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1.  Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) Trial: Baseline Characteristics 
Fertility and sterility  2015;103(4):962-973.e4.
Objective
To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications.
Design
Randomized, prospective clinical trial
Patients
900 couples with unexplained infertility Interventions: Ovarian stimulation with gonadotropins, clomiphene citrate, or letrozole in conjunction with intrauterine insemination.
Setting
Multicenter University based clinical practices.
Main Outcome Measures
Demographic, laboratory, imaging, and survey characteristics.
Interventions
Collection of baseline demographics, blood samples, and ultrasonographic assessments.
Results
Demographic characteristics of women receiving clomiphene citrate, letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7± 25.7 months, with 59% primary infertility. More than 1/3 of the women were current or past smokers. The mean BMI was 27 and mean AMH level was 2.6; only 11 women (1.3%) had antral follicle counts of less than 5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners.
Conclusion
The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, AMH levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment subgroups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and clomiphene citrate treatment.
doi:10.1016/j.fertnstert.2014.12.130
PMCID: PMC4529113  PMID: 25707331
Unexplained Infertility; aromatase inhibitors; letrozole; gonadotropins; clomiphene citrate; multiple gestations
3.  Reduced white matter integrity and verbal fluency impairment in young adults with bipolar disorder: a diffusion tensor imaging study 
Background
Clinical evidence shows that bipolar disorder (BD) is characterized by white matter (WM) microstructural abnormalities. However, little is known about the biological mechanisms associated with these abnormalities and their relationship with cognitive functioning.
Methods
49 adult BD patients ((M±SD): 29.27 ± 7.92 years; 17 males, 32 females; 34 BD-I, 10 BD-II, and 5 BD-NOS) and 28 age-matched normal subjects ((M±SD): 29.19 ± 7.35 years; 10 males and 18 females) underwent diffusion tensor imaging (DTI) imaging. DTI metrics were computed using whole-brain tract-based spatial statistics (TBSS) as part of the FMRIB Software Library. Measures of WM coherence (fractional anisotropy - FA) and axonal structure (mean, axial and radial diffusivity - MD, AD and RD) were employed to characterize the microstructural alterations in the limbic, commissural, association and projection fiber tracts. All participants performed the Brief Assessment of Cognition for Affective disorders (BAC-A).
Results
BD patients performed poorly on verbal fluency tasks and exhibited large clusters of altered FA, RD and MD values within the retrolenticular part of the internal capsule, the superior and anterior corona radiata, and the corpus callosum. Increased FA values in the left IFOF and the forceps minor correlated positively with verbal fluency scores. Altered RD parameters in the corticospinal tract and the forceps minor were associated with reduced visuomotor abilities.
Conclusions
The reported verbal fluency deficits and FA, RD and MD alterations in WM structures are potential cognitive and neural markers of BD. Abnormal RD values may be associated with progressive demyelination.
doi:10.1016/j.jpsychires.2015.01.008
PMCID: PMC4355300  PMID: 25684152
bipolar disorder; diffusion tensor imaging; cognitive; demyelination; TBSS
4.  Mode-Division-Multiplexing of Multiple Bessel-Gaussian Beams Carrying Orbital-Angular-Momentum for Obstruction-Tolerant Free-Space Optical and Millimetre-Wave Communication Links 
Scientific Reports  2016;6:22082.
We experimentally investigate the potential of using ‘self-healing’ Bessel-Gaussian beams carrying orbital-angular-momentum to overcome limitations in obstructed free-space optical and 28-GHz millimetre-wave communication links. We multiplex and transmit two beams (l = +1 and +3) over 1.4 metres in both the optical and millimetre-wave domains. Each optical beam carried 50-Gbaud quadrature-phase-shift-keyed data, and each millimetre-wave beam carried 1-Gbaud 16-quadrature-amplitude-modulated data. In both types of links, opaque disks of different sizes are used to obstruct the beams at different transverse positions. We observe self-healing after the obstructions, and assess crosstalk and power penalty when data is transmitted. Moreover, we show that Bessel-Gaussian orbital-angular-momentum beams are more tolerant to obstructions than non-Bessel orbital-angular-momentum beams. For example, when obstructions that are 1 and 0.44 the size of the l = +1 beam, are placed at beam centre, optical and millimetre-wave Bessel-Gaussian beams show ~6 dB and ~8 dB reduction in crosstalk, respectively.
doi:10.1038/srep22082
PMCID: PMC4772084  PMID: 26926068
5.  Different immune cells mediate mechanical pain hypersensitivity in male and female mice 
Nature neuroscience  2015;18(8):1081-1083.
