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1.  Activation of the NF-κB pathway as a mechanism of alcohol enhanced progression and metastasis of human hepatocellular carcinoma 
Molecular Cancer  2015;14(1):10.
Background
Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related death in human. Alcohol is a known risk factor for HCC. However it is still unclear whether and how alcohol enhances the progression and metastasis of existing HCC.
Methods and results
We first retrospectively investigated 52 HCC patients (24 alcohol-drinkers and 28 non-drinkers), and found a positive correlation between alcohol consumption and advanced Tumor-Node-Metastasis (TNM) stages, higher vessel invasion and poorer prognosis. In vitro and in vivo experiments further indicated that alcohol promoted the progression and migration/invasion of HCC. Specifically, in a 3-D tumor/endothelial co-culture system, we found that alcohol enhanced the migration/invasion of HepG2 cells and increased tumor angiogenesis. Consistently, higher expression of VEGF, MCP-1 and NF-κB was observed in HCC tissues of alcohol-drinkers. Alcohol induced the accumulation of intracellular reactive oxygen species (ROS) and the activation of NF-κB signaling in HepG2 cells. Conversely, blockage of alcohol-mediated ROS accumulation and NF-κB signaling inhibited alcohol-induced expression of VEGF and MCP-1, the tumor growth, angiogenesis and metastasis.
Conclusion
This study suggested that chronic moderate alcohol consumption may promote the progression and metastasis of HCC; the oncogenic effect may be at least partially mediated by the ROS accumulation and NF-ĸB-dependent VEGF and MCP-1 up-regulation.
doi:10.1186/s12943-014-0274-0
PMCID: PMC4320626  PMID: 25622857
Alcohol; Angiogenesis; Human hepatocellular cancer; Metastasis; Reactive oxygen species
2.  Gastrotracheal fistula: Treatment with a covered elf-expanding Y-shaped metallic stent 
A 67-year-old man had a sev-ere cough and pulmonary infection for 1 wk before seeking evaluation at our hospital. He had undergone esophagectomy with gastric pull-up and radiotherapy for esophageal cancer 3 years previously. After admission to our hospital, gastroscopy and bronchoscopy revealed a fistulous communication between the posterior tracheal wall near the carina and the upper residual stomach. We measured the diameter of the trachea and bronchus and determined the site and size of the fistula using multislice computed tomography and gastroscopy. A covered self-expanding Y-shaped metallic stent was implanted into the trachea and bronchus. Subsequently, the fistula was closed completely. The patient tolerated the stent well and had good palliation of his symptoms.
doi:10.3748/wjg.v21.i3.1032
PMCID: PMC4299322  PMID: 25624743
Gastrotracheal fistula; Y-shaped metallic stent; Esophageal cancer; Gastroesophageal surgery
3.  Assessment of Corneal Epithelial Thickness in Dry Eye Patients 
Purpose
To investigate the features of corneal epithelial thickness topography with Fourier-domain optical coherence tomography (OCT) in dry eye patients.
Methods
In this cross-sectional study, 100 symptomatic dry eye patients and 35 normal subjects were enrolled. All participants answered the ocular surface disease index questionnaire and were subjected to OCT, corneal fluorescein staining, tear breakup time, Schirmer 1 test without anesthetic (S1t), and meibomian morphology. Several epithelium statistics for each eye, including central, superior, inferior, minimum, maximum, minimum – maximum, and map standard deviation, were averaged. Correlations of epithelial thickness with the symptoms of dry eye were calculated.
Results
The mean (±SD) central, superior, and inferior corneal epithelial thickness was 53.57 (±3.31) μm, 52.00 (±3.39) μm, and 53.03 (±3.67) μm in normal eyes and 52.71 (±2.83) μm, 50.58 (±3.44) μm, and 52.53 (±3.36) μm in dry eyes, respectively. The superior corneal epithelium was thinner in dry eye patients compared with normal subjects (p=0.037),whereas central and inferior epithelium were not statistically different. In the dry eye group, patients with higher severity grades had thinner superior (p = 0.017) and minimum (p < 0.001) epithelial thickness, more wide range (p = 0.032), and greater deviation (p = 0.003). The average central epithelial thickness had no correlation with tear breakup time, S1t, or the severity of meibomian glands, whereas average superior epithelial thickness positively correlated with S1t (r = 0.238, p = 0.017).
