Diagnostic utility of LunX mRNA in peripheral blood and pleural fluid in patients with primary non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Progress in lung cancer is hampered by the lack of clinically useful diagnostic markers. The goal of this study was to provide a detailed evaluation of lung cancer tumor markers indicative of molecular abnormalities and to assess their diagnostic utility in non-small cell lung cancer (NSCLC) patients.</p> <p>Methods</p> <p>Quantitative real-time RT-PCR was used to determine <it>LunX, CK19, CEA, VEGF-C </it>and <it>hnRNP A2/B1 </it>mRNA levels in peripheral blood and pleural fluid from NSCLC patients, compared with those from patients with other epithelial cancer (esophagus cancer and breast cancer), benign lung disease (pneumonia and tuberculo pleurisy) and from healthy volunteers.</p> <p>Results</p> <p>In peripheral blood <it>LunX </it>mRNA was detectable in 75.0% (33/44) of patients with NSCLC, but not in patients with other epithelial cancer (0/28), benign lung disease (0/10) or in healthy volunteers (0/15). In contrast, all other genetic markers were detected in patients with either NSCLC, other epithelia cancer or benign lung disease, and in healthy volunteers. The expression level and positive rate of <it>LunX </it>mRNA in peripheral blood correlated with the pathologic stage of NSCLC (P < 0.001 and P = 0.010 respectively). Furthermore, <it>LunX </it>mRNA was detected in 92.9% (13/14) of malignant pleural fluid samples and was the only marker whose expression level was significantly different between malignant and benign pleural fluid (P < 0.001). Additionally, expression of <it>LunX </it>mRNA in the peripheral blood of NSCLC patients decreased shortly after clinical treatment (P = 0.005).</p> <p>Conclusion</p> <p>Of several commonly used genetic markers, <it>LunX </it>mRNA is the most specific gene marker for lung cancer and has potential diagnostic utility when measured in the peripheral blood and pleural fluid of NSCLC patients.</p

Tandem mass tag-based quantitative proteomic analysis of effects of multiple sevoflurane exposures on the cerebral cortex of neonatal and adult mice

IntroductionSevoflurane is the most commonly used general anesthetic in pediatric surgery, but it has the potential to be neurotoxic. Previous research found that long-term or multiple sevoflurane exposures could cause cognitive deficits in newborn mice but not adult mice, whereas short-term or single inhalations had little effect on cognitive function at both ages. The mechanisms behind these effects, however, are unclear.MethodsIn the current study, 6- and 60-day-old C57bl mice in the sevoflurane groups were given 3% sevoflurane plus 60% oxygen for three consecutive days, each lasting 2 hours, while those in the control group only got 60% oxygen. The cortex tissues were harvested on the 8th or 62nd day. The tandem mass tags (TMT)pro-based quantitative proteomics combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, Golgi staining, and western blotting analysis were applied to analyze the influences of multiple sevoflurane anesthesia on the cerebral cortex in mice with various ages. The Morris water maze (MWM) test was performed from postnatal day (P)30 to P36 or P84 to P90 after control or multiple sevoflurane treatment. Sevoflurane anesthesia affected spatial learning and memory and diminished dendritic spines primarily in newborn mice, whereas mature animals exhibited no significant alterations.ResultsA total of 6247 proteins were measured using the combined quantitative proteomics methods of TMTpro-labeled and LC-MS/MS, 443 of which were associated to the age-dependent neurotoxic mechanism of repeated sevoflurane anesthesia. Furthermore, western blotting research revealed that sevoflurane-induced brain damage in newborn mice may be mediated by increasing the levels of protein expression of CHGB, PTEN, MAP2c, or decreasing the level of SOD2 protein expression.ConclusionOur findings would help to further the mechanistic study of age-dependent anesthetic neurotoxicity and contribute to seek for effective protection in the developing brain under general anesthesia

Effect of Metformin on Lactate Metabolism in Normal Hepatocytes under High Glucose Stress in Vitro

