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1.  1HNMR-based metabolomic profile of rats with experimental acute pancreatitis 
BMC Gastroenterology  2014;14:115.
Background
Acute pancreatitis (AP) is a common inflammatory disease of the pancreas accompanied by serious metabolic disturbances. Nevertheless, the specific metabolic process of this disease is still unclear. Characterization of the metabolome may help identify biomarkers for AP. To identify potential biomarkers, this study therefore investigated the 1H-nuclear magnetic resonance (NMR)-based metabolomic profile of AP.
Methods
Fourteen male adult Sprague–Dawley rats were randomized into two groups: the AP group, in which AP was induced by retrograde ductal infusion of 3.5% sodium taurocholate; and the sham operation group (SO), in which rats were infused with 0.9% saline. Blood samples were obtained 12 hours later and a 600 MHz superconducting NMR spectrometer was used to detect plasma metabolites. Principal components analysis (PCA) and partial least squares-discriminant analysis after orthogonal signal correction (OSC-PLS-DA) were used to analyze both longitudinal Eddy-delay (LED) and Carr–Purcell–Meiboom–Gill (CPMG) spectra.
Results
Differences in plasma metabolites between the two groups were detected by PCA and PLS-DA of 1HNMR spectra. Compared with the SO group, plasma levels of lactate (δ 1.3, 1.34, 4.1), valine (δ 0.98, 1.02), succinic acid (δ 2.38), 3-hydroxybutyric acid (3-HB, δ 1.18), high density lipoprotein (HDL, δ 0.8), and unsaturated fatty acid (UFA, δ 2.78, 5.3) were elevated in the AP group, while levels of glycerol (δ 3.58, 3.66), choline (δ 3.22), trimethylamine oxide (TMAO, δ 3.26), glucose (δ 3–4), glycine (δ 3.54), very low density lipoprotein (VLDL, δ 1.34) and phosphatidylcholine (Ptd, δ 2.78) were decreased.
Conclusions
AP has a characteristic metabolic profile. Lactate, valine, succinic acid, 3-HB, HDL, UFA, glycerol, choline, TMAO, glucose, glycine, VLDL, and Ptd may be potential biomarkers of early stage AP.
doi:10.1186/1471-230X-14-115
PMCID: PMC4100530  PMID: 24975214
Metabolomics; Acute pancreatitis; 1HNMR; PCA analysis; PLS-DA analysis
2.  A pilot study on acute inflammation and cancer: a new balance between IFN-γ and TGF-β in melanoma 
Recent data have redefined the concept of inflammation as a critical component of tumor progression. However, there has been little development on cases where inflammation on or near a wound and a tumor exist simultaneously. Therefore, this pilot study aims to observe the impact of a wound on a tumor, to build a new mouse tumor model with a manufactured surgical wound representing acute inflammation, and to evaluate the relationship between acute inflammation or wound healing and the process of tumor growth. We focus on the two phases that are present when acute inflammation influences tumor. In the early phase, inhibitory effects are present. The process that produces these effects is the functional reaction of IFN-γ secretions from a wound inflammation. In the latter phase, the inhibited tumor is made resistant to IFN-γ through the release of TGF-β to balance the inflammatory factor effect on the tumor cells. A pair of cytokines IFN-γ/TGF-β established a new balance to protect the tumor from the interference effect of the inflammation. The tumor was made resistant to IFN-γ through the release of TGF-β to balance the inflammatory effect on the tumor cells. This balance mechanism that occurred in the tumor cells increased proliferation and invasion. In vitro and in vivo experiments have confirmed a new view of clinical surgery that will provide more detailed information on the evaluation of tumors after surgery. This study also provides a better understanding of the relationship between tumor and inflammation, as well as tumor cell attacks on inflammatory factors.
doi:10.1186/1756-9966-28-23
PMCID: PMC2683570  PMID: 19228418
3.  Early Identification of Reading Disabilities within a RTI Framework 
Journal of learning disabilities  2013;10.1177/0022219413498115.
Early and accurate identification of children at risk for reading disabilities (RD) is critical for the prevention of RD within a RTI framework. In this study, we investigated the use of universal screening and progress monitoring for the early identification of RD in kindergarten children. Three-hundred sixty-six children were administered a battery of screening measures at the beginning of kindergarten and progress monitoring probes across the school year. A subset of children who showed initial risk for RD also received a 26-week Tier 2 intervention. Participants’ achievement in word reading accuracy and/or fluency was assessed at the end of first grade. Results indicated that a screening battery containing measures of letter naming fluency, phonological awareness, rapid naming or nonword repetition accurately identified good and poor readers at the end of first grade. Findings also showed that children’s response to supplemental and/or classroom instruction measured in terms of growth in letter naming fluency added significantly to the prediction of reading outcomes.
doi:10.1177/0022219413498115
PMCID: PMC3855155  PMID: 23945079
4.  Application of air insufflation to prevent clinical pancreatic fistula after pancreaticoduodenectomy 
AIM: To introduce an air insufflation procedure and to investigate the effectiveness of air insufflation in preventing pancreatic fistula (PF).
