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1.  Wafer-scale synthesis of monodisperse synthetic magnetic multilayer nanorods 
Nano letters  2013;14(1):333-338.
A double exposure technique has been used to fabricate nanoimprint stamps for making monodisperse nanorods with controllable lengths. The nanorod length is defined by a normal photolithography projection process whereas the nanorod width is defined by an edge-lithography process using a soft polydimethylsiloxane (PDMS) contact mask. Taking advantage of edge-lithography, the nanorod width can be less than the diffraction limit of the exposure light. Using these nanorod stamps, synthetic magnetic multilayer (SMM) nanorods have been fabricated using nanoimprint lithography, resulting in a length variation of ~3%. Nanorod magnetic properties have been characterized in both longitudinal and in-plane transverse directions of the nanorods. A theoretical model has been established to explain the magnetic responses and has revealed that both shape anisotropy and interlayer interactions are important in determining the properties of SMM nanorods.
PMCID: PMC3931460  PMID: 24329003
Nanorod; magnetic; synthesis; nanoimprint lithography; nano-patterning
2.  Fecal microbiota transplantation broadening its application beyond intestinal disorders 
Intestinal dysbiosis is now known to be a complication in a myriad of diseases. Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota. This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas, including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors. A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces, with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity, along with increased levels of butyrate-producing intestinal microbiota. Case reports of FMT have also shown favorable outcomes in Parkinson’s disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.
PMCID: PMC4284325  PMID: 25574083
Fecal microbiota transplantation; Intestinal microbiota; Dysbiosis; Extra-intestinal disorders; Therapy
3.  Biological and clinical significance of epigenetic silencing of MARVELD1 gene in lung cancer 
Scientific Reports  2014;4:7545.
Epigenetic silence in cancer frequently altered signal-transduction pathways during the early stages of tumor development. Recent progress in the field of cancer epigenetics has led to new opportunities for diagnosis and treatment of cancer. We previously demonstrated that novel identified nuclear factor MARVELD1 was widely expressed in human tissues, but down-regulated by promoter methylation in multiple cancers. This study was carried out to determine the biological and clinical significance of MARVELD1 gene silencing in lung cancer. Here, we found the reduced MARVELD1 expression significantly correlated with diagnostic histopathology and malignant degree of lung cancers. DNA hypermethylation and histone deacetylation synergistically inactivated MARVELD1 gene in lung cancer cells. Moreover, MARVELD1 modulated the efficiency of nonsense-mediated mRNA decay (NMD) through interaction with NMD core factor SMG1. The decreased MARVELD1 level in lung cancer reduces NMD efficiency through diminishing the association between NMD complex component UPF1/SMG1 and premature termination codons containing mRNA (PTC-mRNA). The results suggested that MARVELD1 silencing is an appealing diagnostic biomarker for lung cancer and epigenetic silencing of MARVELD1 gene links with the regulatory mechanism of NMD pathway in lung cancer, which may be required for tumorigenesis.
PMCID: PMC4269892  PMID: 25520033
4.  Locality and rapidity of the ultra-large elastic deformation of Nb nanowires in a NiTi phase-transforming matrix 
Scientific Reports  2014;4:6753.
This study investigated the elastic deformation behaviour of Nb nanowires embedded in a NiTi matrix. The Nb nanowires exhibited an ultra-large elastic deformation, which is found to be dictated by the martensitic transformation of the NiTi matrix, thus exhibiting unique characteristics of locality and rapidity. These are in clear contrast to our conventional observation of elastic deformations of crystalline solids, which is a homogeneous lattice distortion with a strain rate controlled by the applied strain. The Nb nanowires are also found to exhibit elastic-plastic deformation accompanying the martensitic transformation of the NiTi matrix in the case when the transformation strain of the matrix over-matches the elastic strain limit of the nanowires, or exhibit only elastic deformation in the case of under-matching. Such insight provides an important opportunity for elastic strain engineering and composite design.
PMCID: PMC4208026  PMID: 25341619
5.  Determinants of Fatigue after First-Ever Ischemic Stroke during Acute Phase 
PLoS ONE  2014;9(10):e110037.