A large and rapidly increasing body of evidence indicates that microglia-neuron signaling is essential for chronic pain hypersensitivity. Here we show using multiple approaches that microglia are not required for mechanical pain hypersensitivity in female mice; female mice achieve similar levels of pain hypersensitivity using adaptive immune cells, likely T-lymphocytes. This sexual dimorphism suggests that male mice cannot be used as proxies for females in pain research.
doi:10.1038/nn.4053
PMCID: PMC4772157  PMID: 26120961
6.  Structural development of human brain white matter from mid-fetal to perinatal stage 
The structures of developing human brain white matter (WM) tracts can be effectively quantified by DTI-derived metrics, including fractional anisotropy (FA), mean, axial and radial diffusivity (MD, AD and RD). However, dynamics of WM microstructure during very early developmental period from mid-fetal to perinatal stage is unknown. It is difficult to accurately measure microstructural properties of these WM tracts due to severe contamination from cerebrospinal fluid (CSF). In this study, high resolution DTI of fetal brains at mid-fetal stage (20 weeks of gestation or 20wg), 19 brains in the middle of 3rd trimester (35wg) and 17 brains around term (40wg) were acquired. We established first population-averaged DTI templates at these three time points and extracted WM skeleton. 16 major WM tracts in limbic, projection, commissural and association tract groups were traced with DTI tractography in native space. The WM skeleton in the template space was inversely transformed back to the native space for measuring core WM microstructures of each individual tract. Continuous microstructural enhancement and volumetric increase of WM tracts were found from 20wg to 40wg. The microstructural enhancement from FA measurement is decelerated in late 3rd trimester compared to mid-fetal to middle 3rd trimester, while volumetric increase of prefrontal WM tracts is accelerated. The microstructural enhancement from 35wg to 40wg is heterogeneous among different tract groups with microstructures of association tracts undergoing most dramatic change. Besides decreases of RD indicating active myelination, the decrease of AD for most WM tracts during late 3rd trimester suggests axonal packing process.
doi:10.1117/12.2082418
PMCID: PMC4771190  PMID: 26937064
white matter; tract; microstructure; template; development; fetal; DTI; skeleton
7.  Cisplatin resistance in gastric cancer cells is associated with HER2 upregulation-induced epithelial-mesenchymal transition 
Scientific Reports  2016;6:20502.
Cisplatin remains to be primary chemotherapeutic drug for gastric cancer patients, especially for advanced stage ones. However, primary or acquired resistance often occurs with the mechanisms being not well understood, which results in relapse of the cancer and poor survival. Herein, we found that HER2 upregulation was associated with cisplatin resistance. We observed that cisplatin-resistant gastric cancer cells underwent a morphological change similar to epithelial-mesenchymal transition (EMT) which is mediated by HER2 overexpression. When specific monoclonal antibody Herceptin, small molecular targeted drug CP724714, or small interfering RNA against HER2 was applied, the EMT-like phenotypic change was dramatically reversed. More importantly, the IC50 and Resistance Index of resistant gastric cancer cells to cisplatin were also decreased by any of these treatments.We demonstrated that expression and amplification of HER2 positively correlated with expression of EMT-related transcription factor Snail in gastric cancer tissues. Furthermore, for the first time, we found that HER2/Snail double positive gastric cancer patients had poorer survival than single positive or double negative counterparts, which provided experimental evidence for the necessity of HER2/Snail double testing in gastric cancer. In conclusion, this study provides some clues of the association of cisplatin resistance with HER2 upregulation-induced EMT in gastric cancer cells.
doi:10.1038/srep20502
PMCID: PMC4742832  PMID: 26846307
8.  Spatial Mapping of Structural and Connectional Imaging Data for the Developing Human Brain with Diffusion Tensor Imaging 
During human brain development from fetal stage to adulthood, the white matter (WM) tracts undergo dramatic changes. Diffusion tensor imaging (DTI), a widely used magnetic resonance imaging (MRI) modality, offers insight into the dynamic changes of WM fibers as these fibers can be noninvasively traced and three-dimensionally (3D) reconstructed with DTI tractography. The DTI and conventional T1 weighted MRI images also provide sufficient cortical anatomical details for mapping the cortical regions of interests (ROIs). In this paper, we described basic concepts and methods of DTI techniques that can be used to trace major WM tracts noninvasively from fetal brain of 14 postconceptional weeks (pcw) to adult brain. We applied these techniques to acquire DTI data and trace, reconstruct and visualize major WM tracts during development. After categorizing major WM fiber bundles into five unique functional tract groups, namely limbic, brain stem, projection, commissural and association tracts, we revealed formation and maturation of these 3D reconstructed WM tracts of the developing human brain. The structural and connectional imaging data offered by DTI provides the anatomical backbone of transcriptional atlas of the developing human brain.
