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1.  Recurrent abdominal liposarcoma: Analysis of 19 cases and prognostic factors 
AIM: To evaluate the clinical outcome of re-operation for recurrent abdominal liposarcoma following multidisciplinary team cooperation.
METHODS: Nineteen consecutive patients who had recurrent abdominal liposarcoma underwent re-operation by the retroperitoneal sarcoma team at our institution from May 2009 to January 2012. Patient demographic and clinical data were reviewed retrospectively. Multidisciplinary team discussions were held prior to treatment, and re-operation was deemed the best treatment. The categories of the extent of resection were as follows: gross total resection (GTR), palliative resection and partial resection. Surgical techniques were divided into discrete lesion resection and combined contiguous multivisceral resection (CMR). Tumor size was determined as the largest diameter of the specimen. Patients were followed up at approximately 3-monthly intervals. For survival analysis, a univariate analysis was performed using the Kaplan-Meier method, and a multivariate analysis was performed using the Cox proportional hazards model.
RESULTS: Nineteen patients with recurrent abdominal liposarcoma (RAL) underwent 32 re-operations at our institute. A total of 51 operations were reviewed with a total follow-up time ranging from 4 to 120 (47.4 ± 34.2) mo. The GTR rate in the CMR group was higher than that in the non-CMR group (P = 0.034). CMR was positively correlated with intra-operative bleeding (correlation coefficient = 0.514, P = 0.010). Six cases with severe postoperative complications were recorded. Patients with tumor sizes greater than 20 cm carried a significant risk of profuse intra-operative bleeding (P = 0.009). The ratio of a highly malignant subtype (dedifferentiated or pleomorphic) in recurrent cases was higher compared to primary cases (P = 0.027). Both single-factor survival using the Kaplan-Meier model and multivariate analysis using the Cox proportional hazards model showed that overall survival was correlated with resection extent and pathological subtype (P < 0.001 and P = 0.02), however, relapse-free interval (RFI) was only correlated with resection extent (P = 0.002).
CONCLUSION: Close follow-up should be conducted in patients with RAL. Early re-operation for relapse is preferred and gross resection most likely prolongs the RFI.
PMCID: PMC3703193  PMID: 23840151
Overall survival; Recurrent abdominal liposarcoma; Relapse-free interval
2.  Hybrid luminescence materials assembled by [Ln(DPA)3]3− and mesoporous host through ion-pairing interactions with high quantum efficiencies and long lifetimes 
Scientific Reports  2015;5:8385.
A kind of mesoporous hybrid luminescence material was assembled through the ion exchange method between [Ln(DPA)3]3− and ionic liquid functionalized SBA-15. [Ln(DPA)3]3− was successfully anchored onto positive-charge modified SBA-15 by the strong electrostatic interaction. In [Ln(DPA)3]3−, Ln3+ ions are in 9-fold coordination through six oxygen atoms of carboxyl groups and three nitrogen atoms of pyridine units, leaving no coordination site for water molecules. Therefore the hybrids possess prominent luminescent properties, SBA-15-IMI-Tb(DPA)3 and SBA-15-IMI-Eu(DPA)3 exhibit high quantum yield values of 63% and 79%, and long lifetimes values of 2.38 ms and 2.34 ms, respectively. Especially, SBA-15-IMI-Eu(DPA)3 presents a high color purity, and the red/orange intensity ratio is as high as 7.6. The excellent luminescence properties and ordered mesoporous structures give rise to many potential applications in optical and electronic areas.
PMCID: PMC4323642  PMID: 25669156
3.  Biophysical significance of the inner mitochondrial membrane structure on the electrochemical potential of mitochondria 
The available literature supports the hypothesis that the morphology of the inner mitochondrial membrane is regulated by different energy states, that the three-dimensional morphology of cristae is dynamic and that both are related to biochemical function. Examination of the correlation between the inner mitochondrial membrane (IMM) structure and mitochondrial energetic function is critical to an understanding of the links between meso-scale morphology and function in progressive mitochondrial dysfunction such as aging, neurodegeneration, and disease. To investigate this relationship, we develop a model to examine the effects of three-dimensional IMM morphology on the electrochemical potential of mitochondria. The 2D axisymmetric finite element method is used to simulate mitochondrial electric potential and proton concentration distribution. This simulation model demonstrates that the proton motive force (PMF) produced on the membranes of cristae can be higher than that on the inner boundary membrane. The model also shows that high proton concentration in cristae can be induced by the morphology-dependent electric potential gradient along the outer side of the IMM. Furthermore, simulation results show that a high PMF is induced by the large surface-to-volume ratio of an individual crista, whereas a high capacity for ATP synthesis can primarily be achieved by increasing the surface area of an individual crista. The mathematical model presented here provides compelling support for the idea that morphology at the meso-scale is a significant driver of mitochondrial function.
