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1.  Dimethylenastron suppresses human pancreatic cancer cell migration and invasion in vitro via allosteric inhibition of mitotic kinesin Eg5 
Acta Pharmacologica Sinica  2011;32(12):1543-1548.
The mitotic kinesin Eg5 plays a critical role in bipolar spindle assembly, and its inhibitors have shown impressive anticancer activity in preclinical studies. This study was undertaken to investigate the effect of dimethylenastron, a specific inhibitor of Eg5, on the migration and invasion of pancreatic cancer cells.
Human pancreatic cancer cell lines PANC1, EPP85, BxPC3, CFPAC1, and AsPAC1 were used. Eg5 expression was examined using immunofluorescence microscopy. Cell migration and invasion were analyzed with wound healing and transwell assays. Cell proliferation was examined using sulforhodamine B and MTT assays. The binding of dimethylenastron to Eg5 was analyzed with a molecular modeling study, and the ADP release rate was examined with the MANT-ADP reagent.
Eg5 expression was 9–16-fold up-regulated in the 5 pancreatic cancer cell lines. Treatment of PANC1 pancreatic cancer cells with dimethylenastron (3 and 10 μmol/L) for 24 h suppressed the migratory ability of the cancer cells in a concentration-dependent manner. The invasion ability of the cancer cells was also reduced by the treatment. However, treatment of PANC1 cells with dimethylenastron (3 and 10 μmol/L) for 24 h had no detectable effect on their proliferation, which was inhibited when the cancer cells were treated with the drug for 72 h. Molecular modeling study showed that dimethylenastron could allosterically inhibit the motor domain ATPase of Eg5 by decreasing the rate of ADP release.
Dimethylenastron inhibits the migration and invasion of PANC1 pancreatic cancer cells, independent of suppressing the cell proliferation. The findings provide a novel insight into the mechanisms of targeting Eg5 for pancreatic cancer chemotherapy.
PMCID: PMC4010204  PMID: 21986572
kinesin; Eg5; dimethylenastron; pancreatic cancer; cell migration; cell invasion; cell proliferation; molecular modeling
2.  HIF-1α -1790G>A polymorphism significantly increases the risk of digestive tract cancer: A meta-analysis 
AIM: To investigate the association between hypoxia-inducible factor-1α (HIF-1α) polymorphisms (-1772C>T and -1790G>A) and the risk of digestive tract cancer.
METHODS: A total of 13 eligible studies were retrieved from PubMed, EMBASE, and the China National Knowledge Infrastructure database. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations.
RESULTS: By pooling the eligible studies, we found that the HIF-1α -1772C>T polymorphism was not associated with the risk of developing digestive tract cancer (dominant comparison, OR: 1.156; 95%CI: 0.839-1.593; Pheterogeneity = 0.007), and no significant association was found in the Asian population or the Caucasian population. However, for the -1790G>A polymorphism, carriers of the variant -1790A allele had a significantly increased risk of digestive tract cancer compared with those with the wildtype -1790G allele (dominant comparison, OR: 3.252; 95%CI: 1.661-6.368; Pheterogeneity < 0.001). Additionally, this increased risk of digestive cancer was only detected in Asians; there was no significant association in Caucasians.
CONCLUSION: This meta-analysis demonstrates that the HIF-1α -1790G>A polymorphism is associated with a significantly increased risk of digestive tract cancer, while the -1772C>T polymorphism is not.
PMCID: PMC4316108  PMID: 25663785
Hypoxia-inducible factor-1α; Digestive tract cancer; Polymorphisms; Cancer risk; Meta-analysis
3.  The fate of recent duplicated genes following a fourth-round whole genome duplication in a tetraploid fish, common carp (Cyprinus carpio) 
Scientific Reports  2015;5:8199.
Whole genome duplication (WGD) results in extensive genetic redundancy. In plants and yeast, WGD is followed by rapid gene deletions and intense expression differentiation with slow functional divergence. However, the early evolution of the gene differentiation processes is poorly understood in vertebrates because almost all studied WGDs are extremely ancient, and the genomes have returned to a diploid status. Common carp had a very recent fourth round of WGD dated to 8 million years ago. It therefore constitutes an ideal model to study early-stage functional divergence and expression differentiation in vertebrates. We identified 1,757 pairs of recently duplicated genes (RDGs) originating from this specific WGD and found that most ancestral genes were retained in duplicate. Most RDGs were conserved and under selective pressure. Gene expression analysis across six tissues revealed that 92.5% of RDG pairs were co-expressed in at least one tissue and that the expression of nearly half pairs ceased to be strongly correlated, indicating slow spatial divergence but rapid expression dissociation. Functional comparison revealed that 25% of pairs had functional divergence, of which neo- and sub-functionalization were the main outcomes. Our analysis revealed slow gene loss but rapid and intense expression and function differentiation after WGD.
