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1.  Evidence of liquid–liquid transition in glass-forming La50Al35Ni15 melt above liquidus temperature 
Nature Communications  2015;6:7696.
Liquid–liquid transition, a phase transition of one liquid phase to another with the same composition, provides a key opportunity for investigating the relationship between liquid structures and dynamics. Here we report experimental evidences of a liquid–liquid transition in glass-forming La50Al35Ni15 melt above its liquidus temperature by 27Al nuclear magnetic resonance including the temperature dependence of cage volume fluctuations and atomic diffusion. The observed dependence of the incubation time on the degree of undercooling is consistent with a first-order phase transition. Simulation results indicate that such transition is accompanied by the change of bond-orientational order without noticeable change in density. The temperature dependence of atomic diffusion revealed by simulations is also in agreement with experiments. These observations indicate the need of two-order parameters in describing phase transitions of liquids.
Non-density driven liquid-liquid transition has been predicted in theories, but direct experimental verification is challenging because liquid often remains metastable at transition temperature. Here, Xu et al. provide evidence in a lanthanum-based metallic glass above its liquidus temperature.
PMCID: PMC4510689  PMID: 26165855
2.  Novel Online Dimensionality Reduction Method with Improved Topology Representing and Radial Basis Function Networks 
PLoS ONE  2015;10(7):e0131631.
This paper presents improvements to the conventional Topology Representing Network to build more appropriate topology relationships. Based on this improved Topology Representing Network, we propose a novel method for online dimensionality reduction that integrates the improved Topology Representing Network and Radial Basis Function Network. This method can find meaningful low-dimensional feature structures embedded in high-dimensional original data space, process nonlinear embedded manifolds, and map the new data online. Furthermore, this method can deal with large datasets for the benefit of improved Topology Representing Network. Experiments illustrate the effectiveness of the proposed method.
PMCID: PMC4498733  PMID: 26161960
3.  Oleanolic acid induces mitochondrial-dependent apoptosis and G0/G1 phase arrest in gallbladder cancer cells 
Oleanolic acid (OA), a naturally occurring triterpenoid, exhibits potential antitumor activity in many tumor cell lines. Gallbladder carcinoma is the most common malignancy of the biliary tract, and is a highly aggressive tumor with an extremely poor prognosis. Unfortunately, the effects of OA on gallbladder carcinoma are unknown. In this study, we investigated the effects of OA on gallbladder cancer cells and the underlying mechanism. The results showed that OA inhibits proliferation of gallbladder cancer cells in a dose-dependent and time-dependent manner on MTT and colony formation assay. A flow cytometry assay revealed apoptosis and G0/G1 phase arrest in GBC-SD and NOZ cells. Western blot analysis and a mitochondrial membrane potential assay demonstrated that OA functions through the mitochondrial apoptosis pathway. Moreover, this drug inhibited tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data suggest that OA inhibits proliferation of gallbladder cancer cells by regulating apoptosis and the cell cycle process. Thus, OA may be a promising drug for adjuvant chemotherapy in gallbladder carcinoma.
PMCID: PMC4472077  PMID: 26109845
oleanolic acid; gallbladder carcinoma; apoptosis; cell cycle arrest; mitochondrial pathway
4.  MALAT1 promotes the proliferation and metastasis of gallbladder cancer cells by activating the ERK/MAPK pathway 
Cancer Biology & Therapy  2014;15(6):806-814.
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA (lncRNA), is associated with metastasis and is an independent prognostic factor for lung cancer. Recent studies have demonstrated that MALAT1 plays an important role in other malignancies. However, little is known about the role of MALAT1 in gallbladder carcinoma (GBC), which is the most common cancer of the biliary tract and has an extremely poor prognosis. In this study, we focused on the expression, biological functions and mechanism of MALAT1 in GBC and found that MALAT1 was significantly upregulated in GBC tissues compared with corresponding non-cancerous tissues. Knockdown of MALAT1 in GBC cell lines using lentivirus-mediated RNA interference significantly inhibited the proliferation and metastasis of the GBC cells both in vitro and in vivo. Furthermore, ERK/MAPK pathway was found to be inactivated in the GBC cell lines after MALAT1 knockdown. These results indicated that MALAT1 might serve as an oncogenic lncRNA that promotes proliferation and metastasis of GBC and activates the ERK/MAPK pathway
PMCID: PMC4049796  PMID: 24658096
gallbladder carcinoma; MALAT1; lncRNA; ERK; MAPK; proliferation; metastasis
5.  Actigraph Evaluation of Acupuncture for Treating Restless Legs Syndrome 
We evaluated the effects of acupuncture in patients with restless legs syndrome (RLS) by actigraph recordings. Among the 38 patients with RLS enrolled, 31 (M = 12, F = 19; mean age, 47.2 ± 9.7 years old) completed the study. Patients were treated with either standard acupuncture (n = 15) or randomized acupuncture (n = 16) in a single-blind manner for 6 weeks. Changes in nocturnal activity (NA) and early sleep activity (ESA) between week 0 (baseline), week 2, week 4, and week 6 were assessed using leg actigraph recordings, the International Restless Legs Syndrome Rating Scale (IRLSRS), and Epworth Sleepiness Scale (ESS). Standard but not randomized acupuncture reduced the abnormal leg activity of NA and ESA significantly in week 2, week 4, and week 6 based on the changes in the clinical scores for IRLSRS and ESS in week 4 and week 6 compared with the baseline. No side effects were observed. The results indicate that standard acupuncture might improve the abnormal leg activity in RLS patients and thus is a potentially suitable integrative treatment for long-term use.
