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1.  Sex and Ethnic Differences in Validity of Self-reported Adult Height, Weight and Body Mass Index 
Ethnicity & disease  2012;22(1):72-78.
Objectives
Describe self-reported and measured height, weight, and body mass index (BMI) stratified by sex and ethnicity in the United States, explore ethnic variations in the likelihood of under-reporting BMI, and investigate pathways linking race/ethnicity to the underassessment of BMI.
Design
An observational study.
Setting
The entire United States.
Patients or Participants
Data were from the 2007–2008 National Health and Nutrition Examination Survey, a nationally representative sample of non-institutionalized civilian Americans.
Main Outcome
Objectively measured and subjectively reported BMI.
Measures
Independent variables include race/ethnicity (non-Hispanic Whites, non-Hispanic Blacks, Hispanics, and others), sex, age groups (age 20–29, 30–49, 50–69, and ≥70), marital status (currently married vs other marital categories), education (less than high school, high school graduate or equivalent, some college, college graduate or above), and poverty income ratio (PIR).
Results
This study confirmed that the use of reported BMI led to underestimates of the population prevalence of overweight and obesity due to the general tendency towards over-reporting height and under-reporting weight. Women were more likely than men to under-report BMI. And Whites were more likely than Blacks and Hispanics to under-report BMI. Other factors positively associated with higher likelihood of under-reporting of BMI included overweight and obese weight status, aged ≥60 years, and college education. Among women, family income was an additional positive covariate.
Conclusions
The results from this study underscore the need for frequently monitoring ethnic differences in validity of reported BMI and highlight the care which needs to be taken in making comparisons across sociodemographic groups based on reported BMI.
PMCID: PMC3590903  PMID: 22774312
BMI; Validity; Self-reported; Measurement; Sex; Ethnicity
2.  Neuregulin Facilitates Nerve Regeneration by Speeding Schwann Cell Migration via ErbB2/3-Dependent FAK Pathway 
PLoS ONE  2013;8(1):e53444.
Background
Adequate migration of Schwann cells (Sc) is crucial for axon-guidance in the regenerative process after peripheral nerve injury (PNI). Considering neuregulin-erbB-FAK signaling is an essential pathway participating in the regulation of Sc migration during development, the present study is aimed to examine whether neuregulin would exert its beneficial effects on adult following PNI and further determine the potential changes of downstream pathway engaged in neuro-regeneration by both in vitro and in vivo approaches.
Methodology and Principal Findings
Cultured RSC96 cells treated with neuregulin were processed for erbB2/3 immunofluorescence and FAK immunoblotings. The potential effects of neuregulin on Sc were assessed by cell adherence, spreading, and migration assays. In order to evaluate the functional significance of neuregulin on neuro-regeneration, the in vivo model of PNI was performed by chronic end-to-side neurorrhaphy (ESN). In vitro studies indicated that after neuregulin incubation, erbB2/3 were not only expressed in cell membranes, but also distributed throughout the cytoplasm and nucleus of RSC96 cells. Activation of erbB2/3 was positively correlated with FAK phosphorylation. Neuregulin also increases Sc adherence, spreading, and migration by 127.2±5.0%, 336.8±3.0%, and 80.0±5.7%, respectively. As for in vivo study, neuregulin significantly accelerates the speed of Sc migration and increases Sc expression in the distal stump of injured nerves. Retrograde labeling and compound muscle action potential recordings (CMAP) also showed that neuregulin successfully facilitates nerve regeneration by eliciting noticeably larger CMAP and promoting quick re-innervation of target muscles.
Conclusions
As neuregulin successfully improves axo-glial interaction by speeding Sc migration via the erbB2/3-FAK pathway, therapeutic use of neuregulin may thus serve as a promising strategy to facilitate the progress of nerve regeneration after PNI.
doi:10.1371/journal.pone.0053444
PMCID: PMC3534691  PMID: 23301073
3.  Development and evaluation of a loop-mediated isothermal amplification assay for the rapid detection of porcine cytomegalovirus under field conditions 
Virology Journal  2012;9:321.
Background
Porcine cytomegalovirus (PCMV) induces silent infection in adult pigs but more frequently causes fatal, generalized infection in newborn piglets. This study aimed to develop a new loop-mediated isothermal amplification (LAMP) method for the sensitive, rapid, and inexpensive detection of PCMV under field conditions.
Methods
Tissue obtained from nine-week-old PCMV-free Landrace pigs or pig samples from postmortem examinations were analyzed. The samples were found to have clinical signs and lesions consistent with inclusion body rhinitis. Six specific primers were designed by targeting the PCMV DNA polymerase (DPOL) DNA. The LAMP reaction was optimized in a water bath. The sensitivity and specificity of LAMP and polymerase chain reaction (PCR) were compared.