Conclusions
Fourier-domain OCT demonstrated that the thickness map of the dry eye corneal epithelium was thinner than normal eyes in the superior region. In more severe dry eye disease patients, the superior and minimum epithelium was much thinner, with a greater range of map standard deviation.
doi:10.1097/OPX.0000000000000417
PMCID: PMC4302058  PMID: 25279779
optical coherence tomography; dry eye syndromes; epithelium; corneal; corneal pachymetry; tear film
4.  PLGA-PLL-PEG-Tf-based targeted nanoparticles drug delivery system enhance antitumor efficacy via intrinsic apoptosis pathway 
Chemotherapy offers a systemic cancer treatment; however, it is limited in clinical administration due to its serious side effects. In cancer medicine, the use of nanoparticles (NPs) drug delivery system (DDS) can sustainedly release anticancer drug at the specific site and reduce the incidence of toxicity in normal tissues. In the present study, we aimed to evaluate the benefit of a novel chemotherapeutic DDS and its underlying mechanisms. Daunorubicin (DNR) was loaded into poly (lactic-co-glycolic acid) (PLGA)-poly-l-lysine (PLL)-polyethylene glycol (PEG)-transferrin (Tf) NPs to construct DNR-PLGA-PLL-PEG-Tf-NPs (DNR-loaded NPs) as a DDS. After incubating with PLGA-PLL-PEG-Tf-NPs, DNR, and DNR-loaded NPs, the leukemia K562 cells were collected and the intracellular concentration of DNR was detected by flow cytometry, respectively. Furthermore, the effect of drugs on the growth of tumors in K562 xenografts was observed and the relevant toxicity of therapeutic drugs on organs was investigated in vivo. Meanwhile, cell apoptosis in the excised xenografts was measured by transferase-mediated dUTP nick-end labeling assay, and the expression of apoptosis-related proteins, including Bcl-2, Bax, Caspase-9, Caspase-3, and cleaved-PARP, was determined by Western blotting analysis. Results showed that DNR-loaded NPs increased intracellular concentration of DNR in K562 cells in vitro and induced a remarkable improvement in anticancer activity in the xenografts in vivo. The expression of Bcl-2 protein was downregulated and that of Bax, Caspase-9, Caspase-3, and cleaved-PARP proteins were obviously upregulated in the DNR-loaded NPs group than that in other ones. Interestingly, pathological assessment showed no apparent damage to the main organs. In summary, the results obtained from this study showed that the novel NPs DDS could improve the efficacy of DNR in the treatment of leukemia and induce apoptosis via intrinsic pathway. Thus, it can be inferred that the new drug delivery may be a useful clinical tool.
doi:10.2147/IJN.S75090
PMCID: PMC4298335  PMID: 25609961
PLGA-PLL-PEG; daunorubicin; transferrin; K562 cells; apoptosis
5.  Efficacy of docetaxel combined with oxaliplatin and fluorouracil against stage III/IV gastric cancer 
World Journal of Gastroenterology : WJG  2014;20(48):18413-18419.
AIM: To investigate the clinical efficacy and toxic effects of neoadjuvant chemotherapy using docetaxel combined with oxaliplatin and fluorouracil for treating stage III/IV gastric cancer.
METHODS: A total of 53 stage III/IV gastric cancer patients were enrolled into the study and treated with neoadjuvant chemotherapy. Two of the cases were excluded. The program was as follows: 75 mg/m2 docetaxel and 85 mg/m2 oxaliplatin on day 1 and 1500 mg/m2 fluorouracil on days 1 to 3 for three weeks.
RESULTS: The tumour changes, postoperative remission rate, changes in the symptoms and adverse reactions were observed. The overall clinical efficacy (complete remission + partial remission) of the neoadjuvant chemotherapy was 62.7%. R0 radical resection was performed on 60.8% of the patients, with a remission rate (pathological complete response + pathological subtotal response + pathological partial response) of 74.2%. The Karnofksy score improved in 42 cases. The toxicity reactions mostly included myelosuppression, followed by gastrointestinal mucosal lesions, nausea, vomiting and diarrhoea.
CONCLUSION: Neoadjuvant chemotherapy consisting of docetaxel combined with oxaliplatin and fluorouracil is effective for stage III/IV gastric cancer. However, the treatment is associated with a high incidence of bone marrow suppression, which should be managed clinically.
doi:10.3748/wjg.v20.i48.18413
PMCID: PMC4277980  PMID: 25561810
Gastric cancer; Neoadjuvant chemotherapy; Docetaxel; Oxaliplatin
6.  Association Analysis between g.18873C>T and g.27522G>A Genetic Polymorphisms of OPG and Bone Mineral Density in Chinese Postmenopausal Women 
BioMed Research International  2014;2014:320828.
Several studies report that the OPG is an important candidate gene in the pathogenesis of osteoporosis. This study aimed to detect the potential association of OPG gene polymorphisms with osteoporosis in postmenopausal women. We recruited 928 subjects containing 463 with primary postmenopausal osteoporosis and 465 healthy volunteers as controls. The BMD of neck hip, lumbar spine (L2–4), and total hip were assessed by dual-energy X-ray absorptiometry (DEXA). Through the created restriction site-polymerase chain reaction (CRS-PCR), PCR-restriction fragment length polymorphism (PCR-RFLP), and DNA sequencing methods, the g.18873C>T and g.27522G>A have been investigated. As for g.18873C>T, our data indicated that subjects with CC genotype have significantly higher BMD value than those of CT and TT genotypes (all P values < 0.05). As for g.27522G>A, the BMD values of subjects with GG genotype were significantly higher than those of GA and AA genotypes (all P values < 0.05). Our findings suggest that the OPG g.18873C>T and g.27522G>A genetic polymorphisms are associated with the decreased risk for osteoporosis in Chinese postmenopausal women.