PMCID: PMC4314655  PMID: 25645996
4.  Protective effect of epimedium combined with oligomeric proanthocyanidins on exercise-induced renal ischemia-reperfusion injury of rats 
Objective: This paper studied the protective effect and mechanism of epimedium combined with oligomeric proanthocyanidins on exercise-induced renal ischemia-reperfusion injury of rats. Methods: In the experiment, the rats were given exhaustive swimming training and then their blood urea nitrogen (BUN) and other biochemical indexes were measured after they were given gastric perfusion with 6.01 g/kg doze of epimedium and 50 mg/kg doze of oligomeric proanthocyanidins for 56 days. Results: The result indicated that 8 weeks of over training led to ischemia-reperfusion injury of rats. Moreover, their kidney tissues were significantly changed pathologically and renal functions drastically damaged. BUN and serum creatinine increased and EOM group (P < 0.05), OPCOM group (P < 0.05) and EOPCOM group (P < 0.01) were lower than OM group. EOPCOM group was lower than OPCOM group. SOD activity decreased, EOM group (P < 0.05), OPCOM group (P < 0.05), EOPCOM group (P < 0.01) higher than OM group, and EOPCOM group (P < 0.05) higher than OPCOM group. The content of MDA increased, EOM group (P < 0.05), OPCOM group (P < 0.05), EOPCOM group (P < 0.01) lower than OM group, and EOPCOM group (P < 0.05) lower than OPCOM group. Conclusion: Both epimedium and oligomeric proanthocyanidins can boost SOD activity, clean oxygen radicals, clean and alleviate peroxidation of lipids, which exert protection on exercise-induced renal ischemia-reperfusion. The two combined yield a much better result.
PMCID: PMC4307546  PMID: 25664099
Epimedium; oligomeric proanthocyanidins; exercise-induced ischemia-reperfusion
5.  Sclerosing cholangitis secondary to bleomycin-iodinated embolization for liver hemangioma 
World Journal of Gastroenterology : WJG  2014;20(46):17680-17685.
Sclerosing cholangitis (SC) is a rarely reported morbidity secondary to transcatheter arterial chemoembolization (TACE) with bleomycin-iodinated oil (BIO) for liver cavernous hemangioma (LCH). This report retrospectively evaluated the diagnostic and therapeutic course of a patient with LDH who presented obstructive jaundice 6 years after TACE with BIO. Preoperative imaging identified a suspected malignant biliary stricture located at the convergence of the left and right hepatic ducts. Operative exploration demonstrated a full-thickness sclerosis of the hilar bile duct with right hepatic duct stricture and right lobe atrophy. Radical hepatic hilar resection with right-side hemihepatectomy and Roux-en-Y hepaticojejunostomy was performed because hilar cancer could not be excluded on frozen biopsy. Pathological results showed chronic pyogenic inflammation of the common and right hepatic ducts with SC in the portal area. Secondary SC is a long-term complication that may occur in LCH patients after TACE with BIO and must be differentiated from hilar malignancy. Hepatic duct plasty is a definitive but technically challenging treatment modality for secondary SC.
PMCID: PMC4265633  PMID: 25516686
Sclerosing cholangitis; Secondary; Transcatheter arterial chemoembolization; Bleomycin-iodinated oil; Liver cavernous hemangioma; Hilar stricture; Differential diagnosis; Definitive surgery
6.  Direct Conversion of Adipocyte Progenitors into Functional Neurons 
Cellular Reprogramming  2013;15(6):484-489.
Ectopic expression of a set of transcription factors in somatic cells could reprogram the differentiated cell fate into the pluripotent state, and the resultant so-called induced pluripotent stem cells (iPSCs) have been proposed as seed cells for cell therapy–based regenerative medicine. However, their tumorigenicity limited the further application of iPSCs clinically. More recently, collected evidence has shown that differentiated somatic cells could be directly converted into other types of somatic cells through overexpression of transcription factors enriched in the targeted cell types. Induced neurons have been recently converted from fibroblasts; however, it remains unknown if other cell types could be used for neuron induction. One easily accessible cell type, adipocyte progenitor cells (APCs), has the advantage of steady proliferation in vitro and lower mortality rate. In the present study, we demonstrated that APCs could also be converted into functional neurons using the three transcriptional factors (Ascl1, Brn2, Myt1l) that could convert fibroblasts into neurons. Moreover, we also demonstrated that vitamin C could elevate the efficiency of conversion of the APCs and fibroblasts into neurons. The converted cells represent another appropriate cell resource for clinical application and disease modeling.
