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1.  Correlation between microRNA-34a levels and lens opacity severity in age-related cataracts 
Eye  2013;27(7):883-888.
MicroRNA 34a (miR-34a) is involved in regulating tissue senescence. However, the role of miR-34a in age-related cataracts is unclear. In this study, we evaluated the correlations among the severity of lens opacity, patient age, and miR-34a expression level in the lens epithelium of age-related cataracts for clarifying the role of miR-34a in the lens senescence.
This study was carried as a case control study in the Department of Ophthalmology, Taipei Veterans General Hospital, Taiwan. We recorded age of each patient at the time of their cataract surgery and information regarding lens opacity according to a modified version of the Lens Opacities Classification System III. Correlations among age, lens opacity, and miR-34a expression levels were evaluated.
This study evaluated 110 patients with a mean age of 73.19 years (SD±10.2). Older patients had higher nuclear cataract (NC), cortical (C), and posterior subcapsular cataract (P) scores (one-way analysis of variance (ANOVA), P<0.05). miR-34a expression levels were significantly different between each age group (ANOVA post hoc Bonferroni's test, P<0.001), and there were moderate correlations between high NC, C, and P cataract scores and high miR-34a levels (Pearson correlation coefficient; R=0.606, 0.575, and 0.515, respectively).
The current study demonstrated positive correlations between high miR-34a levels and high lens opacity severity in NC, C, or P cataracts. These results suggest that miR-34a expression has a role in lens senescence.
PMCID: PMC3709404  PMID: 23661155
aging; cataract; microRNA; senescence
2.  Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion 
British Journal of Cancer  2009;102(2):351-360.
Epithelial-to-mesenchymal transition (EMT) is associated with decreased adhesion and acquisition of metastatic potential of breast cancer cells. Epithelial-to-mesenchymal transition is mediated, in part, by two transcription repressors, Snail and Slug, that are known to be targets of the Notch signaling pathway, and JAGGED1-induced Notch activation increases EMT. However, the events that lead to increased Notch activity during EMT of breast cancer cells are unknown.
The accumulation of hypoxia inducible factors (HIFs) under hypoxia was detected by western blot analysis, and their effects on Notch signaling were measured by an in vitro Notch reporter assay. The expression of Notch target genes under hypoxia was tested by real-time PCR. The knockdown of HIF-1α was mediated by retroviral delivery of shRNA. The expression of Slug and Snail under hypoxia was measured by real-time PCR. Breast cancer cell migration and invasion under hypoxia were tested with cell migration and invasion kits.
Hypoxia increased the expression of Notch target genes such as HES1 and HEY1 in breast cancer cells, as was expression of Notch receptors and ligands. The mechanism is likely to involve the accumulation of HIF-1α and HIF-2α in these cells by hypoxia, which synergised with the Notch co-activator MAML1 in potentiating Notch activity. Hypoxia inducible factor-1α was found to bind to HES1 promoter under hypoxia. Knockdown of HIF-1α with shRNA inhibited both HES1 and HEY1 expression under hypoxia. Hypoxia increased the expression of Slug and Snail, and decreased the expression of E-cadherin, hallmarks of EMT. Notch pathway inhibition abrogated the hypoxia-mediated increase in Slug and Snail expression, as well as decreased breast cancer cell migration and invasion.
Hypoxia-mediated Notch signaling may have an important role in the initiation of EMT and subsequent potential for breast cancer metastasis.
PMCID: PMC2816657  PMID: 20010940
Notch; hypoxia; hypoxia inducible factor (HIF); breast cancer; epithelial-to-mesenchymal transition (EMT)
4.  TBX6 Null Variants and a Common Hypomorphic Allele in Congenital Scoliosis 
The New England journal of medicine  2015;372(4):341-350.
Congenital scoliosis is a common type of vertebral malformation. Genetic susceptibility has been implicated in congenital scoliosis.
We evaluated 161 Han Chinese persons with sporadic congenital scoliosis, 166 Han Chinese controls, and 2 pedigrees, family members of which had a 16p11.2 deletion, using comparative genomic hybridization, quantitative polymerase-chain-reaction analysis, and DNA sequencing. We carried out tests of replication using an additional series of 76 Han Chinese persons with congenital scoliosis and a multi-center series of 42 persons with 16p11.2 deletions.
