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1.  Socio-economic factors related with the subjective well-being of the rural elderly people living independently in China 
Many Chinese elderly increasingly face the serious problem of the “empty nest” phenomenon. The elderly living independently, also called empty-nest elderly, refers to elderly people living alone whose children left home. However few studies concerned about the subjective well-being (SWB) of the elderly living independently.
This study employs The Memorial University of Newfoundland Scale of Happiness (MUNSH) to explore the SWB of the elderly living independently in rural areas of Wenzhou, a relatively developed region in China. 536 sampled are randomly selected.
The results indicate that participants obtained low scores in positive affect, positive experience, and the total SWB score, but high scores in negative affect and negative experience. Age, low education, poor health condition and little income were found to be negatively correlated with SWB. The SWB score of the elderly living with a spouse is higher than those who divorced or lost their spouse and the score of women is lower than that of men. In addition, the survey revealed that children’s support has a positive influence on the SWB of the rural elderly living independently.
The elderly living independently in rural Wenzhou, China have unfavorable SWB. Poor socio-economic statuses are negative impact factors. But the children’s support can help to improve. Special attention is needed to those with lower socio-economic status and less children’s support.
PMCID: PMC4299131  PMID: 25595196
MUNSH; SWB; The elderly living independently; Wenzhou; China
2.  Genetic Diversity of Bacterial Communities and Gene Transfer Agents in Northern South China Sea 
PLoS ONE  2014;9(11):e111892.
Pyrosequencing of the 16S ribosomal RNA gene (rDNA) amplicons was performed to investigate the unique distribution of bacterial communities in northern South China Sea (nSCS) and evaluate community structure and spatial differences of bacterial diversity. Cyanobacteria, Proteobacteria, Actinobacteria, and Bacteroidetes constitute the majority of bacteria. The taxonomic description of bacterial communities revealed that more Chroococcales, SAR11 clade, Acidimicrobiales, Rhodobacterales, and Flavobacteriales are present in the nSCS waters than other bacterial groups. Rhodobacterales were less abundant in tropical water (nSCS) than in temperate and cold waters. Furthermore, the diversity of Rhodobacterales based on the gene transfer agent (GTA) major capsid gene (g5) was investigated. Four g5 gene clone libraries were constructed from samples representing different regions and yielded diverse sequences. Fourteen g5 clusters could be identified among 197 nSCS clones. These clusters were also related to known g5 sequences derived from genome-sequenced Rhodobacterales. The composition of g5 sequences in surface water varied with the g5 sequences in the sampling sites; this result indicated that the Rhodobacterales population could be highly diverse in nSCS. Phylogenetic tree analysis result indicated distinguishable diversity patterns among tropical (nSCS), temperate, and cold waters, thereby supporting the niche adaptation of specific Rhodobacterales members in unique environments.
PMCID: PMC4218858  PMID: 25364820
3.  Standard triple therapy for Helicobacter pylori infection in China: A meta-analysis 
World Journal of Gastroenterology : WJG  2014;20(40):14973-14985.
AIM: To assess the efficacy and safety of standard triple therapy compared with other pre-existing and new therapies in China.
METHODS: Literature searches were conducted in the following databases: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the VIP database, the China National Knowledge Infrastructure database, and the Chinese Biomedical Database. A meta-analysis of all randomized controlled trials (RCTs) comparing standard triple therapy for the eradication of Helicobacter pylori with pre-existing and new therapies in China was performed using Comprehensive Meta-Analysis 2.0. There were 49 studies that met our criteria and the qualities of these studies were assessed using the Jadad scale. The Mantel-Haenszel method was used for pooling dichotomous data. We also conducted subgroup analyses according to age, duration of treatment and drug type. Sensitivity analyses and a cumulative meta-analysis were also performed with CMA 2.0. Publication bias was evaluated using Egger’s test, Begg’s test or a funnel plot.
RESULTS: A total of 49 RCTs including 8332 patients were assessed. This meta-analysis showed that standard triple therapy with proton pump inhibitors (PPIs), amoxicillin (AMO) and clarithromycin (CLA) was inferior to sequential therapy [relative risk (RR) = 0.863; 95% confidence interval (CI): 0.824-0.904], but was not superior to quadruple therapy (RR = 1.073; 95%CI: 0.849-1.357) or other triple therapies (RR = 1.01; 95%CI: 0.936-1.089). The meta-analysis also suggested that standard triple therapy is slightly more effective than dual therapy (RR = 1.14; 95%CI: 0.99-1.31). However, the differences were not statistically significant. We removed the only trial with a regimen lasting 14 d by sensitivity analysis and found that 7-d standard triple therapy was superior to 7-d dual therapy (RR = 1.222; 95%CI: 1.021-1.461). Moreover, a sub-analysis based on the duration of quadruple therapy indicated that the 7-d and 10-d standard triple therapies were inferior to sequential therapy (RR = 0.790; 95%CI: 0.718-0.868; RR = 0.917; 95%CI: 0.839-1.002, respectively). Additionally, there were no significant differences in cure rate or adverse events among standard triple therapy, quadruple therapy, and other triple therapies (RR = 0.940; 95%CI: 0.825-1.072; RR = 1.081; 95%CI: 0.848-1.378, respectively). Standard triple therapy had a higher occurrence of side effects than sequential therapy (RR = 1.283; 95%CI: 1.066-1.544).
