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1.  Association between Peripheral Oxidative Stress and White Matter Damage in Acute Traumatic Brain Injury 
BioMed Research International  2014;2014:340936.
The oxidative stress is believed to be one of the mechanisms involved in the neuronal damage after acute traumatic brain injury (TBI). However, the disease severity correlation between oxidative stress biomarker level and deep brain microstructural changes in acute TBI remains unknown. In present study, twenty-four patients with acute TBI and 24 healthy volunteers underwent DTI. The peripheral blood oxidative biomarkers, like serum thiol and thiobarbituric acid-reactive substances (TBARS) concentrations, were also obtained. The DTI metrics of the deep brain regions, as well as the fractional anisotropy (FA) and apparent diffusion coefficient, were measured and correlated with disease severity, serum thiol, and TBARS levels. We found that patients with TBI displayed lower FAs in deep brain regions with abundant WMs and further correlated with increased serum TBARS level. Our study has shown a level of anatomic detail to the relationship between white matter (WM) damage and increased systemic oxidative stress in TBI which suggests common inflammatory processes that covary in both the peripheral and central reactions after TBI.
PMCID: PMC3996315  PMID: 24804213
2.  Peripheral Leukocyte Apoptosis in Patients with Parkinsonism: Correlation with Clinical Characteristics and Neuroimaging Findings 
BioMed Research International  2014;2014:635923.
Apoptosis of both brain neurons and peripheral blood leukocyte is believed to be an important biomarker for evaluating the functional status of Parkinson's disease (PD). However, their correlation remains unknown. A better understanding of the pathophysiology of neurodegeneration is essential for the treatment and prevention of PD. The present study demonstrated that leukocyte apoptosis is significantly higher in PD patients and is associated with central dopamine neuron loss by using 99mTc-TRODAT-1 SPECT. The leukocyte apoptosis and striatal dopamine transporter uptake ratios were further associated with increased severity and longer duration of disease. The interaction between brain and systemic inflammation may be responsible for the neurodegenerative disease progression.
PMCID: PMC3984850  PMID: 24795890
3.  Community-based interventions in hypertensive patients: a comparison of three health education strategies 
BMC Public Health  2015;15:33.
Community-based health education programs may be helpful in improving health outcomes in patients with chronic illnesses. This study aimed to evaluate community-based health education strategies in the management of hypertensive patients with low socioeconomic status in Dongguan City, China.
This was a randomized, non-blinded trial involving 360 hypertensive patients enrolled in the community health service centre of Liaobu Town, Dongguan City, China. Participants were randomized to receive one of the three community-based health education programs over 2 years: self-learning reading (Group 1), monthly regular didactic lecture (Group 2), monthly interactive education workshop (Group 3). Outcomes included the changes in the proportion of subjects with normalized blood pressure (BP), hypertension-related knowledge score, adherence to antihypertensive treatment, lifestyle, body mass index and serum lipids.
After the 2-y intervention, the proportion of subjects with normalized BP increased significantly in Group 2 (from 41.2% to 63.2%, p<0.001), and increased more substantially in Group 3 (from 40.2% to 86.3%, p<0.001), but did not change significantly in Group 1. Improvements in hypertension-related knowledge score, adherence to regular use of medications, appropriate salt intake and regular physical activity were progressively greater from group 1 to group 2 to group 3. Group 3 had the largest reductions in body mass index and serum LDL cholesterol levels.
Interactive education workshops may be the most effective strategy in community-based health promotion education programs for hypertensive patients in improving patients’ knowledge on hypertension and alleviating clinical risk factors for preventing hypertension-related complications.
PMCID: PMC4314804  PMID: 25631224
Community-based intervention; Health education; Hypertension; Blood pressure; Serum lipids
4.  Antiproliferative effects of cinobufacini on human hepatocellular carcinoma HepG2 cells detected by atomic force microscopy 
AIM: To investigate the antiproliferative activity of cinobufacini on human hepatocellular carcinoma HepG2 cells and the possible mechanism of its action.
METHODS: HepG2 cells were treated with different concentrations of cinobufacini. Cell viability was measured by methylthiazolyl tetrazolium (MTT) assay. Cell cycle distribution was analyzed by flow cytometry (FCM). Cytoskeletal and nuclear alterations were observed by fluorescein isothiocyanate-phalloidin and DAPI staining under a laser scanning confocal microscope. Changes in morphology and ultrastructure of cells were detected by atomic force microscopy (AFM) at the nanoscale level.
