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1.  Laser Scanning In Vivo Confocal Microscopy of Clear Grafts after Penetrating Keratoplasty 
BioMed Research International  2016;2016:5159746.
Purpose. To evaluate the changes of keratocytes and dendritic cells in the central clear graft by laser scanning in vivo confocal microscopy after penetrating keratoplasty (PK). Methods. Thirty adult subjects receiving PK at Shandong Eye Institute and with clear grafts and no sign of immune rejection after surgery were recruited into this study, and 10 healthy adults were controls. The keratocytes and dendritic cells in the central graft were evaluated by laser scanning confocal microscopy, as well as epithelium cells, keratocytes, corneal endothelium cells, and corneal nerves (especially subepithelial plexus nerves). Results. Median density of subepithelial plexus nerves, keratocyte density in each layer of the stroma, and density of corneal endothelium cells were all lower in clear grafts than in controls. The dendritic cells of five (16.7%) patients were active in Bowman's membrane and stromal membrane of the graft after PK. Conclusions. Activated dendritic cells and Langerhans cells could be detected in some of the clear grafts, which indicated that the subclinical stress of immune reaction took part in the chronic injury of the clear graft after PK, even when there was no clinical rejection episode.
doi:10.1155/2016/5159746
PMCID: PMC4789369  PMID: 27034940
2.  The Superficial Stromal Scar Formation Mechanism in Keratoconus: A Study Using Laser Scanning In Vivo Confocal Microscopy 
BioMed Research International  2016;2016:7092938.
To investigate the mechanism of superficial stromal scarring in advanced keratoconus using confocal microscopy, the keratocyte density, distribution, micromorphology of corneal stroma, and SNP in three groups were observed. Eight corneal buttons of advanced keratoconus were examined by immunohistochemistry. The keratocyte densities in the sub-Bowman's stroma, anterior stroma, and posterior stroma and the mean SNP density were significantly different among the three groups. In the mild-to-moderate keratoconus group, activated keratocyte nuclei and comparatively highly reflective ECM were seen in the sub-Bowman's stroma, while fibrotic structures with comparatively high reflection were visible in the anterior stroma in advanced keratoconus. The alternating dark and light bands in the anterior stroma of the mild-to-moderate keratoconus group showed great variability in width and direction. The wide bands were localized mostly in the posterior stroma that corresponded to the Vogt striae in keratoconus and involved the anterior stroma only in advanced keratoconus. Histopathologically, high immunogenicity of α-SMA, vimentin, and FAP was expressed in the region of superficial stromal scarring. In vivo confocal microscopy revealed microstructural changes in the keratoconic cone. The activation of superficial keratocytes and abnormal remodeling of ECM may both play a key role in the superficial stromal scar formation in advanced keratoconus.
doi:10.1155/2016/7092938
PMCID: PMC4739471  PMID: 26885515
3.  DNA Methylation mediated down-regulating of MicroRNA-33b and its role in gastric cancer 
Scientific Reports  2016;6:18824.
The discovery of microRNAs (miRNAs) provides a new and powerful tool for studying the mechanism, diagnosis and treatment of human cancers. Currently, down-regulation of tumor suppressive miRNAs by CpG island hypermethylation is emerging as a common hallmark of cancer. Here, we reported that the down-regulation of miR-33b was associated with pM stage of gastric cancer (GC) patients. Ectopic expression of miR-33b in HGC-27 and MGC-803 cells inhibited cell proliferation, migration and invasion, which might be due to miR-33b targeting oncogene c-Myc. Moreover, enhanced methylation level of the CpG island upstream of miR-33b in GC patients with down-regulated miR-33b was confirmed by methylation-specific PCR (MSP) amplification. Furthermore, re-introduction of miR-33b significantly suppressed tumorigenesis of GC cells in the nude mice. In conclusion, miR-33b acts as a tumor suppressor and hypermethylation of the CpG island upstream of miR-33b is responsible for its down-regulation in gastric cancer.
doi:10.1038/srep18824
PMCID: PMC4700416  PMID: 26729612
4.  Dietary Nitrates, Nitrites, and Nitrosamines Intake and the Risk of Gastric Cancer: A Meta-Analysis 
Nutrients  2015;7(12):9872-9895.