doi:10.1016/j.ymeth.2014.10.025
PMCID: PMC4329045  PMID: 25448302
human brain development; fetal brain; DTI; tractography; connection; cortical mapping
9.  Development and Application of a Next Generation Air Sensor Network for the Hong Kong Marathon 2015 Air Quality Monitoring 
This study presents the development and evaluation of a next generation air monitoring system with both laboratory and field tests. A multi-parameter algorithm was used to correct for the impact of environmental conditions on the electrochemical sensors for carbon monoxide (CO) and nitrogen dioxide (NO2) pollutants. The field evaluation in an urban roadside environment in comparison to designated monitors showed good agreement with measurement error within 5% of the pollutant concentrations. Multiple sets of the developed system were then deployed in the Hong Kong Marathon 2015 forming a sensor-based network along the marathon route. Real-time air pollution concentration data were wirelessly transmitted and the Air Quality Health Index (AQHI) for the Green Marathon was calculated, which were broadcast to the public on an hourly basis. The route-specific sensor network showed somewhat different pollutant patterns than routine air monitoring, indicating the immediate impact of traffic control during the marathon on the roadside air quality. The study is one of the first applications of a next generation sensor network in international sport events, and it demonstrated the usefulness of the emerging sensor-based air monitoring technology in rapid network deployment to supplement existing air monitoring.
doi:10.3390/s16020211
PMCID: PMC4801587  PMID: 26861336
marathon; next generation sensor; air network; roadside air quality
10.  Self-assembly of DNA Nanohydrogels with Controllable Size and Stimuli-Responsive Property for Targeted Gene Regulation Therapy 
Here, we report the synthesis and characterization of size-controllable and stimuli-responsive DNA nanohydrogels as effective targeted gene delivery vectors. DNA nanohydrogels were created through a self-assembly process using three kinds of building units, respectively termed Y-shaped monomer A with three sticky ends (YMA), Y-shaped monomer B with one sticky end (YMB), and DNA linker (LK) with two sticky ends. Hybridization at the sticky ends of monomers and LK leads to nanohydrogel formation. DNA nanohydrogels are size-controllable by varying the ratio of YMA to YMB. By incorporating different functional elements, such as aptamers, disulfide linkages, and therapeutic genes into different building units, the synthesized aptamer-based nanohydrogels (Y-gel-Apt) can be used for targeted and stimuli-responsive gene therapy. Y-gel-Apt strongly inhibited cell proliferation and migration in target A549 cells, but not in control cells. By taking advantage of facile modular design and assembly, efficient cellular uptake, and superior biocompatibility, this Y-gel-Apt holds great promise as a candidate for targeted gene or drug delivery and cancer therapy.
doi:10.1021/ja512293f
PMCID: PMC4449038  PMID: 25581100
11.  Dermatological Manifestations of Postural Tachycardia Syndrome Are Common and Diverse 
Background and Purpose
Postural tachycardia syndrome (POTS) is a syndrome of orthostatic intolerance in the setting of excessive tachycardia with orthostatic challenge, and these symptoms are relieved when recumbent. Apart from symptoms of orthostatic intolerance, there are many other comorbid conditions such as chronic headache, fibromyalgia, gastrointestinal disorders, and sleep disturbances. Dermatological manifestations of POTS are also common and range widely from livedo reticularis to Raynaud's phenomenon.
Methods
Questionnaires were distributed to 26 patients with POTS who presented to the neurology clinic. They were asked to report on various characteristics of dermatological symptoms, with their answers recorded on a Likert rating scale. Symptoms were considered positive if patients answered with "strongly agree" or "agree", and negative if they answered with "neutral", "strongly disagree", or "disagree".
Results
The most commonly reported symptom was rash (77%). Raynaud's phenomenon was reported by over half of the patients, and about a quarter of patients reported livedo reticularis. The rash was most commonly found on the arms, legs, and trunk. Some patients reported that the rash could spread, and was likely to be pruritic or painful. Very few reported worsening of symptoms on standing.
