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1.  Characteristics of language impairment in Parkinson’s disease and its influencing factors 
Background
Language impairment is relatively common in Parkinson’s disease (PD), but not all PD patients are susceptible to language problems. In this study, we identified among a sample of PD patients those pre-disposed to language impairment, describe their clinical profiles, and consider factors that may precipitate language disability in these patients.
Methods
A cross-sectional cohort of 31 PD patients and 20 controls were administered the Chinese version of the Western Aphasia Battery (WAB) to assess language abilities, and the Montreal Cognitive Assessment (MoCA) to determine cognitive status. PD patients were then apportioned to a language-impaired PD (LI-PD) group or a PD group with no language impairment (NLI-PD). Performance on the WAB and MoCA was investigated for correlation with the aphasia quotient deterioration rate (AQDR).
Results
The PD patients scored significantly lower on most of the WAB subtests than did the controls. The aphasia quotient, cortical quotient, and spontaneous speech and naming subtests of the WAB were significantly different between LI-PD and NLI-PD groups. The AQDR scores significantly and positively correlated with age at onset and motor function deterioration.
Conclusion
A subset group was susceptible to language dysfunction, a major deficit in spontaneous speech. Once established, dysphasia progression is closely associated with age at onset and motor disability progression.
doi:10.1186/2047-9158-4-2
PMCID: PMC4328233
Aphasia quotient; Language function deterioration rate; Language impairment; Parkinson’s disease; Western aphasia battery
2.  The Predictive Performance and Stability of Six Species Distribution Models 
PLoS ONE  2014;9(11):e112764.
Background
Predicting species’ potential geographical range by species distribution models (SDMs) is central to understand their ecological requirements. However, the effects of using different modeling techniques need further investigation. In order to improve the prediction effect, we need to assess the predictive performance and stability of different SDMs.
Methodology
We collected the distribution data of five common tree species (Pinus massoniana, Betula platyphylla, Quercus wutaishanica, Quercus mongolica and Quercus variabilis) and simulated their potential distribution area using 13 environmental variables and six widely used SDMs: BIOCLIM, DOMAIN, MAHAL, RF, MAXENT, and SVM. Each model run was repeated 100 times (trials). We compared the predictive performance by testing the consistency between observations and simulated distributions and assessed the stability by the standard deviation, coefficient of variation, and the 99% confidence interval of Kappa and AUC values.
Results
The mean values of AUC and Kappa from MAHAL, RF, MAXENT, and SVM trials were similar and significantly higher than those from BIOCLIM and DOMAIN trials (p<0.05), while the associated standard deviations and coefficients of variation were larger for BIOCLIM and DOMAIN trials (p<0.05), and the 99% confidence intervals for AUC and Kappa values were narrower for MAHAL, RF, MAXENT, and SVM. Compared to BIOCLIM and DOMAIN, other SDMs (MAHAL, RF, MAXENT, and SVM) had higher prediction accuracy, smaller confidence intervals, and were more stable and less affected by the random variable (randomly selected pseudo-absence points).
Conclusions
According to the prediction performance and stability of SDMs, we can divide these six SDMs into two categories: a high performance and stability group including MAHAL, RF, MAXENT, and SVM, and a low performance and stability group consisting of BIOCLIM, and DOMAIN. We highlight that choosing appropriate SDMs to address a specific problem is an important part of the modeling process.
doi:10.1371/journal.pone.0112764
PMCID: PMC4226630  PMID: 25383906
3.  De-SUMOylation of FOXC2 by SENP3 promotes the epithelial-mesenchymal transition in gastric cancer cells 
Oncotarget  2014;5(16):7093-7104.
The impact of cellular oxidative stress in promoting the epithelial-mesenchymal transition (EMT) has been noticed. Our previous study shows that SENP3, a redox-sensitive SUMO2/3-specific protease, accumulates in a variety of cancers, but whether SENP3 and SUMOylation involve in the regulation of EMT is unclear. The present study uncovers a novel role of SENP3 in promoting the EMT process in gastric cancer via regulating an EMT-inducing transcription factor, forkhead box C2 (FOXC2). We demonstrate that the expression of mesenchymal marker genes and cell migration ability are enhanced in SENP3-overexpressing gastric cancer cells and attenuated in SENP3-knockdown cells. A nude mouse model and a set of patient's specimens suggest the correlation between SENP3 and gastric cancer metastasis. Biochemical assays identify FOXC2 as a substrate of SENP3. Meanwhile N-cadherin is verified as a target gene of FOXC2, which is transcriptionally activated by a SUMO-less FOXC2. Additionally, reactive oxygen species-induced de-SUMOylation of FOXC2 can be blocked by silencing endogenous SENP3. In conclusion, SENP3, which is increased in gastric cancer cells, potentiates the transcriptional activity of FOXC2 through de-SUMOylation, in favor of the induction of specific mesenchymal gene expression in gastric cancer metastasis.
