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1.  Association between neutrophil-to-lymphocyte ratio and differentiated thyroid cancer: a meta-analysis 
Scientific Reports  2016;6:38551.
The association between neutrophil-to-lymphocyte ratio (NLR) and differentiated thyroid cancer (DTC) is undecided. To rectify this question, we conducted a systematic meta-analysis based on 7 prospective cohort studies published between 2013 and 2015, comprising 7349 patients. Six of these cohorts included pretreatment (baseline) NLR data for patients with thyroid nodules. The meta-analysis of these 6 cohorts showed that the NLR of patients with DTC (4617 cases) was statistically similar to patients with benign nodules only (1666 cases), with a mean difference (MD) of 0.19 (95% CI: −0.09 to 0.46; I2 = 93%; P < 0.001). No significant difference in NLR was found between patients with DTC and patients with benign nodules. Two studies addressed an association between NLR and papillary thyroid carcinoma in patients stratified by age <45 and ≥45 years (496 and 891 cases, respectively); the pooled MD was 0.09 (95% CI: −0.37 to 0.55; I2 = 92.2%, P < 0.001). An elevated NLR seems not a reliable indicator of progressing DTC in patients with goiters, and there was no difference in NLR between patients aged <45 years and those aged ≥45 years. Well-designed and large-scale investigations are warranted to understand the value of NLR in the prognosis of DTC.
doi:10.1038/srep38551
PMCID: PMC5150572  PMID: 27941815
2.  The known genetic loci for telomere length may be involved in the modification of telomeres length after birth 
Scientific Reports  2016;6:38729.
Telomere length varies considerably among individuals. It is highly heritable and decreases with ageing or ageing related diseases. Recently, genome-wide association studies (GWAS) have identified several genetic loci associated with telomere length in adults. However, it is unclear whether these loci represent the genetic basis of telomere length or determine the individual susceptibility to shortening during growth process. Using DNA extracted from peripheral and cord blood of 444 mother-newborn pairs from a Chinese population, we measured relative telomere length (RTL) and genotyped eight known telomere length related variants that were initially identified in populations of European descent. We observed the T allele of rs10936599 and the T allele of rs2736100 were norminally associated with shorter RTL (P = 0.041 and 0.046, respectively) in maternal samples. Furthermore, the Weighted genetic score (WGS) of eight variants was significantly associated with RTL in maternal samples (R2 = 0.012, P = 0.025). However, we didn’t detect any significant associations for any individual variant or the combined WGS with RTL in newborns. These findings didn’t support the hypothesis that telomere length related loci may affect telomere length at birth, and we suggested that these loci may play a role in telomere length modification during life course.
doi:10.1038/srep38729
PMCID: PMC5143977  PMID: 27929092
3.  Intron Lariat RNA Inhibits MicroRNA Biogenesis by Sequestering the Dicing Complex in Arabidopsis 
PLoS Genetics  2016;12(11):e1006422.
Lariat RNAs formed as by-products of splicing are quickly degraded by the RNA debranching enzyme 1 (DBR1), leading to their turnover. Null dbr1 mutants in both animals and plants are embryo lethal, but the mechanism underlying the lethality remains unclear. Here we characterized a weak mutant allele of DBR1 in Arabidopsis, dbr1-2, and showed that a global increase in lariat RNAs was unexpectedly accompanied by a genome-wide reduction in miRNA accumulation. The dbr1-2 mutation had no effects on expression of miRNA biogenesis genes or primary miRNAs (pri-miRNAs), but the association of pri-miRNAs with the DCL1/HYL1 dicing complex was impaired. Lariat RNAs were associated with the DCL1/HYL1 dicing complex in vivo and competitively inhibited the binding of HYL1 with pri-miRNA. Consistent with the impacts of lariat RNAs on miRNA biogenesis, over-expression of lariat RNAs reduced miRNA accumulation. Lariat RNAs localized in nuclear bodies, and partially co-localize with HYL1, and both DCL1 and HYL1 were mis-localized in dbr1-2. Together with our findings that nearly four hundred lariat RNAs exist in wild type plants and that these lariat RNAs also associate with the DCL1/HYL1 dicing complex in vivo, we thus propose that lariat RNAs, as decoys, inhibit miRNA processing, suggesting a hitherto unknown layer of regulation in miRNA biogenesis.
Author Summary
It is known that lariat RNAs formed during pre-mRNA splicing are debranched by DBR1 (RNA debranching enzyme 1). Loss of function of DBR1 causes embryo lethality in both animals and plants. In animals, some debranched lariat RNAs could be further processed into mirtron miRNAs, a class of nonconventional miRNAs that bypass the microprocessor for their biogenesis. However, no mirtron has been functionally validated in plants, and how the accumulation of lariat RNA in dbr1 results in embryo lethality remains unclear. Here, we show that DBR1 is necessary for the regulation of genome-wide miRNA biogenesis in plants. By investigating the correlation between lariat RNA accumulation and miRNA processing, we showed that the DBR1-mediated lariat RNA debranching process provides a safeguard role for the binding of the dicing complex with miRNA precursors. As both the DBR1-mediated lariat RNA debranching process and miRNA biogenesis are common features in higher eukaryotes, the finding that lariat RNAs sequester the dicing complex in plants may have a broad implications for the non-coding RNA field.
doi:10.1371/journal.pgen.1006422
PMCID: PMC5147768  PMID: 27870853
4.  One-Step Synthesis of Microporous Carbon Monoliths Derived from Biomass with High Nitrogen Doping Content for Highly Selective CO2 Capture 
Scientific Reports  2016;6:30049.