The potential associations between dietary consumption of nitrates, nitrites, and nitrosamines and gastric cancer risk have been investigated by several studies, but yielded inconclusive results. We conducted a meta-analysis to provide a quantitative assessment of their relationships. Relevant articles were identified by a systematic literature searching of PubMed and Embase databases prior to August 2015. Random-effects models were employed to pool the relative risks. A total of 22 articles consisting of 49 studies—19 studies for nitrates, 19 studies for nitrites, and 11 studies for N-nitrosodimethylamine (NDMA)—were included. The summary relative risk of stomach cancer for the highest categories, compared with the lowest, was 0.80 (95% confidence interval (CI), 0.69–0.93) for dietary nitrates intake, 1.31 (95% CI, 1.13–1.52) for nitrites, and 1.34 (95% CI, 1.02–1.76) for NDMA (p for heterogeneity was 0.015, 0.013 and <0.001, respectively). The study type was found as the main source of heterogeneity for nitrates and nitrites. The heterogeneity for NDMA could not be eliminated completely through stratified analysis. Although significant associations were all observed in case-control studies, the cohort studies still showed a slight trend. The dose-response analysis indicated similar results as well. High nitrates intake was associated with a weak but statistically significant reduced risk of gastric cancer. Whereas increased consumption of nitrites and NDMA seemed to be risk factors for cancer. Due to the lack of uniformity for exposure assessment across studies, further prospective researches are warranted to verify these findings.
doi:10.3390/nu7125505
PMCID: PMC4690057  PMID: 26633477
diet; nitrates; nitrites; nitrosamines; gastric cancer
5.  Treatment of renal uric acid stone by extracorporeal shock wave lithotripsy combined with sodium bicarbonate: 2 case reports 
Uric acid stone is the most comment radiolucent renal stone with high recurrence rate, which would further cause acute upper urinary tract obstruction and kidney failure. Here we report two cases of renal uric acid stone from December 2012 to April 2013. One 43-year-old male patient suffered from chronic uric acid nephrolithiasis caused by the long-term indwelling of bilateral double-J stent. Another 69-year-old patient was also diagnosed with uric acid nephrolithiasis at the right kidney. Both patients were first treated with extracorporeal shock wave lithotripsy (ESWL), followed by 1.5% sodium bicarbonate dissolution therapy. After a week of the treatment, the uric acid stones in both patients were completely dissolved without retrograde infection. In summary, the use of ESWL and sodium bicarbonate dissolution therapy as a combined modality is a safe, effective, inexpensive treatment for uric acid nephrolithiasis.
PMCID: PMC4613068  PMID: 26550383
Renal acid stone; extracorporeal shock wave lithotripsy; uric acid nephrolithiasis; sodium bicarbonate
6.  Quantitative Evaluation of the Substantially Variable Morphology and Function of the Left Atrial Appendage and Its Relation with Adjacent Structures 
PLoS ONE  2015;10(7):e0126818.
Objective
To investigate quantitatively the morphology, anatomy and function of the left atrial appendage (LAA) and its relation with adjacent structures.
Materials and Methods
A total of 860 patients (533 men, 62.0%, age 55.9±10.4 year) who had cardiac multidetector computed tomography angiography from May to October 2012 were enrolled for analysis.
Results
Seven types and 6 subtypes of LAA morphology were found with Type 2 being the most prevalent. Type 5 was more significantly (P<0.05) present in women (8.0%) than in men (4.2%). LAA orifice was oval in 81.5%, triangular in 7.3%, semicircular in 4%, water drop-like in 3.2%, round in 2.4% and foot-like in 1.6%. The LAA orifice had a significantly greater (P<0.01) major axis in men (24.79±3.81) than in women (22.68±4.07). The LAA orifice long axis was significantly (P<0.05) positively correlated with the height, weight and surface area of the patient. The LAA morphology parameters displayed strong positive correlation with the left atrium volume, aortic cross area long axis or LSPV long axis but poor correlation with the height, weight, surface area and vertebral body height of the patients. Four types of LAA ridge were identified: AI, AII, B and C with the distribution of 17.6%, 69.9%, 5.9% and 6.6%, respectively. The LAA had a significantly (P<0.05) greater distance from its orifice to the mitral ring in women than in men. The LAA had two filling and two emptying processes with the greatest volume at 45% phase but the least volume at 5% phase. The LAA maximal, minimal and emptying volumes were all significantly (P<0.05) positively correlated with the body height, weight and surface area, whereas the LAA ejection fraction had an inverse correlation with the LAA minimal volume but no correlation with the maximal volume.
Conclusion
The LAA has substantially variable morphologies and relation with the adjacent structures, which may be helpful in guiding the LAA trans-catheter occlusion or catheter ablation procedures.
doi:10.1371/journal.pone.0126818
PMCID: PMC4521946  PMID: 26230395
7.  Trans-arterial chemoembolization and external beam radiation therapy for treatment of hepatocellular carcinoma with a tumor thrombus in the inferior vena cava and right atrium 
Cancer Imaging  2015;15(1):7.