RESULTS: MTT assay indicated that cinobufacini significantly inhibited the viability of HepG2 cells in a dose-dependent manner. With the concentration of cinobufacini increasing from 0 to 0.10 mg/mL, the cell viability decreased from 74.9% ± 2.7% to 49.41% ± 2.2% and 39.24% ± 2.1% (P < 0.05). FCM analysis demonstrated cell cycle arrest at S phase induced by cinobufacini. The immunofluorescence studies of cytoskeletal and nuclear morphology showed that after cinobufacini treatment, the regular reorganization of actin filaments in HepG2 cells become chaotic, while the nuclei were not damaged seriously. Additionally, high-resolution AFM imaging revealed that cell morphology and ultrastructure changed a lot after treatment with cinobufacini. It appeared as significant shrinkage and deep pores in the cell membrane, with larger particles and a rougher cell surface.
CONCLUSION: Cinobufacini inhibits the viability of HepG2 cells via cytoskeletal destruction and cell membrane toxicity.
PMCID: PMC4299337  PMID: 25624718
Cinobufacini; Cell viability; Atomic force microscopy; HepG2 cells; Hepatocarcinoma
5.  Pien Tze Huang Inhibits Hypoxia-Induced Angiogenesis via HIF-1α/VEGF-A Pathway in Colorectal Cancer 
Hypoxia-induced angiogenesis plays an important role in the development and metastasis of solid tumors and is highly regulated by HIF-1α/VEGF-A pathway. Therefore, inhibiting tumor angiogenesis via suppression of HIF-1α/VEGF-A signaling represents a promising strategy for anticancer treatment. As a traditional Chinese medicine formula, Pien Tze Huang (PZH) has long been used as a folk remedy for cancer in China and Southeast Asia. Previously, we reported that PZH inhibits colorectal cancer (CRC) growth both in vivo and in vitro. To elucidate the antitumor mechanisms of PZH, in the present study we used human umbilical vein endothelial cells (HUVEC) and colorectal carcinoma HCT-8 cells to evaluate the effects of PZH on hypoxia-induced angiogenesis and investigated the underlying molecular mechanisms. We found that PZH could inhibit hypoxia-induced migration and tube formation of HUVEC cells in a dose-dependent manner, although the low concentrations of PZH had no effect on HUVEC viability. Moreover, PZH inhibited hypoxia-induced activation of HIF-1α signaling and the expression of VEGF-A and/or VEGFR2 in both HCT-8 and HUVEC cells. Collectively, our findings suggest that PZH can inhibit hypoxia-induced tumor angiogenesis via suppression of HIF-1α/VEGF-A pathway.
PMCID: PMC4310443  PMID: 25649293
6.  Effects of Monofunctional Platinum Agents on Bacterial Growth – A Retrospective Study 
The effect of the novel and potent monofunctional platinum(II) agent phenanthriplatin on Escherichia coli and bacteriophage λ lysogens is reported. E. coli filamentation was observed by light microscopy when cells were grown in the presence of phenanthriplatin, cis-[Pt(NH3)2(Am)Cl]+ where Am is phenanthridine. Treatment of lysogenic bacteria with this compound resulted in lysis and the production of viral particles, as indicated by plaque formation in a bacterial lawn. The results obtained with phenanthriplatin are contextualized by comparison with those obtained using cisplatin as well as other, less active, monofunctional compounds such as [Pt(NH3)3Cl]+ and cis-[Pt(NH3)2(py)Cl]+, where py is pyridine. The ability of phenanthriplatin to induce bacterial filamentation and initiate lysis in lysogenic bacteria corroborates the hypothesis that the biological activity of this complex is mediated by its interaction with DNA.
PMCID: PMC3920743  PMID: 24364388
7.  Comparison of Assembled Clostridium botulinum A1 Genomes Revealed Their Evolutionary Relationship 
Genomics  2013;103(1):94-106.
Clostridium botulinum encompasses bacteria that produce at least one of the seven serotypes of botulinum neurotoxin (BoNT/A-G). The availability of genome sequences of four closely related Type A1 or A1(B) strains, as well as the A1-specific microarray, allowed the analysis of their genomic organizations and evolutionary relationship. The four genomes share >90% core genes and >96% functional groups. Phylogenetic analysis based on COG shows closer relations of the A1(B) strain, NCTC 2916, to B1 and F1 than A1 strains. Alignment of the genomes of the three A1 strains revealed a highly similar chromosomal structure with three small gaps in the genome of ATCC 19397 and one additional gap in the genome of Hall A, suggesting ATCC 19379 as an evolutionary intermediate between Hall A and ATCC 3502. Analyses of the four gap regions indicated potential horizontal gene transfer and recombination events important for the evolution of A1 strains.