METHODS: From March 2010 to August 2013, a total of 185 patients underwent pancreaticoduodenectomy (PD) at our institution, and 74 patients were not involved in this study for various reasons. The clinical outcomes of 111 patients were retrospectively analyzed. The air insufflation test was performed in 46 patients to investigate the efficacy of the pancreaticojejunal anastomosis during surgery, and 65 patients who did not receive the air insufflation test served as controls. Preoperative assessments and intraoperative outcomes were compared between the 2 groups. Univariate and multivariate analyses were performed to identify the risk factors for PF.
RESULTS: The two patient groups had similar baseline demographics, preoperative assessments, operative factors, pancreatic factors and pathological results. The overall mortality, morbidity, and PF rates were 1.8%, 48.6%, and 26.1%, respectively. No significant differences were observed in either morbidity or mortality between the two groups. The rate of clinical PF (grade B and grade C PF) was significantly lower in the air insufflation test group, compared with the non-air insufflation test group (6.5% vs 23.1%, P = 0.02). Univariate analysis identified the following parameters as risk factors related to clinical PF: estimated blood loss; pancreatic duct diameter ≤ 3 mm; invagination anastomosis technique; and not undergoing air insufflation test. By further analyzing these variables with multivariate logistic regression, estimated blood loss, pancreatic duct diameter ≤ 3 mm and not undergoing air insufflation test were demonstrated to be independent risk factors.
CONCLUSION: Performing an air insufflation test could significantly reduce the occurrence of clinical PF after PD. Not performing an air insufflation test was an independent risk factor for clinical PF.
doi:10.3748/wjg.v21.i6.1872
PMCID: PMC4323465
Pancreatic fistula; Pancreaticoduodenectomy; Air insufflation test; Surgery; Morbidity
5.  New Reactions and Products Resulting from Alternative Interactions between the P450 Enzyme and Redox Partners 
Cytochrome P450 enzymes are capable of catalyzing a great variety of synthetically useful reactions such as selective C–H functionalization. Surrogate redox partners are widely used for reconstitution of P450 activity based on the assumption that the choice of these auxiliary proteins or their mode of action does not affect the type and selectivity of reactions catalyzed by P450s. Herein, we present an exceptional example to challenge this postulate. MycG, a multifunctional biosynthetic P450 monooxygenase responsible for hydroxylation and epoxidation of 16-membered ring macrolide mycinamicins, is shown to catalyze the unnatural N-demethylation(s) of a range of mycinamicin substrates when partnered with the free Rhodococcus reductase domain RhFRED or the engineered Rhodococcus-spinach hybrid reductase RhFRED-Fdx. By contrast, MycG fused with the RhFRED or RhFRED-Fdx reductase domain mediates only physiological oxidations. This finding highlights the larger potential role of variant redox partner protein–protein interactions in modulating the catalytic activity of P450 enzymes.
doi:10.1021/ja4130302
PMCID: PMC3985502  PMID: 24521145
6.  Unusual case of digestive hemorrhage: Celiac axis-portal vein arteriovenous fistula 
A case of intractable upper gastrointestinal-hemorrhage was reported in a patient with portal hypertension caused by an arterioportal fistula (APF), namely, celiac axis-portal vein arteriovenous fistula. Portal hypertension caused by extrahepatic-APFs is extremely rare. Trauma, malignancy, and hereditary causes are the common etiology of APFs; but were absent in our patient. Our patient represents an unusual case of unexplained APF who presented with portal hypertension and was successfully managed through endovascular aortic repair.
doi:10.3748/wjg.v21.i4.1362
PMCID: PMC4306185  PMID: 25632214
Arterioportal fistula; Portal hypertension; Endovascular aortic repair
7.  Effects of aging, CMV infection, and EBV infection on human B cell repertoires 
Elderly humans show decreased humoral immunity to pathogens and vaccines, yet the effects of aging on B cells are not fully known. Chronic viral infection by cytomegalovirus (CMV) is implicated as a driver of clonal T cell proliferations in some aging humans, but whether CMV or Epstein-Barr virus (EBV) infection contributes to alterations in the B cell repertoire with age is unclear. We have used high-throughput DNA sequencing of immunoglobulin heavy chain (IGH) gene rearrangements to study the B cell receptor repertoires over two successive years in 27 individuals ranging in age from 20 to 89 years. Some features of the B cell repertoire remain stable with age, but elderly subjects show increased numbers of B cells with long CDR3 regions, a trend toward accumulation of more highly mutated IgM and IgG immunoglobulin genes, and persistent clonal B cell populations in the blood. Seropositivity for CMV or EBV infection alters B cell repertoires, regardless of the individual's age: EBV infection correlates with the presence of persistent clonal B cell expansions, while CMV infection correlates with the proportion of highly mutated antibody genes. These findings isolate effects of aging from those of chronic viral infection on B cell repertoires, and provide a baseline for understanding human B cell responses to vaccination or infectious stimuli.
