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1.  Exercise training with negative pressure ventilation improves exercise capacity in patients with severe restrictive lung disease: a prospective controlled study 
Respiratory Research  2013;14(1):22.
Background
Exercise training is of benefit for patients with restrictive lung disease. However, it tends to be intolerable for those with severe disease. We examined whether providing ventilatory assistance by using negative pressure ventilators (NPV) during exercise training is feasible for such patients and the effects of training.
Methods
36 patients with restrictive lung disease were prospectively enrolled for a 12-week multidisciplinary rehabilitation program. During this program, half of them (n:18; 60.3 ± 11.6 years; 6 men; FVC: 32.5 ± 11.7% predicted ) received regular sessions of exercise training under NPV, whilst the 18 others (59.6 ± 12.3 years; 8 men; FVC: 37.7 ± 10.2% predicted) did not. Exercise capacity, pulmonary function, dyspnea and quality of life were measured. The primary endpoint was the between-group difference in change of 6 minute-walk distance (6MWD) after 12 weeks of rehabilitation.
Results
All patients in the NPV-exercise group were able to tolerate and completed the program. The between-group differences were significantly better in the NPV-exercise group in changes of 6MWD (34.1 ± 12.7 m vs. -32.5 ± 17.5 m; P = 0.011) and St George Score (−14.5 ± 3.6 vs. 11.8 ± 6.0; P < 0.01). There was an improvement in dyspnea sensation (Borg’s scale, from 1.4 ± 1.5 point to 0.8 ± 1.3 point, P = 0.049) and a small increase in FVC (from 0.85 ± 0.09 L to 0.91 ± 0.08 L, P = 0.029) in the NPV-exercise group compared to the control group.
Conclusion
Exercise training with NPV support is feasible for patients with severe restrictive lung diseases, and improves exercise capacity and health-related quality of life.
doi:10.1186/1465-9921-14-22
PMCID: PMC3598345  PMID: 23421438
Restrictive lung disease; Negative pressure ventilation; Exercise training; Exercise capacity; Health-related quality of life
2.  Low Molecular Weight Fucoidan against Renal Ischemia–Reperfusion Injury via Inhibition of the MAPK Signaling Pathway 
PLoS ONE  2013;8(2):e56224.
Background
Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) in both native and transplanted kidneys. The objective of the present study was to evaluate whether low-molecular-weight fucoidan (LMWF) could attenuate renal IRI in an animal model and in vitro cell models and study the mechanisms in which LMWF protected from IRI.
Methodology/Principal Findings
Male mice were subjected to right renal ischemia for 30 min and reperfusion for 24 h, or to a sham operation with left kidney removed. Kidneys undergone IR showed characteristic morphological changes, such as tubular dilatation, and brush border loss. However, LMWF significantly corrected the renal dysfunction and the abnormal levels of MPO, MDA and SOD induced by IR. LMWF also inhibited the activation of MAPK pathways, which consequently resulted in a significant decrease in the release of cytochrome c from mitochondria, ratios of Bax/Bcl-2 and cleaved caspase-3/caspase-3, and phosphorylation of p53. LMWF alleviated hypoxia-reoxygenation or CoCl2 induced cell viability loss and ΔΨm dissipation in HK2 renal tubular epithelial cells, which indicates LMWF may result in an inhibition of the apoptosis pathway through reducing activity of MAPK pathways in a dose-dependent manner.
Conclusions/Significance
Our in vivo and in vitro studies show that LMWF ameliorates acute renal IRI via inhibiting MAPK signaling pathways. The data provide evidence that LMWF may serve as a potential therapeutic agent for acute renal IRI.