We identified a total of 17 heterozygous TBX6 null mutations in the 161 persons with sporadic congenital scoliosis (11%); we did not observe any null mutations in TBX6 in 166 controls (P<3.8×10−6). These null alleles include copy-number variants (12 instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants (1 nonsense and 4 frame-shift mutations). However, the discordant intrafamilial phenotypes of 16p11.2 deletion carriers suggest that heterozygous TBX6 null mutation is insufficient to cause congenital scoliosis. We went on to identify a common TBX6 haplotype as the second risk allele in all 17 carriers of TBX6 null mutations (P<1.1×10−6). Replication studies involving additional persons with congenital scoliosis who carried a deletion affecting TBX6 confirmed this compound inheritance model. In vitro functional assays suggested that the risk haplotype is a hypomorphic allele. Hemivertebrae are characteristic of TBX6-associated congenital scoliosis.
Compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital scoliosis cases in the series that we analyzed.
PMCID: PMC4326244  PMID: 25564734
5.  Dynamic and static contributions of the cerebrovasculature to the resting-state BOLD signal 
NeuroImage  2013;84:672-680.
Functional magnetic resonance imaging (fMRI) in the resting state, particularly fMRI based on the blood-oxygenation level-dependent (BOLD) signal, has been extensively used to measure functional connectivity in the brain. However, the mechanisms of vascular regulation that underlie the BOLD fluctuations during rest are still poorly understood. In this work, using dual-echo pseudo-continuous arterial spin labeling and MR angiography (MRA), we assess the spatio-temporal contribution of cerebral blood flow (CBF) to the resting-state BOLD signals and explore how the coupling of these signals is associated with regional vasculature. Using a general linear model analysis, we found that statistically significant coupling between resting-state BOLD and CBF fluctuations is highly variable across the brain, but the coupling is strongest within the major nodes of established resting-state networks, including the default-mode, visual, and task-positive networks. Moreover, by exploiting MRA-derived large vessel (macrovascular) volume fraction, we found that the degree of BOLD–CBF coupling significantly decreased as the ratio of large vessels to tissue volume increased. These findings suggest that the portion of resting-state BOLD fluctuations at the sites of medium-to-small vessels (more proximal to local neuronal activity) is more closely regulated by dynamic regulations in CBF, and that this CBF regulation decreases closer to large veins, which are more distal to neuronal activity.
PMCID: PMC4323159  PMID: 24099842
Cerebral blood flow (CBF); Resting-state BOLD; Arterial-spin labeling (ASL); MR angiography; Blood volume fraction
6.  Real-space anisotropic dielectric response in a multiferroic skyrmion lattice 
Scientific Reports  2015;5:8318.
A magnetic skyrmion lattice is a microstructure consisting of hexagonally aligned skyrmions. While a skyrmion as a topologically protected carrier of information promises a number of applications, an easily accessible probe of the skyrmion and skyrmion lattice at mesoscopic scale is of significance. It is known that neutron scattering, Lorentz transmission electron microscopy, and spin-resolved STM as effective probes of skyrmions have been established. In this work, we propose that the spatial contour of dielectric permittivity in a skyrmion lattice with ferromagnetic interaction and in-plane (xy) Dzyaloshinskii-Moriya (DM) interaction can be used to characterize the skyrmion lattice. The phase field and Monte Carlo simulations are employed to develop the one-to-one correspondence between the magnetic skyrmion lattice and dielectric dipole lattice, both exhibiting the hexagonal symmetry. Under excitation of in-plane electric field in the microwave range, the dielectric permittivity shows the dumbbell-like pattern with the axis perpendicular to the electric field, while it is circle-like for the electric field along the z-axis. The dependences of the spatial contour of dielectric permittivity on external magnetic field along the z-axis and dielectric frequency dispersion are discussed.
PMCID: PMC4321174  PMID: 25661786
7.  Serum C-reactive protein predicts poor prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy 
Current Oncology  2015;22(1):20-24.
We aimed to evaluate the association of serum C-reactive protein (crp) with prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.
We retrospectively reviewed 79 patients with locoregionally advanced nasopharyngeal carcinoma (cT3–4N0–3M0) treated with chemoradiotherapy. Chemoradiotherapy consisted of external-beam radiotherapy to the nasopharynx (70–80 Gy), the lymph node–positive area (60–70 Gy), and the lymph node–negative area (50–60 Gy) combined with 3 cycles of various platinum-based regimens delivered at 3-week intervals. Elevated crp was defined as more than 8 mg/L. The survival rate was calculated using the Kaplan–Meier method, and univariate and multivariate analyses (Cox proportional hazards model) were used to identify factors significantly associated with prognosis.