PMCID: PMC3848438  PMID: 24182316
7.  Stanniocalcin-1 protects bovine intestinal epithelial cells from oxidative stress-induced damage 
Journal of Veterinary Science  2014;15(4):475-483.
Chronic enteritis can produce an excess of reactive oxygen species resulting in cellular damage. Stanniocalcin-1(STC-1) reportedly possesses anti-oxidative activity, the aim of this study was to define more clearly the direct contribution of STC-1 to anti-oxidative stress in cattle. In this study, primary intestinal epithelial cells (IECs) were exposed to hydrogen peroxide (H2O2) for different time intervals to mimic chronic enteritis-induced cellular damage. Prior to treatment with 200 µM H2O2, the cells were transfected with a recombinant plasmid for 48 h to over-express STC-1. Acridine orange/ethidium bromide (AO/EB) double staining and trypan blue exclusion assays were then performed to measure cell viability and apoptosis of the cells, respectively. The expression of STC-1 and apoptosis-related proteins in the cells was monitored by real-time PCR and Western blotting. The results indicated that both STC-1 mRNA and protein expression levels positively correlated with the duration of H2O2 treatment. H2O2 damaged the bovine IECs in a time-dependent manner, and this effect was attenuated by STC-1 over-expression. Furthermore, over-expression of STC-1 up-regulated Bcl-2 protein expression and slightly down-regulated caspase-3 production in the damaged cells. Findings from this study suggested that STC-1 plays a protective role in intestinal cells through an antioxidant mechanism.
PMCID: PMC4269589  PMID: 24962416
Bcl-2; chronic enteritis; oxidative damage; stanniocalcin-1
8.  Increased level of E protein activity during iNKT development promotes differentiation of iNKT2 and iNKT17 subsets 
Journal of immunology (Baltimore, Md. : 1950)  2013;191(10):10.4049/jimmunol.1301546.
E protein transcription factors, and their natural inhibitors, Id proteins, play critical and complex roles during lymphoid development. Here we report that partial maintenance of E protein activity during positive selection results in a change in the cell fate determination of developing iNKT cells, with a block in the development of iNKT1 cells, and a parallel increase in the iNKT2 and iNKT17 subsets. Since the expression levels of the transcription factors that drive these alternative functional fates (GATA-3, RORγT, T-bet and Runx-3) are not altered, our results suggest that E protein activity controls a novel checkpoint that regulates the number of iNKT precursors that choose each fate.
PMCID: PMC3832958  PMID: 24123679
E protein; Id; iNKT; T-bet; Runx-3; GATA-3; RORγT
9.  Evaluation of Hypoglycemic Efficacy of Tangningtongluo Formula, a Traditional Chinese Miao Medicine, in Two Rodent Animal Models 
Journal of Diabetes Research  2014;2014:745419.
Traditional Chinese medicines largely lack adequate and scientifically rigorous evidence regarding efficacy and functional mechanisms. The present study was aimed to confirm the hypoglycemic effect of Tangningtongluo (TNTL) formula, a traditional Chinese Miao medicine, in two animal models: high-fat diet and streptozotocin- (STZ-) induced diabetic rats and C57BL/KsJ-db/db diabetic mice. After 4 weeks, TNTL intervention in STZ-induced diabetic rats yielded in significant improvement on the glucose tolerance test. Moreover, the islet histopathology showed that oral TNTL reduced the severity of islet necrosis in pancreases tissue. Compared with diabetic controls, a 12-week TNTL treatment regimen (dosages = 0.9, 1.8, and 3.6 g/kg) in db/db mice significantly decreased fasting glucose and HbA1c. Additionally, oral glucose tolerance in TNTL-treated mice improved significantly, compared with diabetic mice receiving metformin. Finally, tissue histopathology and biochemical index evaluations revealed significant improvement in TNTL-treated mice. Taken together, our results show that TNTL exerted a strong hypoglycemic effect in two diabetic rodent animal models, preserving β-cells in the pancreas islet and reducing the risk of diabetic retinopathy and nephropathy.
PMCID: PMC4238278  PMID: 25431772
10.  Clinical significance of gefitinib antitumor activity in patients with lung adenocarcinoma 
Oncology Letters  2014;9(1):257-261.
