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1.  Automated characterization of flowering dynamics in rice using field-acquired time-series RGB images 
Plant Methods  2015;11:7.
Flowering (spikelet anthesis) is one of the most important phenotypic characteristics of paddy rice, and researchers expend efforts to observe flowering timing. Observing flowering is very time-consuming and labor-intensive, because it is still visually performed by humans. An image-based method that automatically detects the flowering of paddy rice is highly desirable. However, varying illumination, diversity of appearance of the flowering parts of the panicles, shape deformation, partial occlusion, and complex background make the development of such a method challenging.
We developed a method for detecting flowering panicles of rice in RGB images using scale-invariant feature transform descriptors, bag of visual words, and a machine learning method, support vector machine. Applying the method to time-series images, we estimated the number of flowering panicles and the diurnal peak of flowering on each day. The method accurately detected the flowering parts of panicles during the flowering period and quantified the daily and diurnal flowering pattern.
A powerful method for automatically detecting flowering panicles of paddy rice in time-series RGB images taken under natural field conditions is described. The method can automatically count flowering panicles. In application to time-series images, the proposed method can well quantify the daily amount and the diurnal changes of flowering during the flowering period and identify daily peaks of flowering.
Electronic supplementary material
The online version of this article (doi:10.1186/s13007-015-0047-9) contains supplementary material, which is available to authorized users.
PMCID: PMC4336727
Time-series RGB image; SIFT; BoVWs; SVM
2.  Postoperative recurrence of desmoid tumors: clinical and pathological perspectives 
The clinical features and the pathological changes of desmoid tumors were studied to point out the key factors affecting the recurrence.
The clinical data and specimens of 56 patients who underwent desmoid tumor resection from 2003 to 2008 were reviewed. Possible clinical factors related to the postoperative recurrence were analyzed statistically. The specimens round the lesions were studied histopathologically.
The overall recurrence rate was 39.3%. The postoperative recurrence rate of the patients with negative surgical margins and no tumor invasion of the major vessels and nerves was low (P < 0.05). However, the desmoid tumors could destroy the cortical bone and invade the medullary cavity.
Desmoid tumors were pathologically benign, which could extensively invade tissues around the lesions. The invasion of major vessels and nerves and quality of surgical margins are the key factors for the high postoperative recurrence rate.
PMCID: PMC4329213
Histopathology; Immunohistochemistry; Tumor resection
3.  A Novel Energy-Efficient Pyrolysis Process: Self-pyrolysis of Oil Shale Triggered by Topochemical Heat in a Horizontal Fixed Bed 
Scientific Reports  2015;5:8290.
This paper proposes a novel energy-efficient oil shale pyrolysis process triggered by a topochemical reaction that can be applied in horizontal oil shale formations. The process starts by feeding preheated air to oil shale to initiate a topochemical reaction and the onset of self-pyrolysis. As the temperature in the virgin oil shale increases (to 250–300°C), the hot air can be replaced by ambient-temperature air, allowing heat to be released by internal topochemical reactions to complete the pyrolysis. The propagation of fronts formed in this process, the temperature evolution, and the reaction mechanism of oil shale pyrolysis in porous media are discussed and compared with those in a traditional oxygen-free process. The results show that the self-pyrolysis of oil shale can be achieved with the proposed method without any need for external heat. The results also verify that fractured oil shale may be more suitable for underground retorting. Moreover, the gas and liquid products from this method were characterised, and a highly instrumented experimental device designed specifically for this process is described. This study can serve as a reference for new ideas on oil shale in situ pyrolysis processes.
PMCID: PMC4319157  PMID: 25656294
4.  The role of Sec3p in secretory vesicle targeting and exocyst complex assembly 
Molecular Biology of the Cell  2014;25(23):3813-3822.
The exocyst has been speculated to mediate the tethering of secretory vesicles to the plasma membrane. However, there has been no direct experimental evidence for this notion. An ectopic targeting strategy is used to provide experimental support for this model and investigate the regulators of exocyst assembly and vesicle targeting.
During membrane trafficking, vesicular carriers are transported and tethered to their cognate acceptor compartments before soluble N-ethylmaleimide–sensitive factor attachment protein (SNARE)-mediated membrane fusion. The exocyst complex was believed to target and tether post-Golgi secretory vesicles to the plasma membrane during exocytosis. However, no definitive experimental evidence is available to support this notion. We developed an ectopic targeting assay in yeast in which each of the eight exocyst subunits was expressed on the surface of mitochondria. We find that most of the exocyst subunits were able to recruit the other members of the complex there, and mistargeting of the exocyst led to secretion defects in cells. On the other hand, only the ectopically located Sec3p subunit is capable of recruiting secretory vesicles to mitochondria. Our assay also suggests that both cytosolic diffusion and cytoskeleton-based transport mediate the recruitment of exocyst subunits and secretory vesicles during exocytosis. In addition, the Rab GTPase Sec4p and its guanine nucleotide exchange factor Sec2p regulate the assembly of the exocyst complex. Our study helps to establish the role of the exocyst subunits in tethering and allows the investigation of the mechanisms that regulate vesicle tethering during exocytosis.
