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1.  EIF4EBP1 Overexpression Is Associated with Poor Survival and Disease Progression in Patients with Hepatocellular Carcinoma 
PLoS ONE  2015;10(2):e0117493.
Objective
EIF4EBP1 acts as a crucial effector in mTOR signaling pathway. Studies have suggested that EIF4EBP1 plays a critical role in carcinogenesis. However, the clinical significance and biological role of EIF4EBP1 in hepatocellular carcinoma (HCC) have not been elucidated. Therefore, we aimed to investigate the clinical significance of EIF4EBP1 in HCC.
Methods
Total 128 cases of HCCs were included in this study. EIF4EBP1 expression in HCC tissues was detected by qRT-PCR, Western blot and immunohistochemistry, respectively. Then the relationships between EIF4EBP1 expression and clinical features as well as survival were analyzed.
Results
The expression level of EIF4EBP1 mRNA is significantly higher in 60% (24/40) of fresh HCC tissues than that in the matched adjacent nontumor liver (NCL) tissues (P = 0.044). Similarly, EIF4EBP1 protein is notably upregulated in 8 HCC tissues (randomly selected from the 40 HCCs) measured by Western blot and is significantly increased in another 88 paraffin-embedded HCCs (53%, 47/88) by immunohistochemistry compared with the matched NCLs (P < 0.001). EIF4EBP1 protein expression in HCC tissues is significantly correlated with serum AFP (P = 0.003) and marginally significantly associated with pathological grade (P = 0.085), tumor number (P = 0.084), tumor embolus (P = 0.084) and capsulation (P = 0.073). Patients with higher EIF4EBP1 protein expression have a much worse 5-year overall survival (40.3% vs 73.6%) and 5-year disease-free survival (33.0% vs 49.0%) than those with low expression. Furthermore, Cox regression analysis shows that EIF4EBP1 protein is an independent prognostic factor for overall survival (HR, 2.285; 95% CI, 1.154–4.527; P = 0.018) and disease-free survival (HR, 1.901; 95% CI, 1.067–3.386; P = 0.029) in HCC patients.
Conclusions
Our results demonstrate for the first time that EIF4EBP1 mRNA and protein are markedly up-regulated in HCC tissues, and the protein overexpression is significantly associated with poor survival and progression, which provide a potential new prognostic marker and therapeutic target for HCC patients.
doi:10.1371/journal.pone.0117493
PMCID: PMC4319970  PMID: 25658620
2.  Nasopharyngeal carriage and antimicrobial susceptibility of Haemophilus influenzae among children younger than 5 years of age in Beijing, China 
BMC Microbiology  2015;15:6.
Background
Haemophilus influenzae is one of the main pathogens that cause community-acquired respiratory infections in children. Our previous study showed that H. influenzae is the second most common pathogen causing pneumonia and accounts for 30–50% of bacterial meningitis among Chinese children. H. influenzae carriage in children and its resistance to commonly used antimicrobials varies widely both geographically and over time.
Results
Surveys of the nasopharyngeal carriage of H. influenzae in children younger than 5 years of age with acute respiratory tract infection (ARI) were conducted in Beijing Children’s Hospital, China in 2000, 2002, 2010, and 2012. The overall annual carriage rates of H. influenzae among children younger than 5 years of age with ARI were 35.5%, 20.6%, 14.4%, and 18.7%, and the percentages of H. influenzae isolates producing β-lactamase were 4%, 13%, 27.1%, and 31%, respectively. The percentages of susceptibility to ampicillin progressively decreased from 96% (2000) to 87% (2002) to 63% (2010) to 61% (2012). All of the ampicillin-resistant isolates were found to be beta-lactamase producers. The susceptibility to tetracycline increased from 54% (2000) to 60% (2002) to 91.5% (2010) to 94.5% (2012). No statistically significant differences were observed in the susceptibility to cefaclor, cefuroxime, sulfamethoxazole, and chloramphenicol. Amoxicillin/clavulanic acid and ceftriaxone were the most effective antimicrobials for the isolates of H. influenzae across the 10-year period.
Conclusions
This report on the H. influenzae carriage rates in children and the susceptibility of these bacteria to commonly used antibiotics showed that H. influenzae carriage decreased from 2000 to 2012. Additionally, the percentage of β-lactamase-producing isolates increased while their susceptibility to ampicillin progressively decreased during this time. These results indicate that the appropriate empirical antimicrobial therapy should be changed for pediatric patients in China.
doi:10.1186/s12866-015-0350-7
PMCID: PMC4332420  PMID: 25648185
Haemophilus influenzae; Antimicrobial susceptibility; Acute upper respiratory tract infection; Pediatrics
4.  Gene differential coexpression analysis based on biweight correlation and maximum clique 
BMC Bioinformatics  2014;15(Suppl 15):S3.
