR <2.14 have a lower recurrence rate, which may improve the clinical management of RHCC patients.
doi:10.1371/journal.pone.0110546
PMCID: PMC4203800  PMID: 25330319
12.  MicroRNA-29 mediates TGFβ1-induced extracellular matrix synthesis by targeting wnt/β-catenin pathway in human orbital fibroblasts 
Purpose: Transforming growth factor β1 (TGFβ1) is very important in the synthesis and degradation of extracellular matrix (ECM) and also in the mediation of human orbital fibroblasts (OFs) proliferation. MicroRNA-29 (MiR-29) plays an important role in this process. In the present study, the effects of TGFβ1 on the expression of miR-29 and whether miR-29 is involved in pro-survival signaling pathways mediated by TGFβ1 were examined in human OFs. Methods: Detecting the influence of TGFβ1 on the expression of miR-29a/b/c by real-time PCR analysis. Using 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) to detecting the influence of miR-29 on the increased proliferation caused by TGF-β1 on the human orbital fibroblasts. Using soft agar assay to detecting the influence of miR-29 on the increased colony formation caused by TGF-β1 on the human orbital fibroblasts. Western blot was used to detect the specific mechanisin. Results: TGFβ1 treatment decreases the expression of miR-29 in OFs. In the cultured OFs, the value of optical density (OD) in the group treated with miR-29 is lower than that in the group treated without miR-29 (P < 0.05). In the cultured OFs, the ratio of colony formation in the group treated with miR-29 is lower than that in the group treated without miR-29 (P < 0.05). In OFs, miR-29 decreases the secretion of Wnt3a and activation of β-catenin whether the treatment of TGFβ1 was used or not. MiR-29 decreases expression of Collagen, type I, alpha 1 (COL1A1) through down-regulation of wnt/β-catenin pathway. Conclusions: In OFs TGFβ1 treatment decreases expression of miR-29 which can cause the inhibition of normal ability of TGFβ1. MiR-29 inhibits TGFβ1-induced proliferation of OFS cell and decreases colony formation of OFS cell after TGFβ1 treatment. MiR-29 Mediates TGFβ1-induced Extracellular matrix synthesis through activation of Wnt/β-catenin pathway in human OFs.
PMCID: PMC4270536  PMID: 25550793
Orbital fibrosis; TGFβ1; miR-29; wnt/β-catenin pathway
13.  Influence of polyethylene glycol coating on biodistribution and toxicity of nanoscale graphene oxide in mice after intravenous injection 
In this study, we assessed the in vivo behavior and toxicology of nanoscale graphene oxide (NGO) in mice after intravenous injection. The influence of a polyethylene glycol (PEG) coating on the distribution and toxicity of the NGO was also investigated. The results show that NGO is mainly retained in the liver, lung, and spleen. Retention in the lung is partially due to NGO aggregation. The PEG coating reduces the retention of NGO in the liver, lung, and spleen and promotes the clearance of NGO from these organs, but NGO and NGO-PEG are still present after 3 months. The PEG coating effectively reduces the early weight loss caused by NGO and alleviates NGO-induced acute tissue injuries, which can include damage to the liver, lung, and kidney, and chronic hepatic and lung fibrosis.
doi:10.2147/IJN.S66591
PMCID: PMC4207078  PMID: 25356071
graphene oxide; biodistribution; toxicity; polyethylene glycol
14.  Prognostic value of preoperative absolute lymphocyte count in recurrent hepatocellular carcinoma following thermal ablation: a retrospective analysis 
OncoTargets and therapy  2014;7:1829-1835.
Purpose
To investigate the prognostic value of preoperative absolute lymphocyte count (ALC) in recurrent hepatocellular carcinoma (RHCC) following thermal ablation.
Materials and methods
We retrospectively analyzed the relationship between preoperative ALC and the clinicopathologic factors and long-term prognosis in 423 RHCC patients who underwent curative thermal ablation. Correlation analysis, receiver operating characteristic (ROC) calculation, Kaplan–Meier curves, and multivariate regression were used for statistical analysis.
Results
The median time to recurrence was 12 months for RHCC patients after thermal ablation. On multivariate Cox regression analysis, preoperative ALC was an independent risk factor for cancer recurrence, along with tumor differentiation and α-fetoprotein level. ALC ≥1.64×109/L defined by ROC calculation was associated with prolonged survival (area under the curve 0.741, P<0.001). Patients with ALC ≥1.64×109/L showed a mean survival of 20.2 months versus 11.6 months for patients with ALC <1.64×109/L (P<0.001). Patients were stratified into high and low groups according to ALC status. After excluding the basic parameters between groups, the 1- and 3-year recurrence rates in the high group were 20.9% and 29.5%, respectively, which were significantly lower than those of the low group (58.4% and 71.9%, respectively; P<0.001). The recurrence-free survival rates in the two groups analyzed by Kaplan–Meier curves were significantly different (P<0.001).