Results
PCMV DNA was amplified at 65°C, and the result could be detected as early as 30 min into the reaction. Positive reactions could be visualized by the naked eye as a color change brought on by the addition of SYBR Green. The sensitivity and specificity of LAMP were found to be similar to those of the PCR.
Conclusions
LAMP is a high-throughput technique for the detection of PCMV and has a high specificity, sensitivity and simplicity; these factors make it suitable for detection of PCMV under field conditions.
doi:10.1186/1743-422X-9-321
PMCID: PMC3552788  PMID: 23272902
Porcine cytomegalovirus; Loop-mediated isothermal amplification; Landrace pigs; Field detection
4.  Latino Residential Isolation and the Risk of Obesity in Utah: The Role of Neighborhood Socioeconomic, Built-Environmental, and Subcultural Context 
The prevalence rate of obesity in the United States has been persistently high in recent decades, and disparities in obesity risks are routinely observed. Both individual and contextual factors should be considered when addressing health disparities. This study examines how Latino-white spatial segregation is associated with the risk of obesity for Latinos and whites, whether neighborhood socioeconomic resources, the built environment, and subcultural orientation serve as the underlying mechanisms, and whether neighborhood context helps explain obesity disparities across ethnic and immigrant groups. The study was based on an extensive database containing self-reported BMI measures obtained from driver license records in Utah merged with census data and several GIS-based data. Multilevel analyses were performed to examine the research questions. For both men and women, Latino residential isolation is significantly and positively linked to the risk of obesity; after controlling for immigrant concentration, this effect gets amplified. Moreover, for men and women, the segregation effect is partly attributable to neighborhood SES and the built environment; and only for women is it partly attributable to obesity prevalence in the neighborhood. Place matters for individual risk of obesity for both men and women and there are multifarious pathways linking residence to obesity. Among the demographic, socioeconomic, physical, and cultural aspects of neighborhood context examined in this study, perhaps the most modifiable environment features that could prevent weight gain and its associated problems would be the built environmental factors such as greenness, park access, and mixed land use.
doi:10.1007/s10903-011-9439-8
PMCID: PMC3132271  PMID: 21274631
Obesity; Residential segregation; Immigrant enclave; Built environment
5.  ROBUST FAT SUPPRESSION AT 3T IN HIGH-RESOLUTION DIFFUSION-WEIGHTED SINGLE-SHOT EPI OF HUMAN BRAIN 
Single-shot EPI is the most common acquisition technique for whole-brain diffusion tensor imaging (DTI) studies in vivo. Higher field MRI systems are readily available and advantageous for acquiring DTI due to increased signal. One of the practical issues for DTI with single-shot EPI at high field is incomplete fat suppression resulting in a chemically-shifted fat artifact within the brain image. Unsuppressed fat is especially detrimental in DTI because the diffusion coefficient of fat is two orders of magnitude lower than that of parenchyma, producing brighter appearing fat artifacts with greater diffusion weighting. In this work, several fat suppression techniques were tested alone and in combination with the goal of finding a method that provides robust fat suppression and can be utilized in high-resolution single-shot EPI DTI studies. Combination of chemical shift saturation with slice-select gradient reversal within a dual-spin-echo diffusion preparation period was found to provide robust fat suppression at 3T.
doi:10.1002/mrm.22940
PMCID: PMC3162087  PMID: 21604298
6.  Mutations Derived from the Thermophilic Polyhydroxyalkanoate Synthase PhaC Enhance the Thermostability and Activity of PhaC from Cupriavidus necator H16 
Journal of Bacteriology  2012;194(10):2620-2629.