doi:10.1155/2014/320828
PMCID: PMC4279182  PMID: 25580430
7.  Left ventricular noncompaction cardiomyopathy: a case report and literature review 
Left ventricular noncompaction cardiomyopathy (LVNC) is a relatively rare congenital disorder prominently characterized by prominent trabeculations and intertrabecular recesses that communicate with the ventricular cavity rather than the coronary circulation. LVNC can occur in isolation or coexist with other cardiac and/or systemic anomalies, in especial neuromuscular disorders. The clinical presentation varies ranging from asymptomatic patients to patients who develop ventricular arrhythmias, thromboembolism, heart failure and sudden cardiac death. Although LVNC is commonly diagnosed by echocardiography, there are also other useful diagnostic techniques, including contrast ventriculography, CT and MRI. Now, it is being diagnosed more frequently in patients of all ages because of increased awareness and improvements in imaging methods. We described the case of a woman who presented with heart failure for the first time at 62 years of age. The diagnosis was LVNC. Transthoracic echocardiography showed a trabeculated, sponge-like appearance of the ventricular apical and inferolateral segments. After medical management, the patient was asymptomatic at the 1-month follow-up examination. Now we discussed the diagnosis of this case and reviewed the medical literature that pertained to LVNC.
PMCID: PMC4307462  PMID: 25664015
Trabeculations; left ventricular noncompaction cardiomyopathy; congestive heart failure
8.  Brain-derived neurotrophic factor gene-modified bone marrow mesenchymal stem cells 
The present study aimed to investigate the effects of human brain-derived neurotrophic factor (hBDNF) on the differentiation of bone marrow mesenchymal stem cells (MSCs) into neuron-like cells. Lentiviral vectors carrying the hBDNF gene were used to modify the bone marrow stromal cells (BMSCs) of Sprague-Dawley (SD) rats. The rat BMSCs were isolated, cultured and identified. A lentivirus bearing hBDNF and enhanced green fluorescent protein (eGFP) genes was subcultured and used to infect the SD rat BMSCs. The expression of eGFP was observed under a fluorescence microscope to determine the infection rate and growth of the transfected cells. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) was used to detect the proliferation rate of cells following transfection. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to detect the expression levels of hBDNF. Differentiation of neuron-like cells was induced in vitro and the differentiation rate of the induced neural-like cells was compared with that in control groups and analyzed statistically. In the cultured cells, flow cytometry demonstrated positive expression of cluster of differentiation (CD)90 and CD44, and negative expression of CD34 and CD45. The proliferation rate of the rat BMSCs increased following gene transfection. The expression of hBDNF-eGFP was detected in the BMSCs of the experimental group. The differentiation rate of hBDNF-modified cells into neuron-like cells in the experimental group was higher compared with that in empty plasmid and untransfected negative control groups. The difference was statistically significant (P<0.05). Thus, BDNF gene transfection is able to promote the differentiation of BMSCs into neuron-like cells. BDNF may play an important role in the differentiation of MSCs into neuron-like cells.
doi:10.3892/etm.2014.2113
PMCID: PMC4280929  PMID: 25574226
mesenchymal stem cells; brain-derived neurotrophic factor; differentiation; neuron-like cells
9.  Probing Mechanoregulation of Neuronal Differentiation by Plasma Lithography Patterned Elastomeric Substrates 
Scientific Reports  2014;4:6965.
Cells sense and interpret mechanical cues, including cell-cell and cell-substrate interactions, in the microenvironment to collectively regulate various physiological functions. Understanding the influences of these mechanical factors on cell behavior is critical for fundamental cell biology and for the development of novel strategies in regenerative medicine. Here, we demonstrate plasma lithography patterning on elastomeric substrates for elucidating the influences of mechanical cues on neuronal differentiation and neuritogenesis. The neuroblastoma cells form neuronal spheres on plasma-treated regions, which geometrically confine the cells over two weeks. The elastic modulus of the elastomer is controlled simultaneously by the crosslinker concentration. The cell-substrate mechanical interactions are also investigated by controlling the size of neuronal spheres with different cell seeding densities. These physical cues are shown to modulate with the formation of focal adhesions, neurite outgrowth, and the morphology of neuroblastoma. By systematic adjustment of these cues, along with computational biomechanical analysis, we demonstrate the interrelated mechanoregulatory effects of substrate elasticity and cell size. Taken together, our results reveal that the neuronal differentiation and neuritogenesis of neuroblastoma cells are collectively regulated via the cell-substrate mechanical interactions.
doi:10.1038/srep06965
PMCID: PMC4223667  PMID: 25376886
10.  Nuclear translocation of telomerase reverse transcriptase is a critical process in lymphatic metastasis of nasopharyngeal carcinoma 
Oncology Letters  2014;9(1):265-269.