Background and Purpose
Fatigue after stroke is common and has a negative impact on rehabilitation and survival. However, its pathogenesis and contributing factors remain unclear. The purpose of this study was to identify factors influencing the occurrence of fatigue after first-ever ischemic stroke in acute phase.
We examined 265 consecutive patients with first-ever ischemic stroke during acute phase (within 2 weeks) in two tertiary stroke care hospitals in Henan, China. We documented patients’ demographic and clinical characteristics through face-to-face interviews using structured questionnaires and reviews of medical records. Post-stroke fatigue was defined as a score of ≥4 using the Fatigue Severity Scale. Multivariate logistic regression was used to examine post-stroke fatigue in relation to socio-demographic, lifestyle, clinical characteristics and family function.
About 40% first-ever ischemic stroke patients experienced post-stroke fatigue in acute phase. Post-stroke fatigue was associated with lack of exercise before stroke (adjusted odds ratio 4.01, 95% CI 1.95–8.24), family dysfunction (2.63, 1.20–5.80), depression (2.39, 1.02–5.58), the presence of pre-stroke fatigue (4.89, 2.13–11.21), use of sedative medications (4.14, 1.58–10.88), coronary heart disease (3.38, 1.46–7.79) and more severe Modified Rankin Scale (2.55, 1.65–3.95).
The causes of post-stroke fatigue are multifaceted. More physical exercise, improving family function, reducing depression and appropriate use of sedative medications may be helpful in preventing post-stroke fatigue.
PMCID: PMC4193856  PMID: 25302807
6.  Epigenetic changes of mesenchymal stem cells in three-dimensional (3D) spheroids 
Mesenchymal stem cells (MSCs) hold profound promise in tissue repair/regeneration. However, MSCs undergo remarkable spontaneous differentiation and aging during monolayer culture expansion. In this study, we found that 2–3 days of three-dimensional (3D) spheroid culture of human MSCs (hMSCs) that had been expanded in monolayer for six passages increased their clonogenicity and differentiation potency to neuronal cells. Moreover, in accordance with these changes, the expression levels of miRNA which were involved in stem cell potency were changed and levels of histone H3 acetylation in K9 in promoter regions of Oct4, Sox2 and Nanog were elevated. Our results indicate that spheroid culture increases their multi-potency and changes the epigenetic status of pluripotent genes in hMSCs.
PMCID: PMC4244016  PMID: 25090911
mesenchymal stem cells; miRNA; histone acetylation; 3D culture; multi-potency
7.  Comparison of Chinese inpatients with different types of medical insurance before and after the 2009 healthcare reform 
Since 1994, China has established three major basic medical insurance (MI) schemes that aim to provide greater financial protection to members. The 2009 Chinese medical reform emphasized the enhancement of basic medical insurance. This study aims to investigate changes in hospital services costs for inpatients with different types of MI before and after the new Chinese medical reform.
A total of 532,120 inpatient medical records, completed by 11 different hospitals nationwide in 2008 and 2011, were collected from the Ministry of Health retrospectively. Median and mean values were calculated to describe costs and average length of stay, respectively. A chi-square test was used to compare the distribution of patient visits. Wilcoxon rank-sum tests were conducted to compare costs.
The number of patients hospitalized increased. The average cost per stay in the three basic MI schemes increased, while out-of-pocket (OOP) spending decreased (P < 0.0001). The average cost per day showed similar trends. The purchase of Western medication accounted for the largest proportion of costs in all MI schemes in both years; however, these ratios decreased from 2008 to 2011, while those for other social insurance and OOP patients almost doubled. The average length of stay remained unchanged, and the average lengths of stay in the MI schemes differed before and after the healthcare reform.
Healthcare reform with multipartite policies may make interactional impacts on hospitalization services for patients enrolled in MI schemes.
PMCID: PMC4261594  PMID: 25267508
Basic medical insurance; Hospitalization cost; Average length of stay; China
8.  Matrix-insensitive protein assays push the limits of biosensors in medicine 
Nature medicine  2009;15(11):1327-1332.
