Using a 3D Navigation Template to Increase the Accuracy of Thoracic Pedicle Screws in Patients with Scoliosis.

This study compares the accuracy and safety of pedicle screw placement using a 3D navigation template with the free-hand fluoroscopy technique in scoliotic patients. Fifteen scoliotic patients were recruited and divided into a template group (eight cases) and a free-hand group (seven cases). All patients received posterior corrective surgeries, and the pedicle screw was placed using a 3D navigation template or a free-hand technique. After surgery, the positions of the pedicle screws were evaluated using CT. A total of 264 pedicle screws were implanted in 15 patients. Both the two techniques were found to achieve satisfactory safety of screw insertion in scoliotic patients (89.9% vs. 90.5%). In the thoracic region, the 3D navigation template was able to achieve a much higher accuracy of screw than the free-hand technique (75.3% vs. 60.4%). In the two groups, the accuracy rates on the convex side were slightly higher than on the concave side, while no significance was seen. In terms of rotational vertebrae, no significant differences were seen in Grades I or II vertebrae between the two groups. In conclusion, the 3D navigation template technique significantly increased the accuracy of thoracic pedicle screw placement, which held great potential for extensively clinical application.

Intelligent analysis of excitation-emission matrix fluorescence fingerprint to identify and quantify adulteration in camellia oil based on machine learning.

Camellia oil (CAO) is a premium edible vegetable oil with medical value and biological activity, but it is susceptible to adulteration. Therefore, the demand for intelligent analysis to decipher the category and proportion of adulterated oil in CAO was the main driver of this work. Excitation-emission matrix fluorescence (EEMF) spectra of 933 vegetable oil samples were characterized by a chemometric method to obtain chemically meaningful information. Authenticity identification models were constructed using four machine learning methods to realize the discrimination of oil species adulterated in CAO mixtures. Meanwhile, quantitative models were established aiming at the fraud of CAO proportion in blended oil. Results showed that the specially constructed CNN obtained the optimal performance when evaluating unseen real-world samples, with a classification accuracy of 95.8% and 92.2%, and mean-absolute quantitative errors between 2.6 and 6.7%. Therefore, EEMF fingerprints coupled with machine learning are expected to provide intelligent and accurate analysis for authenticity detection of CAO.

p53 inhibits CTR1-mediated cisplatin absorption by suppressing SP1 nuclear translocation in osteosarcoma.

Background: Osteosarcoma (OS) is a malignant bone tumor mainly affecting children and young adolescents. Cisplatin is a first-line chemotherapy drug for OS, however, drug resistance severely limits the survival of OS. Nevertheless, cellular factors in cisplatin resistance for OS remain obscure. In this study, the function and potential mechanism of p53 in cisplatin absorption were explored in OS cells. Methods: The CRISPR-Cas9 gene editing technology was performed to obtain p53 gene knock-out U2OS cells. The p53 over-expression 143B cell line was established by lentivirus-mediated virus infection. Moreover, the functions of p53 and CTR1 in cisplatin absorption were assessed by inductively coupled plasma mass spectrometry (ICP-MS) through CTR1 over-expression and knock-down. Further, the DNA binding activity of SP1 on CTR1 gene promoter was determined by dual-luciferase assay and chromatin immunoprecipitation (ChIP) assay. The functional regulation of p53 on SP1 was studied by nucleocytoplasmic separation assay and electrophoretic mobility shift assay (EMSA). The interaction between p53 and SP1 was verified by Co-Immunoprecipitation assay. Results: Under cisplatin treatment, p53 knock-out promoted CTR1 expression and cisplatin uptake, while p53 overexpression inhibited CTR1 expression and cisplatin uptake. Moreover, p53 regulated CTR1 level not by binding to CTR1 promoter directly but by suppressing the nuclear translocation of transcription factor specificity protein 1 (SP1). It was verified that SP1 is directly bound with CTR1 promoter. SP1 overexpression stimulated CTR1 expression, and SP1 knock-down attenuated CTR1 expression. Conclusion: The p53 might function as a negative regulator in CTR1 mediated cisplatin absorption, and the p53-SP1-CTR1 axis is a target for cisplatin resistance.