PMCID: PMC4339862  PMID: 25763089
6.  SPOCK1 as a potential cancer prognostic marker promotes the proliferation and metastasis of gallbladder cancer cells by activating the PI3K/AKT pathway 
Molecular Cancer  2015;14(1):12.
Gallbladder cancer (GBC) is a leading cause of cancer-related death worldwide, and its prognosis remains poor, with 5-year survival of approximately 5%. In this study, we analyzed the involvement of a novel proteoglycan, Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1), in the tumor progression and prognosis of human GBC.
SPOCK1 expression levels were measured in fresh samples and stored specimens of GBC and adjacent nontumor tissues. The effect of SPOCK1 on cell growth, DNA replication, migration and invasion were explored by Cell Counting Kit-8, colony formation, EdU retention assay, wound healing, and transwell migration assays, flow cytometric analysis, western blotting, and in vivo tumorigenesis and metastasis in nude mice.
SPOCK1 mRNA and protein levels were increased in human GBC tissues compared with those in nontumor tissues. Immunohistochemical analysis indicated that SPOCK1 levels were increased in tumors that became metastatic, compared with those that did not, which was significantly associated with histological differentiation and patients with shorter overall survival periods. Knockdown of SPOCK1 expression by lentivirus-mediated shRNA transduction resulted in significant inhibition of GBC cell growth, colony formation, DNA replication, and invasion in vitro. The knockdown cells also formed smaller xenografted tumors than control GBC cells in nude mice. Overexpression of SPOCK1 had the opposite effects. In addition, SPOCK1 promoted cancer cell migration and epithelial-mesenchymal transition by regulating the expression of relevant genes. We found that activation of the PI3K/Akt pathway was involved in the oncogenic functions of SPOCK1 in GBC.
SPOCK1 activates PI3K/Akt signaling to block apoptosis and promote proliferation and metastasis by GBC cells in vitro and in vivo. Levels of SPOCK1 increase with the progression of human GBC. SPOCK1 acts as an oncogene and may be a prognostic factor or therapeutic target for patients with GBC.
Electronic supplementary material
The online version of this article (doi:10.1186/s12943-014-0276-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4320842  PMID: 25623055
Gallbladder cancer; SPOCK1; Tumor progression; RNA interference; Epithelial-mesenchymal transition
7.  Baicalein Inhibits Progression of Gallbladder Cancer Cells by Downregulating ZFX 
PLoS ONE  2015;10(1):e0114851.
Baicalein, a widely used Chinese herbal medicine, has multiple pharmacological activities. However, the precise mechanisms of the anti-proliferation and anti-metastatic effects of baicalein on gallbladder cancer (GBC) remain poorly understood. Therefore, the aim of this study was to assess the anti-proliferation and anti-metastatic effects of baicalein and the related mechanism(s) on GBC. In the present study, we found that treatment with baicalein induced a significant inhibitory effect on proliferation and promoted apoptosis in GBC-SD and SGC996 cells, two widely used gallbladder cancer cell lines. Additionally, treatment with baicalein inhibited the metastasis of GBC cells. Moreover, we demonstrated for the first time that baicalein inhibited GBC cell growth and metastasis via down-regulation of the expression level of Zinc finger protein X-linked (ZFX). In conclusion, our studies suggest that baicalein may be a potential phytochemical flavonoid for therapeutics of GBC and ZFX may serve as a molecular marker or predictive target for GBC.
PMCID: PMC4305301  PMID: 25617627
8.  Role of rCBV values derived from dynamic susceptibility contrast-enhanced magnetic resonance imaging in differentiating CNS lymphoma from high grade glioma: a meta-analysis 
Background and purpose: In the preoperative period, discriminating CNS lymphoma from high grade glioma is important as treatment approaches differ significantly. Hence, this meta-analysis was to evaluate the sensitivity and specificity of the relative cerebral blood volume (rCBV) values derived from dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSCE-MRI) in differentiating CNS lymphoma from high grade glioma. Materials and methods: The following databases were searched from January 2000 to July 2014: Medline, PubMed and Embase. No language restrictions were applied. Data analysis was conducted using Meta-Disc 1.4. Results: A total of 79 patients (n = 30 lymphoma, n = 49 high grade glioma) and 89 lesions (n = 40 lymphoma, n = 49 high grade glioma) were included in the rCBV analysis. The pooled sensitivity, specificity, negative likelihood ratio, positive likelihood ratio and diagnostic odds ratio for differentiating CNS lymphoma from high grade glioma were 0.90 (95% CI 0.76-0.97), 0.98 (95% CI 0.89-1.00), 0.13 (95% CI 0.06-0.29), 21.07 (95% CI 5.61-79.19), and 187.63 (95% CI 33.15-1061.86), respectively. And the value of I2 of DOR was 0.0%, indicating that there was no statistically significant heterogeneity of DOR between the included studies. Conclusions: Our meta-analysis suggests that the rCBV values derived from DSCE-MRI could be useful in differentiating CNS lymphoma from high grade glioma in the preoperative. Further well-designed researches involving larger patient cohorts are needed to confirm this conclusion.