The thermophile Cupriavidus sp. strain S-6 accumulated polyhydroxybutyrate (PHB) from glucose at 50°C. A 9.0-kbp EcoRI fragment cloned from the genomic DNA of Cupriavidus sp. S-6 enabled Escherichia coli XL1-Blue to synthesize PHB at 45°C. Nucleotide sequence analysis showed a pha locus in the clone. The thermophilic polyhydroxyalkanoate (PHA) synthase (PhaCCsp) shared 81% identity with mesophilic PhaC of Cupriavidus necator H16. The diversity between these two strains was found dominantly on their N and C termini, while the middle regions were highly homologous (92% identity). We constructed four chimeras of mesophilic and thermophilic phaC genes to explore the mutations related to its thermostability. Among the chimeras, only PhaCH16β, which was PhaCH16 bearing 30 point mutations derived from the middle region of PhaCCsp, accumulated a high content of PHB (65% [dry weight]) at 45°C. The chimera phaCH16β and two parental PHA synthase genes were overexpressed in E. coli BLR(DE3) cells and purified. At 30°C, the specific activity of the chimera PhaCH16β (172 ± 17.8 U/mg) was 3.45-fold higher than that of the parental enzyme PhaCH16 (50 ± 5.2 U/mg). At 45°C, the half-life of the chimera PhaCH16β (11.2 h) was 127-fold longer than that of PhaCH16 (5.3 min). Furthermore, the chimera PhaCH16β accumulated 1.55-fold (59% [dry weight]) more PHA content than the parental enzyme PhaCH16 (38% [dry weight]) at 37°C. This study reveals a limited number of point mutations which enhance not only thermostability but also PhaCH16 activity. The highly thermostable and active PHA synthase will provide advantages for its promising applications to in vitro PHA synthesis and recombinant E. coli PHA fermentation.
doi:10.1128/JB.06543-11
PMCID: PMC3347165  PMID: 22408158
7.  The Effect of Specific Immunotherapy on Natural Killer T cells in Peripheral Blood of House Dust Mite-Sensitized Children with Asthma 
To investigate the effects of specific immunotherapy on the NKT cells in peripheral blood and the ability of NKT cells to proliferate in response to alpha-galactosylceramide (alpha-GalCer) in house-dust-mite- (HDM-) sensitized asthma children, peripheral blood mononuclear cells were isolated from 42 asthmatic children, of whom 24 were on specific immunotherapy (SIT) for more than a year and 20 were healthy. Compared with control group, the ratio of peripheral blood NKT and CD4+NKT cells was significantly decreased (P < 0.01) and was elevated in SIT asthma group (P < 0.05), respectively, but it was still less than the normal control group (P < 0.01). The level of IL-4 in serum secreted by NKT cells in asthma group was significantly higher than that of control group (P < 0.01), particularly apparent after 72 hours. The level of IL-4 in SIT group decreased significantly (P < 0.01). The level of IL-10 in serum secreted by NKT cells in asthma group was decreased significantly than that of the control group (P < 0.01) especially in 48 hours, while that of SIT group was increased significantly (P < 0.01). These results suggest that the pathogenesis of asthma may be related to the ratio and dysfunction of NKT and CD4+NKT cells.
doi:10.1155/2012/148262
PMCID: PMC3449137  PMID: 23008731
8.  Comparative transcript profiling of gene expression between seedless Ponkan mandarin and its seedy wild type during floral organ development by suppression subtractive hybridization and cDNA microarray 
BMC Genomics  2012;13:397.
Background
Seedlessness is an important agronomic trait for citrus, and male sterility (MS) is one main cause of seedless citrus fruit. However, the molecular mechanism of citrus seedlessness remained not well explored.
Results
An integrative strategy combining suppression subtractive hybridization (SSH) library with cDNA microarray was employed to study the underlying mechanism of seedlessness of a Ponkan mandarin seedless mutant (Citrus reticulata Blanco). Screening with custom microarray, a total of 279 differentially expressed clones were identified, and 133 unigenes (43 contigs and 90 singletons) were obtained after sequencing. Gene Ontology (GO) distribution based on biological process suggested that the majority of differential genes are involved in metabolic process and respond to stimulus and regulation of biology process; based on molecular function they function as DNA/RNA binding or have catalytic activity and oxidoreductase activity. A gene encoding male sterility-like protein was highly up-regulated in the seedless mutant compared with the wild type, while several transcription factors (TFs) such as AP2/EREBP, MYB, WRKY, NAC and C2C2-GATA zinc-finger domain TFs were down-regulated.
Conclusion
Our research highlighted some candidate pathways that participated in the citrus male gametophyte development and could be beneficial for seedless citrus breeding in the future.
doi:10.1186/1471-2164-13-397
PMCID: PMC3495689  PMID: 22897898
Citrus; cDNA microarray; Differential transcript; Male sterility-like protein; Seedlessness
9.  Effects of Hyperuricemia on Renal Function of Renal Transplant Recipients: A Systematic Review and Meta-Analysis of Cohort Studies 
PLoS ONE  2012;7(6):e39457.
Background
Hyperuricemia is an independent risk factor of nephropathy, but its role in renal transplant recipients (RTRs) is controversial.