Conclusions
The results suggest that dermatological manifestations in POTS vary but are highly prevalent, and are therefore of important diagnostic and therapeutic significance for physicians and patients alike to gain a better understanding thereof. Further research exploring the underlying pathophysiology, incidence, and treatment strategies is necessary.
doi:10.3988/jcn.2016.12.1.75
PMCID: PMC4712289  PMID: 26610893
postural tachycardia syndrome; Raynaud's phenomenon; livedo reticularis; varicose veins; dermatological manifestations; dysautonomia
12.  Toward Developmental Connectomics of the Human Brain 
Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood, and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and developmental dyslexia). Collectively, we showed that delineation of the brain network from a connectomics perspective offers a unique and refreshing view of both normal development and neuropsychiatric disorders.
doi:10.3389/fnana.2016.00025
PMCID: PMC4814555  PMID: 27064378
connectomics; network; hub; rich club; brain development; ADHD; autism; dyslexia
13.  Complementary annealing mediated by exonuclease: a method for seamless cloning and conditioning site-directed mutagenesis 
Traditional cut-paste DNA cloning is often limited by the availability of restriction enzyme sites. Here, we described the complementary annealing mediated by exonuclease (CAME), in which the insert or vector fragment is amplified to carry sequences complementary to the other, and both fragments are modified by exonuleases to create directional single-stranded overhangs. The two recessed DNA fragments are joined through complementary strand annealing. The CAME is highly efficient for cloning the DNA of at least 12 kb and single DNA fragment out of a complex DNA sample. Moreover, the application of CAME greatly improved the efficiency of site-directed mutagenesis.
doi:10.1080/13102818.2014.988094
PMCID: PMC4686905  PMID: 26740790
complementary annealing mediated by exonuclease; seamless cloning; ligation-independent cloning; site-directed mutagenesis
14.  Smoking in infertile women with polycystic ovary syndrome: baseline validation of self-report and effects on phenotype 
Human Reproduction (Oxford, England)  2014;29(12):2680-2686.
STUDY QUESTION
Do women with polycystic ovary syndrome (PCOS) seeking fertility treatment report smoking accurately and does participation in infertility treatment alter smoking?
SUMMARY ANSWER
Self-report of smoking in infertile women with PCOS is accurate (based on serum cotinine levels) and smoking is unlikely to change over time with infertility treatment.
WHAT IS KNOWN ALREADY
Women with PCOS have high rates of smoking and it is associated with worse insulin resistance and metabolic dysfunction.
STUDY DESIGN, SIZE, DURATION
Secondary study of smoking history from a large randomized controlled trial of infertility treatments in women with PCOS (N = 626) including a nested case–control study (N = 148) of serum cotinine levels within this cohort to validate self-report of smoking.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Women with PCOS, age 18–40, seeking fertility who participated in a multi-center clinical trial testing first-line ovulation induction agents conducted at academic health centers in the USA.
MAIN RESULT(S) AND THE ROLE OF CHANCE
Overall, self-report of smoking in the nested case–control study agreed well with smoking status as determined by measure of serum cotinine levels, at 90% or better for each of the groups at baseline (98% of never smokers had cotinine levels <15 ng/ml compared with 90% of past smokers and 6% of current smokers). There were minor changes in smoking status as determined by serum cotinine levels over time, with the greatest change found in the smoking groups (past or current smokers). In the larger cohort, hirsutism scores at baseline were lower in the never smokers compared with past smokers. Total testosterone levels at baseline were also lower in the never smokers compared with current smokers. At end of study follow-up insulin levels and homeostatic index of insulin resistance increased in the current smokers (P < 0.01 for both) compared with baseline and with non-smokers. The chance for ovulation was not associated with smoking status, but live birth rates were increased (non-significantly) in never or past smokers.
LIMITATIONS, REASONS FOR CAUTION
The limitations include the selection bias involved in our nested case–control study, the possibility of misclassifying exposure to second hand smoke as smoking and our failure to capture self-reported changes in smoking status after enrollment in the trial.
WIDER IMPLICATIONS OF THE FINDINGS
Because self-report of smoking is accurate, further testing of smoking status is not necessary in women with PCOS. Because smoking status is unlikely to change during infertility treatment, extra attention should be focused on smoking cessation in current or recent smokers who seek or who are receiving infertility treatment.
STUDY FUNDING/COMPETING INTEREST(S)
Sponsored by the Eugene Kennedy Shriver National Institute of Child Health and Human Development of the U.S. National Institutes of Health.
CLINICAL TRIAL REGISTRATION NUMBERS
ClinicalTrials.gov numbers, NCT00068861 and NCT00719186.
doi:10.1093/humrep/deu239
PMCID: PMC4227579  PMID: 25324541
cigarette smoking; anovulation; hyperandrogenism; infertility; obesity
15.  Comparative miRNAs analysis of Two contrasting broccoli inbred lines with divergent head-forming capacity under temperature stress 
BMC Genomics  2015;16:1026.
