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1.  Exposure to cooking fuels and birth weight in Lanzhou, China: a birth cohort study 
BMC Public Health  2015;15:712.
Background
Early studies have suggested that biomass cooking fuels were associated with increased risk of low birth weight (LBW). However it is unclear if this reduced birth weight was due to prematurity or intrauterine growth restriction (IUGR).
Methods
In order to understand the relationship between various cooking fuels and risk of LBW and small for gestational age (SGA), we analyzed data from a birth cohort study conducted in Lanzhou, China which included 9,895 singleton live births.
Results
Compared to mothers using gas as cooking fuel, significant reductions in birth weight were observed for mothers using coal (weight difference = 73.31 g, 95 % CI: 26.86, 119.77) and biomass (weight difference = 87.84 g, 95 % CI: 10.76, 164.46). Using biomass as cooking fuel was associated with more than two-fold increased risk of LBW (OR = 2.51, 95 % CI: 1.26, 5.01), and the risk was mainly seen among preterm births (OR = 3.43, 95 % CI: 1.21, 9.74). No significant associations with LBW were observed among mothers using coal or electromagnetic stoves for cooking.
Conclusions
These findings suggest that exposure to biomass during pregnancy is associated with risk of LBW, and the effect of biomass on LBW may be primarily due to prematurity rather than IUGR.
doi:10.1186/s12889-015-2038-1
PMCID: PMC4517486  PMID: 26215397
Cooking fuel; Birth weight; Low birth weight; Small for gestational age; China; Epidemiology
2.  A Novel Mutation of SMAD3 Identified in a Chinese Family with Aneurysms-Osteoarthritis Syndrome 
BioMed Research International  2015;2015:968135.
Aneurysms-osteoarthritis syndrome (AOS) is a recently delineated autosomal dominant disorder characterized by aneurysms, dissections, and tortuosity throughout the arterial tree in association with early onset osteoarthritis, mild craniofacial features, and skeletal and cutaneous anomalies. Previous studies have demonstrated that mutations in SMAD3, a key regulator of TGF-β signal transduction, contribute to AOS. Here, we investigated a family of three generations affected by AOS. A novel SMAD3 mutation, c.266G>A (p.C89Y), was identified and cosegregated with the affected individuals in this family. Our finding expands the mutation spectrum of SMAD3 gene and further strengthens the connection between the presence of aneurysms-osteoarthritis phenotype and SMAD3 mutations, which facilitates the understanding of the genotype-phenotype correlation of AOS.
doi:10.1155/2015/968135
PMCID: PMC4499615  PMID: 26221609
3.  Tetraarsenictetrasulfide and Arsenic Trioxide Exert Synergistic Effects on Induction of Apoptosis and Differentiation in Acute Promyelocytic Leukemia Cells 
PLoS ONE  2015;10(6):e0130343.
Since arsenic trioxide (As3+) has been successfully used in the treatment of acute promyelocytic leukemia (APL), its adverse effects on patients have been problematic and required a solution. Considering the good therapeutic potency and low toxicity of tetraarsenictetrasulfide (As4S4) in the treatment of APL, we investigated the effects of combining As4S4 and As3+ on the apoptosis and differentiation of NB4 and primary APL cells. As4S4, acting similarly to As3+, arrested the G1/S transition, induced the accumulation of cellular reactive oxygen species, and promoted apoptosis. Additionally, low concentrations of As4S4 (0.1–0.4 μM) induced differentiation of NB4 and primary APL cells. Compared with the As4S4- or As3+-treated groups, the combination of As4S4 and As3+ obviously promoted apoptosis and differentiation of NB4 and primary APL cells. Mechanistic studies suggested that As4S4 acted synergistically with As3+ to down-regulate Bcl-2 and nuclear factor-κB expression, up-regulate Bax and p53 expression, and induce activation of caspase-12 and caspase-3. Moreover, the combination of low concentrations of As4S4 and As3+ enhanced degradation of the promyelocytic leukemia-retinoic acid receptor α oncoprotein. In summary, As4S4 and As3+ synergistically induce the apoptosis and differentiation of NB4 and primary APL cells.
doi:10.1371/journal.pone.0130343
PMCID: PMC4481354  PMID: 26110921
4.  Engineering of lipid prodrug-based, hyaluronic acid-decorated nanostructured lipid carriers platform for 5-fluorouracil and cisplatin combination gastric cancer therapy 
Purpose
The first-line chemotherapy treatment protocol for gastric cancer is combination chemotherapy of 5-fluorouracil (5-FU) and cisplatin (CDDP). The aim of this study was to engineer prodrug-based nanostructured lipid carriers (NLC) platform for codelivery of 5-FU and CDDP to enhance therapy and decrease toxicity.