CONCLUSION: The eradication rates with a standard triple therapy consisting of PPI, AMO, and CLA are suboptimal in China, and new treatment agents need to be developed.
PMCID: PMC4209562  PMID: 25356059
Helicobacter pylori; Eradication; Combination drug therapy; Amoxicillin; Clarithromycin; Adverse effects; Meta-analysis
4.  Toxicity assessment of repeated intravenous injections of arginine–glycine–aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice 
Nanotechnology-based near-infrared quantum dots (NIR QDs) have many excellent optical properties, such as high fluorescence intensity, good fluorescence stability, and strong tissue-penetrating ability. Integrin αvβ3 is highly and specifically expressed in tumor angiogenic vessel endothelial cells of almost all carcinomas. Recent studies have shown that NIR QDs linked to peptides containing the arginine–glycine–aspartic acid (RGD) sequence (NIR QDs-RGD) can specifically target integrin αvβ3 expressed in endothelial cells of tumor angiogenic vessels in vivo, and they offer great potential for early cancer diagnosis, in vivo tumor imaging, and tumor individualized therapy. However, the toxicity profile of NIR QDs-RGD has not been reported. This study was conducted to investigate the toxicity of NIR QDs-RGD when intravenously administered to mice singly and repeatedly at the dose required for successful tumor imaging in vivo.
Materials and methods
A NIR QDs-RGD probe was prepared by linking NIR QDs with the maximum emission wavelength of 800 nm (QD800) to the RGD peptide (QD800-RGD). QD800-RGD was intravenously injected to BALB/C mice once or twice (200 pmol equivalent of QD800 for each injection). Phosphate-buffered saline solution was used as control. Fourteen days postinjection, toxicity tests were performed, including complete blood count (white blood cell, red blood cell, hemoglobin, platelets, lymphocytes, and neutrophils) and serum biochemical analysis (total protein, albumin, albumin/globulin, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen). The coefficients of liver, spleen, kidney, and lung weight to body weight were measured, as well as their oxidation and antioxidation indicators, including superoxide dismutase, glutathione, and malondialdehyde. The organs were also examined histopathologically.
After one or two intravenous injections of QD800-RGD, as compared with control, no significant differences were observed in the complete blood count; biochemical indicators of blood serum, organ coefficient, and oxidation and antioxidation indicators; and no cell necrosis or inflammation were seen in the liver, spleen, kidney, or lung through histopathological examination.
Our data demonstrate that the single and repeated intravenous injection of QD800-RGD at a dose needed for successful tumor imaging in vivo is not toxic to mice. Our work lays a solid foundation for further biomedical applications of NIR QDs-RGD.
PMCID: PMC4207583  PMID: 25378922
nanotechnology; RGD peptides; integrin αvβ3; quantum dots; intravenous injection; toxicity
5.  In vivo magnetic resonance imaging tracking of transplanted superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells in rats with myocardial infarction 
Molecular Medicine Reports  2014;11(1):113-120.
Superparamagnetic iron oxide (SPIO) nanoparticles generate superparamagnetism, thereby resulting in an inhomogeneous local magnetic field, which shortens the T2 value on magnetic resonance imaging (MRI). The purpose of the present study was to use MRI to track bone marrow mesenchymal stem cells (BMSCs) labeled with SPIO in a rat model of myocardial infarction. The BMSCs were isolated from rats and labeled with SPIO. The anterior descending branch of the coronary artery was ligated under anesthesia. Two weeks later, the rats received, at random, 5×107 SPIO-labeled BMSCs, 5×107 unlabeled BMSCs or a vehicle (100 μl phosphate-buffered saline) via direct injection into the ischemic area (20 animals/group). MRI was used to track the SPIO-labeled BMSCs and the rats were then sacrificed to verify the presence of BMSCs using immunohistochemistry with an anti-CD90 antibody. The procedure labeled 99% of the BMSCs with SPIO, which exhibited low-intensity signals on T2 and T2* MRI imaging. At 24 h post-BMSC transplantation, low-intensity MRI signals were detected on the T2 and T2* sequences at the infarction margins. After 3 weeks following transplantation, low-intensity signals started to appear within the infarcted area; however, the signal intensity subsequently decreased and became indistinct. Immunohistochemistry revealed that the SPIO-labeled BMSCs migrated from the margin into the infarcted region. In conclusion, the BMSCs were readily labeled with SPIO and in vivo and MRI tracking demonstrated that the SPIO-labeled BMSCs established and grew in the infarcted myocardium.
PMCID: PMC4237077  PMID: 25323652
superparamagnetic iron oxide; bone marrow mesenchymal stem cells; myocardial infarction; magentic resonance imaging
6.  A Review on the Traditional Chinese Medicinal Herbs and Formulae with Hypolipidemic Effect 
BioMed Research International  2014;2014:925302.