PMCID: PMC4307521  PMID: 25664074
CNS lymphoma; high grade glioma; rCBV values; meta-analysis
9.  The potential risk factors for atypical and anaplastic meningiomas: clinical series of 1,239 cases 
Background: Determining factors that could accurately predict pathological features of meningiomas before histological diagnosis would help surgeons to proper balance the risk of operation and the resection grade. The aim of this study was to explore the potential risk factors for atypical (WHO Grade II) and anaplastic (WHO Grade III) meningiomas. Methods: Records of 1,239 patients between January 2009 and January 2013 were included in this research. Furthermore, immunohistochemistry with Ki67 was analysed in 368 samples. Results: The Pearson’s chi-square test showed an increased risk for male gender for atypical and anaplastic meningiomas (P < 0.001) and an increased risk for cerebral convexity for atypical and anaplastic meningiomas (P < 0.001). However, significant differences in the terms of falx/sagittal sinus and intraventricular were not found. Patients with a Ki67 index ≥ 5% were significantly more likely to have atypical and anaplastic meningiomas than those patients with a Ki67 index < 5% (P < 0.001). In addition, the percentage of patients with a Ki67 index ≥ 5% in cerebral convexity meningiomas was higher than in non-cerebral convexity location (P = 0.006). Conclusions: The results indicate that male gender, cerebral convexity are significant risk factors for atypical and anaplastic meningiomas.
PMCID: PMC4307540  PMID: 25664093
Cerebral convexity; risk factor; meningiomas
10.  Classification of grass pollen through the quantitative analysis of surface ornamentation and texture 
Taxonomic identification of pollen and spores uses inherently qualitative descriptions of morphology. Consequently, identifications are restricted to categories that can be reliably classified by multiple analysts, resulting in the coarse taxonomic resolution of the pollen and spore record. Grass pollen represents an archetypal example; it is not routinely identified below family level. To address this issue, we developed quantitative morphometric methods to characterize surface ornamentation and classify grass pollen grains. This produces a means of quantifying morphological features that are traditionally described qualitatively. We used scanning electron microscopy to image 240 specimens of pollen from 12 species within the grass family (Poaceae). We classified these species by developing algorithmic features that quantify the size and density of sculptural elements on the pollen surface, and measure the complexity of the ornamentation they form. These features yielded a classification accuracy of 77.5%. In comparison, a texture descriptor based on modelling the statistical distribution of brightness values in image patches yielded a classification accuracy of 85.8%, and seven human subjects achieved accuracies between 68.33 and 81.67%. The algorithmic features we developed directly relate to biologically meaningful features of grass pollen morphology, and could facilitate direct interpretation of unsupervised classification results from fossil material.
PMCID: PMC3779338  PMID: 24048158
palynology; Poaceae; microscopy; pattern analysis; computational image analysis
11.  Ursolic acid induces cell cycle arrest and apoptosis of gallbladder carcinoma cells 
Ursolic acid (UA), a plant extract used in traditional Chinese medicine, exhibits potential anticancer effects in various human cancer cell lines in vitro. In the present study, we evaluated the anti-tumoral properties of UA against gallbladder carcinoma and investigated the potential mechanisms responsible for its effects on proliferation, cell cycle arrest and apoptosis in vitro.
The anti-tumor activity of UA against GBC-SD and SGC-996 cells was assessed using MTT and colony formation assays. An annexin V/PI double-staining assay was used to detect cell apoptosis. Cell cycle changes were detected using flow cytometry. Rhodamine 123 staining was used to assess the mitochondrial membrane potential (ΔΨm) and validate UA’s ability to induce apoptosis in both cell lines. The effectiveness of UA in gallbladder cancer was further verified in vivo by establishing a xenograft GBC model in nude mice. Finally, the expression levels of cell cycle- and apoptosis-related proteins were analyzed by western blotting.
Our results suggest that UA can significantly inhibit the growth of gallbladder cancer cells. MTT and colony formation assays indicated dose-dependent decreases in cell proliferation. S-phase arrest was observed in both cell lines after treatment with UA. Annexin V/PI staining suggested that UA induced both early and late phases of apoptosis. UA also decreased ΔΨm and altered the expression of molecules regulating the cell cycle and apoptosis. In vivo study showed intraperitoneally injection of UA can significantly inhibited the growth of xenograft tumor in nude mice and the inhibition efficiency is dose related. Activation of caspase-3,-9 and PARP indicated that mitochondrial pathways may be involved in UA-induced apoptosis.
Taken together, these results suggest that UA exhibits significant anti-tumor effects by suppressing cell proliferation, promoting apoptosis and inducing 7cell cycle arrest both in vitro and in vivo. It may be a potential agent for treating gallbladder cancer.