Methods
First, 5-FU-stearic acid lipid conjugate was synthesized by two steps. Second, 5-FU-stearic acid prodrug and CDDP were loaded in NLC. Finally, hyaluronic acid (HA) was coated onto NLC surface. Average size, zeta potential, and drug loading capacity of NLC were evaluated. Human gastric cancer cell line BGC823 (BGC823 cells) was used for the testing of in vitro cytotoxicity assays. In vivo antitumor activity of NLC was evaluated in mice bearing BGC823 cells model.
Results
HA-coated 5-FU-stearic acid prodrug and CDDP-loaded NLC (HA-FU/C-NLC) showed a synergistic effect in combination therapy and displayed the greatest antitumor activity than all of the free drugs or uncoated NLC in vitro and in vivo.
Conclusion
This work reveals that HA-coated NLC could be used as a novel carrier to code-liver 5-FU and CDDP for gastric cancer therapy. HA-FU/C-NLC could be a promising targeted and combinational therapy in nanomedicine.
doi:10.2147/IJN.S83211
PMCID: PMC4468988  PMID: 26089667
gastric cancer; nanostructured lipid carriers; hyaluronic acid; combination chemotherapy; lipid prodrug
5.  Anticancer Effect and Apoptosis Induction of Gambogic Acid in Human Leukemia Cell Line K562 In Vitro 
Background
The aim of this study was to investigate the anticancer effect and related mechanisms of gambogic acid (GA), a traditional Chinese medicine, on human leukemia cell line K562, together with the effect on bone marrow mononuclear cells (MNCs).
Material/Methods
K562 cells and MNCs were treated with various concentrations and treatment times of GA. Inhibitory rate was detected by use of the Cell Counting Kit-8 (CCK-8) assay. Apoptosis was analyzed by morphological detection, Annexin-V/PI doubling staining, and TUNEL assays. The expression changes of pivotal proteins were evaluated by Western blotting.
Results
GA not only suppressed cell proliferation, but also induced apoptosis of K562 cells in a dose-dependent manner. While it did not significantly inhibit cell proliferation of MNCs, it did induce apoptosis in a dose-dependent manner. CCK-8 assay revealed that the proliferation of K562 cells was significantly inhibited when the concentration of GA was more than 0.5 μM. Morphological detection showed the nuclei became denser and more intense orange in K562 cells after GA treatment compared with the untreated group. The expression levels of BCL-2, nuclear factor-κB (NF-κB), c-myc, phosphatidylinositol3-kinase (PI3K), and phosphorylation of serine-threonine kinase (p-AKT) were down-regulated by GA.
Conclusions
GA significantly suppressed the proliferation of K562 cells, but has less effect on MNCs. The inhibition of K562 cells proliferation and apoptosis induced by GA might be related to the down-regulation of BCL-2, NF-κB, c-myc, PI3K, and p-AKT.
doi:10.12659/MSM.893004
PMCID: PMC4463775  PMID: 26049398
Apoptosis; Bone Marrow Mononuclear Cells; Gambogic Acid; Gene Expression; Human Leukemia Cell Line K562
6.  Characterization of Biochemical Properties of Bacillus subtilis RecQ Helicase 
Journal of Bacteriology  2014;196(24):4216-4228.
RecQ family helicases function as safeguards of the genome. Unlike Escherichia coli, the Gram-positive Bacillus subtilis bacterium possesses two RecQ-like homologues, RecQ[Bs] and RecS, which are required for the repair of DNA double-strand breaks. RecQ[Bs] also binds to the forked DNA to ensure a smooth progression of the cell cycle. Here we present the first biochemical analysis of recombinant RecQ[Bs]. RecQ[Bs] binds weakly to single-stranded DNA (ssDNA) and blunt-ended double-stranded DNA (dsDNA) but strongly to forked dsDNA. The protein exhibits a DNA-stimulated ATPase activity and ATP- and Mg2+-dependent DNA helicase activity with a 3′→5′ polarity. Molecular modeling shows that RecQ[Bs] shares high sequence and structure similarity with E. coli RecQ. Surprisingly, RecQ[Bs] resembles the truncated Saccharomyces cerevisiae Sgs1 and human RecQ helicases more than RecQ[Ec] with regard to its enzymatic activities. Specifically, RecQ[Bs] unwinds forked dsDNA and DNA duplexes with a 3′-overhang but is inactive on blunt-ended dsDNA and 5′-overhung duplexes. Interestingly, RecQ[Bs] unwinds blunt-ended DNA with structural features, including nicks, gaps, 5′-flaps, Kappa joints, synthetic replication forks, and Holliday junctions. We discuss these findings in the context of RecQ[Bs]'s possible functions in preserving genomic stability.
doi:10.1128/JB.06367-11
PMCID: PMC4248853  PMID: 25246477
7.  Interleukin-8 for Diagnosis of Neonatal Sepsis: A Meta-Analysis 
PLoS ONE  2015;10(5):e0127170.