PMCID: PMC4230786  PMID: 25232005
5.  miRNA-30 Family Inhibition Protects Against Cardiac Ischemic Injury by Regulating Cystathionine-γ-Lyase Expression 
Antioxidants & Redox Signaling  2015;22(3):224-240.
Aims: Myocardial infarction (MI) is a leading cause of death globally. MicroRNAs (miRNAs) have been identified as a novel class of MI injury regulators. Hydrogen sulfide (H2S) is a gaseous signaling molecule that regulates cardiovascular function. The purpose of this study was to explore the role of the miR-30 family in protecting against MI injury by regulating H2S production. Results: The expression of miR-30 family was upregulated in the murine MI model as well as in the primary cardiomyocyte hypoxic model. However, the cystathionine-γ-lyase (CSE) expression was significantly decreased. The overexpression of miR-30 family decreased CSE expression, reduced H2S production, and then aggravated hypoxic cardiomyocyte injury. In contrast, silencing the whole miR-30 family can protect against hypoxic cell injury by elevating CSE and H2S level. Nonetheless, the protective effect was abolished by cotransfecting with CSE-siRNA. Systemic delivery of a locked nucleic acid (LNA)-miR-30 family inhibitor correspondingly increased CSE and H2S level, then reduced infarct size, decreased apoptotic cell number in the peri-infarct region, and improved cardiac function in response to MI. However, these cardioprotective effects were absent in CSE knockout mice. MiR-30b overexpression in vivo aggravated MI injury because of H2S reduction, and this could be rescued by S-propargyl-cysteine (SPRC), which is a novel modulator of CSE, or further exacerbated by propargylglycine (PAG), which is a selective inhibitor of CSE. Innovation and Conclusion: Our findings reveal a novel molecular mechanism for endogenous H2S production in the heart at the miRNA level and demonstrate the therapeutic potential of miR-30 family inhibition for ischemic heart diseases by increasing H2S production. Antioxid. Redox Signal. 22, 224–240.
PMCID: PMC4283074  PMID: 25203395
6.  siRNA induces gelsolin gene transcription activation in human esophageal cancer cell 
Scientific Reports  2015;5:7901.
Recent studies show that targeting gene promoter or 3′ terminal regions of mRNA with siRNA induces target gene transcription. However, the ability of exon-targeting siRNA to affect transcription has yet to be demonstrated. We designed and synthesized siRNA against various exons in the gelsolin gene (GSN) to knockdown GSN transcript in KYSE150 and KYSE450 cells. Surprisingly, we found that siGSN-2, targeting the GSN twelfth exon, induced GSN gene transcription detected by real time RT-PCR. An siGSN-2 co-precipitation assay was performed and H3 histone, previously shown to correlate with gene transcription, was detected in the siGSN-2 pull-down pellet. However, H3 histone was not detected in an siGSN-1-precipitated pellet, which resulted in GSN knockdown. In addition, siGSN-2 decreased stress fibers, lamellipodia and filopodia, demonstrating that siGSN-2 induced GSN transcription activation and exerted biological function. In conclusion, our finds reveal siRNA, which is derived from target gene exon, can form the complex with H3 histone to be involved in the regulation of gene expression.
PMCID: PMC4298738  PMID: 25600697
7.  Daphnoretin-induced apoptosis in HeLa cells: a possible mitochondria-dependent pathway 
Cytotechnology  2013;66(1):51-61.
Daphnoretin is a bicoumarin compound isolated from a natural product, Wikstroemia indica, which has been used to treat many diseases. It has strong antiviral and anti-tumor activities. Taking the anti-tumor activity of daphnoretin as a starting point, the present study aimed to test the pro-apoptotic effect of daphnoretin and its underlying mechanism in HeLa cells. The inhibitory effects of daphnoretin on viability and proliferation of HeLa cells were determined by the MTT assay. Daphnoretin-induced apoptotic morphological changes were analyzed by mitochondrial membrane potential and Hoechst staining. The number and stage of apoptotic HeLa cells were determined by flow cytometry. Gene expression was determined by reverse-transcription polymerase chain reaction. Protein expression was determined by western blot. The caspase activity of HeLa cells was detected by a caspase-3 and caspase-9 colorimetric assay kit. We found that daphnoretin significantly inhibited HeLa cells’ viability by the MTT assay and flow cytometry. The nuclei of the apoptotic cells exhibited strong, blue fluorescence in Hoechst staining. Bax mRNA and protein levels were increased while bcl-2 mRNA levels were decreased after daphnoretin treatment. Daphnoretin also activated both caspase-3 and caspase-9. These findings suggest that daphnoretin promotes apoptosis of HeLa cells in a mitochondria-mediated way. Daphnoretin therefore has potential to be a promising drug to treat uterine cervix cancer.
