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1.  Extracellular protein analysis of activated sludge and their functions in wastewater treatment plant by shotgun proteomics 
Scientific Reports  2015;5:12041.
In this work, proteins in extracellular polymeric substances extracted from anaerobic, anoxic and aerobic sludges of wastewater treatment plant (WWTP) were analyzed to probe their origins and functions. Extracellular proteins in WWTP sludges were identified using shotgun proteomics, and 130, 108 and 114 proteins in anaerobic, anoxic and aerobic samples were classified, respectively. Most proteins originated from cell and cell part, and their most major molecular functions were catalytic activity and binding activity. The results exhibited that the main roles of extracellular proteins in activated sludges were multivalence cations and organic molecules binding, as well as in catalysis and degradation. The catalytic activity proteins were more widespread in anaerobic sludge compared with those in anoxic and aerobic sludges. The structure difference between anaerobic and aerobic sludges could be associated with their catalytic activities proteins. The results also put forward a relation between the macro characteristics of activated sludges and micro functions of extracellular proteins in biological wastewater treatment process.
PMCID: PMC4498230  PMID: 26160685
2.  Characterization of SMAD3 Gene Variants for Possible Roles in Ventricular Septal Defects and Other Congenital Heart Diseases 
PLoS ONE  2015;10(6):e0131542.
Nodal/TGF signaling pathway has an important effect at early stages of differentiation of human embryonic stem cells in directing them to develop into different embryonic lineages. SMAD3 is a key intracellular messenger regulating factor in the Nodal/TGF signaling pathway, playing important roles in embryonic and, particularly, cardiovascular system development. The aim of this work was to find evidence on whether SMAD3 variations might be associated with ventricular septal defects (VSD) or other congenital heart diseases (CHD).
We sequenced the SMAD3 gene for 372 Chinese Han CHD patients including 176 VSD patients and evaluated SNP rs2289263, which is located before the 5’UTR sequence of the gene. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 13.0). The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE.
Three heterozygous variants in SMAD3 gene, rs2289263, rs35874463 and rs17228212, were identified. Statistical analyses showed that the rs2289263 variant located before the 5’UTR sequence of SMAD3 gene was associated with the risk of VSD (P value=0.013 <0.05).
The SNP rs2289263 in the SMAD3 gene is associated with VSD in Chinese Han populations.
PMCID: PMC4482402  PMID: 26110764
3.  MicroRNA-26b inhibits cell proliferation and cytokine secretion in human RASF cells via the Wnt/GSK-3β/β-catenin pathway 
Diagnostic Pathology  2015;10:72.
Rheumatoid arthritis (RA) is a chronic systemic auto- immune disease characterized by joint synovitis. Recent evidence suggests that rheumatoid arthritis synovial fibroblasts (RASFs) promote joint destruction. In this study, we investigated the role of microRNA-26b (miR-26b) in cell proliferation and inflammatory cytokine secretion using patient-derived Rheumatoid arthritis fibroblast-like synoviocyte (RAFLS) to understand pathways influencing rheumatoid arthritis.
RAFLS were cultured in vitro and transfected with miR-26b mimics (experimental group) and negative sequence (control group). The protein levels of Wnt4, Wnt5ɑ, GSK-3β, CyclinD1, Ser9-GSK-3β and β-catenin were detected by western blot analysis. Tumor Necrosis Factor-ɑ (TNF-ɑ), IL- 1β, and IL-6 levels were quantified by Enzyme-linked Immunosorbent Assay (ELISA). RAFLS proliferation and apoptosis were measured by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry, respectively.
GSK-3β and CyclinD1 expression levels were lower in miR-26b mimic group compared to Mock group and negative control (NC) group. Conversely, GSK-3β and CyclinD1 expression levels were markedly higher in the miR-26b inhibitor group compared to Mock and NC group (P < 0.05). Transfection of miR-26b mimics significantly increased the, levels of Ser9-GSK-3β and β-catenin in comparison to Mock and NC groups, while transfection of miR-26b inhibitors showed the opposite effect. In miR-26b mimic group, TNF-α, IL- 1β and IL-6 levels were lower than the Mock and NC groups, while in miR-26b inhibitor group, these cytokine levels were higher than the Mock and NC groups (P < 0.05). Transfection of miR-26b mimics significantly reduced the cell proliferation of RAFLS, compared to the Mock and NC groups, and miR-26b inhibitors increased the proliferative capacity of RAFLS compared to Mock and NC groups (P < 0.05). The miR-26b mimic group exhibited higher RAFLS apoptosis rate compared to Mock and NC group and miR-26b inhibitor group showed significantly lower RAFLS apoptosis rate compared to Mock and NC groups (P < 0.05).