Background
Hepatocellular carcinoma (HCC) with a tumor thrombus in the inferior vena cava (IVC) and right atrium (RA) rarely occurs and is usually associated with extremely poor prognosis, we carried out this study to evaluate the efficacy and safety of a combination of trans-arterial chemoembolization (TACE) and external beam radiation therapy (EBRT) in the treatment of HCC with a tumor thrombus in the IVC and RA.
Methods
From September 2005 to September 2008, 11 cases of HCC with a tumor thrombus in the IVC and RA were treated with a combination of TACE and EBRT. Clinical adverse events, laboratory toxicity, and survival were retrospectively studied.
Results
Thirty-one interventional procedures were conducted and EBRT was performed 11 times. All treatments were successful and without significant complications. No severe adverse effects were observed. The median survival time of the 11 cases was 21.0 months. One patient was monitored for 97 months and no recurrence was observed.
Conclusion
The combination of TACE and EBRT can be safely performed and may improve the prognosis of the HCC cases with a tumor thrombus in the IVC and RA.
doi:10.1186/s40644-015-0043-3
PMCID: PMC4488985  PMID: 26007646
Chemoembolization; Radiotherapy; Hepatocellular carcinoma; Inferior vena cava; Right atrium; Thrombus
8.  Pretreatment of Adipose Derived Stem Cells with Curcumin Facilitates Myocardial Recovery via Antiapoptosis and Angiogenesis 
Stem Cells International  2015;2015:638153.
The poor survival rate of transplanted stem cells in ischemic myocardium has limited their therapeutic efficacy. Curcumin has potent antioxidant property. This study investigates whether prior curcumin treatment protects stem cells from oxidative stress injury and improves myocardial recovery following cells transplantation. Autologous Sprague-Dawley rat adipose derived mesenchymal stem cells (ADSCs) were pretreated with or without curcumin. The hydrogen peroxide/serum deprivation (H2O2/SD) medium was used to mimic the ischemic condition in vitro. Cytoprotective effects of curcumin on ADSCs were evaluated. Curcumin pretreatment significantly increased cell viability and VEGF secretion, and decreased cell injury and apoptosis via regulation of PTEN/Akt/p53 and HO-1 signal proteins expression. The therapeutic potential of ADSCs implantation was investigated in myocardial ischemia-reperfusion injury (IRI) model. Transplantation of curcumin pretreated ADSCs not only resulted in better heart function, higher cells retention, and smaller infarct size, but also decreased myocardial apoptosis, promoted neovascularization, and increased VEGF level in ischemic myocardium. Together, priming of ADSCs with curcumin improved tolerance to oxidative stress injury and resulted in enhancement of their therapeutic potential of ADSCs for myocardial repair. Curcumin pretreatment is a promising adjuvant strategy for stem cells transplantation in myocardial restoration.
doi:10.1155/2015/638153
PMCID: PMC4436501  PMID: 26074974
9.  Prognostic value of excision repair cross-complementation group 1 expression in gastric cancer: A meta-analysis 
The prognostic impact of excision repair cross-complementation group 1 (ERCC1) expression in gastric cancer (GC) has been investigated for decades, but has yielded controversial results. The aim of the present study was to provide a precise evaluation of whether the expression levels of ERCC1 are associated with overall survival (OS) in patients with GC. A systematic search of Medline and Embase was conducted. Original studies concerning OS and ERCC1 expression were included for critical appraisal. A total of 15 studies comprising 1,425 patients with GC were identified. The results revealed that high/positive ERCC1 expression was an indicator of poor survival in patients with GC [hazard ratio (HR) 1.48; 95% confidence interval (CI) 1.02–2.10; P=0.036; I2=83.8%; random-effects model] compared with low/negative ERCC1 expression. Subgroup analysis indicated that high/positive ERCC1 expression had a significant unfavorable impact on OS in the group of patients evaluated by reverse transcription polymerase chain reaction (RT-PCR; HR 2.57; 95% CI 1.49–4.45). Furthermore, high/positive ERCC1 expression was found to be associated with poor survival in patients receiving platinum-based chemotherapy in the RT-PCR group (HR 2.13; 95% CI 1.06–4.27). These data suggest that ERCC1 may be a useful prognostic factor for GC. In addition, low mRNA levels of ERCC1 appear to be associated with a significant favorable OS benefit from platinum-based chemotherapy.
doi:10.3892/etm.2015.2284
PMCID: PMC4353740  PMID: 25780441
excision repair cross-complementation group 1; gastric cancer; meta-analysis
10.  Big Bubble Deep Anterior Lamellar Keratoplasty for Management of Deep Fungal Keratitis 
Journal of Ophthalmology  2014;2014:209759.