Differential coexpression analysis usually requires the definition of 'distance' or 'similarity' between measured datasets. Until now, the most common choice is Pearson correlation coefficient. However, Pearson correlation coefficient is sensitive to outliers. Biweight midcorrelation is considered to be a good alternative to Pearson correlation since it is more robust to outliers. In this paper, we introduce to use Biweight Midcorrelation to measure 'similarity' between gene expression profiles, and provide a new approach for gene differential coexpression analysis. Firstly, we calculate the biweight midcorrelation coefficients between all gene pairs. Then, we filter out non-informative correlation pairs using the 'half-thresholding' strategy and calculate the differential coexpression value of gene, The experimental results on simulated data show that the new approach performed better than three previously published differential coexpression analysis (DCEA) methods. Moreover, we use the maximum clique analysis to gene subset included genes identified by our approach and previously reported T2D-related genes, many additional discoveries can be found through our method.
doi:10.1186/1471-2105-15-S15-S3
PMCID: PMC4271563  PMID: 25474074
5.  Aberrant Expression of Xist in Aborted Porcine Fetuses Derived from Somatic Cell Nuclear Transfer Embryos 
Cloned pigs generated by somatic cell nuclear transfer (SCNT) show a greater ratio of early abortion during mid-gestation than normal controls. X-linked genes have been demonstrated to be important for the development of cloned embryos. To determine the relationship between the expression of X-linked genes and abortion of cloned porcine fetuses, the expression of X-linked genes were investigated by quantitative real-time polymerase chain reaction (q-PCR) and the methylation status of Xist DMR was performed by bisulfate-specific PCR (BSP). q-PCR analysis indicated that there was aberrant expression of X-linked genes, especially the upregulated expression of Xist in both female and male aborted fetuses compared to control fetuses. Results of BSP suggested that hypomethylation of Xist occurred in aborted fetuses, whether male or female. These results suggest that the abnormal expression of Xist may be associated with the abortion of fetuses derived from somatic cell nuclear transfer embryos.
doi:10.3390/ijms151221631
PMCID: PMC4284668  PMID: 25429426
porcine; somatic cell nuclear transfer; DNA methylation; Xist
6.  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
7.  Higher Fibrinogen Level is Independently Linked with the Presence and Severity of New-Onset Coronary Atherosclerosis among Han Chinese Population 
PLoS ONE  2014;9(11):e113460.
Background
Fibrinogen is a coagulation/inflammatory biomarker strongly associated with atherogenesis. However, no data is currently available regarding the association of fibrinogen level with the presence and severity of new-onset coronary atherosclerosis assessed by Gensini score (GS), particularly in Han Chinese with a large sample size.
Methods and Results
We studied 2288 consecutive, new-onset subjects undergoing coronary angiography with angina-like chest pain. Clinical and laboratory data were collected. Coronary stenotic lesions were considered to be the incidence of coronary atherosclerosis. The severity of coronary stenosis was determined by the GS system. Data indicated that patients with high GS had significantly elevated fibrinogen level (p<0.001). The prevalence and severity of coronary atherosclerosis were dramatically increased according to fibrinogen tertiles. Spearman correlation analysis revealed a positive association between fibrinogen level and GS (r = 0.138, p<0.001). Multivariate logistic regression analysis demonstrated that plasma fibrinogen level was independently associated with high GS (OR = 1.275, 95% CI 1.082–1.502, p = 0.004) after adjusting for potential confounders. Moreover, fibrinogen level was also independently related to the presence of coronary atherosclerosis (fibrinogen tertile 2: OR = 1.192, 95% CI 0.889–1.598, p = 0.241; tertile 3: OR = 2.003, 95% CI 1.383–2.903, p <0.001) and high GS (fibrinogen tertile 2: OR = 1.079, 95% CI 0.833–1.397, p = 0.565; tertile 3: OR = 1.524, 95% CI 1.155–2.011, p = 0.003) in a dose-dependent manner. Receiver-operating characteristic curve analysis showed that the best fibrinogen cut-off value for predicting the severity of coronary stenosis was 3.21 g/L.
Conclusions
Higher fibrinogen level is independently linked with the presence and severity of new-onset coronary atherosclerosis in Han Chinese population.
doi:10.1371/journal.pone.0113460
PMCID: PMC4245131  PMID: 25426943
8.  Role of BC040587 as a predictor of poor outcome in breast cancer 
Cancer Cell International  2014;14(1):123.
Background
Accumulating studies have focused on the oncogenic and tumor suppressive roles of the newly identified lncRNAs. A novel lncRNA BC040587 in 3q13.31 locus which exists frequent copy number alterations was found to be associated with poor survival of osteosarcoma patients. However, its role in breast cancer (BC) remains unknown. The aim of this study was to examine the expression pattern of BC040587 in BC and to evaluate its biological role and clinical significance in prediction of prognosis.