PMCID: PMC3959226  PMID: 24369123
Clostridium botulinum; genomic comparison; microarray
8.  Association of Glutathione S-Transferase P1 (GSTP1) Polymorphism with Tourette Syndrome in Taiwanese Patients 
The etiology of Tourette syndrome (TS) is multifactorial. TS vulnerability may be associated with genetic and environmental factors. From the genetic point of view, TS is heterogeneous. Previous studies showed that some single-nucleotide polymorphisms (SNPs) of the glutathione-S-transferase P1 (GSTP1) gene can affect cellular proliferation and apoptotic activity and TS is a neurodevelopmental disorder. We guessed that there was a relationship between TS and genetic variants of the GSTP1 gene. Therefore, in this study, we aimed to test the hypothesis that GSTP1 SNPs were associated with TS. We performed a case–control study. One hundred twenty-one TS children and 105 normal children were included in the study. Polymerase chain reaction was used to identify the GSTP1 gene polymorphism at position rs6591256 (A/G, promoter polymorphism) in TS patients and normal children. The polymorphism at position rs6591256 in the GSTP1 gene revealed significant differences in the allele (p=0.0135) and genotype (p=0.0159) distributions between the TS patients and the control group. The A allele was present at a higher frequency than the G allele in the TS patients compared with the control group (odds ratio [OR]=1.91, 95% confidence interval [CI]: 1.14–3.21). The AA genotype was associated with susceptibility to TS with an OR of 2.38 for the AA versus AG genotype (95% CI: 1.29–4.41). These findings suggest that variants in the GSTP1 gene may play a role in susceptibility to TS.
PMCID: PMC3887428  PMID: 24205873
9.  Fibroblast Growth Factors Stimulate Hair Growth through β-Catenin and Shh Expression in C57BL/6 Mice 
BioMed Research International  2015;2015:730139.
Growth factors are involved in the regulation of hair morphogenesis and cycle hair growth. The present study sought to investigate the hair growth promoting activities of three approved growth factor drugs, fibroblast growth factor 10 (FGF-10), acidic fibroblast growth factor (FGF-1), and basic fibroblast growth factor (FGF-2), and the mechanism of action. We observed that FGFs promoted hair growth by inducing the anagen phase in telogenic C57BL/6 mice. Specifically, the histomorphometric analysis data indicates that topical application of FGFs induced an earlier anagen phase and prolonged the mature anagen phase, in contrast to the control group. Moreover, the immunohistochemical analysis reveals earlier induction of β-catenin and Sonic hedgehog (Shh) in hair follicles of the FGFs-treated group. These results suggest that FGFs promote hair growth by inducing the anagen phase in resting hair follicles and might be a potential hair growth-promoting agent.
PMCID: PMC4313060
10.  Incidence rates of tuberculosis in chronic hepatitis C infected patients with or without interferon based therapy: a population-based cohort study in Taiwan 
BMC Infectious Diseases  2014;14(1):705.
It is debated whether interferon-based therapy (IBT) would affect the incidence of active tuberculosis (TB) among hepatitis C virus (HCV) infected patients. Although some case reports have demonstrated a possible association, the results are currently inconclusive. Therefore, we conducted a nation-wide population study to investigate the incidence of active TB in HCV infected patients receiving IBT in Taiwan.
This 9-year cohort study was based on the Longitudinal Health Insurance Database 2000 (LHID 2000) consisting of 1,000,000 beneficiaries randomly selected from all Taiwan National Health Insurance enrollees in 2000 ( >23.7 million). This insurance program covers all citizens in Taiwan. We conducted a retrospective cohort study that identified subjects with HCV infection. IBTs were defined as regimens that included interferon α, peginterferon α2a and peginterferon α2b for at least 2 months. Among them, 621 subjects received IBT, and 2,460 age- and gender-matched subjects were enrolled for analysis. The Cox proportional hazards models were used to estimate the hazard ratio (HR) for active TB, and associated confidence intervals (CIs), comparing IBT cohort and untreated cohort. The endpoint in this study was whether an enrolled subject had a new diagnosis of active TB.