Objective. To evaluate the therapeutic effect of big bubble deep anterior lamellar keratoplasty (DALK) in patients with deep fungal keratitis. Methods.Consecutive patients who had DALK for deep fungal keratitis at Shandong Eye Hospital between July 2011 and December 2012 were included. In all patients, the infiltration depth was more than 4/5ths of the corneal thickness. DALK surgery was performed with bare Descemet membrane (DM) using the big bubble technique. Corrected distance visual acuity (CDVA), graft status, and intraoperative and postoperative complications were monitored. Results. Big bubble DALK was performed in 23 patients (23 eyes). Intraoperative perforation of the DM occurred in two eyes (8.7%) during stromal dissection. The patients received lamellar keratoplasty with an air bubble injected into the anterior chamber. Double anterior chamber formed in 3 eyes (13.0%). Mean CDVA of the patients without cataract, amblyopia, and fungal recurrence was improved from preoperative HM/20 cm−1.0 (LogMAR) to 0.23 ± 0.13 (LogMAR) at the last followup (P < 0.01). Fungal recurrence was found in two patients (8.7%). Corneal stromal graft rejection was noted in one patient (4.3%). Conclusions. DALK using the big bubble technique seems to be effective and safe in the treatment of deep fungal keratitis unresponsive to medication.
doi:10.1155/2014/209759
PMCID: PMC4106058  PMID: 25105019
11.  Adaptive mesh refinement techniques for the immersed interface method applied to flow problems 
Computers & structures  2013;122:249-258.
In this paper, we develop an adaptive mesh refinement strategy of the Immersed Interface Method for flow problems with a moving interface. The work is built on the AMR method developed for two-dimensional elliptic interface problems in the paper [12] (CiCP, 12(2012), 515–527). The interface is captured by the zero level set of a Lipschitz continuous function φ(x, y, t). Our adaptive mesh refinement is built within a small band of |φ(x, y, t)| ≤ δ with finer Cartesian meshes. The AMR-IIM is validated for Stokes and Navier-Stokes equations with exact solutions, moving interfaces driven by the surface tension, and classical bubble deformation problems. A new simple area preserving strategy is also proposed in this paper for the level set method.
doi:10.1016/j.compstruc.2013.03.013
PMCID: PMC3686141  PMID: 23794763
Adaptive mesh refinement method; immersed interface method; Stokes equations; Navier-Stokes equations; surface tension; bubble deformation; level set method
12.  Simulation of longitudinal exposure data with variance-covariance structures based on mixed models 
Longitudinal data are important in exposure and risk assessments, especially for pollutants with long half-lives in the human body and where chronic exposures to current levels in the environment raise concerns for human health effects. It is usually difficult and expensive to obtain large longitudinal data sets for human exposure studies. This paper reports a new simulation method to generate longitudinal data with flexible numbers of subjects and days. Mixed models are used to describe the variance-covariance structures of input longitudinal data. Based on estimated model parameters, simulation data are generated with similar statistical characteristics compared to the input data. Three criteria are used to determine similarity: the overall mean and standard deviation, the variance components percentages, and the average autocorrelation coefficients. Upon the discussion of mixed models, a simulation procedure is produced and numerical results are shown through one human exposure study. Simulations of three sets of exposure data successfully meet above criteria. In particular, simulations can always retain correct weights of inter- and intra- subject variances as in the input data. Autocorrelations are also well followed. Compared with other simulation algorithms, this new method stores more information about the input overall distribution so as to satisfy the above multiple criteria for statistical targets. In addition, it generates values from numerous data sources and simulates continuous observed variables better than current data methods. This new method also provides flexible options in both modeling and simulation procedures according to various user requirements.
doi:10.1111/j.1539-6924.2012.01869.x
PMCID: PMC3689546  PMID: 22817762
longitudinal data; simulation; mixed models; variance-covariance structure; autocorrelation
13.  Role of DNA Methylation in Cell Cycle Arrest Induced by Cr (VI) in Two Cell Lines 
PLoS ONE  2013;8(8):e71031.