PMCID: PMC4196186  PMID: 25216525
epithelial-mesenchymal transition (EMT); reactive oxygen species (ROS); SENP3; SUMO2/3; FOXC2; gastric cancer
4.  Absence of 19 known hotspot oncogenic mutations in soft tissue clear cell sarcoma: two cases report with review of the literature 
Clear cell sarcoma (CCS) of the tendons and aponeuroses is a rare soft tissue sarcoma that morphologically resembles cutaneous malignant melanoma but exhibits a distinct molecular profile. Gastrointestinal (GI) CCS is extremely rare. In this study, two cases of CCS were presented: (1) left thumb and (2) jejunum. Case 1 manifested the characteristic CCS morphology. Case 2 was morphologically unusual and difficult to diagnose. Immunohistochemically, the two cases of tumor cells were diffusely positive for S100, vimentin, NSE protein, focal expression of CgA, and CAM2.5 protein. In case 1, the tumor cells were diffusely positive for HMB45, focal expression of CD56, and melan A antigen. Reverse transcriptase-polymerase chain reaction (RT-PCR) results confirmed the presence of the EWS/ATF1 translocation (type 1) in the two cases. Then, we detected 19 hotspot oncogenes in the two cases. To the best of our knowledge, this study is the first to apply a high-throughput OncoCarta panel 1.0 and MassARRAY system to detect 238 known mutations in 19 hotspot oncogenes in soft tissue clear cell sarcoma. In this study, no mutations were observed in these hotspot oncogenes in the two cases.
PMCID: PMC4152094  PMID: 25197404
Clear cell sarcoma; mutations; fuse gene
5.  Resveratrol Increases Nephrin and Podocin Expression and Alleviates Renal Damage in Rats Fed a High-Fat Diet 
Nutrients  2014;6(7):2619-2631.
Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD) and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol). Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-κB (NF-κB) and superoxide dismutase (SOD), the content of malondialdehyde (MDA), and the protein levels of tumor necrosis factor (TNF-α), monocyte chemotactic protein-1 (MCP-1), nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-κB activity, increased TNF-α and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-κB signaling pathway that in turn up-regulate nephrin and podocin protein expression.
doi:10.3390/nu6072619
PMCID: PMC4113760  PMID: 25025298
resveratrol; NF-κB; TNF-α; MCP-1; nephrin; podocin
6.  Structural Insights into SraP-Mediated Staphylococcus aureus Adhesion to Host Cells 
PLoS Pathogens  2014;10(6):e1004169.
Staphylococcus aureus, a Gram-positive bacterium causes a number of devastating human diseases, such as infective endocarditis, osteomyelitis, septic arthritis and sepsis. S. aureus SraP, a surface-exposed serine-rich repeat glycoprotein (SRRP), is required for the pathogenesis of human infective endocarditis via its ligand-binding region (BR) adhering to human platelets. It remains unclear how SraP interacts with human host. Here we report the 2.05 Å crystal structure of the BR of SraP, revealing an extended rod-like architecture of four discrete modules. The N-terminal legume lectin-like module specifically binds to N-acetylneuraminic acid. The second module adopts a β-grasp fold similar to Ig-binding proteins, whereas the last two tandem repetitive modules resemble eukaryotic cadherins but differ in calcium coordination pattern. Under the conditions tested, small-angle X-ray scattering and molecular dynamic simulation indicated that the three C-terminal modules function as a relatively rigid stem to extend the N-terminal lectin module outwards. Structure-guided mutagenesis analyses, in addition to a recently identified trisaccharide ligand of SraP, enabled us to elucidate that SraP binding to sialylated receptors promotes S. aureus adhesion to and invasion into host epithelial cells. Our findings have thus provided novel structural and functional insights into the SraP-mediated host-pathogen interaction of S. aureus.
Author Summary
Staphylococcus aureus is an important pathogen that causes a range of human diseases, such as infective endocarditis, osteomyelitis, septic arthritis and sepsis. The increasing resistance of S. aureus to most of the current antibiotics emphasizes the need to develop new approaches to control staphylococcal infections. As a surface-exposed serine-rich repeat glycoprotein (SRRP), S. aureus SraP is involved in the pathogenesis of infective endocarditis via its ligand-binding region (BR) adhering to human platelets. However, little is known about how SraP interacts with its host receptor(s). Through structural and functional analyses of the BR domain, we have discovered a specific binding of SraP to N-acetylneuraminic acid (Neu5Ac), in agreement with a recent report of the trisaccharide ligand of SraP. Further mutagenesis analysis showed that SraP binding to Neu5Ac and the trisaccharide promotes S. aureus adhesion to and invasion into host epithelial cells. These findings increase our knowledge of surface protein mediated interaction of S. aureus with host epithelial cells.
doi:10.1371/journal.ppat.1004169
PMCID: PMC4047093  PMID: 24901708
7.  The efficacy and safety of pramipexole ER versus IR in Chinese patients with Parkinson’s disease: a randomized, double-blind, double-dummy, parallel-group study 
Objective
To evaluate the non-inferiority of pramipexole extended-release (ER) versus immediate-release (IR) in Chinese patients with Parkinson’s disease (PD) in a double-blind, randomized, parallel-group study.
Methods
Subjects were Chinese patients with idiopathic PD with diagnosis ≥ 2 years prior to trial, age ≥ 30 years old at diagnosis, and Modified Hoehn and Yahr score 2-4 during ‘on’-time. Subjects received treatment with pramipexole ER (n=234) or IR (n=239). Non-inferiority was based on the primary endpoint, the change from baseline to end of maintenance (week 18) in the UPDRS (Parts II + III) total score.