PMCID: PMC3886545  PMID: 24091880
Daphnoretin; Anti-tumor; Apoptosis; Mitochondria; HeLa cells
8.  Sarcoplasmic reticulum Ca2+ release channel ryanodine receptor (RyR2) plays a crucial role in aconitine-induced arrhythmias 
Biochemical pharmacology  2008;75(11):2147-2156.
The present study established a model of RyR2 knockdown cardiomyocytes and elucidated the role of RyR2 in aconitine-induced arrhythmia. Cardiomyocytes were obtained from hearts of neonatal Sprague–Dawlay rats. siRNAs were used to down-regulate RyR2 expression. Reduction of RyR2 expression was documented by RT-PCR, western blot, and immunofluorescence. Ca2+ signals were investigated by measuring the relative intracellular Ca2+ concentration, spontaneous Ca2+ oscillations, caffeine-induced Ca2+ release, and L-type Ca2+ currents. In normal cardiomyocytes, steady and periodic spontaneous Ca2+ oscillations were observed, and the baseline [Ca2+]i remained at the low level. Exposure to 3 μM aconitine increased the frequency and decreased the amplitude of Ca2+ oscillations; the baseline [Ca2+]i and the level of caffeine-induced Ca2+ release were increased but the L-type Ca2+ currents were inhibited after application of 3 μM aconitine for 5 min. In RyR2 knockdown cardiomyocytes, the steady and periodic spontaneous Ca2+ oscillations almost disappeared, but were re-induced by aconitine without affecting the baseline [Ca2+]i level; the level of caffeine-induced Ca2+ release was increased but L-type Ca2+ currents were inhibited. Alterations of RyR2 are important consequences of aconitine-stimulation and activation of RyR2 appear to have a direct relationship with aconitine-induced arrhythmias. The present study demonstrates a potential method for preventing aconitine-induced arrhythmias by inhibiting Ca2+ leakage through the sarcoplasmic reticulum RyR2 channel.
PMCID: PMC4280015  PMID: 18439986
RyR2; Knockdown; Aconitine; Arrhythmia; Excitation–contraction coupling
9.  Complementary Roles for Biomarkers of Biomechanical Strain ST2 and N-Terminal Prohormone B-Type Natriuretic Peptide in Patients With ST-Elevation Myocardial Infarction 
Circulation  2008;117(15):1936-1944.
ST2 is a member of the interleukin-1 receptor family with a soluble form that is markedly upregulated on application of biomechanical strain to cardiac myocytes. Circulating ST2 levels are elevated in the setting of acute myocardial infarction, but the predictive value of ST2 independent of traditional clinical factors and of an established biomarker of biomechanical strain, N-terminal prohormone B-type natriuretic peptide (NT-proBNP), has not been established.
Methods and Results
We measured ST2 at baseline in 1239 patients with ST-elevation myocardial infarction from the CLopidogrel as Adjunctive ReperfusIon TherapY–Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28) trial. Per trial protocol, patients were to undergo coronary angiography after 2 to 8 days and were followed up for 30 days for clinical events. In contrast to NT-proBNP, ST2 levels were independent of clinical factors potentially related to chronic increased left ventricular wall stress, including age, hypertension, prior myocardial infarction, and prior heart failure; levels also were only modestly correlated with NT-proBNP (r=0.14). After adjustment for baseline characteristics and NT-proBNP levels, an ST2 level above the median was associated with a significantly greater risk of cardiovascular death or heart failure (third quartile: adjusted odds ratio, 1.42; 95% confidence interval, 0.68 to 3.57; fourth quartile: adjusted odds ratio, 3.57; 95% confidence interval, 1.87 to 6.81; P<0.0001 for trend). When both ST2 and NT-proBNP were added to a model containing traditional clinical predictors, the c statistic significantly improved from 0.82 (95% confidence interval, 0.77 to 0.87) to 0.86 (95% confidence interval, 0.81 to 0.90) (P=0.017).
In ST-elevation myocardial infarction, high baseline ST2 levels are a significant predictor of cardiovascular death and heart failure independently of baseline characteristics and NT-proBNP, and the combination of ST2 and NT-proBNP significantly improves risk stratification. These data highlight the prognostic value of multiple, complementary biomarkers of biomechanical strain in ST-elevation myocardial infarction.
PMCID: PMC4273564  PMID: 18378613
myocardial infarction; natriuretic peptides; prognosis
10.  Three-field vs two-field lymph node dissection for esophageal cancer: A meta-analysis 
World Journal of Gastroenterology : WJG  2014;20(47):18022-18030.
AIM: To assess the effects of 3-field lymphadenectomy for esophageal carcinoma.
METHODS: We conducted a computerized literature search of the PubMed, Cochrane Controlled Trials Register, and EMBASE databases from their inception to present. Randomized controlled trials (RCTs) or observational epidemiological studies (cohort studies) that compared the survival rates and/or postoperative complications between 2-field lymphadenectomy (2FL) and 3-field lymphadenectomy (3FL) for esophageal carcinoma with R0 resection were included. Meta-analysis was conducted using published data on 3FL vs 2FL in esophageal carcinoma patients. End points were 1-, 3-, and 5-year overall survival rates and postoperative complications, including recurrent nerve palsy, anastomosis leak, pulmonary complications, and chylothorax. Subgroup analysis was performed on the involvement of recurrent laryngeal lymph nodes.