Background
Neonatal sepsis (NS) is a life-threatening disorder and an important cause of morbidity and mortality in neonates. Previous studies showed that interleukin 8 (IL-8) may effectively and rapidly diagnose NS.
Objective
We conducted the systematic review and meta-analysis to investigate the diagnostic value of the IL-8 in NS.
Methods
The literature was searched in PUBMED, EMBASE, Cochrane Library, CNKI, VIP and other Chinese Medical Databases during October 1998 to January 2014 using set search criteria. Each included study was evaluated by quality assessment of diagnostic accuracy studies tool. Two investigators independently extracted the data and study characteristics, and disagreements, if any, were resolved by consensus. Meta-disc software was used to calculate the pooled sensitivity, specificity and summary diagnostic odds ratio (SDOR), I² or Cochrane Q to test heterogeneity, and meta-regression to investigate the source of heterogeneity. Funnel plots were used to test the potential presence of publication bias. False-positive report probability (FPRP) was calculated to confirm the significance of the results.
Results
Eight studies (548 neonates) were included in this meta-analysis. The pooled sensitivity and specificity of IL-8 were 0.78 and 0.84, respectively, which had moderate accuracy in the diagnosis of NS. The pooled diagnostic odds ratio (DOR) and area under curve (AUC) was 21.64 and 0.8908 (Q*=0.8215), respectively. The diagnostic threshold analysis showed that there was no threshold effect. The meta-regression analysis showed the cut-off, QUADAS and onset time have no effect on the heterogeneity. The funnel plots showed the existence of publication bias.
Conclusion
Meta-analysis showed IL-8 had a moderate accuracy (AUC=0.8908) for the diagnosis of NS. IL-8 is a helpful biomarker for early diagnosis of NS. However, we should combine the results with clinical symptoms and signs, laboratory and microbial results.
doi:10.1371/journal.pone.0127170
PMCID: PMC4440704  PMID: 25996378
8.  Association of asthma with the risk of acute leukemia and non-Hodgkin lymphoma 
Molecular and Clinical Oncology  2015;3(4):859-864.
An increasing incidence of hematological malignancies has been observed in children and adults worldwide over the last few decades. Asthma is a common chronic inflammatory disease. The aim of the present meta-analysis was to evaluate the potential association between a history of asthma and the risk of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and non-Hodgkin lymphoma (NHL). A literature search was performed through PubMed and the Cochrane Database of Systematic Reviews and the Newcastle-Ottawa Scale was used to evaluate the quality of the selected studies. The I2 index was used to evaluate heterogeneity and the outcome was measured as the odds ratio (OR) by the random-effects model. A total of 16 case-control studies were included. All the studies were of high quality. The OR for ALL was 0.90 [95% confidence interval (CI): 0.68–1.19; P=0.45; I2=79%]. The OR for AML was 0.85 (95% CI: 0.67–1.08; P=0.19; I2=8%). The OR for NHL was 0.91 (95% CI: 0.83–1.00; P=0.05; I2=0%). Asthma was found to be inversely associated with the risk of NHL. A negative trend of association of asthma with ALL and AML was also observed. However, additional large prospective studies are required to confirm these findings.
doi:10.3892/mco.2015.561
PMCID: PMC4486841  PMID: 26171196
asthma; acute lymphoblastic leukemia; acute myeloid leukemia; non-Hodgkin lymphoma
9.  Identification of Gene and MicroRNA Signatures for Oral Cancer Developed from Oral Leukoplakia 
BioMed Research International  2015;2015:841956.
In clinic, oral leukoplakia (OLK) may develop into oral cancer. However, the mechanism underlying this transformation is still unclear. In this work, we present a new pipeline to identify oral cancer related genes and microRNAs (miRNAs) by integrating both gene and miRNA expression profiles. In particular, we find some network modules as well as their miRNA regulators that play important roles in the development of OLK to oral cancer. Among these network modules, 91.67% of genes and 37.5% of miRNAs have been previously reported to be related to oral cancer in literature. The promising results demonstrate the effectiveness and efficiency of our proposed approach.
doi:10.1155/2015/841956
PMCID: PMC4433644  PMID: 26064958
10.  Locational Determinants of Emissions from Pollution-Intensive Firms in Urban Areas 
PLoS ONE  2015;10(4):e0125348.