Methods
Based on the methods of Cochrane systematic reviews, we searched MEDLINE (1948–2011.6), EMBASE (1956–2011.6), CBM (Chinese Biomedicine Database) (1978–2011.6) to identify cohort studies assessing the association between uric acid level and kidney allograft. Two authors independently screened the studies, assessed the risk of bias of included studies and extracted data. Unadjusted odds ratio(OR), mean difference (MD), adjusted hazard ratio (aHR) and their corresponding 95%CI were pooled to assess the effects of hyperuricemia on kidney allograft.
Results
Twelve cohort studies were included and the quality was moderate to high based on the NEWCASTLE-OTTAWA quality assessment scale. RTRs with hyperuricemia had lower eGFR (P<0.0001, 95%CI−16.34∼6.14) and higher SCr (P<0.00001, 95%CI 0.17∼0.31) than those with normal uric acid level. Meta-analysis showed that hyperuricemia was a risk factor of chronic allograft nephropathy (Unadjusted OR = 2.85, 95%CI 1.84∼4.38, adjusted HR = 1.65, 95%CI 1.02∼2.65) and graft loss (Unadjusted OR = 2.29, 95%CI 1.55∼3.39; adjusted HR = 2.01, 95%CI 1.39∼2.94).
Conclusions
Current evidence suggests that hyperuricemia may be an independent risk factor of allograft dysfunction. Hyperuricemia may modestly increase the risk of poor outcomes of RTRs. Future research is needed to verify whether lowering uric acid level could improve the kidney function and prognosis of RTRs with hyperuricemia.
doi:10.1371/journal.pone.0039457
PMCID: PMC3382160  PMID: 22745759
10.  miREvo: an integrative microRNA evolutionary analysis platform for next-generation sequencing experiments 
BMC Bioinformatics  2012;13:140.
Background
MicroRNAs (miRNAs) are small (~19-24nt) non-coding RNAs that play important roles in various biological processes. To date, the next-generation sequencing (NGS) technology has been widely used to discover miRNAs in plants and animals. Although evolutionary analysis is important to reveal the functional dynamics of miRNAs, few computational tools have been developed to analyze the evolution of miRNA sequence and expression across species, especially the newly emerged ones,
Results
We developed miREvo, an integrated software platform with a graphical user interface (GUI), to process deep-sequencing data of small RNAs and to analyze miRNA sequence and expression evolution based on the multiple-species whole genome alignments (WGAs). Three major features are provided by miREvo: (i) to identify novel miRNAs in both plants and animals, based on a modified miRDeep algorithm, (ii) to detect miRNA homologs and measure their pairwise evolutionary distances among multiple species based on a WGA, and (iii) to profile miRNA expression abundances and analyze expression divergence across multiple species (small RNA libraries). Moreover, we demonstrated the utility of miREvo with Illumina data sets from Drosophila melanogaster and Arabidopsis, respectively.
Conclusion
This work presents an integrated pipline, miREvo, for exploring the expressional and evolutionary dynamics of miRNAs across multiple species. MiREvo is standalone, modular, and freely available at http://evolution.sysu.edu.cn/software/mirevo.htm under the GNU/GPL license.
doi:10.1186/1471-2105-13-140
PMCID: PMC3410788  PMID: 22720726
11.  Paraoxonase-1 Is Not a Major Determinant of Stent Thrombosis in a Taiwanese Population 
PLoS ONE  2012;7(6):e39178.
Background
Clopidogrel is a prodrug that undergoes in vivo bioactivation to show its antiplatelet effects. Recent studies have shown that cytochrome P450 (CYP), ATP-binding cassette transporters (ABCB1), and paraoxonase-1 (PON1) play crucial roles in clopidogrel bioactivation. Here, we aim to determine the effects of genetic polymorphisms of CYP (CYP 2C19*2, CYP 2C19*3, and CYP 2C19*17), ABCB1 (ABCB1 3435C>T, ABCB1 129T>C, and ABCB1 2677G>T/A), and PON1 (PON1 Q192R, PON1 L55M, and PON1 108C>T) on the development of stent thrombosis (ST) in patients receiving clopidogrel after percutaneous coronary intervention (PCI).
Methods and Results
We evaluated the incidence of ST (0.64%) in 4964 patients who were recruited in the CAPTAIN registry (Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions). The presence of genetic polymorphisms was assessed in 20 subjects who developed ST after aspirin and clopidogrel therapy and in 40 age- and sex-matched control subjects who did not develop ST, which was documented after 9 months of angiographic follow-up. ST was acute in 5 subjects, subacute in 7, late in 7, and very late in 1. The presence of CYP 2C19*2 allele was significantly associated with ST (adjusted odds ratio [ORadj]: 4.20, 95% confidence interval [CI], 1.263–9.544; P = 0.031). However, genetic variations in PON1 and ABCB1 showed no significant association with ST.
