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1.  Lipoprotein lipase gene Hind III polymorphism was associated with hemorrhagic stroke 
Objective: To investigate the relevance between lipoprotein lipase (LPL) Hind III gene polymorphism and cerebral hemorrhage. Methods: A case-control study was performed utilizing PCR-RFLP method and sequencing of amplified products to detect LPL Hind III gene polymorphism in 350 cases of hemorrhagic stroke (HS group) and 350 healthy subjects (control group). Blood lipids and glucose levels were also recorded for each attendant. Results: In HS group, T and G allele frequencies were 90.8% and 9.2%, respectively; while those in the control group were 82.3% and 17.7%. In HS group, detection rate of the G allele frequency and GG genotype were significantly lower than those in the control group. In addition, TG, LDL-C, fasting blood glucose , systolic blood pressure , diastolic blood pressure were significantly higher in HS group (P<0.05, P<0.01). Compared with TG+GG genotype, TT genotype population show significantly higher triglycerides concentration (P<0.05). With adjustment for hypertension, high blood sugar, and age -related factors, multivariate logistic regression analysis showed that LPL Hind III G allele could be a protective factor (OR = 0.392, 95% CI: 0.191~0.805, P = 0.011). Conclusion: LPL Hind III gene polymorphism was relevant to hemorrhagic stroke. LPL Hind III G mutant allele could be a protective factor in the pathogenesis of cerebral hemorrhage.
PMCID: PMC4538159  PMID: 26309627
Cerebral hemorrhage; lipoprotein lipase; polymerase chain reaction; gene frequencies; genotype; risk factors
2.  Heat shock protein expression enhances heat tolerance of reptile embryos 
The role of heat shock proteins (HSPs) in heat tolerance has been demonstrated in cultured cells and animal tissues, but rarely in whole organisms because of methodological difficulties associated with gene manipulation. By comparing HSP70 expression patterns among representative species of reptiles and birds, and by determining the effect of HSP70 overexpression on embryonic development and hatchling traits, we have identified the role of HSP70 in the heat tolerance of amniote embryos. Consistent with their thermal environment, and high incubation temperatures and heat tolerance, the embryos of birds have higher onset and maximum temperatures for induced HSP70 than do reptiles, and turtles have higher onset and maximum temperatures than do lizards. Interestingly, the trade-off between benefits and costs of HSP70 overexpression occurred between life-history stages: when turtle embryos developed at extreme high temperatures, HSP70 overexpression generated benefits by enhancing embryo heat tolerance and hatching success, but subsequently imposed costs by decreasing heat tolerance of surviving hatchlings. Taken together, the correlative and causal links between HSP70 and heat tolerance provide, to our knowledge, the first unequivocal evidence that HSP70 promotes thermal tolerance of embryos in oviparous amniotes.
PMCID: PMC4132679  PMID: 25080340
critical thermal maximum; embryonic development; gene overexpression; HSP70; thermal adaptation; thermotolerance
5.  Histological outcome for chronic hepatitis B patients treated with entecavir vs lamivudine-based therapy 
AIM: To compare the histological outcome of chronic hepatitis B (CHB) patients treated with entecavir (ETV) or lamivudine (LAM)-based therapy.
METHODS: We conducted a retrospective analysis of data from 42 CHB patients with advanced fibrosis (baseline Ishak score ≥ 2) or cirrhosis who were treated with ETV or LAM-based therapy in Beilun People’s Hospital, Ningbo between January 2005 and May 2012. The patients enrolled were more than 16 years of age and underwent a minimum of 12 mo of antiviral therapy. We collected data on the baseline characteristics of each patient and obtained paired liver biopsies pre- and post-treatment. The Knodell scoring system and Ishak fibrosis scores were used to evaluate each example. An improvement or worsening of necroinflammation was defined as ≥ 2-point change in the Knodell inflammatory score. The progression or regression of fibrosis was defined as ≥ 1-point change in the Ishak fibrosis score. The continuous variables were compared using t-test or Mann-Whitney test, and the binary variables were compared using χ2 test or Fisher’s exact test. The results of paired liver biopsies were compared with a Wilcoxon signed rank test.
RESULTS: Nineteen patients were treated with ETV and 23 patients were treated with LAM therapy for a mean duration of 39 and 42 mo, respectively. After long-term antiviral treatment, 94.74% (18/19) of the patients in the ETV arm and 95.65% (22/23) in the LAM arm achieved an HBV DNA level less than 1000 IU/mL. The majority of the patients (94.74% in the ETV arm and 73.91% in the LAM arm) had normalized ALT levels. The median Knodell necroinflammatory score decreased from 11 to 0 in the patients receiving ETV, and the median Knodell score decreased from 9 to 3 in the patients receiving LAM (P = 0.0002 and < 0.0001, respectively). The median Ishak fibrosis score showed a 1-point reduction in ETV-treated patients and a 2-point reduction in LAM-treated patients (P = 0.0019 and 0.0205, respectively). The patients receiving ETV showed a more significant improvement in necroinflammation than the LAM-treated patients (P = 0.0003). However, there was no significant difference in fibrotic improvement between the two arms. Furthermore, two patients in each arm achieved a fibrosis score of 0 post-treatment, which indicates a full reversion of fibrosis after antiviral therapy.