Methods
Expression of BC040587 was analyzed in 20 pairs of BC cancer tissues and adjacent noncancerous tissues (ANCT), also in 151 BC tissues, 9 BC cell lines and one normal breast cell line by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Differences between groups were tested for significance using Student’s t-test (two-tailed). Then we analyzed the potential relationship between BC040587 expression and clinic pathological features of BC patients. The correlation was analyzed by SPSS software.
Results
It showed that BC040587 expression was down regulated both in BC samples and in BC cell lines compared with corresponding normal control. BC040587 expression was correlated with menopausal status (p = 0.040) and tumor differentiation (p = 0.035). The Kaplan-Meier survival curves indicated that the overall survival (OS) was significantly poor in low BC040587 expression BC patients (p = 0.023). Furthermore, expression of BC040587 was significantly associated with worse prognosis and was shown to be an independent prognostic marker breast cancer (p = 0.032). Our studies indicate that BC040587 may represent a new marker of prognosis in breast cancer.
Conclusion
Our studies indicate that BC040587 is significantly down-regulated in BC tissues and BC cell lines. BC040587 may represent a new marker of prognosis in breast cancer.
doi:10.1186/s12935-014-0123-7
PMCID: PMC4246536  PMID: 25435812
BC040587; Breast cancer; Tumor suppressor; Prognosis; Long non-coding RNA
9.  Different Inhibitory Effect and Mechanism of Hydroxyapatite Nanoparticles on Normal Cells and Cancer Cells In Vitro and In Vivo 
Scientific Reports  2014;4:7134.
Hydroxyapatite (HAP), similar to inorganic phase in bones, shows good biocompatibility and bioactivity as bone defect repairing material. Recently, nanoscaled HAP shows the special properties differing from bulk HAP in physics, chemistry and biology. This paper demonstrates that HAP nanoparticle (nHAP) possesses the ability for inhibiting cancer cell growth in vitro and in vivo. In vitro, after treatment with nHAP for 3 days, proliferation of human cancer cells are inhibited by more than 65% and by less than 30% for human normal cells. In vivo, injection of nHAP in transplanted tumor results in significant reduction (about 50%) of tumor size. The anticancer effect of nHAP is mainly attributed to high amount by endocytosis in cancer cells and inhibition on protein synthesis in cells. The abundant nHAP internalized in cancer cells around endoplasmic reticulum may inhibit the protein synthesis by decreasing the binding of mRNA to ribosome due to its high adsorption capacity for ribosome and arrest cell cycle in G0/G1 phase. nHAP shows no ROS-involved cytotoxicity and low cytotoxicity to normal cells. These results strongly suggest that nHAP can inhibit cancer cell proliferation and have a potential application in cancer treatment.
doi:10.1038/srep07134
PMCID: PMC4238015  PMID: 25409543
10.  Policosanol Attenuates Statin-Induced Increases in Serum Proprotein Convertase Subtilisin/Kexin Type 9 When Combined with Atorvastatin 
Objective. Statin treatment alone has been demonstrated to significantly increase plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. The effect of policosanol combined with statin on PCSK9 is unknown. Methods. Protocol I: 26 patients with atherosclerosis were randomly assigned to receive either atorvastatin 20 mg/d or policosanol 20 mg/d + atorvastatin 20 mg/d for 8 weeks. Protocol II: 15 healthy volunteers were randomly assigned to either policosanol 20 mg/d or a control group for 12 weeks. Serum levels of PCSK9 were determined at day 0 and the end of each protocol. Results. Protocol I: atorvastatin 20 mg/d significantly increased serum PCSK9 level by 39.4% (256 ± 84 ng/mL versus 357 ± 101 ng/mL, P = 0.002). However, policosanol 20 mg/d + atorvastatin 20 mg/d increased serum PCSK9 level by only 17.4% without statistical significance (264 ± 60 ng/mL versus 310 ± 86 ng/mL, P = 0.184). Protocol II: there was a trend toward decreasing serum PCSK9 levels in the policosanol group (289 ± 71 ng/mL versus 235 ± 46 ng/mL, P = 0.069). Conclusion. Policosanol combined with statin attenuated the statin-induced increase in serum PCSK9 levels. This finding indicates that policosanol might have a modest effect of lowering serum PCSK9 levels.
doi:10.1155/2014/926087
PMCID: PMC4247936  PMID: 25478000
11.  Resting heart rate as a marker for identifying the risk of undiagnosed type 2 diabetes mellitus: a cross-sectional survey 
BMC Public Health  2014;14(1):1052.