Non-small cell lung cancer is a subtype of adenocarcinoma, which has previously shown positive responses to gefitinib. The aim of the current study was to determine a clinical profile of gefitinib-induced disease controls for patients with lung adenocarcinoma. Retrospective evaluation of the clinical characteristics of 52 lung adenocarcinoma patients, enrolled at the Zhejiang Cancer Hospital (Hangzhou, China) between October 2004 and August 2008, was undertaken. All patients received gefitinib (250 mg/day orally) until disease progression or until an unacceptable toxicity was observed. Of the 52 patients, complete response (CR) and partial response (PR) rates were 23.1% (12/52) and 57.7% (30/52), respectively. An additional 19.2% (10/52) of patients demonstrated stable disease (SD) after three months of treatment with gefitinib. Disease control was observed in the primary lesion, and tumor metastasis to the lungs, brain, adrenal glands, pleura, peritoneum, pericardium, bone and lymph nodes was identified. The one-year progression-free survival (PFS) and overall survival (OS) rates were 74.8 and 78.0%, respectively. Multivariate analysis revealed that female patients were associated with significantly longer survival times when compared with males (hazard ratio, 0.077; 95% confidence interval [CI], 0.007–0.083; P=0.035). One-year PFS and OS rates in CR, PR and SD patients were 77.8, 73.9 and 33.3%, and 89.2, 79.8 and 33.7%, respectively, although neither difference was identified to be statistically significant. In addition, the median OS of SD patients was 12 months (95% CI, 7.2–16.8 months). Brain metastasis was the major site of disease progression (23.1%). Gefitinib treatment for patients with lung adenocarcinoma showed a marked long-term survival benefit, even in SD patients. However, further studies are required to analyze the efficacy of gefitinib in penetrating the blood-brain barrier in order to prolong PFS in patients with lung adenocarcinoma.
PMCID: PMC4246704  PMID: 25435970
non-small cell lung cancer; gefitinib; targeted therapy
11.  The Inhibition of the Components from Shengmai Injection towards UDP-Glucuronosyltransferase 
The mechanism of shengmai injection- (SMI-) related drug-drug interaction remains unclear. Evaluation of the inhibition potential of SMI's ingredients towards UDP-glucuronosyltransferases (UGTs) activity will provide a new insight to understand SMI-related drug-drug interaction. In vitro incubation system to model UGT reaction was used. Recombinant UGT isoforms-catalyzed 4-methylumbelliferone (4-MU) glucuronidation and UGT1A4-catalyzed trifluoperazine (TFP) glucuronidation reactions were employed to phenotype the inhibition profile of maidong's components towards the activity of UGT isoforms. Different inhibition potential of maidong's components towards various UGT isoforms was observed. Based on the inhibition kinetic investigation results, ophiopogonin D (OD) noncompetitively inhibited UGT1A6 and competitively inhibited UGT1A8, ophiopogonin D′ (OD′) noncompetitively inhibited UGT1A6 and UGT1A10, and ruscorectal (RU) exhibited competitive inhibition towards UGT1A4. The inhibition kinetic parameters were calculated to be 20.6, 40.1, 5.3, 9.0, and 0.02 μM, respectively. In combination with our previous results obtained for the inhibition of UGT isoforms by ginsenosides and wuweizi components, the important SMI ingredients exhibiting strong inhibition towards UGT isoforms were highlighted. All the results obtained in the present study provide a new insight to understand SMI-related drug-drug interaction.
PMCID: PMC4229968  PMID: 25530784
12.  Data access for the 1,000 Plants (1KP) project 
GigaScience  2014;3:17.
The 1,000 plants (1KP) project is an international multi-disciplinary consortium that has generated transcriptome data from over 1,000 plant species, with exemplars for all of the major lineages across the Viridiplantae (green plants) clade. Here, we describe how to access the data used in a phylogenomics analysis of the first 85 species, and how to visualize our gene and species trees. Users can develop computational pipelines to analyse these data, in conjunction with data of their own that they can upload. Computationally estimated protein-protein interactions and biochemical pathways can be visualized at another site. Finally, we comment on our future plans and how they fit within this scalable system for the dissemination, visualization, and analysis of large multi-species data sets.
PMCID: PMC4306014  PMID: 25625010
Viridiplantae; Biodiversity; Transcriptomes; Phylogenomics; Interactions; Pathways
13.  Octreotide attenuates liver fibrosis by inhibiting hepatic heme oxygenase-1 expression 
Molecular Medicine Reports  2014;11(1):83-90.