PMCID: PMC4315510  PMID: 24483502
4.  Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1 
Nature genetics  2014;46(8):886-890.
In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified three novel genetic loci associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene, P = 8.82 × 10−9), rs10474352 at 5q14.3 (near the ARRDC3 gene, P = 1.67 × 10−9), and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene, P = 4.25 × 10−8). These associations were replicated in European-ancestry populations including 16,003 cases and 41,335 controls (P = 0.030, 0.004, and 0.010, respectively). Data from the ENCODE project suggest that variants rs4951011 and rs10474352 may be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer.
PMCID: PMC4127632  PMID: 25038754
5.  Pharmacokinetic model of unfractionated heparin during and after cardiopulmonary bypass in cardiac surgery 
Unfractionated heparin (UFH) is widely used as a reversible anti-coagulant in cardiopulmonary bypass (CPB). However, the pharmacokinetic characteristics of UFH in CPB surgeries remain unknown because of the lack of means to directly determine plasma UFH concentrations. The aim of this study was to establish a pharmacokinetic model to predict plasma UFH concentrations at the end of CPB for optimal neutralization with protamine sulfate.
Forty-one patients undergoing CPB during cardiac surgery were enrolled in this observational clinical study of UFH pharmacokinetics. Patients received intravenous injections of UFH, and plasma anti-FIIa activity was measured with commercial anti-FIIa assay kits. A population pharmacokinetic model was established by using nonlinear mixed-effects modeling (NONMEM) software and validated by visual predictive check and Bootstrap analyses. Estimated parameters in the final model were used to simulate additional protamine administration after cardiac surgery in order to eliminate heparin rebound. Plans for postoperative protamine intravenous injections and infusions were quantitatively compared and evaluated during the simulation.
A two-compartment pharmacokinetic model with first-order elimination provided the best fit. Subsequent simulation of postoperative protamine administration suggested that a lower-dose protamine infusion over 24 h may provide better elimination and prevent heparin rebound than bolus injection and other infusion regimens that have higher infusion rates and shorter duration.
A two-compartment model accurately reflects the pharmacokinetics of UFH in Chinese patients during CPB and can be used to explain postoperative heparin rebound after protamine neutralization. Simulations suggest a 24-h protamine infusion is more effective for heparin rebound prevention than a 6-h protamine infusion.
PMCID: PMC4326208  PMID: 25638272
Cardiopulmonary bypass; Cardiac surgery; Pharmacokinetic model; Unfractionated heparin
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.  Repressive mutations restore function-loss caused by the disruption of trimerization in Escherichia coli multidrug transporter AcrB 
AcrAB-TolC and their homologs are major multidrug efflux systems in Gram-negative bacteria. The inner membrane component AcrB functions as a trimer. Replacement of Pro223 by Gly in AcrB decreases the trimer stability and drastically reduces the drug efflux activity. The goal of this study is to identify suppressor mutations that restore function to mutant AcrBP223G and explore the mechanism of function recovery. Two methods were used to introduce random mutations into the plasmid of AcrBP223G. Mutants with elevated drug efflux activity were identified, purified, and characterized to examine their expression level, trimer stability, interaction with AcrA, and substrate binding. Nine single-site repressor mutations were identified, including T199M, D256N, A209V, G257V, M662I, Q737L, D788K, P800S, and E810K. Except for M662I, all other mutations located in the docking region of the periplasmic domain. While three mutations, T199M, A209V, and D256N, significantly increased the trimer stability, none of them restored the trimer affinity to the wild type level. M662, the only site of mutation that located in the porter domain, was involved in substrate binding. Our results suggest that the function loss resulted from compromised AcrB trimerization could be restored through various mechanisms involving the compensation of trimer stability and substrate binding.