Advances in biosensor technologies for in vitro diagnostics have the potential to transform the practice of medicine. Despite considerable work in the biosensor field, there is still no general sensing platform that can be ubiquitously applied to detect the constellation of biomolecules in diverse clinical samples (for example, serum, urine, cell lysates or saliva) with high sensitivity and large linear dynamic range. A major limitation confounding other technologies is signal distortion that occurs in various matrices due to heterogeneity in ionic strength, pH, temperature and autofluorescence. Here we present a magnetic nanosensor technology that is matrix insensitive yet still capable of rapid, multiplex protein detection with resolution down to attomolar concentrations and extensive linear dynamic range. The matrix insensitivity of our platform to various media demonstrates that our magnetic nanosensor technology can be directly applied to a variety of settings such as molecular biology, clinical diagnostics and biodefense.
PMCID: PMC4165514  PMID: 19820717
9.  Prevention measures and socio-economic development result in a decrease in malaria in Hainan, China 
Malaria Journal  2014;13(1):362.
Historically, the incidence of malaria in the Hainan Province, China has been high. However, since 2001 the malaria incidence in Hainan has decreased due to large-scale, public educational, promotional campaigns and the adoption of preventative measures against malaria following the fast growth of socio-economic development. The present study analysed the correlation between prevention measures and social economic development on the incidence of malaria in Hainan from 2001 to 2013.
The data of malaria preventative measures and socio-economic development were collected from various cities and counties in Hainan Province from 2001 to 2013 and analysed by the grey correlation analysis system.
Seasonal preventive medication and local fiscal revenue increases are significantly related to the reduction of malaria incidence from 2001 to 2013 (R1 = 0.751677; R5 = 0.764795).
Malaria prevention and control measures and local economic development in Hainan decreased malaria incidence from 2001 to 2013.
PMCID: PMC4177233  PMID: 25223723
Malaria; Integrated vector management; Malaria preventative medication; Grey correlation
10.  Genome organisation of the Acinetobacter lytic phage ZZ1 and comparison with other T4-like Acinetobacter phages 
BMC Genomics  2014;15(1):793.
Phage ZZ1, which efficiently infects pathogenic Acinetobacter baumannii strains, is the fifth completely sequenced T4-like Acinetobacter phage to date. To gain a better understanding of the genetic characteristics of ZZ1, bioinformatics and comparative genomic analyses of the T4 phages were performed.
The 166,687-bp double-stranded DNA genome of ZZ1 has the lowest GC content (34.4%) of the sequenced T4-like Acinetobacter phages. A total of 256 protein-coding genes and 8 tRNA genes were predicted. Forty-three percent of the predicted ZZ1 proteins share up to 73% amino acid identity with T4 proteins, and the homologous genes generally retained the same order and transcriptional direction. Beyond the conserved structural and DNA replication modules, T4 and ZZ1 have diverged substantially by the acquisition and deletion of large blocks of unrelated genes, especially in the first halves of their genomes. In addition, ZZ1 and the four other T4-like Acinetobacter phage genomes (Acj9, Acj61, 133, and Ac42) share a well-organised and highly conserved core genome, particularly in the regions encoding DNA replication and virion structural proteins. Of the ZZ1 proteins, 70, 64, 61, and 56% share up to 86, 85, 81, and 83% amino acid identity with Acj9, Acj61, 133, and Ac42 proteins, respectively. ZZ1 has a different number and types of tRNAs than the other 4 Acinetobacter phages, although some of the ZZ1-encoded tRNAs share high sequence similarity with the tRNAs from these phages. Over half of ZZ1-encoded tRNAs (5 out of 8) are related to optimal codon usage for ZZ1 proteins. However, this correlation was not present in any of the other 4 Acinetobacter phages.
The comparative genomic analysis of these phages provided some new insights into the evolution and diversity of Acinetobacter phages, which might elucidate the evolutionary origin and host-specific adaptation of these phages.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-793) contains supplementary material, which is available to authorized users.
PMCID: PMC4177764  PMID: 25218338
Phage genome annotation; Phage genome organisation; Comparative genomic analyses; T4-like phage
11.  Human Umbilical Cord Mesenchymal Stem Cells Infected with Adenovirus Expressing HGF Promote Regeneration of Damaged Neuron Cells in a Parkinson's Disease Model 
BioMed Research International  2014;2014:909657.