The aim of the present study was to investigate the effects of octreotide treatment on hepatic heme oxygenase-1 (HO-1) expression, together with the influence of altered hepatic HO-1 expression levels on hepatic function and fibrosis in bile duct-ligated rats. The rats were divided randomly into sham, cirrhotic, cobalt protoporphyrin and octreotide treatment groups. The expression levels of hepatic HO-1 mRNA were measured by reverse-transcription polymerase chain reaction, while the protein expression was determined by western blotting and immunohistochemical analysis. Hematoxylin and eosin, and Van Gieson’s staining, along with determination of the hydroxyproline content in the liver, were performed to determine the degree of liver fibrosis. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and carboxyhemoglobin (COHb) in arterial blood, and the mean arterial pressure and portal vein pressure were also measured. As compared with the sham group, hepatic HO-1 mRNA and protein expression levels, serum levels of ALT, AST and TBIL, COHb in arterial blood, hydroxyproline and collagen type I content were all significantly increased in the cirrhotic group. As compared with the cirrhotic group, the octreotide-treated group exhibited significantly reduced hepatic HO-1 expression levels, serum levels of ALT, AST and TBIL, COHb in arterial blood and the extent of hepatic fibrosis, whereas the cobalt protoporphyrin group exhibited significantly increased hepatic HO-1 expression levels, as well as aggravated hepatic function and fibrosis (P<0.05). In conclusion, octreotide inhibited hepatic HO-1 overexpression in cirrhotic rats, reduced hepatic HO-1 expression levels to relieve liver injury and attenuated liver fibrosis.
PMCID: PMC4237075  PMID: 25338529
heme oxygenase-1; carbon monoxide; octreotide; bile duct ligation; liver fibrosis
14.  Reliability and validity of the Chinese version of reporting of clinical adverse events scale (C-RoCAES) 
Background: Adverse event is a crucial issue affecting patient’s safety of healthcare services. To assess nurses’ attitude of reporting adverse events is important to establish a safe environment for patients. However, no relevant instrument has been validated and used in China. This study was to examine validity and reliability of Chinese version of Reporting of Clinical adverse Event Scale (C-RoCAES). Material and methods: Chinese version of 25-item RoCAES was used in a sample of 1557 nurses. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were selected for construct validity test. Internal consistency was also examined. Results: After CFA and EFA, two items were removed and two items loaded on different factors in our sample. Five factors were generated, including perceived blame, perceived criteria for identifying events that should be reported, perceptions of colleagues’ expectations, perceived benefits of reporting and perceived clarity of reporting procedures. Cronbach’s alpha for the total scale and subscales ranged from 0.70 to 0.85. Conclusion: C-RoCAES is applicable to healthcare services of China. The instrument provide information for the providers of healthcare services to develop staff education regarding patient safety, and also help them to evaluate strategies of preventing adverse events in clinical practice in China.
PMCID: PMC4238501  PMID: 25419395
Reporting of clinical adverse events scale (RoCAES); confirmatory factor analysis; exploratory factor analysis
15.  The effects of surface spin on magnetic properties of weak magnetic ZnLa0.02Fe1.98O4 nanoparticles 
Nanoscale Research Letters  2014;9(1):545.
In order to prominently investigate the effects of the surface spin on the magnetic properties, the weak magnetic ZnLa0.02Fe1.98O4 nanoparticles were chosen as studying objects which benefit to reduce as possibly the effects of interparticle dipolar interaction and crystalline anisotropy energies. By annealing the undiluted and diluted ZnLa0.02Fe1.98O4 nanoparticles at different temperatures, we observed the rich variations of magnetic ordering states (superparamagnetism, weak ferromagnetism, and paramagnetism). The magnetic properties can be well understood by considering the effects of the surface spin of the magnetic nanoparticles. Our results indicate that in the nano-sized magnets with weak magnetism, the surface spin plays a crucial rule in the magnetic properties.
PMCID: PMC4186921  PMID: 25294976
Nanoparticles; Ferrite; Surface spin; Magnetic properties
16.  Telekin suppresses human hepatocellular carcinoma cells in vitro by inducing G2/M phase arrest via the p38 MAPK signaling pathway 
Acta Pharmacologica Sinica  2014;35(10):1311-1322.
Telekin, isolated from the Chinese herb Carpesium divaricatum, has shown anti-proliferation effects against various cancer cells, including hepatocellular carcinoma cells. In this study, we investigated the anti-proliferation mechanisms of telekin in human hepatocellular carcinoma HepG2 cells in vitro.
HepG2 cells were treated with telekin. Cell viability was evaluated using MTT assay. Flow cytometry was used to measure cell cycle profiles, ROS level and apoptosis. The protein expression levels were analyzed with Western blotting.