PMCID: PMC4303003  PMID: 25657644
RND; oligomerization; membrane transporter; efflux pump; protein thermal stability
9.  Radiobiological Modeling Based on 18F-Fluorodeoxyglucose Positron Emission Tomography Data for Esophageal Cancer 
We investigated the relationship of standardized uptake values (SUVs) to radiobiological parameters, such a 25 s tumor control probability (TCP), to allow for quantitative prediction of tumor response based on SUVs from 18F fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) before and after treatment for esophageal cancer.
We analyzed data from 20 esophageal cancer patients treated with chemoradiotherapy (CRT) followed by surgery. Tumor pathologic response to CRT was assessed in surgical specimens. Patients underwent 18F-FDG PET imaging before and after CRT. Rigid image registration was performed between both images. Because TCP in a heterogeneous tumor is a function of average cell survival, we modeled TCP as a function of , a possible surrogate for average cell survival (=). TCP was represented by a sigmoid function with two parameters: SUVR50, the at which TCP=0.5, and γ50, the slope of the curve at SUVR50. The two parameters and their confidence intervals (CIs) were estimated using the maximum-likelihood method. The correlation between SUV before CRT and SUV change was also studied.
A TCP model as a function of SUV before and after treatment was developed for esophageal cancer patients. The maximum-likelihood estimate of SUVR50 was 0.47 (90% CI, 0.30-0.61) and for γ50 was 1.62 (90% CI, 0-4.2). High initial SUV and larger metabolic response (larger ) were correlated, and this correlation was stronger among responders.
Our TCP model indicates that is a possible surrogate for cell survival in esophageal cancer patients. Although CIs are large as a result of the small patient sample, parameters for a TCP curve can be derived and an individualized TCP can be calculated for future patients. Initial SUV does not predict response, whereas a correlation is found between surrogates for initial tumor burden and cell kill during therapy.
PMCID: PMC4286330  PMID: 25580368
18F-FDG PET/CT; Tumor response; Esophageal cancer; Quantitative imaging; Radiation therapy
10.  Calibrating a population-based job-exposure matrix using inspection measurements to estimate historical occupational exposure to lead for a population-based cohort in Shanghai, China 
The epidemiologic evidence for the carcinogenicity of lead is inconsistent and requires improved exposure assessment to estimate risk. We evaluated historical occupational lead exposure for a population-based cohort of women (n=74,942) by calibrating a job-exposure matrix (JEM) with lead fume (n=20,084) and lead dust (n=5,383) measurements collected over four decades in Shanghai, China. Using mixed-effect models, we calibrated intensity JEM ratings to the measurements using fixed-effects terms for year and JEM rating. We developed job/industry-specific estimates from the random-effects terms for job and industry. The model estimates were applied to subjects’ jobs when the JEM probability rating was high for either job or industry; remaining jobs were considered unexposed. The models predicted that exposure increased monotonically with JEM intensity rating and decreased 20–50-fold over time. The cumulative calibrated JEM estimates and job/industry-specific estimates were highly correlated (Pearson correlation=0.79–0.84). Overall, 5% of the person-years and 8% of the women were exposed to lead fume; 2% of the person-years and 4% of the women were exposed to lead dust. The most common lead-exposed jobs were manufacturing electronic equipment. These historical lead estimates should enhance our ability to detect associations between lead exposure and cancer risk in future epidemiologic analyses.
PMCID: PMC3508334  PMID: 22910004
lead; cancer; exposure assessment; occupational exposure; job exposure matrix; mixed-effects model
11.  Modeling Pathologic Response of Esophageal Cancer to Chemoradiotherapy Using Spatial-Temporal 18F-FDG PET Features, Clinical Parameters, and Demographics 
International journal of radiation oncology, biology, physics  2013;88(1):10.1016/j.ijrobp.2013.09.037.
To construct predictive models using comprehensive tumor features for the evaluation of tumor response to neoadjuvant chemoradiotherapy (CRT) in patients with esophageal cancer.
Methods and Materials
This study included 20 patients who underwent trimodality therapy (CRT + surgery) and had 18F-FDG PET/CT scans both before and after CRT. Four groups of tumor features were examined: (1) conventional PET/CT response measures (SUVmax, tumor diameter, etc.); (2) clinical parameters (TNM stage, histology, etc.) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, using cross-validations to avoid model over-fitting. Prediction accuracy was assessed via area under the receiver operating characteristic curve (AUC), and precision was evaluated via confidence intervals (CIs) of AUC.