The one-step synthesis method of nitrogen doped microporous carbon monoliths derived from biomass with high-efficiency is developed using a novel ammonia (NH3)-assisted activation process, where NH3 serves as both activating agent and nitrogen source. Both pore forming and nitrogen doping simultaneously proceed during the process, obviously superior to conventional chemical activation. The as-prepared nitrogen-doped active carbons exhibit rich micropores with high surface area and high nitrogen content. Synergetic effects of its high surface area, microporous structure and high nitrogen content, especially rich nitrogen-containing groups for effective CO2 capture (i.e., phenyl amine and pyridine-nitrogen) lead to superior CO2/N2 selectivity up to 82, which is the highest among known nanoporous carbons. In addition, the resulting nitrogen-doped active carbons can be easily regenerated under mild conditions. Considering the outstanding CO2 capture performance, low production cost, simple synthesis procedure and easy scalability, the resulting nitrogen-doped microporous carbon monoliths are promising candidates for selective capture of CO2 in industrial applications.
doi:10.1038/srep30049
PMCID: PMC4973261  PMID: 27488268
5.  Clinical characteristics of fatigued Parkinson’s patients and the response to dopaminergic treatment 
Background
Fatigue, which is commonly observed in Parkinson’s disease (PD), can greatly reduce quality of life and is difficult to treat. We here aimed to investigate the prevalence and characteristics of fatigue among PD patients and to explore an effective strategy to treat PD fatigue.
Method
This was an observational cross-sectional study conducted in northeastern China. We examined fatigue in 222 PD patients from northeastern China using the Parkinson Fatigue Scale-16 (PFS-16). The disease severity, depression, sleep and cognitive functioning were assessed with the Hoehn & Yahr staging (H-Y stage), Unified Parkinson’s Disease Rating Scale (UPDRS), Hamilton Depression Scale (HAMD), Parkinson’s Disease Sleep Scale (PDSS) and Montreal Cognitive Assessment (MoCA) by interview.
Results
The frequency of fatigue in PD patients was 59.46 %. Fatigued patients had longer disease durations and greater disease severity than nonfatigued patients. Additionally, fatigued PD patients scored significantly higher for all motor symptoms, except for tremor, and had more serious depressive symptoms and sleep disturbances than nonfatigued PD patients did. The sleep disturbance severity was an independent factor for fatigue. Furthermore, 43.04 % of fatigued patients taking dopaminergic drugs had fatigue remission. Depression severity was identified as an independent factor for dopaminergic drug non-responsive fatigue.
Conclusions
PD patients with severe sleep disturbances tend to suffer from fatigue. Levodopa improved fatigue only in PD patients with mild depression or no depression, implying that dopaminergic medication is required, but not sufficient, for fatigue suppression in PD patients with moderate or severe depression. Thus, restoring serotonergic neurotransmission as a combination therapy may offer a better strategy for the treatment of fatigue in these patients.
doi:10.1186/s40035-016-0056-2
PMCID: PMC4863328  PMID: 27175281
Parkinson’s disease; Fatigue; Sleep disorder; Depression; Dopaminergic drugs
6.  Effect of hyperbaric oxygen on lipid peroxidation and visual development in neonatal rats with hypoxia-ischemia brain damage 
Biomedical Reports  2016;5(1):136-140.
The aim of the present study was to investigate the effect of hyperbaric oxygen (HBO) on lipid peroxidation and visual development in a neonatal rat model of hypoxic-ischemic brain damage (HIBD). The rat models of HIBD were established by delayed uterus dissection and were divided randomly into two groups (10 rats each): HIBD and HBO-treated HIBD (HIBD+HBO) group. Another 20 rats that underwent sham-surgery were also divided randomly into the HBO-treated and control groups. The rats that underwent HBO treatment received HBO (0.02 MPa, 1 h/day) 24 h after the surgery and this continued for 14 days. When rats were 4 weeks old, their flash visual evoked potentials (F-VEPs) were monitored and the ultrastructures of the hippocampus were observed under transmission electron microscope. The levels of superoxide dismutase (SOD) and malonyldialdehyde (MDA) in the brain tissue homogenate were detected by xanthine oxidase and the thiobarbituric acid colorimetric method. Compared with the control group, the ultrastructures of the pyramidal neurons in the hippocampal CA3 area were distorted, the latencies of F-VEPs were prolonged (P<0.01) and the SOD activities were lower while the MDA levels were higher (P<0.01) in the HIBD group. No significant differences in ultrastructure, the latency of F-VEPs or SOD/MDA levels were identified between the HBO-treated HIBD group and the normal control group (P>0.05). HBO enhances antioxidant capacity and reduces the ultrastructural damage induced by hypoxic-ischemia, which may improve synaptic reconstruction and alleviate immature brain damage to promote the habilitation of brain function.
doi:10.3892/br.2016.673
PMCID: PMC4906592  PMID: 27347417
hyperbaric oxygen; hypoxic-ischemic brain damage; lipid peroxidation; flash visual evoked potential; rat
7.  Serum IL-17 & eotaxin levels in asthmatic patients with allergic rhinitis 
Objective:
To investigate the serum levels of Interleukin (IL)-17 and eotaxin levels and the relationship between serum IL-17, eotaxin and pulmonary function in asthmatic patients with allergic rhinitis.
