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1.  A facile approach to synthesize stable CNTs@MnO electrocatalyst for high energy lithium oxygen batteries 
Scientific Reports  2015;5:8012.
A composite of manganese monoxide loaded onto carbon nanotubes (CNTs@MnO) has been synthesized by a facile approach, in which the CNTs form a continuous conductive network connecting the electrocatalyst MnO nanoparticles together to facilitate good electrochemical performance. The electrocatalyst MnO shows favourable rechargeability, and good phase and morphology stability in lithium oxygen batteries. Excellent cycling performance is also demonstrated, in which the terminal voltage is higher than 2.4 V after 100 cycles at 0.4 mA cm−2, with 1000 mAh g−1(composite) capacity. Therefore, this hybrid material is promising for use as a cathode material for lithium oxygen batteries.
PMCID: PMC4311244  PMID: 25634100
3.  Recurrent Syncope Attributed to Left Main Coronary Artery Severe Stenosis 
Case Reports in Medicine  2015;2015:782347.
Patients with acute coronary syndrome (ACS) rarely manifest as recurrent syncope due to malignant ventricular arrhythmia. We report a case of a 56-year-old Chinese male with complaints of paroxysmal chest burning sensation and distress for 2 weeks as well as loss of consciousness for 3 days. The electrocardiogram (ECG) revealed paroxysmal multimorphologic ventricular tachycardia during attack and normal heart rhythm during intervals. Coronary angiograph showed 90% stenosis in left main coronary artery and 80% stenosis in anterior descending artery. Two stents sized 4.0∗18 mm and 2.75∗18 mm were placed at left main coronary artery and anterior descending artery, respectively, during percutaneous coronary intervention (PCI). The patient was discharged and never had ventricular arrhythmia again during a 3-month follow-up since the PCI. This indicated that ventricular tachycardia was correlated with persistent severe myocardial ischemia. Coronary vasospasm was highly suspected to be the reason of the sudden attack and acute exacerbation. PCI is recommended in patients with both severe coronary artery stenosis and ventricular arrhythmia. Removing myocardial ischemia may stop or relieve ventricular arrhythmia and prevent cardiac arrest.
PMCID: PMC4312630
4.  Efficacy of Combined Vancomycin and Fosfomycin against Methicillin-Resistant Staphylococcus aureus in Biofilms In Vivo 
PLoS ONE  2014;9(12):e113133.
Infection by methicillin-resistant Staphylococcus aureus (MRSA) is a life-threatening condition, and formation of biofilms can lead to treatment failure in a clinical setting. The aim of this study was to demonstrate the in vivo bactericidal effects of a combination of vancomycin (VAN) and fosfomycin (FOS) against MRSA in a rat carboxymethyl cellulose-pouch biofilm model. The results of the time-kill assay showed that the combination therapy was capable of killing at low minimal inhibitory concentrations (MIC) (½× MIC VAN +1× MIC FOS and 1× MIC VAN + 1× MIC FOS). In the in vivo study, a synergistically bactericidal effect was observed when using the combination therapy on MRSA embedded in the mature biofilm model. In comparison with the untreated control group and the groups receiving either VAN or FOS alone, the rats treated with combination therapy had lower MRSA colony counts in exudates from the pouch, lower white blood cell and neutrophil counts, and C-reactive protein (CRP) in peripheral blood. Furthermore, histological analysis of the pouch wall indicated combination therapy resulted in disappearance of biofilm-like structures, marked decrease in necrosis, and formation of granular tissue. In conclusion, the combination of VAN with FOS had a synergistic bactericidal effect on chronic MRSA infection embedded in biofilm, providing an alternative approach to treating this condition.
PMCID: PMC4281042  PMID: 25551618
5.  Caspase-12 mediates carbon tetrachloride-induced hepatocyte apoptosis in mice 
World Journal of Gastroenterology : WJG  2014;20(48):18189-18198.
AIM: To investigate the role of caspase-12 and its downstream targets in carbon tetrachloride (CCl4)-induced hepatocyte apoptosis.
METHODS: The role of caspase-12 was determined by using caspase-12 knock-out (-/-) mice. CCl4 (300 μL/kg body weight) or vehicle (corn oil) was administered to caspase-12+/+ or caspase-12-/- mice as a single intraperitoneal injection. The animals were sacrificed 24 h after the CCl4 treatment. Blood was collected to evaluate liver function by the measurement of the activity of alanine aminotransferase. Liver samples were used for the measurements of reactive oxygen species using plasma malondialdehyde as biomarker, hepatocyte apoptosis was evaluated via terminal transferase-mediated dUTP nick-end labeling and controlled by morphologic study, and cytochrome C release and caspase activations were measured by Western blotting.