Comparison of three chemometric methods for processing HPLC-DAD data with time shifts: Simultaneous determination of ten molecular targeted anti-tumor drugs in different biological samples.

Three intelligent chemometric multi-way calibration methods including alternating trilinear decomposition (ATLD), alternating trilinear decomposition assisted multivariate curve resolution (ATLD-MCR) and multivariate curve resolution-alternating least squares (MCR-ALS) combined with high performance liquid chromatography-diode array detection (HPLC-DAD) were used to quantify ten molecular targeted anti-tumor drugs in three complex biological matrices (plasma, urine and cell culture media matrices). All analytes can be successfully eluted in 6.5 min. In this experiment, various degrees of time shifts occurred in different samples. While slight time shifts exist in the chromatographic analysis, satisfactory results can be obtained by the three proposed methods. When the time shift was large (5.6 s), the average spiked recoveries obtained by ATLD analysis were in the range of 58.9%-116.5%, which was less than satisfactory. However, the average recoveries obtained by MCR-ALS and ATLD-MCR analysis were 89.8%-114.8% and 84.5%-106.1% respectively, and more satisfactory results were obtained. For further research, ATLD-MCR and MCR-ALS methods were compared, and the results were evaluated by statistical tests. Accuracies of concentrations obtained by them were considered to be no significant difference. In addition, compared with other methods currently published, the proposed chemometric methods combined with the HPLC-DAD can rapidly, simultaneously and accurately determine varieties of molecular targeted anti-tumor drugs in different complex biological matrices even in the presence of severe peak overlaps, severe time shifts, slight baseline drifts and different unknown background interferences.

Role of Anti-Epidermal Growth Factor Receptor Therapy Compared with Anti-Vascular Endothelial Growth Factor Therapy for Metastatic Colorectal Cancer: an Update Meta-Analysis of Randomized Clinical Trials.

Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have showed clinical benefit in combination with chemotherapeutic cytotoxic drugs in the first-line therapy of metastatic colorectal cancer (mCRC). Data from randomized studies comparing these monoclonal antibodies as initial therapy is conflicting, and their comparative efficacy remains unknown. This study aimed to evaluate the impact of the combination of anti-epidermal growth factor receptor (anti-EGFR) therapy and anti-vascular endothelial growth factor therapy on mCRC patient outcomes by combining the data from randomized clinical trials. Three trials meeting the eligibility criteria, and four randomized studies were included in the meta-analysis. For MCRC patients with KRAS wild type (KRAS-WT), the ORR was superior in patients treated with anti-EGFR compared with those who treated with anti-VEGF therapy. This effect was even better for all RAS-WT patients. Progression-free survival (PFS) rates were not significantly different for KRAS-WT mCRC and all RAS-WT mCRC between the two groups. The overall survival (OS) was higher for RAS wild-type (RAS-WT) mCRC patients who received anti-EGFR, but the KRAS-WT patients compared to the anti-VEGF therapy. The results of our research indicate that superior ORR and OS between the addition of anti-EGFR therapy VS anti-VEGF therapy in all RAS-WT patients with MCRC. There was no significant difference in OS and PFS between the two groups for KRAS-WT mCRC. These results suggest that anti- EGFR monoclonal antibodies can achieve an equivalent efficacy when compared with anti-VEGF therapy of all RAS-WT mCRC patients.

Rapid identification and quantification of cheaper vegetable oil adulteration in camellia oil by using excitation-emission matrix fluorescence spectroscopy combined with chemometrics.

Camellia oil is a high quality oil mainly produced in southern China. It is common that unscrupulous merchants attempt to make huge profits by adulterating camellia oil with other cheaper or lower-quality vegetable oils. Therefore, this paper proposed excitation-emission matrix fluorescence spectroscopy combined with chemometric methods for the rapid identification and quantification of camellia oil adulteration with other cheaper vegetable oils. A five-component parallel factor analysis (PARAFAC) model roughly completed spectral characterization of oil samples, and obtained chemically meaningful information. Four advanced chemometrics methods were used for the classification of camellia oil and other vegetable oils (model 1) and the classification of camellia oil and adulterated camellia oil (models 2 and 3), respectively. Two-directional two-dimensional linear discriminant analysis ((2D)2LDA) was used for chemical data for the first time and showed huge potential. Furthermore, the developed N-PLS regression model used for the prediction of adulteration level in camellia oil showed satisfactory accuracy.