Methods:
Serum IL-17 and eotaxin levels in asthmatic patients with allergic rhinitis during attacking and remission and in healthy control subjects were measured using enzyme-linked immunosorbent assay (ELISA) kits. Then we studied the correlation between the serum IL-17, eotaxin levels and pulmonary function in patients.
Results:
Serum IL-17 and eotaxin levels were significantly elevated in patients during asthma attack and remission compared with healthy control subjects. These levels in patients during asthma attack were much higher than those during remission. Furthermore, serum IL-17 and eotaxin levels were negatively correlated with pulmonary function in asthmatic patients with allergic rhinitis, respectively.
Conclusion:
Our findings suggest that IL-17 and eotaxin are important factors in asthma with allergic rhinitis, and the correlation between serum IL-17, eotaxin and lung function possibly lead to improvements in the diagnosis and treatment of asthma with allergic rhinitis and related diseases.
doi:10.12669/pjms.323.9914
PMCID: PMC4928426  PMID: 27375717
IL-17; Eotaxin; Asthma; Allergic rhinitis
8.  The Natural Product Resveratrol Inhibits Yeast Cell Separation by Extensively Modulating the Transcriptional Landscape and Reprogramming the Intracellular Metabolome 
PLoS ONE  2016;11(3):e0150156.
An increasing number of studies have shown that the promising compound resveratrol treats multiple diseases, such as cancer and aging; however, the resveratrol mode-of-action (MoA) remains largely unknown. Here, by virtue of multiple omics approaches, we adopted fission yeast as a model system with the goal of dissecting the common MoA of the anti-proliferative activity of resveratrol. We found that the anti-proliferative activity of resveratrol is mainly due to its unique role of inhibiting the separation of sister cells, similar phenotype with the C2H2 zinc finger transcription factor Ace2 knock-out strain. Microarray analysis shown that resveratrol has extensive impact on the fission yeast transcription levels. Among the changed gene’s list, 40% of up-regulated genes are Core Environmental Stress Responses genes, and 57% of the down-regulated genes are periodically expressed. Moreover, resveratrol leverages the metabolome, which unbalances the intracellular pool sizes of several classes of amino acids, nucleosides, sugars and lipids, thus reflecting the remodulated metabolic networks. The complexity of the resveratrol MoA displayed in previous reports and our work demonstrates that multiple omics approaches must be applied together to obtain a complete picture of resveratrol’s anti-proliferative function.
doi:10.1371/journal.pone.0150156
PMCID: PMC4780762  PMID: 26950930
9.  High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma 
Oncology Letters  2016;11(3):2300-2304.
Ubiquitin-conjugating enzyme E2C (UBE2C) is a key regulator of cell cycle progression and is involved in the tumorigenesis of a variety of cancers. Previous studies have demonstrated that UBE2C is an important factor in the malignant progression of astrocytic tumors. However, the association between UBE2C expression and clinical prognosis of glioma patients has not been defined. In the present study, the expression of UBE2C in gliomas and non-cancerous brain tissues were detected by microarray and immunohistochemical analysis. The association between UBE2C expression and clinicopathological characteristics of the glioma patients was evaluated. The Kaplan-Meier method and multivariate Cox's proportional hazards model were used to analyze the survival time of the patients. The results demonstrated that the expression levels of UBE2C in anaplastic gliomas and glioblastoma (GBM) patients were significantly higher compared to low-grade gliomas, in microarray and immunohistochemistry analysis. A higher UBE2C expression was associated with a significantly decreased overall survival time in patients possessing anaplastic gliomas (P<0.01) and GBMs (P<0.05). Multivariate analysis of 80 GBM patients revealed that UBE2C expression was an independent prognostic factor. To the best of our knowledge, the present data suggest for the first time that UBE2C overexpression is strongly associated with an aggressive progression and poor outcome of malignant glioma. Therefore, UBE2C overexpression may be used as a predictor of poor prognosis in patients with malignant glioma.
doi:10.3892/ol.2016.4171
PMCID: PMC4774622  PMID: 26998166
ubiquitin-conjugating enzyme E2C; outcome; biomarker; anaplastic glioma; glioblastoma
10.  1,25-hydroxyvitamin D relieves colitis in rats via down-regulation of toll-like receptor 9 expression 
Croatian Medical Journal  2015;56(6):515-524.
Aim
To investigate the therapeutic and immunoregulatory effects of 1,25-dihydroxyvitamin D (1,25(OH)D3) on 2,4,6-trinitrobenzenesulfonic acid (TNBS) -induced colitis in rats.