RESULTS: Administration of a low dose of CCl4 resulted in hepatocyte apoptosis and acute liver injury in wild-type mice. CCl4 also induced the generation of reactive oxygen species and induction of endoplasmic reticulum stress in the liver followed by activations of caspase-12, -9 and -3 as well as release of small amounts of cytochrome C. However, in the CCl4-treated caspase-12-/- mice, activation of caspase-9 and -3 were significantly attenuated (P < 0.05); no effect was seen in cytochrome C release. CCl4-induced apoptosis and liver damage was markedly reduced in caspase-12-/- mice compared to caspase-12+/+ mice (P < 0.05). The active form of caspase-8 was not detected in either caspase-12+/+ or caspase-12-/- mice. There was no significant different in the formation of reactive oxygen species in the livers of caspase-12+/+ and caspase-12-/- mice treated with CCl4.
CONCLUSION: Caspase-12 plays a pivotal role in CCl4-induced hepatic apoptosis through the activation of the downstream effector caspase-3 directly and/or indirectly via capase-9 activation.
PMCID: PMC4277956  PMID: 25561786
Apoptosis; Carbon tetrachloride; Caspases; Endoplasmic reticulum; Hepatocyte; Reactive oxygen species
6.  Transcriptome Profiles of the Protoscoleces of Echinococcus granulosus Reveal that Excretory-Secretory Products Are Essential to Metabolic Adaptation 
Cystic hydatid disease (CHD) is caused by the larval stages of the cestode and affects humans and domestic animals worldwide. Protoscoleces (PSCs) are one component of the larval stages that can interact with both definitive and intermediate hosts. Previous genomic and transcriptomic data have provided an overall snapshot of the genomics of the growth and development of this parasite. However, our understanding of how PSCs subvert the immune response of hosts and maintains metabolic adaptation remains unclear. In this study, we used Roche 454 sequencing technology and in silico secretome analysis to explore the transcriptome profiles of the PSCs from E. granulosus and elucidate the potential functions of the excretory-secretory proteins (ESPs) released by the parasite.
Methodology/Principal Findings
A large number of nonredundant sequences as unigenes were generated (26,514), of which 22,910 (86.4%) were mapped to the newly published E. granulosus genome and 17,705 (66.8%) were distributed within the coding sequence (CDS) regions. Of the 2,280 ESPs predicted from the transcriptome, 138 ESPs were inferred to be involved in the metabolism of carbohydrates, while 124 ESPs were inferred to be involved in the metabolism of protein. Eleven ESPs were identified as intracellular enzymes that regulate glycolysis/gluconeogenesis (GL/GN) pathways, while a further 44 antigenic proteins, 25 molecular chaperones and four proteases were highly represented. Many proteins were also found to be significantly enriched in development-related signaling pathways, such as the TGF-β receptor pathways and insulin pathways.
This study provides valuable information on the metabolic adaptation of parasites to their hosts that can be used to aid the development of novel intervention targets for hydatid treatment and control.
Author Summary
The successful infection establishment of parasites depends on their ability to combat their host's immune system while maintaining metabolic adaptation to their hosts. The mechanisms of these processes are not well understood. We used the protoscoleces (PSCs) of E. granulosus as a model system to study this complex host-parasite interaction by investigating the role of excretory-secretory proteins (ESPs) in the physiological adaptation of the parasite. Using Roche 454 sequencing technology and in silico secretome analysis, we predicted 2280 ESPs and analyzed their biological functions. Our analysis of the bioinformatic data suggested that ESPs are integral to the metabolism of carbohydrates and proteins within the parasite and/or hosts. We also found that ESPs are involved in mediating the immune responses of hosts and function within key development-related signaling pathways. We found 11 intracellular enzymes, 25 molecular chaperones and four proteases that were highly represented in the ESPs, in addition to 44 antigenic proteins that showed promise as candidates for vaccine or serodiagnostic development purposes. These findings provide valuable information on the mechanisms of metabolic adaptation in parasites that will aid the development of novel hydatid treatment and control targets.
PMCID: PMC4263413  PMID: 25500817
7.  Classifying human operator functional state based on electrophysiological and performance measures and fuzzy clustering method 
Cognitive Neurodynamics  2013;7(6):477-494.
The human operator’s ability to perform their tasks can fluctuate over time. Because the cognitive demands of the task can also vary it is possible that the capabilities of the operator are not sufficient to satisfy the job demands. This can lead to serious errors when the operator is overwhelmed by the task demands. Psychophysiological measures, such as heart rate and brain activity, can be used to monitor operator cognitive workload. In this paper, the most influential psychophysiological measures are extracted to characterize Operator Functional State (OFS) in automated tasks under a complex form of human–automation interaction. The fuzzy c-mean (FCM) algorithm is used and tested for its OFS classification performance. The results obtained have shown the feasibility and effectiveness of the FCM algorithm as well as the utility of the selected input features for OFS classification. Besides being able to cope with nonlinearity and fuzzy uncertainty in the psychophysiological data it can provide information about the relative importance of the input features as well as the confidence estimate of the classification results. The OFS pattern classification method developed can be incorporated into an adaptive aiding system in order to enhance the overall performance of a large class of safety–critical human–machine cooperative systems.