Conclusion
Preoperative ALC is a powerful prognostic factor for RHCC recurrence after thermal ablation, which suggests that maintaining a high ALC in RHCC patients might improve cancer outcomes.
doi:10.2147/OTT.S69227
PMCID: PMC4199816  PMID: 25336974
absolute lymphocyte count; recurrent hepatocellular carcinoma; thermal ablation; recurrence
15.  Amifostine alleviates radiation-induced lethal small bowel damage via promotion of 14-3-3σ-mediated nuclear p53 accumulation 
Oncotarget  2014;5(20):9756-9769.
Amifostine (AM) is a radioprotector that scavenges free radicals and is used in patients undergoing radiotherapy. p53 has long been implicated in cell cycle arrest for cellular repair after radiation exposure. We therefore investigated the protective p53-dependent mechanism of AM on small bowel damage after lethal whole-abdominal irradiation (WAI). AM increased both the survival rate of rats and crypt survival following lethal 18 Gy WAI. The p53 inhibitor PFT-α compromised AM-mediated effects when administered prior to AM administration. AM significantly increased clonogenic survival in IEC-6 cells expressing wild type p53 but not in p53 knockdown cells. AM significantly increased p53 nuclear accumulation and p53 tetramer expression before irradiation through the inhibition of p53 degradation. AM inhibited p53 interactions with MDM2 but enhanced p53 interactions with 14-3-3σ. Knockdown of 14-3-3σ also compromised the effect of AM on clonogenic survival and p53 nuclear accumulation in IEC-6 cells. For the first time, our data reveal that AM alleviates lethal small bowel damage through the induction of 14-3-3σ and subsequent accumulation of p53. Enhancement of the p53/14-3-3σ interaction results in p53 tetramerization in the nucleus that rescues lethal small bowel damage.
PMCID: PMC4259435  PMID: 25230151
amifostine; p53; small bowel; whole-abdominal irradiation; 14-3-3σ; MDM2
16.  Association of Serum Uric Acid and Coronary Artery Disease in Premenopausal Women 
PLoS ONE  2014;9(9):e106130.
Objective
To date, no study in the published literature has investigated the role of various serum uric acid (SUA) concentrations in the development of angiographically-proven coronary artery disease (CAD) in premenopausal women. Therefore, the aim of this study was to investigate the role SUA levels may play in the prevalence, severity, and prognosis of CAD in premenopausal women.
Methods
This cross-sectional retrospective study included 607 premenopausal women who had undergone coronary angiography. The CAD diagnosis was based upon stenosis affecting ≥50% of the luminal diameter. Association of the SUA levels with CAD prevalence, severity, and clinical outcomes were assessed by statistical analysis.
Results
In total, 369 (60.8%) of the patients were diagnosed with CAD. The CAD patients had significantly higher SUA levels than those without CAD (5.3±1.9 vs. 4.8±1.7 mg/dL, P = 0.001). The SUA levels were found to be significantly associated with CAD prevalence (P = 0.013). Patients with higher levels of SUA also showed increased rates of multivessel disease and composite end-points, such as major adverse cardiac events. Furthermore, multivariate analysis identified abnormally high levels of uric acid (hyperuricemia) as an independent risk factor for CAD (OR 1.51 (1.11–2.53), P<0.05).
Conclusions
The SUA levels are significantly associated with the prevalence of CAD. The SUA levels may be a predictor for incidence of major cardiovascular events in premenopausal women.
doi:10.1371/journal.pone.0106130
PMCID: PMC4153543  PMID: 25184207
17.  The catalytic region and PEST domain of PTPN18 distinctly regulate the HER2 phosphorylation and ubiquitination barcodes 
Cell Research  2014;24(9):1067-1090.