Methods
Experimental colitis induced by enema administration of TNBS plus ethanol was treated with 5-aminosalicylic acid (5-ASA) and/or 1,25(OH)D3. Disease activity was measured using the disease activation index (DAI), colon macroscopic damage index (CMDI), histological colonic damage score, and myeloperoxidase (MPO) activity. The expression of toll-like receptor 9 (TLR9) in the colon was determined by reverse transcription-polymerase chain reaction and immunohistochemistry.
Results
Rats with TNBS-induced colitis had significantly elevated DAI, CMDI, histological colonic damage score, and MPO activity (all P < 0.001) compared to rats without colitis. Treatment with 5-ASA or 1,25(OH)D3 ameliorated colitis by lowering CMDI (P = 0.049, P = 0.040, respectively), histological colonic damage score (P = 0.010, P = 0.005, respectively), and MPO activity (P = 0.0003, P = 0.0013, respectively) compared with the TNBS group. Combined treatment with 5-ASA and 1,25(OH)D3 significantly decreased MPO activity (P = 0.003). 1,25(OH)D3 attenuated colitis without causing hypercalcemia or renal insufficiency. TNBS significantly increased the number of TLR9 positive cells compared to control (P < 0.010), while 5-ASA, 1,25(OH)D3, and combined treatment with 5-ASA and 1,25(OH)D3 significantly decreased it compared to TNBS group (all P < 0.010). In TNBS group a moderate correlation was observed between MPO activity and the number of TLR9-positive cells (r = 0.654, P < 0.001).
Conclusion
TLR9 expression correlates with the extent of inflammation in TNBS-induced colitis. 1,25(OH)D3 relieves this inflammation possibly by decreasing TLR9 expression.
doi:10.3325/cmj.2015.56.515
PMCID: PMC4707923  PMID: 26718757
11.  The Common Single-Nucleotide Polymorphism rs2681472 Is Associated With Early-Onset Preeclampsia in Northern Han Chinese Women 
Reproductive Sciences  2014;21(11):1423-1427.
Preeclampsia, characterized by hypertension and proteinuria, remains a leading cause of maternal morbidity and mortality. Recently, a genome-wide association study (GWAS) identified the single-nucleotide polymorphism, rs2681472, as a new hypertension susceptibility genetic variant. The purpose of this study was to evaluate the association between preeclampsia and rs268172 in a Northern Han Chinese population. We genotyped 1218 unrelated Northern Han Chinese women, including 515 patients with preeclampsia and 703 healthy controls. No significant differences were detected in the allele frequencies between patients and controls (P = .23). When patients were divided into early-onset and late-onset preeclampsia according to gestational age of disease onset, the allele frequencies significantly differed between controls and patients with early-onset preeclampsia (P = .02). Genotype frequencies also were significantly different between controls and patients early-onset preeclampsia when data were analyzed under additive (P = .03) and dominant (P = .009) models. We replicated this association in an independent Northern Han Chinese population and observed a significant difference in the allele frequencies between patients with early-onset preeclampsia and controls (P = .011). We report that rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women.
doi:10.1177/1933719114527354
PMCID: PMC4212332  PMID: 24642721
preeclampsia; genetics; ATP2B1; polymorphisms
12.  Evaluation of carotid artery elasticity changes in patients with cerebral small vessel disease 
Background: The purpose of this study is to evaluate the intima-media thickness (IMT) and arterial elasticity of the common carotid artery (CCA) in patients with cerebral small vessel disease (SVD) by applying radiofrequency (RF) ultrasound technology. Methods: Fifty SVD subjects (SVD group) and fifty-three matched controls (Control group) were enrolled in the study. Structural and functional changes in the common carotid arterial wall were investigated by quality intima-media thickness (QIMT) and quanlity arterial stiffness (QAS) with a Mylab Twice ultrasound instrument. The vessel related variables between these two groups were analyzed. Results: There was a significant higher value of CCA-IMT in SVD group than that in control group (P<0.01). Pulse wave velocity (PWV), stiffness coefficient (α) and stiffness index (β) were remarkably greater (P<0.01) while compliance coefficient (CC) decreased significantly (P<0.01) in the SVD group than control group. Furthermore, significant difference was found on IMT between left and right CCA in SVD (P<0.01) and control group (P<0.01) while no significant difference was found on CC, α, β and PWV between left and right CCA in SVD (P>0.05) and control group (P>0.05). Conclusions: Decreased arterial elasticity of the CCA in patients with SVD compared with normal subjects. Ultrasound RF technology can be used to non-invasively and quantitatively detect the change in the structure and function of the CCA in SVD subjects for evaluating preclinical atherosclerosis.
PMCID: PMC4694402  PMID: 26770502
Ultrasound; cerebral small vessel disease; common carotid artery; carotid distensibility
13.  Microbial synthesis of Pd/Fe3O4, Au/Fe3O4 and PdAu/Fe3O4 nanocomposites for catalytic reduction of nitroaromatic compounds 
Scientific Reports  2015;5:13515.