During the 9-year enrollment period, the treated and untreated cohorts were followed for a mean (± SD) duration of 6.97 ± 0.02 years and 8.21 ± 0.01 years, respectively. The cumulative incidence rate of active TB during this study period was 0.150 and 0.151 per 100 person-years in the IBT treated and untreated cohorts, respectively. There was no significant difference in the incidence of active TB in either cohort during a 1-year follow-up (Adjusted Hazard Ratio (AHR): 2.81, 95% Confidence Interval (95% CI): 0.61–12.98) or the long-term follow-up (AHR: 1.02, 95% CI: 0.28 – 3.78). The Cox proportional hazards model demonstrated that IBT was not a risk factor for active TB . The only risk factor for active TB was the occurrence of hepatic encephalopathy.
Our results showed that IBT is associated with increased hazard of active TB in HCV infected patients in 1-year follow-up; however, the effect sizes were not statistically significant.
PMCID: PMC4307221  PMID: 25523602
Interferon; Hepatitis C virus; Tuberculosis
11.  From Rice Bran to High Energy Density Supercapacitors: A New Route to Control Porous Structure of 3D Carbon 
Scientific Reports  2014;4:7260.
Controlled micro/mesopores interconnected structures of three-dimensional (3D) carbon with high specific surface areas (SSA) are successfully prepared by carbonization and activation of biomass (raw rice brans) through KOH. The highest SSA of 2475 m2 g−1 with optimized pore volume of 1.21 cm3 g−1 (40% for mesopores) is achieved for KOH/RBC = 4 mass ratio, than others. The as-prepared 3D porous carbon-based electrode materials for supercapacitors exhibit high specific capacitance specifically at large current densities of 10 A g−1 and 100 A g−1 i.e., 265 F g−1 and 182 F g−1 in 6 M KOH electrolyte, respectively. Moreover, a high power density ca. 1223 W kg−1 (550 W L−1) and energy density 70 W h kg−1 (32 W h L−1) are achieved on the base of active material loading (~10 mg cm2) in the ionic liquid. The findings can open a new avenue to use abundant agricultural by-products as ideal materials with promising applications in high-performance energy-storage devices.
PMCID: PMC4248281  PMID: 25434348
12.  Five-year epidemiological survey of valvular heart disease: changes in morbidity, etiological spectrum and management in a cardiovascular center of Southern China 
Journal of Thoracic Disease  2014;6(12):1724-1730.
The objective of the present study is to analyze the epidemiological profile of patients with abnormal valvular structure and function and highlight the etiological spectrum and management of valvular heart disease (VHD) in a single cardiovascular center of Southern China in five years.
The retrospective study included 19,428 consecutive patients (9,441 men and 9,987 women with a mean age of 52.03±20.50 years) with abnormal valvular structure and function who were screened by transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE) at the in-patient department of Guangdong General Hospital from January 2009 to December 2013. Data on baseline characteristics, potential etiology, treatment strategies and discharge outcomes were collected from electronic medical records.
There were 13,549 (69.7%) patients with relatively definite etiology for VHD. VHD was rheumatic in 7,197 (37.0%) patients, congenital in 2,697 (13.9%), degenerative in 2,241 (11.5%), ischemic in 2,460 (12.7%). The prevalence decreased significantly in rheumatic VHD from 2009 to 2013 (from 42.8% to 32.8%, P<0.001), but increased markedly in congenital VHD (from 9.0% to 12.3%, P<0.001), ischemic VHD (from 9.2% to 11.3%, P=0.003) and degenerative VHD (from 8.8% to 14.5%, P<0.001). Meantime, the prevalence of ischemic VHD increased after the age of 45, similar to that of degenerative VHD. From 2009 to 2013, the proportion of patients with VHD undergoing open cardiac valvular surgery decreased (from 49.5% to 44.3%, P<0.001) and that of patients treated with general medication increased (from 49.2% to 54.1%, P<0.001). However, there was markedly increment in video-assisted thoracoscopic surgery (VATS) from 2009 to 2013 (from 0.3% to 4.4%, P<0.001). Increasing tendencies were showed in aortic mechanical valve replacement (from 32.1% to 34.5%, P=0.001) and double mechanical valve replacement (from 20.9% to 22.3%, P=0.035), especially in mitral valvuloplasty (from 8.5% to 15.7%, P<0.001). However, the proportion of patients undergoing bioprosthetic valve replacement decreased from 2009 to 2013 (from 26.3% to 15.5%, P<0.001).