Conclusion
We conclude that in a Taiwanese population, PON1 Q192R genotype is not associated with ST development after PCI. However, the presence of CYP 2C19*2 allele is a risk factor for ST development after PCI.
doi:10.1371/journal.pone.0039178
PMCID: PMC3377663  PMID: 22723959
14.  Acute Kidney Injury Biomarkers for Patients in a Coronary Care Unit: A Prospective Cohort Study 
PLoS ONE  2012;7(2):e32328.
Background
Renal dysfunction is an established predictor of all-cause mortality in intensive care units. This study analyzed the outcomes of coronary care unit (CCU) patients and evaluated several biomarkers of acute kidney injury (AKI), including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18) and cystatin C (CysC) on the first day of CCU admission.
Methodology/Principal Findings
Serum and urinary samples collected from 150 patients in the coronary care unit of a tertiary care university hospital between September 2009 and August 2010 were tested for NGAL, IL-18 and CysC. Prospective demographic, clinical and laboratory data were evaluated as predictors of survival in this patient group. The most common cause of CCU admission was acute myocardial infarction (80%). According to Acute Kidney Injury Network criteria, 28.7% (43/150) of CCU patients had AKI of varying severity. Cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.05) between patients with AKI versus those without AKI. For predicting AKI, serum CysC displayed an excellent areas under the receiver operating characteristic curve (AUROC) (0.895±0.031, p<0.001). The overall 180-day survival rate was 88.7% (133/150). Multiple Cox logistic regression hazard analysis revealed that urinary NGAL, serum IL-18, Acute Physiology, Age and Chronic Health Evaluation II (APACHE II) and sodium on CCU admission day one were independent risk factors for 6-month mortality. In terms of 6-month mortality, urinary NGAL had the best discriminatory power, the best Youden index, and the highest overall correctness of prediction.
Conclusions
Our data showed that serum CysC has the best discriminative power for predicting AKI in CCU patients. However, urinary NGAL and serum IL-18 are associated with short-term mortality in these critically ill patients.
doi:10.1371/journal.pone.0032328
PMCID: PMC3285210  PMID: 22384218
15.  Diversification of Genes Encoding Granule-Bound Starch Synthase in Monocots and Dicots Is Marked by Multiple Genome-Wide Duplication Events 
PLoS ONE  2012;7(1):e30088.
Starch is one of the major components of cereals, tubers, and fruits. Genes encoding granule-bound starch synthase (GBSS), which is responsible for amylose synthesis, have been extensively studied in cereals but little is known about them in fruits. Due to their low copy gene number, GBSS genes have been used to study plant phylogenetic and evolutionary relationships. In this study, GBSS genes have been isolated and characterized in three fruit trees, including apple, peach, and orange. Moreover, a comprehensive evolutionary study of GBSS genes has also been conducted between both monocots and eudicots. Results have revealed that genomic structures of GBSS genes in plants are conserved, suggesting they all have evolved from a common ancestor. In addition, the GBSS gene in an ancestral angiosperm must have undergone genome duplication ∼251 million years ago (MYA) to generate two families, GBSSI and GBSSII. Both GBSSI and GBSSII are found in monocots; however, GBSSI is absent in eudicots. The ancestral GBSSII must have undergone further divergence when monocots and eudicots split ∼165 MYA. This is consistent with expression profiles of GBSS genes, wherein these profiles are more similar to those of GBSSII in eudicots than to those of GBSSI genes in monocots. In dicots, GBSSII must have undergone further divergence when rosids and asterids split from each other ∼126 MYA. Taken together, these findings suggest that it is GBSSII rather than GBSSI of monocots that have orthologous relationships with GBSS genes of eudicots. Moreover, diversification of GBSS genes is mainly associated with genome-wide duplication events throughout the evolutionary course of history of monocots and eudicots.
doi:10.1371/journal.pone.0030088
PMCID: PMC3264551  PMID: 22291904
16.  Nuclear GRP75 Binds Retinoic Acid Receptors to Promote Neuronal Differentiation of Neuroblastoma 
PLoS ONE  2011;6(10):e26236.