The tyrosine phosphorylation barcode encoded in C-terminus of HER2 and its ubiquitination regulate diverse HER2 functions. PTPN18 was reported as a HER2 phosphatase; however, the exact mechanism by which it defines HER2 signaling is not fully understood. Here, we demonstrate that PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination barcodes. Enzymologic characterization and three crystal structures of PTPN18 in complex with HER2 phospho-peptides revealed the molecular basis for the recognition between PTPN18 and specific HER2 phosphorylation sites, which assumes two distinct conformations. Unique structural properties of PTPN18 contribute to the regulation of sub-cellular phosphorylation networks downstream of HER2, which are required for inhibition of HER2-mediated cell growth and migration. Whereas the catalytic domain of PTPN18 blocks lysosomal routing and delays the degradation of HER2 by dephosphorylation of HER2 on pY1112, the PEST domain of PTPN18 promotes K48-linked HER2 ubiquitination and its rapid destruction via the proteasome pathway and an HER2 negative feedback loop. In agreement with the negative regulatory role of PTPN18 in HER2 signaling, the HER2/PTPN18 ratio was correlated with breast cancer stage. Taken together, our study presents a structural basis for selective HER2 dephosphorylation, a previously uncharacterized mechanism for HER2 degradation and a novel function for the PTPN18 PEST domain. The new regulatory role of the PEST domain in the ubiquitination pathway will broaden our understanding of the functions of other important PEST domain-containing phosphatases, such as LYP and PTPN12.
doi:10.1038/cr.2014.99
PMCID: PMC4152746  PMID: 25081058
phosphatase; receptor; ubiquitination; HER2; PTPN18; EGFR
18.  Impact of invasive treatment strategy on health-related quality of life six months after non-ST-elevation acute coronary syndrome 
Background
Few studies have compared change in the health-related quality of life (HRQL) following treatment of non-ST-elevation acute coronary syndrome (NSTE-ACS) with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). This study is to compare changes in HRQL six months after hospital discharge between NSTE-ACS patients who underwent either PCI or CABG.
Methods
HRQL was assessed using the Seattle angina questionnaire at admission and six months after discharge in 1012 consecutive patients with NSTE-ACS. To assess associations of PCI and CABG with HRQL changes, logistic regression models were constructed treating changes in the score of each dimension of the Seattle angina questionnaire as dependent variables.
Results
Although both the PCI and CABG groups experienced angina relief and other improvements at 6-month follow-up (P < 0.001), the CABG relative to PCI group showed more significant improvements in angina frequency (P = 0.044) and quality of life (P = 0.028). In multivariable logistic analysis, CABG also was an independent predictor for both improvement of angina frequency (OR: 1.62, 95%CI: 1.09−4.63, P = 0.042) and quality of life (OR: 2.04, 95%CI: 1.26−6.92, P = 0.038) relative to PCI.
Conclusions
In patients with NSTE-ACS, both PCI and CABG provide great improvement in disease-specific health status at six months, with that of CABG being more prominent in terms of angina frequency and quality of life.
doi:10.11909/j.issn.1671-5411.2014.03.003
PMCID: PMC4178511  PMID: 25278968
Non-ST elevation acute coronary syndrome; Quality of life; Therapeutic strategy
19.  Distributed Cooperative Regulation for Multiagent Systems and Its Applications to Power Systems: A Survey 
The Scientific World Journal  2014;2014:139028.
Cooperative regulation of multiagent systems has become an active research area in the past decade. This paper reviews some recent progress in distributed coordination control for leader-following multiagent systems and its applications in power system and mainly focuses on the cooperative tracking control in terms of consensus tracking control and containment tracking control. Next, methods on how to rank the network nodes are summarized for undirected/directed network, based on which one can determine which follower should be connected to leaders such that partial followers can perceive leaders' information. Furthermore, we present a survey of the most relevant scientific studies investigating the regulation and optimization problems in power systems based on distributed strategies. Finally, some potential applications in the frequency tracking regulation of smart grids are discussed at the end of the paper.
doi:10.1155/2014/139028
PMCID: PMC4163399  PMID: 25243199
20.  The Treatment of PPCP-Containing Sewage in an Anoxic/Aerobic Reactor Coupled with a Novel Design of Solid Plain Graphite-Plates Microbial Fuel Cell 
BioMed Research International  2014;2014:765652.
Synthetic sewage containing high concentrations of pharmaceuticals and personal care products (PPCPs, mg/L level) was treated using an anoxic/aerobic (A/O) reactor coupled with a microbial fuel cell (MFC) at hydraulic retention time (HRT) of 8 h. A novel design of solid plain graphite plates (SPGRPs) was used for the high surface area biodegradation of the PPCP-containing sewage and for the generation of electricity. The average CODCr and total nitrogen removal efficiencies achieved were 97.20% and 83.75%, respectively. High removal efficiencies of pharmaceuticals, including acetaminophen, ibuprofen, and sulfamethoxazole, were also obtained and ranged from 98.21% to 99.89%. A maximum power density of 532.61 mW/cm2 and a maximum coulombic efficiency of 25.20% were measured for the SPGRP MFC at the anode. Distinct differences in the bacterial community were presented at various locations including the mixed liquor suspended solids and biofilms. The bacterial groups involved in PPCP biodegradation were identified as Dechloromonas spp., Sphingomonas sp., and Pseudomonas aeruginosa. This design, which couples an A/O reactor with a novel design of SPGRP MFC, allows the simultaneous removal of PPCPs and successful electricity production.