Simultaneously quantifying intracellular FAD and FMN using a novel strategy of intrinsic fluorescence four-way calibration.

The simultaneous quantitative analysis of intracellular metabolic coenzymes flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) is of interest because they participate in many electron-transfer reactions of metabolism. But, the simultaneous quantitative analysis of FAD and FMN is hard to be achieved by traditional analytical methods. This paper proposes a novel strategy of intrinsic fluorescence coupled with four-way calibration method for simultaneous quantitative analysis of intracellular metabolic coenzymes FAD and FMN. Through mathematical separation, this proposed analytical method efficiently achieved the simultaneous quantitative analysis of metabolic coenzymes FAD and FMN in the cell, despite the fact that uncalibrated spectral interferents coexist in the system. The predicted concentrations of FAD and FMN in the cell are 217.0 ±â€¯6.9 and 155.0 ±â€¯1.7 pmol/106 cells respectively, which were validated by the approved liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. This analytical method with second-order advantage simply requires the cell solution to be diluted by a buffer, it could introduce an interesting analytical strategy for multianalyte direct quantitative analysis in complex biological systems. In addition, we explore the third-order advantage of four-way calibration by a comparative study based on this real fluorescence data. The comparisons indicate that a four-way calibration method can provide higher sensitivity and more resolving power than a three-way calibration method.

Leisure time physical activity and risk of prostate cancer: a dose-response meta-analysis.

INTRODUCTION: Physical activity (PA) may be a protect factor against prostate cancer (PCa). We aim to investigate and establish the potential relationship between leisure time PA and PCa. EVIDENCE ACQUISITION: PubMed, Embase databases were searched for eligible studies (cohort) before Aug-11, 2016. We conducted a meta-analysis to pool the dose-specific effects between leisure time PA and PCa. Subgroup analysis was employed to investigate the potential variation among each group. Sensitivity analysis was used to examine whether our results were stable. EVIDENCE SYNTHESIS: Twenty-one cohort studies were identified, with a total of 803,872 subjects and 28,707 PCa cases. In our meta-analysis, no obvious evidence of non-linear relationship was observed. The RRs of each 500 MET-s/week increment of leisure time PA was 1.00 (95% CI: 0.99-1.01) for total PCa, 1.00 (95% CI: 0.98-1.01) for local PCa, and 1.00 (95% CI: 0.98-1.02) for advanced PCa. In subgroup analysis, for Americans, the RR of each 500 MET-s/week increment of leisure time PA was 1.00 (95% CI: 0.99-1.01); and for Europeans the RR was 1.00 (95% CI: 0.99-1.01). Sensitivity analysis suggested our results were stable. CONCLUSIONS: Current evidence based on observational studies suggests no obvious association between leisure time activity and risk of prostate cancer, regardless of total PCa, local PCa, or advanced PCa.

Fast and simultaneous determination of 12 polyphenols in apple peel and pulp by using chemometrics-assisted high-performance liquid chromatography with diode array detection.

In this work, a smart chemometrics-enhanced strategy, high-performance liquid chromatography, and diode array detection coupled with second-order calibration method based on alternating trilinear decomposition algorithm was proposed to simultaneously quantify 12 polyphenols in different kinds of apple peel and pulp samples. The proposed strategy proved to be a powerful tool to solve the problems of coelution, unknown interferences, and chromatographic shifts in the process of high-performance liquid chromatography analysis, making it possible for the determination of 12 polyphenols in complex apple matrices within 10 min under simple conditions of elution. The average recoveries with standard deviations, and figures of merit including sensitivity, selectivity, limit of detection, and limit of quantitation were calculated to validate the accuracy of the proposed method. Compared to the quantitative analysis results from the classic high-performance liquid chromatography method, the statistical and graphical analysis showed that our proposed strategy obtained more reliable results. All results indicated that our proposed method used in the quantitative analysis of apple polyphenols was an accurate, fast, universal, simple, and green one, and it was expected to be developed as an attractive alternative method for simultaneous determination of multitargeted analytes in complex matrices.