Hexavalent chromium [Cr(IV)], a well-known industrial waste product and an environmental pollutant, is recognized as a human carcinogen. But its mechanisms of carcinogenicity remain unclear, and recent studies suggest that DNA methylation may play an important role in the carcinogenesis of Cr(IV). The aim of our study was to investigate the effects of Cr(IV) on cell cycle progress, global DNA methylation, and DNA methylation of p16 gene. A human B lymphoblastoid cell line and a human lung cell line A549 were exposed to 5–15 µM potassium dichromate or 1.25–5 µg/cm2 lead chromate for 2–24 hours. Cell cycle was arrested at G1 phase by both compounds in 24 hours exposure group, but global hypomethylation occurred earlier than cell cycle arrest, and the hypomethylation status maintained for more than 20 hours. The mRNA expression of p16 was significantly up-regulated by Cr(IV), especially by potassium dichromate, and the mRNA expression of cyclin-dependent kinases (CDK4 and CDK6) was significantly down-regulated. But protein expression analysis showed very little change of p16 gene. Both qualitative and quantitative results showed that DNA methylation status of p16 remained unchanged. Collectively, our data suggested that global hypomethylation was possibly responsible for Cr(IV) - induced G1 phase arrest,but DNA methylation might not be related to up-regulation of p16 gene by Cr(IV).
doi:10.1371/journal.pone.0071031
PMCID: PMC3735518  PMID: 23940686
14.  Transcatheter arterial chemoembolization followed by immediate radiofrequency ablation for large solitary hepatocellular carcinomas 
AIM: To assess the technical safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with immediate radiofrequency ablation (RFA) for large hepatocellular carcinomas (HCC) (maximum diameter ≥ 5 cm).
METHODS: Individual lesions in 18 patients with HCCs (mean maximum diameter: 7.5 cm; range: 5.1-15.5 cm) were treated by TACE combined with percutaneous RFA between January 2010 and June 2012. All of the patients had previously undergone one to four cycles of TACE treatment. Regular imaging and laboratory tests were performed to evaluate the rate of technical success, technique-related complications, local-regional tumor responses, recurrence-free survival time and survival rate after treatment.
RESULTS: Technical success was achieved for all 18 visible HCCs. Complete response (CR) was observed in 17 cases, and partial response was observed in 1 case 1 mo after intervention. The CR rate was 94.4%. Local tumors were mainly characterized by coagulative necrosis. During follow-up (2-29 mo), the mean recurrence-free survival time was 16.8 ± 4.0 mo in 17 cases of CR. The estimated overall survival rate at 6, 12, and 18 mo was 100%. No major complications were observed. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the blood of 17 patients transiently increased on the third day after treatment (ALT 200.4 ± 63.4 U/L vs 24.7 ± 9.3 U/L, P < 0.05; AST 228.1 ± 25.4 U/L vs 32.7 ± 6.8 U/L, P < 0.05). Severe pain occurred in three patients, which was controlled with morphine and fentanyl.
CONCLUSION: TACE combined with immediate RFA is a safe and effective treatment for large solitary HCCs. Severe pain is a major side effect, but can be controlled by morphine.
doi:10.3748/wjg.v19.i26.4192
PMCID: PMC3710422  PMID: 23864783
Large hepatocellular carcinoma; Transcatheter arterial chemoembolisation; Radiofrequency ablation; Combination therapy; Synchronism
15.  Hepatocellular carcinoma associated with budd-chiari syndrome: imaging features and transcatheter arterial chemoembolization 
BMC Gastroenterology  2013;13:105.
Background
Budd–Chiari syndrome (BCS) often leads to hepatocellular carcinoma (HCC). Transcatheter arterial chemoembolization (TACE) has been increasingly used to treat BCS patients with HCC. The purposes of this study were to illustrate imaging features in BCS patients with HCC, and to analyze the effects of TACE on BCS patients with HCC.
Methods
246 consecutive patients with primary BCS were retrospectively studied. 14 BCS patients with HCC were included in this study. BCS were treated with angioplasty and/or stenting, and HCC were managed with TACE. Imaging features on ultrasonography, CT, MRI, and angiography and the serum AFP level were analyzed.
Results
Inferior vena cava block and stricture of hepatic venous outflow tract more frequently occurred. Portal vein invasion was found in only 2 patients (14.2%). Imaging studies showed that most nodules of HCC were near the edge of liver, irregular, more than 3 cm in diameter, heterogeneous mass and solitary (≤3 nodules). HCC in patients associated with BCS was isointense or hypointense in nonenhanced CT images, and exhibited heterogeneous enhancement during the arterial phase and washout during the portal venous phase on enhanced CT and MRI. The serum AFP level significantly declined after TACE treatment.
Conclusions
BCS patients with inferior vena cava block and stricture of hepatic venous outflow tract seems to be associated with HCC. A single, large, irregular nodule with a peripheral location appears to be HCC. TACE can effectively treat HCC in BCS patients.
doi:10.1186/1471-230X-13-105
PMCID: PMC3693971  PMID: 23800233
Hepatocellular carcinoma; Budd–Chiari syndrome; Transcatheter arterial chemoembolization
16.  A Mass Spectrometry “Sensor” for in Vivo Acetylcholine Monitoring 
Analytical Chemistry  2012;84(11):4659-4664.