Results
For the primary endpoint, the adjusted mean changes (standard error) of UPDRS Parts II + III at week 18 were -13.81 (0.655) and -13.05 (0.643) for ER and IR formulations, respectively, using ANCOVA adjusted for treatment and centre (fixed effect) and baseline (covariate). The adjusted mean between group difference was 0.8 for the 2-sided 95% CI (-1.047, 2.566). Since the lower limit of the 2-sided 95% CI (-1.047) for treatment difference was higher than the non-inferiority margin of -4, non-inferiority between pramipexole ER and IR was demonstrated. The incidence of adverse events (AEs) was 68.8% in the ER arm and 73.6% in the IR arm with few severe AEs (ER: 2.1%; IR: 3.8%).
Conclusion
Based on the UPDRS II + III score, pramipexole ER was non-inferior to pramipexole IR. The safety profiles of pramipexole ER and IR were similar. These results were based on comparable mean daily doses and durations of treatment for both formulations.
doi:10.1186/2047-9158-3-11
PMCID: PMC4128609  PMID: 25114789
Parkinson’s disease; Pramipexole ER; Pramipexole IR; Non-inferiority; Unified Parkinson’s Disease Rating Scale (UPDRS); Safety
8.  Dual effects of ouabain on the regulation of proliferation and apoptosis in human umbilical vein endothelial cells: involvement of Na+-K+-ATPase α-subunits and NF-κB 
Purpose: To elucidate the effect of ouabain on the regulation of proliferation and apoptosis of HUVECs and involvement of different Na+-K+-ATPase α-subunits and NF-κB. Methods: HUVECs were isolated by collagenase perfusion, and MTT assays and cell cycle analysis were performed to study proliferation. NF-κB expression and function were examined by immunohistochemical staining and western blotting. Na+-K+-ATPase activity was determined by measuring released ouabain inhibitable inorganic phosphate (Pi). The expression of different α-subunits was investigated by real RT-PCR, western blotting and cell immunofluorescence. Results: 0.3 nM ouabain treatment for 0.5 h triggered the proliferation of HUVECs, peaking at 1-2 h. At 1.8 nM for 0.5 h, ouabain induced an increase of cell proliferation for a short time, and then triggered a decrease after 1 h. Cell cycle analysis show that 37% of HUVECs were in G2/M phase of the cell cycle following incubation with 1.8 nM ouabain, compared with 18% with 0.3 nM ouabain. NF-κB activity was assessed by western blot analysis of IκB expression, which was significantly reduced with 0.3 nM ouabain treatment; there was no different between 1.8 nM ouabain treatment and untreated cells. Na+-K+-ATPase activity in HUVECs was markedly reduced after treatment with 0.3 nM and 1.8 nM ouabain. Real RT-PCR and western blotting indicated that Na+-K+-ATPase α1-subunit mRNA expression levels increased after 0.3 nM ouabain treatment and decreased after 1.8 nM ouabain treatment. However, α2- and α3-subunit mRNA decreased after 0.3 nM ouabain treatment and increased after 1.8 nM ouabain treatment. Conclusion: Ouabain at different concentrations caused dual effects on proliferation and apoptosis in HUVECs.
PMCID: PMC4073737  PMID: 24995076
Ouabain; endothelium; α subunit; NF-κB
9.  Spectrum of LKB1, EGFR, and KRAS Mutations in Chinese Lung Adenocarcinomas 
Introduction
Somatic LKB1 mutations are found in lung adenocarcinomas at different frequencies in Caucasian and East Asian (Japanese and Korean) populations. This study was designed to characterize the frequency of LKB1 mutations, their relationship to EGFR and KRAS mutations, and their associated clinicopathologic characteristics in Chinese patients.
Methods
Two hundred thirty-nine lung adenocarcinomas consecutively collected from October 2007 to July 2009 were dissected into 3 to 4 small (3 mm) pieces for histopathological analyses of tumor content. Genomic DNA and/or cDNA from 86 samples with more than 70% tumor content were used for sequencing of LKB1 (exons 1–9), EGFR (exons 18–21), and KRAS (exon 2). LKB1 germline mutation status was determined by sequencing of genomic DNA from matched histologically distant lung tissues that are histologically normal.
Results
6.9% of lung adenocarcinomas harbored LKB1 somatic mutations. A total of 10.5% of patients had an LKB1 germline polymorphism, F354L. Interestingly, in two of these patients, tumors displayed loss of heterozygosity at this allele. EGFR kinase domain and KRAS mutations were found in 66.3% and 2.3% of Chinese lung adenocarcinomas, respectively. Concurrent LKB1 and EGFR somatic mutations were observed in one patient. Both KRAS-mutant tumors harbored LKB1 mutations.
Conclusions
These data provide important clinical and molecular characteristics of lung adenocarcinomas from Chinese patients.
doi:10.1097/JTO.0b013e3181e05016
PMCID: PMC4009449  PMID: 20559149
Chinese lung adenocarcinoma; LKB1; EGFR; KRAS; Mutation
10.  Anti-Cyclic Citrullinated Peptide Antibody Is Associated with Interstitial Lung Disease in Patients with Rheumatoid Arthritis 
PLoS ONE  2014;9(4):e92449.