Despite a significant shift from rheumatic towards degenerative etiology from 2009 to 2013, rheumatic VHD remains the leading etiology in Southern China, with a significant increase in the prevalence of ischemic, congenital and degenerative VHD. General medication and cardiac valvular surgery remain the main treatment options. The proportion of VATS increased markedly from 2009 to 2013, and mechanical valve replacement and mitral valvuloplasty showed an increasing tendency.
PMCID: PMC4283290  PMID: 25589965
Epidemiological; valvular heart disease (VHD); etiology; cardiac valvular surgery
13.  Overnight fluid shifts in subjects with and without obstructive sleep apnea 
Journal of Thoracic Disease  2014;6(12):1736-1741.
To investigate the characteristics of baseline body fluid content and overnight fluid shifts between non-obstructive sleep apnea (non-OSA) and obstructive sleep apnea (OSA) subjects.
A case-controlled study was performed between February 2013 and January 2014, with 36 (18 OSA and 18 non-OSA) outpatients enrolled in this study. Polysomnographic parameters and results of body fluid were compared between the two groups.
There were no differences in age, weight, and body mass index (BMI) between groups. Compared with the non-OSA group, OSA group had significantly higher neck circumference (NC) and fluid volume shift in the legs. OSA patients had higher left and right leg fluid indices than non-OSA subjects. There were significant correlations between apnoea-hypopnoea index and baseline fluid indices in both legs as well as the reduction in overnight change in both legs fluid volume. The increase in NC was also significantly correlated with the reduction in overnight change in both legs fluid volume, but not with the change in head and neck fluid volume. There were significant correlations between change in NC and increased fluid shifts in head and neck volume.
OSA patients had a higher baseline fluid content in both legs as compared with non-OSA subjects, which may be the basic factor with regards to fluid shifts in OSA patients. The increase in head and neck fluid shift volume did not directly correlate with the severity of OSA.
PMCID: PMC4283308  PMID: 25589967
Obstructive sleep apnea (OSA); fluid shift; body composition analysis
14.  Cross-strait parasitological research priorities arrived at by historical tracking and advanced dialogue 
To further enhance dialogue and promote cross-strait cooperation in the prevention and control of parasitic diseases, this paper reviewed the progress and current challenges in the cross-strait control and research of parasitic infections, based on three cross-strait meetings on parasitological research in the last decade. The major outcome of the 3rd Meeting of Cross-Strait Parasitological Research held in April 2013 was identifying the research priorities for parasitological research.
Electronic supplementary material
The online version of this article (doi:10.1186/2049-9957-3-40) contains supplementary material, which is available to authorized users.
PMCID: PMC4322646  PMID: 25671120
Cross-strait meeting; Parasitological research priorities; Epidemiology
15.  The n-type Ge photodetectors with gold nanoparticles deposited to enhance the responsivity 
Nanoscale Research Letters  2014;9(1):640.
Gold nanoparticles (AuNPs) have been deposited on n-type Ge photodetectors to improve the responsivity. Two different coverage ratios, including 10.5 and 30.3% of AuNPs have been prepared, and the fabricated photodetectors are compared with the control sample. The 1,310-nm responsivities at -2 V of the control, 10.5% AuNPs, and 30.3% AuNPs samples are 465, 556, and 623 mA/W, respectively. The AuNPs could increase the responsivities due to the plasmon resonance. The reflectance spectra of these samples have been measured to verify that plasmon resonance contributes to the forward scattering of incident light. The reflectance decreases with AuNP deposition, and a denser coverage results in a smaller reflectance. The smaller reflectance indicates more light could penetrate into the Ge active layer, and it results in a larger responsivity.