Objective To study the effect of metformin on lactate metabolism in hepatocytes in vitro under high glucose stress. In vitro LO2 cells, liver cells were randomly divided into blank control group, 25 tendency/L glucose solution, 27 tendency/L glucose solution,29 tendency/L glucose solution, 31 tendency/L glucose solution, 33 tendency/L glucose solution,35 tendency/L glucose solution treatment group, the optimal concentration of 31 tendency after L, use 30 tendency for L metformin solution, and then divided into blank control group, the optimal concentration of glucose solution, normal liver cells + metformin solution normal liver cells. The optimal concentration of glucose solution normal liver cells + metformin solution respectively in the 12 h, 24 h,48 h on cell count plate to calculate the number of liver cells, and using lactic acid determination kit the optimal concentration of glucose solution + normal liver cells and normal liver cells + the optimal concentration of glucose solution + metformin solution respectively in the 12 h, 24 h, 48 h of cell cultures of lactic acid value. There was no significant change in the lactic acid concentration but significant increase in the number of surviving hepatocytes in the highglycemic control group compared with that in the high-glycemic control group without metformin. Metformin has no significant effect on lactic acid metabolism of hepatocytes under high glucose stress in vitro, and has a protective effect on hepatocytes under high glucose stress. Based on this,it is preliminarily believed that metformin is not the direct factor leading to diabetic lactic acidosis

To compare the efficacy of two kinds of Zhizhu pills in the treatment of functional dyspepsia of spleen-deficiency and qi-stagnation syndrome:a randomized group sequential comparative trial

<p>Abstract</p> <p>Background</p> <p>In Traditional Chinese Medicine (TCM) theory, functional dyspepsia (FD) can be divided into different syndromes according to different clinical symptoms and signs, and the most common one is spleen-deficiency and qi-stagnation syndrome that can be treated by Chinese traditional patent medicine ---- two kinds of Zhizhu pills, between which the primary difference in ingredients is that one contains immature orange fruit of Citrus aurantium L.(IFCA) and the other contains that of Citrus sinensis Osbeck (IFCS). The trial's objective was to compare the efficacy of two kinds of Zhizhu pills on symptom changes in patients with FD of spleen-deficiency and qi-stagnation syndrome.</p> <p>Methods</p> <p>A randomized, group sequential, double-blinded, multicenter trial was conducted in patients with FD of spleen-deficiency and qi-stagnation syndrome at 3 hospitals in Beijing between June 2003 and May 2005. Participants were randomly allocated into two groups (IFCA group and IFCS group) in a 1:1 ratio, and respectively took one of the two kinds of Zhizhu pills orally, 6 g each time, 3 times a day, for 4 weeks. Statistical analysis was performed with use of a group sequential method, the triangular test (TT).</p> <p>Results</p> <p>A total of 163 patients were randomized, and 3 patients were excluded from analysis because of early dropouts, leaving 160 patients (IFCA group: n = 82; IFCS group: n = 78) for statistical analysis. Three interim analyses were done after 62, 116, and 160 patients had completed their 4-week treatment, respectively. At the third interim analysis, the sample path crossed the upper boundary and the trial was stopped, the cure-markedly effective rates were 45% for IFCS group and 67% for IFCA group, respectively, the one-sided <it>p</it>-value was 0.0036, the median unbiased estimate of the odds ratio (OR) for the benefit of IFCA relative to IFCS was 2.91 with 95%CI: 1.40 to 6.06.</p> <p>No adverse events were observed in the two groups.</p> <p>Conclusions</p> <p>Zhizhu pills containing IFCA was superior to Zhizhu pills containing IFCS in the treatment of FD of spleen-deficiency and qi-stagnation syndrome. The application of group sequential analysis in clinical trials of TCM may offer some financial and ethical benefits.</p> <p>Trial Registration</p> <p>Chinese Clinical Trial Registry (ChiCTR): ChiCTR-TRC-00000485</p

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Study on early-warning System of Karst Tunnel Collapse