Developing sensors for in vivo chemical monitoring is a daunting challenge. An alternative approach is to couple sampling methods with online analytical techniques; however, such approaches are generally hampered by lower temporal resolution and slow analysis. In this work, microdialysis sampling was coupled with segmented flow electrospray ionization mass spectrometry (ESI-MS) to perform in vivo chemical monitoring. Use of segmented flow to prevent Taylor dispersion of collected zones and rapid analysis with direct ESI-MS allowed 5 s temporal resolution to be achieved. The MS “sensor” was applied to monitoring acetylcholine in the brain of live rats. The detection limit of 5 nM was sufficient to monitor basal acetylcholine as well as dynamic changes elicited by microinjection of neostigmine, an inhibitor of acetycholinesterase that evoked rapid increases in acetycholine, and tetrodotoxin, a blocker of Na+ channels, that lowered the acetylcholine concentration. The versatility of the sensor was demonstrated by simultaneously monitoring metabolites and infused drugs.
doi:10.1021/ac301203m
PMCID: PMC3389145  PMID: 22616788
17.  Induction of CCL8/MCP-2 by Mycobacteria through the Activation of TLR2/PI3K/Akt Signaling Pathway 
PLoS ONE  2013;8(2):e56815.
Pleural tuberculosis (TB), together with lymphatic TB, constitutes more than half of all extrapulmonary cases. Pleural effusions (PEs) in TB are representative of lymphocytic PEs which are dominated by T cells. However, the mechanism underlying T lymphocytes homing and accumulation in PEs is still incompletely understood. Here we performed a comparative analysis of cytokine abundance in PEs from TB patients and non-TB patients by protein array analysis and observed that MCP-2/CCL8 is highly expressed in the TB-PEs as compared to peripheral blood. Meanwhile, we observed that CCR5, the primary receptor used by MCP-2/CCL8, is mostly expressed on pleural CD4+ T lymphocytes. Furthermore, we found that infection with either Mycobacterium bovis Bacillus Calmette-Guérin (BCG) or Mycobacterium tuberculosis H37Rv induced production of MCP-2/CCL8 at both transcriptional and protein level in Raw264.7 and THP-1 macrophage cells, mouse peritoneal macrophages as well as human PBMC monocyte-derived macrophages (MDMs). The induction of MCP-2/CCL8 by mycobacteria is dependent on the activation of TLR2/PI3K/Akt and p38 signaling pathway. We conclude that accumulation of MCP-2/CCL8 in TB-PEs may function as a biomarker for TB diagnosis.
doi:10.1371/journal.pone.0056815
PMCID: PMC3572057  PMID: 23418602
18.  Effect of Electronic Acceptor Segments on Photophysical Properties of Low-Band-Gap Ambipolar Polymers 
The Scientific World Journal  2013;2013:890215.
Stimulated by a recent experimental report, charge transfer and photophysical properties of donor-acceptor ambipolar polymer were studied with the quantum chemistry calculation and the developed 3D charge difference density method. The effects of electronic acceptor strength on the structure, energy levels, electron density distribution, ionization potentials, and electron affinities were also obtained to estimate the transporting ability of hole and electron. With the developed 3D charge difference density, one visualizes the charge transfer process, distinguishes the role of molecular units, and finds the relationship between the role of DPP and excitation energy for the three polymers during photo-excitation.
doi:10.1155/2013/890215
PMCID: PMC3556892  PMID: 23365549
19.  In Vivo Neurochemical Monitoring using Benzoyl Chloride Derivatization and Liquid Chromatography – Mass Spectrometry 
Analytical Chemistry  2011;84(1):412-419.
In vivo neurochemical monitoring using microdialysis sampling is important in neuroscience because it allows correlation of neurotransmission with behavior, disease state, and drug concentrations in the intact brain. A significant limitation of current practice is that different assays are utilized for measuring each class of neurotransmitter. We present a high performance liquid chromatography (HPLC) - tandem mass spectrometry method that utilizes benzoyl chloride for determination of the most common low molecular weight neurotransmitters and metabolites. In this method, 17 analytes were separated in 8 minutes. The limit of detection was 0.03–0.2 nM for monoamine neurotransmitters, 0.05–11 nM for monoamine metabolites, 2–250 nM for amino acids, 0.5 nM for acetylcholine, 2 nM for histamine, and 25 nM for adenosine at sample volume of 5 µL. Relative standard deviation for repeated analysis at concentrations expected in vivo averaged 7% (n = 3). Commercially available 13C benzoyl chloride was used to generate isotope-labeled internal standards for improved quantification. To demonstrate utility of the method for study of small brain regions, the GABAA receptor antagonist bicuculline (50 µM) was infused into rat ventral tegmental area while recording neurotransmitter concentration locally and in nucleus accumbens, revealing complex GABAergic control over mesolimbic processes. To demonstrate high temporal resolution monitoring, samples were collected every 60 s while neostigmine, an acetylcholine esterase inhibitor, was infused into the medial prefrontal cortex. This experiment revealed selective positive control of acetylcholine over cortical glutamate.