Objective
Patients with rheumatoid arthritis (RA) are at risk to develop RA-associated interstitial lung disease (RA-ILD). This retrospective study aimed to investigate the potential association of the positivity of serum anti-cyclic citrullinated peptide antibody (anti-CCP2) and rheumatoid factor (RF) with RA-ILD in RA patients.
Methods
A total of 285 RA patients were recruited at the inpatient service of Peking Union Medical College Hospital in China between 2004 and 2013. Individual patients were evaluated for the evidence of ILD. The concentrations of serum anti-CCP2 and RF in individual patients were measured. The potential risk factors for ILD in RA patients were assessed by univariate and multivariate models.
Results
There were 71 RA patients with RA-ILD, accounting for 24.9% in this population. The positive rates of anti-CCP2 and RF in the patients with RA-ILD were significantly higher than that in the patients with RA-only (88.7% vs. 67.3%, p<0.001; 84.5% vs. 70.6%, p = 0.02, respectively). Univariate and multivariate logistic regression analysis revealed that RA patients with positive serum anti-CCP2, but not RF, were associated with an increased risk of ILD (crude odds ratio [cOR] 3.83, 95% confidence interval [CI] 1.74–8.43, p<0.001; adjusted odds ratio [aOR] 3.50, 95% CI 1.52–8.04, p<0.001).
Conclusion
Our findings suggest that positive serum anti-CCP2, but not RF, may be associated with RA-ILD in RA patients.
doi:10.1371/journal.pone.0092449
PMCID: PMC3990563  PMID: 24743261
11.  Objective assessment of urban built environment related to physical activity — development, reliability and validity of the China Urban Built Environment Scan Tool (CUBEST) 
BMC Public Health  2014;14:109.
Background
Some aspects of the neighborhood built environment may influence residents’ physical activity, which in turn, affects their health. This study aimed to develop an urban built environment evaluation tool and conduct necessary reliability and validity tests.
Methods
A 41-item urban built environment scan tool was developed to objectively assess the neighborhood built environment features related to physical activity. Six neighborhoods in Hangzhou were selected from three types of administrative planning units. A pair of auditors independently assessed all of the 205 street segments at the same time. Half of the segments (n = 104) were audited twice by the same auditor after a two-week time interval. Inter-rater reliability was assessed by comparing the audits of paired observers, while intra-rater reliability was evaluated by comparing an auditor’s repeated assessments of the same segments. The construct validity was tested using factor analysis.
Results
The inter-rater reliability for most items was above 0.8. The intra-rater reliability for most items was above 0.4, and was lower than corresponding inter-rater reliability. Six factors were extracted by factor analysis and the factor loading matrix showed good construct validity.
Conclusions
The CUBEST is a reliable and valid instrument that can be used to assess the physical activity-related built environment in Hangzhou, and potentially other cities in China.
doi:10.1186/1471-2458-14-109
PMCID: PMC3916581  PMID: 24495676
Environmental scan; Physical activity; Reliability; Validity
12.  Possible Association of the GSK3β Gene with the Anxiety Symptoms of Major Depressive Disorder and P300 Waveform 
Glycogen synthase kinase-3β (GSK3β) may play an important role in the brain of patients with major depressive disorder (MDD); therefore, we investigated whether the GSK3β gene is involved in the etiology of MDD and whether it affects MDD endophenotypes. Three single-nucleotide polymorphisms (SNPs) (rs6438552, rs7633279, and rs334558) were genotyped in 559 MDD patients and 486 healthy controls. To explore quantitative traits of MDD, we analyzed the association of these SNPs with the factor scores of the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Hamilton Anxiety Rating Scale (HAMA). We also determined the effects of these SNPs on the measurement of the P300 wave. Although no significant association between GSK3β SNPs and MDD was found, some genotypes and haplotypes were associated with anxiety symptoms in MDD. The three SNPs were associated with the HAMA total score and with the HAMD anxiety and somatization factor score (p<0.05). Three-locus haplotype analysis showed the C-T-G carriers to have a strong association with the HAMA total score (p=0.032). Moreover, the P300 latency and amplitude were also associated with GSK3β genotypes. The individuals with the T allele genotype, both in rs6438552 and rs7633279, have a longer P300 latency than those carrying the C/C (p=0.04) and A/A genotype (p=0.013). The individuals with the G/G genotype in rs334558 have a lower amplitude than those carrying the A allele genotype (p=0.007). Our findings show, for the first time, that GSK3β polymorphisms may play an important role in MDD endophenotypes, especially in anxiety symptoms.
doi:10.1089/gtmb.2012.0227
PMCID: PMC3501115  PMID: 23030648
13.  Isolation and Characterization of Carbendazim-degrading Rhodococcus erythropolis djl-11 
PLoS ONE  2013;8(10):e74810.