PMCID: PMC3825145  PMID: 24427221
Operator functional state; Fuzzy c-means algorithm; Psychophysiological measures; Feature extraction; Pattern classification
8.  High Prevalence of Enterocytozoon bieneusi in Asymptomatic Pigs and Assessment of Zoonotic Risk at the Genotype Level 
Applied and Environmental Microbiology  2014;80(12):3699-3707.
Enterocytozoon bieneusi is an emerging and clinically significant enteric parasite infecting humans and animals and can cause life-threatening diarrhea in immunocompromised people. Pigs are considered to be one of the main reservoir hosts of E. bieneusi based on their high prevalence rates and zoonotic genotypes in pigs. As an opportunistic pathogen, E. bieneusi infection of pigs can be inapparent, which leads to neglect in detecting this parasite in pigs and assessing the epidemiological role of pigs in the transmission of human microsporidiosis. In the present study, 95 healthy pigs aged 2 or 3 months were randomly selected from three areas in Heilongjiang Province, China. E. bieneusi isolates were identified and genotyped based on the small-subunit (SSU) rRNA and internal transcribed spacer (ITS) regions of the rRNA gene by PCR and sequencing. A high prevalence of E. bieneusi was observed, 83.2% (79/95) at the SSU rRNA locus versus 89.5% (85/95) at the ITS locus. Ten ITS genotypes were obtained, comprising six known genotypes—EbpA (n = 30), D (n = 19), H (n = 18), O (n = 11), CS-1 (n = 1), and LW1 (n = 1)—and four novel genotypes named HLJ-I to HLJ-IV; 70.6% (60/85) of E. bieneusi genotypes were zoonotic (genotypes EbpA, D, and O). The findings of a high prevalence of E. bieneusi in pigs and a large percentage of zoonotic genotypes indicate that pigs may play a role in the transmission of E. bieneusi to humans and may become an important source of water contamination in our investigated areas.
PMCID: PMC4054152  PMID: 24727270
9.  Orphan nuclear receptor Nur77 Inhibits Oxidized LDL-induced differentiation of RAW264.7 murine macrophage cell line into dendritic like cells 
BMC Immunology  2014;15(1):54.
Nur77 is an orphan nuclear receptor expressed in human atheroma. In vascular cells in vitro, Nur77 expression is induced by pro-inflammatory factors, such as oxidized LDL (oxLDL).
We analyze the role of Nur77 in the oxLDL-induced differentiation of macrophages into dendritic cells (DC). The murine RAW264.7 macrophage cell line was stably transfected with expression plasmids encoding either GFP or GFP fusions with either full-length Nur77 (GFP-Nur77), Nur77 lacking the DNA binding domain (GFP-Nur77-ΔDBD) or Nur77 lacking the transactivation domain (GFP-Nur77-ΔTAD).
GFP-Nur77 overexpression significantly suppressed the effect of oxLDL treatment on DC morphologic changes, expression of DC maturation markers, endocytic activity, allogeneic activation of T cell proliferation, and the activity and secretion of pro-inflammatory cytokines. Analysis of GFP-Nur77-ΔTAD and GFP-Nur77-ΔDBD indicated that the Nur77 DNA binding and transactivation domains were both required for this effect. GFP-Nur77-ΔDBD consistently had the opposite effect to GFP-Nur77, increasing DC-type differentiation in all assays. Interestingly, GFP-Nur77-ΔDBD protein was cytosolic, whereas GFP-Nur77 and GFP-Nur77-ΔTAD were both nuclear.
These data show that GFP-Nur77 inhibited differentiation of oxLDL-treated macrophages into DC. The effects of Nur77 on the macrophage phenotype may involve changes in its subcellular distribution.
Electronic supplementary material
The online version of this article (doi:10.1186/s12865-014-0054-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4274730  PMID: 25471687
Nuclear receptor; Nur77; Oxidized LDL; Macrophage; Dendritic cell
10.  Identification and verification of Hsp90-beta as a potential serum biomarker for lung cancer 
Background: Hsp90-beta was investigated as prognostic factor because of its apparent association with tumorigenesis. The aim of this study was to investigate the expression of Hsp90-beta in lung cancer patients, to analyze the relationship with respect to the clinicopathological features and to assess whether Hsp90-beta as a potential serum marker for lung cancer. Methods: Expression of Hsp90-beta was examined using immunohistochemistry, in-situ hybridization, western blot and enzyme-linked immunosorbent assay. Sensitivities and specificities for Hsp90-beta serum test were determined using receiver operator characteristic curve and cutoff was defined based on 95% and 85% sensitivities. Results: Lung cancer tissues exhibited higher expression of Hsp90-beta than the normal tissues (P < 0.05) and the serum Hsp90-beta of lung cancer patients also exhibited higher level than control groups (P < 0.05). Moreover, increased serum Hsp90-beta was significantly associated with the pathological grade and clinical stage of lung cancer patients (P < 0.05). Using receiver operator characteristic curve analysis, the cutoffs for distinguishing lung cancer from normal and benign groups were 1.155 and 1.158 ng/ml respectively. The sensitivities of Hsp90-beta for distinguishing lung cancer from normal and benign groups were 98.77% and 95.9%, and specificities were 88.33% and 72.7%. Conclusion: Up-regulation of serum Hsp90-beta was associated with pathological grade and clinical stage of lung cancer patients, which indicated that it could be considered molecular biomarker for diagnosis and prognosis of lung cancer.