doi:10.4049/jimmunol.1301384
PMCID: PMC3947124  PMID: 24337376
8.  ADAMTS-7 Exhibits Elevated Expression in Cartilage of Osteonecrosis of Femoral Head and Has a Positive Correlation with TNF-α and NF-κB P65 
Mediators of Inflammation  2015;2015:196702.
ADAMTS-7 has been reported to exaggerate cartilage degeneration and to be associated with TNF-α and NF-κB signaling pathway. In this study we compared the expression of ADAMTS-7, TNF-α, and Phospho-NF-κB in patients with femoral neck fracture (FNF) and osteonecrosis of femoral head (ONFH) at different stages. We found that expression of ADAMTS-7, TNF-α, and Phospho-NF-κB was significantly upregulated in ONFH patients' articular cartilage and related to the pathogenesis of ONFH. Thus we conclude that ADAMTS-7 level appears to be positively associated with expression of TNF-α and Phospho-NF-κB P65 in cartilage, which may imply its association with cartilage destruction of ONFH.
doi:10.1155/2015/196702
PMCID: PMC4310498  PMID: 25653475
9.  Complete Genome Sequence of Human Enterovirus Strain 71 (EV71/Taipei/3118/2011), Isolated from a Patient in Taiwan 
Genome Announcements  2015;3(1):e01375-14.
This full-length genome sequence of human enterovirus strain 71 (EV71/Taipei/3118/2011) was isolated from a clinical patient in Taiwan in 2011. According to the phylogenetic analysis, the complete genome sequence in this study is part of the subgenotype C4.
doi:10.1128/genomeA.01375-14
PMCID: PMC4290987  PMID: 25573934
10.  Toll-interacting protein (Tollip) negatively regulates pressure overload-induced ventricular hypertrophy in mice 
Cardiovascular Research  2013;101(1):87-96.
Aims
Toll-interacting protein (Tollip) is a critical regulator of the Toll-like receptor-mediated signalling pathway. However, the role of Tollip in chronic pressure overload-induced cardiac hypertrophy remains unclear. This study aimed to determine the functional significance of Tollip in the regulation of aortic banding-induced cardiac remodelling and its underlying mechanisms.
Methods and results
First, we observed that Tollip was down-regulated in human failing hearts and murine hypertrophic hearts, as determined by western blotting and RT–PCR. Using cultured neonatal rat cardiomyocytes, we found that adenovirus vector-mediated overexpression of Tollip limited angiotensin II-induced cell hypertrophy; whereas knockdown of Tollip by shRNA exhibited the opposite effects. We then generated a transgenic (TG) mouse model with cardiac specific-overexpression of Tollip and subjected them to aortic banding (AB) for 8 weeks. When compared with AB-treated wild-type mouse hearts, Tollip-TGs showed a significant attenuation of cardiac hypertrophy, fibrosis, and dysfunction, as measured by echocardiography, immune-staining, and molecular/biochemical analysis. Conversely, a global Tollip-knockout mouse model revealed an aggravated cardiac hypertrophy and accelerated maladaptation to chronic pressure overloading. Mechanistically, we discovered that Tollip interacted with AKT and suppressed its downstream signalling pathway. Pre-activation of AKT in cardiomyocytes largely offset the Tollip-elicited anti-hypertrophic effects.
Conclusion
Our results provide the first evidence that Tollip serves as a negative regulator of pathological cardiac hypertrophy by blocking the AKT signalling pathway.
doi:10.1093/cvr/cvt232
PMCID: PMC3968303  PMID: 24285748
Tollip; Cardiac remodelling; Pressure overload; AKT; Cardiomyocyte hypertrophy
11.  The Aurora B kinase in Trypanosoma brucei undergoes post-translational modifications and is targeted to various subcellular locations through binding to TbCPC1 
Molecular microbiology  2013;91(2):256-274.