MiR-26b regulates β-catenin and CyclinD1 levels by inhibiting GSK-3β expression, which in-turn alters the Wnt/GSK-3β/β-catenin pathway to lower RAFLS proliferation and elevate cell apoptosis and the secretion of TNF-α,IL-1β and IL-6 cytokines. Therefore, our results show that miR-26B plays a central role in inhibiting the inflammation associated with rheumatoid arthritis.
Virtual Slides
The virtual slide(s) for this article can be found here:
PMCID: PMC4472173  PMID: 26088648
MicroRNA-26b; Rheumatoid arthritis; Wnt/GSK-3β/β-catenin pathway; CyclinD1; Cytokine
4.  Prognostic Value of Procalcitonin in Adult Patients with Sepsis: A Systematic Review and Meta-Analysis 
PLoS ONE  2015;10(6):e0129450.
Procalcitonin (PCT) has been widely investigated for its prognostic value in septic patients. However, studies have produced conflicting results. The purpose of the present meta-analysis is to explore the diagnostic accuracy of a single PCT concentration and PCT non-clearance in predicting all-cause sepsis mortality. We searched PubMed, Embase, Web of Knowledge and the Cochrane Library. Articles written in English were included. A 2 × 2 contingency table was constructed based on all-cause mortality and PCT level or PCT non-clearance in septic patients. Two authors independently evaluated study eligibility and extracted data. The diagnostic value of PCT in predicting prognosis was determined using a bivariate meta-analysis model. We used the Q-test and I2 index to test heterogeneity. Twenty-three studies with 3,994 patients were included. An elevated PCT level was associated with a higher risk of death. The pooled relative risk (RR) was 2.60 (95% confidence interval (CI), 2.05–3.30) using a random-effects model (I2 = 63.5%). The overall area under the summary receiver operator characteristic (SROC) curve was 0.77 (95% CI, 0.73–0.80), with a sensitivity and specificity of 0.76 (95% CI, 0.67–0.82) and 0.64 (95% CI, 0.52–0.74), respectively. There was significant evidence of heterogeneity for the PCT testing time (P = 0.020). Initial PCT values were of limited prognostic value in patients with sepsis. PCT non-clearance was a prognostic factor of death in patients with sepsis. The pooled RR was 3.05 (95% CI, 2.35–3.95) using a fixed-effects model (I2 = 37.9%). The overall area under the SROC curve was 0.79 (95% CI, 0.75–0.83), with a sensitivity and specificity of 0.72 (95% CI, 0.58–0.82) and 0.77 (95% CI, 0.55–0.90), respectively. Elevated PCT concentrations and PCT non-clearance are strongly associated with all-cause mortality in septic patients. Further studies are needed to define the optimal cut-off point and the optimal definition of PCT non-clearance for accurate risk assessment.
PMCID: PMC4468164  PMID: 26076027
5.  Effective components of Chinese herbs reduce central nervous system function decline induced by iron overload 
Neural Regeneration Research  2015;10(5):778-785.
Abnormally increased levels of iron in the brain trigger cascade amplification in Alzheimer’s disease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer’s disease patients. An APPswe/PS1ΔE9 double transgenic mouse model of Alzheimer’s disease was used. The intragastric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer’s disease. These compounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer’s disease.
PMCID: PMC4468770  PMID: 26109953
nerve regeneration; neurodegenerative diseases; Alzheimer's disease; transgenic animal models; mice; epimedium herb; milkvetch root; kudzuvine root; divalent metal transporter 1; ferroportin 1; neural regeneration
6.  Single Chain Variable Fragment Against Aβ Expressed in Baculovirus Inhibits Abeta Fibril Elongation and Promotes its Disaggregation 
PLoS ONE  2015;10(4):e0124736.
Alzheimer’s disease (AD) is the most common form of age-related dementia, and the most urgent problem is that it is currently incurable. Amyloid-β (Aβ) peptide is believed to play a major role in the pathogenesis of AD. We previously reported that an Aβ N-terminal amino acid targeting monoclonal antibody (MAb), A8, inhibits Aβ fibril formation and has potential as an immunotherapy for AD based on a mouse model. To further study the underlying mechanisms, we tested our hypothesis that the single chain fragment variable (scFv) without the Fc fragment is capable of regulating either Aβ aggregation or disaggregation in vitro. Here, a model of cell-free Aβ “on-pathway” aggregation was established and identified using PCR, Western blot, ELISA, transmission electron microscopy (TEM) and thioflavin T (ThT) binding analyses. His-tagged A8 scFvs was cloned and solubly expressed in baculovirus. Our data demonstrated that the Ni-NTA agarose affinity-purified A8 scFv inhibited the forward reaction of “on-pathway” aggregation and Aβ fibril maturation. The effect of A8 scFv on Aβ fibrillogenesis was markedly more significant when administered at the start of the Aβ folding reaction. Furthermore, the results also showed that pre-formed Aβ fibrils could be disaggregated via incubation with purified A8 scFv, which suggested that A8 scFv is involved in the reverse reaction of Aβ aggregation. Therefore, A8 scFv was capable of both inhibiting fibrillogenesis and disaggregating matured fibrils. Our present study provides valuable insight into the regulators of ultrastructural dynamics of cell-free “on-pathway” Aβ aggregation and will assist in the development of therapeutic strategies for AD.