doi:10.1371/journal.pone.0056224
PMCID: PMC3572020  PMID: 23418539
3.  Targeted Metabolomics of Serum Acylcarnitines Evaluates Hepatoprotective Effect of Wuzhi Tablet (Schisandra sphenanthera Extract) against Acute Acetaminophen Toxicity 
Possible prevention and therapeutic intervention strategies to counteract acetaminophen (APAP) hepatotoxicity would be of great value. Wuzhi tablet (WZ, extract of Schisandrae sphenanthera) possesses hepatoprotective effects against hepatitis and the hepatic dysfunction induced by various chemical hepatotoxins. In this study, the protective effect of WZ on APAP-induced hepatic injury was evaluated and targeted metabolomics by LC-MS-based metabolomics was used to examine whether WZ influences hepatic metabolism. The results demonstrated significant hepatoprotection of WZ against APAP-induced liver injury; pretreatment with WZ prior to APAP administration blocks the increase in serum palmitoylcarnitine and oleoylcarnitine and thus restores the APAP-impaired fatty acid β-oxidation to normal levels. These studies further revealed a significant and prolonged upregulation of the PPARα target genes Cpt1 and Acot1 by WZ mainly contributing to the maintenance of normal fatty acid metabolism and thus potentially contributing to the hepatic protection of WZ against APAP-induced hepatic toxicity. Taken together, the current study provides new insights into understanding the hepatoprotective effect of WZ against APAP-induced liver toxicity.
doi:10.1155/2013/985257
PMCID: PMC3575671  PMID: 23431354
4.  DNA replication, RNAi and epigenetic inheritance 
Epigenetics  2012;7(1):14-19.
Epigenetic marks, such as histone methylation, play a central role in chromatin structure and gene expression. During DNA replication, chromatin undergoes a wave of disruption and reassembly. Little is known about how the epigenetic marks are faithfully inherited from one generation to the next. In fission yeast, the hallmark of heterochromatin, a condensed chromatin structure, is H3K9 methylation. This conserved epigenetic mark is mediated by small interference RNAs (siRNAs) in a cell cycle-dependent manner: at S phase, heterochromatin is briefly transcribed by RNAP II and the transcripts are subsequently processed into siRNAs. These small RNAs, together with other key silencing factors, including Dos1/Raf1/Clr8/Cmc1, Dos2/Raf2/Clr7/Cmc2 and Rik1, mediate H3K9 methylation by the histone H3K9 methyltransferase Clr4. Our recent findings indicate that the ε subunit of DNA polymerase, Cdc20, associates with the Dos2-Rik1 complex and is essential for H3K9 methylation and heterochromatin function. Moreover, Cdc20 regulates siRNA generation by promoting RNAP II transcription of heterochromatin. These data suggest that DNA polymerase components may play a key role in the inheritance of histone methylation by coordinating DNA replication, RNAi and histone methylation, and explain previously observed cell cycle-regulated RNAi-dependent heterochromatin silencing. We propose a model in which, at DNA replication forks, DNA polymerase subunits mediate the recruitment of epigenetic factors required for RNAi and histone modification to heterochromatin to promote the faithful transmission of histone methylation.
doi:10.4161/epi.7.1.18545
PMCID: PMC3329497  PMID: 22207359
cell cycle; DNA replication; epigenetic inheritance; heterochromatin; histone methylation; RNAi; transcription
5.  NMDA Receptors in Dopaminergic Neurons are Crucial for Habit Learning 
Neuron  2011;72(6):1055-1066.
Summary
Dopamine is crucial for habit learning. Activities of midbrain dopaminergic neurons are regulated by the cortical and subcortical signals among which glutamatergic afferents provide excitatory inputs. Cognitive implications of glutamatergic afferents in regulating and engaging dopamine signals during habit learning however remain unclear. Here we show that mice with dopaminergic neuron-specific NMDAR1 deletion are impaired in a variety of habit learning tasks while normal in some other dopamine-modulated functions such as locomotor activities, goal directed learning, and spatial reference memories. In vivo neural recording revealed that DA neurons in these mutant mice could still develop the cue-reward association responses, but their conditioned response robustness was drastically blunted. Our results suggest that integration of glutamatergic inputs to DA neurons by NMDA receptors, likely by regulating associative activity patterns, is a crucial part of the cellular mechanism underpinning habit learning.
doi:10.1016/j.neuron.2011.10.019
PMCID: PMC3246213  PMID: 22196339
6.  Metabolism of the Lipid Peroxidation Product, 4-Hydroxy-trans-2-nonenal, in Isolated Perfused Rat Heart* 
The Journal of biological chemistry  1998;273(18):10893-10900.