Carbendazim (methyl 1H-benzimidazol-2-yl carbamate) is one of the most widely used fungicides in agriculture worldwide, but has been reported to have adverse effects on animal health and ecosystem function. A highly efficient carbendazim-degrading bacterium (strain dj1-11) was isolated from carbendazim-contaminated soil samples via enrichment culture. Strain dj1-11 was identified as Rhodococcus erythropolis based on morphological, physiological and biochemical characters, including sequence analysis of the 16S rRNA gene. In vitro degradation of carbendazim (1000 mg·L−1) by dj1-11 in minimal salts medium (MSM) was highly efficient, and with an average degradation rate of 333.33 mg·L−1·d−1 at 28°C. The optimal temperature range for carbendazim degradation by dj1-11 in MSM was 25–30°C. Whilst strain dj1-11 was capable of metabolizing cabendazim as the sole source of carbon and nitrogen, degradation was significantly (P<0.05) increased by addition of 12.5 mM NH4NO3. Changes in MSM pH (4–9), substitution of NH4NO3 with organic substrates as N and C sources or replacing Mg2+ with Mn2+, Zn2+ or Fe2+ did not significantly affect carbendazim degradation by dj1-11. During the degradation process, liquid chromatography-mass spectrometry (LC-MS) detected the metabolites 2-aminobenzimidazole and 2-hydroxybenzimidazole. A putative carbendazim-hydrolyzing esterase gene was cloned from chromosomal DNA of djl-11 and showed 99% sequence homology to the mheI carbendazim-hydrolyzing esterase gene from Nocardioides sp. SG-4G.
doi:10.1371/journal.pone.0074810
PMCID: PMC3788055  PMID: 24098350
14.  Downregulation of expression of transporters associated with antigen processing 1 and 2 and human leukocyte antigen I and its effect on immunity in nasopharyngeal carcinoma patients 
The human leukocyte antigen (HLA)-I and antigen-processing machinery (APM) are crucial in the anti-cancer immune response. The aim of this study was to assess the clinical significance of the APM components [transporters associated with antigen processing (TAP)-1 and -2 and HLA-I] in nasopharyngeal carcinoma (NPC). A total of 58 NPC specimens and 20 healthy specimens used as control were evaluated by semiquantitative immunohistochemistry for three APM components (TAP-1, TAP-2 and HLA-I). The expression of the APM components in NPC was downregulated. CD4+ and CD8+ T cells were measured by flow cytometry and IL-10 was measured by ELISA. The number of CD8+ T cells and the expression of IL-10 were higher and the number of CD4+ T cells was lower in NPC, compared to the controls. The number of CD8+ T cells and the expression of IL-10 were negatively correlated with TAP-1, TAP-2 and HLA-I expression. The clinical phase, lymph node metastasis, distant metastasis, pathological type, TAP-1 expression, TAP-2 expression and HLA-I expression were identified as prognostic factors by the Kaplan-Meier analysis. A multivariate analysis using a Cox regression model indicated that distant metastasis and the downregulation of HLA-I expression were independent unfavorable prognostic factors. In conclusion, the lower expression of HLA-I induced immunosuppression in NPC patients and was associated with a poor prognosis.
doi:10.3892/mco.2013.194
PMCID: PMC3916213  PMID: 24649307
nasopharyngeal neoplasms; transporter associated with antigen processing 1; transporter associated with antigen processing 2; human leucocyte antigen I
15.  Characteristics of Tau Oligomers 
In Alzheimer disease (AD) and other tauopathies, microtubule-associated protein tau becomes hyperphosphorylated, undergoes conformational changes, aggregates, eventually becoming neurofibrillary tangles (NFTs). As accumulating evidence suggests that NFTs themselves may not be toxic, attention is now turning toward the role of intermediate tau oligomers in AD pathophysiology. Sarkosyl extraction is a standard protocol for investigating insoluble tau aggregates in brains. There is a growing consensus that sarkosyl-insoluble tau correlates with the pathological features of tauopathy. While sarkosyl-insoluble tau from tauopathy brains has been well characterized as a pool of filamentous tau, other dimers, multimers, and granules of tau are much less well understood. There are protocols for identifying these tau oligomers. In this mini review, we discuss the characteristics of tau oligomers isolated via different methods and materials.
doi:10.3389/fneur.2013.00102
PMCID: PMC3715738  PMID: 23882258
tau; oligomers; dimer; sarkosyl-insoluble; antibody
16.  Prevalence of Hypertension in China: A Cross-Sectional Study 
PLoS ONE  2013;8(6):e65938.
Aims
The present study aimed to assess the prevalence of hypertension among Chinese adults.
Methods
Data were obtained from sphygmomanometer measurements and a questionnaire administered to 46239 Chinese adults ≥20 years of age who participated in the 2007–2008 China National Diabetes and Metabolic Disorders Study. Hypertension was defined as blood pressure ≥140/90 mm Hg or use of antihypertensive medication.
Results
A total of 26.6% of Chinese adults had hypertension, and a significantly greater number of men were hypertensive than women (29.2% vs 24.1%, p<0.001). The age-specific prevalence of hypertension was 13.0%, 36.7%, and 56.5% among persons aged 20 to 44 years (young people), 45 to 64 years (middle-aged people), and ≥65 years (elderly people), respectively. In economically developed regions, the prevalence of hypertension was significantly higher among rural residents than among urban residents (31.3% vs 29.2%, p = 0.001). Among women or individuals who lived in the northern region, the disparity in the prevalence of hypertension between urban and rural areas disappeared (women: 24.0% vs. 24.0%, p = 0.942; northern region: 31.6% vs. 31.2%, p = 0.505). Among hypertensive patients, 45.0% were aware of their condition, 36.2% were treated, and 11.1% were adequately controlled.