When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). Using spatial–temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications), significantly better than using conventional PET/CT measures or clinical parameters and demographics alone. For groups with a large number of tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than the LR model,
The SVM model using all features including spatial–temporal PET features accurately and precisely predicted pathologic tumor response to CRT in esophageal cancer.
PMCID: PMC3875172  PMID: 24189128
12.  The MCART Radiation Physics Core: The Quest for Radiation Dosimetry Standardization 
Health physics  2014;106(1):97-105.
Dose-related radiobiological research results can only be meaningfully compared when radiation dosimetry is standardized. To this purpose, the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Medical Countermeasures Against Radiological Threats (MCART) consortium recently created a Radiation Physics Core (RPC) as an entity to assume responsibility of standardizing radiation dosimetry practices among its member laboratories. The animal research activities in these laboratories utilize a variety of ionizing photon beams from several irradiators such as 250–320 kVp x-ray generators, 137Cs irradiators, 60Co teletherapy machines, and medical linear accelerators (LINACs). In addition to this variety of sources, these centers utilize a range of irradiation techniques and make use of different dose calculation schemes to conduct their experiments. An extremely important objective in these research activities is to obtain a Dose Response Relationship (DRR) appropriate to their respective organ-specific models of acute and delayed radiation effects. A clear and unambiguous definition of the DRR is essential for the development of medical countermeasures. It is imperative that these DRRs are transparent between centers. The MCART RPC has initiated the establishment of standard dosimetry practices among member centers and is introducing a Remote Dosimetry Monitoring Service (RDMS) to ascertain ongoing quality assurance. In this paper we will describe the initial activities of the MCART RPC toward implementing these standardization goals. It is appropriate to report a summary of initial activities with the intent of reporting the full implementation at a later date.
PMCID: PMC3899940  PMID: 24276553
dosimetry; calibration; quality assurance; radiation dose; radiobiology; standards; x-ray machines
13.  Rare Periodontal Ligament Drainage for Periapical Inflammation of an Adjacent Tooth: A Case Report and Review of the Literature 
Case Reports in Dentistry  2014;2014:879562.
Aim. To report a case with an unusual drainage route of periapical inflammation exiting through the gingival sulcus of an adjacent vital tooth and review probable factors determining the diversity of the discharge routes of periapical inflammation. Summary. An 18-year-old male patient presented with periodontal abscess of tooth 46, which was found to be caused by a periapical cyst with an acute abscess of tooth 45. During endodontic surgery, a rarely reported drainage route for periapical inflammation via the gingival sulcus of an adjacent vital tooth was observed for the first time. Complete periodontal healing of the deep pocket of tooth 46 and hiding of the periapical cyst of tooth 45 followed after root canal treatment and periapical surgery with Bio-Oss Collagen implantation on tooth 45. The drainage routes of periapical inflammation are multivariate and the diversity of drainage pathways of periapical inflammation is mainly related to factors such as gravity, barriers against inflammation, and the causative tooth itself.
PMCID: PMC4283423  PMID: 25587462
14.  Gastrointestinal symptom due to lupus peritonitis: a rare form of onset of SLE 
Serositis is commonly seen in systemic lupus erythematosus (SLE). Approximately 16% of patients with SLE have pleural or pericardial involvement. However, peritoneal involvement is extremely rare, and SLE with ascites as the first manifestation is an even rarer condition. This is the case report of a 19-year old male with discoid lupus who evolved with gastrointestinal symptoms as the first manifestation of the disease, characterized by significant abdominal distension and pain, asthenia, vomiting, and signs of ascites. An abdominal CT scan demonstrated ascites and marked edematous thickening of the bowel wall, which appeared as “target sign”, and “double-track sign”. Laboratory tests showed that his serum complement levels decreased and that he was positive for anti-nRNP/Sm antibodies, anti-Sm antibodies, anti-SS-A antibody, and anti-nuclear antibodies. The patient was treated with prednisone and chloroquine, with substantial improvement of his condition.
PMCID: PMC4307580  PMID: 25664133
Systemic lupus erythematosus; serositis; ascites; lupus peritonitis; CT
15.  Nanofabrication of highly ordered, tunable metallic mesostructures via quasi-hard-templating of lyotropic liquid crystals 
Scientific Reports  2014;4:7420.