The metabolism of 4-hydroxy-trans-2-nonenal (HNE), an α,β-unsaturated aldehyde generated during lipid peroxidation, was studied in isolated perfused rat hearts. High performance liquid chromatography separation of radioactive metabolites recovered from [3H]HNE-treated hearts revealed four major peaks. Based on the retention times of synthesized standards, peak I, which accounted for 20% radioactivity administered to the heart, was identified to be due to glutathione conjugates of HNE. Peaks II and III, containing 2 and 37% radioactivity, were assigned to 1,4-dihydroxy-2-nonene (DHN) and 4-hydroxy-2-nonenoic acid, respectively. Peak IV was due to unmetabolized HNE. The electrospray ionization mass spectrum of peak I revealed two prominent metabolites with m/z values corresponding to [M + H]+ of HNE and DHN conjugates with glutathione. The presence of 4-hydroxy-2-nonenoic acid in peak III was substantiated using gas chromatography-chemical ionization mass spectroscopy. When exposed to sorbinil, an inhibitor of aldose reductase, no GS-DHN was recovered in the coronary effluent, and treatment with cyanamide, an inhibitor of aldehyde dehydrogenase, attenuated 4-hydroxy-2-nonenoic acid formation. These results show that the major metabolic transformations of HNE in rat heart involve conjugation with glutathione and oxidation to 4-hydroxy-2-nonenoic acid. Further metabolism of the GS-HNE conjugate involves aldose reductase-mediated reduction, a reaction catalyzed in vitro by homogenous cardiac aldose reductase.
PMCID: PMC3522116  PMID: 9556565
7.  Discovery and pharmacological study of a novel diuretic 
Journal of Translational Medicine  2012;10(Suppl 2):A63.
doi:10.1186/1479-5876-10-S2-A63
PMCID: PMC3479984
8.  Mechanisms of Action of Isothiocyanates in Cancer Chemoprevention: An Update 
Food & function  2011;2(10):579-587.
Isothiocyanates, derived from glucosinolates, are thought to be responsible for the chemoprotective actions conferred by higher cruciferous vegetable intake. Evidence suggests that isothiocyanates exert their effects through a variety of distinct but interconnected signaling pathways important for inhibiting carcinogenesis, including those involved in detoxification, inflammation, apoptosis, and cell cycle and epigenetic regulation, among others. This article provides an update on the latest research on isothiocyanates and these mechanisms, and points out remaining gaps in our understanding of these events. Given the variety of ITC produced from glucosinolates, and the diverse pathways on which these compounds act, a systems biology approach, in vivo, may help to better characterize their integrated role in cancer prevention. In addition, the effects of dose, duration of exposure, and specificity of different ITC should be considered.
doi:10.1039/c1fo10114e
PMCID: PMC3204939  PMID: 21935537
Isothiocyanates; cruciferous vegetables; chemoprevention; glucosinolates; glutathione S-transferase; NF-κB; biotransformation; detoxification; inflammation; apoptosis; cell cycle; epigenetic regulation
9.  MiR-101 Is Involved in Human Breast Carcinogenesis by Targeting Stathmin1 
PLoS ONE  2012;7(10):e46173.
Background
MicroRNA-101 (miR-101) expression is negatively associated with tumor growth and blood vessel formation in several solid epithelial cancers. However, the role of miR-101 in human breast cancer remains elusive.
Results
MiR-101 was significantly decreased in different subtypes of human breast cancer tissues compared with that in adjacent normal breast tissues (P<0.01). Up-regulation of miR-101 inhibited cell proliferation, migration and invasion, and promoted cell apoptosis in ER alpha-positive and ER alpha-negative breast cancer cells and normal breast cells. Down-regulation of miR-101 displayed opposite effects on cell growth and metastasis. Further investigation revealed a significant inverse correlation between the expression of miR-101 and Stathmin1 (Stmn1), and miR-101 could bind to the 3′-untranslated region (UTR) of Stmn1 to inhibit Stmn1 translation. The inhibition of cell growth and metastasis induced by up-regulation of miR-101 was partially restored by overexpresson of Stmn1. Knockdown of Stmn1 attenuates the down-regulation of miR-101-mediated enhancement of cell growth and metastasis. More importantly, in vivo analysis found that Stmn1 mRNA and protein level in different subtypes of human breast cancer tissues, contrary to the down-regulation of miR-101, were significantly elevated.