Hyperlipidemia, characterized by the abnormal blood lipid profiles, is one of the dominant factors of many chronic diseases such as diabetes, obesity, and cardiovascular diseases (CVD). For the low cost, effectiveness, and fewer side effects, the popularity of using traditional Chinese medicine (TCM) to handle hyperlipidemia is increasing and its role in health care has been recognized by the public at large. Despite the importance of TCM herbs and formulations, there is no comprehensive review summarizing their scientific findings on handling hyperlipidemia. This review summarizes the recent experimental and clinical results of nine representative single Chinese herbs and seven classic TCM formulae that could improve lipid profiles so as to help understand and compare their underlying mechanisms. Most of single herbs and formulae demonstrated the improvement of hyperlipidemic conditions with multiple and diverse mechanisms of actions similar to conventional Western drugs in spite of their mild side effects. Due to increasing popularity of TCM, more extensive, well-designed preclinical and clinical trials on the potential synergistic and adverse side effects of herb-drug interactions as well as their mechanisms are warranted. Hyperlipidemic patients should be warned about the potential risks of herb-drug interactions, particularly those taking anticoagulants and antiplatelet drugs.
PMCID: PMC4109135  PMID: 25110708
7.  Thyroid hormone enhanced human hepatoma cell motility involves brain-specific serine protease 4 activation via ERK signaling 
Molecular Cancer  2014;13:162.
The thyroid hormone, 3, 3′, 5-triiodo-L-thyronine (T3), has been shown to modulate cellular processes via interactions with thyroid hormone receptors (TRs), but the secretory proteins that are regulated to exert these effects remain to be characterized. Brain-specific serine protease 4 (BSSP4), a member of the human serine protease family, participates in extracellular matrix remodeling. However, the physiological role and underlying mechanism of T3-mediated regulation of BSSP4 in hepatocellular carcinogenesis are yet to be established.
The thyroid hormone response element was identified by reporter and chromatin immunoprecipitation assays. The cell motility was analyzed via transwell and SCID mice. The BSSP4 expression in clinical specimens was examined by Western blot and quantitative reverse transcription polymerase chain reaction.
Upregulation of BSSP4 at mRNA and protein levels after T3 stimulation is a time- and dose-dependent manner in hepatoma cell lines. Additionally, the regulatory region of the BSSP4 promoter stimulated by T3 was identified at positions -609/-594. BSSP4 overexpression enhanced tumor cell migration and invasion, both in vitro and in vivo. Subsequently, BSSP4-induced migration occurs through the ERK 1/2-C/EBPβ-VEGF cascade, similar to that observed in HepG2-TRα1 and J7-TRα1 cells. BSSP4 was overexpressed in clinical hepatocellular carcinoma (HCC) patients, compared with normal subjects, and positively associated with TRα1 and VEGF to a significant extent. Importantly, a mild association between BSSP4 expression and distant metastasis was observed.
Our findings collectively support a potential role of T3 in cancer cell progression through regulation of the BSSP4 protease via the ERK 1/2-C/EBPβ-VEGF cascade. BSSP4 may thus be effectively utilized as a novel marker and anti-cancer therapeutic target in HCC.
PMCID: PMC4087245  PMID: 24980078
Thyroid hormone receptor; Secreted protein; BSSP4; SILAC; ERK 1/2-C/EBPβ-VEGF; Mmotility
8.  Circulating Tumor Cells (CTCs) Detected by RT-PCR and Its Prognostic Role in Gastric Cancer: A Meta-Analysis of Published Literature 
PLoS ONE  2014;9(6):e99259.
The prognostic significance of circulating tumor cells (CTCs) is controversial in gastric cancer (GC). We performed a meta-analysis of available studies to assess its prognostic value detected by RT-PCR for patients diagnosed with GC.
EMBase, PubMed, Ovid, Web of Science, Cochrane library and Google Scholar database search was conducted on all studies reporting the outcomes of interest. The studies were set up according to the inclusion/exclusion criteria. Meta-analysis was performed by using a random-effects model; hazard ratio (HR), risk ratio (RR) and their 95% confidence intervals (95% CIs) were set as effect measures. The information about trial design, results from the data was independently extracted. Heterogeneity of the studies was tested for each pooled analysis.
Nineteen studies published matched the selection criteria and were included in this meta-analysis. CTCs positivity was significantly associated with poor relapse free survival (RFS) (HR 2.42, 95% CI: [1.94–3.02]; P<0.001) and poor overall survival (OS) (HR 2.42, 95% CI: [1.94–3.02]; P<0.001). CTCs positivity were also significantly associated with regional lymph nodes (RLNs) metastasis (RR 1.42, 95% CI: [1.20–1.68]; p<0.0001), depth of infiltration (RR 1.51, 95% CI: [1.27–1.79]; p<0.0001), vascular invasion (RR  = 1.43, 95% CI: [1.18–1.74], p = 0.0002) and TNM stage(I,II versus III) (RR 0.63, 95% CI [0.48–0.84]; p = 0.001).
Preoperative CTCs positivity indicates poor prognosis in patients with gastric cancer, and associated with poor clinicopathological prognostic factors.