RESULTS: Two RCTs and 18 observational studies with over 7000 patients were included. There was a clear benefit for 3FL in the 1- (RR = 1.16; 95%CI: 1.09-1.24; P < 0.01), 3- (RR = 1.44; 95%CI: 1.19-1.75; P < 0.01), and 5-year overall survival rates (RR = 1.37; 95%CI: 1.18-1.59; P < 0.01). For postoperative complications, 3FL was associated with significantly more recurrent nerve palsy (RR = 1.43; 95%CI: 1.28-1.60; P = 0.02) and anastomosis leak (RR = 1.26; 95%CI: 1.05-1.52; P = 0.09). In contrast, there was no significant difference for pulmonary complications (RR = 0.93; 95%CI: 0.75-1.16, random-effects model; P = 0.27) or chylothorax (RR = 0.77; 95%CI: 0.32-1.85; P = 0.69).
CONCLUSION: This meta-analysis shows that 3FL improves overall survival rate but has more complications. Because of the high heterogeneity among outcomes, definite conclusions are difficult to draw.
PMCID: PMC4273154  PMID: 25548502
Oesophagus; Cancer; Lymph node dissection; Survival; Complication
11.  Aberrant methylation of the SPARC gene promoter and its clinical implication in gastric cancer 
Scientific Reports  2014;4:7035.
Secreted protein acidic and rich in cysteine (SPARC) gene has been shown to be epigenetically silenced in several cancers. We investigated the loss of expression and promoter methylation of this tumor suppressor gene in gastric cancers and correlated the data with clinicopathological features. We observed the loss of SPARC mRNA and SPARC protein expression in 7 of 10 (70%) gastric cancer cell lines. Upon treatment of expression-negative cell lines with a demethylating agent, expression of mRNA and protein was restored in all cells. Methylation rate of SPARC gene was 80% in ten gastric cancer cell lines and 74% (163 of 220) in primary tumors, while it was 5% in normal gastric mucosa (n = 40). In intestinal gastric cancer, SPARC methylation correlated with a negative prognosis (P < 0.001; relative risk 2.754, 95% confidence interval 1.780–4.261). Immunostaining revealed that SPARC protein was overexpressed in stromal fibroblasts adjacent to neoplastic epithelium but rarely expressed in the primary gastric cancer cells. These results implicate SPARC promoter methylation as an important factor in the tumorigenesis of gastric carcinomas and provide new insights into the potential use of SPARC as a novel biomarker and the potential clinical importance in human gastric cancers.
PMCID: PMC4268651  PMID: 25516351
12.  Abieslactone Induces Cell Cycle Arrest and Apoptosis in Human Hepatocellular Carcinomas through the Mitochondrial Pathway and the Generation of Reactive Oxygen Species 
PLoS ONE  2014;9(12):e115151.
Abieslactone is a triterpenoid lactone isolated from Abies plants. Previous studies have demonstrated that its derivative abiesenonic acid methyl ester possesses anti-tumor-promoting activity in vitro and in vivo. In the present study, cell viability assay demonstrated that abieslactone had selective cytotoxicity against human hepatoma cell lines. Immunostaining experiments revealed that abieslactone induced HepG2 and SMMC7721 cell apoptosis. Flow cytometry and western blot analysis showed that the apoptosis was associated with cell cycle arrest during the G1 phase, up-regulation of p53 and p21, and down-regulation of CDK2 and cyclin D1. Furthermore, our results revealed that induction of apoptosis through a mitochondrial pathway led to upregulation of Bax, down-regulation of Bcl-2, mitochondrial release of cytochrome c, reduction of mitochondrial membrane potential (MMP), and activation of caspase cascades (Casp-9 and -3). Activation of caspase cascades also resulted in the cleavage of PARP fragment. Involvement of the caspase apoptosis pathway was confirmed using caspase inhibitor Z-VAD-FMK pretreatment. Recent studies have shown that ROS is upstream of Akt signal in mitochondria-mediated hepatoma cell apoptosis. Our results showed that the accumulation of ROS was detected in HepG2 cells when treated with abieslactone, and ROS scavenger partly blocked the effects of abieslactone-induced HepG2 cell death. In addition, inactivation of total and phosphorylated Akt activities was found to be involved in abieslactone-induced HepG2 cell apoptosis. Therefore, our findings suggested that abieslactone induced G1 cell cycle arrest and caspase-dependent apoptosis via the mitochondrial pathway and the ROS/Akt pathway in HepG2 cells.
PMCID: PMC4263740  PMID: 25502685
13.  Serum Clusterin as a Tumor Marker and Prognostic Factor for Patients with Esophageal Cancer 
Disease Markers  2014;2014:168960.