CONCLUSION: CHB patients with advanced fibrosis or cirrhosis benefit from antiviral treatment. ETV is superior to LAM therapy in improving necroinflammatory but not fibrotic outcome.
PMCID: PMC4548120  PMID: 26327767
Advanced fibrosis; Chronic hepatitis B; Cirrhosis; Entecavir; Histological outcome; Lamivudine
6.  Cemented allograft-prosthesis composite reconstruction for the proximal femur tumor 
OncoTargets and therapy  2015;8:2261-2269.
Cemented allograft-prosthesis composite (APC) reconstruction is one option following resection of the proximal femur tumor. However, rare studies have focused on the indications and complications. The goal of the present study was to (1) ascertain the indications for cemented APC arthroplasty in the proximal femur; (2) identify the detailed perioperative management; and (3) illustrate our experiences to avoid the complications of cemented APC.
Materials and methods
A total 28 patients who underwent cemented APC reconstruction of the proximal femur after tumor resection were retrospectively evaluated at a median follow-up of 56 months. Clinical records and radiographs were reviewed to evaluate patients’ outcome.
In our series, excluding three cases of death that had a short follow-up period, union occurred in 22 (88.0%) patients (range 9–18 months). Nonunion of the greater trochanter was seen in six of the 12 patients (50.0%). Eight (32.0%) hips had resorption. There were two (8.0%) hips that were observed to have asymptomatic wear of the acetabulum. The average Musculoskeletal Tumor Society (MSTS) score was 26.5 points. The average Harris Hip Score (HHS) score was 80.6 points. There were no cases of recurrence, but metastasis was found in two hips.
Mastering indications, perioperative management, and complication prevention are all very important in the APC reconstruction after resection of the proximal femur.
PMCID: PMC4556043  PMID: 26345329
bone tumor; surgical treatment; limb salvage
7.  Potential role of nuclear receptor ligand all-trans retinoic acids in the treatment of fungal keratitis 
Fungal keratitis (FK) is a worldwide visual impairment disease. This infectious fungus initiates the primary innate immune response and, later the adaptive immune response. The inflammatory process is related to a variety of immune cells, including macrophages, helper T cells, neutrophils, dendritic cells, and Treg cells, and is associated with proinflammatory, chemotactic and regulatory cytokines. All-trans retinoic acids (ATRA) have diverse immunomodulatory actions in a number of inflammatory and autoimmune conditions. These retinoids regulate the transcriptional levels of target genes through the activation of nuclear receptors. Retinoic acid receptor α (RAR α), retinoic acid receptor γ (RAR γ), and retinoid X receptor α (RXR α) are expressed in the cornea and immune cells. This paper summarizes new findings regarding ATRA in immune and inflammatory diseases and analyzes the perspective application of ATRA in FK.
PMCID: PMC4539647  PMID: 26309886
nuclear receptor; all-trans retinoic acid; fungal keratitis; cornea
8.  Rhizosphere bacterial communities of dominant steppe plants shift in response to a gradient of simulated nitrogen deposition 
We evaluated effects of 9-year simulated nitrogen (N) deposition on microbial composition and diversity in the rhizosphere of two dominant temperate grassland species: grass Stipa krylovii and forb Artemisia frigida. Microbiomes in S. krylovii and A. frigida rhizosphere differed, but changed consistently along the N gradient. These changes were correlated to N-induced shifts to plant community. Hence, as plant biomass changed, so did bacterial rhizosphere communities, a result consistent with the role that N fertilizer has been shown to play in altering plant-microbial mutualisms. A total of 23 bacterial phyla were detected in the two rhizospheric soils by pyrosequencing, with Proteobacteria, Acidobacteria, and Bacteroidetes dominating the sequences of all samples. Bacterioidetes and Proteobacteria tended to increase, while Acidobacteria declined with increase in N addition rates. TM7 increased >5-fold in the high N addition rates, especially in S. krylovii rhizosphere. Nitrogen addition also decreased diversity of OTUs (operational taxonomic units), Shannon and Chao1 indices of rhizospheric microbes regardless of plant species. These results suggest that there were both similar but also specific changes in microbial communities of temperate steppes due to N deposition. These findings would contribute to our mechanistic understanding of impacts of N deposition on grassland ecosystem by linking changes in plant traits to their rhizospheric microbes-mediated processes.