PMCID: PMC4412524  PMID: 25919299
7.  Dynamic Changes in Amino Acid Concentration Profiles in Patients with Sepsis 
PLoS ONE  2015;10(4):e0121933.
The goal of this work was to explore the dynamic concentration profiles of 42 amino acids and the significance of these profiles in relation to sepsis, with the aim of providing guidance for clinical therapies.
Thirty-five critically ill patients with sepsis were included. These patients were further divided into sepsis (12 cases) and severe sepsis (23 cases) groups or survivor (20 cases) and non-survivor (15 cases) groups. Serum samples from the patients were collected on days 1, 3, 5, 7, 10, and 14 following intensive care unit (ICU) admission, and the serum concentrations of 42 amino acids were measured.
The metabolic spectrum of the amino acids changed dramatically in patients with sepsis. As the disease progressed further or with poor prognosis, the levels of the different amino acids gradually increased, decreased, or fluctuated over time. The concentrations of sulfur-containing amino acids (SAAs), especially taurine, decreased significantly as the severity of sepsis worsened or with poor prognosis of the patient. The serum concentrations of SAAs, especially taurine, exhibited weak negative correlations with the Sequential Organ Failure Assessment (SOFA) (r=-0.319) and Acute Physiology and Chronic Health Evaluation (APACHE) II (r=-0.325) scores. The areas under the receiver operating characteristic curves of cystine, taurine, and SAA levels and the SOFA and APACHE II scores, which denoted disease prognosis, were 0.623, 0.674, 0.678, 0.86, and 0.857, respectively.
Critically ill patients with disorders of amino acid metabolism, especially of SAAs such as cystine and taurine, may provide an indicator of the need for the nutritional support of sepsis in the clinic.
Trial Registration identifier NCT01818830.
PMCID: PMC4388841  PMID: 25849571
8.  Prognostic value of different scoring models in patients with multiple organ dysfunction syndrome associated with acute COPD exacerbation 
Journal of Thoracic Disease  2015;7(3):329-336.
Background and objective
Chronic obstructive pulmonary disease (COPD) represents an increasing healthcare concern as a leading cause of morbidity and mortality worldwide. Our objective was to predict the outcome of COPD patients associated with multiple organ dysfunction syndrome (MODS) by scoring models.
A retrospective study was performed on severe COPD patients within 24 hours of the onset of MODS. The Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, Multiple Organ Dysfunction Score (MODS), Simplified Acute Physiology Score II (SAPS II), and Sepsis-related Organ Failure Assessment (SOFA) scores were calculated for patients.
A total of 153 elderly patients were recruited. Compared to 30-day survivors, the number of failing organs and all of the scoring models were significantly higher in 30-day non-survivors. The SOFA showed the highest sensitivity and area under the curve (AUC) for predicting the prognosis of patients with MODS induced by acute exacerbation of COPD. The results of logistic regression indicated that factors that were correlated with the prognosis of COPD included the exacerbation history, SOFA score, number of failing organs, and duration of ICU stay. The value of exacerbation frequency for predicting the outcome of COPD was excellent (AUC: 0.892), with a sensitivity of 0.851 and a specificity of 0.797.
The SOFA score, determined at the onset of MODS in elderly patients with COPD, was a reliable predictor of the prognosis. The exacerbation frequency, number of failing organs, and the SOFA score were risk factors of a poor prognosis, and the exacerbation frequency could also effectively predict the outcome of COPD.
PMCID: PMC4387415  PMID: 25922710
Acute exacerbation (AE); chronic obstructive pulmonary disease (COPD); multiple organ dysfunction syndrome (MODS); prognosis
9.  Crystal structure of human Fanconi-associated nuclease 1 
Protein & Cell  2014;6(3):225-228.
PMCID: PMC4348246  PMID: 25547363
10.  Crystal structure of human Fanconi-associated nuclease 1 
Protein & Cell  2014;6(3):225-228.
PMCID: PMC4348246  PMID: 25547363
11.  Statin Therapy Decreased the Recurrence Frequency of Atrial Fibrillation after Electrical Cardioversion: A Meta-Analysis 
It is unclear whether statin agents provide clinical benefit in preventing the relapse of atrial fibrillation (AF) after electrical cardioversion (EC). The purpose of this study was to assess the effect of statin agents on the recurrence of AF after EC by conducting a meta-analysis of randomized controlled trials (RCTs).