PMCID: PMC4047117  PMID: 24901848
9.  Aerobic Exercise Inhibits Sympathetic Nerve Sprouting and Restores β-Adrenergic Receptor Balance in Rats with Myocardial Infarction 
PLoS ONE  2014;9(5):e97810.
Cardiac sympathetic nerve sprouting and the dysregulation of β-adrenergic receptor (β-AR) play a critical role in the deterioration of cardiac function after myocardial infarction (MI). Growing evidence indicates that exercise provides protection against MI. The aims of this study were to investigate whether aerobic exercise following MI could inhibit sympathetic nerve sprouting and restore the balance of β3-AR/β1-AR.
Male Sprague-Dawley rats were divided into three groups: sham-operated control group (SC), MI group (MI), and MI with aerobic exercise group (ME). The rats in ME group were assigned to 8 weeks of exercise protocol (16 m/min, 50 min/d, 5 d/wk). The expression of nerve growth factor (NGF), the sympathetic nerve marker-tyrosine hydroxylase (TH), the nerve sprouting marker-growth associated protein 43 (GAP43), and β1- and β2-AR expression in the peri-infarct area of the left ventricle (LV) were measured by Western blot and immunohistochemistry, while β3-AR expression was determined by Western blot and immunofluorescence. Endothelial nitric oxide synthase (NOS2), phospho-NOS2 (p-NOS2), and neuronal nitric oxide synthase (NOS1) were measured by Western blot.
MI increased LV end-diastolic pressure (LVEDP), and decreased LV systolic pressure (LVSP). Compared with the MI group, aerobic exercise significantly decreased LVEDP and increased LVSP. The protein expression of TH, GAP43 and NGF was significantly increased after MI, which was normalized by exercise. Compared with the SC group, the ratios of β2-AR/β1-AR and β3-AR/β1-AR were elevated in the MI group, and the protein expression of β3-AR and NOS1 increased after MI. Compared with the MI group, the ratios of β2-AR/β1-AR and β3-AR/β1-AR were normalized in the ME group, while the protein expression of β3-AR and NOS1 significantly increased, and NOS2 was activated by exercise.
Aerobic exercise inhibits cardiac sympathetic nerve sprouting, restores β3-AR/β1-AR balance and increases β3-AR expression through the activation of NOS2 and NOS1 after myocardial infarction.
PMCID: PMC4026473  PMID: 24842290
10.  FOXM1 Modulates Cisplatin Sensitivity by Regulating EXO1 in Ovarian Cancer 
PLoS ONE  2014;9(5):e96989.
Cisplatin is commonly used in ovarian cancer chemotherapy, however, chemoresistance to cisplatin remains a great clinical challenge. Oncogenic transcriptional factor FOXM1 has been reported to be overexpressed in ovarian cancer. In this study, we aimed to investigate the potential role of FOXM1 in ovarian cancers with chemoresistance to cisplatin. Our results indicate that FOXM1 is upregulated in chemoresistant ovarian cancer samples, and defends ovarian cancer cells against cytotoxicity of cisplatin. FOXM1 facilitates DNA repair through regulating direct transcriptional target EXO1 to protect ovarian cancer cells from cisplatin-mediated apoptosis. Attenuating FOXM1 and EXO1 expression by small interfering RNA, augments the chemotherapy efficacy against ovarian cancer. Our findings indicate that targeting FOXM1 and its target gene EXO1 could improve cisplatin effect in ovarian cancer, confirming their role in modulating cisplatin sensitivity.
PMCID: PMC4019642  PMID: 24824601
11.  Preparation of uniform magnetic recoverable catalyst microspheres with hierarchically mesoporous structure by using porous polymer microsphere template 
Nanoscale Research Letters  2014;9(1):163.
Merging nanoparticles with different functions into a single microsphere can exhibit profound impact on various applications. However, retaining the unique properties of each component after integration has proven to be a significant challenge. Our previous research demonstrated a facile method to incorporate magnetic nanoparticles into porous silica microspheres. Here, we report the fabrication of porous silica microspheres embedded with magnetic and gold nanoparticles as magnetic recoverable catalysts. The as-prepared multifunctional composite microspheres exhibit excellent magnetic and catalytic properties and a well-defined structure such as uniform size, high surface area, and large pore volume. As a result, the very little composite microspheres show high performance in catalytic reduction of 4-nitrophenol, special convenient magnetic separability, long life, and good reusability. The unique nanostructure makes the microspheres a novel stable and highly efficient catalyst system for various catalytic industry processes.
