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1.  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
2.  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
3.  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
4.  High expression of microRNA-130b correlates with poor prognosis of patients with hepatocellular carcinoma 
Diagnostic Pathology  2014;9(1):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
5.  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
6.  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
7.  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
8.  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
9.  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
10.  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
11.  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
12.  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
13.  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
14.  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
15.  RNA-Seq Reveals Infection-Related Gene Expression Changes in Phytophthora capsici 
PLoS ONE  2013;8(9):e74588.
Phytophthora capsici is a soilborne plant pathogen capable of infecting a wide range of plants, including many solanaceous crops. However, genetic resistance and fungicides often fail to manage P. capsici due to limited knowledge on the molecular biology and basis of P. capsici pathogenicity. To begin to rectify this situation, Illumina RNA-Seq was used to perform massively parallel sequencing of three cDNA samples derived from P. capsici mycelia (MY), zoospores (ZO) and germinating cysts with germ tubes (GC). Over 11 million reads were generated for each cDNA library analyzed. After read mapping to the gene models of P. capsici reference genome, 13,901, 14,633 and 14,695 putative genes were identified from the reads of the MY, ZO and GC libraries, respectively. Comparative analysis between two of samples showed major differences between the expressed gene content of MY, ZO and GC stages. A large number of genes associated with specific stages and pathogenicity were identified, including 98 predicted effector genes. The transcriptional levels of 19 effector genes during the developmental and host infection stages of P. capsici were validated by RT-PCR. Ectopic expression in Nicotiana benthamiana showed that P. capsici RXLR and Crinkler effectors can suppress host cell death triggered by diverse elicitors including P. capsici elicitin and NLP effectors. This study provides a first look at the transcriptome and effector arsenal of P. capsici during the important pre-infection stages.
PMCID: PMC3760852  PMID: 24019970
16.  Effects of Vitamin B6 Therapy for Sepsis Patients with Linezolid-Associated Cytopenias: A Retrospective Study☆ 
The common adverse effects of linezolid for treating septic patients with gram-positive cocci is anemia and thrombocytopenia, which limit its clinical application.
We determined the effects of vitamin B6 adjunctive therapy on linezolid-associated cytopenias, and retrospectively studied 75 septic patients who received at least 7 days of linezolid treatment.
Patients were divided into a linezolid treatment group (LTG; n = 41) that received linezolid only and a combination treatment group (CTG; n = 34) that received both linezolid and vitamin B6. Each group was further subdivided into those with sepsis and those with severe sepsis. Each patient had red blood cell (RBC), hemoglobin (Hb), hematocrit (Hct), and platelet (PLT) measurements at baseline (day 0) and every other day for 2 weeks during treatment; these parameters were compared between the groups and assessed for time-dependent trends.
For patients in the LTG, RBC, Hb, and Hct values showed statistically significant reductions over time, and these values were lower compared with the values in the CTG. The CTG also showed downward trends, except on the first day of treatment. The PLT count also decreased in both groups. Patients with severe sepsis had lower PLT counts in both treatment groups compared with the septic patients.
Septic patients who received a combination treatment of linezolid and vitamin B6 might show positive effects for linezolid-associated reductions in some hematologic parameters (RBC, Hb, and Hct). This combined treatment might also slow PLT reduction, which was more evident in patients with severe sepsis. identifier: NCT01295801.
PMCID: PMC3862191  PMID: 24385027
linezolid; linezolid-associated cytopenias; sepsis; vitamin B6
17.  Mitochondria-targeted antioxidant attenuates high glucose-induced P38 MAPK pathway activation in human neuroblastoma cells 
Molecular Medicine Reports  2012;5(4):929-934.
Excessive mitochondrial free radical production and the related mitogen-activated protein kinase P38 (P38 MAPK) activation are key regulators in the pathogenesis of high glucose-induced cell stress. Increasing evidence has emphasized the impact of hyperglycemia on neurons and the consequent neuronal stresses eventually resulting in neurodegeneration and neuronal death. In this study, we employed a novel mitochondria-targeted antioxidant, SS31 peptide, on high glucose-insulted neuroblastoma cells (SH-SY5Y). Our results showed that high glucose promoted significantly increased P38 phosphorylation which was efficiently suppressed by the application of the SS31 peptide under the experimental conditions. The inhibition of high glucose-induced P38 activation by the SS31 peptide was associated with the impact of the SS31 peptide on attenuating high glucose-induced mitochondrial ROS (reactive oxygen species) elevation and mitochondrial membrane potential collapse. The addition of SS31 peptide significantly attenuated high-gluose-induced apoptosis. Therefore, our study suggests that elimination of high glucose-induced mitochondrial oxidative stress helps to rescue SH-SY5Y cells from high glucose-related P38 MAPK pathway disturbances, and the SS31 peptide has the potential to serve as a new treatment strategy against hyperglycemia-instigated neuronal perturbations.