Conclusions
This study demonstrates that down-regulation of miR-101 in different subtypes of human breast cancer tissues is linked to the increase of cellular proliferation and invasiveness via targeting Stmn1, which highlights novel regulatory mechanism in breast cancer and may provide valuable clues for the future clinical diagnosis of breast cancer.
doi:10.1371/journal.pone.0046173
PMCID: PMC3469601  PMID: 23071542
10.  Correction: Exploring the Midgut Transcriptome and Brush Border Membrane Vesicle Proteome of the Rice Stem Borer, Chilo suppressalis (Walker) 
PLoS ONE  2012;7(9):10.1371/annotation/46dce407-4b4f-476b-b405-8dff023e17da.
doi:10.1371/annotation/46dce407-4b4f-476b-b405-8dff023e17da
PMCID: PMC3465271
11.  Preparation and in vitro studies of MRI-specific superparamagnetic iron oxide antiGPC3 probe for hepatocellular carcinoma 
Background
The aim of this study was to develop an antiGPC3-ultrasuperparamagnetic iron oxide (USPIO) probe for early detection of hepatocellular carcinoma.
Methods
GPC3 and AFP receptors were selected as biomarkers and conjugated with USPIO nanoparticles coated by dextran with carboxylate groups to synthesize antiGPC3-USPIO and antiAFP-USPIO probes. HepG2 cells (a human hepatocellular carcinoma cell model with high expression of GPC3) were used along with SMMC-7721 cells (a hepatocellular carcinoma cell model with no expression of GPC3), HeLa cells (a cervical cancer model), and HL-7702 (normal hepatocytes) which were used as controls. After incubation with the probes, the iron content in the cells was calculated, USPIO nanoparticles in cells were observed using transmission electron microscopy, and T1 and T2 relaxation times were measured with a 1.5 T magnetic resonance scanner.
Results
AntiGPC3-USPIO probes with a mean hydrodynamic diameter of 47 nm showed good biological compatibility. Transmission electron microscopic images indicated that the amount of USPIO nanoparticles taken up was significantly higher in HepG2 cells incubated with antiGPC3-USPIO than that in HepG2 cells incubated with antiAFP-USPIO or USPIO nanoparticles and that in the SMMC-7721 or HeLa cells incubated with antiGPC3-USPIO probes, antiAFP-USPIO probes, or USPIO nanoparticles. The higher the concentration and the longer the incubation time, the greater the number of USPIO nanoparticles found in the cells. No USPIO nanoparticles were found in the HL-7702 cells. All of the HepG2, SMMC-7721, and HeLa cells incubated with antiGPC3-USPIO, antiAFP-USPIO, or USPIO nanoparticles were able to shorten the T1 and T2 values in agar solution, especially the T2 images of HepG2 cells incubated with antiGPC3-USPIO probes.
Conclusion
AntiGPC3-USPIO probes can be utilized as a specific magnetic resonance targeting contrast agent for early detection of hepatocellular carcinoma. Using a 1.5 T magnetic resonance scanner, the optimal time for imaging HepG2 cells was around 2–4 hours after incubation with antiGPC3-USPIO probes.
doi:10.2147/IJN.S32196
PMCID: PMC3431973  PMID: 22956868
magnetic resonance imaging; hepatocellular carcinoma; HepG2 cells; superparamagnetic iron oxide antiGPC3-USPIO probe
12.  Identification of Genes Required for Nonhost Resistance to Xanthomonas oryzae pv. oryzae Reveals Novel Signaling Components 
PLoS ONE  2012;7(8):e42796.
Background
Nonhost resistance is a generalized, durable, broad-spectrum resistance exhibited by plant species to a wide variety of microbial pathogens. Although nonhost resistance is an attractive breeding strategy, the molecular basis of this form of resistance remains unclear for many plant-microbe pathosystems, including interactions with the bacterial pathogen of rice, Xanthomonas oryzae pv. oryzae (Xoo).