During the median follow-up of 3.9 years (range: 1–5.5 years), 23 patients died from nasopharyngeal cancer. The 5-year cancer-specific survival (css) rate was 62.90%. Before chemoradiotherapy, 18 patients had high serum crp; the css rate in that subgroup was significantly worse than the rate in the remaining patients (p = 0.0002). Multivariate analysis showed that crp was an independent prognostic indicator of css, with a hazard ratio of 3.04 (95% confidence interval: 1.22 to 7.55; p = 0.017). Among the 18 patients with elevated serum crp, 9 achieved normal serum crp after chemoradiotherapy, of whom 5 remained living with no evidence of recurrence or metastasis during follow-up. By contrast, the remaining 9 patients in whom serum crp did not normalize after chemoradiotherapy died within 4.2 years.
Elevated serum crp before treatment predicts poor prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.
PMCID: PMC4324340
Nasopharyngeal carcinoma; C-reactive protein; chemoradiotherapy; cancer-specific survival
8.  Distribution and clinical significance of tumour-associated macrophages in pancreatic ductal adenocarcinoma: a retrospective analysis in China 
Current Oncology  2015;22(1):e11-e19.
We aimed to characterize the localization and prognostic significance of tumour-associated macrophages (tams) in pancreatic ductal adenocarcinoma (pdac).
Tumour specimens from 70 patients with pdac and inflammatory specimens from 13 patients with chronic pancreatitis were collected and analyzed for tam and M2 macrophage counts by immunohistochemistry. Correlations between tam distributions and clinicopathologic features were determined.
Immunohistochemical analysis showed that tam and M2 macrophage counts were higher in tissues from pdac than from chronic pancreatitis. The tams and M2 macrophages both infiltrated more into peritumour. Both macrophage types were positively associated with lymph node metastasis (p = 0.041 for tams in peritumour, p = 0.013 for M2 macrophages in introtumour, p = 0.006 for M2 macrophage in peritumour). In addition, abdominal pain was significantly more frequent in pdac patients with a greater tams count. The survival rate was much lower in patients having high infiltration by M2 macrophages than in those having low infiltration.
The tam count might be associated with neural invasion in pdac, and M2 macrophages might play an important role in lymph node metastasis. Higher counts of either macrophage type were associated with increased risk of lymph node metastasis, and the M2 macrophage count could potentially be a marker for evaluating prognosis.
PMCID: PMC4324348
Pancreatic cancer; tumour-associated macrophages; lymph node metastasis; neural invasion
9.  In Vitro Ultrasound Measurements of Powered and Unpowered Total Cavopulmonary Connection 
Three-staged Fontan palliation is performed on children suffering from single ventricle congenital heart disease. The series of surgical procedures reroutes blood from the vena cavae directly to the pulmonary arteries, creating a total cavopulmonary connection (TCPC). A viscous impeller pump (VIP) is currently being developed as a cavopulmonary assist device that can modestly augment cavopulmonary flow, reduce systemic venous pressure, and improve ventricular preload. This study used ultrasound to visualize complex flow patterns in powered and unpowered in vitro mock Fontan circulations. The idealized TCPC was modeled with a silicone mold and blood analog made of water and glycerol that was seeded with 10-μm glass beads. B-mode, color Doppler, and pulsed-wave Doppler images were used to visualize complex flow patterns in the idealized TCPC with (1) no VIP, (2) static VIP, and powered VIP rotation rates of (3) 500 and (4) 2,000 rotations per minute (RPM). Pulsed-wave Doppler data showed higher mean velocities and greater variance in the outlets relative to the larger inlets. The maximum inlet velocity ± SD increased from 10.9 ± 3.53 cm/s with no VIP to 15.9 ± 1.03 when the VIP was rotating at 2,000 RPM. Likewise, the maximum outlet velocity increased from 14.9 ± 11.2 cm/s to 18.9 ± 7.25 cm/s at 2,000 RPM. The faster mean velocities with the VIP rotating suggest that the pump augments cavopulmonary flow. The results of this study suggest that measuring complex flow patterns with ultrasound in vivo could be used clinically to optimize VIP positioning and rotation rate during and after implantation.