Parkinson's disease (PD) is a neurodegenerative movement disorder that is characterized by the progressive degeneration of the dopaminergic (DA) pathway. Mesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have great potential for developing a therapeutic agent as such. HGF is a multifunctional mediator originally identified in hepatocytes and has recently been reported to possess various neuroprotective properties. This study was designed to investigate the protective effect of hUC-MSCs infected by an adenovirus carrying the HGF gene on the PD cell model induced by MPP+ on human bone marrow neuroblastoma cells. Our results provide evidence that the cultural supernatant from hUC-MSCs expressing HGF could promote regeneration of damaged PD cells at higher efficacy than the supernatant from hUC-MSCs alone. And intracellular free Ca2+ obviously decreased after treatment with cultural supernatant from hUC-MSCs expressing HGF, while the expression of CaBP-D28k, an intracellular calcium binding protein, increased. Therefore our study clearly demonstrated that cultural supernatant of MSC overexpressing HGF was capable of eliciting regeneration of damaged PD model cells. This effect was probably achieved through the regulation of intracellular Ca2+ levels by modulating of CaBP-D28k expression.
PMCID: PMC4167956  PMID: 25276829
12.  Isolation and mutational analysis of circulating tumor cells from lung cancer patients with magnetic sifters and biochips† 
Lab on a chip  2014;14(1):78-88.
Detection and characterization of circulating tumor cells (CTCs) may reveal insights into the diagnosis and treatment of malignant disease. Technologies for isolating CTCs developed thus far suffer from one or more limitations, such as low throughput, inability to release captured cells, and reliance on expensive instrumentation for enrichment or subsequent characterization. We report a continuing development of a magnetic separation device, the magnetic sifter, which is a miniature microfluidic chip with a dense array of magnetic pores. It offers high efficiency capture of tumor cells, labeled with magnetic nanoparticles, from whole blood with high throughput and efficient release of captured cells. For subsequent characterization of CTCs, an assay, using a protein chip with giant magnetoresistive nanosensors, has been implemented for mutational analysis of CTCs enriched with the magnetic sifter. The use of these magnetic technologies, which are separate devices, may lead the way to routine preparation and characterization of “liquid biopsies” from cancer patients.
PMCID: PMC4144998  PMID: 23969419
13.  Emerging Protein Array Technologies for Proteomics 
Expert review of proteomics  2013;10(1):65-75.
Numerous efforts have been made to understand fundamental biology of diseases based on gene expressions. However, the relationship between gene expressions and onset of diseases often remains obscure. The great advances in protein microarrays allow us to investigate this unclear question through protein profiles, which are regarded as more reliable than gene expressions to serve as the harbinger of disease onset or as the biomarker of disease treatment monitoring. We review two relatively new platforms of protein arrays, along with an introduction to the common basis of protein array technologies. Immobilization of proteins on the surface of arrays and neutralizing reactive areas after the immobilization are key practical issues in the field of protein array. One of the emerging protein array technologies is the magneto-nanosensor array where giant magnetoresistive (GMR) sensors are used to quantitatively measure analyte of interest which are labeled with magnetic nanoparticles (MNP). Similar to GMR, several different ways of utilizing magnetic properties for biomolecular detection have been developed and are reviewed here. Another emerging protein array technology is Nucleic Acid Programmable Protein Arrays (NAPPA), which have thousands of protein features directly expressed by nucleic acids on array surface. We anticipate these two emerging protein array platforms can be combined to produce synergistic benefits and open new applications in proteomics and clinical diagnostics.
PMCID: PMC4143142  PMID: 23414360
Protein array; GMR sensors; Magnetic Immunoassays; Self-assembling assays; Molecular detection; Protein interactions
14.  Infection of equine monocyte-derived macrophages with an attenuated equine infectious anemia virus (EIAV) strain induces a strong resistance to the infection by a virulent EIAV strain 
Veterinary Research  2014;45(1):82.