Methods and Findings
Virus-induced gene silencing (VIGS) and an assay to detect the hypersensitive response (HR) were used to screen for genes required for nonhost resistance to Xoo in N. benthamiana. When infiltrated with Xoo strain YN-1, N. benthamiana plants exhibited a strong necrosis within 24 h and produced a large amount of H2O2 in the infiltrated area. Expression of HR- and defense-related genes was induced, whereas bacterial numbers dramatically decreased during necrosis. VIGS of 45 ACE (Avr/Cf-elicited) genes revealed identified seven genes required for nonhost resistance to Xoo in N. benthamiana. The seven genes encoded a calreticulin protein (ACE35), an ERF transcriptional factor (ACE43), a novel Solanaceous protein (ACE80), a hydrolase (ACE117), a peroxidase (ACE175) and two proteins with unknown function (ACE95 and ACE112). The results indicate that oxidative burst and calcium-dependent signaling pathways play an important role in nonhost resistance to Xoo. VIGS analysis further revealed that ACE35, ACE80, ACE95 and ACE175, but not the other three ACE genes, interfered with the Cf-4/Avr4-dependent HR.
Conclusions/Significance
N. benthamiana plants inoculated with Xoo respond by rapidly eliciting an HR and nonhost resistance. The oxidative burst and other signaling pathways are pivotal in Xoo-N. benthamiana nonhost resistance, and genes involved in this response partially overlap with those involved in Cf/Avr4-dependent HR. The seven genes required for N. benthamiana-mediated resistance to Xoo provide a basis for further dissecting the molecular mechanism of nonhost resistance.
doi:10.1371/journal.pone.0042796
PMCID: PMC3418293  PMID: 22912739
13.  RNAi promotes heterochromatic silencing through replication-coupled release of RNA polII 
Nature  2011;479(7371):135-138.
Heterochromatin comprises tightly compacted repetitive regions of eukaryotic chromosomes. The inheritance of heterochromatin through mitosis requires RNA interference (RNAi), which guides histone modification 1 during the DNA replication phase of the cell cycle2. Here, we show that the alternating arrangement of origins of replication and non-coding RNA in pericentromeric heterochromatin results in competition between transcription and replication. Co-transcriptional RNAi releases RNA polymerase II (PolII), allowing completion of DNA replication by the leading strand DNA polymerase, and associated histone modifying enzymes3 which spread heterochromatin with the replication fork. In the absence of RNAi, stalled forks are repaired by homologous recombination without histone modification.
doi:10.1038/nature10501
PMCID: PMC3391703  PMID: 22002604
14.  Consensus Rules in Variant Detection from Next-Generation Sequencing Data 
PLoS ONE  2012;7(6):e38470.
A critical step in detecting variants from next-generation sequencing data is post hoc filtering of putative variants called or predicted by computational tools. Here, we highlight four critical parameters that could enhance the accuracy of called single nucleotide variants and insertions/deletions: quality and deepness, refinement and improvement of initial mapping, allele/strand balance, and examination of spurious genes. Use of these sequence features appropriately in variant filtering could greatly improve validation rates, thereby saving time and costs in next-generation sequencing projects.
doi:10.1371/journal.pone.0038470
PMCID: PMC3371040  PMID: 22715385
15.  Influence of Domain Size on the Scaling Effects in Pb(Mg1/3Nb2/3)O3-PbTiO3 Ferroelectric Crystals 
Scripta materialia  2011;64(12):1149-1151.
The property degradation observed in thin Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) crystals is believed to relate to large domains and subsequent clamping induced by surface-boundary. In this work, the properties were investigated as function of domain size, using controlled poling. The degraded piezoelectric and dielectric properties of thin PMN-PT were found to increase significantly, by decreasing domain size. Furthermore, the fine domain structure was found to be stable at 3kV/cm after 7.0×105 negative-pulse cycles, hence, enabling PMN-PT crystals for high-frequency (>20 MHz) ultrasound-transducers.
doi:10.1016/j.scriptamat.2011.03.018
PMCID: PMC3086291  PMID: 21552347
Crystalline oxides; electrical properties; dielectrics; piezoelectricity; ferroelectricity
16.  Female Condom Use in the Rural Sex Industry in China: Analysis of Users and Non-users at Post-Intervention Surveys 
AIDS care  2011;23(Suppl 1):66-74.