Background
MicroRNAs (miRNAs) play a vital role in growth, development, and stress response at the post-transcriptional level. Broccoli (Brassica oleracea L. var italic) is an important vegetable crop, and the yield and quality of broccoli are decreased by heat stress. The broccoli inbred lines that are capable of producing head at high temperature in summer are unique varieties in Taiwan. However, knowledge of miRNAomes during the broccoli head formation under heat stress is limited.
Methods
In this study, molecular characterization of two nearly isogenic lines with contrasting head-forming capacity was investigated. Head-forming capacity was better for heat-tolerant (HT) than heat-sensitive (HS) broccoli under heat stress.
Results
By deep sequencing and computational analysis, 20 known miRNAs showed significant differential expression between HT and HS genotypes. According to the criteria for annotation of new miRNAs, 24 novel miRNA sequences with differential expression between the two genotypes were identified. To gain insight into functional significance, 213 unique potential targets of these 44 differentially expressed miRNAs were predicted. These targets were implicated in shoot apical development, phase change, response to temperature stimulus, hormone and energy metabolism. The head-forming capacity of the unique HT line was related to autonomous regulation of Bo-FT genes and less expression level of heat shock protein genes as compared to HS. For the genotypic comparison, a set of miRNAs and their targets had consistent expression patterns in various HT genotypes.
Conclusions
This large-scale characterization of broccoli miRNAs and their potential targets is to unravel the regulatory roles of miRNAs underlying heat-tolerant head-forming capacity.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-2201-1) contains supplementary material, which is available to authorized users.
doi:10.1186/s12864-015-2201-1
PMCID: PMC4667509  PMID: 26625945
Broccoli; Deep sequencing; Genotype; Head-forming capacity; High temperature; MicroRNA
16.  Developmental Profile, Morphology, and Synaptic Connectivity of Cajal–Retzius Cells in the Postnatal Mouse Hippocampus 
Cerebral Cortex (New York, NY)  2015;26(2):855-872.
Cajal–Retzius (CR) cells are early generated neurons, involved in the assembly of developing neocortical and hippocampal circuits. However, their roles in networks of the postnatal brain remain poorly understood. In order to get insights into these latter functions, we have studied their morphological and synaptic properties in the postnatal hippocampus of the CXCR4-EGFP mouse, where CR cells are easily identifiable. Our data indicate that CR cells are nonuniformly distributed along different subfields of the hippocampal formation, and that their postnatal decline is regulated in a region-specific manner. In fact, CR cells persist in distinct areas of fully mature animals. Subclasses of CR cells project and target either local (molecular layers) or distant regions [subicular complex and entorhinal cortex (EC)] of the hippocampal formation, but have similar firing patterns. Lastly, CR cells are biased toward targeting dendritic shafts compared with spines, and produce large-amplitude glutamatergic unitary postsynaptic potentials on γ-aminobutyric acid (GABA) containing interneurons. Taken together, our results suggest that CR cells are involved in a novel excitatory loop of the postnatal hippocampal formation, which potentially contributes to shaping the flow of information between the hippocampus, parahippocampal regions and entorhinal cortex, and to the low seizure threshold of these brain areas.
doi:10.1093/cercor/bhv271
PMCID: PMC4712808  PMID: 26582498
CXCR4-EGFP mice; hippocampal Cajal–Retzius cells; light- and electron microscopy; patch-clamp recordings; synaptic connectivity
17.  miR-27b-3p suppresses cell proliferation through targeting receptor tyrosine kinase like orphan receptor 1 in gastric cancer 
Background
The receptor tyrosine kinase-like orphan receptors (ROR) family contains the atypical member ROR1, which plays an oncogenic role in several malignant tumors. However, the clinical potentials and underlying mechanisms of ROR1 in gastric cancer progression remain largely unknown. In this study, we validated the microRNA-mediated gene repression mechanism involved in the role of ROR1.
Methods
Bioinformatic prediction, luciferase reporter assay, quantitative real-time PCR (qRT-PCR) and western blotting were used to reveal the regulatory relationship between miR-27b-3p and ROR1. The expression patterns of miR-27b-3p and ROR1 in human gastric cancer (GC) specimens and cell lines were determined by microRNA RT-PCR and western blotting. Cell proliferation, colony formation assay in soft agar in vitro and tumorigenicity in vivo were performed to observe the effects of downregulation and upregulation miR-27b-3p expression on GC cell phenotypes.