PMCID: PMC4533001  PMID: 26322024
nitrogen deposition; microbial diversity; rhizosphere; Illumina Miseq; temperate steppe; Artemisia frigida; Stipa kerlovii
9.  The Structural Characterization of Tumor Fusion Genes and Proteins 
Chromosomal translocation, which generates fusion proteins in blood tumor or solid tumor, is considered as one of the major causes leading to cancer. Recent studies suggested that the disordered fragments in a fusion protein might contribute to its carcinogenicity. Here, we investigated the sequence feature near the breakpoints in the fusion partner genes, the structure features of breakpoints in fusion proteins, and the posttranslational modification preference in the fusion proteins. Results show that the breakpoints in the fusion partner genes have both sequence preference and structural preference. At the sequence level, nucleotide combination AG is preferred before the breakpoint and GG is preferred at the breakpoint. At the structural level, the breakpoints in the fusion proteins prefer to be located in the disordered regions. Further analysis suggests the phosphorylation sites at serine, threonine, and the methylation sites at arginine are enriched in disordered regions of the fusion proteins. Using EML4-ALK as an example, we further explained how the fusion protein leads to the protein disorder and contributes to its carcinogenicity. The sequence and structural features of the fusion proteins may help the scientific community to predict novel breakpoints in fusion genes and better understand the structure and function of fusion proteins.
PMCID: PMC4546970  PMID: 26347798
10.  Halogenated Diarylacetylenes Repress c-Myc Expression in Cancer Cells 
Halogenated diarylacetylenes that possess fluorine or chlorine substituents in one aryl ring and N-methylamino or N,N-dimethylamino in the other aryl ring inhibit the proliferation of LS174T colon cancer cells through the repression of c-myc expression and induction of the cyclin-dependent kinase inhibitor-1 (i.e., p21(Wif1/Cip1)) and represent potentially useful antineoplastic agents.
PMCID: PMC4096707  PMID: 24930834
11.  Spatiotemporal Clustering Analysis and Risk Assessments of Human Cutaneous Anthrax in China, 2005–2012 
PLoS ONE  2015;10(7):e0133736.
To investigate the epidemic characteristics of human cutaneous anthrax (CA) in China, detect the spatiotemporal clusters at the county level for preemptive public health interventions, and evaluate the differences in the epidemiological characteristics within and outside clusters.
CA cases reported during 2005–2012 from the national surveillance system were evaluated at the county level using space-time scan statistic. Comparative analysis of the epidemic characteristics within and outside identified clusters was performed using using the χ2 test or Kruskal-Wallis test.
The group of 30–39 years had the highest incidence of CA, and the fatality rate increased with age, with persons ≥70 years showing a fatality rate of 4.04%. Seasonality analysis showed that most of CA cases occurred between May/June and September/October of each year. The primary spatiotemporal cluster contained 19 counties from June 2006 to May 2010, and it was mainly located straddling the borders of Sichuan, Gansu, and Qinghai provinces. In these high-risk areas, CA cases were predominantly found among younger, local, males, shepherds, who were living on agriculture and stockbreeding and characterized with high morbidity, low mortality and a shorter period from illness onset to diagnosis.
CA was geographically and persistently clustered in the Southwestern China during 2005–2012, with notable differences in the epidemic characteristics within and outside spatiotemporal clusters; this demonstrates the necessity for CA interventions such as enhanced surveillance, health education, mandatory and standard decontamination or disinfection procedures to be geographically targeted to the areas identified in this study.
PMCID: PMC4514625  PMID: 26208355
12.  TMEM140 is associated with the prognosis of glioma by promoting cell viability and invasion 
Gliomas are the most common types of primary brain tumors in the adult central nervous system. TMEM140 is identified as an amplified gene in the human gastric cancer genome. However, the function of TMEM140 in gliomas has not been thoroughly elucidated. The aim of the current study was to determine the clinical significance of TMEM140 expression in patients with gliomas and its effect on tumor cell malignant phenotypes.
Immunohistochemical analysis and real-time reverse transcription PCR were performed to detect the expression levels of TMEM140 in 70 glioma brain tissue samples. Next, the correlation between the TMEM140 expression levels and the clinical characteristics and outcomes of glioma patients was statistically analyzed. TMEM140 expression was inhibited in two glioma cell lines (i.e., U87 and U373) using a knockdown method with small interfering RNA. Cell Counting Kit-8 and Transwell assays were used to investigate TMEM140 function during cell proliferation, invasion, and migration, respectively. Using flow cytometry and Western blot analysis, we subsequently determined the cell cycle and apoptosis profile of the TMEM140-silenced cells.
TMEM140 protein expression was significantly higher in gliomas than in normal brain tissues (p < 0.0001). TMEM140 overexpression was strongly correlated with tumor size, histologic grade, and overall survival time (P < 0.05). TMEM140 decreased cell viability in vitro and dramatically decreased tumor volume in vivo. This phenomenon might be caused by G1 phase cell cycle arrest and cell apoptosis. TMEM140 silencing could suppress the viability, migration, and invasion of glioma cells.