PMCID: PMC4304092  PMID: 25621311
Fontan; Ultrasound; Doppler; Hemodynamics; Total cavopulmonary connection
10.  Vibrational Excitations and Low Energy Electronic Structure of Epoxide-decorated Graphene 
We report infrared studies of adsorbed atomic oxygen (epoxide functional groups) on graphene. Two different systems are used as a platform to explore these interactions, namely, epitaxial graphene/SiC(0001) functionalized with atomic oxygen (graphene epoxide, GE) and chemically reduced graphene oxide (RGO). In the case of the model GE system, IR reflectivity measurements show that epoxide groups distort the graphene π bands around the K-point, imparting a finite effective mass and contributing to a band gap. In the case of RGO, epoxide groups are found to be present following the reduction treatment by a combination of polarized IR reflectance and transmittance measurements. Similar to the GE system, a band gap in the RGO sample is observed as well.
PMCID: PMC3929940  PMID: 24563725
epitaxial graphene; oxygen; adsorbates; vibrations; band structure; reduced graphene oxide
12.  Whole-Genome Sequence of “Candidatus Liberibacter solanacearum” Strain R1 from California 
Genome Announcements  2014;2(6):e01353-14.
The draft whole-genome sequence of “Candidatus Liberibacter solanacearum” strain R1, isolated from and maintained in tomato plants in California, is reported. The R1 strain has the genome size of 1,204,257 bp, G+C content of 35.3%, 1,101 predicted open reading frames, and 57 RNA genes.
PMCID: PMC4276833  PMID: 25540355
13.  The impact of body mass index on complication and survival in resected oesophageal cancer: a clinical-based cohort and meta-analysis 
British Journal of Cancer  2013;109(11):2894-2903.
Body mass index (BMI) has been associated with the risk of oesophageal cancer. But the influence of BMI on postoperative complication and prognosis has always been controversial.
In total, 2031 consecutive patients who underwent oesophagectomy between 1998 and 2008 were classified according to Asian-specific BMI (kg m−2) cutoff values. The impact of BMI on overall survival (OS) was estimated using the Kaplan–Meier method and Cox proportional hazard models. We performed a meta-analysis to examine the association of BMI with OS and postoperative complication.
Patients with higher BMI had more postoperative complication (P=0.002), such as anastomotic leakage (P=0.016) and cardiovascular diseases (P<0.001), but less incidence of chylous leakage (P=0.010). Logistic regression analysis showed that BMI (P=0.005) was a confounding factor associated with postoperative complication. Multivariate analysis showed that overweight and obese patients had a more favourable survival than normal weight patients (HR (hazard ratio) = 0.80, 95% CI (confidence interval): 0.70–0.92, P=0.001). Subgroup analysis showed that the association with higher BMI and increased OS was observed in patients with oesophageal squamous cell carcinoma (ESCC) (P<0.001), oesophageal adenocarcinoma (EA) (P=0.034), never-smoking (P=0.035), ever-smoking (P=0.035), never alcohol consumption (P=0.005), weight loss (P=0.003) and advanced pathological stage (P<0.001). The meta-analysis further corroborated that higher BMI was associated with increased complication of anastomotic leakage (RR (risk ratio)=1.04, 95% CI: 1.02–1.06, P=0.001), wound infection (RR=1.03, 95% CI: 1.00–1.05, P=0.031) and cardiovascular diseases (RR=1.02, 95% CI: 1.00–1.05, P=0.039), but decreased incidence of chylous leakage (RR=0.98, 95% CI: 0.96–0.99, P<0.001). In addition, high BMI could significantly improved OS (HR=0.78, 95% CI: 0.71–0.85, P<0.001).
Preoperative BMI was an independent prognostic factor for survival, and strongly associated with postoperative complications in oesophageal cancer.
PMCID: PMC3844915  PMID: 24201750
body mass index; oesophageal cancer; meta-analysis; postoperative complication; survival
14.  Deletion of CXCR4 in cardiomyocytes exacerbates cardiac dysfunction following isoproterenol administration 
Gene therapy  2014;21(5):496-506.