Results
miR-27b-3p suppressed ROR1 expression by binding to the 3’UTR of ROR1 mRNA in GC cells. miR-27b-3p was significantly downregulated and reversely correlated with ROR1 protein levels in clinical samples. Analysis of the clinicopathological significance showed that miR-27b-3p and ROR1 were closely correlated with GC characteristics. Ectopic miR-27b-3p expression suppressed cell proliferation, colony formation in soft agar, xenograft tumors of GC cells. By contrast, miR-27b-3p knockdown enhanced these malignant behaviors. Our studies further revealed that the c-Src/STAT3 signaling pathway was involved in miR-27b-3p-ROR1-mediated cell proliferation regulation.
Conclusions
These results show that miR-27b-3p suppresses ROR1 expression through the binding site in the 3’UTR inhibiting the cell proliferation. These findings indicate that miR-27b-3p exerts tumor-suppressive effects in GC through the suppression of oncogene ROR1 expression and suggest a therapeutic application of miR-27b-3p in GC.
doi:10.1186/s13046-015-0253-3
PMCID: PMC4650850  PMID: 26576539
miR-27b-3p; ROR1; Gastric cancer; Cell proliferation; c-Src/STAT3
18.  Efficacy and safety of stenting for elderly patients with severe and symptomatic carotid artery stenosis: a critical meta-analysis of randomized controlled trials 
Clinical Interventions in Aging  2015;10:1733-1742.
Objective
To investigate both short-term and long-term therapeutic efficacy and safety of carotid artery stenting (CAS) and carotid artery endarterectomy (CEA) for elderly patients with severe and symptomatic carotid artery stenosis.
Methods
PubMed, EMBASE, Cochrane Library, Clinical Trials Register Centers, and Google Scholar were comprehensively searched. After identifying relevant randomized controlled trials, methodological quality was assessed by using Cochrane tools of bias assessment. Meta-analysis was performed by RevMan software, and subgroup analyses according to different follow-up periods were also conducted.
Results
Sixteen articles of nine randomized controlled trials containing 6,984 patients were included. Compared with CEA, CAS was associated with high risks of stroke during periprocedural 30 days (risk ratio [RR]=1.47, 95% confidence interval [CI]: 1.15–1.88), 48 months (RR=1.37, 95% CI: 1.11–1.70), and >48 months (RR=1.76, 95% CI: 1.34–2.31). There was no significant difference in the aspects of death, disabling stroke, or death at any time between the groups. For other periprocedural complications, CAS decreased the risk of myocardial infarction (RR=0.44, 95% CI: 0.26–0.75), cranial nerve palsy (RR=0.09, 95% CI: 0.04–0.22) and hematoma (RR=0.31, 95% CI: 0.14–0.68) compared with CEA, while it increased the risk of bradycardia or hypotension (RR=8.45, 95% CI 2.91–24.58).
Conclusion
Compared with CEA, CAS reduced hematoma, periprocedural myocardial infarction, and cranial nerve palsy, while it was associated with higher risks of both short-term and long-term nondisabling stroke. And they seemed to be equivalent in other outcome measures. As regards to its minimal invasion, it should be applied only in specific patients.
doi:10.2147/CIA.S91721
PMCID: PMC4631412  PMID: 26604720
symptomatic carotid artery stenosis; carotid artery stenting; carotid artery endarterectomy
19.  Aluminum plasmonic photocatalysis 
Scientific Reports  2015;5:15288.
The effectiveness of photocatalytic processes is dictated largely by plasmonic materials with the capability to enhance light absorption as well as the energy conversion efficiency. Herein, we demonstrate how to improve the plasmonic photocatalytic properties of TiO2/Al nano-void arrays by overlapping the localized surface plasmon resonance (LSPR) modes with the TiO2 band gap. The plasmonic TiO2/Al arrays exhibit superior photocatalytic activity boasting an enhancement of 7.2 folds. The underlying mechanisms concerning the radiative energy transfer and interface energy transfer processes are discussed. Both processes occur at the TiO2/Al interface and their contributions to photocatalysis are evaluated. The results are important to the optimization of aluminum plasmonic materials in photocatalytic applications.
doi:10.1038/srep15288
PMCID: PMC4620498  PMID: 26497411
20.  Clinical Significance of Preoperative Thrombin Time in Patients with Esophageal Squamous Cell Carcinoma following Surgical Resection 
PLoS ONE  2015;10(10):e0140323.
Background
Noninvasive tools for the prognosis of ESCC are urgently needed. To this end, serum coagulation tests have been researched in some cancers, but the prognostic value of the TT in ESCC has not been described.
Methods
The levels of pre-treatment serum coagulation markers (including the PT, APTT, PTA, INR, fibrinogen level, TT and PLT) were retrospectively analyzed in 204 patients with ESCC who underwent surgical resection at our department and in 200 healthy controls, and the two groups were compared. The prognostic significance of the coagulation tests was then determined with univariate and multivariate cox hazard analyses in patients with ESCC.