The chromosomal passenger complex (CPC) in animals, consisting of Aurora B kinase and three evolutionarily conserved proteins, plays crucial roles in mitosis and cytokinesis. However, Trypanosoma brucei expresses an unusual CPC consisting of an Aurora-like kinase, TbAUK1, and two kinetoplastid-specific proteins, TbCPC1 and TbCPC2. Despite their essential functions, little is known about the regulation of TbAUK1 and the roles of TbCPC1 and TbCPC2. Here, we investigate the effect of post-translational modification on the activity and spatiotemporal control of TbAUK1, and demonstrate that phosphorylation of two conserved threonine residues in the activation loop of the kinase domain contributes to TbAUK1 activation and function. TbAUK1 is SUMOylated in vivo, and mutation of the SUMO-conjugation site compromises TbAUK1 function. Degradation of TbAUK1 requires two destruction boxes and is mediated by the anaphase-promoting complex/cyclosome (APC/C), whereas degradation of TbCPC1 and TbCPC2 is not dependent on the predicted destruction boxes and is APC/C-independent. Moreover, we determine the domains in CPC subunits that mediate the pairwise interactions, and show that disruption of the interaction impairs the localization of TbAUK1 and TbCPC2 but not TbCPC1. Our results demonstrate the requirement of post-translational modifications for TbAUK1 function and a crucial role of TbCPC1 in mediating TbAUK1 localization.
doi:10.1111/mmi.12458
PMCID: PMC3894614  PMID: 24224936
12.  The influence of astragalus polysaccharide and β-elemene on LX-2 cell growth, apoptosis and activation 
BMC Gastroenterology  2014;14(1):224.
Background
Activated hepatic stellate cells are the main source of excessive collagen deposition in liver fibrosis. Here we report the inhibitory effects of the combinational treatment of two natural products, astragalus polysaccharide (APS) and β-elemene (ELE) on the activation of human liver hepatic stellate cell line LX-2 cells.
Methods
Cultured LX-2 cells were treated with different concentrations of APS or ELE for 24 or 48 hours. Cell viability/apoptosis was measured by MTT assay and Annexin V/PI staining , activation related genes including α-SMA and CD44 expressions were measured by real-time PCR and western blot respectively.
Results
The majority of LX-2 cells showed morphological change in the presence of APS or ELE for 24 hours. Treatment with APS + ELE for 24 or 48 hours significantly inhabited the cell proliferation compared with APS or ELE treatment alone on LX-2 cells. APS + ELE may block the up-regulation of α-SMA and CD44 both in mRNA and protein levels through TGF-β pathway in LX-2 cells.
Conclusion
APS or ELE treatment alone on LX-2 cells could inhibit cell proliferation and induce apoptosis. The combinational treatment using APS + ELE significantly increased the killing efficiency on LX-2 cells. α-SMA and CD44 expressions was inhibited upon APS + ELE treatment through TGF-β pathway in LX-2 cells. The results indicated a novel treatment using natural products for liver diseases with anti-fibrotic effect.
doi:10.1186/s12876-014-0224-8
PMCID: PMC4297370  PMID: 25551689
Astragalus polysaccharide; β-elemene; Hepatic stellate cells
13.  Three-dimensional periodic supramolecular organic framework ion sponge in water and microcrystals 
Nature Communications  2014;5:5574.
Self-assembly has emerged as a powerful approach to generating complex supramolecular architectures. Despite there being many crystalline frameworks reported in the solid state, the construction of highly soluble periodic supramolecular networks in a three-dimensional space is still a challenge. Here we demonstrate that the encapsulation motif, which involves the dimerization of two aromatic units within cucurbit[8]uril, can be used to direct the co-assembly of a tetratopic molecular block and cucurbit[8]uril into a periodic three-dimensional supramolecular organic framework in water. The periodicity of the supramolecular organic framework is supported by solution-phase small-angle X-ray-scattering and diffraction experiments. Upon evaporating the solvent, the periodicity of the framework is maintained in porous microcrystals. As a supramolecular ‘ion sponge’, the framework can absorb different kinds of anionic guests, including drugs, in both water and microcrystals, and drugs absorbed in microcrystals can be released to water with selectivity.
The construction of soluble periodic supramolecular three-dimensional networks is challenging. Here, the authors use an encapsulated dimerization strategy to direct the assembly of a periodic three-dimensional supramolecular organic framework and evaluate its absorption properties.
doi:10.1038/ncomms6574
PMCID: PMC4268711  PMID: 25470406
14.  Efficacy and Safety of Celecoxib in Chinese Patients with Ankylosing Spondylitis: A 6-Week Randomized, Double-Blinded Study with 6-Week Open-Label Extension Treatment 
Background
Nonsteroidal anti-inflammatory drugs are the first-line option for treating ankylosing spondylitis (AS) in China. However, no large-scale controlled trials have been conducted in this ethnic population.