Telekin (3.75–30 μmol/L) dose-dependently inhibited the viability of HepG2 cells and induced l apoptosis. Furthermore, the treatment induced cell cycle arrest at G2/M phase, accompanied by significantly increased the phosphorylation of Cdc25A and Cdc2, and decreased Cyclin B1 level. Moreover, the treatment significantly stimulated ROS production, and increased the phosphorylation of p38 and MAPKAPK-2 in the cells. Pretreatment with the antioxidant NAC (2.5, 5, and 10 mmol/L), or the p38 MAPK inhibitor SB203580 (2.5 and 5 μmol/L) dose-dependently attenuated these telekin-induced effects in the cells.
Telekin suppresses hepatocellular carcinoma cells in vitro by inducing G2/M phase arrest via activating the p38 MAPK pathway.
PMCID: PMC4186990  PMID: 25176399
Telekin; hepatocellular carcinoma; HepG2 cell; cell cycle arrest; ROS; p38 MAPK pathway; apoptosis; antioxidant; NAC; SB203580
17.  The Impact of Clickers Instruction on Cognitive Loads and Listening and Speaking Skills in College English Class 
PLoS ONE  2014;9(9):e106626.
Clickers might own a bright future in China if properly introduced although they have not been widely acknowledged as an effective tool to facilitate English learning and teaching in Chinese contexts. By randomly selecting participants from undergraduates in a university in China over four academic years, this study aims to identify the impact of clickers on college English listening and speaking skills, and differences in cognitive loads between clickers and traditional multimedia assisted instruction modes. It was concluded that in China's college English class, compared with multimedia assisted instruction, (1) clickers could improve college English listening skills; (2) clickers could improve college English speaking skills; and (3) clickers could reduce undergraduates' cognitive loads in College English Class. Reasons for the results and defects in this study were also explored and discussed, based on learning, teaching and cognitive load theories. Some Suggestions for future research were also raised.
PMCID: PMC4156364  PMID: 25192424
18.  Released micromachined beams utilizing laterally uniform porosity porous silicon 
Nanoscale Research Letters  2014;9(1):426.
Suspended micromachined porous silicon beams with laterally uniform porosity are reported, which have been fabricated using standard photolithography processes designed for compatibility with complementary metal-oxide-semiconductor (CMOS) processes. Anodization, annealing, reactive ion etching, repeated photolithography, lift off and electropolishing processes were used to release patterned porous silicon microbeams on a Si substrate. This is the first time that micromachined, suspended PS microbeams have been demonstrated with laterally uniform porosity, well-defined anchors and flat surfaces.
81.16.-c; 81.16.Nd; 81.16.Rf
PMCID: PMC4151280  PMID: 25221457
Porous silicon; Photolithography; Microbeams; Release
19.  Analysis of peripapilary retinal nerve fiber layer thickness of healthy Chinese from northwestern Shanghai using Cirrus HD-OCT 
To investigate peripapillary retinal nerve fiber layer (RNFL) thickness of healthy Chinese individuals from northwestern Shanghai using Cirrus HD-OCT (Carl Zeiss Meditec, Inc. Dublin, CA, USA).
The peripapillary RNFL thickness of 720 eyes from 360 healthy Chinese participants were measured using the Optic Disc Cube 200×200 protocol. Each eye was scanned 3 times. Global and each quadrant's RNFL thickness around the optic nerve were compared between genders, and interocular differences were analyzed. The correlation between global RNFL thickness and age were also assessed in this study.
The mean global, superior, nasal, inferior and temporal RNFL thickness of all the eyes were 96.04±7.40 µm, 118.36±13.52 µm, 67.63±8.60 µm, 125.17±13.48 µm, 72.49±10.70 µm, respectively. When analyzing between genders, the mean nasal RNFL thickness of male and female were 68.29±8.44 µm and 66.97±8.70 µm, with statistically significant difference (P=0.038), while the data of global, superior, inferior and temporal quadrant showed no significant difference (all P>0.05). When analyzing interocular differences, the mean RNFL thickness of all the right eyes and all the left eyes were 116.46±13.17 µm and 120.27±13.61 µm in superior quadrant (P<0.001); 68.74±8.80 µm and 66.52±8.25 µm in nasal quadrant (P<0.001); 73.16±10.95 and 71.83±10.41 in temporal quadrant (P<0.001), all having statistically significant differences. There were no statistically significant interocular differences of global and inferior RNFL thickness (both P>0.05). There was a significantly negative correlation (r=-0.618, P<0.001) between the mean global RNFL thickness and the age.
In healthy Chinese from northwestern Shanghai, there were no significant differences detected interocular difference and between genders in the mean global RNFL thickness. Nevertheless, significant difference existed in the nasal quadrant between genders, and interocular differences existed in the superior, nasal and temporal quadrants. The RNFL thickness appeared to gradually decrease with age.