Our results suggest that TMEM140 expression is a prognostic factor that might play an important role in the viability, migration, and invasion of glioma cells. This study highlights the importance of TMEM140 as a novel prognostic marker and as an attractive therapeutic target for gliomas.
PMCID: PMC4511541  PMID: 26198430
TMEM140; Glioma; Cell viability; Invasion; Prognosis
13.  CRISPR-Cas9-Mediated Genome Editing in Leishmania donovani 
mBio  2015;6(4):e00861-15.
The prokaryotic CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9, an RNA-guided endonuclease, has been shown to mediate efficient genome editing in a wide variety of organisms. In the present study, the CRISPR-Cas9 system has been adapted to Leishmania donovani, a protozoan parasite that causes fatal human visceral leishmaniasis. We introduced the Cas9 nuclease into L. donovani and generated guide RNA (gRNA) expression vectors by using the L. donovani rRNA promoter and the hepatitis delta virus (HDV) ribozyme. It is demonstrated within that L. donovani mainly used homology-directed repair (HDR) and microhomology-mediated end joining (MMEJ) to repair the Cas9 nuclease-created double-strand DNA break (DSB). The nonhomologous end-joining (NHEJ) pathway appears to be absent in L. donovani. With this CRISPR-Cas9 system, it was possible to generate knockouts without selection by insertion of an oligonucleotide donor with stop codons and 25-nucleotide homology arms into the Cas9 cleavage site. Likewise, we disrupted and precisely tagged endogenous genes by inserting a bleomycin drug selection marker and GFP gene into the Cas9 cleavage site. With the use of Hammerhead and HDV ribozymes, a double-gRNA expression vector that further improved gene-targeting efficiency was developed, and it was used to make precise deletion of the 3-kb miltefosine transporter gene (LdMT). In addition, this study identified a novel single point mutation caused by CRISPR-Cas9 in LdMT (M381T) that led to miltefosine resistance, a concern for the only available oral antileishmanial drug. Together, these results demonstrate that the CRISPR-Cas9 system represents an effective genome engineering tool for L. donovani.
Leishmania donovani is the causative agent of fatal visceral leishmaniasis. To understand Leishmania infection and pathogenesis and identify new drug targets for control of leishmaniasis, more-efficient ways to manipulate this parasite genome are required. In this study, we have implemented CRISPR-Cas9 genome-editing technology in L. donovani. Both single- and dual-gRNA expression vectors were developed using a strong RNA polymerase I promoter and ribozymes. With this system, it was possible to generate loss-of-function insertion and deletion mutations and introduce drug selection markers and the GFP sequence precisely into the L. donovani genome. These methods greatly improved the ability to manipulate this parasite genome and will help pave the way for high-throughput functional analysis of Leishmania genes. This study further revealed that double-stranded DNA breaks created by CRISPR-Cas9 were repaired by the homology-directed repair (HDR) pathway and microhomology-mediated end joining (MMEJ) in Leishmania.
PMCID: PMC4513079  PMID: 26199327
14.  Plasma levels of lysophosphatidic acid in ovarian cancer versus controls: a meta-analysis 
In this study, using a meta-analysis approach, we examined the correlation between serum levels of lysophosphastidic acid (LPA) and ovarian cancer (OC).
Relevant published studies were identified from multiple scientific literature databases by using a pre-determined electronic and manual search strategy. The search results were screened through a multi-step process to select high-quality case–control studies suitable for the present meta-analysis. Mean values and standardized mean differences (SMD) were calculated for plasma LPA levels. Two investigators independently extracted the data from the studies and performed data analysis using STATA software version 12.0 (Stata Corp, College Station, TX, USA).
Nineteen case–control studies met our selection criteria and contained a total of 980 OC patients, 872 benign controls and 668 healthy controls. Our meta-analysis results revealed that the plasma levels of LPA in OC patients were significantly higher than benign controls (SMD = 2.36, 95 % CI: 1.61–3.10, P <0.001) and healthy controls (SMD = 2.32, 95 % CI: 1.77–2.87, P <0.001). Subgroup analysis by ethnicity showed that the plasma LPA levels in OC patients were significantly higher than the benign controls only in Asian populations (SMD = 2.52, 95 % CI: 1.79–3.25, P <0.001). However, a comparison between healthy controls and OC patients revealed that, in both Asians and Caucasians, the OC patients displayed significantly higher plasma LPA levels compared to healthy controls (all P <0.05).
Our meta-analysis showed strong evidence that a significantly higher plasma LPA levels are present in OC patients, compared to benign controls and healthy controls, and plasma LPA levels may be used as a biomarker or target of OC.