Conclusions
The prevalence of hypertension in China is increasing. The trend of an increase in prevalence is striking in young people and rural populations. Hypertension awareness, treatment, and control are poor. Public health efforts for further improving awareness and enhancing effective control are urgently needed in China, especially in emerging populations.
doi:10.1371/journal.pone.0065938
PMCID: PMC3679057  PMID: 23776574
17.  Risk factors associated with severe manifestations of 2009 pandemic influenza A (H1N1) infection in China: a case–control study 
Virology Journal  2013;10:149.
Background
No studies on the risk factors of 2009 pandemic influenza A (H1N1) in China have been reported. We aimed to investigate the risk factors for severe manifestations of 2009 pandemic H1N1 influenza in China
Methods
A case–control study with 343 severe hospitalized patients and 343 randomly selected mild controls was conducted. The diagnosis was established by assessment of clinical symptoms and confirmed by the real-time reverse-transcriptase-polymerase chain reaction assay. Severe or mild patients were classified by uniform criteria issued by the Ministry of Health in China.
Results
The multivariable logistic regression analysis showed that the overweight or obese subjects admitted to hospital with H1N1 influenza were more likely to experience severe manifestations. The ORs were 3.70 (95% CI: 2.04-6.72) and 35.61 (95% CI: 7.96-159.21) respectively. Subjects at age less than 5 years or older than 60 years had an increased risk of severe manifestations (OR = 21.14, 95% CI: 7.79-57.33). We also observed increased risk among subjects with longer time interval from symptom onset to hospital admission (OR = 3.26, 95% CI: 2.08-5.11) or peasants (OR = 9.79, 95% CI: 5.11-18.78). Those with chronic disorders had increased risk of severe manifestations of H1N1 influenza.
Conclusion
We provide evidence on the risk factors associated with severe manifestations of 2009 pandemic H1N1 influenza in a study of hospitalized subjects in China.
doi:10.1186/1743-422X-10-149
PMCID: PMC3656780  PMID: 23672278
Severe manifestation; Novel influenza A; Risk factor
18.  Genome Sequence of a Freshwater Low-Nucleic-Acid-Content Bacterium, Betaproteobacterium Strain CB 
Genome Announcements  2013;1(2):e00135-13.
Betaproteobacterium strain CB is a typical minute freshwater bacterium, representing the small-cell bacteria that are numerically dominant in most freshwater environments. The genome of betaproteobacterium CB consists of a circular 2,045,720-bp chromosome, and the information we report will provide insights into the mechanisms underlying its survival and ecological function.
doi:10.1128/genomeA.00135-13
PMCID: PMC3630399  PMID: 23599288
19.  Aberrant CD200/CD200R1 expression contributes to painful synovium hyperplasia in a patient with primary hypertrophic osteoarthropathy 
Rheumatology International  2013;33(10):2509-2512.
We present a case of hypertrophic osteoarthropathy (PHO), with painful synovium hyperplasia involving both knees that was refractory to corticosteroid treatment. His rheumatoid factor and anti-CCP antibody was negative, and his serum ESR and CRP level was within normal range. Histological examination of the synovium obtained from his right knee revealed endothelial hyperplasia and vascular thickening without inflammation that was in association with aberrant expression of CD200/CD200R1, which highlighted the importance of aberrant CD200/CD200R1 in the regulation of the endothelial activation that contributed to the development of synovium hyperplasia in this PHO patient.
doi:10.1007/s00296-013-2732-1
PMCID: PMC3782638  PMID: 23595568
Primary hypertrophic osteoarthropathy; CD200/CD200R1; Endothelial activity
20.  Utilization of PET-CT in target volume delineation for three-dimensional conformal radiotherapy in patients with non-small cell lung cancer and atelectasis 
Background
To investigate the utilization of PET-CT in target volume delineation for three-dimensional conformal radiotherapy in patients with non-small cell lung cancer (NSCLC) and atelectasis.
Methods
Thirty NSCLC patients who underwent radical radiotherapy from August 2010 to March 2012 were included in this study. All patients were pathologically confirmed to have atelectasis by imaging examination. PET-CT scanning was performed in these patients. According to the PET-CT scan results, the gross tumor volume (GTV) and organs at risk (OARs, including the lungs, heart, esophagus and spinal cord) were delineated separately both on CT and PET-CT images. The clinical target volume (CTV) was defined as the GTV plus a margin of 6-8 mm, and the planning target volume (PTV) as the GTV plus a margin of 10-15mm. An experienced physician was responsible for designing treatment plans PlanCT and PlanPET-CT on CT image sets. 95% of the PTV was encompassed by the 90% isodose curve, and the two treatment plans kept the same beam direction, beam number, gantry angle, and position of the multi-leaf collimator as much as possible. The GTV was compared using a target delineation system, and doses distributions to OARs were compared on the basis of dose-volume histogram (DVH) parameters.