Altered alpha- and beta-adrenergic receptor signaling is associated with cardiac hypertrophy and failure. Stromal cell-derived factor-1α (SDF-1α) and its cognate receptor CXCR4 have been reported to mediate cardioprotection after injury through the mobilization of stem cells into injured tissue. However, little is known regarding whether SDF-1/CXCR4 induces acute protection following pathological hypertrophy and if so, by what molecular mechanism. We have previously reported that CXCR4 physically interacts with the beta-2 adrenergic receptor and modulates its down stream signaling. Here we have shown that CXCR4 expression prevents beta-adrenergic receptor induced hypertrophy. Cardiac beta-adrenergic receptors were stimulated with the implantation of a subcutaneous osmotic pump administrating isoproterenol and CXCR4 expression was selectively abrogated in cardiomyocytes using Cre-loxP-mediated gene recombination. CXCR4 knockout mice showed worsened fractional shortening and ejection fraction. CXCR4 ablation increased susceptibility to isoproterenol-induced heart failure, by upregulating apoptotic markers and reducing mitochondrial function; cardiac function decreases while fibrosis increases. Additionally, CXCR4 expression was rescued with the use of cardiotropic Adeno-associated viral-9 (AAV9) vectors. CXCR4 gene transfer reduced cardiac apoptotic signaling, improved mitochondrial function and resulted in a recovered cardiac function. Our results represent the first evidence that SDF-1/CXCR4 signaling mediates acute cardioprotection through modulating beta-adrenergic receptor signaling in vivo.
PMCID: PMC4016112  PMID: 24646609
heart failure; cardiac remodeling; gene delivery; adeno-associated virus; chemokines
15.  Draft Genome Sequence of “Candidatus Liberibacter asiaticus” from California 
Genome Announcements  2014;2(5):e00999-14.
We report here the draft genome sequence of “Candidatus Liberibacter asiaticus” strain HHCA, collected from a lemon tree in California. The HHCA strain has a genome size of 1,150,620 bp, 36.5% G+C content, 1,119 predicted open reading frames, and 51 RNA genes.
PMCID: PMC4183884  PMID: 25278540
16.  Prognostic value of the trichorhinophalangeal syndrome-1 (TRPS-1), a GATA family transcription factor, in early-stage breast cancer 
Annals of Oncology  2013;24(10):2534-2542.
TRPS-1 is a new GATA transcription factor that is differentially expressed in breast cancer (BC) where it been found recently to regulate epithelial-to-mesenchymal transition (EMT).
Patients and methods
We carried out a quantitative immunohistochemistry (qIHC) analysis of TRPS-1 expression in 341 primary-stage I–III BC samples in relation to patient clinical characteristics as well as its prognostic value, especially in an estrogen receptor-positive (ER+) subgroup.
Higher TRPS-1 expression was significantly associated with a number of clinical and pathological characteristics as well as with improved overall survival (OS) and disease-free survival (DFS). Among stage I/II ER+ BC patients who received endocrine therapy alone, those with high TRPS-1 expression had significantly longer OS and DFS. There was also a strong association between TRPS-1 levels and the EMT marker E-cadherin in the ER+ invasive ductal carcinoma cases. Analysis of gene expression data on a panel of BC lines found that TRPS-1 expression was low or absent in BC lines having enriched mesenchymal features.
Our data indicated that TRPS-1 is an independent prognostic marker in early-stage BC and a new EMT marker that can distinguish patients with ER+ BC who will respond longer to adjuvant endocrine therapy.
PMCID: PMC3784330  PMID: 23729783
breast cancer; immunohistochemistry; prognostic marker; TRPS-1
17.  Integrin-Mediated Interactions with Extracellular Matrix Proteins for Nucleus Pulposus Cells of the Human Intervertebral Disc 
The extracellular matrix (ECM) of the human intervertebral disc is rich in molecules that interact with cells through integrin-mediated attachments. Porcine nucleus pulposus (NP) cells have been shown to interact with laminin (LM) isoforms LM-111 and LM-511 through select integrins that regulate biosynthesis and cell attachment. Since human NP cells lose many phenotypic characteristics with age, attachment and interaction with the ECM may be altered. Expression of LM-binding integrins was quantified for human NP cells using flow cytometry. The cell-ECM attachment mechanism was determined by quantifying cell attachment to LM-111, LM-511, or type II collagen after functionally blocking specific integrin subunits. Human NP cells express integrins β1, α3, and α5, with over 70% of cells positive for each subunit. Blocking subunit β1 inhibited NP cell attachment to all substrates. Blocking subunits α1, α2, α3 and α5 simultaneously, but not individually, inhibits NP cell attachment to laminins. While integrin α6β1 mediated porcine NP cell attachment to LM-111, we found integrins α3, α5, and β1 instead contributed to human NP cell attachment. These findings identify integrin subunits that may mediate interactions with the ECM for human NP cells and could be used to promote cell attachment, survival and biosynthesis in cell-based therapeutics.