Background
Fast resting heart rate might increase the risk of developing type 2 diabetes mellitus (T2DM). However, it is unclear whether resting heart rate could be used to predict the risk of undiagnosed T2DM. Therefore, the purposes of this study were to examine the association between resting heart rate and undiagnosed T2DM, and evaluate the feasibility of using resting heart rate as a marker for identifying the risk of undiagnosed T2DM.
Methods
A cross-sectional survey was conducted. Resting heart rate and relevant covariates were collected and measured. Fasting blood samples were obtained to measure blood glucose using the modified hexokinase enzymatic method. Predictive performance was analyzed by Receiver Operating Characteristic (ROC) curve.
Results
This study included 16, 636 subjects from rural communities aged 35–78 years. Resting heart rate was significantly associated with undiagnosed T2DM in both genders. For resting heart rate categories of <60, 60–69, 70–79, and ≥80 beats/min, adjusted odds ratios for undiagnosed T2DM were 1.04, 2.32, 3.66 and 1.05, 1.57, 2.98 in male and female subjects, respectively. For male subjects, resting heart rate ≥70 beats/min could predict undiagnosed T2DM with 76.56% sensitivity and 48.64% specificity. For female subjects, the optimum cut-off point was ≥79 beats/min with 49.72% sensitivity and 67.53% specificity. The area under the ROC curve for predicting undiagnosed T2DM was 0.65 (95% CI: 0.64-0.66) and 0.61(95% CI: 0.60-0.62) in male and female subjects, respectively.
Conclusions
Fast resting heart rate is associated with an increased risk of undiagnosed T2DM in male and female subjects. However, resting heart rate as a marker has limited potential for screening those at high risk of undiagnosed T2DM in adults living in rural areas.
doi:10.1186/1471-2458-14-1052
PMCID: PMC4210587  PMID: 25297916
Marker; Resting heart rate; Type 2 diabetes mellitus
12.  Screening and Characterization of Purine Nucleoside Degrading Lactic Acid Bacteria Isolated from Chinese Sauerkraut and Evaluation of the Serum Uric Acid Lowering Effect in Hyperuricemic Rats 
PLoS ONE  2014;9(9):e105577.
Hyperuricemia is well known as the cause of gout. In recent years, it has also been recognized as a risk factor for arteriosclerosis, cerebrovascular and cardiovascular diseases, and nephropathy in diabetic patients. Foods high in purine compounds are more potent in exacerbating hyperuricemia. Therefore, the development of probiotics that efficiently degrade purine compounds is a promising potential therapy for the prevention of hyperuricemia. In this study, fifty-five lactic acid bacteria isolated from Chinese sauerkraut were evaluated for the ability to degrade inosine and guanosine, the two key intermediates in purine metabolism. After a preliminary screening based on HPLC, three candidate strains with the highest nucleoside degrading rates were selected for further characterization. The tested biological characteristics of candidate strains included acid tolerance, bile tolerance, anti-pathogenic bacteria activity, cell adhesion ability, resistance to antibiotics and the ability to produce hydrogen peroxide. Among the selected strains, DM9218 showed the best probiotic potential compared with other strains despite its poor bile resistance. Analysis of 16S rRNA sequences showed that DM9218 has the highest similarity (99%) to Lactobacillus plantarum WCFS1. The acclimated strain DM9218-A showed better resistance to 0.3% bile salt, and its survival in gastrointestinal tract of rats was proven by PCR-DGGE. Furthermore, the effects of DM9218-A in a hyperuricemia rat model were evaluated. The level of serum uric acid in hyperuricemic rat can be efficiently reduced by the intragastric administration of DM9218-A (P<0.05). The preventive treatment of DM9218-A caused a greater reduction in serum uric acid concentration in hyperuricemic rats than the later treatment (P<0.05). Our results suggest that DM9218-A may be a promising candidate as an adjunctive treatment in patients with hyperuricemia during the onset period of disease. DM9218-A also has potential as a probiotic in the prevention of hyperuricemia in the normal population.
doi:10.1371/journal.pone.0105577
PMCID: PMC4153548  PMID: 25184445
13.  Clinical features of coronary artery ectasia in the elderly 
Objective
To investigate the incidence, imaging and clinical characteristics in elderly patients with coronary artery ectasia (CAE).
Methods
A retrospective analysis was conducted on patients with CAE who underwent coronary angiography between January 2006 and December 2012. According to age, the enrolled patients were divided into two groups (elderly group, age ≥ 65 years; non-elderly group, age < 65 years). The clinical feature, imaging characteristics and the 5-year survival rate of the two groups were compared.