doi:10.1155/2014/765652
PMCID: PMC4150452  PMID: 25197659
21.  Age as a risk factor for acute mountain sickness upon rapid ascent to 3,700 m among young adult Chinese men 
Background
The aim of this study was to explore the relationship between age and acute mountain sickness (AMS) when subjects are exposed suddenly to high altitude.
Methods
A total of 856 young adult men were recruited. Before and after acute altitude exposure, the Athens Insomnia Scale score (AISS) was used to evaluate the subjective sleep quality of subjects. AMS was assessed using the Lake Louise scoring system. Heart rate (HR) and arterial oxygen saturation (SaO2) were measured.
Results
Results showed that, at 500 m, AISS and insomnia prevalence were higher in older individuals. After acute exposure to altitude, the HR, AISS, and insomnia prevalence increased sharply, and the increase in older individuals was more marked. The opposite trend was observed for SaO2. At 3,700 m, the prevalence of AMS increased with age, as did severe AMS, and AMS symptoms (except gastrointestinal symptoms). Multivariate logistic regression analysis showed that age was a risk factor for AMS (adjusted odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01–1.13, P<0.05), as well as AISS (adjusted OR 1.39, 95% CI 1.28–1.51, P<0.001).
Conclusion
The present study is the first to demonstrate that older age is an independent risk factor for AMS upon rapid ascent to high altitude among young adult Chinese men, and pre-existing poor subjective sleep quality may be a contributor to increased AMS prevalence in older subjects.
doi:10.2147/CIA.S67052
PMCID: PMC4128797  PMID: 25120358
acute mountain sickness; age; Athens Insomnia Scale; rapid ascent; sleep
22.  The Possibility of Traditional Chinese Medicine as Maintenance Therapy for Advanced Nonsmall Cell Lung Cancer 
Lung cancer has become the leading cause of cancer deaths, with nonsmall cell lung cancer (NSCLC) accounting for around 80% of lung cancer cases. Chemotherapy is the main conventional therapy for advanced NSCLC. However, the disease control achieved with classical chemotherapy in advanced NSCLC is usually restricted to only a few months. Thus, sustaining the therapeutic effect of first-line chemotherapy is an important problem that requires study. Maintenance therapy is given for patients with advanced NSCLC if three is no tumor progression after four to six cycles of first-line platinum-based chemotherapy. However, selection of appropriate maintenance therapy depends on several factors, while traditional Chinese medicine (TCM) as maintenance therapy is recommended for all kinds of patients. It has been demonstrated that TCM can prolong the survival time, improve the quality of life (QOL), and reduce the side effects for advanced NSCLC. Although the trials we searched about TCM serving as maintenance therapy is only 9 studies, the results indicate TCM can prolong the progression free survival (PFS) and improve the QOL. So it is possible for TCM to be as maintenance therapy for advanced NSCLC. More rigorous trials are required to further verify its efficacy.
doi:10.1155/2014/278917
PMCID: PMC4137694  PMID: 25165478
23.  A CBR-Based and MAHP-Based Customer Value Prediction Model for New Product Development 
The Scientific World Journal  2014;2014:459765.
In the fierce market environment, the enterprise which wants to meet customer needs and boost its market profit and share must focus on the new product development. To overcome the limitations of previous research, Chan et al. proposed a dynamic decision support system to predict the customer lifetime value (CLV) for new product development. However, to better meet the customer needs, there are still some deficiencies in their model, so this study proposes a CBR-based and MAHP-based customer value prediction model for a new product (C&M-CVPM). CBR (case based reasoning) can reduce experts' workload and evaluation time, while MAHP (multiplicative analytic hierarchy process) can use actual but average influencing factor's effectiveness in stimulation, and at same time C&M-CVPM uses dynamic customers' transition probability which is more close to reality. This study not only introduces the realization of CBR and MAHP, but also elaborates C&M-CVPM's three main modules. The application of the proposed model is illustrated and confirmed to be sensible and convincing through a stimulation experiment.
doi:10.1155/2014/459765
PMCID: PMC4138884  PMID: 25162050
24.  hsa-mir-30c promotes the invasive phenotype of metastatic breast cancer cells by targeting NOV/CCN3 
Background
For treatment and prevention of metastatic disease, one of the premier challenges is the identification of pathways and proteins to target for clinical intervention. Micro RNAs (miRNAs) are short, non-coding RNAs, which regulate cellular activities by either mRNA degradation or translational inhibition. Our studies focused on the invasive properties of hsa-mir30c based on its high expression in MDA-MB-231 metastatic cells and our bioinformatic analysis of the Cancer Genome Atlas that identified aberrant hsa-mir-30c to be associated with poor survival.