PMCID: PMC4501043  PMID: 26174150
Lysophosphatidic acid; Ovarian cancer; Bioactive phospholipid; Meta-analysis
15.  Corneal Stroma Regeneration with Acellular Corneal Stroma Sheets and Keratocytes in a Rabbit Model 
PLoS ONE  2015;10(7):e0132705.
Acellular corneal stroma matrix has been used for corneal stroma engineering. However, because of its compact tissue structure, regrowth of keratocytes into the scaffold is difficult. Previously, we developed a sandwich model for cartilage engineering using acellular cartilage sheets. In the present study, we tested this model for corneal stroma regeneration using acellular porcine corneal stroma (APCS) sheets and keratocytes. Porcine corneas were decellularized by NaCl treatment, and the APCS was cut into 20-μm-thick sheets. A rabbit corneal stroma defect model was created by lamellar keratoplasty and repaired by transplantation of five pieces of APCS sheets with keratocytes. Six months after transplantation, transparent corneas were present in the experimental group, which were confirmed by anterior segment optical coherence tomography examination and transmittance examination. The biomechanical properties in the experimental group were similar to those of normal cornea. Histological analyses showed an even distribution of keratocytes and well-oriented matrix in the stroma layer in the experimental group. Together, these results demonstrated that the sandwich model using acellular corneal stroma sheets and keratocytes could be potentially useful for corneal stroma regeneration.
PMCID: PMC4500565  PMID: 26167895
16.  Transcriptional Activation of Multiple Operons Involved in para-Nitrophenol Degradation by Pseudomonas sp. Strain WBC-3 
Pseudomonas sp. strain WBC-3 utilizes para-nitrophenol (PNP) as a sole carbon and energy source. The genes involved in PNP degradation are organized in the following three operons: pnpA, pnpB, and pnpCDEFG. How the expression of the genes is regulated is unknown. In this study, an LysR-type transcriptional regulator (LTTR) is identified to activate the expression of the genes in response to the specific inducer PNP. While the LTTR coding gene pnpR was found to be not physically linked to any of the three catabolic operons, it was shown to be essential for the growth of strain WBC-3 on PNP. Furthermore, PnpR positively regulated its own expression, which is different from the function of classical LTTRs. A regulatory binding site (RBS) with a 17-bp imperfect palindromic sequence (GTT-N11-AAC) was identified in all pnpA, pnpB, pnpC, and pnpR promoters. Through electrophoretic mobility shift assays and mutagenic analyses, this motif was proven to be necessary for PnpR binding. This consensus motif is centered at positions approximately −55 bp relative to the four transcriptional start sites (TSSs). RBS integrity was required for both high-affinity PnpR binding and transcriptional activation of pnpA, pnpB, and pnpR. However, this integrity was essential only for high-affinity PnpR binding to the promoter of pnpCDEFG and not for its activation. Intriguingly, unlike other LTTRs studied, no changes in lengths of the PnpR binding regions of the pnpA and pnpB promoters were observed after the addition of the inducer PNP in DNase I footprinting.
PMCID: PMC4272733  PMID: 25326309
17.  Effects of combined aerobic and resistance training on the glycolipid metabolism and inflammation levels in type 2 diabetes mellitus 
Journal of Physical Therapy Science  2015;27(7):2365-2371.
[Purpose] To investigate the effects of combined aerobic and resistance training on glycolipid metabolism and inflammation levels in type 2 diabetes mellitus patients. [Subjects and Methods] Forty-two diabetes patients were randomized to the conventional therapy group (n = 20) or intensive therapy group (n = 22). The control group contained 20 healthy people. The conventional therapy group received routine drug therapy and diet control, while the intensive therapy group additionally underwent combined aerobic and resistance training for 12 weeks. The oral glucose tolerance test and cardiopulmonary exercise testing were performed. Toll-like receptor 4 and NF-κBp65 protein and mRNA expressions were determined by qPCR and western blotting. ELISA was used to determine the expression levels of interleukin-18, interleukin-33, pentraxin-related protein 3, and human cartilage glycoprotein 39. [Results] After exercise training, the intensive therapy group had significantly lower postprandial blood glucose, postprandial insulin, and glycated hemoglobin level and insulin resistance index than the conventional therapy group. The intensive therapy group had significantly lower toll-like receptor 4 and NF-κBp65 protein and mRNA expressions, and serum interleukin-18 levels but significantly higher serum interleukin-33 levels. [Conclusion] Combined aerobic and resistance training can improve glycolipid metabolism and reduce low-grade inflammation in patients with diabetes mellitus patients.
PMCID: PMC4540883  PMID: 26311110
Type 2 diabetes mellitus; Exercise therapy; Inflammation
18.  Distribution of cervical intraepithelial neoplasia on the cervix in Chinese women: pooled analysis of 19 population based screening studies 
BMC Cancer  2015;15:485.