PMCID: PMC3826265  PMID: 23737292
intervertebral disc; nucleus pulposus; integrin; extracellular matrix; human
18.  Genetic polymorphisms and tissue expression of interleukin-22 associated with risk and therapeutic response of gastric mucosa-associated lymphoid tissue lymphoma 
Blood Cancer Journal  2014;4(10):eXX-.
Chronic Helicobacter pylori-stimulated immune reactions determine the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. We aimed to explore the genetic predisposition to this lymphoma and its clinical implication. A total of 68 patients and 140 unrelated controls were genotyped for 84 single-nucleotide polymorphisms in genes encoding cytokines, chemokines and related receptors that play important roles in T cell-mediated gastrointestinal immunity. Five genotypes in IL-22, namely CC at rs1179246, CC at rs2227485, AA at rs4913428, AA at rs1026788 and TT at rs7314777, were associated with disease susceptibility. The former four genotypes resided in the same linkage disequilibrium block (r2=0.99) that conferred an approximately threefold higher risk. In vitro experiments demonstrated that co-culturing peripheral mononuclear cells or CD4+ T cells with H. pylori stimulated the secretion of interleukin-22 (IL-22), and that IL-22 induced the expression of antimicrobial proteins, RegIIIα and lipocalin-2, in gastric epithelial cells. Furthermore, patients with gastric tissue expressing IL-22 were more likely to respond to H. pylori eradication (14/22 vs 4/19, P<0.006). We conclude that susceptibility of gastric MALT lymphoma is influenced by genetic polymorphisms in IL-22, the product of which is involved in mucosal immunity against H. pylori and associated with tumor response to H. pylori eradication.
PMCID: PMC4220648  PMID: 25303370
19.  HDAC1 and Klf4 interplay critically regulates human myeloid leukemia cell proliferation 
Huang, Y | Chen, J | Lu, C | Han, J | Wang, G | Song, C | Zhu, S | Wang, C | Li, G | Kang, J | Wang, J
Cell Death & Disease  2014;5(10):e1491-.
Acute myeloid leukemia (AML) is recognized as a complex disease of hematopoietic stem cell disorders, but its pathogenesis mechanisms, diagnosis, and treatment remain unclear. General histone deacetylase (HDAC) inhibitors have been used in blood cancers including AML, but the lack of gene specificity greatly limits their anti-cancer effects and clinical applications. Here, we found that HDAC1 expression was negatively correlated with that of Krüppel-like factor 4 (Klf4) and that AML patients with lower HDAC1 level had better prognosis. Further, knockdown of HDAC1 in leukemia cells K562, HL-60, and U937 significantly increased Klf4 expression and inhibited cell cycle progression and cell proliferation, similar results were found for HDAC inhibitors (VPA and mocetinostat). Moreover, overexpression or knockdown of Klf4 could markedly block the effects of HDAC1 overexpression or knockdown on leukemia cells in vitro and in vivo, respectively. Mechanistic analyses demonstrated that HDAC1 and Klf4 competitively bound to the promoter region of Klf4 and oppositely regulated Klf4 expression in myeloid leukemia. We identified HDAC1 as a potential specific target for repressing cell proliferation and inducing cell cycle arrest through interplay and modulation of Klf4 expression, suggests that HDAC1 and Klf4 are potential new molecular markers and targets for clinical diagnosis, prognosis, and treatment of myeloid leukemia.
PMCID: PMC4237257  PMID: 25341045
20.  Concern and Risk Perception: Effects on Osteoprotective Behaviour 
Journal of Osteoporosis  2014;2014:142546.