PMCID: PMC4224689  PMID: 25383044
Ursolic acid; Gallbladder cancer; Proliferation; Cell cycle; Apoptosis; Mitochondrial-mediated pathway
12.  Potential role of fractional anisotropy derived from diffusion tensor imaging in differentiating high-grade gliomas from low-grade gliomas: a meta-analysis 
Background and purpose: It is crucial to accurately differentiate high-grade gliomas (HGGs) from low-grade gliomas (LGGs) preoperatively, as treatment strategies vary. So we performed a meta-analysis to assess the sensitivity and specificity of fractional anisotropy (FA) value derived from diffusion tensor imaging (DTI) in differentiating HGGs from LGGs. Materials and methods: Between January 2005 and June 2014, relevant articles were searched from the Embase and Medline databases for analysis. Statistical analyses were performed using Meta-Disc 1.4. Results: A total of 221 patients included in the FA analysis: 127 with HGGs and 94 LGGs. The pooled sensitivity, specificity and diagnostic odds ratio (DOR) for differentiating HGGs from LGGs were 93% (95% CI 0.87-0.97), 85% (95% CI 0.76-0.92), and 55.41 (95% CI 16.77-183.07), respectively. And computation of heterogeneity metrics revealed an acceptable level of the between-study heterogeneity of DOR (I2=30.9%). Conclusions: The results of our meta-analysis present that the FA derived from DTI act as a useful diagnostic marker could be used in distinguishing the HGGs from LGGs in the preoperative and the clinical application values are to be confirmed by further larger case-control studies.
PMCID: PMC4238464  PMID: 25419413
Diffusion tensor imaging; fractional anisotropy; high grade gliomas; low grade gliomas
13.  Meta-analysis of peritumoural rCBV values derived from dynamic susceptibility contrast imaging in differentiating high-grade gliomas from intracranial metastases 
Background and purpose: In the preoperative period, it is very important to accurately differentiate high-grade gliomas from intracranial metastases, as treatment strategies vary. Hence we performed a meta-analysis to evaluate the sensitivity and specificity of peritumoural relative cerebral blood volume (rCBV) values derived from dynamic susceptibility contrast imaging (DSCI) in differentiating high-grade gliomas from intracranial metastases. Materials and methods: Between 2004 and June 2014, relevant studies were searched from the databases of Medline and Embase for analysis. A total of 3 eligible studies were included in this analysis. Statistical analysis was performed with Meta-Disc 1.4. Results: A total of 136 patients included in the rCBV analysis: 79 with high-grade glioma and 57 with metastasis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR) and diagnostic odds ratio (DOR) for differentiating high-grade glioma from metastasis were 82% (95% CI 0.72-0.90), 96% (95% CI 0.88-1.00), 18.04 (95% CI 5.41-60.15), 0.19 (95% CI 0.12-0.31), and 90.20 (95% CI 23.10-352.27), respectively. The value of Cochran’s Q of DOR was 0.78 (P = 0.6774), and I2 was 0.0%, revealing that no statistically significant between-study heterogeneity was found. Conclusions: The results of this present study clearly present that the peritumoural rCBV values derived from DSCI could be used in distinguishing high-grade gliomas from intracranial metastases in the preoperative.
PMCID: PMC4211781  PMID: 25356131
Relative cerebral blood volume; dynamic susceptibility contrast imaging; high grade gliomas; metastases; meta-analysis
14.  Clinical and prognostic significance of preoperative plasma hyperfibrinogenemia in gallbladder cancer patients following surgical resection: a retrospective and in vitro study 
BMC Cancer  2014;14:566.
Coagulation and fibrinolysis activation is frequently observed in cancer patients, and the tumors in these cases are thought to be associated with a higher risk of invasion, metastasis, and worse long-term outcome. The objective of this study was to elucidate the prognostic significance of blood coagulation tests and various clinicopathological characteristics in patients with gallbladder cancer (GBC) after surgical resection.
We retrospectively reviewed the medical records of 115 patients with histologically confirmed GBC who underwent surgical resection in our department. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), international normalized ratio (INR), fibrinogen levels, and platelet counts were measured pretreatment at the time of diagnosis. The predictive value of fibrinogen levels for tumor staging was evaluated using a receiver operating characteristic (ROC) curve analysis. Correlations between the preoperative hyperfibrinogenemia and clinicopathological characteristics were analyzed, and univariate and multivariate survival analyses were performed to identify the factors associated with overall survival (OS). Cancer cell migration and invasion in vitro were examined to investigate the function of fibrinogen in GBC cell migration.
The plasma levels for all coagulation tests, with the exception of INR, were significantly different between the GBC patients and control patients (p < 0.001). Hyperfibrinogenemia (>402 mg/dL) was associated with poorly differentiated tumors, advanced tumor invasion, lymphatic metastasis, and advanced tumor stage (p < 0.001), and had a statistically significant adverse effect on survival (p = 0.001). In the multivariate analysis, hyperfibrinogenemia (p = 0.031) was independently associated with worse OS, tumor stage (p = 0.016), margin status (p < 0.001), and lymphatic metastasis (p = 0.035). Moreover, cell migration and invasion in vitro were significantly enhanced by fibrinogen.