Background. Recent studies have revealed that clusterin is implicated in many physiological and pathological processes, including tumorigenesis. However, the relationship between serum clusterin expression and esophageal squamous cell carcinoma (ESCC) is unclear. Methods. The serum clusterin concentrations of 87 ESCC patients and 136 healthy individuals were examined. An independent-samples Mann-Whitney U test was used to compare serum clusterin concentrations of ESCC patients to those of healthy controls. Univariate analysis was conducted using the log-rank test and multivariate analyses were performed using the Cox proportional hazards model. Results. In healthy controls, the mean clusterin concentration was 288.8 ± 75.1 μg/mL, while in the ESCC patients, the mean clusterin concentration was higher at 412.3 ± 159.4 μg/mL (P < 0.0001). The 1-, 2-, and 4-year survival rates for the 87 ESCC patients were 89.70%, 80.00%, and 54.50%. Serum clusterin had an optimal diagnostic cut-off point (serum clusterin concentration = 335.5 μg/mL) for esophageal squamous cell carcinoma with sensitivity of 71.26% and specificity of 77.94%. And higher serum clusterin concentration (>500 μg/mL) indicated better prognosis (P = 0.030). Conclusions. Clusterin may play a key role during tumorigenesis and tumor progression of ESCC and it could be applied in clinical work as a tumor marker and prognostic factor.
PMCID: PMC4276701  PMID: 25574066
14.  Exo70 Isoform Switching upon Epithelial-Mesenchymal Transition Mediates Cancer Cell Invasion 
Developmental cell  2013;27(5):560-573.
Epithelial-mesenchymal transition (EMT) is an important developmental process hijacked by cancer cells for their dissemination. Here we show that Exo70, a component of the exocyst complex, undergoes isoform switching mediated by ESRP1, a pre-mRNA splicing factor that regulates EMT. Expression of the epithelial isoform of Exo70 affects the levels of key EMT transcriptional regulators such as Snail and ZEB2, and is sufficient to drive the transition to epithelial phenotypes. Differential Exo70 isoforms expression in human tumors correlates with cancer progression, and increased expression of the epithelial isoform of Exo70 inhibits tumor metastasis in mice. At the molecular level, the mesenchymal but not the epithelial isoform of Exo70 interacts with the Arp2/3 complex and stimulates actin polymerization for tumor invasion. Our findings provide a mechanism by which the exocyst function and actin dynamics are modulated for EMT and tumor invasion.
PMCID: PMC3908839  PMID: 24331928
EMT; exocyst; Exo70; the Arp2/3 complex; ESRP; alternative splicing; tumor invasion
15.  Interfractional Variations of Tumor Centroid Position and Tumor Regression during Stereotactic Body Radiotherapy for Lung Tumor 
BioMed Research International  2014;2014:372738.
Purpose. To determine interfractional changes of lung tumor centroid position and tumor regression during stereotactic body radiation therapy (SBRT). Methods and Materials. 34 patients were treated by SBRT in 4-5 fractions to a median dose of 50 Gy. The CT scans acquired for verification were registered with simulation CT scans. The gross target volume (GTV) was contoured on all verification CT scans and compared to the initial GTV in treatment plan system. Results. The mean (±standard deviation, SD) three-dimension vector shift was 5.2 ± 3.1 mm. The mean (±SD) interfractional variations of tumor centroid position were −0.7 ± 4.5 mm in anterior-posterior (AP) direction, 0.2 ± 3.1 mm in superior-inferior (SI) direction, and 0.4 ± 2.4 mm in right-left (RL) direction. Large interfractional variations (≥5 mm) were observed in 5 fractions (3.3%) in RL direction, 16 fractions (10.5%) in SI direction, and 36 fractions (23.5%) in AP direction. Tumor volume did not decrease significantly during lung SBRT. Conclusions. Small but insignificant tumor volume regression was observed during lung SBRT. While the mean interfractional variations of tumor centroid position were minimal in three directions, variations more than 5 mm account for approximately a third of all, indicating additional margin for PTV, especially in AP direction.
PMCID: PMC4274869  PMID: 25548770
16.  Association Between MTHFR Polymorphisms and Congenital Heart Disease: A Meta-analysis based on 9,329 cases and 15,076 controls 
Scientific Reports  2014;4:7311.
The aim of our study was to evaluate the association between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and the risk for congenital heart disease (CHD). Electronic literature databases were searched to identify eligible studies published before Jun, 2014. The association was assessed by the odds ratio (OR) with a 95% confidence interval (CI). The publication bias was explored using Begg's test. Sensitivity analysis was performed to evaluate the stability of the crude results. A total of 35 studies were included in this meta-analysis. For the MTHFR C677T polymorphism, we detected significant association in all genetic models for Asian children and the maternal population. Significant association was also detected in T vs. C for a Caucasian paediatric population (OR = 1.163, 95% CI: 1.008–1.342) and in both T vs. C (OR = 1.125, 95% CI: 1.043–1.214) and the dominant model (OR = 1.216, 95% CI:b1.096–1.348) for a Caucasian maternal population. For the MTHFR A1298C polymorphism, the association was detected in CC vs. AC for the Caucasian paediatric population (OR = 1.484, 95% CI: 1.035–2.128). Our results support the MTHFR -677T allele as a susceptibility factor for CHD in the Asian maternal population and the -1298C allele as a risk factor in the Caucasian paediatric population.