Industrial pollution has remained as one of the most daunting challenges for many regions around the world. Characterizing the determinants of industrial pollution should provide important management implications. Unfortunately, due to the absence of high-quality data, rather few studies have systematically examined the locational determinants using a geographical approach. This paper aimed to fill the gap by accessing the pollution source census dataset, which recorded the quantity of discharged wastes (waste water and solid waste) from 717 pollution-intensive firms within Huzhou City, China. Spatial exploratory analysis was applied to analyze the spatial dependency and local clusters of waste emissions. Results demonstrated that waste emissions presented significantly positive autocorrelation in space. The high-high hotspots generally concentrated towards the city boundary, while the low-low clusters approached the Taihu Lake. Their locational determinants were identified by spatial regression. In particular, firms near the city boundary and county road were prone to discharge more wastes. Lower waste emissions were more likely to be observed from firms with high proximity to freight transfer stations or the Taihu Lake. Dense populous districts saw more likelihood of solid waste emissions. Firms in the neighborhood of rivers exhibited higher waste water emissions. Besides, the control variables (firm size, ownership, operation time and industrial type) also exerted significant influence. The present methodology can be applicable to other areas, and further inform the industrial pollution control practices. Our study advanced the knowledge of determinants of emissions from pollution-intensive firms in urban areas.
doi:10.1371/journal.pone.0125348
PMCID: PMC4416044  PMID: 25927438
11.  Diagnostic Accuracy of Computed Tomography for Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review and Meta-Analysis 
PLoS ONE  2015;10(4):e0126985.
This study aimed to determine the diagnostic accuracy of computed tomography imaging for the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH). Additionally, the effect of test and study characteristics was explored. Studies published between 1990 and 2015 identified by PubMed, OVID search and citation tracking were examined. Of the 613 citations, 11 articles (n=712) met the inclusion criteria. The patient-based analysis demonstrated a pooled sensitivity of 76% (95% confidence interval [CI]: 69% to 82%), and a pooled specificity of 96% (95%CI: 93% to 98%). This resulted in a pooled diagnostic odds ratio (DOR) of 191 (95%CI: 75 to 486). The vessel-based analyses were divided into 3 levels: total arteries、main+ lobar arteries and segmental arteries. The pooled sensitivity were 88% (95%CI: 87% to 90%)、95% (95%CI: 92% to 97%) and 88% (95%CI: 87% to 90%), respectively, with a pooled specificity of 90% (95%CI: 88% to 91%)、96% (95%CI: 94% to 97%) and 89% (95% CI: 87% to 91%). This resulted in a pooled diagnostic odds ratio of 76 (95%CI: 23 to 254),751 (95%CI: 57 to 9905) and 189 (95%CI: 21 to 1072), respectively. In conclusion, CT is a favorable method to rule in CTEPH and to rule out pulmonary endarterectomy (PEA) patients for proximal branches. Furthermore, dual-energy and 320-slices CT can increase the sensitivity for subsegmental arterials, which are promising imaging techniques for balloon pulmonary angioplasty (BPA) approach. In the near future, CT could position itself as the key for screening consideration and for surgical and interventional operability.
doi:10.1371/journal.pone.0126985
PMCID: PMC4414539  PMID: 25923810
12.  Value of bevacizumab in treatment of colorectal cancer: A meta-analysis 
AIM: To assess the efficacy and safety of bevacizumab in the treatment of colorectal cancer.
METHODS: All randomized controlled trials of bevacizumab for the treatment of colorectal cancer from January 2003 to June 2013 were collected by searching the Cochrane Library, PubMed, Chinese National Knowledge Infrastructure and Wanfang databases. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival, overall response rate and adverse events. Two reviewers extracted data independently. Statistical analyses were performed with Stata 12.0. The degree of bias was assessed using funnel plots for the effect size of OS at the primary endpoint.
RESULTS: Following the inclusion criteria and exclusion criteria, ten studies comprising 6977 cases were finally included, of which nine were considered to be of high quality (4-7 points) and one of low quality (1-3 points). Our meta-analysis revealed the efficacy of bevacizumab in patients with colorectal cancer in terms of OS (HR = 0.848, 95%CI: 0.747-0.963), progression-free survival (HR = 0.617, 95%CI: 0.530-0.719), and overall response rate (OR = 1.627, 95%CI: 1.199-2.207). Regarding safety, higher rates of grade ≥ 3 hypertension, proteinuria, bleeding, thrombosis, and gastrointestinal perforation were observed in the bevacizumab treatment group (P < 0.05); however, the incidence of serious toxicity was very low. There was no publication bias in the 10 reports included in this meta-analysis.
CONCLUSION: The clinical application of bevacizumab in colorectal cancer is effective with good safety.
doi:10.3748/wjg.v21.i16.5072
PMCID: PMC4408482  PMID: 25945023
Bevacizumab; Colorectal cancer; Clinical application; Randomized controlled trials; Meta-analysis
13.  Influences of Different Land Use Spatial Control Schemes on Farmland Conversion and Urban Development 
PLoS ONE  2015;10(4):e0125008.