Preoperative plasma fibrinogen levels was associated with tumor progression and may be an independent marker of poor prognosis in GBC patients. Furthermore, fibrinogen may contribute to cell migration by inducing epithelial-mesenchymal transition.
PMCID: PMC4131047  PMID: 25096189
Gallbladder cancer; Coagulation assays; Hyperfibrinogenemia; Prognosis
15.  Neurological Effects of Pesticide Use among Farmers in China 
The intensive use of pesticides has attracted great attention from the Chinese government. However, current regulations have had limited influence on their safe use. Although the acute neurologic effects of pesticides have been well documented, little is known about their cumulative effects. Knowledge of the impact of pesticides on health may convince farmers to minimize their use. We conducted a cross-sectional study in three provinces of China to evaluate the relationship between pesticide exposure and neurological dysfunction. Crop farmers were divided into two groups depending on their level of pesticide exposure. A total of 236 participants were assessed by questionnaire and neurological examination for symptoms and signs of neuropathy. Characteristics of neurologic dysfunction following cumulative low-level exposure were assessed with logistic regression analysis. Farmers exposed to high-level pesticide use had greater risk of developing sensations of numbness or prickling (odds ratio (OR) 2.62, 95% confidence interval (CI): 1.08–6.36). After adjusting for recent exposure, the risk of numbness or prickling symptoms (OR 2.55, 95% CI: 1.04–6.25) remained statistically significant. Loss of muscle strength and decreased deep tendon reflexes had OR > 2, however, this did not reach statistical significance. These findings suggest that overuse of pesticides increased risk of neurologic dysfunction among farmers, with somatosensory small fibers most likely affected. Measures that are more efficient should be taken to curb excessive use of pesticides.
PMCID: PMC4025041  PMID: 24736684
China; health effect; neurological deficit; pesticide overuse
16.  Combined use of non-biological artificial liver treatments for patients with acute liver failure complicated by multiple organ dysfunction syndrome 
Acute liver failure (ALF) caused by viral and non-viral hepatitis is often accompanied with severe metabolic disorders, the accumulation of toxic substances and continuous release and accumulation of a large number of endogenous toxins and inflammatory mediators. The present study aimed to investigate the effects of various combined non-biological artificial liver treatments for patients with acute liver failure (ALF) complicated by multiple organ dysfunction syndrome (MODS).
Thirty-one patients with mid- or late-stage liver failure complicated by MODS (score 4) were randomly divided into three treatment groups: plasmapheresis (PE) combined with hemoperfusion (HP) and continuous venovenous hemodiafiltration (CVVHDF), PE+CVVHDF, and HP+CVVHDF, respectively. Heart rate (HR) before and after treatment, mean arterial pressure (MAP), respiratory index (PaO2/FiO2), hepatic function, platelet count, and blood coagulation were determined.
Significant improvement was observed in HR, MAP, PaO2/FiO2, total bilirubin (TBIL) and alanine aminotransferase (ALT) levels after treatment (P<0.05). TBIL and ALT decreased more significantly after treatment in the PE+CVVHDF and PE+HP+CVVHDF groups (P<0.01). Prothrombin time (PT) and albumin were significantly improved only in the PE+CVVHDF and PE+HP+CVVHDF groups (P<0.05). TBIL decreased more significantly in the PE+HP+CVVHDF group than in the HP+CVVHDF and PE+CVVHDF groups (P<0.05). The survival rate of the patients was 58.1% (18/31), viral survival rate 36.4% (4/11), and non-viral survival rate 70% (14/20).
Liver function was relatively improved after treatment, but PE+HP+CVVHDF was more efficient for the removal of toxic metabolites, especially bilirubin. The survival rate was significantly higher in the patients with non-viral liver failure than in those with viral liver failure.
PMCID: PMC4163812  PMID: 25225587
Severe acute liver failure; Artificial liver; Plasma exchange; Hemoperfusion; Continuous veno-venous hemodiafiltration
17.  Calcineurin/NFAT pathway mediates wear particle-induced TNF-α release and osteoclastogenesis from mice bone marrow macrophages in vitro 
Acta Pharmacologica Sinica  2013;34(11):1457-1466.
To investigate the roles of the calcineurin/nuclear factor of activated T cells (NFAT) pathway in regulation of wear particles-induced cytokine release and osteoclastogenesis from mouse bone marrow macrophages in vitro.
Osteoclasts were induced from mouse bone marrow macrophages (BMMs) in the presence of 100 ng/mL receptor activator of NF-κB ligand (RANKL). Acridine orange staining and MTT assay were used to detect the cell viability. Osteoclastogenesis was determined using TRAP staining and RT-PCR. Bone pit resorption assay was used to examine osteoclast phenotype. The expression and cellular localization of NFATc1 were examined using RT-PCR and immunofluorescent staining. The production of TNFα was analyzed with ELISA.