Telomerase reverse transcriptase (TERT) is the predominant functional unit of telomerase and maintains the telomere length and the stability of chromosomes. Recently, TERT has been shown to be a critical factor in a number of other biological processes, including cell proliferation and cancer metastasis. In addition, although numerous studies have been conducted, the subcellular localization of the TERT protein and the association of such with cancer metastasis remains unclear. To investigate the involvement of TERT in in vivo metastasis, quantum dots-based immunofluorescence and western blot analysis were conducted to detect changes in the subcellular localization of TERT in human nasopharyngeal carcinoma (NPC) tissues and metastatic lymph nodes. To further investigate, metastatic and non-metastatic models of NPC were generated using 5–8F (high metastasis capability) and 6–10B (low metastasis capability) cell lines, respectively. It was found that TERT protein was overexpressed in NPC tissue samples and metastatic lymph nodes and TERT was predominantly located in the cytoplasm of primary NPC tissues, while TERT was predominantly located in the nucleus of the metastatic lymph nodes. The ratio of cytoplasmic TERT/nuclear TERT for the primary tumor of the 6–10B cell line was almost six-fold higher than that of the metastatic lymph nodes of the 5–8F cell line. TERT translocation from the cytoplasm to nucleus may present a critical step in the lymphatic metastasis of NPC. Thus, TERT translocation may be more useful than TERT expression level and telomerase activity for predicting the metastasis of NPC.
doi:10.3892/ol.2014.2689
PMCID: PMC4246691  PMID: 25435972
nasopharyngeal carcinoma; metastasis; translocation; telomerase reverse transcriptase
11.  Ultrasound Guidance for Radial Artery Catheterization: An Updated Meta-Analysis of Randomized Controlled Trials 
PLoS ONE  2014;9(11):e111527.
Background
Since a previous meta-analysis reported that ultrasound guidance was associated with a higher first-attempt success rate in catheterization of the radial artery, a number of randomized controlled trials (RCTs) have reported inconsistent results. The aim of the present study is to conduct an updated meta-analysis to clarify the role of ultrasound guidance for radial artery catheterization.
Methods
A systematic literature search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted using specific search terms. Eligible studies were RCTs that compared ultrasound guidance with traditional palpation for radial artery catheterization. The Mantel-Haenszel method using the random effects model was adopted in this meta-analysis.
Results
Seven RCTs with 482 patients were included. Compared with traditional palpation, ultrasound guidance significantly increased the first-attempt success rate of radial artery catheterization (RR 1.51, 95% CI 1.07–2.14, P = 0.02). Subgroup analyses suggested that the superiority of ultrasound guidance for radial artery catheterization was significant when the technique was operated by experienced users, performed in small children and infants, and on elective procedures in the operating room. In addition, ultrasound guidance significantly reduced mean-attempts to success (WMD −1.13, 95% CI −1.58 to −0.69, P<0.00001), mean-time to success (WMD −74.77s, 95% CI −137.89s to −11.64s, P = 0.02), and the occurrence of hematoma (RR 0.17, 95% CI 0.07–0.41, P = 0.0001).
Conclusions
The present meta-analysis suggests a clear benefit from ultrasound guidance for radial artery catheterization compared with the traditional palpation. Preliminary training and familiarization with the ultrasound-guided technique is needed before applying it for radial artery catheterization, especially for inexperienced operators.
doi:10.1371/journal.pone.0111527
PMCID: PMC4222952  PMID: 25375152
12.  Cofactor Molecules Induce Structural Transformation During Infectious Prion Formation 
Structure (London, England : 1993)  2013;21(11):10.1016/j.str.2013.08.025.
Summary
The spread of misfolded proteins has been implicated in a wide variety of neurodegenerative diseases. Prions associated with spongiform encephalopathy are currently the only misfolded proteins in which high specific biological infectivity can be produced in vitro. Using a system that generates infectious prions de novo from purified recombinant PrP and conversion cofactors palmitoyl-oleoyl-phosphatidylglycerol (POPG) and RNA, we examined by deuterium exchange mass spectrometry (DXMS) the stepwise protein conformational changes that occur during prion formation. We found that initial incubation with POPG causes major structural changes in PrP involving all three α-helices and one β-strand, with subsequent RNA rendering the N-terminus highly exposed. Final conversion into the infectious PrPSc form was accompanied by globally decreased solvent exposure, with persistence of the major cofactor-induced conformational features. Thus, we report that cofactor molecules appear to induce major structural rearrangements during prion formation, initiating a dynamic sequence of conformational changes resulting in biologically active prions.