doi:10.1021/ac202794q
PMCID: PMC3259198  PMID: 22118158
Neurotransmitter; Microdialysis; Benzoylation; Liquid Chromatography; Mass Spectrometry
20.  Therapeutic effect of nerve growth factor on cerebral infarction in dogs using the hemisphere anomalous volume ratio of diffusion-weighted magnetic resonance imaging★ 
Neural Regeneration Research  2012;7(24):1873-1880.
A model of focal cerebral ischemic infarction was established in dogs through middle cerebral artery occlusion of the right side. Thirty minutes after occlusion, models were injected with nerve growth factor adjacent to the infarct locus. The therapeutic effect of nerve growth factor against cerebral infarction was assessed using the hemisphere anomalous volume ratio, a quantitative index of diffusion-weighted MRI. At 6 hours, 24 hours, 7 days and 3 months after modeling, the hemisphere anomalous volume ratio was significantly reduced after treatment with nerve growth factor. Hematoxylin-eosin staining, immunohistochemistry, electron microscopy and neurological function scores showed that infarct defects were slightly reduced and neurological function significantly improved after nerve growth factor treatment. This result was consistent with diffusion-weighted MRI measurements. Experimental findings indicate that nerve growth factor can protect against cerebral infarction, and that the hemisphere anomalous volume ratio of diffusion-weighted MRI can be used to evaluate the therapeutic effect.
doi:10.3969/j.issn.1673-5374.2012.24.005
PMCID: PMC4298901  PMID: 25624813
diffusion-weighted MRI; nerve growth factor; hemisphere anomalous volume ratio; cerebral infarction; treatment; neuroprotection; brain; regeneration; neural regeneration
21.  Microdialysis and Mass Spectrometric Monitoring of Dopamine and Enkephalins in the Globus Pallidus Reveal Reciprocal Interactions that Regulate Movement 
Journal of neurochemistry  2011;118(1):24-33.
Pallidal dopamine, GABA and the endogenous opioid peptides enkephalins have independently been shown to be important controllers of sensorimotor processes. Using in vivo microdialysis coupled to liquid chromatography-mass spectrometry (LC-MS) and a behavioral assay, we explored the interaction between these three neurotransmitters in the rat globus pallidus. Amphetamine (3 mg/kg i.p.) evoked an increase in dopamine, GABA and methionine/leucine enkephalin. Local perfusion of the dopamine D1 receptor antagonist SCH 23390 (100 μM) fully prevented amphetamine stimulated enkephalin and GABA release in the globus pallidus and greatly suppressed hyperlocomotion. In contrast, the dopamine D2 receptor antagonist raclopride (100 μM) had only minimal effects suggesting a greater role for pallidal D1 over D2 receptors in the regulation of movement. Under basal conditions, opioid receptor blockade by naloxone perfusion (10 μM) in the globus pallidus stimulated GABA and inhibited dopamine release. Amphetamine-stimulated dopamine release and locomotor activation were attenuated by naloxone perfusion with no effect on GABA. These findings demonstrate a functional relationship between pallidal dopamine, GABA and enkephalin systems in the control of locomotor behavior under basal and stimulated conditions. Moreover, these findings demonstrate the usefulness of LC-MS as an analytical tool when coupled to in vivo microdialysis.
doi:10.1111/j.1471-4159.2011.07293.x
PMCID: PMC3112281  PMID: 21534957
Globus pallidus; dopamine; enkephalins; mass spectrometry; microdialysis; amphetamine
22.  An Adaptive Mesh Refinement Strategy for Immersed Boundary/Interface Methods 
An adaptive mesh refinement strategy is proposed in this paper for the Immersed Boundary and Immersed Interface methods for two-dimensional elliptic interface problems involving singular sources. The interface is represented by the zero level set of a Lipschitz function φ(x,y). Our adaptive mesh refinement is done within a small tube of |φ(x,y)|≤ δ with finer Cartesian meshes. The discrete linear system of equations is solved by a multigrid solver. The AMR methods could obtain solutions with accuracy that is similar to those on a uniform fine grid by distributing the mesh more economically, therefore, reduce the size of the linear system of the equations. Numerical examples presented show the efficiency of the grid refinement strategy.
doi:10.4208/cicp.070211.150811s
PMCID: PMC3366192  PMID: 22670155
Adaptive mesh refinement; immersed boundary method; immersed interface method; elliptic interface problem; Cartesian grid method; level set representation; singular sources
23.  A diffuse-interface method for two-phase flows with soluble surfactants 
Journal of computational physics  2011;230(2):375-393.