The synthesis of metal frameworks perforated with nanotunnels is a challenge because metals have high surface energies that favor low surface area structures; traditional liquid-crystal templating techniques cannot achieve the synthetic control required. We report a synthetic strategy to fabricate metal nanomaterials with highly ordered, tunable mesostructures in confined systems based on a new quasi-hard-templating liquid-crystals mechanism. The resulting platinum nanowires exhibit long range two-dimensional hexagonally ordered mesopore structures. In addition, single crystalline hexagonal mesoporous platinum nanowires with dominant {110} facets have been synthesized. Finally, we demonstrate that the mesostructures of metal nanomaterials can be tuned from hexagonal to lamellar mesostructures.
PMCID: PMC4262821  PMID: 25502015
16.  Influence of Trace Elements Mixture on Bacterial Diversity and Fermentation Characteristics of Liquid Diet Fermented with Probiotics under Air-Tight Condition 
PLoS ONE  2014;9(12):e114218.
Cu2+, Zn2+, Fe2+ and I− are often supplemented to the diet of suckling and early weaning piglets, but little information is available regarding the effects of different Cu2+, Zn2+, Fe2+ and I− mixtures on bacteria growth, diversity and fermentation characteristics of fermented liquid diet for piglets. Pyrosequencing was performed to investigate the effect of Cu2+, Zn2+, Fe2+ and I− mixtures on the diversity, growth and fermentation characteristics of bacteria in the liquid diet fermented with Bacillus subtilis and Enterococcus faecalis under air-tight condition. Results showed that the mixtures of Cu2+, Zn2+, Fe2+ and I− at different concentrations promoted Bacillus growth, increased bacterial diversity and lactic acid production and lowered pH to about 5. The importance of Cu2+, Zn2+, Fe2+ and I− is different for Bacillus growth with the order Zn2+> Fe2+>Cu2+> I− in a 21-d fermentation and Cu2+>I−>Fe2+>Zn2+ in a 42-d fermentation. Cu2+, Zn2+, Fe2+ and I− is recommended at a level of 150, 60, 150 and 0.6 mg/kg respectively for the production of fermented liquid diet with Bacillus subtilis. The findings improve our understanding of the influence of trace elements on liquid diet fermentation with probiotics and support the proper use of trace elements in the production of fermented liquid diet for piglets.
PMCID: PMC4259320  PMID: 25486254
17.  Curcumin protects against lipopolysaccharide-induced vasoconstriction dysfunction via inhibition of thrombospondin-1 and transforming growth factor-β1 
Sepsis is a complex syndrome characterized by the development of progressive dysfunction in multiple organs. The aim of the present study was to investigate the protective effect of curcumin against lipopolysaccharide (LPS)-induced vasoconstrictive dysfunction, and to investigate the possible underlying mechanism. Male Sprague-Dawley rats were randomly divided into the following groups: Control, sepsis and curcumin. A sepsis model was established by an intraperitoneal (i.p.) injection of 5 mg/kg LPS. Thoracic aortic rings obtained from the rats were mounted in an organ bath and the vasoconstriction of the rings was recorded. In addition, the serum E-selectin levels were determined by an enzyme-linked immunosorbent assay. The expression levels of thrombospondin (TSP)-1 and transforming growth factor (TGF)-β1 in the aortic tissue were detected by immunohistochemistry. Vasoconstriction of the aortic rings was found to significantly decrease in the sepsis rats when compared with the control group. However, curcumin (10 or 20 mg/kg, i.p.) prevented the vasoconstrictive dysfunction induced by LPS. The serum level of E-selectin and the expression levels of TSP-1 and TGF-β1 significantly increased in the sepsis rats when compared with the control group rats; however, the levels decreased significantly following treatment with curcumin (10 or 20 mg/kg). Furthermore, hematoxylin and eosin staining revealed that curcumin alleviated the LPS-induced damage in the aortic tunica intima and tunica media. Therefore, the results indicated that curcumin alleviates LPS-induced vasoconstrictive dysfunction in the thoracic aorta of rats. In addition, the inhibition of TSP-1 and TGF-β1 expression may be involved in the mechanism underlying this protective effect.