PMCID: PMC3493100  PMID: 22245807
high-glucose; SS31 peptide; antioxidant; mitogen-activated protein kinase P38; mitochondrial reactive oxygen species; neuroblastoma cell
18.  Multicenter Study of Creatinine- and/or Cystatin C-Based Equations for Estimation of Glomerular Filtration Rates in Chinese Patients with Chronic Kidney Disease 
PLoS ONE  2013;8(3):e57240.
To establish equations for the estimation of glomerular filtration rates (eGFRs) based on serum creatinine (SCr) and/or serum cystatin C (SCysC) in Chinese patients with chronic kidney disease (CKD), and to compare the new equations with both the reference GFR (rGFR) and the literature equations to evaluate their applicability.
The 788 Chinese CKD patients were randomly divided into two groups, the training group and the testing group, to establish new eGFR-formulas based on serum CysC and to validate the established formulas, respectively. 99mTc-DTPA clearance (as the rGFR), serum Cr, and serum CysC were determined for all patients, and GFR was calculated using the Cockcroft-Gault equation (eGFR1), the MDRD formula (eGFR2), the CKD-EPI formulas (eGFR3, eGFR4), and the Chinese eGFR Investigation Collaboration formulas (eGFR5, eGFR6). The accuracy of each eGFR was compared with the rGFR.
The training and testing groups' mean GFRs were 50.84±31.36 mL/min/1.73 m2 and 54.16±29.45 mL/min/1.73 m2, respectively. The two newly developed eGFR formulas were fitted using iterative computation: and . Significant correlation was observed between each eGFR and the rGFR. However, proportional errors and constant errors were observed between rGFR and eGFR1, eGFR2, eGFR4, eGFR5 or eGFR6, and constant errors were observed between eGFR3 and rGFR, as revealed by the Passing & Bablok plot analysis. The Bland-Altman analysis illustrated that the 95% limits of agreement of all equations exceeded the previously accepted limits of <60 mL/min •1.73 m2, except the equations of eGFR7 and eGFR8.
The newly developed formulas, eGFR7 and eGFR8, provide precise and accurate GFR estimation using serum CysC detection alone or in combination with serum Cr detection. Differences in detection methods should be carefully considered when choosing literature eGFR equations to avoid misdiagnosis and mistreatment.
PMCID: PMC3602457  PMID: 23526939
19.  Photodynamic Therapy With Hyperbranched Poly(Ether-Ester) Chlorin(e6) Nanoparticles On Human Tongue Carcinoma Cal-27 Cells 
Hyperbranched polymers represent a new class of drug delivery vehicle that can be used to prepare nanoparticles with uniform size distribution.
In this study we prepared covalent conjugates between the photosensitizer chlorin(e6) and hyperbranched poly(ether-ester), HPEE. HPEE-ce6 nanoparticles were synthesized by carbodiimide-mediated reaction between HPEE and ce6, and characterized by ultraviolet-visible absorption spectroscopy (UV-Vis), and transmission electron microscopy (TEM). The uptake and phototoxicity of HPEE-ce6 nanoparticles towards human oral tongue cancer CAL-27 cells was detected by confocal laser scanning microscopy (CLSM) and MTT assay respectively.
The absorption peak of HPEE-ce6 nanoparticles was red-shifted 12-nm compared with ce6, and TEM showed uniform nanoparticles with a diameter of 50-nm. HPEE-ce6 nanoparticles were taken up by CAL-27 cells after 4 hour incubation and localized in the cytoplasm. The MTT assay showed a significantly (P<0.05) higher phototoxicity compared to free ce6 after 12 J/cm2 of 660-nm laser illumination.
This is the first time to our knowledge that hyperbranched polymers have been used in PDT drug delivery.
PMCID: PMC3292741  PMID: 22369732
Photodynamic therapy (PDT); Chlorin e6; hyperbranched poly(ether-ester) (HPEE); drug delivery system (DDS); nanoparticles; transmission electron microscopy
20.  (2S,4R)-2-[(1R)-1-(4-Bromo­phen­yl)-2-nitro­eth­yl]-4-ethyl­cyclo­hexa­none 
The crystal structure of the title compound, C16H20BrNO3, contains three chiral centers in the configuration 1R,2S,6R. The cyclo­hexane ring is in a chair conformation. In the crystal, mol­ecules are linked by weak C—H⋯O inter­actions, forming chains along the a-axis direction.
PMCID: PMC3569793  PMID: 23424539
21.  Diagnostic value of urine sCD163 levels for sepsis and relevant acute kidney injury: a prospective study 
BMC Nephrology  2012;13:123.