An Atypical Right Atrial Myxoma With Spontaneous Rupture.

Typically, cardiac maxomas arise from the interatrial septum at the border of the fossa ovalis in the left atrium, whereas atypical right atrial myxoma, especially with spontaneous rupture, is extremely rare. Here we report the diagnostic evaluation and successful surgical resection of an atypical myxoma with spontaneous rupture arising from the posterior wall of the right atrium in a 34-year-old male.

Determination of benzo[a]pyrene in cigarette mainstream smoke by using mid-infrared spectroscopy associated with a novel chemometric algorithm.

Determination of benzo[a]pyrene (BaP) in cigarette smoke can be very important for the tobacco quality control and the assessment of its harm to human health. In this study, mid-infrared spectroscopy (MIR) coupled to chemometric algorithm (DPSO-WPT-PLS), which was based on the wavelet packet transform (WPT), discrete particle swarm optimization algorithm (DPSO) and partial least squares regression (PLS), was used to quantify harmful ingredient benzo[a]pyrene in the cigarette mainstream smoke with promising result. Furthermore, the proposed method provided better performance compared to several other chemometric models, i.e., PLS, radial basis function-based PLS (RBF-PLS), PLS with stepwise regression variable selection (Stepwise-PLS) as well as WPT-PLS with informative wavelet coefficients selected by correlation coefficient test (rtest-WPT-PLS). It can be expected that the proposed strategy could become a new effective, rapid quantitative analysis technique in analyzing the harmful ingredient BaP in cigarette mainstream smoke.

Additive anticancer effects of chrysin and low dose cisplatin in human malignant glioma cell (U87) proliferation and evaluation of the mechanistic pathway.

PURPOSE: To evaluate the anticancer effect of chrysin and its additive combination with low-dose cisplatin in human glioma (U87) cancer cells and to study its underlying mechanism. METHODS: Inverted phase and fluorescence microscopic studies were done to demonstrate the effect of chrysin and its combination with cisplatin on cellular morphology and apoptosis. Annexin V-FITC assay was used to quantify the extent of apoptosis in chrysin and chrysin+cisplatin treated cells. Flow cytometry using propidium iodide (PI) as a staining agent was used to study the effect of chrysin and its combination with cisplatin on cell cycle phase distribution. RESULTS: The results showed chrysin brought about a potent and dose-dependent antiproliferative effect in human glioma cancer cells. However, the combination of chrysin with low dose cisplatin led to a much higher growth inhibitory effects indicating an additive effect between the two compounds. The combined effect of chrysin and cisplatin also gave rise to a greater apoptosis induction as well as cell cycle arrest in comparison to the treatment by chrysin or cisplatin alone. Fluorescence microscopy as well as inverted phase contrast microscopy also revealed that the combination of chrysin plus cisplatin resulted in greater apoptosis induction as well as cell morphology alterations. Combination treatment of chrysin and cisplatin resulted in greater percentage of cells in early as well as in late apoptotic stages. The combination effect was also seen in mitochondrial membrane potential loss. CONCLUSION: Chrysin additively potentiates the antiproliferative, cell cycle arrest and apoptotic activity of cisplatin in human glioma cancer (U87) cells.

Fast HPLC-DAD quantification of nine polyphenols in honey by using second-order calibration method based on trilinear decomposition algorithm.

This paper describes the use of second-order calibration for development of HPLC-DAD method to quantify nine polyphenols in five kinds of honey samples. The sample treatment procedure was simplified effectively relative to the traditional ways. Baselines drift was also overcome by means of regarding the drift as additional factor(s) as well as the analytes of interest in the mathematical model. The contents of polyphenols obtained by the alternating trilinear decomposition (ATLD) method have been successfully used to distinguish different types of honey. This method shows good linearity (r>0.99), rapidity (t<7.60 min) and accuracy, which may be extremely promising as an excellent routine strategy for identification and quantification of polyphenols in the complex matrices.

Fast analysis of synthetic antioxidants in edible vegetable oil using trilinear component modeling of liquid chromatography-diode array detection data.