PMCID: PMC4266719  PMID: 25520875
Lung cancer; serum; Hsp90-beta; biomarker; diagnosis
11.  In-situ One-step Hydrothermal Synthesis of a Lead Germanate-Graphene Composite as a Novel Anode Material for Lithium-Ion Batteries 
Scientific Reports  2014;4:7030.
Lead germanate-graphene nanosheets (PbGeO3-GNS) composites have been prepared by an efficient one-step, in-situ hydrothermal method and were used as anode materials for Li-ion batteries (LIBs). The PbGeO3 nanowires, around 100–200 nm in diameter, are highly encapsulated in a graphene matrix. The lithiation and de-lithiation reaction mechanisms of the PbGeO3 anode during the charge-discharge processes have been investigated by X-ray diffraction and electrochemical characterization. Compared with pure PbGeO3 anode, dramatic improvements in the electrochemical performance of the composite anodes have been obtained. In the voltage window of 0.01–1.50 V, the composite anode with 20 wt.% GNS delivers a discharge capacity of 607 mAh g−1 at 100 mA g−1 after 50 cycles. Even at a high current density of 1600 mA g−1, a capacity of 406 mAh g−1 can be achieved. Therefore, the PbGeO3-GNS composite can be considered as a potential anode material for lithium ion batteries.
PMCID: PMC4229670  PMID: 25391220
12.  Mental Practice Combined with Physical Practice to Enhance Hand Recovery in Stroke Patients 
Behavioural Neurology  2014;2014:876416.
Objectives. To evaluate whether combining mental practice with physical practice training enhances hand function in patients with stroke. Methods. 10 for treatment and 10 for control were recruited for this pre/posttraining matched case control study. In the treatment group, subjects underwent combining mental practice with physical practice for four weeks. In the control group, subjects only participated in physical practice. Change of hand function and the number of activated voxels of the contralateral somatosensory motor cortex (SMC) acquired by functional magnetic resonance imaging were measured. Results. After training, the Action Research Arm Test score increased by 12.65 for treatment and by 5.20 for control. There was a significant difference in the Action Research Arm Test score between the two groups (P = 0.04). The activated voxels number of the contralateral SMC increased in both groups, but the activated voxels number in the contralateral SMC and the improvement of hand function for treatment were greater than for control. In the treatment group, the number of activated voxels of the contralateral SMC was positively correlated with better hand function scores. Conclusions. Combining mental practice with physical practice may be a more effective treatment strategy than physical training alone for hand recovery in stroke patients.
PMCID: PMC4241695  PMID: 25435713
13.  Safety of fast-track rehabilitation after gastrointestinal surgery: Systematic review and meta-analysis 
World Journal of Gastroenterology : WJG  2014;20(41):15423-15439.
AIM: To compare the safety of fast-track rehabilitation protocols (FT) and conventional care strategies (CC), or FT and laparoscopic surgery (LFT) and FT and open surgery (OFT) after gastrointestinal surgery.
METHODS: We searched MEDLINE, WHO International Trial Register, Embase and The Cochrane Central Register of Controlled Trials up to 2014 for randomized controlled trials (RCTs) comparing FT and CC or comparing LFT and OFT, with 10 or more randomized participants and about 30 d follow-up. Two reviewers independently extracted data on complications, anastomotic leak, obstruction, wound infection, re-admission between FT and CC or LFT and OFT after gastrointestinal surgery.
RESULTS: Twenty-four RCTs of FT vs CC or LFT vs OFT were included. Compared with CC, FT reduced overall complications and wound infection. However, anastomotic leak, obstruction and re-admission were not significantly reduced. The pooled risk ratio (RR) of 0.69 (95%CI: 0.60-0.78; P < 0.001), pooled RR of 0.71 (95%CI: 0.57-0.88; P < 0.001), pooled RR of 0.93 (95%CI: 0.68-1.25; P > 0.05), a pooled RR of 0.87 (95%CI: 0.67-1.15; P > 0.05) and pooled RR of 0.94 (95%CI: 0.73-1.22; P > 0.05) respectively. Compared with OFT, LFT reduced complications, with a pooled RR of 0.66 (95%CI: 0.54-0.81; P < 0.001).
CONCLUSION: FTs are safe after gastrointestinal surgery. Additional large, prospective RCTs should be conducted to establish further the safety of this approach.