Changes in sexual attitudes and behaviors and resurgence of the sex industry in China have increased concerns about HIV/AIDS and STI epidemics. Little attention has been paid to the significant and growing sex industry in rural China. Promotion of barrier protection in this context is most effective to prevent STIs and pregnancy. The female condom (FC) is a barrier method that gives women more autonomy in its application, and has other advantages, but has been little promoted and tested in high risk contexts in China. The China/U.S. Women’s Health Project was designed to promote FC use in addition to male condoms (MC) through outreach intervention conducted in sex-work establishments in rural and small urban towns in southern China, using the original prototype FC1. The study used quantitative and qualitative methods to document the pre-intervention context, intervention delivery process, and post-intervention outcomes of FC use. In this paper we compare post-intervention FC users and non-users in the first study sites, two rural towns in a single county in Hainan Province. Examination of cross-sectional 6-month and 12-month surveys indicated that, despite relatively high MC use, about one-third of the women in sex-work establishments in these rural towns had adopted FC at each post-intervention survey. Compared to non-users, FC users were more likely to be freelance woman in boarding houses, more sexually experienced, married with children, more sexually active in the prior month, and more exposed to the intervention. The rural context hampered intervention implementation, particularly the significant limits in health and human resources available to manage prevention of HIV/STIs among women in the sex industry. These challenges highlight the need to better understand the context of the rural sex industry and capacity of local resources for better prevention efforts and the benefits that new prevention technologies like FC can offer.
doi:10.1080/09540121.2011.555742
PMCID: PMC3117276  PMID: 21660752
female condom; sex workers; China; HIV/AIDS prevention; establishment-based intervention
17.  Exploring the Midgut Transcriptome and Brush Border Membrane Vesicle Proteome of the Rice Stem Borer, Chilo suppressalis (Walker) 
PLoS ONE  2012;7(5):e38151.
The rice stem borer, Chilo suppressalis (Walker) (Lepidoptera: Pyralidae), is one of the most detrimental pests affecting rice crops. The use of Bacillus thuringiensis (Bt) toxins has been explored as a means to control this pest, but the potential for C. suppressalis to develop resistance to Bt toxins makes this approach problematic. Few C. suppressalis gene sequences are known, which makes in-depth study of gene function difficult. Herein, we sequenced the midgut transcriptome of the rice stem borer. In total, 37,040 contigs were obtained, with a mean size of 497 bp. As expected, the transcripts of C. suppressalis shared high similarity with arthropod genes. Gene ontology and KEGG analysis were used to classify the gene functions in C. suppressalis. Using the midgut transcriptome data, we conducted a proteome analysis to identify proteins expressed abundantly in the brush border membrane vesicles (BBMV). Of the 100 top abundant proteins that were excised and subjected to mass spectrometry analysis, 74 share high similarity with known proteins. Among these proteins, Western blot analysis showed that Aminopeptidase N and EH domain-containing protein have the binding activities with Bt-toxin Cry1Ac. These data provide invaluable information about the gene sequences of C. suppressalis and the proteins that bind with Cry1Ac.
doi:10.1371/journal.pone.0038151
PMCID: PMC3362559  PMID: 22666467
18.  Identification of a Known Mutation in Notch 3 in Familiar CADASIL in China 
PLoS ONE  2012;7(5):e36590.
Background
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease leading to recurrent ischemic stroke and vascular dementia. Numerous mutations in the 23 exons of the NOTCH3 gene have been reported to cause CADASIL in Caucasian populations, but the full spectrum of genetic changes leading to this disease is yet to be known and, especially, very few reports are available on CADASIL in Asian populations.
Methods and Results
We genotyped members of a 5-generational Han Chinese family with CADASIL patients and identified an R133C mutation in the NOTCH3 gene. Clinical analysis demonstrated that the penetrance of the mutation was not complete. Five of the mutation carriers, not exposed to the known vascular risk factors, did not show any clinical feature of CADASIL, suggesting the importance of environmental factors to the development of this disease.
Conclusions
Members of a 5-generational Han Chinese family with CADASIL patients had an R133C mutation in the NOTCH3 gene but only individuals exposed to known vascular risk factors developed CADASIL.
doi:10.1371/journal.pone.0036590
PMCID: PMC3356370  PMID: 22623959
19.  Vitamin D Deficiency Is Associated with Decreased Lung Function in Chinese Adults with Asthma 
Respiration  2010;81(6):469-475.