Land use planning is always officially implemented as an effective tool to control urban development and protect farmland. However, its impact on land use change remains untested in China. Using a case study of Hang-Jia-Hu region, the main objective of this paper was to investigate the influence of different land use spatial control schemes on farmland conversion and urban development. Comparisons of farmland conversion and urban development patterns between the urban planning area and the non-urban planning area were characterized by using remote sensing, geographical information systems, and landscape metrics. Results indicated that farmland conversion in the non-urban planning area was more intensive than that in the urban planning area, and that farmland patterns was more fragmented in the non-urban planning area. Built-up land patterns in the non-urban planning area showed a trend of aggregation, while those in the urban planning area had a dual trend of fragmentation and aggregation. Existing built-up areas had less influence on built-up land sprawl in the non-urban planning area than that in the urban planning area. Built-up land sprawl in the form of continuous development in the urban planning area led to farmland conversion; and in the non-urban planning area, built-up land sprawl in the form of leapfrogging development resulted in farmland areal declines and fragmentation. We argued that it is a basic requirement to integrate land use plans in urban and non-urban planning areas for land use planning and management.
doi:10.1371/journal.pone.0125008
PMCID: PMC4411046  PMID: 25915897
14.  Selective Uptake and Imaging of Aptamer- and Antibody-Conjugated Hollow Nanospheres Targeted to Epidermal Growth Factor Receptors Overexpressed in Head and Neck Cancer 
ACS Nano  2014;8(5):4530-4538.
The purpose of this study was to compare the binding affinity and selective targeting of aptamer- and antibody-coated hollow gold nanospheres (HAuNS) targeted to epidermal growth factor receptors (EGFR). EGFR-targeting aptamers were conjugated to HAuNS (apt-HAuNS) by attaching a thiol-terminated single-stranded DNA to the HAuNS and then adding the complementary RNA targeted to EGFR. Apt-HAuNS was characterized in terms of size, surface charge, absorption, and number of aptamers per particle. The in vivo pharmacokinetics, in vivo biodistribution, and micro-SPECT/CT imaging of 111In-labeled apt-HAuNS and anti-EGFR antibody (C225)-conjugated HAuNS were evaluated in nude mice bearing highly malignant human OSC-19 oral tumors. 111In-labeled PEG-HAuNS was used as a control (n = 5/group). Apt-HAuNS did not have an altered absorbance profile or size (λmax = 800 nm; diameter = 55 nm) compared to C225-HAuNS or PEG-HAuNS. The surface charge became more negative upon conjugation of the aptamer (−51.4 vs −19.0 for PEG-HAuNS and −25.0 for C225-HAuNS). The number of aptamers/particle was ∼250. In vitro cell binding and in vivo biodistribution showed selective binding of the apt-HAuNS to EGFR. μSPECT/CT imaging confirmed that there was more tumor uptake of apt-HAuNS than C225-HAuNS. Aptamer is a promising ligand for image-guided delivery of nanoparticles for treatment of tumor cells overexpressing EGFR.
doi:10.1021/nn406632u
PMCID: PMC4046795  PMID: 24754567
hollow gold nanospheres; SPECT/CT; biodistribution; epidermal growth factor receptor; head and neck cancer; aptamer
15.  1,25-Dihydroxyvitamin D3 Promotes High Glucose-Induced M1 Macrophage Switching to M2 via the VDR-PPARγ Signaling Pathway 
BioMed Research International  2015;2015:157834.
Macrophages, especially their activation state, are closely related to the progression of diabetic nephropathy. Classically activated macrophages (M1) are proinflammatory effectors, while alternatively activated macrophages (M2) exhibit anti-inflammatory properties. 1,25-Dihydroxyvitamin D3 has renoprotective roles that extend beyond the regulation of mineral metabolism, and PPARγ, a nuclear receptor, is essential for macrophage polarization. The present study investigates the effect of 1,25-dihydroxyvitamin D3 on macrophage activation state and its underlying mechanism in RAW264.7 cells. We find that, under high glucose conditions, RAW264.7 macrophages tend to switch to the M1 phenotype, expressing higher iNOS and proinflammatory cytokines, including TNFα and IL-12. While 1,25-dihydroxyvitamin D3 significantly inhibited M1 activation, it enhanced M2 macrophage activation; namely, it upregulated the expression of MR, Arg-1, and the anti-inflammatory cytokine IL-10 but downregulated the M1 markers. However, the above effects of 1,25-dihydroxyvitamin D3 were abolished when the expression of VDR and PPARγ was inhibited by VDR siRNA and a PPARγ antagonist. In addition, PPARγ was also decreased upon treatment with VDR siRNA. The above results demonstrate that active vitamin D promoted M1 phenotype switching to M2 via the VDR-PPARγ pathway.