Retinoic acid (RA) has been approved for the differentiation therapy of neuroblastoma (NB). Previous work revealed a correlation between glucose-regulated protein 75 (GRP75) and the RA-elicited neuronal differentiation of NB cells. The present study further demonstrated that GRP75 translocates into the nucleus and physically interacts with retinoid receptors (RARα and RXRα) to augment RA-elicited neuronal differentiation. GRP75 was required for RARα/RXRα-mediated transcriptional regulation and was shown to reduce the proteasome-mediated degradation of RARα/RXRαin a RA-dependent manner. More intriguingly, the level of GRP75/RARα/RXRα tripartite complexes was tightly associated with the RA-induced suppression of tumor growth in animals and the histological grade of differentiation in human NB tumors. The formation of GRP75/RARα/RXRα complexes was intimately correlated with a normal MYCN copy number of NB tumors, possibly implicating a favorable prognosis of NB tumors. The present findings reveal a novel function of nucleus-localized GRP75 in actively promoting neuronal differentiation, delineating the mode of action for the differentiation therapy of NB by RA.
doi:10.1371/journal.pone.0026236
PMCID: PMC3194821  PMID: 22022577
17.  “A multi-level analysis of urban/rural and socioeconomic differences in functional health status transition among older Chinese” 
Social science & medicine (1982)  2010;71(3):559-567.
The main purpose of the study is to assess urban versus rural differences in functional status transitions among older Chinese, aged 55+, and to examine how individual and community level socioeconomic indicators alter the rural/urban effects and themselves influence transitions. The study uses a hierarchical linear modeling approach that considers individual responses to be embedded within communities. Data come from the 2004 and 2006 rounds of the Chinese Health and Nutrition Survey. The study considers the functional transitions of 2,944 individuals living across 209 communities in nine Chinese provinces. Functioning is measured at baseline as being able or not being able to conduct all of the following: walking, standing, climbing stairs, lifting, kneeling. Outcomes include having or not having a functional limitation, measured the same way, dying, or not responding. Outcomes are modeled adjusted for baseline functional status. Findings indicate urbanites have substantial advantages. They are less likely to have a limitation at follow-up and less likely to die over the study period. Some of this is explained by socioeconomic indicators measured at two levels. Cross-level interactions suggest education and having insurance operate differently in urban and rural areas. Community-level indicators are somewhat less predictive, and much of the urban advantage is unexplained. In conclusion, the study suggests differences in the influences of socioeconomic indicators in China versus what has been found in the past, and that place of residence in China is a particularly robust predictor of functional health transitions.
doi:10.1016/j.socscimed.2010.03.048
PMCID: PMC2904335  PMID: 20621749
China; disability; health transition; mortality; rural; social class; urban; older people
18.  Surgicopathological classification of hepatic space-occupying lesions: A single-center experience with literature review 
Accompanying rapid developments in hepatic surgery, the number of surgeries and identifications of histological types of primary hepatic space-occupying lesions (PHSOLs) have increased dramatically. This has led to many changes in the surgicopathological spectrum of PHSOLs, and has contributed to a theoretical basis for modern hepatic surgery and oncological pathology. Between 1982 and 2009 at the Eastern Hepatobiliary Surgery Hospital (EHBH) in Shanghai, 31 901 patients underwent surgery and were diagnosed as having a PHSOL. In this paper, we present an analysis of the PHSOL cases at the EHBH for this time period, along with results from a systematic literature review. We describe a surgicopathological spectrum comprising more than 100 types of PHSOLs that can be stratified into three types: tumor-like, benign, and malignant. We also stratified the PHSOLs into six subtypes derived from hepatocytes; cholangiocytes; vascular, lymphoid and hemopoietic tissues; muscular, fibrous and adipose tissues; neural and neuroendocrine tissues; and miscellaneous tissues. The present study provides a new classification system that can be used as a current reference for clinicians and pathologists to make correct diagnoses and differential diagnoses among various PHSOLs.
doi:10.3748/wjg.v17.i19.2372
PMCID: PMC3103789  PMID: 21633636
Liver tumors; Tumor-like lesions; Pathology; Immunohistochemistry; Classification
19.  Defective CFTR-Dependent CREB Activation Results in Impaired Spermatogenesis and Azoospermia 
PLoS ONE  2011;6(5):e19120.
Cystic fibrosis (CF) is the most common life-limiting recessive genetic disease among Caucasians caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) with over 95% male patients infertile. However, whether CFTR mutations could affect spermatogenesis and result in azoospermia remains an open question. Here we report compromised spermatogenesis, with significantly reduced testicular weight and sperm count, and decreased cAMP-responsive element binding protein (CREB) expression in the testes of CFTR knockout mice. The involvement of CFTR in HCO3− transport and the expression of the HCO3− sensor, soluble adenylyl cyclase (sAC), are demonstrated for the first time in the primary culture of rat Sertoli cells. Inhibition of CFTR or depletion of HCO3− could reduce FSH-stimulated, sAC-dependent cAMP production and phosphorylation of CREB, the key transcription factor in spermatogenesis. Decreased CFTR and CREB expression are also observed in human testes with azoospermia. The present study reveals a previously undefined role of CFTR and sAC in regulating the cAMP-CREB signaling pathway in Sertoli cells, defect of which may result in impaired spermatogenesis and azoospermia. Altered CFTR-sAC-cAMP-CREB functional loop may also underline the pathogenesis of various CF-related diseases.
doi:10.1371/journal.pone.0019120
PMCID: PMC3090391  PMID: 21625623
20.  Modeling Hemodynamic Responses in Auditory Cortex at 1.5T Using Variable Duration Imaging Acoustic Noise 
NeuroImage  2009;49(4):3027.