Controversy remains whether a pattern of cervical intraepithelial neoplasia exists on the cervix. Our study aims at determining if the prevalence of histologically proven lesions differs by cervical four-quadrant location or by 12 o'clock surface locations of diagnosis.
We conducted a retrospective, histopathological study of 19 different population based cervical cancer screening studies from 1999 to 2010 by Cancer Hospital of Chinese Academy of Medical Sciences. The Institutional Review Board for human research subjects at CHCAMS approved all of the studies. During the colposcopy procedure, participant received either 4-quadrant biopsy or directed biopsy with/without endocervical curettage. Data of all samples were stratified by the methods of sampling. Kruskal-Wallis test was used to determine overall distribution of normal/CIN1, CIN2 and CIN3+ on the cervix.
In total, 53,088 cervical samples were included in distribution analysis. 66.9 % samples were obtained by random biopsy, 16.1 % were by directed biopsy, and 17.0 % were by endocervical curettage. 95.9%of the biopsied samples were diagnosed as normal/CIN1, 2.0 % were CIN2, and 2.1 % were CIN3 + . CIN2 and CIN3+ were most often found in quadrants 2 and 3 (χKW2 = 46.6540, p < 0.0001) and at the 4- and 7-o'clock positions by directed biopsy (ORCIN2 = 2.572, 1.689, ORCIN3+ = 3.481, 1.678, respectively), and at the 5-, 6-, 7-, 9- and 12-o’clock positions by random biopsy. CIN3+ was least often found at the 11-o’clock position by directed biopsy (OR = 0.608).
Our results suggest a predisposition of specific locations on the cervix to CIN occurrence. Quadrants 2 and 3, especially the 4- and 7-o’clock positions should be preferentially targeted during biopsy. The decision for random biopsy should be reconsidered in future studies.
Electronic supplementary material
The online version of this article (doi:10.1186/s12885-015-1494-4) contains supplementary material, which is available to authorized users.
PMCID: PMC4485364  PMID: 26122004
Colposcopy; Cervical intraepithelial neoplasia; Lesion location; Biopsy; Cervical cancer
19.  Spatiotemporal Distribution, Sources, and Photobleaching Imprint of Dissolved Organic Matter in the Yangtze Estuary and Its Adjacent Sea Using Fluorescence and Parallel Factor Analysis 
PLoS ONE  2015;10(6):e0130852.
To investigate the seasonal and interannual dynamics of dissolved organic matter (DOM) in the Yangtze Estuary, surface and bottom water samples in the Yangtze Estuary and its adjacent sea were collected and characterized using fluorescence excitation-emission matrices (EEMs) and parallel factor analysis (PARAFAC) in both dry and wet seasons in 2012 and 2013. Two protein-like components and three humic-like components were identified. Three humic-like components decreased linearly with increasing salinity (r>0.90, p<0.001), suggesting their distribution could primarily be controlled by physical mixing. By contrast, two protein-like components fell below the theoretical mixing line, largely due to microbial degradation and removal during mixing. Higher concentrations of humic-like components found in 2012 could be attributed to higher freshwater discharge relative to 2013. There was a lack of systematic patterns for three humic-like components between seasons and years, probably due to variations of other factors such as sources and characteristics. Highest concentrations of fluorescent components, observed in estuarine turbidity maximum (ETM) region, could be attributed to sediment resuspension and subsequent release of DOM, supported by higher concentrations of fluorescent components in bottom water than in surface water at two stations where sediments probably resuspended. Meanwhile, photobleaching could be reflected from the changes in the ratios between fluorescence intensity (Fmax) of humic-like components and chromophoric DOM (CDOM) absorption coefficient (a355) along the salinity gradient. This study demonstrates the abundance and composition of DOM in estuaries are controlled not only by hydrological conditions, but also by its sources, characteristics and related estuarine biogeochemical processes.
PMCID: PMC4479555  PMID: 26107640
20.  Genotype 4 Hepatitis E Virus Prevalent in Eastern China Shows Diverse Subtypes 
Hepatitis Monthly  2015;15(6):e25367.
Hepatitis E Virus (HEV), a zoonotic pathogen, uses several species of animal as reservoirs. Swine is considered as the major reservoir for HEV infection in humans. Genotype 4 HEV is the dominant cause of hepatitis E disease in humans in China.
Although many researches revealed that genotype 4 HEV is the main genotype that prevalent in eastern China, few researches have done to study the subtype of HEV in this area. Thus, this study aimed to investigate the subtype of HEV prevalent in eastern China.
Materials and Methods:
A total of 125 anti-HEV IgM positive human serum and 290 swine fecal samples were subjected to reverse transcription polymerase chain reaction (RT-PCR) screening of HEV RNA. Positive PCR products were sequenced and phylogenetically analyzed.