doi:10.1155/2015/157834
PMCID: PMC4417570  PMID: 25961000
16.  Size- and morphology-dependent optical properties of ZnS:Al one-dimensional structures 
Typical morphology substrates can improve the efficiency of surface-enhanced Raman scattering; the need for SERS substrates of controlled morphology requires an extensive study. In this paper, one-dimensional ZnS:Al nanostructures with the width of approximately 300 nm and the length of tens um, and micro-scale structures with the width of several um and the length of tens um were synthesized via thermal evaporation on Au-coated silicon substrates and were used to study their size effects on Raman scattering and photoluminescent spectra. The photoluminescence spectra reveal the strongest green emission at a 5 at% Al source, which originates from the Al-dopant emission. The Raman spectra reveal that the size and morphology of the ZnS:Al nanowires greatly influences the Raman scattering, whereas the Al-dopant concentration has a lesser effect on the Raman scattering. The observed Raman scattering intensity of the saw-like ZnS:Al nanowires with the width of tens nm was eight times larger than that of the bulk sample. The enhanced Raman scattering can be regarded as multiple scattering and weak exciton—phonon coupling. The branched one-dimensional nanostructure can be used as an ideal substrate to enhance Raman scattering.
doi:10.1007/s11051-015-3000-y
PMCID: PMC4412203  PMID: 25960688
Al-doped ZnS; Morphology; Surface-enhanced Raman scattering; PL spectra
17.  Matrine regulates immune functions to inhibit the proliferation of leukemic cells 
Aims: To investigate the roles of matrine in regulating immune functions and its effect on the proliferation of leukemic cells. Methods: Human leukemia K562, OUN-1, HL-60, U937, K562/AO2 cell lines and primary leukemic cells were used to detect the NKG2D ligands (NKG2DL) expression such as MICA/B, ULBP-1, ULBP-2, ULBP-3, and NK cells receptor NKG2D, CD158a, CD158b were detected by flow cytometry. Cell cytotoxic activity of human NK cells and CIK cells against K562 leukemia cells was detected using CFSE/PI double staining. Pro-inflammatory cytokines and adhesion molecules in K562 or NK cells supernatant after matrine treatment were detected. Results: Matrine could upregulate the expression of NKG2DL on leukemic cell lines, and primary leukemic cells and enhance the NK and CIK cytotoxicity targeted to K562 cells. After matrine treatment, pro-inflammatory cytokines and adhesion molecular such as IL-6, IL-1, IL-2, IL-4, IL-5, GRO and TNF-α in K562 cells supernatant were significantly decreased (P < 0.05). Flow cytometry analysis showed that the NKG2D expression was up-regulated significantly as well as the CD158a and CD158b expression decreased after treatment with different concentration of matrine in a dose-dependent manner in K562 cells. A significant decrease of supernatant concentrations of IL-1α, IL-5, IL-6, IL-10, IFN-γ, GRO and TNF-α in NK cells was also observed after exposure to the matrine. Conclusion: Matrine regulates immune functions to inhibit the proliferation of leukemic cells.
PMCID: PMC4484016  PMID: 26131142
Matrine; luekemia cells; immune functions; NK cells
18.  Synergistic effects of high dietary calcium and exogenous parathyroid hormone in promoting osteoblastic bone formation in mice 
The British Journal of Nutrition  2015;113(6):909-922.
In the present study, we investigated whether high dietary Ca and exogenous parathyroid hormone 1–34 fragments (PTH 1–34) have synergistic effects on bone formation in adult mice, and explored the related mechanisms. Adult male mice were fed a normal diet, a high-Ca diet, a PTH-treated diet, or a high-Ca diet combined with subcutaneously injected PTH 1–34 (80 μg/kg per d) for 4 weeks. Bone mineral density, trabecular bone volume, osteoblast number, alkaline phosphatase (ALP)- and type I collagen-positive areas, and the expression levels of osteoblastic bone formation-related genes and proteins were increased significantly in mice fed the high-Ca diet, the PTH-treated diet, and, even more dramatically, the high-Ca diet combined with PTH. Osteoclast number and surface and the ratio of receptor activator for nuclear factor-κB ligand (RANKL):osteoprotegerin (OPG) were decreased in the high-Ca diet treatment group, increased in the PTH treatment group, but not in the combined treatment group. Furthermore, third-passage osteoblasts were treated with high Ca (5 mm), PTH 1–34 (10− 8 m) or high Ca combined with PTH 1–34. Osteoblast viability and ALP activity were increased in either the high Ca-treated or PTH-treated cultures and, even more dramatically, in the cultures treated with high Ca plus PTH, with consistent up-regulation of the expression levels of osteoblast proliferation and differentiation-related genes and proteins. These results indicate that dietary Ca and PTH play synergistic roles in promoting osteoblastic bone formation by stimulating osteoblast proliferation and differentiation.
doi:10.1017/S0007114514004309
PMCID: PMC4392706  PMID: 25744000
Parathyroid hormone; High-calcium diet; Osteoblasts; Osteoclasts; Synergistic effects; Bone formation
19.  Spatial Organization of NG2 Glial Cells and Astrocytes in Rat Hippocampal CA1 Region 
Hippocampus  2013;24(4):383-395.