This study aimed to determine the effect that level of concern for osteoporosis, as well as self-perceived risk of osteoporosis and fracture, has on supplementation use, seeking medical advice, bone mineral density (BMD) testing, and antiosteoporosis medication (AOM) use. Study subjects were 1,095 female Australian participants of the Global Longitudinal study of Osteoporosis in Women (GLOW) untreated for osteoporosis at baseline. Study outcomes from self-administered questionnaires included calcium and vitamin D supplementation, self-reported seeking of medical advice regarding osteoporosis, BMD testing, and AOM use in the last 12 months at the late assessment. Logistic regression was used in the analysis. Concern significantly increased the likelihood of seeking medical advice and, however, had no significant impact on screening or treatment. Heightened self-perceived risks of osteoporosis and fracture both significantly increased the likelihood of seeking medical advice and BMD testing while elevated self-perceived risk of fracture increased AOM use. Supplementation use was not significantly associated with concern levels and risk perception. Concern and risk perceptions to osteoporosis and fracture were significantly associated with certain bone-protective behaviours. However, the disconnect between perceived osteoporosis risk and AOM use illustrates the need to emphasize the connection between osteoporosis and fracture in future education programs.
PMCID: PMC4172925  PMID: 25276471
21.  Correlation of endogenous hormonal levels, fibroglandular tissue volume and percent density measured using 3D MRI during one menstrual cycle 
Annals of Oncology  2013;24(9):2329-2335.
We measured breast density (BD) on MRI and correlated with endogenous hormonal levels.
Patients and methods
Twenty-four premenopausal women received four weekly breast MRI. A blood sample was collected on the same day of MRI. BD was measured using a computer-based algorithm. The generalized estimation equation method was applied to model mean fibroglandular tissue volume (FV) and mean percent density (PD) from predictor variables including estradiol, progesterone, and week during a cycle.
In week 3, a borderline significant correlation between estradiol and PD (r = 0.43, P = 0.04), estradiol and FV (r = 0.40, P = 0.05) and between progesterone and FV (r = 0.42, P = 0.04) was noted. The FV and PD measured in weeks 4 and 1 were higher than in weeks 2 and 3, adjusted for variation in endogenous estradiol and progesterone, indicating that the hormone change could not account for the changes in density. No lag effect of endogenous hormone on the change of FV or PD was noted (all P-values > 0.05).
Our results showed that BD is not strongly associated with the endogenous hormone. Their association with breast cancer risk was likely coming from different mechanisms, and they should be considered as independent risk factors.
PMCID: PMC3755325  PMID: 23661294
breast density; endogenous hormone; fibroglandular tissue volume; lag effect; MRI; percent density
22.  Factors that can minimize bleeding complications after renal biopsy 
International Urology and Nephrology  2014;46(10):1969-1975.
Renal biopsy is a very important diagnostic tool in the evaluation of renal diseases. However, bleeding remains to be one of the most serious complications in this procedure. Many new techniques have been improved to make it safer. The risk factors and predictors of bleeding after percutaneous renal biopsy have been extensively reported in many literatures, and generally speaking, the common risk factors for renal biopsy complications focus on hypertension, high serum creatinine, bleeding diatheses, amyloidosis, advanced age, gender and so on. Our primary purpose of this review is to summarize current measures in recent years literature aiming at minimizing the bleeding complication after the renal biopsy, including the drug application before and after renal biopsy, operation details in percutaneous renal biopsies, nursing and close monitoring after the biopsy and other kinds of biopsy methods.
PMCID: PMC4176568  PMID: 25150849
Renal biopsy; Bleeding complication; Risk factors; Measures
23.  Associations of blood glucose and prevalent diabetes with risk of cardiovascular disease in 500 000 adult Chinese: the China Kadoorie Biobank 
Diabetic Medicine  2014;31(5):540-551.
To examine the relationship of self‐reported diabetes, and of random blood glucose levels among individuals without known diabetes, with the prevalence of cardiovascular disease in Chinese adults.
We examined cross‐sectional data from the China Kadoorie Biobank of 0.5 million people aged 30–79 years recruited from 10 diverse regions of China in the period 2004–2008. Logistic regression was used to estimate the odds ratios of prevalent cardiovascular disease associated with self‐reported diabetes, and with measured random blood glucose levels among participants with no history of diabetes, adjusting simultaneously for age, sex, area, education, smoking, alcohol, blood pressure and physical activity.