Magnetically recoverable noble metal nanoparticles are promising catalysts for chemical reactions. However, the chemical synthesis of these nanocatalysts generally causes environmental concern due to usage of toxic chemicals under extreme conditions. Here, Pd/Fe3O4, Au/Fe3O4 and PdAu/Fe3O4 nanocomposites are biosynthesized under ambient and physiological conditions by Shewanella oneidensis MR-1. Microbial cells firstly transform akaganeite into magnetite, which then serves as support for the further synthesis of Pd, Au and PdAu nanoparticles from respective precursor salts. Surface-bound cellular components and exopolysaccharides not only function as shape-directing agent to convert some Fe3O4 nanoparticles to nanorods, but also participate in the formation of PdAu alloy nanoparticles on magnetite. All these three kinds of magnetic nanocomposites can catalyze the reduction of 4-nitrophenol and some other nitroaromatic compounds by NaBH4. PdAu/Fe3O4 demonstrates higher catalytic activity than Pd/Fe3O4 and Au/Fe3O4. Moreover, the magnetic nanocomposites can be easily recovered through magnetic decantation after catalysis reaction. PdAu/Fe3O4 can be reused in at least eight successive cycles of 4-nitrophenol reduction. The biosynthesis approach presented here does not require harmful agents or rigorous conditions and thus provides facile and environmentally benign choice for the preparation of magnetic noble metal nanocatalysts.
doi:10.1038/srep13515
PMCID: PMC4550933  PMID: 26310728
14.  Temporal and Spatial Variation in the Abundance of Total and Pathogenic Vibrio parahaemolyticus in Shellfish in China 
PLoS ONE  2015;10(6):e0130302.
We investigated the abundance of total and pathogenic Vibrio parahaemolyticus in shellfish sampled from four provinces in China during May 2013 and March 2014 using the most probable number-polymerase chain reaction (MPN-PCR) method. Total V. parahaemolyticus was detected in 67.7% of 496 samples. A total of 38.1% and 10.1% of samples exceeded 1,000 MPN g-1 and 10,000 MPN g-1, respectively. V. parahaemolyticus densities followed a seasonal and geographical trend, with Guangxi and Sichuan shellfish possessing total V. parahaemolyticus levels that were 100-fold higher than those of the Liaoning and Shandong regions. Moreover, the levels of V. parahaemolyticus were at least 10-fold higher in the summer and autumn than in the cooler seasons. Pathogenic V. parahaemolyticus levels were generally lower than total V. parahaemolyticus levels by several log units and tended to be high in samples contaminated with high total V. parahaemolyticus levels. The aqua farms had a lower prevalence but higher abundance of total V. parahaemolyticus compared to retail markets. The catering markets showed the lowest levels of total V. parahaemolyticus, but 20.0% of samples exceeded 1,000 MPN g-1. The levels of both total and pathogenic V. parahaemolyticus in oysters were higher than in clams. The log-transformed abundance of V. parahaemolyticus was significantly correlated with both water temperature and air temperature but not water salinity. These results provide baseline contamination data of V. parahaemolyticus in shellfish in China, which can be applied to local risk assessments to prioritize risk control to key sectors and evaluate the effectiveness of future control measures.
doi:10.1371/journal.pone.0130302
PMCID: PMC4465338  PMID: 26061712
15.  Targeting hypoxia-inducible factor-2α enhances sorafenib antitumor activity via β-catenin/C-Myc-dependent pathways in hepatocellular carcinoma 
Oncology Letters  2015;10(2):778-784.
Sorafenib is a type of multikinase inhibitor that exhibits antiangiogenic and antiproliferative effects; in addition, sorafenib is a unique first-line drug recommended for the treatment of advanced hepatocellular carcinoma (HCC). However, the effectiveness of HCC treatment remains poor due to acquired drug resistance. It has been suggested that hypoxia, induced as a results of the antiangiogenic effects of sustained sorafenib treatment, may be an important factor in sorafenib resistance. The transcription factor hypoxia-inducible factor (HIF)-2α has been reported to be associated with cell proliferation under hypoxic conditions; therefore, it was hypothesized that hypoxia may enhance tumor cell proliferation via this mechanism. The present study aimed to evaluate whether the knock-down of HIF-2α was able to enhance the therapeutic efficacy of sorafenib in order to effectively treat HCC. The results demonstrated that hypoxia protected HCC cells against sorafenib; however, short hairpin RNA-HIF-2α transfection in combination with sorafenib treatment exhibited a significantly synergistic effect against HCC cell proliferation. In addition, HCC cells acquired increased β-catenin/C-Myc expression, which enhanced proliferation under hypoxic conditions; however, targeted knock-down of HIF-2α or C-Myc markedly decreased cell proliferation in HCC cells. In conclusion, the results of the present study indicated that the targeted knock-down of HIF-2α in combination with sorafenib may be a promising strategy for the treatment of HCC.
