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1.  Long-term outcomes after radical gastrectomy in gastric cancer patients with overt bleeding 
World Journal of Gastroenterology  2015;21(47):13316-13324.
AIM: To investigate the difference in long-term outcomes between gastric cancer patients with and without a primary symptom of overt bleeding (OB).
METHODS: Consecutive patients between January 1, 2007 and March 1, 2012 were identified retrospectively by reviewing a gastric cancer database at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. A follow-up examination was performed on patients who underwent a radical gastrectomy. OB due to gastric cancer included hematemesis, melena or hematochezia, and gastric cancer was confirmed as the source of bleeding by endoscopy. Patients without OB were defined as cases with occult bleeding and those with other initial presentations, including epigastric pain, weakness, weight loss and obstruction. The 3-year overall survival (OS) rate, age, gender, AJCC T stage, AJCC N stage, overall AJCC stage, tumor size, histological type, macroscopic (Borrmann) type, lymphovascular invasion and R status were compared between patients with and without OB. Moreover, we carried out a subgroup analysis based on tumor location (upper, middle and lower).
RESULTS: We identified 939 patients. Of these, 695 (74.0%) were hospitalized for potential radical gastrectomy and another 244 received palliative resection, rerouting of the gastrointestinal tract, chemotherapy, radiotherapy or no treatment due to the presence of unresectable tumors. Notably, there was no significant difference in the percentage of OB patients between resectable cases and unresectable cases (20.3% vs 22.1%, P = 0.541). Follow-up examination was performed on 653 patients (94%) who underwent radical gastrectomy. We found no significant difference in 3-year OS rate (68.2% vs 61.2%, P = 0.143) or clinicopathological characteristics (P > 0.05) between these patients with and without OB. Subgroup analysis based on tumor location showed that the 3-year OS rate of upper gastric cancer was significantly higher in patients with OB (84.6%) than in those without OB (48.1%, P < 0.01) and that AJCC stages I-II (56.4% vs 35.1%, P = 0.017) and T1-T2 category tumors (30.8% vs 13%, P = 0.010) were more frequent in patients with OB than in those without OB. There was no significant difference in 3-year OS rate or clinicopathological characteristics between patients with and without OB (P > 0.05) for middle or lower gastric cancer.
CONCLUSION: Upper gastric cancer patients with OB exhibited tumors at less advanced pathological stages and had a better prognosis than upper gastric cancer patients without OB.
doi:10.3748/wjg.v21.i47.13316
PMCID: PMC4679764  PMID: 26715815
Gastric cancer; Overt bleeding; Tumor location; Prognosis; Pathological stage
2.  Frequency and risk factor analysis of cognitive and anxiety-depressive disorders in patients with amyotrophic lateral sclerosis/motor neuron disease 
Objectives
To examine the frequency and risk factors of cognitive and anxiety-depressive disorders in patients with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND).
Methods
This was an observational study of 100 ALS/MND patients treated at our hospital outpatient and inpatient departments between January 2009 and April 2010 and 100 matched healthy controls. Subjects were surveyed using Mini Mental State Examination (MMSE), Zung Self-Rating Anxiety Scale (SAS), and Zung Self-Rating Depression Scale (SDS). Patient neurological status was graded by the ALS Functional Rating Scale (ALSFRS). Multivariate linear regression was used to identify factors associated with the MMSE, SAS, SDS, and ALSFRS scores.
Results
Patients had significantly lower MMSE scores than controls (P<0.05). MMSE score did not differ by sex or age (<50/≥50 years) (P>0.05). Patients with higher educational level (college and above), shorter disease course (<2 years), and lower ALSFRS score (<20) had significantly higher MMSE scores (all P<0.05). Multivariate analysis revealed that higher education, shorter disease course, and lower ALSFRS score were independent predictors of better cognitive function (higher MMSE score). Patients had significantly higher mean SAS and SDS total scores than controls (both P<0.05), indicating higher subjective anxiety and depression. Female patients, patients with higher education, and those with higher ALSFRS scores had significantly higher SAS and SDS scores (all P<0.05). Age, occupation, diagnostic classification, disease duration, and disease awareness did not influence SAS or SDS scores. Multivariate analysis indicated that lower education and lower ALSFRS were protective factors against anxiety and depression.
