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Objective:To investigate the value of number of negative lymph nodes (NLNs) in predicting the prognosis of patients with esophageal cancer after neoadjuvant therapy and the construction of nomogram prodiction model.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 924 patients with esophageal cancer after neoadjuvant therapy uploaded to the Surveillance, Epidemiology, and End Results Database of the National Cancer Institute from 2004 to 2015 were collected. There were 1 624 males and 300 females, aged 63 (range, 23?85)years. All 1 924 patients were randomly divided into the training dataset of 1 348 cases and the validation dataset of 576 cases with a ratio of 7:3 based on random number method in the R software (3.6.2 version). The training dataset was used to constructed the nomogram predic-tion model, and the validation dataset was used to validate the performance of the nomogrram prediction model. The optimal cutoff values of number of NLNs and number of examined lymph nodes (ELNs) were 8, 14 and 10, 14, respectively, determined by the X-tile software (3.6.1 version), and then data of NLNs and ELNs were converted into classification variables. Observation indicators: (1) clinicopathological characteristics of patients in the training dataset and the validation dataset; (2) survival of patients in the training dataset and the validation dataset; (3) prognostic factors analysis of patients in the training dataset; (4) survival of patients in subgroup of the training dataset; (5) prognostic factors analysis in subgroup of the training dataset; (6) construction of nomogram prediction model and calibration curve. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and Log-Rank test was used for survival analysis. The COX proportional hazard model was used for univariate and multivariate analyses. Based on the results of multivariate analysis, the nomogram prediction model was constructed. The prediction efficacy of nomogram prediction model was evaluated using the area under curve (AUC) of the receiver operating characteristic curve and the Harrell′s c index. Errors of the nomogram prediction model in predicting survival of patients for the training dataset and the validation dataset were evaluated using the calibration curve. Results:(1) Clinicopathological characteristics of patients in the training dataset and the validation dataset. There was no significant difference in clinicopatholo-gical characteristics between the 1 348 patients of the training dataset and the 576 patients of the validation dataset ( P>0.05). (2) Survival of patients in the training dataset and the validation dataset. All 1 924 patients were followed up for 50(range, 3?140)months, with 3-year and 5-year cumulative survival rate as 59.4% and 49.5%, respectively. The 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 in the training dataset was 46.7%, 62.0% and 66.0%, respectively, and the 5-year cumulative survival rate was 38.1%, 52.1% and 59.7%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=33.70, P<0.05). The 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 in the validation dataset was 51.1%, 54.9% and 71.2%, respectively, and the 5-year cumulative survival rate was 39.3%, 42.5% and 55.7%, respectively. There was a significant difference in the survival of these patients in the validation dataset ( χ2=14.49, P<0.05). The 3-year cumulative survival rate of patients with number of ELNs as <10, 10?14 and >14 in the training dataset was 53.9%, 60.0% and 62.7%, respectively, and the 5-year cumulative survival rate was 44.7%, 49.1% and 56.9%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=9.88, P<0.05). The 3-year cumulative survival rate of patients with number of ELNs as <10, 10?14 and >14 in the validation dataset was 56.2%, 47.9% and 69.3%, respectively, and the 5-year cumula-tive survival rate was 44.9%, 38.4% and 51.9%, respectively. There was a significant difference in the survival of these patients in the validation dataset ( χ2=9.30, P<0.05). (3) Prognostic factors analysis of patients in the training dataset. Results of multivariate analysis showed that gender, neoadjuvant pathological (yp) T staging, ypN staging (stage N1, stage N2, stage N3) and number of NLNs (8?14, >14) were independent influencing factors for the prognosis of patients with esophageal cancer after neoadjuvant therapy ( hazard ratio=0.65, 1.44, 1.96, 2.41, 4.12, 0.69, 0.56, 95% confidence interval as 0.49?0.87, 1.17?1.78, 1.59?2.42, 1.84?3.14, 2.89?5.88, 0.56?0.86, 0.45?0.70, P<0.05). (4) Survival of patients in subgroup of the training dataset. Of the patients with NLNs in the training dataset, the 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 was 61.1%, 71.6% and 76.8%, respectively, and the 5-year cumulative survival rate was 50.7%, 59.9% and 70.1%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=12.66, P<0.05). Of the patients with positive lymph nodes in the training dataset, the 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 was 26.1%, 42.9% and 44.7%, respectively, and the 5-year cumulative survival rate was 20.0%, 36.5% and 39.3%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=20.39, P<0.05). (5) Prognostic factors analysis in subgroup