PMCID: PMC4113952  PMID: 24708885
Magnetic nanoparticles; Gold nanoparticles; Mesoporous silica microspheres; Hierarchical pores; Catalysts; 61.46.-w; 75.75.-c; 81.07.-b
12.  Aerobic Interval Training Attenuates Mitochondrial Dysfunction in Rats Post-Myocardial Infarction: Roles of Mitochondrial Network Dynamics 
Aerobic interval training (AIT) can favorably affect cardiovascular diseases. However, the effects of AIT on post-myocardial infarction (MI)—associated mitochondrial dysfunctions remain unclear. In this study, we investigated the protective effects of AIT on myocardial mitochondria in post-MI rats by focusing on mitochondrial dynamics (fusion and fission). Mitochondrial respiratory functions (as measured by the respiratory control ratio (RCR) and the ratio of ADP to oxygen consumption (P/O)); complex activities; dynamic proteins (mitofusin (mfn) 1/2, type 1 optic atrophy (OPA1) and dynamin-related protein1 (DRP1)); nuclear peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α); and the oxidative signaling of extracellular signal-regulated kinase (ERK) 1/2, c-Jun NH2-terminal protein kinase (JNK) and P53 were observed. Post-MI rats exhibited mitochondrial dysfunction and adverse mitochondrial network dynamics (reduced fusion and increased fission), which was associated with activated ERK1/2-JNK-P53 signaling and decreased nuclear PGC-1α. After AIT, MI-associated mitochondrial dysfunction was improved (elevated RCR and P/O and enhanced complex I, III and IV activities); in addition, increased fusion (mfn2 and OPA1), decreased fission (DRP1), elevated nuclear PGC-1α and inactivation of the ERK1/2-JNK-P53 signaling were observed. These data demonstrate that AIT may restore the post-MI mitochondrial function by inhibiting dynamics pathological remodeling, which may be associated with inactivation of ERK1/2-JNK-P53 signaling and increase in nuclear PGC-1α expression.
PMCID: PMC4013565  PMID: 24675698
myocardial infarction; mitochondrial dysfunction; fusion; fission; mitochondrial dynamics; aerobic interval training
13.  MicroRNA-7 Regulates the mTOR Pathway and Proliferation in Adult Pancreatic β-Cells 
Diabetes  2013;62(3):887-895.
Elucidating the mechanism underlying the poor proliferative capacity of adult pancreatic β-cells is critical to regenerative therapeutic approaches for diabetes. Here, we show that the microRNA (miR)-7/7ab family member miR-7a is enriched in mouse adult pancreatic islets compared with miR-7b. Remarkably, miR-7a targets five components of the mTOR signaling pathway. Further, inhibition of miR-7a activates mTOR signaling and promotes adult β-cell replication in mouse primary islets, which can be reversed by the treatment with a well-known mTOR inhibitor, rapamycin. These data suggest that miR-7 acts as a brake on adult β-cell proliferation. Most importantly, this miR-7–mTOR proliferation axis is conserved in primary human β-cells, implicating miR-7 as a therapeutic target for diabetes.
PMCID: PMC3581216  PMID: 23223022
14.  Comparison of Drip, Pipe and Surge Spring Root Irrigation for Jujube (Ziziphus jujuba Mill.) Fruit Quality in the Loess Plateau of China 
PLoS ONE  2014;9(2):e88912.
Loess Plateau is a typical rain-fed farming region, facing the threat of drought. Irrigation method is among the most important factors affecting jujube quality. This study investigated the response of Ziziphus jujuba Mill. cv. Lizao quality to three different irrigation methods (drip-, pipe- and surge spring root irrigation) combining two water levels (20 m3/hm2 and 120 m3/hm2). The effects of the trials were evaluated by taking into account the physical-chemical characteristics of jujubes and the antioxidant activity. Concomitant to this, the concentration of some taste-related (viz. glucose, fructose, TSS and malic acid) and health-related compounds/parameters (viz. catechin and epicatechin) were generally much greater in jujube fruit treated with drip irrigation (120 m3/hm2). Different irrigation treatments had no significant effects on antioxidant capacity, total phenolics and proanthocyanidins (except for pipe irrigation 20 m3/hm2). The best compromise between quality and irrigation of jujube fruit was achieved with drip irrigation (120 m3/hm2).
PMCID: PMC3925179  PMID: 24551188
15.  PCR-Based Diagnosis of Prosthetic Joint Infection 
Journal of Clinical Microbiology  2013;51(8):2742-2746.
We performed a meta-analysis to evaluate use of PCR assays for diagnosis of prosthetic joint infection (PJI). The pooled sensitivity and specificity were 0.86 (95% confidence interval [CI], 0.77 to 0.92) and 0.91 (CI, 0.81 to 0.96), respectively. Subgroup analyses showed that use of tissue samples may improve sensitivity, and quantitative PCR and sonication of prostheses fluid may improve specificity. The results showed that PCR is reliable and accurate for detection of PJI.
PMCID: PMC3719604  PMID: 23740731
16.  Optical imaging of head and neck squamous cell carcinoma in vivo using arginine-glycine-aspartic acid peptide conjugated near-infrared quantum dots 
OncoTargets and therapy  2013;6:1779-1787.