We conducted a systematic literature search of Medline, EMBASE, ISI Web of Science, and Cochrane databases. RCTs comparing clinical endpoint of the recurrence of AF associated with statin administration vs. no statin treatment (placebo or conventional medical therapy) in patients with AF after EC were eligible. Combined results are presented as risk ratios (RRs) with 95% confidence intervals (CIs).
A total of 5 trials with 524 patients were available for analysis. The pooling analysis showed that statin agents significantly reduced the recurrence of AF after EC compared with no statin treatment (RR=0.76, 95% CI 0.63–0.92; p=0.004; I2=44%). The beneficial effect was shown both in AF subjects receiving atorvastatin or rosuvastatin treatment (atorvastatin 80 mg: RR=0.82, p=0.05; atorvastatin 10 mg: RR=0.27, p=0.03; rosuvastatin: RR=0.38, p=0.04) and in younger patients (<65 years; RR=0.58, p=0.0005). Furthermore, the benefit of statin agents on preventing AF recurrence after EC was demonstrated within 3-month follow-up (p=0.03), and the clinical benefit seemed likely to remain until no less than 12 months after EC (p=0.05).
Based on the currently available data, administration of statin agents, especially atorvastatin or rosuvastatin, is beneficial in lowering the frequency of AF recurrence after EC.
PMCID: PMC4280056  PMID: 25529758
Atrial Fibrillation; Electric Countershock; Hydroxymethylglutaryl-CoA Reductase Inhibitors
12.  Association between vitamin D deficiency and mortality in critically ill adult patients: a meta-analysis of cohort studies 
Critical Care  2014;18(6):684.
Vitamin D deficiency is common in critically ill patients, and was reported to be associated with adverse outcomes. However, the effect of vitamin D deficiency on mortality in critically ill patients remains unclear.
We searched PubMed and EMBASE from the inception to July 2014 for cohort studies to assess the effect of vitamin D deficiency on the incidence of mortality in critically ill patients. Mortality-specific odds ratio (OR) with 95% confidence interval (CI) were pooled with a random- or fixed-effect models when appropriate.
Seven cohort studies with a total of 4,204 participants including 1,679 cases of vitamin D deficiency were included in this meta-analysis. Vitamin D deficiency was significantly associated with an increased hospital mortality (OR 1.76; 95% CI, 1.38 to 2.24; P <0.001), with very low heterogeneity (I2 = 2.3%; P = 0.402). The finding of increased hospital mortality in critically ill adult patients was consistently found in every stratum of our subgroup analyses.
This meta-analysis suggests that vitamin D deficiency is associated with increased incidence of hospital mortality in critically ill adult patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-014-0684-9) contains supplementary material, which is available to authorized users.
PMCID: PMC4274763  PMID: 25498305
13.  Discrimination of sepsis stage metabolic profiles with an LC/MS-MS-based metabolomics approach 
BMJ Open Respiratory Research  2014;1(1):e000056.
To identify metabolic biomarkers that can be used to differentiate sepsis from systemic inflammatory response syndrome (SIRS), assess severity and predict outcomes.
65 patients were involved in this study, including 35 patients with sepsis, 15 patients with SIRS and 15 normal patients. Small metabolites that were present in patient serum samples were measured by liquid chromatography mass spectrometry techniques and analysed using multivariate statistical methods.
The metabolic profiling of normal patients and patients with SIRS or sepsis was markedly different. A significant decrease in the levels of lactitol dehydrate and S-phenyl-d-cysteine and an increase in the levels of S-(3-methylbutanoyl)-dihydrolipoamide-E and N-nonanoyl glycine were observed in patients with sepsis in comparison to patients with SIRS (p<0.05). Patients with severe sepsis and septic shock displayed lower levels of glyceryl-phosphoryl-ethanolamine, Ne, Ne dimethyllysine, phenylacetamide and d-cysteine (p<0.05) in their sera. The profiles of patients with sepsis 48 h before death illustrated an obvious state of metabolic disorder, such that S-(3-methylbutanoyl)-dihydrolipoamide-E, phosphatidylglycerol (22:2 (13Z, 16Z)/0:0), glycerophosphocholine and S-succinyl glutathione were significantly decreased (p<0.05). The receiver operating characteristic curve of the differential expression of these metabolites was also performed.
The body produces significant evidence of metabolic disorder during SIRS or sepsis. Seven metabolites may potentially be used to diagnose sepsis.
Trial registration number identifier NCT01649440.
PMCID: PMC4265126  PMID: 25553245
Respiratory Infection
14.  Advantages of CyberKnife for inoperable stage I peripheral non-small-cell lung cancer compared to three-dimensional conformal radiotherapy 
Molecular and Clinical Oncology  2014;3(2):442-448.