A new chromatographic methodology is presented for fast quantitative analysis of ten synthetic phenolic antioxidants in five kinds of oil samples: propyl gallate (PG), 2,4,5-trihydroxybutyrophenone (THBP), tert-butylhydroquinone (TBHQ), nordihydroguaiaretic acid (NDGA), ethoxyquin (EQ), 3-tert-butyl-4- hydroxyanisole (BHA), octyl gallate (OG), 2,6-di-tert-butyl-4-hydroxymethyphenol (Ionox-100), dodecyl gallate (DG), 3,5-di-tert-butyl-4-hydroxytoluene (BHT). The second-order calibration, with second-order advantage, based on the alternating penalty trilinear decomposition (APTLD) algorithm has shown to be an excellent tool for modeling the three-way data, where overlapping peaks, uncalibrated inteferences, and baseline drift existed, making the fast determination and resolution of the phenolic antioxidants in oils possible. Such extraction procedure in which the antioxidants of interest would be seperated is unnecessary and the ten antioxidants can be eluted within 6 mins. For the validation of the method, linearity, root-mean-square error of prediction (RMSEP) and limit of detection (LOD) have been performed. The average recovery of antioxidants ranges from 94.9 to 106.1% and the ten analytes can be adequately determined with limits of detection of 0.18-5.72 µgm l(-1).

Prevalence of vertebral endplate modic changes in degenerative lumbar scoliosis and its associated factors analysis.

STUDY DESIGN: A retrospective study of modic changes (MCs) in degenerative lumbar scoliosis (DLS). OBJECTIVE: To investigate the prevalence of vertebral endplate MCs in DLS and explore their associated factors. SUMMARY OF BACKGROUND DATA: MCs are common in spinal degenerative diseases. Presently, most of the researches have been focused on investigating the relationship between MCs and chronic low back pain. Little has been known on the distribution of MCs in DLS and the relationship between MCs and scoliosis. METHODS: The image data of 120 patients who had been diagnosed with DLS in our hospital from March 2005 to March, 2011 were retrospectively reviewed as the study group. The image data of 89 patients who had been diagnosed with degenerative lumbar diseases without scoliosis were selected as the control group. The prevalence, type, and distribution of MCs in 2 groups were observed and compared. Disc degeneration, Cobb angle, body weight, and smoking were recorded in the study group, and the relationship of MCs with these influential factors was analyzed. RESULTS: Of 1440 endplates from 120 patients in the study group, 247 (17.2%) from 71 (59.2%) patients were found to have MCs. Compared with the control group, of 1068 endplates from 89 patients, 49 (4.5%) endplates from 21 (23.6%) patients were found to have MCs. The prevalence of MCs was significantly higher in the study group than that in the control group (P < 0.01). The MCs in DLS usually had asymmetric distribution with more frequent occurrence on the concave side than on the convex side of major or compensatory curve and mainly occurred at L2-L3, L4-L5, and L5-S1, which were in accordance with the common levels of apex vertebrae. Intervertebral disc degeneration, lumbar scoliosis, overweight and heavy smoking are considered as risk factors to MCs. By multinomial logistic regression analysis on these factors, the regression function was obtained: logit Y = -0.82 + 1.27D + 0.55S + 1.77 D × S (Y for MCs, D for intervertebral disc degeneration, S for scoliosis Cobb's angle and D × S for interaction of D and S). CONCLUSION: The prevalence of MCs in patients with DLS was significantly higher than that of patients without DLS. Most of them were type 2 and usually located on the concave side of apex vertebrae. MCs were significantly associated with intervertebral disc degeneration and lumbar scoliosis.

Unimodal transform of variables selected by interval segmentation purity for classification tree modeling of high-dimensional microarray data.

As a greedy search algorithm, classification and regression tree (CART) is easily relapsing into overfitting while modeling microarray gene expression data. A straightforward solution is to filter irrelevant genes via identifying significant ones. Considering some significant genes with multi-modal expression patterns exhibiting systematic difference in within-class samples are difficult to be identified by existing methods, a strategy that unimodal transform of variables selected by interval segmentation purity (UTISP) for CART modeling is proposed. First, significant genes exhibiting varied expression patterns can be properly identified by a variable selection method based on interval segmentation purity. Then, unimodal transform is implemented to offer unimodal featured variables for CART modeling via feature extraction. Because significant genes with complex expression patterns can be properly identified and unimodal feature extracted in advance, this developed strategy potentially improves the performance of CART in combating overfitting or underfitting while modeling microarray data. The developed strategy is demonstrated using two microarray data sets. The results reveal that UTISP-based CART provides superior performance to k-nearest neighbors or CARTs coupled with other gene identifying strategies, indicating UTISP-based CART holds great promise for microarray data analysis.