Molecular imaging plays a key role in personalized medicine and tumor diagnosis. Quantum dots with near-infrared emission spectra demonstrate excellent tissue penetration and photostability, and have recently emerged as important tools for in vivo tumor imaging. Integrin αvβ3 has been shown to be highly and specifically expressed in endothelial cells of tumor angiogenic vessels in almost all types of tumors, and specifically binds to the peptide containing arginine-glycine-aspartic acid (RGD). In this study, we conjugated RGD with quantum dots with emission wavelength of 800 nm (QD800) to generate QD800-RGD, and used it via intravenous injection as a probe to image tumors in nude mice bearing head and neck squamous cell carcinoma (HNSCC). Twelve hours after the injection, the mice were still alive and were sacrificed to isolate tumors and ten major organs for ex vivo analysis to localize the probe in these tissues. The results showed that QD800-RGD was specifically targeted to integrin αvβ3 in vitro and in vivo, producing clear tumor fluorescence images after the intravenous injection. The tumor-to-background ratio and size of tumor image were highest within 6 hours of the injection and declined significantly at 9 hours after the injection, but there was still a clearly visible tumor image at 12 hours. The greatest amount of QD800-RGD was found in liver and spleen, followed by tumor and lung, and a weak fluorescence signal was seen in tibia. No detectable signal of QD800-RGD was found in brain, heart, kidney, testis, stomach, or intestine. Our study demonstrated that using integrin αvβ3 as target, it is possible to use intravenously injected QD800-RGD to generate high quality images of HNSCC, and the technique offers great potential in the diagnosis and personalized therapy for HNSCC.
PMCID: PMC3855103  PMID: 24324343
nanotechnology; near-infrared fluorescence; tumor angiogenic vessel; head and neck cancer; in vivo imaging
17.  Akt-p53-miR-365-cyclin D1/cdc25A axis contributes to gastric tumorigenesis induced by PTEN deficiency 
Nature Communications  2013;4:2544.
Although PTEN/Akt signaling is frequently deregulated in human gastric cancers, the in vivo causal link between its dysregulation and gastric tumorigenesis has not been established. Here we show that inactivation of PTEN in mouse gastric epithelium initiates spontaneous carcinogenesis with complete penetrance by 2 months of age. Mechanistically, activation of Akt suppresses the abundance of p53, leading to decreased transcription of miR-365, thus causing upregulation of cyclin D1 and cdc25A, which promotes gastric cell proliferation. Importantly, genetic ablation of Akt1 restores miR-365 expression and effectively rescues gastric tumorigenesis in PTEN-mutant mice. Moreover, orthotopic restoration of miR-365 represses PTEN-deficient-induced hyperplasia. In human gastric cancer tissues, miR-365 reduction correlates with poorly differentiated histology, deep invasion and advanced stage, as well as the deregulation of PTEN, phosphorylated Akt, p53, cyclin D1 and cdc25A. These data demonstrate that the PTEN-Akt-p53-miR-365-cyclin D1/cdc25A axis serves as a new mechanism underlying gastric tumorigenesis, providing potential new therapeutic targets.
The PTEN/Akt signalling pathway has been implicated in the pathogenesis of gastric cancer. Here, Guo et al. show that activation of Akt signalling results in the dysregulation of miR-365, which promotes tumorigenesis and that miR-365 reduction correlates with advance-stage tumours in gastric cancer patients.
PMCID: PMC3826643  PMID: 24149576
18.  Salvage irrigation-suction in gracilis muscle repair of complex rectovaginal and rectourethral fistulas 
AIM: To evaluate the efficacy of gracilis muscle transposition and postoperative salvage irrigation-suction in the treatment of complex rectovaginal fistulas (RVFs) and rectourethral fistulas (RUFs).
METHODS: Between May 2009 and March 2012, 11 female patients with complex RVFs and 8 male patients with RUFs were prospectively enrolled. Gracilis muscle transposition was undertaken in all patients and postoperative wound irrigation-suction was performed in patients with early leakage. Efficacy was assessed in terms of the success rate and surgical complications. SF-36 quality of life (QOL) scores and Wexner fecal incontinence scores were compared before and after surgery.
RESULTS: The fistulas healed in 14 patients after gracilis muscle transposition; the initial healing rate was 73.7%. Postoperative leakage occurred and continuous irrigation-suction of wounds was undertaken in 5 patients: 4 healed and 1 failed, and postoperative fecal diversions were performed for the patient whose treatment failed. At a median follow-up of 17 mo, the overall healing rate was 94.7%. Postoperative complications occurred in 4 cases. Significant improvement was observed in the quality outcomes framework scores (P < 0.001) and Wexner fecal incontinence scores (P = 0.002) after the successful healing of complex RVFs or RUFs. There was no significant difference in SF-36 QOL scores between the initial healing group and irrigation-suction-assisted healing group.
CONCLUSION: Gracilis muscle transposition and postoperative salvage wound irrigation-suction gained a high success rate in the treatment of complex RVFs and RUFs. QOL and fecal incontinence were significantly improved after the successful healing of RVFs and RUFs.