This study was conducted to compare the clinical curative effect and acute radiation lung reactions between CyberKnife (CK) and three-dimensional conformal radiotherapy (3DCRT) treatment for inoperable stage I peripheral non-small-cell lung cancer (NSCLC). We retrospectively analyzed 68 patients with inoperable stage I peripheral NSCLC between 2012 and 2013 in our institution. The CK patients were treated with 42–60 Gy in three fractions, while the 3DCRT patients were treated with a total of 60 Gy, at 2 Gy per fraction. The patients were followed up and the clinical outcome was evaluated according to the Response Evaluation Criteria in Solid Tumours. We assessed the presence of acute radiation pneumonitis and pulmonary function status by thoracic scan and pulmonary function tests following CK and 3DCRT treatment. The binary univariate logistic regression analysis demonstrated that treatment method and forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC) prior to treatment (pre-FEV1/FVC) were the main factors affecting the risk of radiation pneumonitis. The analysis of these factors through multivariate logistic regression method demonstrated that treatment method for grade 1 and 2 [odds ratio (OR)= 7.866 and 11.334, respectively) and pre-FEV1/FVC for grade 1, 2 and 3 (OR = 5.062, 11.498 and 15.042, respectively) were significant factors affecting the risk of radiation pneumonitis (P<0.05). The 68 patients were divided into two subgroups using the threshold of pre-FEV1/FVC selected by the receiver operating characteristic curve. There were significant differences between the 3DCRT and CK treatment in both the pre-FEV1/FVC <68% and ≥68% subgroups for radiation pneumonitis (P=0.023 and 0.002, respectively). There was no statistically significant change in FVC, FEV1 and carbon monoxide diffusion capacity (DCLO) in the CK group, whereas there was a decrease in DCLO in the 3DCRT group. The complete remission rate was 40 vs. 34.2% at 1 year in the CK and 3DCRT groups, respectively. In conclusion, in this cohort of patients with inoperable stage I peripheral NSCLC, CK appears to be a safe and superior alternative to conventionally fractionated radiotherapy.
PMCID: PMC4360859  PMID: 25798283
CyberKnife; three-dimensional conformal radiotherapy; non-small-cell lung cancer; radiation pneumonitis
15.  High expression of microRNA-130b correlates with poor prognosis of patients with hepatocellular carcinoma 
Diagnostic Pathology  2014;9:160.
Whether microRNA-130b(miR-130b) can serve as a prognostic biomarker of hepatocellular carcinoma (HCC) has not been investigated. In the present study, we investigated the feasibility of miR-130b as a novel prognostic biomarker for HCC.
We retrospectively investigated 97 patients diagnosed with HCC who underwent routine curative surgery between May 2007 and July 2012. miR-130b expression in HCC tissues and paired normal adjacent liver tissues was measured by reverse transcription and real-time PCR (RT-PCR). Survival curves were plotted using the Kaplan-Meier method and differences in survival rates were analyzed using the log-rank test.
miR-130b expression level was significantly higher in HCC tissues compared with normal adjacent liver tissues (P < 0.0001). The 5-year overall survival (OS) of high miR-130b expression group was significantly shorter than that of low miR-130b expression group (43.6% vs. 71.5%; P = 0.022). Moreover, the 5-year disease-free survival (DFS) of high miR-130b expression group was also significantly shorter than that of low miR-130b expression group (25.9% vs. 63.9%; P = 0.012). In a multivariate Cox model, we found that miR-130b expression was an independent prognostic factor for both 5-year OS (hazards ratio [HR] = 2.523, 95% confidence interval [CI] = 1.024-7.901, P = 0.011) and 5-year DFS (HR = 4.003, CI = 1.578-7.899, P = 0.005) in HCC.
The results indicated that high expression of microRNA-130b was correlated with significant characteristics of patients with HCC, and it might be useful as a novel prognostic biomarker for HCC.
Virtual Slides
The virtual slide(s) for this article can be found here:
PMCID: PMC4141946  PMID: 25123453
16.  Characterization of Nodal/TGF-Lefty Signaling Pathway Gene Variants for Possible Roles in Congenital Heart Diseases 
PLoS ONE  2014;9(8):e104535.
Nodal/TGF-Lefty signaling pathway has important effects at early stages of differentiation of human embryonic stem cells in directing them to differentiate into different embryonic lineages. LEFTY, one of transforming growth factors in the Nodal/TGF-Lefty signaling pathway, plays an important role in the development of heart. The aim of this work was to find evidence on whether Lefty variations are associated with congenital heart diseases (CHD).
We sequenced the Lefty gene for 230 Chinese Han CHD patients and evaluated SNPs rs2295418, rs360057 and g.G169A, which are located within the translated regions of the genes. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 13.0). The Hardy-Weinberg equilibrium test of the population was carried out using online software OEGE, and multiple-sequence alignments of LEFTY proteins were carried out using the Vector NTI software.