Sepsis is a common syndrome in critically ill patients and easily leads to the occurrence of acute kidney injury (AKI), with high mortality rates. This study aimed to investigate the diagnostic value of urine soluble CD163 (sCD163) for identification of sepsis, severity of sepsis, and for secondary AKI, and to assess the patients’ prognosis.
We enrolled 20 cases with systemic inflammatory response syndrome (SIRS), 40 cases with sepsis (further divided into 17 sepsis cases and 23 severe sepsis cases) admitted to the intensive care unit (ICU), and 20 control cases. Results for urine sCD163 were recorded on the day of admission to the ICU, and AKI occurrence was noted.
On the day of ICU admission, the sepsis group exhibited higher levels of urine sCD163 (74.8 ng/ml; range: 47.9-148.3 ng/ml) compared with those in the SIRS group (31.9 ng/ml; 16.8-48.0, P < 0.001). The area under the curve (AUC) was 0.83 (95% confidence interval [CI]: 0.72-0.94, P < 0.001) the sensitivity was 0.83, and the specificity was 0.75 (based on a cut-off point of 43.0 ng/ml). Moreover, the severe sepsis group appeared to have a higher level of sCD163 compared with that in the sepsis group (76.2; 47.2-167.5 ng/ml vs. 74.2; 46.2-131.6 ng/ml), but this was not significant. For 15 patients with AKI, urine sCD163 levels at AKI diagnosis were significantly higher than those of the remaining 35 sepsis patients upon ICU admission (121.0; 74.6-299.1 ng/ml vs. 61.8; 42.8-128.3 ng/ml, P = 0.049). The AUC for urine sCD163 was 0.688 (95% CI: 0.51-0.87, P = 0.049). Sepsis patients with a poor prognosis showed a higher urine sCD163 level at ICU admission (98.6; 50.3-275.6 ng/ml vs. 68.0; 44.8-114.5 ng/ml), but this was not significant. Patients with AKI with a poor prognosis had higher sCD163 levels than those in patients with a better prognosis (205.9; 38.6-766.0 ng/ml vs. 80.9; 74.9-141.0 ng/ml), but this was not significant.
This study shows, for the first time, the potential value of urine sCD163 levels for identifying sepsis and diagnosing AKI, as well as for assessment of patients’ prognosis.
Trial Registration
PMCID: PMC3506529  PMID: 23013330
Urine; Soluble CD163 (sCD163); Sepsis; Systemic inflammatory response syndrome (SIRS); Prognosis; Acute kidney injury (AKI)
22.  Value of soluble TREM-1, procalcitonin, and C-reactive protein serum levels as biomarkers for detecting bacteremia among sepsis patients with new fever in intensive care units: a prospective cohort study 
BMC Infectious Diseases  2012;12:157.
The purpose of this study was to explore the diagnostic value of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1), procalcitonin (PCT), and C-reactive protein (CRP) serum levels for differentiating sepsis from SIRS, identifying new fever caused by bacteremia, and assessing prognosis when new fever occurred.
We enrolled 144 intensive care unit (ICU) patients: 60 with systemic inflammatory response syndrome (SIRS) and 84 with sepsis complicated by new fever at more than 48 h after ICU admission. Serum sTREM-1, PCT, and CRP levels were measured on the day of admission and at the occurrence of new fever (>38.3°C) during hospitalization. Based on the blood culture results, the patients were divided into a blood culture-positive bacteremia group (33 patients) and blood culture-negative group (51 patients). Based on 28-day survival, all patients, both blood culture-positive and -negative, were further divided into survivor and nonsurvivor groups.
On ICU day 1, the sepsis group had higher serum sTREM-1, PCT, and CRP levels compared with the SIRS group (P <0.05). The areas under the curve (AUC) for these indicators were 0.868 (95% CI, 0.798–0.938), 0.729 (95% CI, 0.637–0.821), and 0.679 (95% CI, 0.578–0.771), respectively. With 108.9 pg/ml as the cut-off point for serum sTREM-1, sensitivity was 0.83 and specificity was 0.81. There was no statistically significant difference in serum sTREM-1 or PCT levels between the blood culture-positive and -negative bacteremia groups with ICU-acquired new fever. However, the nonsurvivors in the blood culture-positive bacteremia group had higher levels of serum sTREM-1 and PCT (P <0.05), with a prognostic AUC for serum sTREM-1 of 0.868 (95% CI, 0.740–0.997).
Serum sTREM-1, PCT, and CRP levels each have a role in the early diagnosis of sepsis. Serum sTREM-1, with the highest sensitivity and specificity of all indicators studied, is especially notable. sTREM-1, PCT, and CRP levels are of no use in determining new fever caused by bacteremia in ICU patients, but sTREM-1 levels reflect the prognosis of bacteremia.