PMCID: PMC3801378  PMID: 24151391
Rectovaginal fistula; Rectourethral fistula; Gracilis muscle; Quality of life; Therapeutic irrigation
19.  Identification of microRNA-Like RNAs in the Filamentous Fungus Trichoderma reesei by Solexa Sequencing 
PLoS ONE  2013;8(10):e76288.
microRNAs (miRNAs) are non-coding small RNAs (sRNAs) capable of negatively regulating gene expression. Recently, microRNA-like small RNAs (milRNAs) were discovered in several filamentous fungi but not yet in Trichoderma reesei, an industrial filamentous fungus that can secrete abundant hydrolases. To explore the presence of milRNA in T. reesei and evaluate their expression under induction of cellulose, two T. reesei sRNA libraries of cellulose induction (IN) and non-induction (CON) were generated and sequenced using Solexa sequencing technology. A total of 726 and 631 sRNAs were obtained from the IN and CON samples, respectively. Global expression analysis showed an extensively differential expression of sRNAs in T. reesei under the two conditions. Thirteen predicted milRNAs were identified in T. reesei based on the short hairpin structure analysis. The milRNA profiles obtained in deep sequencing were further validated by RT-qPCR assay. Computational analysis predicted a number of potential targets relating to many processes including regulation of enzyme expression. The presence and differential expression of T. reesei milRNAs imply that milRNA might play a role in T. reesei growth and cellulase induction. This work lays foundation for further functional study of fungal milRNAs and their industrial application.
PMCID: PMC3788729  PMID: 24098464
20.  Protective effect of hydrogen-rich saline on ischemia/reperfusion injury in rat skin flap*  
Objective: Skin damage induced by ischemia/reperfusion (I/R) is a multifactorial process that often occurs in plastic surgery. The mechanisms of I/R injury include hypoxia, inflammation, and oxidative damage. Hydrogen gas has been reported to alleviate cerebral I/R injury by acting as a free radical scavenger. Here, we assessed the protective effect of hydrogen-rich saline (HRS) on skin flap I/R injury. Methods: Abdominal skin flaps of rats were elevated and ischemia was induced for 3 h; subsequently, HRS or physiological saline was administered intraperitoneally 10 min before reperfusion. On postoperative Day 5, flap survival, blood perfusion, the accumulation of reactive oxygen species (ROS), and levels of cytokines were evaluated. Histological examinations were performed to assess inflammatory cell infiltration. Results: Skin flap survival and blood flow perfusion were improved by HRS relative to the controls. The production of malondialdehyde (MDA), an indicator of lipid peroxidation, was markedly reduced. A multiplex cytokine assay revealed that HRS reduced the elevation in the levels of inflammatory cytokines, chemokines and growth factors, with the exception of RANTES (regulated on activation, normal T-cell expressed and secreted) growth factor. HRS treatment also reduced inflammatory cell infiltration induced by I/R injury. Conclusions: Our findings suggest that HRS mitigates I/R injury by decreasing inflammation and, therefore, has the potential for application as a therapy for improving skin flap survival.
PMCID: PMC3650452  PMID: 23645175
Hydrogen-rich saline; Ischemia/reperfusion; Skin flaps; Oxidative damage; Inflammation
21.  Hypoxia inducible factor 1α-mediated LOX expression correlates with migration and invasion in epithelial ovarian cancer 
International Journal of Oncology  2013;42(5):1578-1588.
This study investigated the role of LOX in promoting invasion and metastasis of epithelial ovarian cancer in a hypoxic environment and its specific signal transduction pathway. Immunohistochemical detection of HIF-1α and LOX protein expression was performed on formalin-fixed paraffin sections of normal ovary, benign ovarian tumors, borderline and malignant epithelial ovarian tumor paraffin sample, using Mann-Whitney U test for independent comparisons and Wilcoxon signed-ranks test for paired comparisons. HIF-1α and LOX were knocked down in epithelial ovarian cancer cells (EOC), and HIF-1α/LOX regulation mechanism and LOX catalytic activity under hypoxia/reoxygenation microenvironment were explored. Cell migration and invasion ability in LOX inhibited HO8910 cells were investigated under hypoxia/reoxygenation conditions, using matrigel cell invasion and migration assays. We found that HIF-1α and LOX are highly expressed in epithelial ovarian cancer tissues, and the expression of both proteins is significantly correlated with the tumor grade, tumor diameter and lymph node metastasis. HIF-1α expression is positively correlated with the expression of LOX. Specifically, the expression of LOX and HIF-1α markedly increases under hypoxic conditions and decreases after reoxygenation. siRNA knockdown of LOX or β-aminoproprionitrile (βAPN), an inhibitor of LOX activity, that attenuates LOX activity, downregulates HIF-1α protein expression and inhibits HO8910 migratory and invasive abilities. LOX catalytic activity is significantly reduced under hypoxic conditions. Moreover, EOC cells display a marked increase in LOX-dependent FAK/AKT activation and cell migration following hypoxia/reoxygenation. Collectively, our study demonstrates that the hypoxia-HIF-1α, LOX-FAK/AKT pathway regulates the migration and invasion of epithelial ovarian cancer cells under hypoxia/reoxygenation conditions, thus, promoting metastasis of ovarian cancer.
PMCID: PMC3661201  PMID: 23545606
lysyl oxidase; ovarian cancer; metastasis; hypoxia; hypoxia-inducible factor; reoxygenation
22.  Effects of Decabromodiphenyl Ether (BDE-209) on Inter-Specific Competition between Two Species of Marine Bloom-Forming Microalgae 
PLoS ONE  2013;8(3):e56084.