Conclusion
The frequency of anxiety-depressive disorders was high among patients with ALS/MND. High educational level, short course of disease, and lower ALSFRS were associated with preserved cognitive function. Female sex, higher education, and lower ALSFRS score conferred a greater risk of anxiety and depression. Tailored pharmacotherapy and psychological interventions may help in reducing anxiety and depression in these patients.
doi:10.2147/NDT.S90520
PMCID: PMC4639547  PMID: 26604769
motor neuron disease; amyotrophic lateral sclerosis; cross-sectional study; anxiety; depression
3.  Zero-profile implant (Zero-p) versus plate cage benezech implant (PCB) in the treatment of single-level cervical spondylotic myelopathy 
Background
Anterior cervical discectomy and fusion is the golden standard for anterior surgery treating elderly cervical degenerative disease, but the previous implant has some problems such as looseness, translocation, sinking and dysphagia, So Zero-p implant and PCB implant have been developed to decrease the complications.
Methods
The clinical data of 57 patients with single level cervical spondylotic myelopathy were retrospectively analyzed. 27 patients adopting Zero-p interbody fusion cage as implant (Zero-p group) and 30 patients adopting integrated plate cage benezech (PCB) as implant (PCB group) from January 2010 to October 2012. Observe whether are differences between the two groups of patients on operation time, intraoperatve blood loss,Japanese Orthopaedic Association (JOA) scores before and after operation, intervertebral height, cervical physiological curvature, fusion rate, Postoperative dysphagia rate and complications.
Results
Zero-p group’s operation time is 98.2 + 15.2 min and its intraoperatve blood loss is 88.2 + 12.9 ml, both of which are lower than those of PCB group (109.8 + 16.9 min,95.2 + 11.6 ml ), so their differences are statistically significant (P < 0.05). The two groups’ JOA scores 3 months after operation and in the last follow-up are significantly higher than those before operation, so the differences are statistically significant (P < 0.05). Coob angle 3 months after operation and in the last follow-up improves obviously compared with before operation, so the difference is statistically significant (P < 0.05). The two groups’ operation segments intervertebral height 3 months after operation and in the last follow-up improves obviously compared with before operation, so the difference is statistically significant (P < 0.05) Zero-p group has one patient with dysphagia after operation and PCB group has four patients with dysphagia after operation, so there is no statistical differences between the two groups on dysphagia rate (P > 0.05, P = 0.415). PCB group has two patients with screws backing out and two patients with hoarseness after operation, the two groups’ operation segments all saw bony union in the last follow-up. Zero-p group postoperative complications are lower than PCB group (P < 0.05, P = 0.044).
Conclusions
Zero-profile implant and PCB implant both achieved good clinical effects on the treatment of cervical spondylotic myelopathy, the two groups both saw bony union in operation segments, but Zero-profile implant has the advantages of easy operation, short operation time, less intraoperatve blood loss and less complications.
doi:10.1186/s12891-015-0746-4
PMCID: PMC4603765  PMID: 26459625
Intervertebral fusion device; Spinal fusion; Efficacy; Internal fixation; Cervical spondylotic myelopathy
4.  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.
doi:10.1038/ncomms8696
PMCID: PMC4510689  PMID: 26165855
5.  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.
doi:10.1371/journal.pone.0131631
PMCID: PMC4498733  PMID: 26161960
6.  Sarcomatoid carcinoma of the stomach: A case report and literature review 
Oncology Letters  2015;10(3):1385-1389.
Sarcomatoid carcinoma of the stomach is a rare type of malignant tumor, characterized by distinct cellular morphology. This type of tumor is even more rare in giant size. The present study reports a case of giant sarcomatoid carcinoma, which developed in the distal stomach. A 49-year-old male underwent medical investigation for gastrointestinal hemorrhage. Endoscopic examination, computed tomography (CT) and positron emission tomography-CT scan identified a giant neoplasm, which involved the gastric antrum and body, gallbladder and hepatic flexure of the colon. Surgery was performed to excise the tumor, which was ~14×13×8 cm in size. A diagnosis of sarcomatoid carcinoma was made since the tumor was positive for epithelial markers, even within the mesenchymal elements. To the best of our knowledge, only 5 cases of sarcomatoid carcinoma of the stomach have been previously reported, and a tumor that has been able to be resected despite such a large size has never been reported.
doi:10.3892/ol.2015.3460
PMCID: PMC4533308  PMID: 26622678
immunohistochemistry; sarcomatoid carcinoma; stomach
7.  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.
doi:10.2147/DDDT.S84448
PMCID: PMC4472077  PMID: 26109845
oleanolic acid; gallbladder carcinoma; apoptosis; cell cycle arrest; mitochondrial pathway
8.  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
doi:10.4161/cbt.28584
PMCID: PMC4049796  PMID: 24658096
gallbladder carcinoma; MALAT1; lncRNA; ERK; MAPK; proliferation; metastasis
9.  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.