Results
The GTVCT and GTVPET-CT had varying degrees of change in all 30 patients, and the changes in the GTVCT and GTVPET-CT exceeded 25% in 12 (40%) patients. The GTVPET-CT decreased in varying degrees compared to the GTVCT in 22 patients. Their median GTVPET-CT and median GTVPET-CT were 111.4 cm3 (range, 37.8 cm3-188.7 cm3) and 155.1 cm3 (range, 76.2 cm3-301.0 cm3), respectively, and the former was 43.7 cm3 (28.2%) less than the latter. The GTVPET-CT increased in varying degrees compared to the GTVCT in 8 patients. Their median GTVPET-CT and median GTVPET-CT were 144.7 cm3 (range, 125.4 cm3-178.7 cm3) and 125.8 cm3 (range, 105.6 cm3-153.5 cm3), respectively, and the former was 18.9 cm3 (15.0%) greater than the latter. Compared to PlanCT parameters, PlanPET-CT parameters showed varying degrees of changes. The changes in lung V20, V30, esophageal V50 and V55 were statistically significant (Ps< 0.05 for all), while the differences in mean lung dose, lung V5, V10, V15, heart V30, mean esophageal dose, esophagus Dmax, and spinal cord Dmax were not significant (Ps> 0.05 for all).
Conclusions
PET-CT allows a better distinction between the collapsed lung tissue and tumor tissue, improving the accuracy of radiotherapy target delineation, and reducing radiation damage to the surrounding OARs in NSCLC patients with atelectasis.
doi:10.1186/2049-6958-8-21
PMCID: PMC3608960  PMID: 23506629
Atelectasis; PET-CT; Non-small cell lung cancer; Target volume; Three-dimensional conformal radiotherapy
21.  In vivo functional brain mapping in a conditional mouse model of human tauopathy (taup301l) reveals reduced neural activity in memory formation structures 
Background
Tauopathies are characterized by intracellular deposition of the microtubule-associated protein tau as filamentous aggregates. The rTg4510 mouse conditionally expresses mutant human tau protein in various forebrain areas under the Tet-off expression system. Mice develop neurofibrillary tangles, with significant neuronal loss and cognitive deficits by 6 months of age. Previous behavioral and biochemical work has linked the expression and aggregates of mutant tau to functional impairments. The present work used manganese-enhanced magnetic resonance imaging (MEMRI) to investigate basal levels of brain activity in the rTg4510 and control mice.
Results
Our results show an unmistakable curtailment of neural activity in the amygdala and hippocampus, two regions known for their role in memory formation, but not the cortex, cerebellum, striatum and hypothalamus in tau expressing mice.
Conclusion
Behavioral impairments associated with changes in activity in these areas may correspond to age progressive mutant tauP301L-induced neurodegeneration.
doi:10.1186/1750-1326-8-9
PMCID: PMC3579718  PMID: 23379588
Tauopathy; Neurodegenerative disease; Alzheimer’s disease; rTg4510; Manganese enhanced MRI
22.  Effect of β-sodium aescinate on hypoxia-inducible factor-1α expression in rat brain cortex after cardiopulmonary resuscitation 
BACKGROUND:
This study was undertaken to investigate the expression of hypoxia-inducible factor-1α (HIF-1α) in rat cerebral cortex and the effects of β-sodium aescinate (SA) administration after return of spontaneous circulation (ROSC).
METHODS:
Sixty rats were divided into three groups: SA group, injected intraperitoneally with SA instantly after ROSC; control group, injected intraperitoneally with normal saline; and sham-operated group, without cardiac arrest or SA. The cardiac arrest model was established using asphyxiation and intravenous potassium chloride. Blood was sampled 1, 6, 12, and 24 hours after ROSC. Protein and mRNA levels of HIF-1α, VEGF and EPO were detected in the cerebral cortex by immunohistochemistry and real-time RT-PCR; serum levels of NSE and S100β were determined by enzyme-linked immunosorbent assays.
RESULTS:
Serum S100β and NSE were significantly increased in the control group versus the sham-operated group 1, 6, 12 and 24 hours after ROSC (P<0.05). Protein and mRNA levels of HIF-1α, VEGF and EPO were significantly increased in the control rats (P<0.05). Serum NSE and S100β were significantly decreased in the SA group versus the control group 1, 6, 12 and 24 hours after ROSC (P<0.05). Protein and mRNA levels of HIF-1α, VEGF and EPO were significantly increased in the SA group (P<0.05).