From a total of 125 human serum samples, 19.2% (24.125) were positive, while 9.66% (28.290) of the 290 swine fecal samples were positive for HEV RNA. Phylogenetic analysis based on partial capsid gene showed that the 51 HEV strains in the current study all belonged to genotype 4, clustering into 6 different subtypes. Our results also revealed that some of HEV isolates prevalent in the human and swine populations were classified into the same clusters.
Genotype 4 HEV in eastern China shows subtype diversity and some HEV isolates are involved in cross-species transmission.
PMCID: PMC4533028  PMID: 26288632
Hepatitis E Virus; Genotype; Subtype; Genetic Diversity
21.  Abundance and significance of neuroligin-1 and glutamate in Hirschsprung’s disease 
AIM: To investigate the abundance and potential diagnostic significance of neuroligin-1 and glutamate (Glu) in Hirschsprung’s disease (HSCR).
METHODS: Ninety children with HSCR and 50 children without HSCR matched for similar nutritional status, age and basal metabolic index were studied. The expression and localization of neuroligin-1 and Glu were assessed using double-labeling immunofluorescence staining of longitudinal muscles with adherent myenteric plexus from the surgically excised colon of children with HSCR. Western blot analysis, quantitative real-time PCR (qRT-PCR) and immunohistochemistry were performed to evaluate the abundance of neuroligin-1 and Glu in different HSCR-affected segments (ganglionic, transitional, and aganglionic segments). Enzyme-linked immunosorbent assay (ELISA) was used to detect and compare serum Glu levels in the long-segment HSCR, short-segment HSCR and non-HSCR samples.
RESULTS: Neuroligin-1 and Glu were co-expressed highest to lowest in the ganglionic, transitional and aganglionic segments based on Western blot (neuroligin-1: 0.177 ± 0.008 vs 0.101 ± 0.006, 0.177 ± 0.008 vs 0.035 ± 0.005, and 0.101 ± 0.006 vs 0.035 ± 0.005, P < 0.005; Glu: 0.198 ± 0.006 vs 0.115 ± 0.008, 0.198 ± 0.006 vs 0.040 ± 0.003, and 0.115 ± 0.008 vs 0.040 ± 0.003, P < 0.005) and qRT-PCR (neuroligin-1: 9.58 × 10-5 ± 9.94 × 10-6 vs 2.49 × 10-5 ± 1.38 × 10-6, 9.58 × 10-5 ± 9.94 × 10-6 vs 7.17 × 10-6 ± 1.12 × 10-6, and 2.49 × 10-5 ± 1.38 × 10-6 vs 7.17 × 10-6 ± 1.12 × 10-6, P < 0.005). Serum Glu level was the highest to lowest in the non-HSCR, short-type HSCR and long-type HSCR samples based on ELISA (in nmol/μL, 0.93 ± 0.31 vs 0.57 ± 0.25, 0.93 ± 0.31 vs 0.23 ± 0.16, and 0.57 ± 0.25 vs 0.23 ± 0.16, P < 0.005).
CONCLUSION: Neuroligin-1 and Glu may represent new markers of ganglion cells, whose expression may correlate with the pathogenesis, diagnosis, differential diagnosis or classification of HSCR.
PMCID: PMC4476878  PMID: 26109803
Neuroligin-1; Hirschsprung’s disease; Glutamate; Ganglion cells; Pathogenesis
22.  Comparison of non-schistosomal rectosigmoid cancer and schistosomal rectosigmoid cancer 
AIM: To compare the clinicopathological features of patients with non-schistosomal rectosigmoid cancer and schistosomal rectosigmoid cancer.
METHODS: All the patients with rectosigmoid carcinoma who underwent laparoscopic radical surgical resection in the Shanghai Minimally Invasive Surgical Center at Ruijin Hospital affiliated to Shanghai Jiao-Tong University between October 2009 and October 2013 were included in this study. Twenty-six cases of colonic schistosomiasis diagnosed through colonoscopy and pathological examinations were collected. Symptoms, endoscopic findings and clinicopathological characteristics were evaluated retrospectively.
RESULTS: There were no significant differences between patients with and without schistosomiasis in gender, age, CEA, CA19-9, preoperative biopsy findings or postoperative pathology. Patients with rectosigmoid schistosomiasis had a significantly higher CA-125 level and a larger proportion of these patients were at an early tumor stage (P = 0.003). Various morphological characteristics of schistosomiasis combined with rectosigmoid cancer could be found by colonoscopic examination: 46% were fungating mass polyps, 23% were congestive and ulcerative polyps, 23% were cauliflower-like masses, 8% were annular masses. Only 27% of the patients were diagnosed with rectal carcinoma preoperatively after the biopsy. Computed tomography (CT) scans showed thickened intestinal walls combined with linear and tram-track calcifications in 26 patients.
CONCLUSION: Rectosigmoid carcinoma combined with schistosomiasis is associated with higher CA-125 values and early tumor stages. CA-125 and CT scans have a reasonable sensitivity for the accurate diagnosis.