Results
The prevalence of CAE in elderly patients was 0.33%. Patients in elderly group were found to have significantly higher proportion of female (30.1% vs. 10.1%, P < 0.001), three-vessel disease (60.5% vs. 45.2%, P = 0.003) and localized ectasia (55.0% vs. 40.2%, P = 0.003). In addition, body mass index (20.90 ± 2.71 kg/m2 vs. 22.31 ± 2.98 kg/m2, P < 0.001) and percentage of current smokers (45.0% vs. 64.6%, P < 0.001) were significantly lower in elderly group. Cumulative survival curves demonstrated reduced 5-year cumulative survival at the follow-up in the elderly group compared with the non-elderly group (88.0% vs. 96.0%, P = 0.002). But the 5-year event free survival rate failed to show a significant difference between the two groups (31.0% vs. 35.0%, P = 0.311).
Conclusion
The prevalence of CAE in elderly patients was 0.33%, which was about 1/3 of the entire numbers of CAE patients. There were significant differences between the elderly and the non-elderly patients with CAE in terms of coronary artery disease risk factors and coronary artery ectatic characteristics. CAE might be associated with increased mortality risk in the elderly.
doi:10.11909/j.issn.1671-5411.2014.03.012
PMCID: PMC4178508  PMID: 25278965
Coronary artery ectasia; Elderly patients; Clinical feature
14.  Relationship of Glycated Hemoglobin Levels with Myocardial Injury following Elective Percutaneous Coronary Intervention in Patients with Type 2 Diabetes Mellitus 
PLoS ONE  2014;9(7):e101719.
Background
Glycated hemoglobin (HbA1c) predicts clinical cardiovascular disease or cardiovascular mortality. However, the relationship between HbA1c and myocardial injury following elective percutaneous coronary intervention (PCI) in patients with type 2 diabetes mellitus (DM) has not been investigated.
Objectives
The study sought to assess the relationship between HbA1c and myocardial injury following elective PCI in patients with type 2 DM.
Methods
We studied a cohort of consecutive 994 diabetic patients with coronary artery disease (CAD) undergoing elective PCI. Periprocedural myocardial injury was evaluated by analysis of troponin I (cTnI). The association between preprocedural HbA1c levels and the peak values of cTnI within 24 hours after PCI was evaluated.
Results
Peak postprocedural cTnI >1×upper limit of normal (ULN), >3×ULN and >5×ULN were detected in 543 (54.6%), 337 (33.9%) and 245 (24.6%) respectively. In the multivariate model, higher HbA1c levels were associated with less risk of postprocedural cTnI >1×ULN (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.76–0.95; P = 0.005). There was a trend that higher HbA1c levels were associated with less risk of postprocedural cTnI >3×ULN (OR, 0.90; 95% CI, 0.81–1.02; P = 0.088). HbA1c was not associated with the risk of postprocedural cTnI elevation above 5×ULN (OR, 0.95; 95% CI, 0.84–1.08; P = 0.411).
Conclusions
The present study provided the first line of evidence that higher preprocedural HbA1c levels were associated with less risk of myocardial injury following elective PCI in diabetic patients.
doi:10.1371/journal.pone.0101719
PMCID: PMC4079566  PMID: 24988213
15.  Glycosylated hemoglobin A1c as a marker predicting the severity of coronary artery disease and early outcome in patients with stable angina 
Background
Glycosylated hemoglobin A1C (HbA1c) has been widely recognized as a marker for predicting the severity of diabetes mellitus (DM) and several cardiovascular diseases. However, whether HbA1c could predict the severity and clinical outcomes in patients with stable coronary artery disease (CAD) remains largely unknown. We determine relationship of HbA1c with severity and outcome in patients with stable CAD.
Methods
We enrolled 1433 patients with stable angina who underwent coronary angiography and were followed up for an average 12 months. The patients were classified into three groups by tertiles of baseline HbA1c level (low group <5.7%, n = 483; intermediate group 5.7 - 6.3%, n = 512; high group >6.3%, n = 438). The relationships between the plasma HbA1c and severity of CAD and early clinical outcomes were evaluated.
Results
High HbA1c was associated with three-vessel disease. Area under the receivers operating characteristic curve (AUC = 0.67, 95% CI: 0.63-0.71, P < 0.001) and multivariate logistic regression analysis suggested that HbA1C was an independent predictor of severity of CAD (OR = 1.60, 95% CI: 1.29-1.99, P < 0.001) even after adjusting for gender, age, risk factor of CAD, lipid profile and fasting blood glucose. During follow-up, 133 patients underwent pre-specified outcomes. After adjusting for multiple variables in the Cox regression model, HbA1C remained to be an independent predictor of poor prognosis (HR = 1.28, 95% CI: 1.12-1.45, P < 0.001).
Conclusions
We concluded that high level of baseline HbA1c appeared to be an independent predictor for the severity of CAD and poor outcome in patients with stable CAD.
doi:10.1186/1476-511X-13-89
PMCID: PMC4070346  PMID: 24884794
Hemoglobin A1c; Stable angina pectoris; Coronary artery disease; Outcome
16.  Impact of admission triglyceride for early outcome in diabetic patients with stable coronary artery disease 
Background
The role of triglyceride (TG) in predicting the outcomes in diabetic patients with coronary artery disease (CAD) has not been well investigated.