PMCID: PMC4255188  PMID: 25472587
17.  Primary mediastinal sarcoma: surgical outcomes of 21 cases 
Primary sarcomas of the mediastinum are relatively rare. This article reviews the surgical outcomes of 21 cases diagnosed with localized mediastinal sarcomas receiving multidisciplinary treatment modalities in Sichuan province, China, from January 1996 to January 2011.
Twenty-one cases of histologically diagnosed primary mediastinal sarcoma undergoing surgical treatment were reviewed retrospectively. Disease-free survival (DFS) and overall survival (OS) were statistically analysed. All the patients presented with localized tumours consisting of 5 females and 16 males with a median age of 41.0 years (range: 9.0–68.0 years). Among all cases, 17 (81.0%) had an Eastern Cooperative Oncology Group performance status score of ≤1 at diagnosis. Eight (38.1%) underwent macroscopically complete resection (R0–R1) and 13 (61.9%) had incomplete resection (R2). Ten (47.6%) received postoperative radiotherapy and 7 (33.3%) postoperative chemotherapy.
The median DFS was 17 months (range: 0.4–79.8 months) and the median OS was 27.2 months (range: 0.4–79.8 months). Patients receiving complete resection showed significantly improved DFS (P = 0.031) and OS (P = 0.035) compared with those with incomplete resection. Neither postoperative radiotherapy nor chemotherapy significantly improved DFS (P = 0.770, P = 0.756) or OS (P = 0.905, P = 0.738). However, 7 patients (R2) and 2 (R0–R1 and grade 3) had improved local control with a local recurrence-free survival of 28.9 months (range: 7.6–73.2 months).
Complete resection should be preferentially attempted compared with incomplete resection and postoperative radiotherapy might yield good local control.
PMCID: PMC3829490  PMID: 24027167
Mediastinum; Sarcoma; Surgery; Radiotherapy; Chemotherapy
18.  Identification and Characterization of an eIF4e DNA Aptamer That Inhibits Proliferation With High Throughput Sequencing 
Development of DNA aptamer screens that are both simple and informative can increase the success rate of DNA aptamer selection and induce greater adoption. High eIF4e levels contribute to malignancies, thus eIF4e presents itself as a valuable target for DNA aptamer-based inhibition screen. Here, we demonstrate a method for the rapid selection of looped DNA aptamers against eIF4e by combining negative selection and purification in a single step, followed by characterization with high throughput sequencing. The resulting aptamers show functional binding to eIF4e and inhibit translation initiation in biochemical assays. When transfected into cells, eIF4e aptamers cause a dramatic loss of cell proliferation in tumor cells as seen with eIF4e knockdown with antisense oligonucleotides, shRNAs, and siRNAs, hinting at therapeutic possibilities. With the large data set provided by high throughput sequencing, we demonstrate that selection happens in waves and that sequencing data can be used to infer aptamer structure. Lastly, we show that ligation of looped aptamers can enhance their functional effects. These results demonstrate a rapid protocol to screen and optimize aptamers against macromolecules of interest.
PMCID: PMC4272410  PMID: 25514650
Aptamer; eIF4e; SELEX; proliferation
19.  Genetic, Epigenetic, and HPLC Fingerprint Differentiation between Natural and Ex Situ Populations of Rhodiola sachalinensis from Changbai Mountain, China 
PLoS ONE  2014;9(11):e112869.
Rhodiola sachalinensis is an endangered species with important medicinal value. We used inter-simple sequence repeat (ISSR) and methylation-sensitive amplified polymorphism (MSAP) markers to analyze genetic and epigenetic differentiation in different populations of R. sachalinensis, including three natural populations and an ex situ population. Chromatographic fingerprint was used to reveal HPLC fingerprint differentiation. According to our results, the ex situ population of R. sachalinensis has higher level genetic diversity and greater HPLC fingerprint variation than natural populations, but shows lower epigenetic diversity. Most genetic variation (54.88%) was found to be distributed within populations, and epigenetic variation was primarily distributed among populations (63.87%). UPGMA cluster analysis of ISSR and MSAP data showed identical results, with individuals from each given population grouping together. The results of UPGMA cluster analysis of HPLC fingerprint patterns was significantly different from results obtained from ISSR and MSAP data. Correlation analysis revealed close relationships among altitude, genetic structure, epigenetic structure, and HPLC fingerprint patterns (R2 = 0.98 for genetic and epigenetic distance; R2 = 0.90 for DNA methylation level and altitude; R2 = –0.95 for HPLC fingerprint and altitude). Taken together, our results indicate that ex situ population of R. sachalinensis show significantly different genetic and epigenetic population structures and HPLC fingerprint patterns. Along with other potential explanations, these findings suggest that the ex situ environmental factors caused by different altitude play an important role in keeping hereditary characteristic of R. sachalinensis.