doi:10.1016/j.str.2013.08.025
PMCID: PMC3863764  PMID: 24120764
deuterium exchange; protein misfolding; PrP; scrapie; cofactor
13.  Genetic Diversity Analysis Reveals that Geographical Environment Plays a More Important Role than Rice Cultivar in Villosiclava virens Population Selection 
Rice false smut caused by Villosiclava virens is an economically important disease of grains worldwide. The genetic diversity of 153 isolates from six fields located in Wuhan (WH), Yichang Wangjia (YCW), Yichang Yaohe (YCY), Huanggang (HG), Yangxin (YX), and Jingzhou (JZ) in Hubei province of China were phylogenetically analyzed to evaluate the influence of environments and rice cultivars on the V. virens populations. Isolates (43) from Wuhan were from two rice cultivars, Wanxian 98 and Huajing 952, while most of the other isolates from fields YCW, YCY, HG, YX, and JZ originated from different rice cultivars with different genetic backgrounds. Genetic diversity of isolates was analyzed using random amplified polymorphic DNA (RAPD) and single-nucleotide polymorphisms (SNP). The isolates from the same cultivars in Wuhan tended to group together, indicating that the cultivars had an important impact on the fungal population. The 110 isolates from individual fields tended to cluster according to geographical origin. The values of Nei's gene diversity (H) and Shannon's information index (I) showed that the genetic diversity among isolates was higher between than within geographical populations. Furthermore, mean genetic distance between groups (0.006) was higher than mean genetic distance within groups (0.0048) according to MEGA 5.2. The pairwise population fixation index (FST) values also showed significant genetic differentiation between most populations. Higher genetic similarity of isolates from individual fields but different rice cultivars suggested that the geographical factor played a more important role in the selection of V. virens isolates than rice cultivars. This information could be used to improve the management strategy for rice false smut by adjusting the cultivation measures, such as controlling fertilizer, water, and planting density, in the rice field to change the microenvironment.
doi:10.1128/AEM.03936-13
PMCID: PMC3993286  PMID: 24584249
14.  Development and bin mapping of gene-associated interspecific SNPs for cotton (Gossypium hirsutum L.) introgression breeding efforts 
BMC Genomics  2014;15(1):945.
Background
Cotton (Gossypium spp.) is the largest producer of natural fibers for textile and is an important crop worldwide. Crop production is comprised primarily of G. hirsutum L., an allotetraploid. However, elite cultivars express very small amounts of variation due to the species monophyletic origin, domestication and further bottlenecks due to selection. Conversely, wild cotton species harbor extensive genetic diversity of prospective utility to improve many beneficial agronomic traits, fiber characteristics, and resistance to disease and drought. Introgression of traits from wild species can provide a natural way to incorporate advantageous traits through breeding to generate higher-producing cotton cultivars and more sustainable production systems. Interspecific introgression efforts by conventional methods are very time-consuming and costly, but can be expedited using marker-assisted selection.
Results
Using transcriptome sequencing we have developed the first gene-associated single nucleotide polymorphism (SNP) markers for wild cotton species G. tomentosum, G. mustelinum, G. armourianum and G. longicalyx. Markers were also developed for a secondary cultivated species G. barbadense cv. 3–79. A total of 62,832 non-redundant SNP markers were developed from the five wild species which can be utilized for interspecific germplasm introgression into cultivated G. hirsutum and are directly associated with genes. Over 500 of the G. barbadense markers have been validated by whole-genome radiation hybrid mapping. Overall 1,060 SNPs from the five different species have been screened and shown to produce acceptable genotyping assays.
Conclusions
This large set of 62,832 SNPs relative to cultivated G. hirsutum will allow for the first high-density mapping of genes from five wild species that affect traits of interest, including beneficial agronomic and fiber characteristics. Upon mapping, the markers can be utilized for marker-assisted introgression of new germplasm into cultivated cotton and in subsequent breeding of agronomically adapted types, including cultivar development.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-945) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2164-15-945
PMCID: PMC4298081  PMID: 25359292
Cotton; Gossypium barbadense; Gossypium tomentosum; Gossypium mustelinum; Gossypium armourianum; Gossypium longicalyx; RNA-seq; Interspecific SNP
15.  Clinical Significance of Resistin Expression in Osteoarthritis: A Meta-Analysis 
BioMed Research International  2014;2014:208016.
Background. The objective of this study was to conduct a systematic review of literature evaluating human resistin expression as a diagnostic factor in osteoarthritis development and to quantify the overall diagnostic effect. Method. Relevant studies were identified and evaluated for quality through multiple search strategies. Studies analyzing resistin expression in the development of OA were eligible for inclusion. Data from eligible studies were extracted and included into the meta-analysis using a random-effects model. Results. Four case-control studies consisting of a total of 375 OA patients and 214 controls as well as three sex-stratified analyses composed of 53 males and 104 females were incorporated into our meta-analysis. Our results revealed that resistin levels were significantly higher in male OA subjects and OA patients overall. Country-stratified analysis yielded significantly different estimates in resistin levels between male OA subjects and female OA subjects in the Canadian subgroup but not among the French and USA subgroups. Based on the resistin levels in OA cases and controls, resistin levels were heightened in OA patients in the Dutch population. Conclusion. These results support the hypothesis that high expression of resistin represents a significant and reproducible marker of poor progression in OA patients, especially in males.
doi:10.1155/2014/208016
PMCID: PMC4230214  PMID: 25530956
16.  Bio-mimetic Nanostructure Self-assembled from Au@Ag Heterogeneous Nanorods and Phage Fusion Proteins for Targeted Tumor Optical Detection and Photothermal Therapy 
Scientific Reports  2014;4:6808.