PMCID: PMC4256966  PMID: 25489291
AuNP; Ge photodetector; Responsivity
16.  Pien Tze Huang Overcomes Multidrug Resistance and Epithelial-Mesenchymal Transition in Human Colorectal Carcinoma Cells via Suppression of TGF-β Pathway 
The traditional Chinese medicine formula Pien Tze Huang (PZH) has long been used as a folk remedy for cancer. To elucidate the mode of action of PZH against cancer, in the present study we used a 5-FU resistant human colorectal carcinoma cell line (HCT-8/5-FU) to evaluate the effects of PZH on multidrug resistance (MDR) and epithelial-mesenchymal transition (EMT) as well as the activation of TGF-β pathway. We found that PZH dose-dependently inhibited the viability of HCT-8/5-FU cells which were insensitive to treatment of 5-FU and ADM, demonstrating the ability of PZH to overcome chemoresistance. Furthermore, PZH increased the intercellular accumulation of Rhodamine-123 and downregulated the expression of ABCG2 in HCT-8/5-FU cells. In addition, drug resistance induced the process of EMT in HCT-8 cells as evidenced by EMT-related morphological changes and alteration in the expression of EMT-regulatory factors, which however was neutralized by PZH treatment. Moreover, PZH inhibited MDR/EMT-enhanced migration and invasion capabilities of HCT-8 cells in a dose-dependent manner and suppressed MDR-induced activation of TGF-β signaling in HCT-8/5-FU cells. Taken together, our study suggests that PZH can effectively overcome MDR and inhibit EMT in human colorectal carcinoma cells via suppression of the TGF-β pathway.
PMCID: PMC4253702  PMID: 25505925
17.  A Two-Step Strategy to Enhance Activity of Low Potency Peptides 
PLoS ONE  2014;9(11):e110502.
Novel strategies are needed to expedite the generation and optimization of peptide probes targeting G protein-coupled receptors (GPCRs). We have previously shown that membrane tethered ligands (MTLs), recombinant proteins comprised of a membrane anchor, an extracellular linker, and a peptide ligand can be used to identify targeted receptor modulators. Although MTLs provide a useful tool to identify and/or modify functionally active peptides, a major limitation of this strategy is the reliance on recombinant protein expression. We now report the generation and pharmacological characterization of prototype peptide-linker-lipid conjugates, synthetic membrane anchored ligands (SMALs), which are designed as mimics of corresponding MTLs. In this study, we systematically compare the activity of selected peptides as MTLs versus SMALs. As prototypes, we focused on the precursor proteins of mature Substance P (SubP) and Cholecystokinin 4 (CCK4), specifically non-amidated SubP (SubP-COOH) and glycine extended CCK4 (CCK4-Gly-COOH). As low affinity soluble peptides these ligands each presented a challenging test case for assessment of MTL/SMAL technology. For each ligand, MTLs and corresponding SMALs showed agonist activity and comparable subtype selectivity. In addition, our results illustrate that membrane anchoring increases ligand potency. Furthermore, both MTL and SMAL induced signaling can be blocked by specific non-peptide antagonists suggesting that the anchored constructs may be orthosteric agonists. In conclusion, MTLs offer a streamlined approach for identifying low activity peptides which can be readily converted to higher potency SMALs. The ability to recapitulate MTL activity with SMALs extends the utility of anchored peptides as probes of GPCR function.
PMCID: PMC4229100  PMID: 25391026
18.  Particle Lithography Enables Fabrication of Multicomponent Nanostructures 
Multicomponent nanostructures with individual geometries have attracted much attention because of their potential to carry out multiple functions synergistically. The current work reports a simple method using particle lithography to fabricate multicomponent nanostructures of metals, proteins, and organosiloxane molecules, each with its own geometry. Particle lithography is well-known for its capability to produce arrays of triangular-shaped nanostructures with novel optical properties. This paper extends the capability of particle lithography by combining a particle template in conjunction with surface chemistry to produce multicomponent nanostructures. The advantages and limitations of this approach will also be addressed.
PMCID: PMC3972815  PMID: 24707328
19.  Investigation of the caspase-dependent mitochondrial apoptotic pathway in mononuclear cells of patients with systemic lupus erythematosus 
This study aimed to explore the role of apoptosis initiators, caspase-9, caspase-10, mitochondrial anti-viral signaling protein (MAVS), and interferon regulatory factor 7 (pIRF7), in patients with systemic lupus erythematosus (SLE).
Leukocyte apoptosis was determined by flow cytometry, including annexin V, APO2.7, and 7-amino-actinomycin D (7-AAD) on each subtype of leukocyte in 35 patients with SLE, 15 disease controls, and 17 volunteer normal controls. Levels of caspase-9, caspase-10, MAVS, and pIRF7 in mononuclear cells and the disease activity index (SLEDAI) in the SLE patients were determined. Correlation among intracellular adaptor proteins and caspase levels were calculated.