Titanium (Ti) or polymethylmethacrylate (PMMA) particles (0.1 mg/mL) did not significantly change the viability of BMMs, but twice increased the differentiation of BMMs into mature osteoclasts, and markedly increased TNF-α production. The TNF-α level in the PMMA group was significantly higher than in the Ti group (96 h). The expression of NFATc1 was found in BMMs in the presence of the wear particles and RANKL. In bone pit resorption assay, the wear particles significantly increased the resorption area and total number of resorption pits in BMMs-seeded ivory slices. Addition of 11R-VIVIT peptide (a specific inhibitor of calcineurin-mediated NFAT activation, 2.0 μmol/L) did not significantly affect the viability of BMMs, but abolished almost all the wear particle-induced alterations in BMMs. Furthermore, VIVIT reduced TNF-α production much more efficiently in the PMMA group than in the Ti group (96 h).
Calcineurin/NFAT pathway mediates wear particles-induced TNF-α release and osteoclastogenesis from BMMs. Blockade of this signaling pathway with VIVIT may provide a promising therapeutic modality for the treatment of periprosthetic osteolysis.
PMCID: PMC4006473  PMID: 24056707
wear particle; bone marrow macrophage; osteoclast; TNF-α; calcineurin; nuclear factor of activated T cells (NFAT); 11R-VIVIT peptide; arthroplasty; periprosthetic osteolysis; aseptic loosening
18.  The Function and Significance of SELENBP1 Downregulation in Human Bronchial Epithelial Carcinogenic Process 
PLoS ONE  2013;8(8):e71865.
Our quantitative proteomic study showed that selenium-binding protein 1 (SELENBP1) was progressively decreased in human bronchial epithelial carcinogenic process. However, there is little information on expression and function of SELENBP1 during human lung squamous cell cancer (LSCC) carcinogenesis.
iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed proteins in the human bronchial epithelial carcinogenic process. SELENBP1, member of selenoproteins family and progressively downregulated in this process, was selected to further study. Both Western blotting and immunohistochemistry were performed to detect SELENBP1 expression in independent sets of tissues of bronchial epithelial carcinogenesis, and ability of SELENBP1 for discriminating NBE (normal bronchial epithelium) from preneoplastic lesions from invasive LSCC was evaluated. The effects of SELENBP1 downregulation on the susceptibility of benzo(a)pyrene (B[a]P)-induced human bronchial epithelial cell transformation were determined.
102 differentially expressed proteins were identified by quantitative proteomics, and SELENBP1 was found and confirmed being progressively decreased in the human bronchial epithelial carcinogenic process. The sensitivity and specificity of SELENBP1 were 80% and 79% in discriminating NBE from preneoplastic lesions, 79% and 82% in discriminating NBE from invasive LSCC, and 77% and 71% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, knockdown of SELENBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation.
The present data shows for the first time that decreased SELENBP1 is an early event in LSCC, increases B[a]P-induced human bronchial epithelial cell transformation, and might serve as a novel potential biomarker for early detection of LSCC.
PMCID: PMC3747066  PMID: 23977169
19.  Isolated complete caudate lobectomy for hepatic tumor of the anterior transhepatic approach: surgical approaches and perioperative outcomes 
How to resect the caudate lobe safely is a major challenge to current liver surgery which requires further study.
Nine cases (6 hepatic cell carcinoma, 2 cavernous hemangioma and 1 intrahepatic cholangiocacinoma) were performed using the anterior transhepatic approach in the isolated complete caudate lobe resection. During the operation, we used the following techniques: the intraoperative routine use of Peng’s multifunction operative dissector (PMOD), inflow and outflow of hepatic blood control, low central venous pressure and selective use of liver hanging maneuver.
There were no perioperative deaths observed after the operation. The median operating time was 230 ± 43.6 minutes, the median intraoperative blood loss was 606.6 ± 266.3 ml and the median length of postoperative hospital stay was 12.6 ± 2.9 days. The incidence of complications was 22.22% (2/9).
PMOD and “curettage and aspiration” technique can be of great help of in the dissection of vessels and parenchyma, clearly making caudate lobe resection safer, easier and faster.
PMCID: PMC3765966  PMID: 23947911
20.  Surgical management of patients with bowel obstructions secondary to gastric cancer 
AIM: To assess whole-body fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the management of small bowel obstructions (SBOs) secondary to gastric cancer and its role in treatment strategies.
METHODS: The medical records of all of the patients who were admitted for an intestinal obstruction after curative resection for gastric cancer were retrospectively reviewed. PET/CT was performed before a clinical treatment strategy was established for each patient. The patients were divided into 2 groups: patients with no evidence of a tumor recurrence and patients with evidence of a tumor recurrence. Tumor recurrences included a local recurrence, peritoneal carcinomatosis or distant metastases. The primary endpoint was the 1-year survival rate, and other variables included patient demographics, the length of hospital stay, complications, and mortality.