PMCID: PMC4476884  PMID: 26109809
Schistosomiasis; Rectosigmoid cancer; Colonoscopy; Biomarker; Diagnosis
23.  2′,6′-Dihalostyrylanilines, Pyridines, and Pyrimidines for the Inhibition of the Catalytic Subunit of Methionine S-Adenosyltransferase-2 
Journal of Medicinal Chemistry  2014;57(14):6083-6091.
Inhibition of the catalytic subunit of the heterodimeric methionine S-adenosyl transferase-2 (MAT2A) with fluorinated N,N-dialkylaminostilbenes (FIDAS agents) offers a potential avenue for the treatment of liver and colorectal cancers where upregulation of this enzyme occurs. A study of structure–activity relationships led to the identification of the most active compounds as those with (1) either a 2,6-difluorostyryl or 2-chloro-6-fluorostyryl subunit, (2) either an N-methylamino or N,N-dimethylamino group attached in a para orientation relative to the 2,6-dihalostyryl subunit, and (3) either an N-methylaniline or a 2-(N,N-dimethylamino)pyridine ring. These modifications led to FIDAS agents that were active in the low nanomolar range, that formed water-soluble hydrochloride salts, and that possessed the desired property of not inhibiting the human hERG potassium ion channel at concentrations at which the FIDAS agents inhibit MAT2A. The active FIDAS agents may inhibit cancer cells through alterations of methylation reactions essential for cancer cell survival and growth.
PMCID: PMC4111374  PMID: 24950374
24.  Do nuclear-encoded core subunits of mitochondrial complex I confer genetic susceptibility to schizophrenia in Han Chinese populations? 
Scientific Reports  2015;5:11076.
Schizophrenia is one of the most prevalent psychiatric disorders with complex genetic etiology. Accumulating evidence suggests that energy metabolism and oxidative stress play important roles in the pathophysiology of schizophrenia. Dysfunction of mitochondrial respiratory chain and altered expression of complex I subunits were frequently reported in schizophrenia. To investigate whether nuclear-encoded core subunit genes of mitochondrial complex I are associated with schizophrenia, we performed a genetic association study in Han Chinese. In total, 46 tag single nucleotide polymorphisms (SNPs) from 7 nuclear-encoded core genes of mitochondrial complex I were genotyped in 918 schizophrenia patients and 1042 healthy controls. We also analyzed these SNPs in a large sample mainly composed of Europeans through using the available GWAS datasets from the Psychiatric Genomics Consortium (PGC). No significant associations were detected between these SNPs and schizophrenia in Han Chinese and the PGC data set. However, we observed nominal significant associations of 2 SNPs in the NDUFS1 gene and 4 SNPs in the NDUFS2 gene with early onset schizophrenia (EOS), but none of these associations survived the Bonferroni correction. Taken together, our results suggested that common SNPs in the nuclear-encoded core subunit genes of mitochondrial complex I may not confer genetic susceptibility to schizophrenia.
PMCID: PMC4459149  PMID: 26053550
25.  Identification and characterization of long non-coding RNAs involved in osmotic and salt stress in Medicago truncatula using genome-wide high-throughput sequencing 
BMC Plant Biology  2015;15:131.
Long non-coding RNAs (lncRNAs) have been shown to play crucially regulatory roles in diverse biological processes involving complex mechanisms. However, information regarding the number, sequences, characteristics and potential functions of lncRNAs in plants is so far overly limited.
Using high-throughput sequencing and bioinformatics analysis, we identified a total of 23,324 putative lncRNAs from control, osmotic stress- and salt stress-treated leaf and root samples of Medicago truncatula, a model legume species. Out of these lncRNAs, 7,863 and 5,561 lncRNAs were identified from osmotic stress-treated leaf and root samples, respectively. While, 7,361 and 7,874 lncRNAs were identified from salt stress-treated leaf and root samples, respectively. To reveal their potential functions, we analyzed Gene Ontology (GO) terms of genes that overlap with or are neighbors of the stress-responsive lncRNAs. Enrichments in GO terms in biological processes such as signal transduction, energy synthesis, molecule metabolism, detoxification, transcription and translation were found.
LncRNAs are likely involved in regulating plant’s responses and adaptation to osmotic and salt stresses in complex regulatory networks with protein-coding genes. These findings are of importance for our understanding of the potential roles of lncRNAs in responses of plants in general and M. truncatula in particular to abiotic stresses.
Electronic supplementary material
The online version of this article (doi:10.1186/s12870-015-0530-5) contains supplementary material, which is available to authorized users.
PMCID: PMC4457090  PMID: 26048392
Long non-coding RNAs (lncRNAs); Osmotic stress; Salt stress; Medicago truncatula; Legume plants; High-throughput sequencing; Transcriptional regulation

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