Decabromodiphenyl ether (BDE-209), a new kind of persistent organic pollutants, was selected to investigate its influence on population growth and inter-specific competition between two species of marine bloom-forming microalgae, Heterosigma akashiwo and Karenia mikimotoi. (1)BDE-209 showed acute toxic effects on both microalgae and H. akashiwo was more sensitive from view of 96 h-EC50 and the ultrastructure variation. (2)The microalgal population growth patterns in mono-culture were density-dependent and the growth of both species in the normal co-culture was significantly depressed by competition (P<0.05) with different initial biomass ratios. BDE-209 exposure significantly changed the growth. (3) Lotka-Volterra competition model was used to simulate the interaction between the microalgae. BDE-209 exposure broke the competitive balance to make competition gradually shift in favor of H. akashiwo. Results suggested BDE-209 did have toxic effects on either microalgal growth or the inter-specific competition, which was quite different from previous reports. Further exploration of the mechanism is needed.
PMCID: PMC3605422  PMID: 23555557
23.  CD106 Identifies a Subpopulation of Mesenchymal Stem Cells with Unique Immunomodulatory Properties 
PLoS ONE  2013;8(3):e59354.
Mesenchymal stem cells (MSCs) reside in almost all of the body tissues, where they undergo self-renewal and multi-lineage differentiation. MSCs derived from different tissues share many similarities but also show some differences in term of biological properties. We aim to search for significant differences among various sources of MSCs and to explore their implications in physiopathology and clinical translation. We compared the phenotype and biological properties among different MSCs isolated from human term placental chorionic villi (CV), umbilical cord (UC), adult bone marrow (BM) and adipose (AD). We found that CD106 (VCAM-1) was expressed highest on the CV-MSCs, moderately on BM-MSCs, lightly on UC-MSCs and absent on AD-MSCs. CV-MSCs also showed unique immune-associated gene expression and immunomodulation. We thus separated CD106+cells and CD106−cells from CV-MSCs and compared their biological activities. Both two subpopulations were capable of osteogenic and adipogenic differentiation while CD106+CV-MSCs were more effective to modulate T helper subsets but possessed decreased colony formation capacity. In addition, CD106+CV-MSCs expressed more cytokines than CD106−CV-MSCs. These data demonstrate that CD106 identifies a subpopulation of CV-MSCs with unique immunoregulatory activity and reveal a previously unrecognized mechanism underlying immunomodulation of MSCs.
PMCID: PMC3595282  PMID: 23555021
24.  Nickel-titanium shape-memory sawtooth-arm embracing fixator for periprosthetic femoral fractures 
International Orthopaedics  2011;36(3):619-626.
We reviewed data to determine outcomes for 21 consecutive Vancouver type B1 or type C periprosthetic fractures that we treated between 2001 and 2008 using a nickel–titanium shape-memory sawtooth-arm embracing fixator.
The study participants were 12 men and 9 women (mean age, 70.8 years; range, 42–85 years). The average duration of follow-up monitoring was 39.7 months (range, 1–78 months). In five cases, cables and screws were used for further stabilisation. No bone grafting was performed for any of the patients.
Results were satisfactory, except for one patient who died one month after surgery from a cause unrelated to arthroplasty. Bone union was achieved in the remaining 20 cases within an average of 5.25 months. No implant failures or malunions occurred in any of the patients. The average Harris hip score at the final follow-up examination was 79.3 points.
Our results show that the embracing fixator is a valid alternative treatment for Vancouver type B1 or type C periprosthetic femoral fractures.
PMCID: PMC3291776  PMID: 21805070
25.  A Dibutyl Phthalate Sensor Based on a Nanofiber Polyaniline Coated Quartz Crystal Monitor 
Sensors (Basel, Switzerland)  2013;13(3):3765-3775.
Dibutyl phthalate (DBP) is a commonly used plasticizer and additive to adhesives, printing inks and nail polishes. Because it has been found to be a powerful reproductive and developmental toxicant, a sensor to monitor DBP in some working spaces and the environment is required. In this work polyaniline nanofibers were deposited on the electrode of a quartz crystal oscillator to form a Quartz Crystal Microbalance gas sensor. The coated quartz crystal and a non-coated quartz crystal were mounted in a sealed chamber, and their frequency difference was monitored. When DBP vapor was injected into the chamber, gas adsorption decreased the frequency of the coated quartz crystal oscillator and thereby caused an increase in the frequency difference between the two crystals. The change of the frequency difference was recorded as the sensor response. The sensor was extremely sensitive to DBP and could be easily recovered by N2 purging. A low measurement limit of 20 ppb was achieved. The morphologies of the polyaniline films prepared by different approaches have been studied by SEM and BET. How the nanofiber-structure can improve the sensitivity and stability is discussed, while its selectivity and long-term stability were investigated.
PMCID: PMC3658774  PMID: 23507822
QCM; gas sensor; dibutyl phthalate; nanofiber; polyaniline; PACS 07.07.Df (Gas sensor); 77.65.Fs (Quartz resonator); 82.35.Np (Polymers nanoparticles in); 81.07.-b (Nanoscale materials fabrication and characterization)

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