PMCID: PMC4137201  PMID: 25161937
retinal nerve fiber layer; optical coherence tomography; Chinese
20.  Comparison of primary target volumes delineated on four-dimensional CT and 18 F-FDG PET/CT of non-small-cell lung cancer 
To determine the optimal threshold of 18 F-fluorodexyglucose (18 F-FDG) positron emission tomography CT (PET/CT) images that generates the best volumetric match to internal gross target volume (IGTV) based on four-dimensional CT (4DCT) images.
Twenty patients with non-small cell lung cancer (NSCLC) underwent enhanced three-dimensional CT (3DCT) scan followed by enhanced 4DCT scan of the thorax under normal free breathing with the administration of intravenous contrast agents. A total of 100 ml of ioversol was injected intravenously, 2 ml/s for 3DCT and 1 ml/s for 4DCT. Then 18 F-FDG PET/CT scan was performed based on the same positioning parameters (the same immobilization devices and identical position verified by laser localizer as well as skin marks). Gross target volumes (GTVs) of the primary tumor were contoured on the ten phases images of 4DCT to generate IGTV10. GTVPET were determined with eight different threshold using an auto-contouring function. The differences in the position, volume, concordance index (CI) and degree of inclusion (DI) of the targets between GTVPET and IGTV10 were compared.
The images from seventeen patients were suitable for further analysis. Significant differences between the centric coordinate positions of GTVPET (excluding GTVPET15%) and IGTV10 were observed only in z axes (P < 0.05). GTVPET15%, GTVPET25% and GTVPET2.0 were not statistically different from IGTV10 (P < 0.05). GTVPET15% approximated closely to IGTV10 with median percentage volume changes of 4.86%. The best CI was between IGTV10 and GTVPET15% (0.57). The best DI of IGTV10 in GTVPET was IGTV10 in GTVPET15% (0.80).
None of the PET-based contours had both close spatial and volumetric approximation to the 4DCT IGTV10. At present 3D-PET/CT should not be used for IGTV generation.
PMCID: PMC4150978  PMID: 25123450
Non-small cell lung cancer; Fluorodeoxyglucose positron emission tomography; Four-dimensional computed tomography; Standardized uptake value
21.  Higher blood pressure control rate in a real life management program provided by the community health service center in China 
BMC Public Health  2014;14(1):801.
Community health service center (CHSC) in China is always regarded as a good facility of primary care, which plays an important role in chronic non-communicable disease management. This study aimed to investigate the blood pressure (BP) control rate in a real life CHSC-based management program and its determinants.
The study enrolled 3191 patients (mean age of 70 ± 10 years, 43% males) in a hypertension management program provided by the Yulin CHSC (Chengdu, China), which had been running for 9 years. Uncontrolled BP was defined as the systolic BP of ≥140 mmHg and/or the diastolic BP of ≥90 mmHg, and its associated factors were analyzed by using logistic regression.
The duration of stay in the program was 33 ± 25 months. When compared with the BP at entry, the recent BP was significantly lowered (147 ± 17 vs. 133 ± 8 mmHg; 83 ± 11 vs. 75 ± 6 mmHg) and the BP control rate was dramatically increased (32 vs. 85%) (all p < 0.001). The age of >70 years [1.40 (odds ratio), 1.15-1.71 (95% confidence interval)], female gender (0.76, 0.63-0.93), longer stay of >33 months (0.77, 0.63-0.94), doctor in charge (0.97, 0.95-0.99), and the use of calcium channel blocker (1.35, 1.09-1.67) were significantly related to uncontrolled BP at the recent follow up (all p < 0.05).
This CHSC-run hypertension program provides an ideal platform of multi-intervention management, which is effective in achieving higher BP control rate in community patient population. However, the BP control status could be affected by age, gender and adherence of the patients, as well as practice behavior of the doctors.
PMCID: PMC4133080  PMID: 25098940
Hypertension; Blood pressure; Disease management; Public health; Community
22.  The clinical characteristics and treatment outcome of 57 children and adolescents with primary central nervous system germ cell tumors 
Chinese Journal of Cancer  2014;33(8):395-401.