Nanomaterials with near-infrared (NIR) absorption have been widely studied in cancer detection and photothermal therapy (PTT), while it remains a great challenge in targeting tumor efficiently with minimal side effects. Herein we report a novel multifunctional phage-mimetic nanostructure, which was prepared by layer-by-layer self-assembly of Au@Ag heterogenous nanorods (NRs) with rhodamine 6G, and specific pVIII fusion proteins. Au@Ag NRs, first being applied for PTT, exhibited excellent stability, cost-effectivity, biocompatibility and tunable NIR absorption. The fusion proteins were isolated from phage DDAGNRQP specifically selected from f8/8 landscape phage library against colorectal cancer cells in a high-throughput way. Considering the definite charge distribution and low molecular weight, phage fusion proteins were assembled on the negatively charged NR core by electrostatic interactions, exposing the N-terminus fused with DDAGNRQP peptide on the surface. The fluorescent images showed that assembled phage fusion proteins can direct the nanostructure into cancer cells. The nanostructure was more efficient than gold nanorods and silver nanotriangle-based photothermal agents and was capable of specifically ablating SW620 cells after 10 min illumination with an 808 nm laser in the light intensity of 4 W/cm2. The prepared nanostructure would become an ideal reagent for simutaneously targeted optical imaging and PTT of tumor.
doi:10.1038/srep06808
PMCID: PMC4210868  PMID: 25348392
19.  The effect of goal-directed therapy on mortality in patients with sepsis - earlier is better: a meta-analysis of randomized controlled trials 
Critical Care  2014;18(5):570.
Introduction
The Surviving Sepsis Campaign guidelines recommend goal-directed therapy (GDT) for the early resuscitation of patients with sepsis. However, the findings of the ProCESS (Protocolized Care for Early Septic Shock) trial showed no benefit from GDT for reducing mortality rates in early septic shock. We performed a meta-analysis to integrate these findings with existing literature on this topic and evaluate the effect of GDT on mortality due to sepsis.
Methods
We searched the PubMed, Embase and CENTRAL (Cochrane Central Register of Controlled Trials) databases and reference lists of extracted articles. Randomized controlled trials comparing GDT with standard therapy or usual care in patients with sepsis were included. The prespecified primary outcome was overall mortality.
Results
In total, 13 trials involving 2,525 adult patients were included. GDT significantly reduced overall mortality in the random-effects model (relative risk (RR), 0.83; 95% confidence interval (CI), 0.71 to 0.96; P =0.01; I2 = 56%). Predefined subgroup analysis according to the timing of GDT for resuscitation suggested that a mortality benefit was seen only in the subgroup of early GDT within the first 6 hours (seven trials; RR, 0.77; 95% CI, 0.67 to 0.89; P =0.0004; I2 = 40%), but not in the subgroup with late or unclear timing of GDT (six trials; RR, 0.92; 95% CI, 0.69 to 1.24; P =0.59; I2 = 56%). GDT was significantly associated with the use of dobutamine (five trials; RR, 2.71; 95% CI, 1.20 to 6.10; P =0.02).
Conclusions
The results of the present meta-analysis suggest that GDT significantly reduces overall mortality in patients with sepsis, especially when initiated early. However, owing to the variable quality of the studies, strong and definitive recommendations cannot be made.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-014-0570-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s13054-014-0570-5
PMCID: PMC4232636  PMID: 25327977
20.  Diversity of wetland plants used traditionally in China: a literature review 
Background
In comparison with terrestrial plants, those growing in wetlands have been rarely studied ethnobotanically, including in China, yet people living in or near wetlands can accumulate much knowledge of the uses of local wetland plants. A characteristic of wetlands, cutting across climatic zones, is that many species are widely distributed, providing opportunities for studying general patterns of knowledge of the uses of plants across extensive areas, in the present case China. There is urgency in undertaking such studies, given the rapid rates of loss of traditional knowledge of wetland plants as is now occurring.
Methods
There have been very few studies specifically on the traditional knowledge of wetland plants in China. However, much information on such knowledge does exist, but dispersed through a wide body of literature that is not specifically ethnobotanical, such as regional Floras. We have undertaken an extensive study of such literature to determine which species of wetland plants have been used traditionally and the main factors influencing patterns shown by such knowledge. Quantitative techniques have been used to evaluate the relative usefulness of different types of wetland plants and regression analyses to determine the extent to which different quantitative indices give similar results.