PMCID: PMC4223277  PMID: 25386092
Fast-track rehabilitation protocols; Laparoscopic surgery; Open surgery; Enhanced recovery; Gastrointestinal surgery; Complications; Readmission; Anastomotic leak; Wound infection; Obstruction
14.  Cryptosporidium andersoni as a novel predominant Cryptosporidium species in outpatients with diarrhea in Jiangsu Province, China 
BMC Infectious Diseases  2014;14(1):555.
Cryptosporidium hominis and C. parvum are usually considered to be the major pathogens responsible for human cryptosporidiosis. However, there have been few studies regarding the molecular epidemiology of Cryptosporidium in human infections in China. Here we investigated Cryptosporidium infection in patients with diarrhea, in Danyang Hospital of Jiangsu Province, China, at the genotype level.
A total of 232 stool specimens were collected from outpatients with diarrhea in Danyang Hospital of Jiangsu Province, China, from February 2012 to January 2013. Each specimen was stained from direct fecal smears and examined for Cryptosporidium using modified acid fast staining and microscopy. Moreover, genomic DNA of each fecal sample was screened for the presence of Cryptosporidium with nested PCR, which was genotyped by analyzing the DNA sequences of small subunit rRNA (SSU rRNA).
The average infection rate of Cryptosporidium was 1.3% (3/232) by microscopy and subjected to PCR amplification of the SSU rRNA gene of Cryptosporidium, with 9.91% (23/232) being positive for Cryptosporidium with a significant peak in autumn. Based on the SSU rRNA gene, two Cryptosporidium spp. were identified, including C. andersoni (n =21) and C. hominis (n =2). Two types of C. andersoni, designated as A370+ and A370- , were found in the SSU rRNA gene in our present study, which was 100% homologous to C. andersoni infections derived from dairy calves and goats, respectively. The clinical questionnaires showed no significant difference in age, gender and frequency of diarrhea, but duration of diarrhea was shorter for C. andersoni than that of C. hominis (mean, 2 vs. 4 days; p <0.01).
C. andersoni is the dominant species in Danyang City of Jiangsu Province. The fact that SSU rRNA sequences of C. andersoni obtained from human stools exhibited 100% homologous to those derived from dairy calves and goats supported that C. andersoni infection might be attributable to animal origin. The difference in the duration of diarrhea of C. andersoni and C. hominis indicated that different Cryptosporidium species might cause different clinical manifestations.
PMCID: PMC4225042  PMID: 25344387
Cryptosporidium andersoni; Diarrhea; Stool specimens; Predominant species; Prevalence
15.  Genetic Characterization of Human-Derived Hydatid Cysts of Echinococcus granulosus Sensu Lato in Heilongjiang Province and the First Report of G7 Genotype of E. canadensis in Humans in China 
PLoS ONE  2014;9(10):e109059.
Cystic echinococcosis (CE) caused by the larval stage of Echinococcus granulosus sensu lato (s.l.) is one of the most important zoonotic parasitic diseases worldwide and 10 genotypes (G1–G10) have been reported. In China, almost all the epidemiological and genotyping studies of E. granulosus s.l. are from the west and northwest pasturing areas. However, in Heilongjiang Province of northeastern China, no molecular information is available on E. granulosus s.l. To understand and to speculate on possible transmission patterns of E. granulosus s.l., we molecularly identified and genotyped 10 hydatid cysts from hepatic CE patients in Heilongjiang Province based on mitochondrial cytochrome c oxidase subunit I (cox1), cytochrome b (cytb) and NADH dehydrogenase subunit 1 (nad1) genes. Two genotypes were identified, G1 genotype (n = 6) and G7 genotype (n = 4). All the six G1 genotype isolates were identical to each other at the cox1 locus; three and two different sequences were obtained at the cytb and nad1 loci, respectively, with two cytb gene sequences not being described previously. G7 genotype isolates were identical to each other at the cox1, cytb and nad1 loci; however, the cytb gene sequence was not described previously. This is the first report of G7 genotype in humans in China. Three new cytb gene sequences from G1 and G7 genotypes might reflect endemic genetic characterizations. Pigs might be the main intermediate hosts of G7 genotype in our investigated area by homology analysis. The results will aid in making more effective control strategies for the prevention of transmission of E. granulosus s.l.