The Chinese attenuated equine infectious anemia virus (EIAV) vaccine has successfully protected millions of equine animals from EIA disease in China. Given that the induction of immune protection results from the interactions between viruses and hosts, a better understanding of the characteristics of vaccine strain infection and host responses would be useful for elucidating the mechanism of the induction of immune protection by the Chinese attenuated EIAV strain. In this study, we demonstrate in equine monocyte-derived macrophages (eMDM) that EIAVFDDV13, a Chinese attenuated EIAV strain, induced a strong resistance to subsequent infection by a pathogenic strain, EIAVUK3. Further experiments indicate that the expression of the soluble EIAV receptor sELR1, Toll-like receptor 3 (TLR3) and interferon β (IFNβ) was up-regulated in eMDM infected with EIAVFDDV13 compared with eMDM infected with EIAVUK3. Stimulating eMDM with poly I:C resulted in similar resistance to EIAV infection as induced by EIAVFDDV13 and was correlated with enhanced TLR3, sELR1 and IFNβ expression. The knock down of TLR3 mRNA significantly impaired poly I:C-stimulated resistance to EIAV, greatly reducing the expression of sELR1 and IFNβ and lowered the level of infection resistance induced by EIAVFDDV13. These results indicate that the induction of restraining infection by EIAVFDDV13 in macrophages is partially mediated through the up-regulated expression of the soluble viral receptor and IFNβ, and that the TLR3 pathway activation plays an important role in the development of an EIAV-resistant intracellular environment.
Electronic supplementary material
The online version of this article (doi:10.1186/s13567-014-0082-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4283155  PMID: 25106750
15.  Magnetically ultraresponsive nanoscavengers for next-generation water purification systems 
Nature communications  2013;4:1866.
The development of sustainable, robust and energy efficient water purification technology is still challenging. Although use of nanoparticles is promising, methods are needed for their efficient recovery post treatment. Here we address this issue by fabrication of magnetically ultraresponsive ‘nanoscavengers’, nanoparticles containing synthetic antiferromagnetic core layers and functional capping layers. When dispersed in water, the nanoscavengers efficiently interact with contaminants to remove them from the water. They are then quickly collected (<5 min) with a permanent magnet, owing to their magnetically ultraresponsive core layers. Specifically, we demonstrate fabrication and deployment of Ag-capped nanoscavengers for disinfection followed by application of an external magnetic field for separation. We also develop and validate a collision-based model for pathogen inactivation, and propose a cyclical water purification scheme in which nanoscavengers are recovered and recycled for contaminant removal.
PMCID: PMC4123635  PMID: 23673651
16.  Vasohibin-1 Expression Is Regulated by Transforming Growth Factor-β/Bone Morphogenic Protein Signaling Pathway Between Tumor-Associated Macrophages and Pancreatic Cancer Cells 
Vasohibin-1 has been detected in endothelial cells as an intrinsic angiogenesis inhibitor. Both tumor-associated macrophages (TAMs) and transforming growth factor-β (TGF-β)/bone morphogenic protein (BMP) signaling have been reported to promote angiogenesis in cancer. However, whether vasohibin-1 expression is regulated by TGF-β/BMP signaling between TAMs and cancer cells remains unclear. The expression of TGF-β1, TGF-β2, BMP-4, and BMP-7 in TAMs and the expression of vasohibin-1, vascular endothelial growth factor-A (VEGF-A), and VEGF-C in two pancreatic cancer cell lines (a nonmetastatic cell line Panc-1 and a distant metastatic cell line HPAF-II) were measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). The TGF-β receptor 1 and BMP receptor 1 were inhibited by the inhibitor SB-431542 and LDN193189, respectively. Thereafter, vasohibin-1, VEGF-A, and VEGF-C expression was detected by real-time RT-PCR. We found that the expression of TGF-β1, TGF-β2, BMP-4, and BMP-7 was upregulated in TAMs cocultured with pancreatic cancer cells. Vasohibin-1, VEGF-A, and VEGF-C mRNA expression in pancreatic cancer cells was upregulated by TAMs. Vasohibin-1 expression in pancreatic cancer cells cocultured with TAMs was upregulated significantly when TGF-β receptors or BMP receptors were inhibited, but VEGF-C expression was downregulated. Therefore, Vasohibin-1 expression is regulated by the TGF-β/BMP signaling between TAMs and pancreatic cancer cells. These results might shed a new light on the antiangiogenesis therapy in the pancreatic cancer.