Methods
A total of 329 cases with stable angina pectoris (SAP) were prospectively enrolled and followed up for an average of 12 months. They were classified into the two groups according to the cut-off values of predicting early outcome of fasting TG level (low group <1.2 mmol/L, n = 103; High group ≥1.2 mmol/L, n = 226). The relationship between the TG levels and early outcomes were evaluated.
Results
High TG group showed severer lipid profile and elevated inflammatory markers. During an average of 12-month follow-up, 47 out of 329 patients suffered from pre-specified outcomes. Area under the receivers operating characteristic curve suggested that TG, similar to serum Hemoglobin A1C (HbA1C), was a significant predictor of early outcome for diabetic patients with SAP (P = 0.002). In Cox regression models, after adjusted age, gender, body mass index, other lipid parameters, fasting blood glucose, high sensitivity C-reactive protein, neutrophil count and HbA1C, TG remained as an independent predictor of adverse prognosis.
Conclusions
High level of fasting TG (≥1.2 mmol/L) was an independent predictor for early outcome of diabetic patients with SAP as like as HBA1c and number of affected coronary arteries in the era of revascularization and statin therapeutics.
doi:10.1186/1476-511X-13-73
PMCID: PMC4013537  PMID: 24766776
Triglyceride; Hemoglobin A1C; Stable angina pectoris; Coronary artery disease; Outcome
17.  Expert consensus on acute exacerbation of chronic obstructive pulmonary disease in the People’s Republic of China 
Chronic obstructive pulmonary disease (COPD) is a common disease that severely threatens human health. Acute exacerbation of COPD (AECOPD) is a major cause of disease progression and death, and causes huge medical expenditures. This consensus statement represents a description of clinical features of AECOPD in the People’s Republic of China and a set of recommendations. It is intended to provide clinical guidelines for community physicians, pulmonologists and other health care providers for the prevention, diagnosis, and treatment of AECOPD.
doi:10.2147/COPD.S58454
PMCID: PMC4008287  PMID: 24812503
COPD; AECOPD; recommendations; guidelines
18.  Association of Fibrinogen with Severity of Stable Coronary Artery Disease in Patients with Type 2 Diabetic Mellitus 
Disease Markers  2014;2014:485687.
Background. Some studies have suggested a relation of plasma fibrinogen to the severity of coronary artery disease (CAD). However, whether plasma fibrinogen can predict the presence and severity of CAD in patients with diabetes mellitus has not been determined. Methods. A total of consecutive 373 diabetic patients with typical angina pectoris who received coronary angiography were enrolled and classified into three groups by tertiles of Gensini score (GS, low group <8; intermediate group 8~28; high group >28). The relationship between fibrinogen and GS was evaluated. Results. There were correlations of fibrinogen with hemoglobin A1c, C-reactive protein, and GS (r = 0.17, r = 0.52, and r = 0.21, resp.; all P < 0.001). Area under the receivers operating characteristic curve of fibrinogen was 0.62 (95% CI 0.56–0.68, P < 0.001) for predicting a high GS. Multivariate analysis suggested that plasma fibrinogen was an independent predictor of a high GS for diabetic patients (OR = 1.40, 95% CI 1.04–1.88, and P = 0.026) after adjusting for traditional risk factors of CAD. Conclusions. The present data indicated that plasma fibrinogen, a readily measurable systematic inflammatory marker, appeared to be an independent predictor for the severity of CAD in diabetic patients.
doi:10.1155/2014/485687
PMCID: PMC3997864  PMID: 24803720
19.  Monitoring Powdery Mildew of Winter Wheat by Using Moderate Resolution Multi-Temporal Satellite Imagery 
PLoS ONE  2014;9(4):e93107.
Powdery mildew is one of the most serious diseases that have a significant impact on the production of winter wheat. As an effective alternative to traditional sampling methods, remote sensing can be a useful tool in disease detection. This study attempted to use multi-temporal moderate resolution satellite-based data of surface reflectances in blue (B), green (G), red (R) and near infrared (NIR) bands from HJ-CCD (CCD sensor on Huanjing satellite) to monitor disease at a regional scale. In a suburban area in Beijing, China, an extensive field campaign for disease intensity survey was conducted at key growth stages of winter wheat in 2010. Meanwhile, corresponding time series of HJ-CCD images were acquired over the study area. In this study, a number of single-stage and multi-stage spectral features, which were sensitive to powdery mildew, were selected by using an independent t-test. With the selected spectral features, four advanced methods: mahalanobis distance, maximum likelihood classifier, partial least square regression and mixture tuned matched filtering were tested and evaluated for their performances in disease mapping. The experimental results showed that all four algorithms could generate disease maps with a generally correct distribution pattern of powdery mildew at the grain filling stage (Zadoks 72). However, by comparing these disease maps with ground survey data (validation samples), all of the four algorithms also produced a variable degree of error in estimating the disease occurrence and severity. Further, we found that the integration of MTMF and PLSR algorithms could result in a significant accuracy improvement of identifying and determining the disease intensity (overall accuracy of 72% increased to 78% and kappa coefficient of 0.49 increased to 0.59). The experimental results also demonstrated that the multi-temporal satellite images have a great potential in crop diseases mapping at a regional scale.