Results
350 wetland plant species, belonging to 66 families and 187 genera, were found to have been used traditionally in China for a wide range of purposes. The top ten families used, in terms of numbers of species, were Poaceae, Polygonaceae, Cyperaceae, Lamiaceae, Asteraceae, Ranunculaceae, Hydrocharitaceae, Potamogetonaceae, Fabaceae, and Brassicaceae, in total accounting for 58.6% of all species used. These families often dominate wetland vegetation in China. The three most widely used genera were Polygonum, Potamogeton and Cyperus. The main uses of wetlands plants, in terms of numbers of species, were for medicine, food, and forage. Three different ways of assigning an importance value to species (Relative Frequency of Citation RFC; Cultural Importance CI; Cultural Value Index CV) all gave similar results.
Conclusions
A diverse range of wetland plants, in terms of both taxonomic affiliation and type of use, have been used traditionally in China. Medicine, forage and food are the three most important categories of use, the plants providing basic resources used by local people in their everyday lives. Local availability is the main factor influencing which species are used. Quantitative indexes, especially Cultural Value Index, proved very useful for evaluating the usefulness of plants as recorded in the literature.
doi:10.1186/1746-4269-10-72
PMCID: PMC4210556  PMID: 25318542
Wetland plants; Traditional knowledge; Literature study; China
21.  Evaluation of a Loop-Mediated Isothermal Amplification Suite for the Rapid, Reliable, and Robust Detection of Shiga Toxin-Producing Escherichia coli in Produce 
Shiga toxin-producing Escherichia coli (STEC) strains are a leading cause of produce-associated outbreaks in the United States. Rapid, reliable, and robust detection methods are needed to better ensure produce safety. We recently developed a loop-mediated isothermal amplification (LAMP) suite for STEC detection. In this study, the STEC LAMP suite was comprehensively evaluated against real-time quantitative PCR (qPCR) using a large panel of bacterial strains (n = 156) and various produce items (several varieties of lettuce, spinach, and sprouts). To simulate real-world contamination events, produce samples were surface inoculated with a low level (1.2 to 1.8 CFU/25 g) of individual STEC strains belonging to seven serogroups (O26, O45, O103, O111, O121, O145, and O157) and held at 4°C for 48 h before testing. Six DNA extraction methods were also compared using produce enrichment broths. All STEC targets and their subtypes were accurately detected by the LAMP suite. The detection limits were 1 to 20 cells per reaction in pure culture and 105 to 106 CFU per 25 g (i.e., 103 to 104 CFU per g) in produce, except for strains harboring the stx2c, eae-β, and eae-θ subtypes. After 6 to 8 h of enrichment, the LAMP suite achieved accurate detection of low levels of STEC strains of various stx2 and eae subtypes in lettuce and spinach varieties but not in sprouts. A similar trend of detection was observed for qPCR. The PrepMan Ultra sample preparation reagent yielded the best results among the six DNA extraction methods. This research provided a rapid, reliable, and robust method for detecting STEC in produce during routine sampling and testing. The challenge with sprouts detection by both LAMP and qPCR calls for special attention to further analysis.
doi:10.1128/AEM.04203-13
PMCID: PMC3993192  PMID: 24509927
22.  Comparison of the Clinical Effects of Open and Closed Chain Exercises after Medial Patellofemoral Ligament Reconstruction 
Journal of Physical Therapy Science  2014;26(10):1557-1560.
[Purpose] To compare the effects of open-chain exercise (OCE) and closed-chain exercise (CCE) for patients after medial patellofemoral ligament (MPFL) reconstruction. [Subjects and Methods] Forty patients after MPFL reconstruction were randomly divided into an OCE group and a CCE group. All the patients were evaluated at four different time points. [Results] The mean change of thigh circumference decrease in the CCE group was lower than that in the OCE group at both the 3rd and 6th month after surgery. The Lysholm score of the CCE group was higher than that of the OCE group at both the 3rd and 6th month. At the 3rd month after surgery, the visual analog scale score of the CCE group was lower than that of the OCE group. [Conclusion] CCE is better than OCE for both short and long term outcomes of patients after MPFL reconstruction.
doi:10.1589/jpts.26.1557
PMCID: PMC4210397  PMID: 25364112
Medial patellofemoral ligament reconstruction; Open-chain exercise; Closed-chain exercise
23.  Breast cancer awareness among women in Eastern China: a cross-sectional study 
BMC Public Health  2014;14(1):1004.
Background
High breast cancer mortality has been attributed to lack of public awareness, which leads to late diagnoses. As little is known about the level of knowledge and awareness of breast cancer in China, this study was designed to explore it among women in Eastern China.
Methods
We conducted a cross-sectional survey covering 122,058 females around Shandong, Hebei, Jiangsu and Tianjin, in Eastern China, using in-person interviews based on a self-designed structured questionnaire. Student’s t-test, Pearson’s χ2 test, reliability analysis, exploratory factor analysis, univariate and multivariate logistic regression analyses were performed in the statistical analysis.