RESULTS: The median time between a diagnosis of gastric cancer and the detection of a SBO was 1.4 years. Overall, 31 of 65 patients (47.7%) had evidence of a tumor recurrence on the PET/CT scan, which was the only factor that was associated with poor survival. Open and close surgery was the main type of surgical procedure reported for the patients with tumor recurrences. R0 resections were performed in 2 patients, including 1 who underwent combined adjacent organ resection. In the group with no evidence of a tumor recurrence on PET/CT, bowel resections were performed in 7 patients, adhesiolysis was performed in 7 patients, and a bypass was performed in 1 patient. The 1-year survival curves according to PET/CT evidence of a tumor recurrence vs no PET/CT evidence of a tumor recurrence were significantly different, and the 1-year survival rates were 8.8% vs 93.5%, respectively. There were no significant differences (P = 0.71) in the 1-year survival rates based on surgical vs nonsurgical management (0% with nonoperative treatment vs 20% after exploratory laparotomy).
CONCLUSION: 18F-FDG PET/CT can be used to identify the causes of bowel obstructions in patients with a history of gastric cancer, and this method is useful for planning the surgical management of these patients.
PMCID: PMC3725382  PMID: 23901233
Positron emission tomography/computed tomography; Small bowel obstructions; Gastric cancer; Clinical treatment strategy
21.  Impact of being overweight on the surgical outcomes of patients with gastric cancer: A meta-analysis 
AIM: To investigate the effect of being overweight on the surgical results of patients with gastric cancer.
METHODS: Comprehensive electronic searches of the PubMed, Web of Science, and Cochrane Library databases were conducted. Studies were identified that included patients with surgical complications from gastric cancer who were classified as normal weight [body mass index (BMI) < 25 kg/m2] or overweight (BMI ≥ 25 kg/m2). The operative time, retrieved lymph nodes, blood loss, and long-term survival were analyzed. A subgroup analysis was conducted based on whether patients received laparoscopic or open gastrectomy procedures. All statistical tests were performed using ReviewerManager 5.1.2 software.
RESULTS: This meta-analysis included 23 studies with 20678 patients (15781 with BMI < 25 kg/m2; 4897 with BMI ≥ 25 kg/m2). Overweight patients had significantly increased operation times [MD: -29.14; 95%CI: -38.14-(-20.21); P < 0.00001], blood loss [MD: -194.58; 95%CI: -314.21-(-74.95); P = 0.001], complications (RR: 0.75; 95%CI: 0.66-0.85; P < 0.00001), anastomosis leakages (RR: 0.59; 95%CI: 0.42-0.82; P = 0.002), and pancreatic fistulas (RR: 0.486; 95%CI: 0.34-0.63; P < 0.00001), whereas lymph node retrieval was decreased significantly in the overweight group (MD: 1.69; 95%CI: 0.75-2.62; P < 0.0001). In addition, overweight patients had poorer long-term survival (RR: 1.14; 95%CI: 1.07-1.20; P < 0.0001). No significant difference was detected for the mortality and length of hospital stay.
CONCLUSION: This meta-analysis demonstrates that a high BMI not only increases the surgical difficulty and complications but also impairs the long-term survival of patients with gastric cancer.
PMCID: PMC3725387  PMID: 23901238
Overweight; Body mass index; Gastric cancer; Gastrectomy
22.  Curcumin induces apoptosis in gallbladder carcinoma cell line GBC-SD cells 
Gallbladder carcinoma is a malignant tumor with a very low 5-year survival rate because of the difficulty with its early diagnosis and the very poor prognosis of the advanced cancer state. The aims of this study were to determine whether curcumin could induce the apoptosis of a gallbladder carcinoma cell line, GBC-SD, and to clarify its related mechanism.
First, the anti-proliferative activities of curcumin-treated and untreated GBC-SD cells were determined using the MTT and colony formation assays. Then, the early apoptosis of cells was detected by the annexin V/propidium iodide double-staining assay and Hoechst 33342 staining assay. Detection of mitochondrial membrane potential was used to validate the ability of curcumin on inducing apoptosis in GBC-SD cells. Cell cycle changes were detected by flow cytometric analysis. Finally, the expressions of the apoptosis-related proteins or genes caspase-3, PARP, Bcl-2, and Bax were analyzed by western blot and quantitative real time PCR assay. Statistical analyses were performed using the Student’s t-test for comparison of the results obtained from cells with or without curcumin treatment.
The MTT assay revealed that curcumin had induced a dose- and a time-dependent decrease in cell viability. Colony counting indicated that curcumin had induced a dose-dependent decrease in the colony formation ability in GBC-SD cells. Cells treated with curcumin were arrested at the S phase, according to the flow cytometric analysis. A significant induction of both the early and late phases of apoptosis was shown by the annexin V-FITC and PI staining. Morphological changes in apoptotic cells were also found by the Hoechst 33342 staining. After treatment with curcumin fluorescence shifted from red to green as ΔΨm decreased. Furthermore, western blot and quantitative real time PCR assays demonstrated that the curcumin induced apoptosis in GBC-SD cells by regulating the ratio of Bcl-2/Bax and activating the expression of cleaved caspase-3.
Taken together, the results indicate that curcumin may be a potential agent for the treatment of gallbladder cancer.