A total of 3.2% of participants had self‐reported diabetes (men 2.9%; women 3.3%) and 2.8% had screen‐detected diabetes (men 2.6%; women 2.8%), i.e. they had no self‐reported history of diabetes but a blood glucose level suggestive of a diagnosis of diabetes. Compared with individuals without a history of diabetes, the odds ratios associated with self‐reported diabetes were 2.18 (95% CI 2.06–2.30) and 1.88 (95% CI 1.75–2.01) for prevalent ischaemic heart disease and stroke/transient ischaemic attack, respectively. Among participants without self‐reported diabetes there was a positive association between random blood glucose and ischaemic heart disease and stroke/transient ischaemic attack prevalence (P for trend <0.0001). Below the diabetic threshold (<11.1 mmol/l) each additional 1 mmol/l of random blood glucose was associated with 4% (95% CI 2–5%) and 5% (95% CI 3–7%) higher odds of prevalent ischaemic heart disease and stroke/transient ischaemic attack, respectively.
In this adult Chinese population, self‐reported diabetes was associated with a doubling of the odds of prevalent cardiovascular disease. Below the threshold for diabetes there was still a modest, positive association between random blood glucose and prevalent cardiovascular disease.
PMCID: PMC4114560  PMID: 24344928
24.  A Novel Moisture Adjusted Vegetation Index (MAVI) to Reduce Background Reflectance and Topographical Effects on LAI Retrieval 
PLoS ONE  2014;9(7):e102560.
A new moisture adjusted vegetation index (MAVI) is proposed using the red, near infrared, and shortwave infrared (SWIR) reflectance in band-ratio form in this paper. The effectiveness of MAVI in retrieving leaf area index (LAI) is investigated using Landsat-5 data and field LAI measurements in two forest and two grassland areas. The ability of MAVI to retrieve forest LAI under different background conditions is further evaluated using canopy reflectance of Jack Pine and Black Spruce forests simulated by the 4-Scale model. Compared with several commonly used two-band vegetation index, such as normalized difference vegetation index, soil adjusted vegetation index, modified soil adjusted vegetation index, optimized soil adjusted vegetation index, MAVI is a better predictor of LAI, on average, which can explain 70% of variations of LAI in the four study areas. Similar to other SWIR-related three-band vegetation index, such as modified normalized difference vegetation index (MNDVI) and reduced simple ratio (RSR), MAVI is able to reduce the background reflectance effects on forest canopy LAI retrieval. MAVI is more suitable for retrieving LAI than RSR and MNDVI, because it avoids the difficulty in properly determining the maximum and minimum SWIR values required in RSR and MNDVI, which improves the robustness of MAVI in retrieving LAI of different land cover types. Moreover, MAVI is expressed as ratios between different spectral bands, greatly reducing the noise caused by topographical variations, which makes it more suitable for applications in mountainous area.
PMCID: PMC4099373  PMID: 25025128
25.  Association between tuberculosis infections and non-pulmonary malignancies: a nationwide population-based study 
British Journal of Cancer  2013;109(1):229-234.
In addition to lung cancers, tuberculosis infections have been associated with increased risk of non-pulmonary malignancies in case reports. Our population-based study employed standardized incidence ratios (SIRs) to systemically survey non-pulmonary cancer risks after tuberculosis infections.
Data of patients who had newly diagnosed tuberculosis, were aged 20 years or older, and had no prior cancer or tuberculosis were sampled from the Taiwan National Health Insurance database between 2000 and 2010. SIRs compared cancer incidence in patients with tuberculosis infections to the general population. SIRs of specific cancers were further analyzed with respect to gender and time after tuberculosis infections.
After a follow-up period of 28 866 person–years, 530 tuberculosis cases developed cancers compared with 256 cases in the general populations (2.07, 95% confidence interval (CI), 1.90–2.26). The SIR of non-pulmonary malignancies was also increased (1.71, 95% CI, 1.54–1.90). For males, SIRs were increased within 1 year after tuberculosis diagnosis for the following cancers: head and neck, esophageal, colorectal, liver, lung, melanomas, and Hodgkin's disease. SIRs were increased for liver, biliary, lung, and bladder cancers beyond the first year after tuberculosis diagnosis. For females, SIRs were increased for leukemia, esophageal, and lung cancers within the first year, and only for leukemia beyond 1 year post diagnosis.
Having found increased risks of several cancers that differ with gender and time after tuberculosis diagnosis, physicians may consider these factors in patients following tuberculosis diagnosis.
PMCID: PMC3708573  PMID: 23652313
tuberculosis infections; standardized incidence ratios

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