PMCID: PMC4199617  PMID: 25329820
16.  Elevated serum annexin A1 as potential diagnostic marker for lung cancer: a retrospective case-control study 
Background: Annexin A1 was investigated as prognostic factor because of its apparent association with tumorigenesis. The aim of this study was to investigate the expression of annexin A1 in lung cancer patients, and analysed the relationship with respect to the clinico-pathological features and assessed whether annexin A1 as a potential serum marker for lung cancer. Methods: Expression of annexin A1 was examined using immunohistochemistry, in-situ hybridization, western blot and enzyme-linked immunosorbent assay. Sensitivities and specificities for annexin A1 serum test were determined using receiver operator characteristic curve and cutoff was defined based on 95% and 85% sensitivities. Results: Lung cancer tissues exhibited higher expression of annexin A1 than the normal tissues (P < 0.05) and the serum annexin A1 of lung cancer patients also exhibited higher level than control groups (P < 0.05). Moreover, increased serum annexin A1 was significantly associated with the pathological grade and clinical stage of lung cancer patients (P < 0.05). Using receiver operator characteristic curve analysis, the cutoffs for distinguishing lung cancer from normal and benign groups were 4.77 and 4.84 ng/ml respectively. The sensitivities of annexin A1 for distinguishing lung cancer from normal and benign groups were 98.9% and 97.4%, and specificities were 88.3% and 66.4%. Conclusions: Up-regulation of serum annexin A1 was associated with pathological grade and clinical stage of lung cancer patients, which indicated that it could be considered molecular biomarker for diagnosis and prognosis of lung cancer.
PMCID: PMC4212930  PMID: 25360220
Lung cancer; serum; annexin A1; biomarker; diagnosis
17.  Focus on China: should clinicians engage in research? and lessons from other countries 
Following tremendous economic progress, society in China is also undergoing fundamental changes, as is the healthcare system. Currently the training of Chinese young doctors and their future work placement are all undergoing re-structuring. We compiled some thoughts and opinions on the topic of ‘should clinicians in China engage in research?’, and publish them as a special report in this issue of Quantitative Imaging in Medicine and Surgery (QIMS). The contributors included some editorial members of this journal, and a few personal friends. Besides a few minor linguistic corrections, opinions from the contributors have not been edited, as we want authors’ to write their own independent views. However, it is possible there is a selection bias of the contributors of this paper; more likely those who are interested in the medical research are selected and therefore the views of the contributors may not be generalizable. To compare the structure and funding of China with other countries, authors from UK, The Netherlands, France, and USA are also invited.
PMCID: PMC4213419  PMID: 25392826
China; Chinese; doctors; medical research; medical training; research funding
18.  A Statistical Parametric Mapping Toolbox Used for Voxel-Wise Analysis of FDG-PET Images of Rat Brain 
PLoS ONE  2014;9(9):e108295.
PET (positron emission tomography) imaging researches of functional metabolism using fluorodeoxyglucose (18F-FDG) of animal brain are important in neuroscience studies. FDG-PET imaging studies are often performed on groups of rats, so it is desirable to establish an objective voxel-based statistical methodology for group data analysis.
Material and Methods
This study establishes a statistical parametric mapping (SPM) toolbox (plug-ins) named spmratIHEP for voxel-wise analysis of FDG-PET images of rat brain, in which an FDG-PET template and an intracranial mask image of rat brain in Paxinos & Watson space were constructed, and the default settings were modified according to features of rat brain. Compared to previous studies, our constructed rat brain template comprises not only the cerebrum and cerebellum, but also the whole olfactory bulb which made the later cognitive studies much more exhaustive. And with an intracranial mask image in the template space, the brain tissues of individuals could be extracted automatically. Moreover, an atlas space is used for anatomically labeling the functional findings in the Paxinos & Watson space. In order to standardize the template image with the atlas accurately, a synthetic FDG-PET image with six main anatomy structures is constructed from the atlas, which performs as a target image in the co-registration.
The spatial normalization procedure is evaluated, by which the individual rat brain images could be standardized into the Paxinos & Watson space successfully and the intracranial tissues could also be extracted accurately. The practical usability of this toolbox is evaluated using FDG-PET functional images from rats with left side middle cerebral artery occlusion (MCAO) in comparison to normal control rats. And the two-sample t-test statistical result is almost related to the left side MCA.
We established a toolbox of SPM8 named spmratIHEP for voxel-wise analysis of FDG-PET images of rat brain.
PMCID: PMC4178133  PMID: 25259529
19.  Low-magnitude high-frequency loading, by whole-body vibration, accelerates early implant osseointegration in ovariectomized rats 
Molecular Medicine Reports  2014;10(6):2835-2842.
Osteoporosis deteriorates jaw bone quality and may compromise early implant osseointegration and early implant loading. The influence of low-magnitude, high-frequency (LMHF) vibration on peri-implant bone healing and implant integration in osteoporotic bones remains poorly understood. LMHF loading via whole-body vibration (WBV) for 8 weeks has previously been demonstrated to significantly enhance bone-to-implant contact, peri-implant bone fraction and implant mechanical properties in osteoporotic rats. In the present study, LMHF loading by WBV was performed in osteoporotic rats, with a loading duration of 4 weeks during the early stages of bone healing. The results indicated that 4-week LMHF loading by WBV partly reversed the negative effects of osteoporosis and accelerated early peri-implant osseointegration in ovariectomized rats.