Results
The results showed poor awareness of breast cancer among women aged 25–70 years in Eastern China. Only 18.6% of women were highly aware in the study, whereas 81.4% were poorly aware. Among all participants, family history of breast cancer was the best accepted risk factor for breast cancer (awareness rate 31.5%), followed by menarche at age before 12 (11.2%), no parity or late childbirth (13.9%), menopause at a late age (13.7%), high-fat diets (19.1%), long time drinking (19.5%) and long-term use of estrogen drugs (20.7%). Multivariate logistic regression analysis (α = 0.05) identified nine variables that predicted awareness of breast cancer: age (OR = 0.975, 95% CI: 0.960–0.990), location (OR = 1.675, 95% CI: 1.602–1.752), occupation (OR = 4.774, 95% CI: 4.316–5.281), family history of breast cancer (OR = 1.234, 95% CI: 1.073–1.420), household annual income (OR = 0.418, 95% CI: 0.400–0.436), behavioral prevention score (OR = 4.137, 95% CI: 3.991–4.290), no smoking (OR = 2.113, 95% CI: 1.488–2.999), no drinking (OR = 1.427, 95% CI: 1.018–2.000), overall life satisfaction (OR = 0.707, 95% CI: 0.683–0.731).
Conclusions
Our study indicates insufficient awareness of breast cancer among women in Eastern China, and an urgent need for health education programs on this subject.
doi:10.1186/1471-2458-14-1004
PMCID: PMC4180963  PMID: 25257142
Breast cancer; Knowledge; Chinese women; Cancer awareness
24.  Significance of hypoxia-inducible factor-1α expression with atrial fibrosis in rats induced with isoproterenol 
Atrial interstitial fibrosis plays a dual role in inducing and maintaining atrial fibrillation (AF). Hypoxia-inducible factor-1α (HIF-1α) has been reported as closely associated with renal, liver and pulmonary fibrosis diseases. However, whether HIF-1α is involved in myocardial fibrosis, and the associations between HIF-1α, transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) remain unknown. Therefore, this area warrants studying for the significance of AF diagnosis and treatment. The present study investigated the expression of HIF-1α in atrial fibrosis and its possible mechanism in isoproterenol (ISO)-induced rats. The three groups of rats; control, ISO and ISO plus sirolimus [also known as rapamycin (Rapa)], were treated for 15 days and sacrificed to remove the myocardial tissues. The expression levels of HIF-1α, TGF-β1 and MMP-9 and their associations with atrial fibrosis were examined through histomorphology and protein and mRNA levels. The protein and mRNA levels of HIF-1α, TGF-β1 and MMP-9 in the ISO group were increased markedly (P<0.01) compared with the control group, while those in the Rapa group were clearly decreased (P<0.01) compared with the ISO group. The protein and mRNA levels of HIF-1α, TGF-β1 and MMP-9 were positively correlated (P<0.01) with atrial fibrosis (collagen volume fraction index), as were the HIF-1α, TGF-β1 and MMP-9 mRNA levels (P<0.01) and the mRNA levels between MMP-9 and TGF-β1 (P<0.01). During the process of atrial fibrosis in ISO-induced rats, HIF-1α promotes the expression of TGF-β1 and MMP-9 protein, and thus is involved in in atrial fibrosis.
doi:10.3892/etm.2014.1989
PMCID: PMC4218706  PMID: 25371714
hypoxia inducible factor-1α; atrial; fibrosis; transforming growth factor-β1; matrix metalloproteinase-9
25.  Telocytes in liver regeneration: possible roles 
Telocytes (TCs) are a novel type of interstitial cells which are potentially involved in tissue regeneration and repair (http://www.telocytes.com). Previously, we documented the presence of TCs in liver. However, the possible roles of TCs in liver regeneration remain unknown. In this study, a murine model of partial hepatectomy (PH) was used to induce liver regeneration. The number of TCs detected by double labelling immunofluorescence methods (CD34/PDGFR-α, CD34/PDGFR-ß and CD34/Vimentin) was significantly increased when a high level of hepatic cell proliferation rate (almost doubled) as shown by 5-ethynyl-2′-deoxyuridine (EdU) immunostaining and Western Blot of Proliferating cell nuclear antigen (PCNA) was found at 48 and 72 hrs post-PH. Meanwhile, the number of CK-19 positive-hepatic stem cells peaked at 72 hrs post-PH, co-ordinating with the same time-point, when the number of TCs was most significantly increased. Taken together, the results indicate a close relationship between TCs and the cells essentially involved in liver regeneration: hepatocytes and stem cells. It remains to be determined how TCs affect hepatocytes proliferation and/or hepatic stem cell differentiation in liver regeneration. Besides intercellular junctions, we may speculate a paracrine effect via ectovesicles.
doi:10.1111/jcmm.12355
PMCID: PMC4196648  PMID: 25130653
telocytes; liver regeneration; hepatocytes; CK-19 positive-hepatic stem cells; CD34; PDGFR-α, ß; EdU; PCNA

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