PMCID: PMC4227887  PMID: 25386983
20.  20(S)-Protopanaxadiol Inhibition of Progression and Growth of Castration-Resistant Prostate Cancer 
PLoS ONE  2014;9(11):e111201.
Castration-resistant progression of prostate cancer after androgen deprivation therapies remains the most critical challenge in the clinical management of prostate cancer. Resurgent androgen receptor (AR) activity is an established driver of castration-resistant progression, and upregulation of the full-length AR (AR-FL) and constitutively-active AR splice variants (AR-Vs) has been implicated to contribute to the resurgent AR activity. We reported previously that ginsenoside 20(S)-protopanaxadiol-aglycone (PPD) can reduce the abundance of both AR-FL and AR-Vs. In the present study, we further showed that the effect of PPD on AR expression and target genes was independent of androgen. PPD treatment resulted in a suppression of ligand-independent AR transactivation. Moreover, PPD delayed castration-resistant regrowth of LNCaP xenograft tumors after androgen deprivation and inhibited the growth of castration-resistant 22Rv1 xenograft tumors with endogenous expression of AR-FL and AR-Vs. This was accompanied by a decline in serum prostate-specific antigen levels as well as a decrease in AR levels and mitoses in the tumors. Notably, the 22Rv1 xenograft tumors were resistant to growth inhibition by the next-generation anti-androgen enzalutamide. The present study represents the first to show the preclinical efficacy of PPD in inhibiting castration-resistant progression and growth of prostate cancer. The findings provide a rationale for further developing PPD or its analogues for prostate cancer therapy.
PMCID: PMC4222907  PMID: 25375370
21.  Multiscale Multiphysics and Multidomain Models I: Basic Theory 
Journal of theoretical & computational chemistry  2013;12(8):10.1142/S021963361341006X.
This work extends our earlier two-domain formulation of a differential geometry based multiscale paradigm into a multidomain theory, which endows us the ability to simultaneously accommodate multiphysical descriptions of aqueous chemical, physical and biological systems, such as fuel cells, solar cells, nanofluidics, ion channels, viruses, RNA polymerases, molecular motors and large macromolecular complexes. The essential idea is to make use of the differential geometry theory of surfaces as a natural means to geometrically separate the macroscopic domain of solvent from the microscopic domain of solute, and dynamically couple continuum and discrete descriptions. Our main strategy is to construct energy functionals to put on an equal footing of multiphysics, including polar (i.e., electrostatic) solvation, nonpolar solvation, chemical potential, quantum mechanics, fluid mechanics, molecular mechanics, coarse grained dynamics and elastic dynamics. The variational principle is applied to the energy functionals to derive desirable governing equations, such as multidomain Laplace-Beltrami (LB) equations for macromolecular morphologies, multidomain Poisson-Boltzmann (PB) equation or Poisson equation for electrostatic potential, generalized Nernst-Planck (NP) equations for the dynamics of charged solvent species, generalized Navier-Stokes (NS) equation for fluid dynamics, generalized Newton's equations for molecular dynamics (MD) or coarse-grained dynamics and equation of motion for elastic dynamics. Unlike the classical PB equation, our PB equation is an integral-differential equation due to solvent-solute interactions. To illustrate the proposed formalism, we have explicitly constructed three models, a multidomain solvation model, a multidomain charge transport model and a multidomain chemo-electro-fluid-MD-elastic model. Each solute domain is equipped with distinct surface tension, pressure, dielectric function, and charge density distribution. In addition to long-range Coulombic interactions, various non-electrostatic solvent-solute interactions are considered in the present modeling. We demonstrate the consistency between the non-equilibrium charge transport model and the equilibrium solvation model by showing the systematical reduction of the former to the latter at equilibrium. This paper also offers a brief review of the field.
PMCID: PMC4220694  PMID: 25382892
Multiscale; Multiphysics; Multidomain; Laplace-Beltrami equation; Poisson-Boltzmann equation; Nernst-Planck equation; Fluid dynamics; Molecular dynamics; Elastic dynamics
22.  Automated Detection Framework of the Calcified Plaque with Acoustic Shadowing in IVUS Images 
PLoS ONE  2014;9(11):e109997.