Two heterozygous variants in Lefty1 gene, g.G169A and g.A1035C, and one heterozygous variant in Lefty2 gene, g.C925A, were identified. Statistical analyses showed that the rs2295418 (g.C925A) variant in Lefty2 gene was obviously associated with the risk of CHD (P value = 0.016<0.05). The genotype frequency of rs360057 (g.A1035C) variant in Lefty1 gene was associated with the risk of CHD (P value = 0.007<0.05), but the allele frequency was not (P value = 0.317>0.05).
The SNP rs2295418 in the Lefty2 gene is associated with CHD in Chinese Han populations.
PMCID: PMC4128709  PMID: 25111179
17.  Prolonged electrical stimulation causes no damage to sacral nerve roots in rabbits 
Neural Regeneration Research  2014;9(12):1217-1221.
Previous studies have shown that, anode block electrical stimulation of the sacral nerve root can produce physiological urination and reconstruct urinary bladder function in rabbits. However, whether long-term anode block electrical stimulation causes damage to the sacral nerve root remains unclear, and needs further investigation. In this study, a complete spinal cord injury model was established in New Zealand white rabbits through T9–10 segment transection. Rabbits were given continuous electrical stimulation for a short period and then chronic stimulation for a longer period. Results showed that compared with normal rabbits, the structure of nerve cells in the anterior sacral nerve roots was unchanged in spinal cord injury rabbits after electrical stimulation. There was no significant difference in the expression of apoptosis-related proteins such as Bax, Caspase-3, and Bcl-2. Experimental findings indicate that neurons in the rabbit sacral nerve roots tolerate electrical stimulation, even after long-term anode block electrical stimulation.
PMCID: PMC4146294  PMID: 25206785
nerve regeneration; spinal cord injury; sacral nerve root; electrical stimulation; anode block; spinal cord reconstruction; bladder function; nerve prosthesis; neural regeneration
18.  Prediction of outcome following paraquat poisoning by arterial lactate concentration-time data 
The present study retrospectively analyzed 170 patients diagnosed with paraquat (PQ) poisoning with the aim of clarifying whether the arterial lactate-time (arterial lactate concentration × time between ingestion and arterial lactate measurement) was a good predictor of mortality in patients with acute PQ poisoning. The results indicated that there was a positive correlation between the arterial lactate-time and PQ concentration-time (ρ=0.485). In addition, the arterial lactate-time data exhibited a similar discriminative power to the plasma PQ concentration-time data (z=0.712; P=0.864). For the receiver operating characteristic curve analysis, the lactate-time data had an area of 0.782 with a cut-off value of 11.95 mmol/l.h (sensitivity, 64.52%; specificity, 84.42%). To calculate the predicted probability of survival for any specified time and initial arterial lactate concentration, the following formula was derived based on the logistic regression coefficients: Logit(p) = 3.066 − 0.139 × (time lag following PQ ingestion) − 0.177 × (initial arterial lactate concentration); where the probability of survivors = 1/1 + e−logit(p). Therefore, the arterial lactate-time data exhibited a good predictive power for evaluating the prognosis of patients with acute PQ poisoning.
PMCID: PMC4079403  PMID: 25009635
arterial lactate; paraquat; poisoning; prognosis
19.  Evaluation of a Prednisolone Acetate-Loaded Subconjunctival Implant for the Treatment of Recurrent Uveitis in a Rabbit Model 
PLoS ONE  2014;9(5):e97555.
To assess the efficacy of a biodegradable, prednisolone acetate implant in a rabbit uveitis model.
Randomized, controlled study of biodegradable microfilms preloaded with prednisolone acetate (PA) in a rabbit uveitis model. Experimental uveitis was induced by unilateral intravitreal injection of Mycobacterium tuberculosis H37Ra antigen (50 ug; 1 ug/uL) in preimmunized rabbits. PA-loaded poly[d,l-lactide-co-ε-caprolactone] (PLC) microfilms (n = 10) and blank microfilms (n = 6) were implanted subconjunctivally. An estimate of PA release in vivo was calculated from measured residual PA amounts in microfilms after the rabbits were sacrificed. The eyes were clinically monitored for ocular inflammation for 28 days. Histopathological examination of the enucleated eyes was performed at the end of the study period.
In vitro studies revealed that sandwich PA-loaded microfilm formulations exhibited higher release kinetic compared to homogenous PA-loaded microfilms. The 60–40–60% microfilm released an average of 0.034 mg/day of PA over the period of 60 days in vitro; and we found that approximately 0.12 mg/day PA was released in vivo. Animals implanted with the PA-loaded microfilms exhibited significantly lowered median inflammatory scores when compared against the control group in this model for recurrent uveitis (P<0.001). The implants were clinically well tolerated by all the animals. Histology results showed no significant scarring or inflammation around the PA-loaded microfilms.