Similar to astrocytes, NG2 glial cells are uniformly distributed in the central nervous system (CNS). However, little is known about the interspatial relationship, nor the functional interactions between these two star-shaped glial subtypes. Confocal morphometric analysis showed that NG2 immunostained cells are spatially organized as domains in rat hippocampal CA1 region and that each NG2 glial domain occupies a spatial volume of ~ 178, 364 μm3. The processes of NG2 glia and astrocytes overlap extensively; each NG2 glial domain interlaces with the processes deriving from 5.8 ± 0.4 neighboring astrocytes, while each astrocytic domain accommodates processes stemming from 4.5 ± 0.3 abutting NG2 glia. In CA1 stratum radiatum, the cell bodies of morphologically identified glial cells often appear to make direct somatic-somata contact, termed as doublets. We used dual patch recording and post-recording NG2/GFAP double staining to determine the glial identities of these doublets. We show that among 44 doublets, 50% were NG2 glia-astrocyte pairs, while another 38.6% and 11.4% were astrocyte-astrocyte and NG2 glia-NG2 glia pairs, respectively. In dual patch recording, neither electrical coupling nor intercellular biocytin transfer was detected in astrocyte-NG2 glia or NG2 glia-NG2 glia doublets. Altogether, although NG2 glia and astrocytes are not gap junction coupled, their cell bodies and processes are interwoven extensively. The anatomical and physiological relationships revealed in this study should facilitate future studies to understand the metabolic coupling and functional communication between NG2 glia and astrocytes.
doi:10.1002/hipo.22232
PMCID: PMC3971479  PMID: 24339242
NG2 glia; astrocyte; rat hippocampus; confocal microscopy; patch clamp
20.  Risk factors for preterm birth: a case-control study in rural area of western China 
Preterm birth is the leading cause of perinatal morbidity and mortality in China, the study is to learn risk factors for preterm birth in rural area of western China. A 1:1 case-control study in which cases included the pregnant women of preterm birth and controls included the matched pregnant women of normal deliver was conducted in 5 counties in western China. Data about the general situation, pregnancy history, reproductive health infection (RTI) symptoms, pregnancy complications, et al were obtained by using questionnaire. The results showed that the risk factors related to preterm birth were including: family income, mother’s age ≥ 35 years old, antennal visiting ≤ 4 times, low education level, preterm birth history, abnormal vaginal discharge, pregnancy complications. The logistic regression analysis showed that only 3 factors of preterm birth were left at the last step, which of antenatal visiting ≤ 4 times, PROM and placenta previa had significant difference. We show that family income, age, antennal visiting, low education level, preterm birth history, abnormal vaginal discharge, pregnancy complications are the risk factors of preterm birth.
PMCID: PMC4443213  PMID: 26064379
Preterm birth; western rural china; a case-control study; preterm birth history; pregnancy complications
21.  PTEN–Foxo1 signaling triggers HMGB1-mediated innate immune responses in acute lung injury 
Immunologic Research  2015;62(1):95-105.
PTEN is a multifunctional phosphatase that regulates immune responses through a PI3K/Akt signaling cascade. HMGB1 plays an important role in the initiation of innate immune responses to induce acute lung injury (ALI). This study was designed to investigate the role of PTEN/Foxo1 signaling in the regulation of in vivo and in vitro innate immune responses in ALI. Using a mouse model of ALI, wild-type (WT) and myeloid-specific PTEN knockout (PTENM-KO) mice were instilled with a recombinant HMGB1 (rHMGB1) or PBS. In some experiments, Foxo1 siRNA or non-specific siRNA was injected into mice 6 h prior to rHMGB1 instillation into lung. We found that rHMGB1 treatment in WT mice increased the expression of PTEN, Foxo1, TLR4, and NF-κB in alveolar macrophages from WT mice. However, macrophage-specific PTEN ablation resulted in reduced Foxo1 and TLR4 while increasing β-catenin (Ser552) and Akt (Ser473) phosphorylation in these cells. Knockdown of Foxo1 with siRNA administration in WT mice ameliorated lung injury and inhibited myeloperoxidase activity followed by rHMGB1 treatment, which was accompanied by decreased mRNA expression coding for TNF-α, IL-1β, MIP2, and IP-10. Moreover, Foxo1 knockdown inhibited the expression of TLR4-dependent IRF3 and IFN-β both in vitro and in vivo. These results demonstrate that PTEN/Foxo1 signaling is critical for triggering HMGB1-mediated innate TLR4 activation during ALI. By identifying the molecular signaling pathways within innate immune system, our studies provide the potential therapeutic targets for ALI.