Nano nickel oxide modified non-enzymatic glucose sensors with enhanced sensitivity through an electrochemical process strategy at high potential.

Development of fast and sensitive sensors for glucose determination is important in food industry, clinic diagnostics, biotechnology and many other areas. In these years, considerable attention has been paid to develop non-enzymatic electrodes to solve the disadvantages of the enzyme-modified electrodes, such as instability, high cost, complicated immobilization procedure and critical operating situation et al. Nano nickel oxide (NiO) modified non-enzymatic glucose sensors with enhanced sensitivity were investigated. Potential scanning nano NiO modified carbon paste electrodes up to high potential in alkaline solution greatly increases the amount of redox couple Ni(OH)(2)/NiOOH derived from NiO, and thus improves their electrochemical properties and electrocatalytical performance toward the oxidation of glucose. The non-enzymatic sensors response quickly to glucose and the response time is less than 5s, demonstrating excellent electrocatalytical activity and assay performance. The calibration plot is linear over the wide concentration range of 1-110 µM with a sensitivity of 43.9 nA/µM and a correlation coefficient of 0.998. The detection limit of the electrode was found to be 0.16 µM at a signal-to-noise ratio of 3. The proposed non-enzymatic sensors can be used for the assay of glucose in real sample.

[Correlation between intervertebral disc-endplate degeneration and bony structural parameter in adult degenerative scoliosis and its significance].

OBJECTIVES: To analyze the correlation between intervertebral disc-endplate degeneration and bony construction parameter and to explore its roles in adult degenerative scoliosis. METHODS: The imaging data of 79 patients with adult degenerative scoliosis from March 2005 to March 2010 were retrospectively reviewed as the study group. The imaging data of 41 patients with adolescent idiopathic scoliosis were selected as the control group. The vertebral body and intervertebral height in both sides on frontal X-ray, and the facet joint orientation in both sides on CT scan were measured respectively. The average vertebral body height, average intervertebral disc height and average facet orientation were regarded as bony structural parameters. The quantitative grading methods were used in the intervertebral disc and endplate degeneration. The relationship of bony construction parameter and intervertebral disc-endplate degeneration, and the relationship of bony construction parameter and Cobb's angle of scoliosis were analyzed by comparing all bony construction parameters in both groups. RESULTS: Analyzed by paired-t test, the intervertebral height, vertebral body height and facet joint orientation between convex and concave sides of the study group were of significant difference (t = 3.411, 2.623 and 2.085, P < 0.05). The intervertebral height between convex and concave sides of the control group were of significant difference (t = 3.276, P < 0.01), while the vertebral body height and the facet joint orientation were of no statistical significance (t = 1.572 and 1.493, P > 0.05). By linear correlation and regression analysis, the asymmetric degree of bony construction parameter showed good correlation with the score of intervertebral disc-endplate degeneration (-1 < r < 1, P < 0.05), which was positively correlated with Cobb's angle of scoliosis (0 < r < 1, P < 0.05). Linear regression existed between asymmetric degree of bony construction parameter and Cobb's angle (F = 427.342, P < 0.01). The regression function was obtained: Cobb's angle = -8.904+8.136 × IAD + 3.274 × VAD-0.713 × FAD (IAD: intervertebral asymmetry degree, VAD: vertebral asymmetry degree, FAD: facet joint asymmetry degree). CONCLUSIONS: The asymmetric change of bony construction exists in adult degenerative scoliosis, which significantly correlated with intervertebral disc-endplate degeneration and Cobb's angle of scoliosis. The asymmetric bony construction parameter probably plays a biomechanical role in the progression of scoliosis, which maybe the reason for the asymmetric degeneration of intervertebral disc-endplate.

Expression and significance of TLR4 and HIF-1alpha in pancreatic ductal adenocarcinoma.