Our pilot study demonstrated that a subconjunctival PA-loaded implant is effective in suppressing inflammation in the rabbit model of uveitis, by providing therapeutic levels of PA that attenuated the inflammatory response even after a rechallenge. Longer term studies are now needed to establish the therapeutic potential of such a delivery system for treatment of ocular inflammation.
PMCID: PMC4026472  PMID: 24842851
20.  Second- versus first-generation drug-eluting stents for diabetic patients: a meta-analysis 
Archives of Medical Science : AMS  2014;10(2):213-221.
The issue of whether various drug-eluting stents (DES) provide similar benefit in diabetic patients with coronary artery disease remains unclear. The purpose of the study is to assess the clinical utility of the second-generation and first-generation DES in patients with diabetes mellitus by a meta-analysis.
Material and methods
A systematic literature search of PubMed, EMBASE, and Cochrane databases was conducted. We included randomized trials involving head-to-head comparison of clinical outcomes of second- versus first-generation DES in patients with a diagnosis of diabetes with at least 6-month follow-up data. Summary statistics were calculated using random-effects models.
A total of 10 trials with 4503 patients were available for analysis. The pooled analyses showed that the second-generation everolimus-eluting stent (EES) significantly lowered all-cause mortality (risk ratio (RR) = 0.58, 95% CI: 0.37–0.90; p = 0.01) and the risk of stent thrombosis (RR = 0.46, 95% CI: 0.22–0.95; p = 0.03) compared with the first-generation sirolimus-eluting stents (SES) and the overall first-generation DES, respectively. Moreover, the EES showed a tendency toward reducing the incidence of recurrent myocardial infarction when compared with paclitaxel-eluting stents (PES) (RR = 0.58, p = 0.08). In contrast, the second-generation zotarolimus-eluting stents (ZES) were associated with increased rates of stent thrombosis and risk of target lesion revascularization in comparison with the SES (both p < 0.05) or the overall first-generation DES (both p < 0.05).
The second-generation EES are highly effective in reducing the risk of major cardiac events in diabetic patients with coronary artery disease.
PMCID: PMC4042041  PMID: 24904652
everolimus-eluting stents; zotarolimus-eluting stents; diabetes; meta-analysis
21.  Prognostic analysis and comparison of colon cancer in Han and Hui patients 
AIM: To investigate the relevant prognostic factors and their differences between colorectal cancer (CRC) patients of Chinese Han and Hui ethnicities in the Beijing region.
METHODS: A retrospective analysis of 880 patients diagnosed with CRC at Xuanwu Hospital, Capital Medical University between September 2001 and September 2011 was performed. Among the 880 patients, 398 and 482 were Hui and Han, respectively. Characteristics including sex, age, diet, tumor size, primary tumor site, Dukes’ stage and degree of differentiation were analyzed for their influence on prognosis. Data on dietary structures were recorded through a questionnaire survey conducted during the patient’s first visit, return visit or follow-up checkups.
RESULTS: Among patients with colon cancer, the 5-year survival rate for patients of Hui ethnicity was lower than that for Han patients (P = 0.025). Six risk factors (age of onset, dietary structure, tumor size, Dukes’ stage, location of cancer and degree of differentiation) in both Han and Hui patients were identified as prognostic factors (P < 0.05). Multivariate analysis showed that age of onset (P = 0.002), diet (P = 0.000), Dukes’ stage (P = 0.000) and degree of differentiation (P = 0.000) are prognostic factors affecting both ethnic groups. Comparison of prognostic factors between Han and Hui patients with CRC showed that dietary structure was a statistically significant factor, and diet varied significantly between the two ethnic groups.
CONCLUSION: Dietary structure has a significant influence on colon cancer prognosis among Han and Hui patients with colon cancer in Beijing, which may cause a difference in their survival rates.
PMCID: PMC4009544  PMID: 24803822
Colon cancer; Colorectal cancer; Han patients; Hui patients; Prognosis; Multivariate analysis
22.  Fano resonance in anodic aluminum oxide based photonic crystals 
Scientific Reports  2014;4:3601.
Anodic aluminum oxide based photonic crystals with periodic porous structure have been prepared using voltage compensation method. The as-prepared sample showed an ultra-narrow photonic bandgap. Asymmetric line-shape profiles of the photonic bandgaps have been observed, which is attributed to Fano resonance between the photonic bandgap state of photonic crystal and continuum scattering state of porous structure. And the exhibited Fano resonance shows more clearly when the sample is saturated ethanol gas than air-filled. Further theoretical analysis by transfer matrix method verified these results. These findings provide a better understanding on the nature of photonic bandgaps of photonic crystals made up of porous materials, in which the porous structures not only exist as layers of effective-refractive-index material providing Bragg scattering, but also provide a continuum light scattering state to interact with Bragg scattering state to show an asymmetric line-shape profile.