PMCID: PMC4280923  PMID: 25574201
lipopolysaccharide; curcumin; vasoconstriction; thrombospondin-1; transforming growth factor-β1
18.  Prevalence and risk factors of anxiety status among students aged 13-26 years 
Previous study revealed that 8%-12% adolescents suffered from various types of anxiety disorders, and which had interfered with adolescent daily life function and affected adolescent social function. The aim of this study was to evaluate anxiety status and its related factors among students aged 13-26 years from Wuhu, China. This was a cross-sectional observational study. A sample of school students who come from a university, four high schools and four middle schools in Wuhu city were recruited, Self-Rating Anxiety Scale (SAS) was used to measure the anxiety status among students aged 13-26 years, and some demographic characteristics of students also was determined. A total of 5249 students were included in our study. The overall rate of anxiety status among students was 14.1%. A significant difference was observed between anxiety status and sex, mothers education level, dietary and siesta habit (P < 0.05), only-child family, gentle temper, regular breakfast habit, friend support was associated with lower scores on anxiety status. The findings indicated that anxiety status is common among school students. Preventive and treatment strategies are highly recommended.
PMCID: PMC4276221  PMID: 25550963
China; students; anxiety status; self-rating anxiety scale; influencing factors
19.  Selective antegrade cerebral perfusion reduces brain injury following deep hypothermic circulatory arrest in the piglets’ model by decreasing the levels of protein SUMO2/3-ylation 
Selective antegrade cerebral perfusion (SACP), which was adopted by many surgical groups for complex neonatal cardiac surgery, especially aortic arch repair, is a proven adjunct for neuroprotection during deep hypothermic circulatory arrest (DHCA). Several recent studies suggest that SUMO2/3 modification of proteins is markedly activated during deep hypothermia and believed to be an endogenous neuroprotective stress response. Here, we report that SACP reduces the increasing degree of SUMO2/3 conjugation following DHCA. Piglets were subjected to 1 h SACP and/or 1 h DHCA. DHCA was sufficient to markedly increase in protein SUMOylation by SUMO2/3 both in the hippocampus and cerebral cortex. SACP, especially at flow rate of 50 ml/kg/min, reduces the increasing degree of SUMO2/3 conjugation and also reduces levels of pro-apoptotic factors, Bax and Caspase 3, and increases levels of antiapoptotic factors, Bcl-2, following DHCA both in the hippocampus and cerebral cortex. This suggests that SACP at flow rate of 50 ml/kg/min is more appropriate for neuroprotection during DHCA in the pig model and level of protein SUMO2/3-ylation maybe an indicator of the degree of brain injury.
PMCID: PMC4276245  PMID: 25550987
Selective antegrade cerebral perfusion; SUMO2/3; deep hypothermic circulatory arrest; piglet; apoptosis; brain injury
20.  Blocking and reversing hepatic fibrosis in patients with chronic hepatitis B treated by traditional Chinese medicine (tablets of biejia ruangan or RGT): study protocol for a randomized controlled trial 
Trials  2014;15(1):438.
Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC) and ultimately liver-related death. Although oral antiviral therapy for patients with CHB reduces the risk of such complications, once cirrhosis is established, the benefits of antiviral therapy are not robustly demonstrated. According to traditional Chinese medicine (TCM), some Chinese herbal medicines promote blood circulation and soften hard masses, and therefore they may block and reverse hepatic fibrosis. The aim of this study is to evaluate the effects of TCM tablets of the compound biejia ruangan (RGT) administered for fibrosis, and entecavir (ETV), on the development of HCC in patients with CHB or hepatitis B virus (HBV)-related compensated cirrhosis.
This multicenter, centrally randomized, double-blind, placebo-controlled, parallel-group study is planned to complete within 5 years. For the study, 1,000 with CHB or HBV-related compensated cirrhosis are randomly assigned in a 1:1 ratio to a treatment group (0.5 mg ETV once daily; 2 g RGT three times daily) or a control group (0.5 mg ETV once daily; 2 g RGT dummy agent three times daily). The primary end points are the development of HCC and liver-related death. Secondary end points include disease progression and overall survival.
Although antiviral therapy can achieve sustained suppression of HBV replication, thereby preventing cirrhosis, patients with CHB treated with nucleos(t)ide analogs (NUCs) retain a higher risk for HCC compared with patients with inactive disease. Although previous clinical trials with RGT have confirmed the efficacy of blocking and reversing hepatic fibrosis in patients with CHB or compensated cirrhosis, the long-term risk for HCC or disease progression in these patients treated with combination of RGT and NUCs compared with NUCs alone is unclear. Therefore, it is necessary to investigate the effects of the RGT blockade and reversal of hepatic fibrosis on the development of HCC in patients with CHB or HBV-related compensated cirrhosis in large, prospective, multicenter, double-blind, randomized, controlled trials in China.