doi:10.3892/ol.2015.3315
PMCID: PMC4509096  PMID: 26622569
sorafenib; hepatocellular carcinoma; hypoxia-indicuble factor-2α; C-Myc; β-catenin
16.  Novel gemini cationic lipids with carbamate groups for gene delivery 
To obtain efficient non-viral vectors, a series of Gemini cationic lipids with carbamate linkers between headgroups and hydrophobic tails were synthesized. They have the hydrocarbon chains of 12, 14, 16 and 18 carbon atoms as tails, designated as G12, G14, G16 and G18, respectively. These Gemini cationic lipids were prepared into cationic liposomes for the study of the physicochemical properties and gene delivery. The DNA-bonding ability of these Gemini cationic liposomes was much better than their mono-head counterparts (designated as M12, M14, M16 and M18, respectively). In the same series of liposomes, bonding ability declined with an increase in tail length. They were tested for their gene-transferring capabilities in Hep-2 and A549 cells. They showed higher transfection efficiency than their mono-head counterparts and were comparable or superior in transfection efficiency and cytotoxicity to the commercial liposomes, DOTAP and Lipofectamine 2000. Our results convincingly demonstrate that the gene-transferring capabilities of these cationic lipids depended on hydrocarbon chain length. Gene transfection efficiency was maximal at a chain length of 14, as G14 can silence about 80 % of luciferase in A549 cells. Cell uptake results indicate that Gemini lipid delivery systems could be internalised by cells very efficiently. Thus, the Gemini cationic lipids could be used as synthetic non-viral gene delivery carriers for further study.
doi:10.1039/C3TB21506G
PMCID: PMC4100725  PMID: 25045521
17.  Influence of diabetes on cardiac resynchronization therapy in heart failure patients: a meta-analysis 
Background
Diabetes mellitus is an independent risk factor of increased morbidity and mortality in patients with heart failure. Cardiac resynchronization therapy (CRT), a pacemaker-based therapy for dyssynchronous heart failure, improves cardiac performance and quality of life, but its effect on mortality in patients with diabetes is uncertain.
Methods
We performed a meta-analysis of results from randomized controlled trials (RCTs) of the long-term outcome of cardiac resynchronization therapy for heart failure in diabetic and non-diabetic patients. Literature search of MEDLINE via Pubmed for reports of randomized controlled trials of Cardiac resynchronization for chronic symptomatic left-ventricular dysfunction in patients with and without diabetes mellitus, with death as the outcome. Relevant data were analyzed by use of a random-effects model. Reports published from 1994 to 2011 that described RCTs of CRT for treating chronic symptomatic left ventricular dysfunction in patients with and without diabetes, with all-cause mortality as an outcome.
Results
A total of 5 randomized controlled trials met the inclusion criteria, for 2,923 patients. The quality of studies was good to moderate. Cardiac resynchronization significantly reduced the mortality for heart failure patients with or without diabetes mellitus. Mortality was 24.3% for diabetic patients with heart failure and 20.4 % for non-diabetics (odds ratio 1.28, 95% confidence interval 1.06–1.55; P = 0.010).
Conclusions
Cardiac resynchronization therapy (CRT) may reduce mortality from progressive heart failure in patients with or without diabetes mellitus, but mortality may be higher for patients with than without diabetes after CRT for heart failure.
doi:10.1186/s12872-015-0018-0
PMCID: PMC4461910  PMID: 25880202
Cardiac resynchronization therapy; Diabetes mellitus; Heart failure; Outcome; All-cause mortality
18.  c-Jun N-terminal kinase 3 expression in the retina of ocular hypertension mice: a possible target to reduce ganglion cell apoptosis 
Neural Regeneration Research  2015;10(3):432-437.
Glaucoma, a type of optic neuropathy, is characterized by the loss of retinal ganglion cells. It remains controversial whether c-Jun N-terminal kinase (JNK) participates in the apoptosis of retinal ganglion cells in glaucoma. This study sought to explore a possible mechanism of action of JNK signaling pathway in glaucoma-induced retinal optic nerve damage. We established a mouse model of chronic ocular hypertension by reducing the aqueous humor followed by photocoagulation using the laser ignition method. Results showed significant pathological changes in the ocular tissues after the injury. Apoptosis of retinal ganglion cells increased with increased intraocular pressure, as did JNK3 mRNA expression in the retina. These data indicated that the increased expression of JNK3 mRNA was strongly associated with the increase in intraocular pressure in the retina, and correlated positively with the apoptosis of retinal ganglion cells.