PMCID: PMC3733655  PMID: 23802572
Curcumin; Gallbladder carcinoma GBC-SD cell; Proliferation; Apoptosis
23.  Duct-to-duct biliary reconstruction after radical resection of Bismuth IIIa hilar cholangiocarcinoma 
At present, radical resection remains the only effective treatment for patients with hilar cholangiocarcinoma. The surgical approach for R0 resection of hilar cholangiocarcinoma is complex and diverse, but for the biliary reconstruction after resection, almost all surgeons use Roux-en-Y hepaticojejunostomy. A viable alternative to Roux-en-Y reconstruction after radical resection of hilar cholangiocarcinoma has not yet been proposed. We report a case of performing duct-to-duct biliary reconstruction after radical resection of Bismuth IIIa hilar cholangiocarcinoma. End-to-end anastomosis between the left hepatic duct and the distal common bile duct was used for the biliary reconstruction, and a single-layer continuous suture was performed along the bile duct using 5-0 prolene. The patient was discharged favorably without biliary fistula 2 wk later. Evidence for tumor recurrence was not found after an 18 mo follow-up. Performing bile duct end-to-end anastomosis in hilar cholangiocarcinoma can simplify the complex digestive tract reconstruction process.
PMCID: PMC3632000  PMID: 23613642
Hilar cholangiocarcinoma; Biliary reconstruction; Duct-to-duct; Radical resection; Digestive tract reconstruction; Hepaticojejunostomy; Bile duct anastomosis
24.  The Patatin-Containing Phospholipase A pPLAIIα Modulates Oxylipin Formation and Water Loss in Arabidopsis thaliana 
Molecular Plant  2012;5(2):452-460.
The patatin-related phospholipase A (pPLA) hydrolyzes membrane glycerolipids to produce monoacyl compounds and free fatty acids. Phospholipids are cleaved by pPLAIIα at the sn-1 and sn-2 positions, and galactolipids, including those containing oxophytodienoic acids, can also serve as substrates. Ablation of pPLAIIα decreased lysophosphatidylcholine and lysophosphatidylethanolamine levels, but increased free linolenic acid. pPLAIIα-deficient plants displayed a higher level of jasmonic acid and methyl jasmonate, as well as the oxylipin-biosynthetic intermediates 13-hydroperoxylinolenic acid and 12-oxophytodienoic acid than wild-type (WT) plants. The expression of genes involved in oxylipin production was also higher in the pPLAIIα-deficient mutant than in WT plants. The mutant plants lost water more quickly than WT plants. The stomata of WT and mutant plants responded similarly to abscisic acid. In response to desiccation, the mutant and WT leaves produced abscisic acid at the same rate, but, after 4 h of desiccation, the jasmonic acid level was much higher in mutant than WT leaves. These results indicate that pPLAIIα negatively regulates oxylipin production and suggest a role in the removal of oxidatively modified fatty acids from membranes.
PMCID: PMC3351082  PMID: 22259021
patatin-related phospholipase A; oxidative modified lipids; jasmonate synthesis; water loss; Arabidopsis thaliana
25.  Comparative genomic analyses of Mycoplasma hyopneumoniae pathogenic 168 strain and its high-passaged attenuated strain 
BMC Genomics  2013;14:80.
Mycoplasma hyopneumoniae is the causative agent of porcine enzootic pneumonia (EP), a mild, chronic pneumonia of swine. Despite presenting with low direct mortality, EP is responsible for major economic losses in the pig industry. To identify the virulence-associated determinants of M. hyopneumoniae, we determined the whole genome sequence of M. hyopneumoniae strain 168 and its attenuated high-passage strain 168-L and carried out comparative genomic analyses.
We performed the first comprehensive analysis of M. hyopneumoniae strain 168 and its attenuated strain and made a preliminary survey of coding sequences (CDSs) that may be related to virulence. The 168-L genome has a highly similar gene content and order to that of 168, but is 4,483 bp smaller because there are 60 insertions and 43 deletions in 168-L. Besides these indels, 227 single nucleotide variations (SNVs) were identified. We further investigated the variants that affected CDSs, and compared them to reported virulence determinants. Notably, almost all of the reported virulence determinants are included in these variants affected CDSs. In addition to variations previously described in mycoplasma adhesins (P97, P102, P146, P159, P216, and LppT), cell envelope proteins (P95), cell surface antigens (P36), secreted proteins and chaperone protein (DnaK), mutations in genes related to metabolism and growth may also contribute to the attenuated virulence in 168-L. Furthermore, many mutations were located in the previously described repeat motif, which may be of primary importance for virulence.
We studied the virulence attenuation mechanism of M. hyopneumoniae by comparative genomic analysis of virulent strain 168 and its attenuated high-passage strain 168-L. Our findings provide a preliminary survey of CDSs that may be related to virulence. While these include reported virulence-related genes, other novel virulence determinants were also detected. This new information will form the foundation of future investigations into the pathogenesis of M. hyopneumoniae and facilitate the design of new vaccines.
PMCID: PMC3626624  PMID: 23384176
Mycoplasma hyopneumoniae; Genetic variation; Virulence attenuation; Sequence analysis; Repetitive sequences; Virulence factors

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