Intravascular Ultrasound (IVUS) is one ultrasonic imaging technology to acquire vascular cross-sectional images for the visualization of the inner vessel structure. This technique has been widely used for the diagnosis and treatment of coronary artery diseases. The detection of the calcified plaque with acoustic shadowing in IVUS images plays a vital role in the quantitative analysis of atheromatous plaques. The conventional method of the calcium detection is manual drawing by the doctors. However, it is very time-consuming, and with high inter-observer and intra-observer variability between different doctors. Therefore, the computer-aided detection of the calcified plaque is highly desired. In this paper, an automated method is proposed to detect the calcified plaque with acoustic shadowing in IVUS images by the Rayleigh mixture model, the Markov random field, the graph searching method and the prior knowledge about the calcified plaque. The performance of our method was evaluated over 996 in-vivo IVUS images acquired from eight patients, and the detected calcified plaques are compared with manually detected calcified plaques by one cardiology doctor. The experimental results are quantitatively analyzed separately by three evaluation methods, the test of the sensitivity and specificity, the linear regression and the Bland-Altman analysis. The first method is used to evaluate the ability to distinguish between IVUS images with and without the calcified plaque, and the latter two methods can respectively measure the correlation and the agreement between our results and manual drawing results for locating the calcified plaque in the IVUS image. High sensitivity (94.68%) and specificity (95.82%), good correlation and agreement (>96.82% results fall within the 95% confidence interval in the Student t-test) demonstrate the effectiveness of the proposed method in the detection of the calcified plaque with acoustic shadowing in IVUS images.
PMCID: PMC4220935  PMID: 25372784
23.  An Elevated Peripheral Blood Lymphocyte-to-Monocyte Ratio Predicts Favorable Response and Prognosis in Locally Advanced Breast Cancer following Neoadjuvant Chemotherapy 
PLoS ONE  2014;9(11):e111886.
Neoadjuvant chemotherapy (NCT) is a standard treatment option for locally advanced breast cancer. However, the lack of an efficient method to predict treatment response and patient prognosis hampers the clinical evaluation of patient eligibility for NCT. An elevated lymphocyte-to-monocyte ratio (LMR) has been reported to be associated with a favorable prognosis for certain hematologic malignancies and for nasopharyngeal carcinoma; however, this association has not been investigated in breast cancer. The purpose of this study was to evaluate whether pre-NCT LMR analysis could predict the prognosis of patients with locally advanced breast cancer.
A retrospective cohort of 542 locally advanced breast cancer patients (T3/T4 and/or N2/N3 disease) receiving NCT followed by radical surgery was recruited between May 2002 and August 2011 at the Fudan University Shanghai Cancer Center. Counts for pre-NCT peripheral absolute lymphocytes and monocytes were obtained and used to calculate the LMR.
Univariate and multivariate analysis revealed that higher LMR levels (≥4.25) were significantly associated with favorable DFS (P = 0.009 and P = 0.011, respectively). Additionally, univariate analysis revealed that a higher lymphocyte count (≥1.5×109/L) showed borderline significance for improved DFS (P = 0.054), while a lower monocyte count (<0.4×109/L) was associated with a significantly better DFS (P = 0.010).
An elevated pre-NCT peripheral LMR level was a significantly favorable factor for locally advanced breast cancer patient prognosis. This easily obtained variable may serve as a valuable marker to predict the outcomes of locally advanced breast cancer.
PMCID: PMC4221197  PMID: 25372468
24.  Molecular cloning and analysis of gonadal expression of Foxl2 in the rice-field eel Monopterus albus 
Scientific Reports  2014;4:6884.
We isolated the complete Foxl2 (Foxl2a) cDNA from the Monopterus albus ovary. An alignment of known Foxl2 amino-acid sequences confirmed the conservation of the Foxl2 open reading frame, especially the forkhead domain and C-terminal region. The expression of Foxl2 was detected in the brain, eyes, and gonads. A high level of Foxl2 expression in the ovary before sex reversal, but its transcripts decreased sharply when the gonad developed into the ovotestis and testis. The correlation between the Foxl2 expression and the process of sex development revealed the important function of Foxl2 during the sex reversal of M. albus. Immunohistochemical analysis showed that Foxl2 was expressed abundantly in granulosa cells and in the interstitial cells of the ovotestis and testis. These results suggest that Foxl2 plays a pivotal role in the development and maintenance of ovarian function. Foxl2 may be also involved in the early development of testis and the development of ocular structures of M. albus.
PMCID: PMC4217102  PMID: 25363394
25.  Modulation of Mcl-1 expression reduces age-related cochlear degeneration 
Neurobiology of aging  2013;34(11):2647-2658.
Mcl-1 is an anti-apoptotic member of the Bcl-2 family that modulates apoptosis-related signaling pathways and promotes cell survival. We have previously demonstrated a reduction of Mcl-1 expression in aging cochleae. To investigate whether restoring Mcl-1 expression would reduce aging-related cochlear degeneration, we developed a rat model of Mcl-1 overexpression. A plasmid encoding human Mcl-1/enhanced green fluorescent protein was applied to the round window of the cochlea. This in vivo treatment transfected both the sensory and supporting cells of the cochlear sensory epithelium and enhanced Mcl-1 expression at both the mRNA and the protein level. The upregulation of Mcl-1 expression reduced the progression of age-related cochlear dysfunction and sensory cell death. Furthermore, the transfection of Mcl-1 exerted its protective effect by suppressing cochlear apoptosis at the mitochondrial level. This study demonstrates that the genetic modulation of Mcl-1 expression reduces the progression of age-related cochlear degeneration.
PMCID: PMC3742618  PMID: 23790646
Mcl-1; gene delivery; cochlea; aging; intervention; hair cells; rat

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