Objective
To evaluate the efficacy and safety of 6 weeks’ treatment with celecoxib in patients with AS in China.
Methods
This Phase 3, double-blind, parallel-group study randomized patients with AS aged ≥18 to 65 years 1:1 to receive celecoxib 200 mg once daily or diclofenac sustained release 75 mg once daily. After 6 weeks, patients could use celecoxib 400 mg once daily or maintain blinded therapy. The primary efficacy end point was mean change from baseline at Week 6 for Patient’s Global Assessment of Pain Intensity score (100-mm visual analog scale). Noninferiority was established if the upper bound of the CI was <10 mm. Secondary objectives included patients’ and physicians’ assessments of disease activity, change from baseline in C-reactive protein level, and safety.
Results
In the per-protocol analysis set the least squares mean change from baseline in the Patient’s Global Assessment of Pain Intensity score at Week 6 was –23.8 mm and –27.1 mm in patients receiving celecoxib (n = 111) and diclofenac (n = 108), respectively. The 2-sided 95% CI for the treatment difference (celecoxib – diclofenac) was –2.2 to 8.8. Overall, 4.2% and 6.7% of patients in the celecoxib and diclofenac groups, respectively, reported treatment-related adverse events. All were mild to moderate in severity.
Conclusions
Celecoxib 200 mg once daily is noninferior to diclofenac sustained release 75 mg once daily for pain treatment in Chinese patients with AS. ClinicalTrials.gov identifier: NCT00762463.
doi:10.1016/j.curtheres.2014.08.002
PMCID: PMC4266770  PMID: 25516774
ankylosing spondylitis; COX-2 inhibitors; musculoskeletal system; nonsteroidal anti-inflammatory drugs
15.  Prevalence of wearing-off and dyskinesia among the patients with Parkinson’s disease on levodopa therapy: a multi-center registry survey in mainland China 
Objective
Chronic levodopa (L-dopa) treatment in Parkinson’s disease (PD) is often associated with the development of motor complications, but the corresponding epidemiological data is rare in Chinese PD patients. The present survey was to investigate the prevalence rate of wearing-off (WO) and dyskinesia among the patients with PD in China.
Methods
From May 2012 to October 2012, a 3-step registry survey for wearing off (WO) and dyskinesia patients with PD receiving levodopa therapy was performed simultaneously at 28 movement disorders clinics in China.
Results
There were 1,558 PD patients fulfilling the inclusion criteria. Among them, 1,051 had at least one positive response of 9-item wearing off questionnaire (WOQ-9), 724 and 160 patients were finally diagnosed with WO and dyskinesia by movement disorders specialists, respectively. The overall prevalence rates of WO and dyskinesia were 46.5% (95% CI 44.0% - 48.9%) and 10.3% (95% CI 8.8% - 11.8%), respectively. The mean score of WOQ-9 for those with WO was 3.8 (SD = 1.8), with movement slowness being the most common motor symptoms and pain/aching being the most common non-motor symptoms. Better improvement of motor symptoms (n = 354, 87.8%) and long-term disease control and drug selection (n = 288, 71.5%) were the two most frequently considered factors when movement disorders specialists adjusted therapeutic strategies for patients with WO.
Conclusions
This survey provided the first multi-center epidemiological data of motor complications among PD patients on L-dopa therapy from mainland China. WO prevalence rate among Chinese PD patients was in line with, while dyskinesia prevalence rate was lower than previous reports from other Countries.
Electronic supplementary material
The online version of this article (doi:10.1186/2047-9158-3-26) contains supplementary material, which is available to authorized users.
doi:10.1186/2047-9158-3-26
PMCID: PMC4323338  PMID: 25671102
Parkinson’s disease; Wearing-off; Dyskinesia; Epidemiology
16.  Neurochemical Effects of Chronic Administration of Calcitriol in Rats 
Nutrients  2014;6(12):6048-6059.
Despite accumulating data showing the various neurological actions of vitamin D (VD), its effects on brain neurochemistry are still far from fully understood. To further investigate the neurochemical influence of VD, we assessed neurotransmitter systems in the brain of rats following 6-week calcitriol (1,25-dihydroxyvitamin D) administration (50 ng/kg/day or 100 ng/kg/day). Both the two doses of calcitriol enhanced VDR protein level without affecting serum calcium and phosphate status. Rats treated with calcitriol, especially with the higher dose, exhibited elevated γ-aminobutyric acid (GABA) status. Correspondingly, the mRNA expression of glutamate decarboxylase (GAD) 67 was increased. 100 ng/kg of calcitriol administration also increased glutamate and glutamine levels in the prefrontal cortex, but did not alter glutamine synthetase (GS) expression. Additionally, calcitriol treatment promoted tyrosine hydroxylase (TH) and tryptophan hydroxylase 2 (TPH2) expression without changing dopamine and serotonin status. However, the concentrations of the metabolites of dopamine and serotonin were increased and the drug use also resulted in a significant rise of monoamine oxidase A (MAOA) expression, which might be responsible to maintain the homeostasis of dopaminergic and serotonergic neurotransmission. Collectively, the present study firstly showed the effects of calcitriol in the major neurotransmitter systems, providing new evidence for the role of VD in brain function.