PMCID: PMC4227418  PMID: 25270245
low-magnitude high-frequency loading; whole-body vibration; osteoporosis; dental implants; osseointegration; rat
20.  Efficient Isolation of Bone Marrow Adipocyte Progenitors by Silica Microbeads Incubation 
Stem Cells and Development  2013;22(18):2520-2531.
Excessive bone marrow adipocytes (BMAs) formation is tightly associated with development of osteoporosis. Considering the high heterogeneity of bone marrow stromal cells (BMSCs), identification of bone marrow adipocyte progenitors (BMAPs) within heterogeneous BMSCs may provide better cellular models for research regarding osteoporosis development and therapy. However, currently there is no efficient method or specific surface makers that are available for BMAPs isolation. In the current study, we developed a novel BMAPs isolation method based on silica microbeads incubation and subsequent centrifugation in ficoll-paque. The “Sca-1+CD73−CD90−CD105+” subpopulation selected by this method exhibited significantly stronger adipogenic potential than nonselected BMSCs in vitro and could homogeneously differentiate into mature adipocytes within 4 days. Moreover, these cells also highly expressed a series of adipogenesis-related genes even before differentiation. After long-term culture, however, BMAPs would gradually lose high adipogenic ability, but sorting CD105+ cells from BMAPs in later passages was able to retrieve the highly adipogenic subpopulation. In conclusion, this study demonstrated that BMAPs subpopulation could be effectively isolated from heterogeneous BMSCs by a special silica microbeads incubation method and re-enriched by sorting CD105+ cells. These findings offer convenient and repeatable approaches to obtain pure BMAPs for research regarding pathogenic mechanisms and therapeutics development of osteoporosis.
PMCID: PMC3760029  PMID: 23806125
21.  Relation of JAGGED 1 and collagen type 1 alpha 1 polymorphisms with bone mineral density in Chinese postmenopausal women 
Osteoporosis is a complex disease characterized by low bone mineral density (BMD), which is determined by an interaction of genetics and environmental factors. Collagen type alpha 1 (COL1A) and JAGGED (JAG1) genes have been implicated in relation to BMD. The aim of this study was to investigate possible association among BMD and rs2273061 of JAG1, rs1107946 and rs1800012 of Col1A1 polymorphisms, as well as their haplotypes with BMD in postmenopausal Chinese women. A structured questionnaire for risk factors was recorded and BMD in lumbar spine and total hip was measured by dual-energy X-ray absorptiomety. Genomic DNA was obtained from 367 postmenopausal Chinese women. Genomic DNA was extracted from EDTA-preserved peripheral venous blood by phenol-chloroform extraction method and analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). As a result, the rs1800012 polymorphism of COL1A1 showed an association with BMD of the lumbar spine under a dominant model. Besides, haplotype analysis of COL1A1 gene showed that G-G haplotype presented higher BMD in lumbar spine. No significant association between genotypes and alleles distributions of the rs1107946 polymorphism of COL1A1 and rs2273061 polymorphism of the JAG1 was found. In conclusion, our results suggest that the rs1800012 polymorphism of the COL1A1 and one haplotype were significantly associated with lumbar spine BMD variations in Chinese postmenopausal women.
PMCID: PMC4230153  PMID: 25400810
Bone mineral density; polymorphism; JAG1; COL1A1; haplotypes; Chinese postmenopausal women
22.  The Prognostic Value of Serum Neuron-Specific Enolase in Traumatic Brain Injury: Systematic Review and Meta-Analysis 
PLoS ONE  2014;9(9):e106680.
Several studies have suggested that neuron-specific enolase (NSE) in serum may be a biomarker of traumatic brain injury. However, whether serum NSE levels correlate with outcomes remains unclear. The purpose of this review was to evaluate the prognostic value of serum NSE protein after traumatic brain injury.
PubMed and Embase were searched for relevant studies published up to October 2013. Full-text publications on the relationship of NSE to TBI were included if the studies concerned patients with closed head injury, NSE levels in serum after injury, and Glasgow Outcome Scale (GOS) or Extended GOS (GOSE) scores or mortality. Study design, inclusion criteria, assay, blood sample collection time, NSE cutoff, sensitivity and specificity of NSE for mortality prediction (if sufficient information was provided to calculate these values), and main outcomes were recorded.
Sixteen studies were eligible for the current meta-analysis. In the six studies comparing NSE concentrations between TBI patients who died and those who survived, NSE concentrations correlated with mortality (M.D. 0.28, 95% confidence interval (CI), 0.21 to 0.34; I2 55%). In the eight studies evaluating GOS or GOSE, patients with unfavorable outcomes had significantly higher NSE concentrations than those with favorable outcomes (M.D. 0.24, 95% CI, 0.17 to 0.31; I2 64%). From the studies providing sufficient data, the pooled sensitivity and specificity for mortality were 0.79 and 0.50, and 0.72 and 0.66 for unfavorable neurological prognosis, respectively. The areas under the SROC curve (AUC) of NSE concentrations were 0.73 (95% CI, 0.66–0.80) for unfavorable outcome and 0.76 (95% CI, 0.62–0.90) for mortality.