doi:10.1371/journal.pone.0093107
PMCID: PMC3972229  PMID: 24691435
20.  Significance of red cell distribution width measurement for the patients with isolated coronary artery ectasia 
Background
Red cell distribution width (RDW) has been recognized as a novel marker for several cardiovascular diseases. The aim of this study was to evaluate the association between RDW levels and the presence of isolated coronary artery ectasia (CAE).
Methods
We studied 414 subjects including 113 patients with isolated CAE (Group A), 144 patients with coronary artery disease (CAD, group B) and 157 angiographically normal controls (group C). Baseline clinical characteristics and laboratory findings including RDW were compared among three groups.
Results
The levels of RDW were significantly higher in group A and B compared with that in group C (12.97 ± 1.4 and 12.88 ± 1.0 vs 12.34 ± 0.9, p = 0.020) while no difference was found between CAE and CAD (p = 0.17). Additionally, the levels of CRP were also higher in patients with CAE and CAD compared with normal controls (0.26 ± 0.14 mg/L, 0.31 ± 0.27 mg/L vs 0.20 ± 0.06 mg/L, p = 0.04). The multivariate analysis indicated that RDW and CRP were the independent variables most strongly associated with the presence of isolated CAE and CAD. There was a positive correlation between levels of RDW and CRP in patients with isolated CAE (γ=0.532, p = 0.001).
Conclusions
Our data suggested that RDW may be a useful marker and independent predictor for the presence of isolated CAE.
doi:10.1186/1479-5876-12-62
PMCID: PMC3975450  PMID: 24606910
Red cell distribution width; Coronary artery ectasia; Coronary artery disease; C-reactive protein
21.  Relation of Leukocytes and Its Subsets Counts with the Severity of Stable Coronary Artery Disease in Patients with Diabetic Mellitus 
PLoS ONE  2014;9(3):e90663.
Background
Both coronary artery disease (CAD) and diabetes mellitus (DM) are associated with inflammation. However, whether and which leukocytes can predict the presence and extent of CAD in patients with DM has not been investigated. The aim of the present study was to examine the association of leukocyte and its subsets counts with the severity of CAD in patients with DM.
Methods and Findings
Three hundred and seventy-three diabetic patients who were scheduled for coronary angiography due to typical stable angina pectoris were enrolled in this study. They were classified into the three groups according to tertiles of Gensini score (GS, low group <8, n = 143; intermediate group 8∼28, n = 109; high group >28, n = 121). The relationship between the leukocyte and its subsets counts with the severity of CAD were evaluated. The data indicated that there were significant correlations between leukocyte and neutrophil counts with GS (r = 0.154 and 0.156, respectively, all P<0.003 for Pearson's correlation). Similarly, area under the receivers operating characteristic curve of leukocyte and neutrophil counts were 0.61 and 0.60 respectively (95%CI: 0.55–0.67, all P = 0.001) for predicting high GS. Multivariate logistic regression analysis demonstrated that leukocyte count was an independent predictor for high GS patients with DM (OR = 1.20, 95%CI 1.03–1.39, P = 0.023) after adjusting for conventional risk factors of CAD.
Conclusions
Compared with its subsets, leukocyte count appeared to be an independent predictor for the severity of CAD and the optimal cut-off value for predicting high GS (>28 points) was 5.0×109 cells/L in diabetic patients.
doi:10.1371/journal.pone.0090663
PMCID: PMC3944194  PMID: 24599246
22.  Luteoloside Suppresses Proliferation and Metastasis of Hepatocellular Carcinoma Cells by Inhibition of NLRP3 Inflammasome 
PLoS ONE  2014;9(2):e89961.