doi:10.3390/nu6126048
PMCID: PMC4277014  PMID: 25533012
vitamin D; calcitriol; neurotransmitter systems; brain function
17.  Expression of VEGFR2 and NRP-1 in non-small cell lung cancer and their clinical significance 
Objective
Vascular-targeted therapy is gradually becoming more appealing for patients with lung cancer. It is unclear whether vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) can be biomarkers for clinical treatment. We aimed to investigate the expression levels of VEGFR2 and NRP-1 in human non-small cell lung cancer (NSCLC) and their clinical significance by observing patient prognosis.
Methods
VEGFR2 and NRP-1 were assessed by immunohistochemistry (IHC) in 40 patients with NSCLC and in 10 patients with benign lesions of lung; kinase insert domain receptor (KDR) and NRP-1 copy number gain (CNG) was assessed by fluorescence in situ hybridization (FISH). The distributions of overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared between groups by log-rank test.
Results
Rates of positive immunostaining for VEGFR2 and NRP-1 were 58% and 55%, respectively. KDR and NRP-1 CNG (+) were detected in 32.5% and 30% of tumors, respectively. Levels of both VEGFR2 and NRP-1 in lung tumors were significantly different than in the control tissue (χ2=11.22, P=0.001; χ2=9.82, P=0.001, respectively); similar results were obtained using CNGs (χ2=4.39, P=0.036; χ2=3.95, P=0.046, respectively). Statistically significant correlations were observed with histological grade, clinical TNM stage and the lymph node status (P<0.05), but not age, gender or pathology type (P>0.05). VEGFR2 showed a strong correlation with NRP-1 (Rs=0.68, P=0.00); similar results were observed with KDR and NRP-1 CNG (Rs=0.32, P=0.04). Significant differences in OS and PFS were observed between the groups with higher VEGFR2 and NRP-1 and those with lower expression (P<0.05).
Conclusions
According to these data, VEGFR2 and NRP-1 are highly expressed in NSCLC. We can conclude that they play a key role in NSCLC occurrence, development and metastasis and are associated with patient prognosis (P<0.05 for OS and PFS). This information will be beneficial for clinical anti-angiogenic treatment in NSCLC.
doi:10.3978/j.issn.1000-9604.2014.12.04
PMCID: PMC4279211  PMID: 25561764
Non-small cell lung cancer (NSCLC); vascular endothelial growth factor receptor 2 (VEGFR2); neuropilin-1 (NRP-1); fluorescence in situ hybridization (FISH)
18.  Uniportal video assisted thoracoscopic lobectomy: primary experience from an Eastern center 
Journal of Thoracic Disease  2014;6(12):1751-1756.
Background
Uniportal video-assisted thoracoscopic surgery (VATS) lobectomy is an emerging technique for the surgical resection of non-small cell lung cancer (NSCLC). Besides its wide debates on safety and efficacy throughout the world, there were few report on uniportal VATS from the Eastern countries. In this article, we summarized our primary experience on uniportal VATS lobectomy in an Eastern center.
Methods
From October 2013 till February 2014, 54 consecutive uniportal VATS lobectomy were performed in the Department of Thoracic Surgery, Zhongshan Hospital of Fudan University. Patients’ clinical features and operative details were recorded. Post-operatively, the morbidity and mortality were recorded to analyze the safety and efficacy of uniportal VATS lobectomy for NSCLCs.
Results
Among the 54 planned uniportal VATS lobectomy, there was one conversion to mini-thoracotomy due to lymph node sticking. Extra ports were required in two patients. The uniportal VATS lobectomy was achieved in 51 out of 54 patients (94.4%). The average operation duration was 122.2±37.5 min (90-160 min). The average volume of estimated blood loss during the operation was 88.8±47.1 mL (50-200 mL). The mean chest tube duration and hospital stay were 3.2±1.9 days and 4.6±2.0 days, respectively. There was no postoperative mortality in this study. Two patients suffered from prolonged air leakage (5 and 7 days), and one atrial fibrillation was observed in this cohort.