Mortality and unfavorable outcome were significantly associated with greater NSE concentrations. In addition, NSE has moderate discriminatory ability to predict mortality and neurological outcome in TBI patients. The optimal discrimination cutoff values and optimal sampling time remain uncertain because of significant variations between studies.
PMCID: PMC4154726  PMID: 25188406
23.  Novel Germanium/Polypyrrole Composite for High Power Lithium-ion Batteries 
Scientific Reports  2014;4:6095.
Nano-Germanium/polypyrrole composite has been synthesized by chemical reduction method in aqueous solution. The Ge nanoparticles were directly coated on the surface of the polypyrrole. The morphology and structural properties of samples were determined by X-ray diffraction, scanning electron microscopy and transmission electron microscopy. Thermogravimetric analysis was carried out to determine the polypyrrole content. The electrochemical properties of the samples have been investigated and their suitability as anode materials for the lithium-ion battery was examined. The discharge capacity of the Ge nanoparticles calculated in the Ge-polypyrrole composite is 1014 mAh g−1 after 50 cycles at 0.2 C rate, which is much higher than that of pristine germanium (439 mAh g−1). The composite also demonstrates high specific discharge capacities at different current rates (1318, 1032, 661, and 460 mAh g−1 at 0.5, 1.0, 2.0, and 4.0 C, respectively). The superior electrochemical performance of Ge-polypyrrole composite could be attributed to the polypyrrole core, which provides an efficient transport pathway for electrons. SEM images of the electrodes have demonstrated that polypyrrole can also act as a conductive binder and alleviate the pulverization of electrode caused by the huge volume changes of the nanosized germanium particles during Li+ intercalation/de-intercalation.
PMCID: PMC4148674  PMID: 25168783
24.  In Vivo Hypoglycaemic Effect and Inhibitory Mechanism of the Branch Bark Extract of the Mulberry on STZ-Induced Diabetic Mice 
The Scientific World Journal  2014;2014:614265.
Branch bark extract (BBE) derived from the mulberry cultivar Husang 32 (Morus multicaulis L.) with aqueous alcohol solution has been investigated as an inhibitor of α-glycosidase in vitro. Mulberry BBE was orally administered to STZ-induced diabetic mice for three weeks, and it improved the weight gain and ameliorated the swelling of liver and kidney in diabetic mice. Obviously, mulberry BBE not only can reduce the abnormally elevated levels of serum insulin and ameliorate insulin resistance induced by STZ, but also it regulates dyslipidemia in diabetic mice. To understand this therapeutic effect and the regulatory mechanisms of BBE in diabetic mice, a qRT-PCR experiment was performed, indicating that the mulberry BBE can regulate the mRNA expression of glycometabolism genes in diabetic mice, including glucose-6-phosphatase (G6Pase), glucokinase (GCK), and phosphoenolpyruvate carboxykinase (PEPCK), thereby regulating sugar metabolism and reducing the blood glucose level in diabetic mice. The mulberry BBE can increase the mRNA expression of the genes Ins1, Ins2 and pancreatic duodenal homeobox-1 (PDX-1) and may decrease the insulin resistance in diabetic mice. Those results provide an important basis for making the best use of mulberry branch resources and producing biomedical drugs with added value.
PMCID: PMC4142180  PMID: 25177729
25.  Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6 
BioMed Research International  2014;2014:902842.
Accumulating evidence has shown that diabetes accelerates aging and endothelial cell senescence is involved in the pathogenesis of diabetic vascular complications, including diabetic retinopathy. Oxidative stress is recognized as a key factor in the induction of endothelial senescence and diabetic retinopathy. However, specific mechanisms involved in oxidative stress-induced endothelial senescence have not been elucidated. We hypothesized that Sirt6, which is a nuclear, chromatin-bound protein critically involved in many pathophysiologic processes such as aging and inflammation, may have a role in oxidative stress-induced vascular cell senescence. Measurement of Sirt6 expression in human endothelial cells revealed that H2O2 treatment significantly reduced Sirt6 protein. The loss of Sirt6 was associated with an induction of a senescence phenotype in endothelial cells, including decreased cell growth, proliferation and angiogenic ability, and increased expression of senescence-associated β-galactosidase activity. Additionally, H2O2 treatment reduced eNOS expression, enhanced p21 expression, and dephosphorylated (activated) retinoblastoma (Rb) protein. All of these alternations were attenuated by overexpression of Sirt6, while partial knockdown of Sirt6 expression by siRNA mimicked the effect of H2O2. In conclusion, these results suggest that Sirt6 is a critical regulator of endothelial senescence and oxidative stress-induced downregulation of Sirt6 is likely involved in the pathogenesis of diabetic retinopathy.
PMCID: PMC4138737  PMID: 25162034

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