doi:10.1155/2015/343201
PMCID: PMC4339862  PMID: 25763089
10.  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.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/s12943-014-0276-y
PMCID: PMC4320842  PMID: 25623055
Gallbladder cancer; SPOCK1; Tumor progression; RNA interference; Epithelial-mesenchymal transition
11.  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.
doi:10.1371/journal.pone.0114851
PMCID: PMC4305301  PMID: 25617627
12.  Identification of Putative Carboxylesterase and Glutathione S-transferase Genes from the Antennae of the Chilo suppressalis (Lepidoptera: Pyralidae) 
Journal of Insect Science  2015;15(1):103.
In insects, rapid degradation of odorants in antennae is extremely important for the sensitivity of olfactory receptor neurons. Odorant degradation in insect antennae is mediated by multiple enzymes, especially the carboxylesterases (CXEs) and glutathione S-transferases (GSTs). The Asiatic rice borer, Chilo suppressalis, is an economically important lepidopteran pest which causes great economic damage to cultivated rice crops in many Asian countries. In this study, we identified 19 putative CXE and 16 GST genes by analyzing previously constructed antennal transcriptomes of C. suppressalis. BLASTX best hit results showed that these genes are most homologous to their respective orthologs in other lepidopteran species. Phylogenetic analyses revealed that these CXE and GST genes were clustered into various clades. Reverse-transcription quantitative polymerase chain reaction assays showed that three CXE genes (CsupCXE8, CsupCXE13, and CsupCXE18) are antennae-enriched. These genes are candidates for involvement in odorant degradation. Unexpectedly, none of the GST genes were found to be antennae-specific. Our results pave the way for future researches of the odorant degradation mechanism of C. suppressalis at the molecular level.
doi:10.1093/jisesa/iev082
PMCID: PMC4677501  PMID: 26198868
Chilo suppressalis; odorant-degrading enzyme; phylogenetic analysis; expression pattern
13.  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
14.  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
15.  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.
doi:10.1098/rspb.2013.1905
PMCID: PMC3779338  PMID: 24048158
palynology; Poaceae; microscopy; pattern analysis; computational image analysis
16.  Ursolic acid induces cell cycle arrest and apoptosis of gallbladder carcinoma cells 
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/s12935-014-0096-6
PMCID: PMC4224689  PMID: 25383044
Ursolic acid; Gallbladder cancer; Proliferation; Cell cycle; Apoptosis; Mitochondrial-mediated pathway
17.  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
18.  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
19.  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.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1471-2407-14-566
PMCID: PMC4131047  PMID: 25096189
Gallbladder cancer; Coagulation assays; Hyperfibrinogenemia; Prognosis
20.  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.
doi:10.3390/ijerph110403995
PMCID: PMC4025041  PMID: 24736684
China; health effect; neurological deficit; pesticide overuse
21.  Combined use of non-biological artificial liver treatments for patients with acute liver failure complicated by multiple organ dysfunction syndrome 
BACKGROUND:
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).
METHODS:
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.
RESULTS:
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).
CONCLUSION:
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.
doi:10.5847/wjem.j.issn.1920-8642.2014.03.010
PMCID: PMC4163812  PMID: 25225587
Severe acute liver failure; Artificial liver; Plasma exchange; Hemoperfusion; Continuous veno-venous hemodiafiltration
22.  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.
Aim:
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.
Methods:
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.
Results:
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).
Conclusion:
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.
doi:10.1038/aps.2013.99
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
23.  The Function and Significance of SELENBP1 Downregulation in Human Bronchial Epithelial Carcinogenic Process 
PLoS ONE  2013;8(8):e71865.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1371/journal.pone.0071865
PMCID: PMC3747066  PMID: 23977169
24.  Isolated complete caudate lobectomy for hepatic tumor of the anterior transhepatic approach: surgical approaches and perioperative outcomes 
Background
How to resect the caudate lobe safely is a major challenge to current liver surgery which requires further study.
Methods
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.
Results
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).
Conclusion
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.
doi:10.1186/1477-7819-11-197
PMCID: PMC3765966  PMID: 23947911
25.  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.
doi:10.3748/wjg.v19.i28.4559
PMCID: PMC3725382  PMID: 23901233
Positron emission tomography/computed tomography; Small bowel obstructions; Gastric cancer; Clinical treatment strategy

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