doi:10.1007/s12026-015-8639-z
PMCID: PMC4424276  PMID: 25759027
Macrophages; β-Catenin; Akt; TLR4; Lung inflammation
22.  Prognostic factors of laryngeal solitary extramedullary plasmacytoma: a case report and review of literature 
A paucity of data exists concerning the presentation, natural course and outcome of extramedullary plasmcytoma (EMP). It is difficult to determine the optimal treatment strategy and prognostic factors for EMP. We present an additional case of laryngeal EMP and systemic review relevant reports in the English and Chinese literature. We found, to our knowledge, 147 cases in larynx in the English-language literature and Chinese-literature. The most common treatment modality was radiotherapy alone. The mean survival duration was ~184 months, and the 5- and 10- year survival rates were 76.1% and 67.4%, respectively. The univariate analysis suggested that progression to multiple myeloma and amyloid deposits may be poor prognostic factors. The multivariate analysis suggested that only progression to multiple myeloma may be a poor prognostic factor. Laryngeal EMP is uncommon. Progression to multiple myeloma may be a poor prognostic factor.
PMCID: PMC4440058  PMID: 26045749
Extramedullary plasmcytoma; larynx; progression to multiple myeloma; amyloid deposits; prognosis
23.  Inflammatory myofibroblastic tumors of the head and nec 
Inflammatory myofibroblastic tumors (IMT) rarely affect the head and neck region. IMTs of the head and neck regions account for 14-18% of extra-pulmonary IMTs. Most commonly, they are located in the region of the orbits and upper airways, and less often at other sites. In the present study, we reviewed the English-language literature regarding the etiology, clinical features, diagnosis, treatment, and prognosis of IMTs of the head and neck.
PMCID: PMC4402736  PMID: 25932089
Inflammatory myofibroblastic tumors; head and neck; treatment; prognosis
24.  Clinical performance of biodegradable versus permanent polymer drug-eluting stents: A meta-analysis of randomized clinical trials at long-term follow-up 
Several types of biodegradable polymer drug-eluting stents (BPDES) have been used for percutaneous transluminal angioplasty; however, the safety and efficiency of these BPDES have not been fully evaluated. A meta-analysis was, therefore, conducted to compare the clinical performance of BPDES with that of permanent polymer drug-eluting stents (PPDES) in unselected patients with coronary stenosis. PubMed, Web of Science, Medline and The Cochrane Library were searched for randomized clinical trials (RCTs) from January 2005 to January 2014. Trials that compared BPDES with PPDES in patients with coronary stenosis were considered. Twelve RCTs with a total of 15,938 patients with coronary stenosis were included in this meta-analysis. No significant difference was found between the two arms in the incidence of major adverse cardiac events (MACE) and definite or probable stent thrombosis (DpST) at the one-year follow-up (P>0.10). The use of BPDES, however, showed a tendency towards a lower risk of MACE (P=0.09) and a beneficial effect by reducing DpST episodes (P=0.04) at long-term follow-up, particularly when compared with the incidence of DpST at the one-year follow-up. BPDES also tended to be associated with a decreased late lumen loss in patients with coronary stenosis [instrumental variable =−0.04; 95% confidence interval =−0.08–0.00; P=0.05). In conclusion, the one-year outcomes following drug-eluting stent implantation showed BPDES were noninferior to PPDES in unselected patients with coronary stenosis. Long-term clinical outcomes, however, indicated that BPDES appeared to a present a lower risk of MACE and DpST.
doi:10.3892/etm.2015.2293
PMCID: PMC4353767  PMID: 25780467
percutaneous transluminal angioplasty; endovascular therapy; drug-eluting stent; biodegradable polymer; permanent polymer; outcome analysis; meta-analysis
25.  Evaluation of Non-Local Means Based Denoising Filters for Diffusion Kurtosis Imaging Using a New Phantom 
PLoS ONE  2015;10(2):e0116986.
Image denoising has a profound impact on the precision of estimated parameters in diffusion kurtosis imaging (DKI). This work first proposes an approach to constructing a DKI phantom that can be used to evaluate the performance of denoising algorithms in regard to their abilities of improving the reliability of DKI parameter estimation. The phantom was constructed from a real DKI dataset of a human brain, and the pipeline used to construct the phantom consists of diffusion-weighted (DW) image filtering, diffusion and kurtosis tensor regularization, and DW image reconstruction. The phantom preserves the image structure while minimizing image noise, and thus can be used as ground truth in the evaluation. Second, we used the phantom to evaluate three representative algorithms of non-local means (NLM). Results showed that one scheme of vector-based NLM, which uses DWI data with redundant information acquired at different b-values, produced the most reliable estimation of DKI parameters in terms of Mean Square Error (MSE), Bias and standard deviation (Std). The result of the comparison based on the phantom was consistent with those based on real datasets.
doi:10.1371/journal.pone.0116986
PMCID: PMC4313935  PMID: 25643162

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