doi:10.4103/1673-5374.153692
PMCID: PMC4396106  PMID: 25878592
nerve regeneration; ocular hypertension; JNK3; retinal ganglion cell; glaucoma; laser photocoagulation; intraocular pressure; neural regeneration
19.  Biomechanical comparison of three types of internal fixation in a type C zone II pelvic fracture model 
Objective: This study aimed to compare the stability of Tile C pelvic fractures fixed with two iliosacral (IS) screws, tension band plate (TBP), and minimally invasive adjustable plate (MIAP). Methods: Six embalmed specimens of adult pelvis were used. The soft tissue was removed from the specimens, but spines from the fourth lumbar vertebra to the proximal one-third of both femurs were retained. The pubic symphysis, bilateral sacroiliac joints and ligaments, bilateral hip joints, bilateral sacrotuberous ligaments, and bilateral sacrospinous ligaments were intact. Tile C pelvic fractures were created on the specimens. The symphysis pubis was fixed with a plate, and the fracture on the posterior pelvic ring was fixed with three types of internal fixation in a randomized block design. The specimens were placed in a biomechanical machine at a standing neutral posture. A cyclic vertical load of up to 500N was applied, and displacement was recorded. Shifts in the fracture gap were measured by a grating displacement sensor. Results: Under different vertical loads, the shift in the fracture gap and displacement of the pelvic fractures fixed with two IS screws were similar to those in fractures fixed with MIAP. However, the shift in the fracture gap and displacement of fractures fixed with MIAP was significantly smaller than those of fractures fixed with TBP. Conclusion: The stability of the Tile C pelvic fractures fixed with MIAP was similar to that of fractures fixed with IS screws. MIAP performed better than TBP under vertical load.
PMCID: PMC4402760  PMID: 25932113
Pelvis; biomechanics; unstable; internal fixation
20.  Therapeutic effects of minimally invasive adjustable and locking compression plate for unstable pelvic fractures via posterior approach 
Objective: Unstable pelvic fractures are clinically complex injuries. Selecting appropriate treatment remains a challenging problem for orthopedic physicians. The aim of this study is to compare the clinical effects of minimally invasive adjustable plate and locking compression plate in treatment of unstable pelvic fractures via posterior approach. Methods: From January 2009 to June 2012, fifty-six patients with unstable pelvic fractures were included. After at least 12-month follow-up, forty-four patients treated with two methods were enrolled in the study and divided into two groups: minimally invasive adjustable plate (group A) and locking compression plate (group B). Preoperative and postoperative radiography was taken to assess the fracture displacement and reduction quality. The size of incision, operation duration, blood loss, duration of X-ray exposures, Majeed postoperative functional evaluation and Lindahl postoperative reduction evaluation were analyzed. Results: The mean follow-up in group A was 27.3 months (range, 13-48 months), and that in group B was 21.8 months (range, 12-42 months). There were no iatrogenic neurovascular injuries during the operations in the two groups. In group B, malunion was observed in one patient, and infection of incision was observed in one case. The operation duration, blood loss, and size of incision of group A were significantly less than that of group B. There was no significant difference in the duration of X-ray exposures between the two groups. The Majeed functional evaluation score in group A was significantly higher than that in group B. The difference of the imaging score of the retained displacement was not statistically significant. Conclusions: Both the two methods can effectively stabilize the unstable pelvic fractures. However, the minimally invasive adjustable plate has the advantages of minimally invasive, less radiation exposure, technically safe and time saving. Minimally invasive adjustable plate is a good supplementary option for treating posterior pelvic ring injuries.
PMCID: PMC4358518  PMID: 25785063
Unstable pelvic fractures; fracture fixation; internal; minimally invasive reduction; posterior approach; minimally invasive adjustable plate
21.  Effects of transcutaneous electrical nerve stimulation on pain in patients with spinal cord injury: a randomized controlled trial 
[Purpose] To investigate the effects of transcutaneous electrical nerve stimulation (TENS) on pain in patients with spinal cord injury. [Subjects and Methods] Fifty-two spinal cord injury patients with central pain were randomly allocated into two groups TENS and control with 26 subjects per group. The patients in TENS and control groups were treated with TENS and sham TENS for 20 min (three times a week) for 12 consecutive weeks, respectively. The two group’s pain was assessed using visual analog scale (VAS) and the McGill Pain Questionnaire (including pain rating index-total, pain rating index-affective, pain rating index-sensory, present pain intensity, and number of words chosen) before and after the treatment. [Results] After the intervention, we found significant differences in VAS, pain rating index-total, pain rating index-affective, pain rating index-sensory, present pain intensity, and number of words chosen between the TENS group and the control group. [Conclusion] Our results suggest that TENS effectively decreases pain in patients with spinal cord injury.
doi:10.1589/jpts.27.23
PMCID: PMC4305569  PMID: 25642029
Transcutaneous electrical nerve stimulation; Pain; Spinal cord injury
22.  Seizure Control of Current Shunt on Rats with Temporal Lobe Epilepsy and Neocortical Epilepsy 
PLoS ONE  2014;9(1):e86477.
Purpose
To examine the effects of current shunt on rats with temporal lobe epilepsy and neocortex epilepsy.
Experimental Design
A kainic acid (KA)-induced model of temporal lobe seizure and a penicillin-induced model of neocortical partial seizure were used in this study. Rats of each model were randomly allocated into two groups: control and model groups. The model group was further divided into the KA or penicillin group, sham conduction group and conduction group. The current shunt was realized through the implantation of a customized conduction electrode. After surgery, electroencephalogram (EEG) was recorded for two hours for each rat under anesthesia. Subsequently, the rats were video monitored for 72 h to detect the occurrence of behavioral seizures upon awakening. The average number and duration of seizures on EEG and the number of behavioral seizures were measured.