PMCID: PMC3741417  PMID: 23651239
17.  Modeling and experiments of magneto-nanosensors for diagnostics of radiation exposure and cancer 
Biomedical microdevices  2013;15(4):665-671.
We present a resistive network model, protein assay data, and outlook of the giant magnetoresistive (GMR) spin-valve magneto-nanosensor platform ideal for multiplexed detection of protein biomarkers in solutions. The magneto-nanosensors are designed to have optimal performance considering several factors such as sensor dimension, shape anisotropy, and magnetic nanoparticle tags. The resistive network model indicates that thinner spin-valve sensors with narrower width lead to higher signals from magnetic nanoparticle tags. Standard curves and real-time measurements showed a sensitivity of ~10 pM for phosphorylated-structural maintenance of chromosome 1 (phosphor-SMC1), ~53 fM for granulocyte colony stimulation factor (GCSF), and ~460 fM for interleukin-6 (IL6), which are among the representative biomarkers for radiation exposure and cancer.
PMCID: PMC3674217  PMID: 22763391
Radiation biomarker; Cancer biomarker; Nanosensor; Magnetic nanoparticles; Immunoassay
18.  Crystal structure of diethyl [(4-chloro­anilino)(4-hy­droxy­phen­yl)meth­yl]phospho­nate N,N-di­methyl­formamide monosolvate 
In the title compound, C17H21ClNO4P·C3H7NO, the dihedral angle formed by the aromatic rings is 83.98 (7)°. In the crystal, O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds link the mol­ecules into double layers parallel to (011).
PMCID: PMC4186167  PMID: 25309252
crystal structure; hydrogen bond; phospho­nate
19.  Eliminating Plasmodium falciparum in Hainan, China: a study on the use of behavioural change communication intervention to promote malaria prevention in mountain worker populations 
Malaria Journal  2014;13:273.
In the island of Hainan, the great majority of malaria cases occur in mountain worker populations. Using the behavioral change communication (BCC) strategy, an interventional study was conducted to promote mountain worker malaria prevention at a test site. This study found the methods and measures that are suitable for malaria prevention among mountain worker populations.
During the Plasmodium falciparum elimination stage in Hainan, a representative sampling method was used to establish testing and control sites in areas of Hainan that were both affected by malaria and had a relatively high density of mountain workers. Two different methods were used: a BCC strategy and a conventional strategy as a control. Before and after the intervention, house visits, core group discussions, and structural surveys were utilized to collect qualitative and quantitative data regarding mountain worker populations (including knowledge, attitudes, and practices [KAPs]; infection status; and serological data), and these data from the testing and control areas were compared to evaluate the effectiveness of BCC strategies in the prevention of malaria.
In the BCC malaria prevention strategy testing areas, the accuracy rates of malaria-related KAP were significantly improved among mountain worker populations. The accuracy rates in the 3 aspects of malaria-related KAP increased from 37.73%, 37.00%, and 43.04% to 89.01%, 91.53%, and 92.25%, respectively. The changes in all 3 aspects of KAP were statistically significant (p < 0.01). In the control sites, the changes in the indices were not as marked as in the testing areas, and the change was not statistically significant (p > 0.05). Furthermore, in the testing areas, both the percentage testing positive in the serum malaria indirect fluorescent antibody test (IFAT) and the number of people inflicted decreased more significantly than in the control sites (p < 0.01).
The use of the BCC strategy significantly improved the ability of mountain workers in Hainan to avoid malarial infection. Educational and promotional materials and measures were developed and selected in the process, and hands-on experience was gained that will help achieve the goal of total malaria elimination in Hainan.
PMCID: PMC4112993  PMID: 25017319
20.  Decreased pain threshold and enhanced synaptic transmission in the anterior cingulate cortex of experimental hypothyroidism mice 
Molecular Pain  2014;10:38.
Thyroid hormones are essential for the maturation and functions of the central nervous system. Pain sensitivity is related to the thyroid status. However, information on how thyroid hormones affect pain processing and synaptic transmission in the anterior cingulate cortex (ACC) is limited. Nociceptive threshold and synaptic transmission in the ACC were detected in the experimental hypothyroidism (HT) mice.