Background
Vitamin D deficiency has been associated with markers for allergy and asthma severity in children with asthma. However, its association with Chinese adult asthmatics has not been studied.
Objective
To examine whether vitamin D status is associated with lung function and total serum IgE in Chinese adults with newly diagnosed asthma.
Methods
We conducted a cross-sectional study including 435 Chinese patients aged >18 years with newly diagnosed asthma. Vitamin D status was assessed by measuring serum 25 hydroxyvitamin D (25OHD) concentrations. The primary outcomes included airflow limitation, as measured by the forced expiratory volume in 1 s (FEV1), FEV1 % predicted, and FEV1/forced vital capacity (FVC), and serum total IgE concentration.
Results
Vitamin D deficiency was prevalent in Chinese adults with asthma, with 88.9% of the subjects having 25OHD <50 nmol/l. Serum 25OHD concentration was positively correlated with FEV1 % predicted (p = 0.02, r = 0.12). After adjusting for age, sex, body mass index, smoking, month of blood collection, and symptom duration, we found significant positive associations between 25OHD concentrations and FEV1 (in liters), FEV1 % predicted, and FEV1/FVC (p for trend < 0.05 for all). The adjusted odds ratios for the highest versus the lowest 25OHD quartile were 0.50 (0.26–0.96) for FEV1 <75% predicted and 0.44 (0.20–0.95) for FEV1/FVC% <0.75. There was no significant association between 25OHD concentrations and total IgE.
Conclusions
Vitamin D deficiency was highly prevalent in Chinese asthma patients, and vitamin D status was associated with lung function.
doi:10.1159/000322008
PMCID: PMC3124457  PMID: 21124013
Vitamin D; Asthma; Lung function; FEV1; IgE
20.  Prevalence of Childhood Atopic Dermatitis: An Urban and Rural Community-Based Study in Shanghai, China 
PLoS ONE  2012;7(5):e36174.
Background
Atopic dermatitis (AD) is a common inflammatory and chronically relapsing disorder with increasing prevalence. However, little is known about its prevalence in Shanghai, the top metropolitan of China. This study will estimate and compare the prevalence of AD in urban and rural areas in representative samples of 3 to 6-year-old children in Shanghai.
Methodology/Principal Findings
A descriptive cross-sectional study was performed. Pre-school children were obtained by cluster sampling from 8 communities in different districts in Shanghai. The main instrument was the core questionnaire module for AD used in the U.K. Working Party's study. All the data were statistically analyzed by EpiData 3.1 and SPSS16.0. A total of 10436 children completed the study satisfactorily, with a response rate of 95.8%. The prevalence of AD in 3 to 6-year-old children was 8.3% (Male: 8.5%, Female: 8.2%). The prevalence in urban areas of Shanghai was gradiently and significantly higher than that in rural areas. The highest prevalence was in the core urban area (10.2% in Xuhui Tianping) vs. the lowest far from the urban areas (4.6% in Chongming Baozhen).
Conclusions/Significance
The prevalence of AD was 8.3% (95%CI: 7.6%–9.1%) in children aged 3 to 6 in Shanghai. The prevalence of AD decreased from the center to the rural areas in Shanghai.
doi:10.1371/journal.pone.0036174
PMCID: PMC3341360  PMID: 22563481
21.  DW-MRI as a Biomarker to Compare Therapeutic Outcomes in Radiotherapy Regimens Incorporating Temozolomide or Gemcitabine in Glioblastoma 
PLoS ONE  2012;7(4):e35857.