Conclusions
Based on our primary experience, uniportal VATS lobectomy is a safe and effective procedure for the surgical resection of NSCLCs. The surgical refinements and instrumental improvements would facilitate the technique. Further studies based on larger population are required to determine its benefits towards patients with NSCLCs.
doi:10.3978/j.issn.2072-1439.2014.11.20
PMCID: PMC4283325  PMID: 25589969
Lobectomy; minimally invasive surgery; non-small-cell-lung carcinoma (NSCLC)
19.  Identification and characterization of telocytes in the uterus of the oviduct in the Chinese soft-shelled turtle, Pelodiscus sinensis: TEM evidence 
Telocytes (Tcs) are cells with telopodes (Tps), which are very long cellular extensions with alternating thin segments (podomers) and dilated bead-like thick regions known as podoms. Tcs are a distinct category of interstitial cells and have been identified in many mammalian organs including heart, lung and kidney. The present study investigates the existence, ultrastructure, distribution and contacts of Tcs with surrounding cells in the uterus (shell gland) of the oviduct of the Chinese soft-shelled turtle, Pelodiscus sinensis. Samples from the uterine segment of the oviduct were examined by transmission electron microscopy. Tcs were mainly located in the lamina propria beneath the simple columnar epithelium of the uterus and were situated close to nerve endings, capillaries, collagen fibres and secretory glands. The complete morphology of Tcs and Tps was clearly observed and our data confirmed the existence of Tcs in the uterus of the Chinese soft-shelled turtle Pelodiscus sinensis. Our results suggest these cells contribute to the function of the secretory glands and contraction of the uterus.
doi:10.1111/jcmm.12392
PMCID: PMC4302644  PMID: 25230849
telocytes; uterus; Chinese soft-shelled turtle (Pelodiscus sinensis); ultrastructure
20.  Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman 
Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels.
PMCID: PMC4313977
Mixed germ cell tumor; ovary; clear cell carcinoma
21.  Hydrothermal synthesis of 3D hollow porous Fe3O4 microspheres towards catalytic removal of organic pollutants 
Nanoscale Research Letters  2014;9(1):648.
Three-dimensional hollow porous superparamagnetic Fe3O4 microspheres were synthesized via a facile hydrothermal process. A series of characterizations done with X-ray diffraction, Brunauer-Emmett-Teller method, Fourier transform infrared spectroscopy, scanning electron microscopy, and transmission electron microscopy indicated that the production of Fe3O4 microspheres possessed good monodispersity, uniform size distribution, hollow and porous structural characters, and strong superparamagnetic behavior. The obtained Fe3O4 microspheres have a diameter of ca. 300 nm, which is composed of many interconnected nanoparticles with a size of ca. 20 nm. The saturation magnetization is 80.6 emu·g-1. The as-prepared products had promising applications as novel catalysts to remove organic pollutants (methylene blue) from wastewater in the presence of H2O2 and ultrasound irradiation.
doi:10.1186/1556-276X-9-648
PMCID: PMC4266516  PMID: 25520596
Hydrothermal synthesis; Fe3O4 microspheres; Porous; Enzyme mimetics; Organic pollutants
22.  A microchip electrophoresis-mass spectrometric platform for fast separation and identification of enantiomers employing the partial filling technique 
Journal of chromatography. A  2013;1318:251-256.
A microchip electrophoresis-mass spectrometric (MCE-MS) method was developed for fast chiral analysis. The proposed MCE-MS platform deployed a glass /PDMS hybrid microchip with an easy-to-fabricate monolithic nanoelectrospray emitter. Enantiomeric MCE separation was achieved by means of the partial filling technique. A novel chip design with an arm channel connecting to the middle of the MCE separation channel for delivering the chiral selector was tested and proven valid. Enantiomeric separation of 3.4-dihydroxyphenylalanine (DOPA), glutamic acid (Glu), and serine (Ser), the selected test compounds, were achieved within 130 s with resolution values (Rs) of 2.4, 1.1, and 1.0, respectively. The proposed chiral MCE-MS assay was sensitive and had detection limits of 43 nM for L-DOPA and 47 nM for D-DOPA. The analytical platform was well suited for studies of stereochemical preference in living cells because it integrated cell culture, sample injection, chiral separation, and MS detection into a single platform. Metabolism of DOPA in human SH-SY5Y neuronal cells was studied as a model system. On-chip incubation of SH-SY5Y cells with racemic DOPA was carried out, and the incubation solution was injected and in-line assayed at time intervals. It was found that L-DOPA concentration decreased gradually as incubation time increased while the concentration of coexisting D-DOPA remained constant. The results firmly indicated that SH-SY5Y cells metabolized L-DOPA effectively while left D-DOPA intact.