of the training dataset. Results of multivariate analysis in patients with NLNs in the training dataset showed that gender, ypT staging and number of NLNs (>14) were independent influencing factors for the prognosis of patients with esophageal cancer after neoadju-vant therapy ( hazard ratio=0.67, 1.44, 0.56, 95% confidence interval as 0.47?0.96, 1.09?1.90, 0.41?0.77, P<0.05). Results of multi-variate analysis in patients with positive lymph nodes in the training dataset showed that race as others, histological grade as G2, ypN staging as stage N3 and number of NLNs (8?14, >14) were independent influencing factors for the prognosis of patients with esophageal cancer after neoadjuvant therapy ( hazard ratio=2.73, 0.70, 2.08, 0.63, 0.59, 95% confidence interval as 1.43?5.21, 0.54?0.91, 1.44?3.02, 0.46?0.87, 0.44?0.78, P<0.05). (6) Construction of nomogram prediction model and calibration curve. Based on the multivariate analysis of prognosis in patients of the training dataset ,the nomogram prediction model for the prognosis of patients with esophageal cancer after neoadju-vant treatment was constructed based on the indicators of gender, ypT staging, ypN staging and number of NLNs. The AUC of nomogram prediction model in predicting the 3-, 5-year cumulative survival rate of patients in the training dataset and the validation dataset was 0.70, 0. 70 and 0.71, 0.71, respectively. The Harrell′s c index of nomogram prediction model of patients in the training dataset and the validation dataset was 0.66 and 0.63, respectively. Results of calibration curve showed that the predicted value of the nomogram prediction model of patients in the training dataset and the validation dataset was in good agreement with the actual observed value. Conclusion:The number of NLNs is an independent influencing factor for the prognosis of esophageal cancer patients after neoadjuvant therapy, and the nomogram prediction model based on number of NLNs can predict the prognosis of esophageal cancer patients after neoadjuvant therapy.
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Esophageal cancer is the eighth most common cancer worldwide and one of the most common malignant tumors in China.Despite the continuous improvement in the methods of comprehensive treatment such as surgery,radiotherapy and chemotherapy,the prognosis and five-year survival rate of patients with esophageal cancer remain poor.Targeted therapy for esophageal cancer inhibits the proliferation and migration of esophageal cancer cells and promotes apoptosis by regulating related signaling pathways.Up to now,a variety of molecular targets and related regulatory mechanisms of esophageal cancer have been discovered,and a variety of targeted therapeutic drugs have been designed,some of which have achieved certain effects in clinical trials.At present,targeted molecular therapeutic targets such as HER-2,VEGFR,EGFR and other targeted therapeutic drugs (monoclonal antibodies and tyrosinase inhibitors) have achieved clinical effects in esophageal cancer treatments.Preliminary progress have been made in the study of some key kinases,such as such as mTOR,AXL,C-MET,AURKA,etc,in various signaling pathways,and the development of the relevant targeted therapeutic agents for esophageal cancer.Meanwhile,esophageal cancer immunotherapy targeting PD-1 shows good prospects,and the immunotherapy drugs,such as Pembrolizumab,have achieved good therapeutic effects.Additionally,new targets for esophageal cancer,such as MMP-9 and COX-2,have been found to be potential targets for esophageal cancer treatments.
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Objective To observe the effect of saccharomyces boulardii combined with chiropractics in asphyxial newborn with feeding intolerance. Methods One hundred and twenty asphyxial newborn with feeding intolerance were allocated into observation group (68 patients) and control group (52 patients) by random digits table. The newborn in control group accepted trace feeding and parenteral nutrition treatment, and the newborn in observation group accepted additional oral saccharomyces boulardii and chiropractic therapy on the base of control group. The time of reaching to full enteral feeding, the time of restoring to birth weight, the incidence of hyperbilirubinemia and the total efficiency of treatment were observed. Results The time of reaching to full enteral feeding, the time of restoring to birth weight in either mild asphyxial newborn or severe asphxial newborn in observation group were significantly lower than those in control group (P<0.01 or<0.05). The incidence of hyperbilirubinemia in mild asphyxial newborn or severe asphxial newborn in observation group was 16.7%(8/48) and 5/20, in control group was 36.8%(14/38) and 9/14, and there were significant differences (P<0.05). The total efficiency of treatment in observation group was significantly higher than that in control group:91.2%(62/68) vs. 69.2%(36/52), P<0.05. Conclusions Saccharomyces boulardii combined with chiropractics in asphyxial newborn with feeding intolerance can reduce the time of reaching to full enteral feeding and the time of restoring to birth weight. It can decrease the incidence of hyperbilirubinemia, and the treatment effect is obvious.