HT was induced by methimazole and potassium perchlorate in distilled drinking water for 4 weeks. The threshold of pain perception to hot insults, but not mechanical ones, decreased in hypothyroid mice. After treatment with tri-iodothyronine (T3) or thyroxine (T4) for 2 weeks, thermal pain threshold recovered. Electrophysiological recordings revealed enhanced glutamatergic synaptic transmission and reduced GABAergic synaptic transmission in the ACC. Supplementation with T3 or T4 significantly rescued this synaptic transmission imbalance. In the same model, HT caused the up-regulation of the GluR1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor and NR2B-containing N-methyl-D-aspartate receptors, but it down-regulated γ-aminobutyric acid A receptors in the ACC. Supplementation with T3 or T4 notably recovered the levels of above proteins.
These results suggest that HT promotes hypersensitivity to noxious thermal, and that supplementation with T3 or T4 rescues the imbalance between excitatory and inhibitory transmission in the ACC.
PMCID: PMC4072477  PMID: 24943008
Thyroid hormone; Pain; Anterior cingulate cortex
21.  Blastocyst Transfer Ameliorates Live Birth Rate Compared with Cleavage-Stage Embryos Transfer in Fresh In Vitro Fertilization or Intracytoplasmic Sperm Injection Cycles: Reviews and Meta-Analysis 
Yonsei Medical Journal  2014;55(3):815-825.
Blastocyst transfer has been recommended to raise the implantation rate without affecting the pregnancy rate. The objective of this meta-analysis is to systematically evaluate whether the live birth rate and other pregnancy outcomes can be improved by blastocyst transfer compared with cleavage-stage embryos transfer.
Materials and Methods
EMBASE and MEDLINE databases were searched for papers published between March 2004 and March 2013. An extensive range of the electronic databases yielded initially 317 studies from which seven trials met the inclusion criteria for further analysis. Our outcome measures were the live birth rate, clinical pregnancy rate, implantation rate, ongoing pregnancy rate, multiple pregnancy rate, first trimester miscarriage rate and ectopic pregnancy rate. Fixed effects models were chosen to calculate the odds ratio (OR).
Seven trials (n=1446 cases) were finally analyzed. Compared with cleavage-stage embryos transfer, the blastocyst transfer was statistically significantly associated with an increase in clinical pregnancy rate [OR 1.43; 95% confidence interval (CI), 1.15-1.78], implantation rate (OR 1.38; 95% CI, 1.09-1.74) and ongoing pregnancy rate (OR 2.15; 95% CI, 1.57-2.94), and also a reduction in the probability of first trimester miscarriage rate (OR 0.51; 95% CI, 0.30-0.87). The improvement in the live birth rate was also observed (OR 1.77; 95% CI, 1.32-2.37). Moreover, there was no evidence of difference in multiple pregnancy and ectopic pregnancy rates.
The available evidences suggest that live birth and other pregnancy outcomes after fresh in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) are significantly improved following blastocyst transfer as compared to cleavage-stage embryo transfer.
PMCID: PMC3990083  PMID: 24719153
Blastocyst; cleavage stage; embryo transfer; live birth rate; meta-analysis
22.  Gender Differences in Myocardial Perfusion Defect in Asymptomatic Postmenopausal Women and Men With and Without Diabetes Mellitus 
Journal of Women's Health  2013;22(5):439-444.
To compare the results of myocardial perfusion imaging (MPI) of asymptomatic postmenopausal women and age-matched men and to investigate the effect of diabetes mellitus (DM) on gender differences and the risk estimation of coronary heart disease (CHD).
Sixty-seven postmenopausal women and 27 men low in Framingham Global Risk Score (FGRS) were recruited from year 2008 to 2009 in northern Taiwan. Each subject underwent blood tests, a cardiopulmonary exercise test, an electrocardiograph (ECG), and MPI.
Women had similar percentages of predicted oxygen consumption and ECG changes at peak exercise, but lower oxygen pulse and rate–pressure product. They also had significantly higher summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) than men, despite showing much lower scores for the FGRS than men. Women with DM had a lower 10-year risk of CHD assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine, but significantly higher SSS and SDS than men. In the subjects with abnormal MPI, the extent of ischemia was small to moderate in men, whereas in 50% of the women, the extent of ischemia was large.