During the construction of karst Tunnel, tunnel collapse often occurs. The establishment of early-warning system of tunnel collapse can effectively ensure the construction safety, but the research is insufficient. Based on the combination of theoretical analysis and engineering practice, this paper puts forward to early-warning system for karst tunnel collapse. (1) The evaluation index system of karst tunnel collapse is composed of anchor axial force, displacement, anchor pull-out force and steel arch stress. (2) The relationship between evaluation index and warning level is determined, and the early-warning system of tunnel collapse is established. (3) The model applied to Chong’anjiang tunnel collapse warning, and achieved good results

Performance Investigation and Cost&ndash;Benefit Analysis of Recycled Tire Polymer Fiber-Reinforced Cemented Paste Backfill

To alleviate the environmental problems caused by scrap tire and tailings disposal, the performance of recycled tire polymer fiber (RTPF)-reinforced cemented paste backfill (CPB) was investigated. Ordinary CPB, commercial poly-propylene fiber (CPPF) and reinforced CPB were also investigated for comparison. Slump tests, unconfined compression tests and a cost&ndash;benefit analysis were conducted. The results indicate that the flowability of the RTPF-reinforced CPB decreased with the increasing fiber content. The failure strain, unconfined compressive strength, and toughness values were generally higher than that of ordinary CPB (i.e., CPB without any fiber reinforcement). However, the mechanical properties would not be improved continuously with increasing RTPF content. It was found that the inclusion of RTPFs achieved the best improvement effect with the best mechanical properties of CPB at the fiber content of 0.6%. The failure mode of the RTPF-reinforced CPB was safer than that of the ordinary CPB. Microscopic observations indicated that the bond between RTPFs and the CPB matrix could affect the mechanical properties of the RTPF-reinforced CPB. From the cost&ndash;benefit analysis, the inclusion of RTPFs to reinforce CPB could gain relatively high mechanical properties with a low material cost

A Support Vector Machine and Particle Swarm Optimization Based Model for Cemented Tailings Backfill Materials Strength Prediction

This study aimed to investigate the feasibility of using a model based on particle swarm optimization (PSO) and support vector machine (SVM) to predict the unconfined compressive strength (UCS) of cemented paste backfill (CTB). The dataset was built based on the experimental UCS values. Results revealed that the categorized randomly segmentation was a suitable approach to establish the training set. The PSO performed well in the SVM hyperparameters tuning; the optimal hyperparameters for the SVM to predict the UCS of CTB in this study were C = 71.923, &epsilon; = 0.0625, and &gamma; = 0.195. The established model showed a high accuracy and efficiency on the prediction work. The R2 value was 0.97 and the MSE value was 0.0044. It was concluded that the model was feasible to predict the UCS of CTB with high accuracy and efficiency. In the future, the accuracy and robustness of the prediction model will be further improved as the size of the dataset continues to grow

A novel prognostic model of breast cancer based on cuproptosis-related lncRNAs

Abstract Objective Breast cancer (BC) is a deadly form of malignancy responsible for the death of a large number of women every year. Cuproptosis is a newly discovered form of cell death that may have implications for the prognosis of BC. Long non‐coding RNAs (lncRNAs) have been shown to be involved in the progression and development of BC. Here within, a novel model capable of predicting the prognosis of patients with BC was established based on cuproptosis-related lncRNAs. Methods Data of breast cancer patients was downloaded, including clinical information from The Cancer Genome Atlas (TCGA) database and lncRNAs related to cuproptosis were isolated. In total, nine lncRNAs related to copper death were obtained by Cox regression model based on Least Absolute Shrinkage and Selector Operation (LASSO) algorithm for model construction. The model was verified by overall survival (OS), progression-free survival (PFS) and receiver operating characteristic (ROC) curve. The differences in immune function, tumor mutation burden (TMB) and tumor immune dysfunction and exclusion (TIDE) between patients with different risk scores were analyzed. Results Based on cuproptosis-related lncRNAs, a prognostic model for predicting BC was constructed. Each patient was assigned a risk score based on our model formula. We found that patients with higher risk scores had significantly lower OS and PFS, increased TMB, and higher sensitivity to immunotherapy. Conclusions The model established in this study based on cuproptosis-related lncRNAs may be capable of improving the OS of patients with BC