The effectiveness of the radiosensitizer gemcitabine (GEM) was evaluated in a mouse glioma along with the imaging biomarker diffusion-weighted magnetic resonance imaging (DW-MRI) for early detection of treatment effects. A genetically engineered murine GBM model [Ink4a-Arf−/− PtenloxP/loxP/Ntv-a RCAS/PDGF(+)/Cre(+)] was treated with gemcitabine (GEM), temozolomide (TMZ) +/− ionizing radiation (IR). Therapeutic efficacy was quantified by contrast-enhanced MRI and DW-MRI for growth rate and tumor cellularity, respectively. Mice treated with GEM, TMZ and radiation showed a significant reduction in growth rates as early as three days post-treatment initiation. Both combination treatments (GEM/IR and TMZ/IR) resulted in improved survival over single therapies. Tumor diffusion values increased prior to detectable changes in tumor volume growth rates following administration of therapies. Concomitant GEM/IR and TMZ/IR was active and well tolerated in this GBM model and similarly prolonged median survival of tumor bearing mice. DW-MRI provided early changes to radiosensitization treatment warranting evaluation of this imaging biomarker in clinical trials.
doi:10.1371/journal.pone.0035857
PMCID: PMC3334987  PMID: 22536446
22.  Tissue-specific Function of Farnesoid X Receptor in Liver and Intestine 
Nuclear receptors (NRs) are ligand-activated transcriptional factors that are involved in various physiological, developmental, and toxicological processes. Farnesoid X receptor (FXR) is a NR that belongs to the NR superfamily. The endogenous ligands of FXR are bile acids. FXR is essential in regulating a network of genes involved in maintaining bile acid and lipid homeostasis. It is clear that FXR is critical for liver and intestinal function. In mice FXR deficiency leads to the development of cholestasis, gallstone disease, nonalcoholic steatohepatitis, liver tumor, and colon tumor. Using mouse models where FXR is deleted either in the whole-body, or selectively in hepatocytes or enterocytes, we start to reveal the importance of tissue-specific FXR function in regulating bile acid and lipid homeostasis. However, a great challenge exists for developing tissue-specific FXR modulators to prevent and treat diseases associated with bile acid or lipid disorders. With further understanding of FXR function in both rodents and humans, this nuclear receptor may emerge as a novel target to prevent and treat liver, gastrointestinal and systemic diseases.
doi:10.1016/j.phrs.2010.12.018
PMCID: PMC3063452  PMID: 21211565
23.  Prediagnosis of Obstructive Sleep Apnea via Multiclass MTS 
Obstructive sleep apnea (OSA) has become an important public health concern. Polysomnography (PSG) is traditionally considered an established and effective diagnostic tool providing information on the severity of OSA and the degree of sleep fragmentation. However, the numerous steps in the PSG test to diagnose OSA are costly and time consuming. This study aimed to apply the multiclass Mahalanobis-Taguchi system (MMTS) based on anthropometric information and questionnaire data to predict OSA. Implementation results showed that MMTS had an accuracy of 84.38% on the OSA prediction and achieved better performance compared to other approaches such as logistic regression, neural networks, support vector machine, C4.5 decision tree, and rough set. Therefore, MMTS can assist doctors in prediagnosis of OSA before running the PSG test, thereby enabling the more effective use of medical resources.
doi:10.1155/2012/212498
PMCID: PMC3321537  PMID: 22545062
24.  Methyl 2-{[(3-methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-4-yl­idene)(4-nitro­phen­yl)meth­yl]amino}-3-phenyl­propano­ate 
The mol­ecule of the title compound, C27H24N4O5, exists in the keto–enamine tautomeric form, stabilized by an intra­molecular N—H⋯O hydrogen bond. An intra­molecular C—H⋯·O hydrogen bond also occurs. In the crystal, C—H⋯O hydrogen bonds link the mol­ecules into chains.
doi:10.1107/S1600536812010343
PMCID: PMC3344020  PMID: 22589929
25.  catena-Poly[[dichloridomercury(II)]-N′-nicotinoylnicotinohydrazide] 
The title complex, [HgCl2(C12H10N4O2)]n, is composed of one HgII ion, one nnh ligand (nnh = N′-nicotinoylnicotinohydrazide) and two coordinated chloride ions. The HgII ion shows a distorted tetra­hedral geometry, being surrounded by two N atoms from two nnh ligands and two chloride ions. Due to the bridging role of nnh, the HgII atoms are connected into polymeric chains along the c axis, which are further inter­linked via N—H⋯O and C—H⋯Cl hydrogen-bonding inter­actions, forming a three-dimensional network.
doi:10.1107/S1600536812008884
PMCID: PMC3343788  PMID: 22589762

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