The inflammasome is a multi-protein complex which when activated regulates caspase-1 activation and IL-1β secretion. Inflammasome activation is mediated by NLR proteins that respond to stimuli. Among NLRs, NLRP3 senses the widest array of stimuli. NLRP3 inflammasome plays an important role in the development of many cancer types. However, Whether NLRP3 inflammasome plays an important role in the process of hepatocellular carcinoma (HCC) is still unknown. Here, the anticancer effect of luteoloside, a naturally occurring flavonoid isolated from the medicinal plant Gentiana macrophylla, against HCC cells and the underlying mechanisms were investigated. Luteoloside significantly inhibited the proliferation of HCC cells in vitro and in vivo. Live-cell imaging and transwell assays showed that the migration and invasive capacities of HCC cells, which were treated with luteoloside, were significantly inhibited compared with the control cells. The inhibitory effect of luteoloside on metastasis was also observed in vivo in male BALB/c-nu/nu mouse lung metastasis model. Further studies showed that luteoloside could significantly reduce the intracellular reactive oxygen species (ROS) accumulation. The decreased levels of ROS induced by luteoloside was accompanied by decrease in expression of NLRP3 inflammasome resulting in decrease in proteolytic cleavage of caspase-1. Inactivation of caspase-1 by luteoloside resulted in inhibition of IL-1β. Thus, luteoloside exerts its inhibitory effect on proliferation, invasion and metastasis of HCC cells through inhibition of NLRP3 inflammasome. Our results indicate that luteoloside can be a potential therapeutic agent not only as an adjuvant therapy for HCC, but also, in the control and prevention of metastatic HCC.
doi:10.1371/journal.pone.0089961
PMCID: PMC3935965  PMID: 24587153
23.  The Anticoagulant Effect of PGI2S and tPA in Transgenic Umbilical Vein Endothelial Cells Is Linked to Up-Regulation of PKA and PKC 
The selection of vascular grafts for coronary artery bypass surgery is crucial for a positive outcome. This study aimed to establish a novel line of vascular endothelial cells with a potent anticoagulant effect. A lentiviral vector was used to stably transfect human umbilical vein endothelial cells (HUVECs) with PGI2S alone (HUVEC-PGI2S) or both PGI2S and tPA (HUVEC-PGI2S-tPA). Both HUVEC-PGI2S and HUVEC-PGI2S-tPA cells over-expressing PGI2S and tPA were compared to mock-transfected cells. The enzyme-linked immuno sorbent assay (ELISAs) demonstrated that the anticoagulation components, ATIII and PLG, were up-regulated and coagulation factor FVIII was down-regulated in both cell lines. QRT-PCR and western blotting demonstrated the vasodilation and platelet disaggregation proteins PKA, PKC, and PTGIR were up-regulated in both cell lines, but MAPK expression was not altered in either cell line. However, cell viability and colony formation assays and cell cycle analysis demonstrated that both cell lines had a lower rate of cell growth and induced G1 phase arrest. HUVEC-PGI2S and HUVEC-PGI2S-tPA cells have a potent anticoagulant effect and their use in vascular heterografts may decrease the risk of thrombosis.
doi:10.3390/ijms15022826
PMCID: PMC3958884  PMID: 24557578
anticoagulant; coronary artery bypass graft; endothelial cells; PGI2S; tPA
24.  Pathogenic Pseudorabies Virus, China, 2012 
Emerging Infectious Diseases  2014;20(1):102-104.
In 2012, an unprecedented large-scale outbreak of disease in pigs in China caused great economic losses to the swine industry. Isolates from pseudorabies virus epidemics in swine herds were characterized. Evidence confirmed that the pathogenic pseudorabies virus was the etiologic agent of this epidemic.
doi:10.3201/eid2001.130531
PMCID: PMC3884716  PMID: 24377462
pseudorabies; highly pathogenic PRV; China; viruses; pigs; swine
25.  Lipid rafts participate in aberrant degradative autophagic-lysosomal pathway of amyloid-beta peptide in Alzheimer's disease 
Neural Regeneration Research  2014;9(1):92-100.
Amyloid-beta peptide is the main component of amyloid plaques, which are found in Alzheimer's disease. The generation and deposition of amyloid-beta is one of the crucial factors for the onset and progression of Alzheimer's disease. Lipid rafts are glycolipid-rich liquid domains of the plasma membrane, where certain types of protein tend to aggregate and intercalate. Lipid rafts are involved in the generation of amyloid-beta oligomers and the formation of amyloid-beta peptides. In this paper, we review the mechanism by which lipid rafts disturb the aberrant degradative autophagic-lysosomal pathway of amyloid-beta, which plays an important role in the pathological process of Alzheimer's disease. Moreover, we describe this mechanism from the view of the Two-system Theory of fasciology and thus, suggest that lipid rafts may be a new target of Alzheimer's disease treatment.
doi:10.4103/1673-5374.125335
PMCID: PMC4146310  PMID: 25206748
nerve regeneration; lipid rafts; amyloid precursor protein; autophagy; lysosome; Alzheimer's disease; Two-system Theory; amyloid beta peptide; autophagosome; National Financial Major Project of China; neural regeneration

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