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Along with the rapid research of neural molecular biology, abundant data are produced so that the collection and coordination of high-throughout data about nervous system relative proteins and genes are imperative. Through analyzing the biological primary databases maintained by NCBI and RCSB as the main data source and designing a new data model, a local specialized secondary database is constructed, which mainly includes nucleotide sequences, protein sequences and protein structures, and is established on Sun Blade 2000 System and Oracle 9i. All programs are developed by Java technology. A method of web information automatic retrieval with XML is proposed for sequence data collection and submission to the database. JSP + JavaBean technology is used to support data promulgation on Internet. The establishment of this database provides an excellent platform for the research of neural molecular biology and the pathogenesis of related diseases.
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Humans , Database Management Systems , Databases, Nucleic Acid , Databases, Protein , Gene Expression Profiling , Nervous System , Proteins , ChemistryABSTRACT
Using patch clamp technique the effects of dragon's blood and its component loureirin B on tetrodotoxin-sensitive sodium channel currents in dorsal root ganglion cells were observed. The experimental data were simulated with Hodgkin-Huxley model and the corresponding parameters were estimated. In addition, computer-simulated neuron action potentials in the absence and presence of drugs were produced using Hodgkin-Huxley model. The results show that the conductance of tetrodotoxin-sensitive sodium channel was fitted with m3h model well, the half-activated potentials of the sodium channel in the presence of drugs were shifted to the depolarizing direction and the threshold intensity of the cells in the presence of drugs was increased. These results demonstrate that dragon's blood and loureirin B did not resemble the tetrodotoxin which inhibited tetrodotoxin-sensitive sodium channel currents completely. Perhaps the analgesic effects of dragon's blood were partly caused by loureirin B affecting the activation, blocking the action potential generation and interfering with the transmission of painful signals into the central nervous system.
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Animals , Rats , Action Potentials , Analgesics, Non-Narcotic , Pharmacology , Computer Simulation , Drugs, Chinese Herbal , Chemistry , Pharmacology , Ganglia, Spinal , Cell Biology , Models, Biological , Neurons , Resins, Plant , Pharmacology , Sodium Channels , Tetrodotoxin , PharmacologyABSTRACT
Aim To explore the modulation of Salvia miltiorrhiza on hyperpolarization-activated current (Ih) channels in dorsal root ganglion (DRG) neurons of rats and identify the mechanism of Salvia miltiorrhiza in alleviating pain and inhibiting calcium overload. Methods The effect of Salvia miltiorrhiza injection on Ih channels in DRG neurons of rats were examined by using whole-cell patch clamp technique. Results The experimental results showed that the amplitude of Ih evoked by -150 mV was (-1.06±0.18) nA. The Ih could be fitted well into the single kinetics and the time constant of activation, τ was clearly voltage-dependent with τ=(322.14±28.81) ms at -100 mV, decreasing to τ=(62.51±9.78) ms at -150 mV. The reversal potential of Ih was (-35.03±1.12) mV measured from tail currents. But no significant differences were found between the DRG neurons in the absence and presence of Salvia miltiorrhiza injection (10%, 25%, 50%) in the current amplitude, the time constant of activation and the reversal potential. The only difference between the DRG neurons in the absence and presence of Salvia miltiorrhiza injection was the half-activation potential of Ih. In control recordings the half-activation potential was (-106.07±3.59) mV. By comparison, the half-activation potentials changed to (-111.59±3.79) mV (n=31 neurons, P＜0.05), (-119.37±4.96) mV (n=31 neurons, P＜0.05) and (-121.23±3.86) mV (n=31 neurons, P＜0.05) in the presence of 10%, 25%, 50% Salvia miltiorrhiza injection, respectively. Conclusion Only the half-activation potential of Ih in the arthritic and neuropathic rat models shifted in the depolarizing direction, which increased the electrophysiological activity of Ih and made it related to peripheral hyperalgesia. The selective inhibition of Salvia miltiorrhiza on the electrophysiological activity of Ih may be one of the mechanisms underlying its analgesic effects.