Results
Compared with those in normal controls, the PT, APTT, and fibrinogen levels were significantly increased, whereas the TT values significantly decreased in the 204 ESCC patients. The TT directly correlated with the 5-year survival rate, not only in the entire ESCC cohort (p = 0.023) but also in the subgroups stratified according to the T and N classifications and metastasis. Conversely, the other tests were not independent prognostic factors for ESCC. Of the clotting markers, the TT inversely correlated with the fibrinogen level (p = 0.005).
Conclusions
The 5-year survival was shorter in ESCC patients exhibiting decreased pre-treatment TT values. Thus, the serum TT may be a clinical prognostic factor for ESCC patients.
doi:10.1371/journal.pone.0140323
PMCID: PMC4607453  PMID: 26469700
21.  Mode division multiplexing using an orbital angular momentum mode sorter and MIMO-DSP over a graded-index few-mode optical fibre 
Scientific Reports  2015;5:14931.
Mode division multiplexing (MDM)– using a multimode optical fiber’s N spatial modes as data channels to transmit N independent data streams – has received interest as it can potentially increase optical fiber data transmission capacity N-times with respect to single mode optical fibers. Two challenges of MDM are (1) designing mode (de)multiplexers with high mode selectivity (2) designing mode (de)multiplexers without cascaded beam splitting’s 1/N insertion loss. One spatial mode basis that has received interest is that of orbital angular momentum (OAM) modes. In this paper, using a device referred to as an OAM mode sorter, we show that OAM modes can be (de)multiplexed over a multimode optical fiber with higher than −15 dB mode selectivity and without cascaded beam splitting’s 1/N insertion loss. As a proof of concept, the OAM modes of the LP11 mode group (OAM−1,0 and OAM+1,0), each carrying 20-Gbit/s polarization division multiplexed and quadrature phase shift keyed data streams, are transmitted 5km over a graded-index, few-mode optical fibre. Channel crosstalk is mitigated using 4 × 4 multiple-input-multiple-output digital-signal-processing with <1.5 dB power penalties at a bit-error-rate of 2 × 10−3.
doi:10.1038/srep14931
PMCID: PMC4598738  PMID: 26450398
22.  Down-regulated Na+/K+-ATPase activity in ischemic penumbra after focal cerebral ischemia/reperfusion in rats 
This study was aimed to examine whether the Na+/K+ adenosine triphosphatase (Na+/K+-ATPase) activity in ischemic penumbra is associated with the pathogenesis of ischemia/reperfusion-induced brain injury. An experimental model of cerebral ischemia/reperfusion was made by transient middle cerebral artery occlusion (tMCAO) in rats and the changes of Na+/K+-ATPase activity in the ischemic penumbra was examined by Enzyme Assay Kit. Extensive infarction was observed in the frontal and parietal cortical and subcortical areas at 6 h, 24 h, 48 h, 3 d and 7 d after tMCAO. Enzyme Assay analyses revealed the activity of Na+/K+-ATPase was decreased in the ischemic penumbra of model rats after focal cerebral ischemia/reperfusion compared with sham-operated rats, and reduced to its minimum at 48 h, while the infarct volume was enlarged gradually. In addition, accompanied by increased brain water content, apoptosis-related bcl-2 and Bax proteins, apoptotic index and neurologic deficits Longa scores, but fluctuated the ratio of bcl-2/Bax. Correlation analysis showed that the infarct volume, apoptotic index, neurologic deficits Longa scores and brain water content were negatively related with Na+/K+-ATPase activity, while the ratio of bcl-2/Bax was positively related with Na+/K+-ATPase activity. Our results suggest that down-regulated Na+/K+-ATPase activity in ischemic penumbra might be involved in the pathogenesis of cerebral ischemia/reperfusion injury presumably through the imbalance ratio of bcl-2/Bax and neuronal apoptosis, and identify novel target for neuroprotective therapeutic intervention in cerebral ischemic disease.
PMCID: PMC4680405  PMID: 26722460
Cerebral ischemia/reperfusion; Na+/K+-ATPase; penumbra; apoptosis; bcl-2; bax
23.  Multifunctional Fe3O4@Polydopamine Core–Shell Nanocomposites for Intracellular mRNA Detection and Imaging-Guided Photothermal Therapy 
ACS nano  2014;8(4):3876-3883.