CONCLUSIONS:
The expression of HIF-1α is increased in rat cerebral cortex after ROSC, and SA up-regulates the expression of HIF-1α. The up-regulation of HIF-1α improves the resistance of the cortex to ischemia and hypoxia and contributes to neuroprotection, possibly because of up-regulation of EPO and VEGF expression.
doi:10.5847/wjem.j.issn.1920-8642.2013.01.012
PMCID: PMC4129896  PMID: 25215095
Cardiopulmonary resuscitation; HIF-1α; Erythropoietin; Vascular endothelial growth factor; β-sodium aescinate; Neuroprotection
23.  Characteristics of TBS-extractable hyperphosphorylated tau species: Aggregation intermediates in rTg4510 mouse brain 
Conditional overexpression of four-repeat human tau containing the P301L missense mutation in the rTg4510 mouse model of tauopathy leads to progressive accumulation of neurofibrillary tangles and hyperphosphorylated, sarkosyl-insoluble tau species, which are biochemically comparable to abnormal tau characteristic of hereditary tauopathies termed FTDP-17. To fully understand the impact of tau species at different stages of self-assembly on neurodegeneration, we fractionated rTg4510 brain representing several stages of tauopathy to obtain TBS-extractable (S1), high salt/sarkosyl-extractable (S3), and sarkosyl-insoluble (P3) fractions. Under reducing condition, the S1 fraction was demonstrated by Western blotting to contain both 50–60 kDa normally-sized and 64 kDa tau. Both are thermo-stable, but the 64 kDa tau showed a higher degree of phosphorylation. Under non-reducing condition, nearly all TBS-extractable 64 kDa tau were detected as ~130 kDa species consistent with the size of dimer. Quantitative analysis showed ~80 times more 64 kDa tau in S1 than P3 fraction. Immunoelectron microscopy revealed tau-positive granules/short filaments in S1 fraction. These structures displayed MC1 immunoreactivities indicative of conformational/pathological change of tau. MC1 immunoreactivity was detected by dot blotting in samples from 2.5 month-old mice, whereas Ab39 immunoreactivity indicative of late stages of tau assembly was detected only in P3 fraction. Quantitative analysis also demonstrated a significant inverse correlation between brain weight and 64 kDa tau, but the level of TBS-extractable 64 kDa tau reflects neurodegeneration better than that of sarkosyl-insoluble 64 kDa tau. Together, the findings suggest that TBS-extractable 64 kDa tau production is a potential target for therapeutic intervention of tauopathies.
doi:10.3233/JAD-2012-121093
PMCID: PMC3514650  PMID: 22941973
tau protein; tauopathy; transgenic mice; FTDP-17; hyperphosphorylation; dimer
24.  Long CAG Repeat Sequence and Protein Expression of Androgen Receptor Considered as Prognostic Indicators in Male Breast Carcinoma 
PLoS ONE  2012;7(12):e52271.
Background
The androgen receptor (AR) expression and the CAG repeat length within the AR gene appear to be involved in the carcinogenesis of male breast carcinoma (MBC). Although phenotypic differences have been observed between MBC and normal control group in AR gene, there is lack of correlation analysis between AR expression and CAG repeat length in MBC. The purpose of the study was to investigate the prognostic value of CAG repeat lengths and AR protein expression.
Methods
81 tumor tissues were used for immunostaining for AR expression and CAG repeat length determination and 80 normal controls were analyzed with CAG repeat length in AR gene. The CAG repeat length and AR expression were analyzed in relation to clinicopathological factors and prognostic indicators.
Results
AR gene in many MBCs has long CAG repeat sequence compared with that in control group (P = 0.001) and controls are more likely to exhibit short CAG repeat sequence than MBCs. There was statistically significant difference in long CAG repeat sequence between AR status for MBC patients (P = 0.004). The presence of long CAG repeat sequence and AR-positive expression were associated with shorter survival of MBC patients (CAG repeat: P = 0.050 for 5y-OS; P = 0.035 for 5y-DFS AR status: P = 0.048 for 5y-OS; P = 0.029 for 5y-DFS, respectively).
Conclusion
The CAG repeat length within the AR gene might be one useful molecular biomarker to identify males at increased risk of breast cancer development. The presence of long CAG repeat sequence and AR protein expression were in relation to survival of MBC patients. The CAG repeat length and AR expression were two independent prognostic indicators in MBC patients.
doi:10.1371/journal.pone.0052271
PMCID: PMC3522691  PMID: 23272232
25.  Urine Metabolite Profiling of Human Colorectal Cancer by Capillary Electrophoresis Mass Spectrometry Based on MRB 
Aim. The study was to investigate the metabolic profile of urine metabolites and to elucidate their clinical significance in patients with colorectal cancer. Methods. Colorectal cancers from early stage and advanced stage were used in this study. Urine samples of colorectal cancer patients and healthy adults were collected and subjected to capillary electrophoresis mass spectrometry based on moving reaction boundary analysis. The metabolic data were analyzed by SPSS 17.0 to find urinary biomarkers for colorectal cancer. Results. The results indicated that the urine metabolic profiling of colorectal cancer patients had significant changes compared with the normal controls, and there were also differences between early stage and advanced colorectal cancer patients. Compared with the control group, the levels of isoleucine, valine, arginine, lactate acid and leucine increased (P < 0.05), but those of histidine, methionine, serine, aspartic acid, citric acid, succinate, and malic acid decreased in urine samples from colorectal cancer (P < 0.05). Furthermore, the levels of isoleucine and valine were lower in urine of patients with advanced colorectal cancer than those in early stage colorectal cancer (P < 0.05). Conclusion. The technique of capillary electrophoresis mass spectrometry based on MRB could reveal the significant metabolic alterations during progression of colorectal cancer, and the method is feasible and may be useful for the early diagnosis of colorectal cancer.
doi:10.1155/2012/125890
PMCID: PMC3518074  PMID: 23243419

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