A method is presented to solve two-phase problems involving soluble surfactants. The incompressible Navier–Stokes equations are solved along with equations for the bulk and interfacial surfactant concentrations. A non-linear equation of state is used to relate the surface tension to the interfacial surfactant concentration. The method is based on the use of a diffuse interface, which allows a simple implementation using standard finite difference or finite element techniques. Here, finite difference methods on a block-structured adaptive grid are used, and the resulting equations are solved using a non-linear multigrid method. Results are presented for a drop in shear flow in both 2D and 3D, and the effect of solubility is discussed.
doi:10.1016/j.jcp.2010.09.020
PMCID: PMC3015195  PMID: 21218125
Multiphase flows; interfacial dynamics; surfactant; soluble surfactant; surface phase; bulk phase; adsorption; desorption; complex geometry; diffuse interface; phase field; multigrid; adaptive grid; finite difference
24.  Fraction Collection from Capillary Liquid Chromatography and Off-line Electrospray Ionization Mass Spectrometry using Oil Segmented Flow 
Analytical chemistry  2010;82(12):5260-5267.
Off-line analysis and characterization of samples separated by capillary liquid chromatography (LC) has been problematic using conventional approaches to fraction collection. We demonstrate collection of nanoliter fractions by forming plugs of effluent from a 75 μm inner diameter LC column segmented by an immiscible oil such as perfluorodecalin. The plugs are stored in tubing that can then be used to manipulate the samples. Off-line electrospray ionization mass spectrometry (ESI-MS) was used to characterize the samples. ESI-MS was performed by directly pumping the segmented plugs into a nanospray emitter tip. Critical parameters including the choice of oils, ESI voltage, and flow rates that allows successful direct infusion analysis were investigated. Best signals were obtained under conditions in which the oil did not form an electrospray but was siphoned away from the tip. Off-line analysis showed preservation of the chromatogram with no loss of resolution. The method was demonstrated to allow changes in flow rate during the analysis. Specifically, decreases in flow rate were used to allow extended MS analysis time on selected fractions, similar to “peak parking”.
doi:10.1021/ac100669z
PMCID: PMC2894538  PMID: 20491430
25.  Stent-grafts placement for treatment of massive hemorrhage from ruptured hepatic artery after pancreaticoduodenectomy 
AIM: To present a series of cases with life-threatening hemorrhage from ruptured hepatic artery pseudoaneurysm after pancreaticoduodenectomy (PD) treated with placement of stent-grafts.
METHODS: Massive hemorrhage from ruptured hepatic artery pseudoaneurysm after PD in 9 patients (6 men, 3 women) at the age of 23-75 years (mean 48 years), were treated with placement of percutaneous endovascular balloon-expandable coronary stent-grafts. All patients were not suitable for embolization because of a non-patent portal vein. One or more stent-grafts, ranging 3-6 mm in diameter and 16-55 mm in length, were placed to exclude ruptured pseudoaneurysm. Follow-up data, including clinical condition, liver function tests, and Doppler ultrasound examination, were recorded at the outpatient clinic.
RESULTS: Immediate technical success was achieved in all the 9 patients. All stent-grafts were deployed in the intended position for immediate cessation of bleeding and preservation of satisfactory hepatic arterial blood flow. No significant procedure-related complications occurred. Recurrent bleeding occurred in 2 patients at 16 and 24 h, respectively, after placement of stent-grafts and treated with surgical revision. One patient died of sepsis 12 d after the interventional procedure. The remaining 6 patients were survived when they were discharged. The mean follow-up time was 10.5 mo (range 4-16 mo). No patient had recurrent bleeding after discharge. Doppler ultrasound examination verified the patency of hepatic artery and stent-grafts during the follow-up.
CONCLUSION: Placement of stent-grafts is an effective and safe procedure for acute life-threatening hemorrhage from ruptured hepatic artery pseudoaneurysm.
doi:10.3748/wjg.v16.i29.3716
PMCID: PMC2915434  PMID: 20677346
Pancreaticoduodenectomy; Hemorrhage; Hepatic artery; Pseudoaneurysm; Stent-graft

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