PMCID: PMC3884230  PMID: 24398625
23.  Comparative Efficacy and Acceptability of Antidepressants in Parkinson's Disease: A Network Meta-Analysis 
PLoS ONE  2013;8(10):e76651.
Depression is a common non-motor symptom in patients with Parkinson's disease (PD). There are many kinds of antidepressants being used, such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and Dopamine agonists which are suggested as alternative antidepressants for the treatment of depression in PD. Which one should we choose first? Literatures have shown inconsistent results.
We conducted a network meta-analysis of randomized controlled trials to compare the efficacy and acceptability of therapeutic methods for the treatment of depression in Parkinson's disease.
We used the odds ratios (OR) as effect size firstly and the results indicated no statistical significance between each compared intervention. Then we used the logarithm of the individual odds ratios as effect size. With efficacy of TCAs as the standard of comparison, the degree of incoherence (a measure of how closely the entire network fits together) was small (ω =  4.824827e-05). The logor were: SSRIs −0.69 (95% CI −1.28– −0.10); Pramipexole −0.73 (−1.71– −0.26); Pergolide −1.97 (−3.67– 0.27); SNRIs −0.86 (−1.86– 0.15); Placebo −1.24 (−1.99– −0.50). With Placebo as the standard of comparison, the logor were: TCAs 1.24 (0.50– 1.99); SSRIs 0.55 (−0.03– 1.13); Pramipexole 0.51 (−0.12– 1.15); Pergolide −0.73 (−2.25– 0.80); SNRIs 0.38 (−0.42– 1.19); TCAs, pramipexole, pergolide and SNRIs showed better profile of acceptability, leading to significant fewer discontinuations than that of SSRIs.
There is insufficient evidence to support antidepressant efficacy for SSRIs, pramipexole, pergolide and SNRIs. TCAs might be the best choice when starting antidepressant treatment in patients of Parkinson's disease because it has the most favorable balance between benefits and acceptability, followed by pramipexole and SNRIs, SSRIs might be the last choice.
PMCID: PMC3788746  PMID: 24098546
24.  Analysis of the severity and prognosis assessment of aged patients with community-acquired pneumonia: a retrospective study 
Journal of Thoracic Disease  2013;5(5):626-633.
Community-acquired pneumonia (CAP) is a prevalent and potentially life-threatening infection, and has poor prognosis in aged patients. The objective of this study was to compare the potential of admission N-terminal pro B-type natriuretic peptide (proBNP) levels and scoring models [CURB-65, Pneumonia Severity Index (PSI), and Acute Physiology and Chronic Health Evaluation (APACHE) II scores] to predict outcomes for aged patients with CAP admitted to Intensive Care Unit (ICU), and to explore the prognostic factors.
Clinical data of the patients were collected retrospectively, whose CURB-65, PSI, APACHE II scores were calculated and in whom measurements of proBNP was performed. The outcomes of interest were severity evaluation, prediction of need for mechanical ventilation and 28-day mortality. Receiver operating characteristic (ROC) curve was conducted to predict the assessment ability of proBNP and scoring models on different outcomes, and the logistic regression analysis was performed to screen factors affecting prognosis.
240 patients were enrolled, with the mean age of 75±8 years old. Admission levels of NT-proBNP, scoring models were significantly higher in SCAP patients, MV group, and non-survivors compared to non-SCAP patients, no-MV group, and 28-day survivors, respectively (P<0.001). PSI had the highest area under the curve (AUC) and specificity for the three outcomes considered (AUC: 0.868 and specificity: 0.906 for 28-day mortality, AUC: 0.864 and specificity: 0.831 for requirement of MV, and AUC: 0.888 and specificity: 0.894 for severity evaluation). NT-proBNP had the highest sensitivity of 0.987 and 0.903 on prediction of mortality and need for MV. And APACHE II scoring model with the highest sensitivity of 0.890 was used to evaluate severity. Logistic regression analysis showed that the odd ratio (OR) of systolic blood pressure, PSI, and APACHE II scores were 0.886, 1.019, and 1.249.
PSI scores was the best indicator in predicting different clinical outcomes of aged patients with CAP among the proBNP and three scoring systems. Systolic blood pressure might be as a protective factor for prognosis while PSI and APACHE II scores as risk factors for prognosis of aged patients with CAP.
PMCID: PMC3815733  PMID: 24255776
Aged; community-acquired pneumonia (CAP); severity; prognosis
25.  Correction: RNA-Seq Reveals Infection-Related Gene Expression Changes in Phytophthora capsici 
PLoS ONE  2013;8(9):10.1371/annotation/3be2cab2-9116-49c1-acce-7d51f4ccd887.
PMCID: PMC3778096

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