Trial registration Identifier: NCT01965418. Date registered: 17 October 2013
PMCID: PMC4234899  PMID: 25381721
Compound biejia ruangan tablet; multicenter randomized controlled trial; chronic hepatitis B; hepatocellular carcinoma; hepatic fibrosis
21.  Whole exome sequencing reveals novel COL4A3 and COL4A4 mutations and resolves diagnosis in Chinese families with kidney disease 
BMC Nephrology  2014;15(1):175.
Collagen IV-related nephropathies, including thin basement membrane nephropathy and Alport Syndrome (AS), are caused by defects in the genes COL4A3, COL4A4 and COL4A5. Diagnosis of these conditions can be hindered by variable penetrance and the presence of non-specific clinical or pathological features.
Three families with unexplained inherited kidney disease were recruited from Shanghai, China. Whole exome sequencing (WES) was performed in the index case from each family and co-segregation of candidate pathogenic mutations was tested by Sanger sequencing.
We identified COL4A4 missense variants [c.G2636A (p.Gly879Glu) and c.C4715T (p.Pro1572Leu)] in the 21-year-old male proband from family 1, who had been diagnosed with mesangial proliferative nephropathy at age 14. COL4A4 c.G2636A, a novel variant, co-segregated with renal disease among maternal relatives. COL4A4 c.C4715T has previously been associated with autosomal recessive AS and was inherited from his clinically unaffected father. In family 2, a novel COL4A3 missense mutation c.G2290A (p.Gly997Glu) was identified in a 45-year-old male diagnosed with focal segmental glomerulosclerosis and was present in all his affected family members, who exhibited disease ranging from isolated microscopic hematuria to end stage renal disease (ESRD). In family 3, ESRD occurred in both male and females who were found to harbor a known AS-causing COL4A5 donor splice site mutation (c.687 + 1G > A). None of these variants were detected among 100 healthy Chinese individuals.
WES identified 2 novel and 2 known pathogenic COL4A3/COL4A4/COL4A5 mutations in 3 families with previously unexplained inherited kidney disease. These findings highlight the clinical range of collagen IV-related nephropathies and resolved diagnostic confusion arising from atypical or incomplete clinical/histological findings, allowing appropriate counselling and treatment advice to be given.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2369-15-175) contains supplementary material, which is available to authorized users.
PMCID: PMC4233041  PMID: 25381091
Collagen IV-related nephropathies; Whole exome sequencing; Novel mutation; Misdiagnosis
22.  Genome editing of BmFib-H gene provides an empty Bombyx mori silk gland for a highly efficient bioreactor 
Scientific Reports  2014;4:6867.
Evolution has produced some remarkable creatures, of which silk gland is a fascinating organ that exists in a variety of insects and almost half of the 34,000 spider species. The impressive ability to secrete huge amount of pure silk protein, and to store proteins at an extremely high concentration (up to 25%) make the silk gland of Bombyx mori hold great promise to be a cost-effective platform for production of recombinant proteins. However, the extremely low production yields of the numerous reported expression systems greatly hindered the exploration and application of silk gland bioreactors. Using customized zinc finger nucleases (ZFN), we successfully performed genome editing of Bmfib-H gene, which encodes the largest and most abundant silk protein, in B. mori with efficiency higher than any previously reported. The resulted Bmfib-H knocked-out B. mori showed a smaller and empty silk gland, abnormally developed posterior silk gland cells, an extremely thin cocoon that contain only sericin proteins, and a slightly heavier pupae. We also showed that removal of endogenous Bmfib-H protein could significantly increase the expression level of exogenous protein. Furthermore, we demonstrated that the bioreactor is suitable for large scale production of protein-based materials.
PMCID: PMC4215353  PMID: 25359576
23.  Indium segregation measured in InGaN quantum well layer 
Scientific Reports  2014;4:6734.
The indium segregation in InGaN well layer is confirmed by a nondestructive combined method of experiment and numerical simulation, which is beyond the traditional method. The pre-deposited indium atoms before InGaN well layer growth are first carried out to prevent indium atoms exchange between the subsurface layer and the surface layer, which results from the indium segregation. The uniform spatial distribution of indium content is achieved in each InGaN well layer, as long as indium pre-deposition is sufficient. According to the consistency of the experiment and numerical simulation, the indium content increases from 16% along the growth direction and saturates at 19% in the upper interface, which cannot be determined precisely by the traditional method.