Primary central nervous system germ cell tumors (CNS-GCTs) in children and adolescents have unique clinical features and methods of treatment compared with those in adults. There is little information about Chinese children and adolescents with CNS-GCTs. Therefore, in this study we retrospectively analyzed the clinical features and treatment outcome of Chinese children and adolescents with primary CNS-GCTs. Between January 2002 and December 2012, 57 untreated patients from a single institution were enrolled. They were diagnosed with CNS-GCTs after pathologic or clinical assessment. Of the 57 patients, 41 were males and 16 were females, with a median age of 12.8 years (range, 2.7 to 18.0 years) at diagnosis; 43 (75.4%) had non-germinomatous germ cell tumors (NGGCTs) and 14 (24.6%) had germinomas; 44 (77.2%) had localized disease and 13 (22.8%) had extensive lesions. Fifty-three patients completed the prescribed treatment, of which 18 underwent monotherapy of surgery, radiotherapy, or chemotherapy, and 35 underwent multimodality therapies that included radiotherapy combined with chemotherapy or surgery combined with chemotherapy and/or radiotherapy. PEB (cisplatin, etoposide, and bleomycin) protocol was the major chemotherapy regimen. The median follow-up time was 32.3 months (range, 1.2 to 139 months). Fourteen patients died of relapse or disease progression. The 3-year event-free survival (EFS) and overall survival rates for all patients were 72.2% and 73.8%, respectively. The 3-year EFS was 92.9% for germinomas and 64.8% for NGGCTs (P = 0.064). The 3-year EFS rates for patients with NGGCTs who underwent monotherapy and multimodality therapies were 50.6% and 73.5%, respectively (P = 0.042). Our results indicate that multimodality therapies including chemotherapy plus radiotherapy were better treatment option for children and adolescents with CNS-GCTs.
PMCID: PMC4135369  PMID: 25011460
Primary central nervous system germ cell tumors; chemotherapy; radiotherapy; survival rate; children
23.  Notch-regulated periphery B cell differentiation involves suppression of E protein function 
Notch signaling pathway plays important roles in promoting the generation of marginal zone (MZ) B cells at the expense of follicular (FO) B cells during periphery B cell maturation, but the underlying molecular mechanisms are not well understood. We hypothesize that Notch favors the generation of MZ B cells by down-regulating E protein activity. Here, we demonstrated that expression of Id2 and ankyrin-repeat SOCS box-containing protein 2 (Asb2) was elevated in MZ B cells and by Notch signaling. Id2 inhibits the DNA binding activity of E proteins whereas Asb2 facilitates E protein ubiquitination. Next, we examined the phenotypes of splenic B cells in mice expressing constitutively active Notch1 and/or two gain-of-function mutants of E proteins that counteract Id2-mediated inhibition or Notch-induced degradation. We found that up-regulation of E proteins promoted the formation of FO B cells while it suppressed the maturation of MZ B cells. In contrast, excessive amounts of Notch1 stimulated the differentiation of MZ B cells and inhibited the production of FO B cells. More interestingly, the effects of Notch1 were reversed by gain of E protein function. Furthermore, high levels of Bcl-6 expression in FO B cells was shown to be diminished by Notch signaling and restored by E proteins. In addition, E proteins facilitated and Notch hindered the differentiation of transitional B cells. Taken together, it appears that Notch regulates peripheral B cell differentiation, at least in part, through opposing E protein function.
PMCID: PMC3702643  PMID: 23752615
24.  Porphyria cutanea tarda and Sjogren's syndrome* 
Anais Brasileiros de Dermatologia  2014;89(4):689-691.
Porphyria cutanea tarda is prevalent in connective tissue disease, common in systemic lupus erythematosus. However, the co-existence of primary sjogren's syndrome and porphyria cutanea tarda is rare and poses diagnostic and therapeutic challenges. We report a case of porphyria cutanea tarda associated with primary sjogren's syndrome.
PMCID: PMC4148296  PMID: 25054769
Porphyria cutanea tarda; Sjogren's syndrome; Skin and connective tissue diseases
25.  Id1 expression promotes peripheral CD4+ T cell proliferation and survival upon TCR activation without co-stimulation 
Although the role of E proteins in the thymocyte development is well documented, much less is known about their function in peripheral T cells. Here we demonstrated that CD4 promoter-driven transgenic expression of Id1, a naturally occurring dominant-negative inhibitor of E proteins, can substitute for the co-stimulatory signal delivered by CD28 to facilitate the proliferation and survival of naïve CD4+ cells upon anti-CD3 stimulation. We next discovered that IL-2 production and NF-κB activity after anti-CD3 stimulation were significantly elevated in Id1-expressing cells, which may be, at least in part, responsible for the augmentation of their proliferation and survival. Taken together, results from this study suggest an important role of E and Id proteins in peripheral T cell activation. The ability of Id proteins to by-pass co-stimulatory signals to enable T cell activation has significant implications in regulating T cell immunity.
PMCID: PMC3955101  PMID: 23707719
Inhibitor of differentiation; E protein; CD4+ T cell; co-stimulation; T cell activation

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