Results
In KA model, the number of total EEG seizures in conduction group (9.57±2.46) was significantly less than that in sham conduction group (15.13±3.45) (p<0.01). The duration of EEG seizures in conduction group (26.13±7.81 s) was significantly shorter than that in sham conduction group (34.17±7.25 s) (p = 0.001). A significant reduction of behavioral seizures was observed in the conduction group compared with KA (p = 0.000) and sham conduction groups (p = 0.000). In penicillin model, there was a 61% reduction in total EEG seizures in conduction group compared with sham conduction group (p<0.01), and the duration of EEG seizures in conduction group (6.29±2.64 s) was significantly shorter than that in the sham conduction group (12.07±3.81 s) (p = 0.002). A significant reduction of behavioral seizures was observed in conduction group compared with penicillin (p<0.01) and sham conduction groups (p<0.01).
Conclusion
Current shunt effectively reduces the onset and severity of seizures. Current shunt therapy could be an effective alternative minimally invasive approach for temporal lobe epilepsy and neocortex epilepsy.
doi:10.1371/journal.pone.0086477
PMCID: PMC3907408  PMID: 24497949
23.  In-Situ Formation of Cobalt-Phosphate Oxygen-Evolving Complex-Anchored Reduced Graphene Oxide Nanosheets for Oxygen Reduction Reaction 
Scientific Reports  2013;3:2263.
Oxygen conversion process between O2 and H2O by means of electrochemistry or photochemistry has lately received a great deal of attention. Cobalt-phosphate (Co-Pi) catalyst is a new type of cost-effective artificial oxygen-evolving complex (OEC) with amorphous features during photosynthesis. However, can such Co-Pi OEC also act as oxygen reduction reaction (ORR) catalyst in electrochemical processes? The question remains unanswered. Here for the first time we demonstrate that Co-Pi OEC does be rather active for the ORR. Particularly, Co-Pi OEC anchoring on reduced graphite oxide (rGO) nanosheet is shown to possess dramatically improved electrocatalytic activities. Differing from the generally accepted role of rGO as an “electron reservoir”, we suggest that rGO serves as “peroxide cleaner” in enhancing the electrocatalytic behaviors. The present study may bridge the gap between photochemistry and electrochemistry towards oxygen conversion.
doi:10.1038/srep02263
PMCID: PMC3719074  PMID: 23877331
24.  HPV genotypes in paraffin sections of non-cervical squamous cell carcinoma in Qingdao of China 
Oncology Letters  2013;5(4):1219-1222.
Human papillomaviruses (HPVs) are the cause of cervical cancer and possibly a subset of squamous cell carcinomas (SCCs) in other sites. However, the prevalence and distribution of HPV subtypes remain unclear. In the present study, we collected and analyzed 511 paraffin sections of non-cervical SCC from patients in Qingdao, China, for the presence of HPV using polymerase chain reaction (PCR). We identified that 55.77% (285/511) of the samples were positive for HPV infection. There was a significant association between HPV type and the different sites of SCC. An association between HPV-positive cases and tobacco, alcohol, age and tumor differentiation was demonstrated. The information provided by this study may be important for further investigation into the association between HPV and SCC. High-risk HPV subtypes were associated with the malignant degree of SCC. This study provided a theoretical basis for the preventative treatment of non-cervical SCC using HPV vaccines.
doi:10.3892/ol.2013.1181
PMCID: PMC3629125  PMID: 23599766
squamous cell carcinomas; human papillomavirus genotype; polymerase chain reaction
25.  Association between paraoxonase gene and stroke in the Han Chinese population 
BMC Medical Genetics  2013;14:16.
Background
The human paraoxonase (PON) gene family has three isoforms: PON1, PON2 and PON3. These genes are implicated as potential risk factors of cerebrovascular disease and can prevent oxidative modification of low-density lipoproteins and atherosclerosis. This study evaluated the association between the genetic variants of all three PON genes and the risks of total stroke, ischemic stroke and hemorrhagic stroke in the Han Chinese population.
Methods
A total of 1016 subjects were recruited, including 508 healthy controls and 498 patients (328 with ischemic stroke and 170 with hemorrhagic stroke). A total of 11 single nucleotide polymorphisms (SNPs) covering the PON genes were genotyped for statistical analysis. Two of the 11 SNPs (rs662 and rs854560) were contextualized in a meta-analysis of ischemic stroke.
Results
The presence of rs705381 (−162) in the promoter region of PON1 was significantly associated with total stroke (Padjusted = 0.0007, OR = 0.57 [95% CI = 0.41-0.79]) and ischemic stroke (Padjusted = 0.0017, OR = 0.54 [95% CI = 0.37-0.79]) when analyzed using a dominant model, but was not associated with hemorrhagic stroke. There was also a nominal association between rs854571 (−824) and total stroke. Meta-analysis demonstrated a significant nominal association between rs662 and ischemic stroke, but there was no evidence of an association between rs662 and ischemic stroke risk in a single site association study.
Conclusions
These findings indicate that polymorphisms of PON1 gene may be a risk factor of stroke.
doi:10.1186/1471-2350-14-16
PMCID: PMC3562169  PMID: 23356507
Polymorphisms; Paraoxanase gene; Hemorrhagic stroke; Ischemic stroke; Association

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