The SLE patients had higher APO2.7 in total leukocyte, lymphocyte, and monocytes, and higher late apoptosis markers in total leukocytes and neutrophils than normal controls (all p < 0.05). Disease activity was positively associated with the APO2.7 of CD19+ cells in SLE, but negatively associated with MAVS and caspase-9 levels (all p < 0.05). Markers of viral infection and anti-virus transcription factors like MDA5, MAVS, and pIRF7 were significantly higher in SLE patients than in disease controls (p < 0.05). Caspase-9 and caspase-10 levels positively correlated with MAVS and pIRF7 in SLE patients (p < 0.05).
The disease activity of SLE is positively associated with APO2.7 level of CD19+ cells but negatively associated with MAVS and caspase-9 levels, which all point to a mitochondrial pathway.
PMCID: PMC4226892  PMID: 25370148
Caspase; Leukocyte apoptosis; Systemic lupus erythematosus; Interferon
20.  The Feasibility of Using CT-Guided ROI for Semiquantifying Striatal Dopamine Transporter Availability in a Hybrid SPECT/CT System 
The Scientific World Journal  2014;2014:879497.
A hybrid SPECT/CT system provides accurate coregistration of functional and morphological images. CT-guided region of interest (ROI) for semiquantifying striatal dopamine transporter (DAT) availability may be a feasible method. We therefore assessed the intra- and interobserver reproducibility of manual SPECT and CT-guided ROI methods and compared their semiquantitative data with data from MRI-guided ROIs. We enrolled twenty-eight patients who underwent Tc-99m TRODAT-1 brain SPECT/CT and brain MRI. ROIs of the striatal, caudate, putamen, and occipital cortex were manually delineated on the SPECT, CT, and MRI. ROIs from CT and MRI were transferred to the coregistered SPECT for semiquantification. The striatal, caudate, and putamen nondisplaceable binding potential (BPND) were calculated. Using CT-guided ROIs had higher intra- and interobserver concordance correlation coefficients, closer Bland-Altman biases to zero, and narrower limits of agreement than using manual SPECT ROIs. The correlation coefficients of striatal, caudate, and putamen BPND were good between manual SPECT and MRI-guided ROI methods and even better between CT-guided and MRI-guided ROI methods. Conclusively, CT-guided ROI delineation for semiquantifying striatal DAT availability in a hybrid SPECT/CT system is highly reproducible, and the semiquantitative data correlate well with data from MRI-guided ROIs.
PMCID: PMC4233671  PMID: 25531005
21.  Prediction of trabecular bone qualitative properties using scanning quantitative ultrasound 
Acta astronautica  2012;92(1):79-88.
Microgravity induced bone loss represents a critical health problem in astronauts, particularly occurred in weight-supporting skeleton, which leads to osteopenia and increase of fracture risk. Lack of suitable evaluation modality makes it difficult for monitoring skeletal status in long term space mission and increases potential risk of complication. Such disuse osteopenia and osteoporosis compromise trabecular bone density, and architectural and mechanical properties. While X-ray based imaging would not be practical in space, quantitative ultrasound may provide advantages to characterize bone density and strength through wave propagation in complex trabecular structure. This study used a scanning confocal acoustic diagnostic and navigation system (SCAN) to evaluate trabecular bone quality in 60 cubic trabecular samples harvested from adult sheep. Ultrasound image based SCAN measurements in structural and strength properties were validated by μCT and compressive mechanical testing. This result indicated a moderately strong negative correlations observed between broadband ultrasonic attenuation (BUA) and μCT-determined bone volume fraction (BV/TV, R2=0.53). Strong correlations were observed between ultrasound velocity (UV) and bone’s mechanical strength and structural parameters, i.e., bulk Young’s modulus (R2=0.67) and BV/TV (R2=0.85). The predictions for bone density and mechanical strength were significantly improved by using a linear combination of both BUA and UV, yielding R2=0.92 for BV/TV and R2=0.71 for bulk Young’s modulus. These results imply that quantitative ultrasound can characterize trabecular structural and mechanical properties through measurements of particular ultrasound parameters, and potentially provide an excellent estimation for bone’s structural integrity.
PMCID: PMC3747567  PMID: 23976803
quantitative ultrasound; scanning confocal ultrasound; ultrasound attenuation; ultrasound velocity; bone loss in space; disuse osteoporosis; bone adaptation; bone mineral density; speed of sound; dual-energy X-ray absorptiometry; bone quality
22.  Predictors and long-term outcome of seizures in human immuno-deficiency virus (HIV)-negative cryptococcal meningitis 
BMC Neurology  2014;14(1):208.