PMCID: PMC4206869  PMID: 25339386
24.  A Comparative Study of Hollow Copper Sulfide Nanoparticles and Hollow Gold Nanospheres on Degradability and Toxicity 
ACS nano  2013;7(10):10.1021/nn403202w.
Gold and copper nanoparticles have been widely investigated for photothermal therapy of cancer. However, degradability and toxicity of these nanoparticles remain concerns. Here, we compare hollow CuS nanoparticles (HCuSNPs) with hollow gold nanospheres (HAuNS) in similar particle sizes and morphology following intravenous administration to mice. The injected pegylated HCuSNPs (PEG-HCuSNPs) are eliminated through both hepatobiliary (67 percentage of injected dose, %ID) and renal (23 %ID) excretion within one month post injection. By contrast, 3.98 %ID of Au is excreted from liver and kidney within one month after i.v. injection of pegylated HAuNS (PEG-HAuNS). Comparatively, PEG-HAuNS are almost non-metabolizable, while PEG-HCuSNPs are considered biodegradable nanoparticles. PEG-HCuSNPs do not show significant toxicity by histological or blood chemistry analysis. Principal component analysis and 2-D peak distribution plots of data from matrix-assisted laser desorption ionization-time of flight imaging mass spectrometry (MALDI-TOF IMS) of liver tissues demonstrated a reversible change in the proteomic profile in mice receiving PEG-HCuSNPs. This is attributed to slow dissociation of Cu ion from CuS nanoparticles along with effective Cu elimination for maintaining homeostasis. Nonetheless, an irreversible change in the proteomic profile is observed in the liver from mice receiving PEG-HAuNS by analysis of MALDI-TOF IMS data, probably due to the non-metabolizability of Au. This finding correlates with the elevated serum lactate dehydrogenase at 3 months after PEG-HAuNS injection, indicating potential long-term toxicity. The comparative results between the two types of nanoparticles will advance the development of HCuSNPs as a new class of biodegradable inorganic nanomaterials for photothermal therapy.
PMCID: PMC3870179  PMID: 24053214
hollow CuS nanoparticles (HCuSNPs); hollow gold nanospheres (HAuNS); degradability; toxicity; matrix-assisted laser desorption ionization-time of flight imaging mass spectrometry (MALDI-TOF IMS)
25.  Effect of atorvastatin on the expression of gamma-glutamyl transferase in aortic atherosclerotic plaques of apolipoprotein E–knockout mice 
Gamma-glutamyl transpeptidase (GGT) is now considered to be one of the risk factors for cardiovascular disease. However, whether statins can alter GGT levels in arterial atheromatous plaque has not yet been studied. Therefore, the aim of this study is to determine whether statins can effectively decrease the expression of GGT in arterial atheromatous plaques.
We randomly divided 45 apolipoprotein E–knockout (ApoE KO) male mice into three groups: normal diet (ND) group,high-cholesterol diet (HCD) group and high-cholesterol diet and atorvastatin (HCD + Ato) group. We fed high-cholesterol food to the HCD and HCD + Ato group. After eight weeks, atorvastatin 5 mg•kg−1•d−1 was given to HCD + Ato group mice. The serum GGT-1, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell-adhesion molecule-1 (VCAM-1) levels were measured at end of 16 weeks by using ELISA methods. The expressions of GGT-1, ICAM-1 and VCAM-1 in aorta were measured by RT-PCR and Western Blot.
The ApoE KO mice with HCD were associated with a marked increase in plasma lipid, inflammatory factors, GGT-1, ICAM-1 and VCAM-1. The expressions of GGT-1, ICAM-1 and VCAM-1 in HCD aortic tissue were increased. At the HCD + Ato group were treated with atorvastatin, the levels of lipid, GGT-1, ICAM-1 and VCAM-1were suppressed. Meanwhile, the expressions of GGT-1, ICAM-1 and VCAM-1 were significantly decreased in the whole aorta plaques.
The effect of statins on the expression of GGT in aorta plaque was firstly observed in animal model. The research shows that statins can significantly decrease the expression of GGT in aortic atherosclerotic plaques.
PMCID: PMC4210575  PMID: 25326709
Statins; Atherosclerosis; Gamma-glutamyltransferase; Inflammation

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