Multifunctional nanocomposites have the potential to integrate sensing, diagnostic, and therapeutic functions into a single nanostructure. Herein, we synthesize Fe3O4@polydopamine core–shell nanocomposites (Fe3O4@PDA NCs) through an in situ self-polymerization method. Dopamine, a melanin-like mimic of mussel adhesive proteins, can self-polymerize to form surface-adherent polydopamine (PDA) films onto a wide range of materials including Fe3O4 nanoparticles used here. In such nanocomposites, PDA provides a number of advantages, such as near-infrared absorption, high fluorescence quenching efficiency, and a surface for further functionalization with biomolecules. We demonstrate the ability of the Fe3O4@PDA NCs to act as theranostic agents for intracellular mRNA detection and multimodal imaging-guided photothermal therapy. This work would stimulate interest in the use of PDA as a useful material to construct multifunctional nanocomposites for biomedical applications.
doi:10.1021/nn500722y
PMCID: PMC4564054  PMID: 24654734
polydopamine; multifunctional nanocomposites; mRNA recognition; magnetic resonance imaging; photoacoustic imaging; photothermal therapy
24.  Levels of plasma Epstein-Barr virus DNA prior and subsequent to treatment predicts the prognosis of nasopharyngeal carcinoma 
Oncology Letters  2015;10(5):2888-2894.
The level of Epstein-Barr virus DNA (EBV-DNA) in the plasma prior and subsequent to treatment is a reliable biomarker for the screening, diagnosis, monitoring and prognosis of nasopharyngeal carcinoma (NPC). The present retrospective study aimed to determine whether pre- and post-treatment levels of plasma EBV-DNA were predictive of survival in a large sample of patients with NPC. The level of plasma EBV-DNA in 637 NPC patients prior and subsequent to treatment was determined by quantitative polymerase chain reaction. The value of pre- and post-treatment plasma EBV-DNA in predicting the survival of NPC patients was then analyzed. The results revealed that pre-treatment plasma EBV-DNA loads were significantly higher in patients with NPC than those in healthy controls (P<0.001). The percentage of patients with positive plasma EBV-DNA was markedly higher prior to treatment (70.64%; median, 1150 copies/ml; range, 0–9.75×106 copies/ml) than following treatment (25.99%; median, 0 copies/ml; range, 0–3.83×106 copies/ml) (P<0.001). Patients with a high plasma EBV-DNA load presented with a higher clinical tumor classification, lymph node status, metastatic status and overall cancer stage. The risk of NPC relapse and mortality was higher in patients with pre-treatment plasma EBV-DNA levels of ≥1,500 copies/ml than that in patients with <1,500 copies/ml. Furthermore, the risk of relapse and mortality was higher in patients with positive post-treatment plasma EBV-DNA than in patients with negative post-treatment plasma EBV-DNA. Detectable post-treatment plasma EBV-DNA was the most significant prognostic factor to affect relapse-free survival, whilst metastasis was the prognostic factor with the greatest effect on overall survival. These data indicated that pre- and post-treatment levels of plasma EBV-DNA were able to predict the prognosis of NPC. This finding may provide novel references for research and clinical practice.
doi:10.3892/ol.2015.3628
PMCID: PMC4665674  PMID: 26722258
nasopharyngeal carcinoma; Epstein-Barr virus DNA; prognosis
25.  GSH2 promoter methylation in pancreatic cancer analyzed by quantitative methylation-specific polymerase chain reaction 
Oncology Letters  2015;10(1):387-391.
Tumor suppressor gene silencing via promoter hypermethylation is an important event in pancreatic cancer pathogenesis. Aberrant DNA hypermethylation events are highly tumor specific, and may provide a diagnostic tool for pancreatic cancer patients. The objective of the current study was to identify novel methylation-related genes that may potentially be used to establish novel therapeutic and diagnostic strategies against pancreatic cancer. The methylation status of the GS homeobox 2 (GSH2) gene was analyzed using the sodium bisulfite sequencing method. The GSH2 methylation ratio was examined in primary carcinomas and corresponding normal tissues derived from 47 patients with pancreatic cancer, using quantitative methylation-specific polymerase chain reaction. Methylation ratios were found to be associated with the patient's clinicopathological features. GSH2 gene methylation was detected in 26 (55.3%) of the 47 pancreatic cancer patients, indicating that it occurs frequently in pancreatic cancer. A significant association with methylation was observed for tumor-node-metastasis stage (P=0.031). GSH2 may be a novel methylation-sensitive tumor suppressor gene in pancreatic cancer and may be a tumor-specific biomarker of the disease.
doi:10.3892/ol.2015.3241
PMCID: PMC4487178  PMID: 26171036
pancreatic cancer; GSH2; methylation

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