PMCID: PMC4097118  PMID: 24354006
Microchip electrophoresis; nano-electrospray ionization-mass spectrometry; chiral separation; partial filling technique; DOPA; serine
23.  Novel, Broad-Spectrum Anticonvulsants Containing a Sulfamide Group: Pharmacological Properties of (S)-N-[(6-Chloro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]sulfamide (JNJ-26489112) 
Journal of medicinal chemistry  2013;56(22):9019-9030.
Broad-spectrum anticonvulsants are of considerable interest as antiepileptic drugs, especially because of their potential for treating refractory patients. Such “neurostabilizers” have also been used to treat other neurological disorders, including migraine, bipolar disorder, and neuropathic pain. We synthesized a series of sulfamide derivatives (4–9, 10a–i, 11a, 11b, 12) and evaluated their anticonvulsant activity. Thus, we identified promising sulfamide 4 (JNJ-26489112) and explored its pharmacological properties. Compound 4 exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically-induced, and chemically-induced seizures. Mechanistically, 4 inhibited voltage-gated Na+ channels and N-type Ca2+ channels, and was effective as a K+ channel opener. The anticonvulsant profile of 4 suggests that it may be useful for treating multiple forms of epilepsy (generalized tonic-clonic, complex partial, absence seizures), including refractory (or pharmacoresistant) epilepsy, at dose levels that confer a good safety margin. On the basis of its pharmacology and other favorable characteristics, 4 was advanced into human clinical studies.
doi:10.1021/jm400894u
PMCID: PMC4004761  PMID: 24205976
24.  Adoptive Immunotherapy of Cytokine-Induced Killer Cell Therapy in the Treatment of Non-Small Cell Lung Cancer 
PLoS ONE  2014;9(11):e112662.
Aim
The aim of this study was to systemically evaluate the therapeutic efficacy of cytokine-induced killer (CIK) cells for the treatment of non-small cell lung cancer.
Materials and Methods
A computerized search of randomized controlled trials for CIK cell-based therapy was performed. The overall survival, clinical response rate, immunological assessment and side effects were evaluated.
Results
Overall, 17 randomized controlled trials of non-small cell lung cancer (NSCLC) with a total of 1172 patients were included in the present analysis. Our study showed that the CIK cell therapy significantly improved the objective response rate and overall survival compared to the non-CIK cell-treated group. After CIK combined therapy, we observed substantially increased percentages of CD3+, CD4+, CD4+CD8+, CD3+CD56+ and NK cells, whereas significant decreases were noted in the percentage of CD8+ and regulatory T cell (Treg) subgroups. A significant increase in Ag-NORs was observed in the CIK-treated patient group (p = 0.00001), whereas carcinoembryonic antigen (CEA) was more likely to be reduced to a normal level after CIK treatment (p = 0.0008). Of the possible major side effects, only the incidence of fever in the CIK group was significantly higher compared to the group that received chemotherapy alone.
Conclusion
The CIK cell combined therapy demonstrated significant superiority in the overall survival, clinical response rate, and T lymphocytes responses and did not present any evidence of major adverse events in patients with NSCLC.
doi:10.1371/journal.pone.0112662
PMCID: PMC4239020  PMID: 25412106
25.  Epigenetic Regulation of TSP1/TGFβ/SMAD3 Autocrine Loop Determines Benign Tumor Stem Cell Fate in Ossifying Fibroma 
Cell stem cell  2013;13(5):10.1016/j.stem.2013.08.010.
Summary
Abnormal stem cell function contributes to tumorigenesis of many malignant tumors, but until now, the role of stem cells in benign tumor formation has remained elusive. Here we show that ossifying fibroma (OF) contains mesenchymal stem cells (OFMSCs), capable of generating OF-like tumor xenografts. Mechanistically, enhanced TGFβ signaling induces aberrant proliferation and deficient osteogenesis of OFMSCs via Notch and BMP signaling pathways, respectively. The elevated TGFβ activity is tightly regulated by JHDM1D-mediated epigenetic regulation of thrombospondin-1 (TSP1), forming a JHDM1D/TSP1/TGFβ/SMAD3 autocrine loop. Inhibition of TGFβ signaling in OFMSCs can rescue their abnormal osteogenic differentiation and elevated cell proliferation. Furthermore, normal MSCs, by chronic activation of TGFβ, can be converted to OF-like MSCs via establishment of the JHDM1D/TSP1/TGFβ/SMAD3 autocrine loop. These results reveal a novel mechanism of epigenetic regulation of TGFβ signaling in MSCs that determines benign tumor phenotype in OF neoplasm.
doi:10.1016/j.stem.2013.08.010
PMCID: PMC3861239  PMID: 24209761

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