Trial registration identifier NCT01410578
PMCID: PMC3426475  PMID: 22809118
Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1); Fever; Sepsis; Bacteremia; Diagnosis; Prognosis
23.  Over-expression of the Gerbera hybrida At-SOC1-like1 gene Gh-SOC1 leads to floral organ identity deterioration 
Annals of Botany  2011;107(9):1491-1499.
Background and Aims
The family of MADS box genes is involved in a number of processes besides controlling floral development. In addition to supplying homeotic functions defined by the ABC model, they influence flowering time and transformation of vegetative meristem into inflorescence meristem, and have functions in roots and leaves. Three Gerbera hybrida At-SOC1-like genes (Gh-SOC1–Gh-SOC3) were identified among gerbera expressed sequence tags.
Evolutionary relationships between SOC1-like genes from gerbera and other plants were studied by phylogenetic analysis. The function of the gerbera gene Gh-SOC1 in gerbera floral development was studied using expression analysis, protein–protein interaction assays and reverse genetics. Transgenic gerbera lines over-expressing or downregulated for Gh-SOC1 were obtained using Agrobacterium transformation and investigated for their floral phenotype.
Key Results
Phylogenetic analysis revealed that the closest paralogues of At-SOC1 are Gh-SOC2 and Gh-SOC3. Gh-SOC1 is a more distantly related paralogue, grouping together with a number of other At-SOC1 paralogues from arabidopsis and other plant species. Gh-SOC1 is inflorescence abundant and no expression was seen in vegetative parts of the plant. Ectopic expression of Gh-SOC1 did not promote flowering, but disturbed the development of floral organs. The epidermal cells of ray flower petals appeared shorter and their shape was altered. The colour of ray flower petals differed from that of the wild-type petals by being darker red on the adaxial side and greenish on the abaxial surface. Several protein–protein interactions with other gerbera MADS domain proteins were identified.
The At-SOC1 paralogue in gerbera shows a floral abundant expression pattern. A late petal expression might indicate a role in the final stages of flower development. Over-expression of Gh-SOC1 led to partial loss of floral identity, but did not affect flowering time. Lines where Gh-SOC1 was downregulated did not show a phenotype. Several gerbera MADS domain proteins interacted with Gh-SOC1.
PMCID: PMC3108810  PMID: 21572092
Gerbera hybrida; MADS box gene; Gh-SOC1; flower development; floral organ identity; gene transfer
24.  catena-Poly[(dichloridozinc)-μ-1-{4-[(1H-imidazol-1-yl)meth­yl]benz­yl}-1H-imidazole-κ2 N 3:N 3′] 
The asymmetric unit of the title compound, [ZnCl2(C14H14N4)]n, contains a ZnII ion situated on a twofold rotation axis and one-half of a 1-{4-[(1H-imidazol-1-yl)meth­yl]benz­yl}-1H-imidazole (L) ligand with the benzene ring situated on an inversion center. The ZnII ion is coordinated by two chloride anions and two N atoms from two L ligands in a distorted tetra­hedral geometry. The L ligands bridge ZnCl2 fragments into polymeric chains parallel to [20-1].
PMCID: PMC3344354  PMID: 22590120
25.  Analysis of the optical quality by determining the modulation transfer function for anterior corneal surface in myopes 
To describe the characteristics of modulation transfer function (MTF) of anterior corneal surface, and obtain the the normal reference range of MTF at different spatial frequencies and optical zones of the anterior corneal surface in myopes.
Four hundred eyes from 200 patients were examined under SIRIUS corneal topography system. Phoenis analysis software was applied to simulate the MTF curves of anterior corneal surface at vertical and horizontal meridians at the 3, 4, 5, 6, 7mm optical zones of cornea. The MTF values at spatial frequencies of 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55 and 60 cycles/degree (c/d) were selected.
The MTF curve of anterior corneal surface decreased rapidly from low to intermediate frequency (0-15cpd) at various optical zones of cornea, the value decreased to 0 slowly at higher frequency (>15cpd). With the increase of the optical zones of cornea, MTF curve decreased gradually. 3) In the range of 3 mm- 6 mm optical zones of the cornea, the MTF values measured at horizontal meridian were greater than the corresponding values at horizontal meridian of each spatial frequency, the difference was statistically significant (P<0.05). At 7 mm optical zones of cornea, the MTF values measured at horizontal meridian were less than the corresponding values at vertical meridian at 10-60 spatial frequencies(cpd), and the difference was statistically significant in 25, 30, 35, 40, 45, 50 cpd (P<0.05).
MTF can be used to describe the imaging quality of optical systems at anterior corneal surface objectively in detail.
PMCID: PMC3359037  PMID: 22762049
modulation transfer function; optical quality; cornea; point spread function; optical transfer function; phase transfer function

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