A confound for functional magnetic resonance imaging (fMRI), especially for auditory studies, is the presence of imaging acoustic noise generated mainly as a byproduct of rapid gradient switching during volume acquisition and to a lesser extent, the radio-frequency transmit. This work utilized a novel pulse sequence to present actual imaging acoustic noise for characterization of the induced hemodynamic responses and assessment of linearity in the primary auditory cortex with respect to noise duration. Results show that responses to brief duration (46ms) imaging acoustic noise is highly nonlinear while responses to longer duration (>1s) imaging acoustic noise becomes approximately linear, with the right primary auditory cortex exhibiting a higher degree of nonlinearity than the left for the investigated noise durations. This study also assessed the spatial extent of activation induced by imaging acoustic noise, showing that the use of modeled responses (specific to imaging acoustic noise) as the reference waveform revealed additional activations in the auditory cortex not observed with a canonical gamma variate reference waveform, suggesting an improvement in detection sensitivity for imaging acoustic noise-induced activity. Longer duration (1.5s) imaging acoustic noise was observed to induce activity that expanded outwards from Heschl’s gyrus to cover the superior temporal gyrus as well as parts of the middle temporal gyrus and insula, potentially affecting higher level acoustic processing.
doi:10.1016/j.neuroimage.2009.11.051
PMCID: PMC2818577  PMID: 19948232
imaging acoustic noise; functional MRI; hemodynamic response; linear systems
21.  Beyond Histone and Deacetylase: An Overview of Cytoplasmic Histone Deacetylases and Their Nonhistone Substrates 
Acetylation of lysines is a prominent form of modification in mammalian proteins. Deacetylation of proteins is catalyzed by histone deacetylases, traditionally named after their role in histone deacetylation, transcriptional modulation, and epigenetic regulation. Despite the link between histone deacetylases and chromatin structure, some of the histone deacetylases reside in various compartments in the cytoplasm. Here, we review how these cytoplasmic histone deacetylases are regulated, the identification of nonhistone substrates, and the functional implications of their nondeacetylase enzymatic activities.
doi:10.1155/2011/146493
PMCID: PMC3014693  PMID: 21234400
22.  Microbial and Physicochemical Characteristics of Compact Anaerobic Ammonium-Oxidizing Granules in an Upflow Anaerobic Sludge Blanket Reactor ▿  
Anaerobic ammonium oxidation (anammox) is a promising new process to treat high-strength nitrogenous wastewater. Due to the low growth rate of anaerobic ammonium-oxidizing bacteria, efficient biomass retention is essential for reactor operation. Therefore, we studied the settling ability and community composition of the anaerobic ammonium-oxidizing granules, which were cultivated in an upflow anaerobic sludge blanket (UASB) reactor seeded with aerobic granules. With this seed, the start-up period was less than 160 days at a NH4+-N removal efficiency of 94% and a loading rate of 0.064 kg N per kg volatile suspended solids per day. The formed granules were bright red and had a high settling velocity (41 to 79 m h−1). Cells and extracellular polymeric substances were evenly distributed over the anaerobic ammonium-oxidizing granules. The high percentage of anaerobic ammonium-oxidizing bacteria in the granules could be visualized by fluorescent in situ hybridization and electron microscopy. The copy numbers of 16S rRNA genes of anaerobic ammonium-oxidizing bacteria in the granules were determined to be 4.6 × 108 copies ml−1. The results of this study could be used for a better design, shorter start-up time, and more stable operation of anammox systems for the treatment of nitrogen-rich wastewaters.
doi:10.1128/AEM.02271-09
PMCID: PMC2849188  PMID: 20190088
23.  Novel biomarkers predict liver fibrosis in hepatitis C patients: alpha 2 macroglobulin, vitamin D binding protein and apolipoprotein AI 
Background
The gold standard of assessing liver fibrosis is liver biopsy, which is invasive and not without risk. Therefore, searching for noninvasive serologic biomarkers for liver fibrosis is an importantly clinical issue.