Methods
Contributions of hsa-mir-30c to breast cancer cell invasion were examined by Matrigel invasion transwell assays following modulation of hsa-mir-30c or hsa-mir-30c* levels in MDA-MB-231 cells. hsa-mir-30c in silico predicted targets linked to cell invasion were screened for targeting by hsa-mir-30c in metastatic breast cancer cells by RT-qPCR. The contribution to invasion by a target of hsa-mir-30c, Nephroblastoma overexpressed (NOV), was characterized by siRNA and invasion assays. Significant effects were determined using Student’s T-tests with Welch’s correction for unequal variance.
Results
MCF-7 and MDA-MB-231 cells were used as models of poorly invasive and late-stage metastatic disease, respectively. By modulating the levels of hsa-mir-30c in these cells, we observed concomitant changes in breast cancer cell invasiveness. From predicted targets of hsa-mir-30c that were related to cellular migration and invasion, NOV/CCN3 was identified as a novel target of hsa-mir-30c. Depleting NOV by siRNA caused a significant increase in the invasiveness of MDA-MB-231 cells is a regulatory protein associated with the extracellular matrix.
Conclusions
NOV/CCN3 expression, which protects cells from invasion, is known in patient tumors to inversely correlate with advanced breast cancer and metastasis. This study has identified a novel target of hsa-mir-30c, NOV, which is an inhibitor of the invasiveness of metastatic breast cancer cells. Thus, hsa-mir-30c-mediated inhibition of NOV levels promotes the invasive phenotype of MDA-MB-231 cells and significantly, the miR-30/NOV pathways is independent of RUNX2, a known target of hsa-mir-30c that promotes osteolytic disease in metastatic breast cancer cells. Our findings allow for mechanistic insight into the clinical observation of poor survival of patients with elevated hsa-mir-30c levels, which can be considered for miRNA-based translational studies.
doi:10.1186/s12935-014-0073-0
PMCID: PMC4129468  PMID: 25120384
miRNA; Hsa-mir-30c breast cancer; Invasion; Metastasis; NOV/CCN3
25.  Sleep quality changes in insomniacs and non-insomniacs after acute altitude exposure and its relationship with acute mountain sickness 
Objective
We aimed to observe the changes in subjective sleep quality among insomniacs and non-insomniacs after acute ascending to 3,700 m and its possible relationship with acute mountain sickness (AMS).
Methods
A total of 600 adult men were recruited. Subjects’ subjective sleep quality was evaluated by the Athens Insomnia Scale. AMS was assessed using the Lake Louise scoring system. Arterial oxygen saturation was measured.
Results
Despite insomnia resolution in only a few subjects, the prevalence of insomnia among insomniacs remained stable at 90% after rapid ascent to 3,700 m. However, among non-insomniacs, the prevalence of insomnia sharply increased to 32.13% in the first day of altitude exposure and progressively reduced to 4.26% by the 60th day of altitude stay. Moreover, the prevalences of insomnia symptoms decreased more markedly from day 1 to day 60 at 3,700 m among non-insomniacs than among insomniacs. At 3,700 m, the prevalence of AMS among insomniacs was 79.01%, 60.49%, and 32.10% on the first, third, and seventh days, respectively, which was significantly higher than that among non-insomniacs. Multivariate regression revealed that elevated Athens Insomnia Scale scores are an independent risk factor for AMS (adjusted odds ratio 1.388, 95% confidence interval: 1.314–1.464, P<0.001), whereas high arterial oxygen saturation and long duration of altitude exposure are protective factors against AMS.
Conclusion
Our results suggest that the effect of high-altitude exposure on subjective sleep quality is more marked, but disappears more quickly, among non-insomniacs than among insomniacs, whereas AMS is especially common among insomniacs. Moreover, poor subjective sleep quality is a risk factor for AMS.
doi:10.2147/NDT.S67218
PMCID: PMC4124070  PMID: 25114534
Athens Insomnia Scale; arterial oxygen saturation; rapid ascent; sleep

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