AIM: To investigate the expression of toll-like receptor (TLR) 4, nuclear factor-kappaB (NF-kappaB) p65 and hypoxia-inducible transcription factor 1alpha (HIF-1alpha) in pancreatic ductal adenocarcinoma and their clinical significance. METHODS: The mRNA of TLR4 and HIF-1alpha were investigated by real-time polymerase chain reaction in 30 cases of pancreatic ductal adenocarcinoma and its adjacent tissues, and expression of TLR4, NF-kappaB p65 and HIF-1alpha protein were detected by immunohistochemistry in 65 cases of pancreatic ductal adenocarcinoma tissues and 38 cases of corresponding adjacent tissues. The relationship between TLR4 or HIF-1alpha and pathologic features, as well as the association between TLR4 and HIF-1alpha, were also analyzed. Kaplan-Meier method was used to assess the impact of expression of TLR4 and HIF-1alpha on survival of patients with pancreatic cancer. RESULTS: The relative quantification of TLR4 and HIF-1alpha mRNA in tumor tissues was 0.81 +/- 0.10 and 0.87 +/- 0.11, respectively, significantly higher than that in adjacent tissues (0.81 +/- 0.10 vs 0.70 +/- 0.16, P = 0.002; 0.87 +/- 0.11 vs 0.68 +/- 0.13, P = 0.000). The protein expression of TLR4, NF-kappaB p65 and HIF-1alpha in tumor tissues was 69.20%, 66.15% and 70.80%, respectively, being significantly higher than that in adjacent normal tissues (69.20% vs 39.50%, P = 0.003; 66.15% vs 31.58%, P = 0.001; 70.80% vs 36.80%, P = 0.001). There was no significant correlation between TLR4 or HIF-1alpha expression and the age, gender, tumor location, the degree of tumor differentiation in the patients (P > 0.05). However, there was significant correlation between the expression of TLR4 or HIF-1alpha and tumor size, lymph node metastasis, venous invasion and clinical staging (P < 0.05). The expression of TLR4 and HIF-1alpha had a significant impact on survival of patients with pancreatic adenocarcinoma. CONCLUSION: TLR4, NF-kappaB p65 and HIF-1alpha are overexpressed in pancreatic adenocarcinoma, TLR4 may be partly involved in up-regulating HIF-1alpha, and both synergestically promote development of pancreatic adenocarcinoma.

Surface-enhanced Raman spectroscopic detection of a bacteria biomarker using gold nanoparticle immobilized substrates.

The development of ultrasensitive and rapid methods for the detection of dipicolinic acid (DPA), a biomarker for bacterial spores including Bacillus anthracis, is increasingly important. This paper reports the results of an investigation of surface enhanced Raman spectroscopy (SERS) based ultrasensitive detection of DPA using a gold nanoparticle/polyvinylpyrrolidone/gold substrate (AuNPs/PVP/Au). The strong SERS effect of this substrate exploits the particle-particle and particle-substrate plasmonic coupling, which is optimized by manipulating the diameter of the nanoparticles (50-70 nm). The correlation between the SERS intensity of the diagnostic band and the DPA concentration (0.1 ppb to 100 ppm) was shown to exhibit two linear regions, i.e., the low- (<0.01 ppm) and high-concentration (>1 ppm) regions, with an intermediate region in between. The presence of a linear relationship in the low-concentration region was observed for the first time in SERS detection of DPA. A detection limit of 0.1 ppb was obtained from the substrates with 60 nm sized Au NPs, which is, to our knowledge, the lowest detection limit reported for DPA using this type of SERS substrate. This finding was also supported by the estimated enhancement factor (approximately 10(6)) and a large adsorption equilibrium constant for the low-concentration region (1.7 x 10(7) M(-1)). The adsorption characteristics of DPA on the SERS substrates were analyzed in terms of monolayer and multilayer adsorption isotherms to gain insights into the correlation between the SERS intensity and the DPA concentration. The observed transition from the low- to high-concentration linear regions was found to correspond to the transition from a monolayer to multilayer adsorption isotherm, which was in agreement with the estimated minimum DPA concentration for a monolayer coverage (approximately 0.01 ppm).