The results of this preliminary study suggest that asymptomatic postmenopausal women had more abnormalities in MPI and those with DM had a higher SSS and SDS than age-matched men. The risk of CAD may still be underestimated by the UKPDS.
PMCID: PMC3653376  PMID: 23600438
23.  Enhancing intervertebral disc repair and regeneration through biology: platelet-rich plasma as an alternative strategy 
Intervertebral disc degeneration (IDD) is a common orthopedic disease associated with mechanical changes that may result in significant pain. Current treatments for IDD mainly depend on conservative therapies and spinal surgeries that are only able to relieve the symptoms but do not address the cause of the degeneration and even accelerate the degeneration of adjacent segments. This has prompted research to improve our understanding of the biology of intervertebral disc healing and into methods to enhance the regenerative process. Recently, biological therapies, including active substances, gene therapy and tissue engineering based on certain cells, have been attracting more attention in the field of intervertebral disc repair and regeneration. Early selection of suitable biological treatment is an ideal way to prevent or even reverse the progressive trend of IDD. Growth factors have been enjoying more popularity in the field of regeneration of IDD and many have been proved to be effective in reversing the degenerative trend of the intervertebral disc. Identification of these growth factors has led to strategies to deliver platelet-derived factors to the intervertebral disc for regeneration. Platelet-rich plasma (PRP) is the latest technique to be evaluated for promoting intervertebral disc healing. Activation of the PRP leads to the release of growth factors from the α-granules in the platelet cytoplasm. These growth factors have been associated with the initiation of a healing cascade that leads to cellular chemotaxis, angiogenesis, synthesis of collagen matrix, and cell proliferation. This review describes the current understanding of IDD and related biological therapeutic strategies, especially the promising prospects of PRP treatment. Future limitations and perspectives of PRP therapy for IDD are also discussed.
PMCID: PMC3978730  PMID: 24165687
24.  Qingkailing Suppresses the Activation of BV2 Microglial Cells by Inhibiting Hypoxia/Reoxygenation-Induced Inflammatory Responses 
Qingkailing (QKL) is a well-known composite extract used in traditional Chinese medicine. This extract has been extensively administered to treat the acute phase of cerebrovascular disease. Our previous experiments confirmed that QKL exerts an inhibitory effect on cerebral ischemia-induced inflammatory responses. However, whether QKL suppresses the activation of microglia, the primary resident immune cells in the brain, has yet to be determined. In this study, BV2 microglial cells were used to validate the protective effects of QKL treatment following ischemia-reperfusion injury simulated via hypoxia/reoxygenation in vitro. Under these conditions, high expression levels of ROS, COX-2, iNOS, and p-p38 protein were detected. Following ischemia/reperfusion injury, QKL significantly increased the activity of BV2 cells to approximately the basal level by modulating microglial activation via inhibition of inflammatory factors, including TNF-α, COX-2, iNOS, and p-p38. However, QKL treatment also displayed dose-dependent differences in its inhibitory effects on p38 phosphorylation and inflammatory factor expression.
PMCID: PMC4020462  PMID: 24864157
25.  Rapid Characterization of Magnetic Moment of Cells for Magnetic Separation 
IEEE transactions on magnetics  2013;49(7):3434-3437.
NCI-H1650 lung cancer cell lines labeled with magnetic nanoparticles via the Epithelial Cell Adhesion Molecule (EpCAM) antigen were previously shown to be captured at high efficiencies by a microfabricated magnetic sifter. If fine control and optimization of the magnetic separation process is to be achieved, it is vital to be able to characterize the labeled cells’ magnetic moment rapidly. We have thus adapted a rapid prototyping method to obtain the saturation magnetic moment of these cells. This method utilizes a cross-correlation algorithm to analyze the cells’ motion in a simple fluidic channel to obtain their magnetophoretic velocity, and is effective even when the magnetic moments of cells are small. This rapid characterization is proven useful in optimizing our microfabricated magnetic sifter procedures for magnetic cell capture.
PMCID: PMC3996843  PMID: 24771946
Cell separation; magnetic devices; magnetic microspheres; magnetic nanoparticles; magnetic separation

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