Seizures are one of the most important neurologic complications of human immuno-deficiency virus (HIV)-negative cryptococcal meningitis. A better understanding of the risk associated factors can help predict those who will require treatment.
This 22-year retrospective study enrolled 180 patients. Prognostic variables independently associated with seizures or fatality were analyzed using stepwise logistic regression.
Twenty-eight patients with HIV-negative cryptococcal meningitis had seizures, including 13 with early seizures and 15 with late seizures. The mean time interval from HIV-negative cryptococcal meningitis to first seizure in the early and late seizure groups were 1.5 and 51.4 days, respectively. Nine out of the 28 cases (32%) occurred within 24 hours of presentation. The overall mortality rate was 54% (15/28) and two patients progressed to epilepsy.
Patients with seizure have worse outcomes and longer hospitalization. Most first seizures occur within one year after the diagnosis of HIV-negative cryptococcal meningitis.
PMCID: PMC4203868  PMID: 25307800
Outcome; Risk factors; Seizures; HIV-negative cryptococcal meningitis
23.  Primary malignant non-Hodgkin’s lymphoma of the breast: A case report 
Oncology Letters  2014;8(6):2597-2600.
Primary malignant lymphoma of the breast (PLB) is a rare disease. Treatment options include surgical resection, systemic chemotherapy, radiation and immunotherapy. At present, the optimum treatment combination remains controversial. The present study reports the case of a 39-year-old female with a six month history of a painless mass in the left breast. The mass was excised following medical examination. A diagnosis of diffuse large B-cell lymphoma was determined as a result of histological and immunohistochemical profile analysis. Further examinations excluded metastatic disease. Thus, finally, PLB (diffuse large B-cell lymphoma type) was diagnosed. The patient was treated with adjuvant systemic chemotherapy and consolidated radiation and a positive response was observed. During the 10 months of follow-up, no evidence of disease recurrence was identified. At present, the patient is scheduled for regular follow-up appointments. As the prevalence of PLB is increasing, the details of this rare case may aid clinicians treating similar patients, and highlight the importance of this disease.
PMCID: PMC4214428  PMID: 25360172
malignant lymphoma; breast lymphoma; immunohistochemistry
24.  Bidentate Ligands on Osmium(VI) Nitrido Complexes Control Intracellular Targeting and Cell Death Pathways 
Journal of the American Chemical Society  2013;135(38):14060-14063.
The cellular response evoked by anti-proliferating osmium(VI) nitrido compounds of general formula OsN(N^N)Cl3 (N^N = 2,2′-bipyridine 1, 1,10-phenanthroline 2, 3,4,7,8-tetramethyl-1,10-phenanthroline 3, or 4,7-diphenyl-1,10-phenanthroline 4) can be tuned by subtle ligand modifications. Complex 2 induces DNA damage, resulting in activation of the p53 pathway, cell cycle arrest at the G2/M phase, and caspase-dependent apoptotic cell death. In contrast, 4 evokes ER stress leading to the upregulation of proteins of the unfolded protein response pathway, increase in ER size, and p53-independent apoptotic cell death. To the best of our knowledge, 4 is the first osmium compound to induce ER stress in cancer cells.
PMCID: PMC3791136  PMID: 24041161
25.  Cervical squamous cell carcinoma with isolated tibial metastasis: A case report and review of the literature 
Oncology Letters  2014;8(6):2535-2538.
Bone metastasis resulting from carcinoma of the cervix is rare, particularly in the isolated distal appendicular bone. A 43-year-old female was diagnosed with a right tibial tumor with progressive right knee pain for three months, which was diagnosed as poorly differentiated metastatic squamous cell carcinoma, and further confirmed by biopsy of the proximal tibia. The patient was diagnosed with cervical squamous cell carcinoma with tibial metastasis following further examination, despite a lack of gynecological symptoms. In contrast to the poor outcome commonly observed in patients with bone metastasis, the patient survived and remained disease-free 41 months after surgical excision of the metastatic tumor and radical hysterectomy followed by chemoradiotherapy. The present case is one of the few documented cases of metastasis to the tibia arising from carcinoma of the uterine cervix and may be the first regarding isolated metastasis at this site.
PMCID: PMC4214447  PMID: 25364422
cervical carcinoma; bone metastasis; tibia

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