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@#ObjectiveTo determine whether the β2-agonist, clenbuterol, can improve recovery of locomotor function following spinal cord injury.MethodsThe spinal cords of rats were contused with a weight-drop apparatus similar to the NYU impactor at the lever of T10. Locomotor function was determined with the Basso, Beattie, Bresnahan (BBB) Scale. Following 6 weeks of behavioral evaluation, the spinal cords were received histological examination.ResultsClenbuterol improved the recovery of locomotor function and increased the amount of spared spinal cord tissue.ConclusionClenbuterol caused the enhancement of recovery of locomotor function and spared spinal cord tissue following contusion.
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The aim of this study was to investigate the culture conditions of skin-derived mesenchymal stem cell (sMSCs) and to explore a new cell source for central nervous system cell transplantation. The cells from skins of mice were primarily isolated and cultured in serum-free medium, and they were transferred into serum-containing medium after passaged 2, and the passaged cells were identified by immunocytochemistry and induced to differentiate into multiple lineages. The results indicated that a population of sMSCs could be isolated from skins, they could be maintained in vitro for extended periods with stable population doubling, and they were expanded as undifferentiated cells in culture for more than 10 passages, indicating their proliferative capacity. About 60% of sMSCs expressed vimentin and the majorities of these cells expressed fibronectin. They could differentiate into adipocytes, osteogenic cells and fibroblast-like cells, they could differentiate into neurons with a simple protocol, and almost 50-60% of these cells expressed neuron specific enolase (NSE) and neurofilament (NF); and the differentiated neurons showed typical complicated morphology of neurons. In conclusion, skin contains stem cells that are capable of multiple differentiation; they could be cultured in vitro for long time and could maintain their characteristics of stem cells, and they may represent an alternative autologous stem cell source for CNS cell transplantation.
Subject(s)
Animals , Mice , Adipocytes , Cell Biology , Cell Culture Techniques , Cell Differentiation , Cells, Cultured , Culture Media, Serum-Free , Fibroblasts , Cell Biology , Immunohistochemistry , Mesenchymal Stem Cells , Cell Biology , Neurons , Cell Biology , Skin , Cell BiologyABSTRACT
In order to overcome the effects of the anti-aliasing filter and the colored background noise, an adaptive algorithm is proposed to estimate the parameters of ion channel kinetics and the background noise, and whereafter the ion channel signal could be restored from the strong noisy patch-clamp recordings. The algorithm cross-couples the recursive expectation-maximization algorithm, which estimates optimally the parameters of hidden Markov model, and the recursive extended least square algorithm, which estimates optimally the characteristics of the background noise. Simulation suggests that this cross-coupling algorithm convergences consistently, and is very robust to the inexact conformation number.
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Algorithms , Ion Channels , Physiology , Least-Squares Analysis , Likelihood Functions , Models, Theoretical , Noise , Patch-Clamp Techniques , Methods , Signal Processing, Computer-AssistedABSTRACT
ObjectiveTo investigate the culture conditions of skin-derived precursors (SKPs) and to explore a new cell source for central nervous system cell transplantation.MethodCells from skins of juvenile and adult mice were isolated and cultured in serum -free medium, and mechanical methods were adapted to passage these cells and ce lls were identified by immunocytochemistry.ResultsA population of SKPs could be isolated from adult and neonatal skins. They co uld be maintained in vitro for extended periods with stable population doubling, and they were expanded as undifferentiated cells in culture for more than 8 pas sages, indicating their proliferative capacity. About 50?% of SKPs expressed n estin and the majorities of these cells expressed fibronectin when they were pla ted on polyornithine and laminin coated plates. About 5?% cells showed typical complicated neuronal states and expressed NF-M and NSE when SKPs were plated i n serum-containing medium. These cell could also differentiate into adipocytes and fibroblast-like cells.ConclusionsAdult skin contains stem cells capable of differentiating into neurons, adipocyt es and fibroblast-like cells. SKPs may represent an alternative autologous stem cell source for CNS cell transplantation.
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Aim To investigate effects of loureirin B on capsaicin-evoked currents in rat dorsal root ganglion (DRG) neurons. Methods In acutely isolated rat DRG neurons, effects of loureirin B on capsaicin-evoked currents were observed using whole-cell patch-clamp technique. Results ① The holding potential was maintained at -60 mV and VR1 antagonist capsazepine inhibited capsaicin-evoked currents completely; ② Loureirin B concentration-dependently inhibited capsaicin-evoked currents. Loureirin B at the concentrations of 2.0, 4.0, 8.0 and 16.0 ?mol?L-1 reduced capsaicin-evoked currents by 15.36%?2.12%、36.41%?2.43%、76.26%?2.16% and 96.69%?3.21% (n=10, P