Methods
A total of 16 healthy volunteers and 45 patients with chronic hepatitis C virus (HCV) were enrolled (F0: n = 16, F1: n = 7, F2: n = 17, F3: n = 8 and F4: n = 13, according to the METAVIR classification). Three serum samples of each fibrotic stage were analyzed by two-dimension difference gel electrophoresis (2D-DIGE). The differential proteins were identified by the cooperation of MALDI-TOF/TOF and MASCOT; then western blotting and Bio-Plex Suspension Array were used to quantify the protein levels.
Results
Three prominent candidate biomarkers were identified: alpha 2 macroglobulin (A2M) is up regulated; vitamin D binding protein (VDBP) and apolipoprotein AI (ApoAI) are down regulated. The serum concentration of A2M was significantly different among normal, mild (F1/F2) and advanced fibrosis (F3/F4) (p < 0.01). The protein levels of VDBP and ApoAI were significantly higher in normal/mild fibrosis, when compared to those in advanced fibrosis (both p < 0.01).
Conclusions
This study not only reveals three putative biomarkers of liver fibrosis (A2M, VDBP and ApoAI) but also proves the differential expressions of those markers in different stages of fibrosis. We expect that combination of these novel biomarkers could be applied clinically to predict the stage of liver fibrosis without the need of liver biopsy.
doi:10.1186/1423-0127-17-58
PMCID: PMC2914022  PMID: 20630109
24.  Characterizing Response to Elemental Unit of Acoustic Imaging Noise: An fMRI Study 
Acoustic imaging noise produced during functional magnetic resonance imaging (fMRI) studies can hinder auditory fMRI research analysis by altering the properties of the acquired time-series data. Acoustic imaging noise can be especially confounding when estimating the time course of the hemodynamic response (HDR) in auditory event-related fMRI (fMRI) experiments. This study is motivated by the desire to establish a baseline function that can serve not only as a comparison to other quantities of acoustic imaging noise for determining how detrimental is one's experimental noise, but also as a foundation for a model that compensates for the response to acoustic imaging noise. Therefore, the amplitude and spatial extent of the HDR to the elemental unit of acoustic imaging noise (i.e., a single ping) associated with echoplanar acquisition were characterized and modeled. Results from this fMRI study at 1.5 T indicate that the group-averaged HDR in left and right auditory cortex to acoustic imaging noise (duration of 46 ms) has an estimated peak magnitude of 0.29% (right) to 0.48% (left) signal change from baseline, peaks between 3 and 5 s after stimulus presentation, and returns to baseline and remains within the noise range approximately 8 s after stimulus presentation.
doi:10.1109/TBME.2009.2016573
PMCID: PMC2845537  PMID: 19304477
Acoustic noise; auditory system; biomedical image processing; magnetic resonance imaging; modeling
25.  Dual specimens increase the diagnostic accuracy and reduce the reaction duration of rapid urease test 
AIM: To evaluate the influence of multiple samplings during esophagogastroduodenoscopy (EGD) on the accuracy of the rapid urease test, and the validity of newly developed rapid urease tests, HelicotecUT plus test and HelicotecUT test, CLO test and ProntoDry test.
METHODS: A total of 355 patients undergoing EGD for dyspepsia were included. Their Helicobacter pylori (H. pylori) treatment status was either naïve or eradicated. Six biopsy specimens from antrum and gastric body, respectively, were obtained during EGD. Single antral specimens and dual (antrum + body) specimens were compared. Infection status of H. pylori was evaluated by three different tests: culture, histology, and four different commercially available rapid urease tests (RUTs)-including the newly developed HelicotecUT plus test and HelicotecUT test, and established CLO test and ProntoDry test. H. pylori status was defined as positive when the culture was positive or if there were concordant positive results among histology, CLO test and ProntoDry test.
RESULTS: When dual specimens were applied, sensitivity was enhanced and RUT reaction time was significantly reduced, regardless of their treatment status. Thirty minutes were enough to achieve an agreeable positive rate in all the RUTs. Both newly developed RUTs showed comparable sensitivity, specificity and accuracy to the established RUTs, regardless of patient treatment status, RUT reaction duration, and EGD biopsy sites.
CONCLUSION: Combination of antrum and body biopsy specimens greatly enhances the sensitivity of rapid urease test and reduces the reaction duration to 30 min.
doi:10.3748/wjg.v16.i23.2926
PMCID: PMC2887590  PMID: 20556840
Rapid urease test; Helicobacter pylori eradication; HelicotecUT plus test; HelicotecUT test; Esophagogastroduodenoscopy

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