[Research Progress in Preoperative Evaluation of Lymph Node Metastasis of Bladder Cancer].

Bladder cancer is a common malignant tumor of the urinary system.The prognosis of patients with positive lymph nodes is worse than that of patients with negative lymph nodes.An accurate assessment of preoperative lymph node statushelps to make treatmentdecisions,such as the extent of pelvic lymphadenectomy and the use of neoadjuvant chemotherapy.Imaging examination and pathological examination are the primary methods used to assess the lymph node status of bladder cancer patients before surgery.However,these methods have low sensitivity and may lead to inaccuate staging of patients.We reviewed the research progress and made an outlook on the application of clinical diagnosis,imaging techniques,radiomics,and genomics in the preoperative evaluation of lymph node metastasis in bladder cancer patients at different stages.

A brain network model for depression: From symptom understanding to disease intervention.

Understanding the neural substrates of depression is crucial for diagnosis and treatment. Here, we review recent studies of functional and effective connectivity in depression, in terms of functional integration in the brain. Findings from these studies, including our own, point to the involvement of at least four networks in patients with depression. Elevated connectivity of a ventral limbic affective network appears to be associated with excessive negative mood (dysphoria) in the patients; decreased connectivity of a frontal-striatal reward network has been suggested to account for loss of interest, motivation, and pleasure (anhedonia); enhanced default mode network connectivity seems to be associated with depressive rumination; and diminished connectivity of a dorsal cognitive control network is thought to underlie cognitive deficits especially ineffective top-down control of negative thoughts and emotions in depressed patients. Moreover, the restoration of connectivity of these networks-and corresponding symptom improvement-following antidepressant treatment (including medication, psychotherapy, and brain stimulation techniques) serves as evidence for the crucial role of these networks in the pathophysiology of depression.

Incapacity to control emotion in major depression may arise from disrupted white matter integrity and OFC-amygdala inhibition.

BACKGROUND: Disturbances in emotion regulation are the hallmarks of major depressive disorder (MDD). The incapacity to control negative emotion in patients has been associated with abnormal hyperactivation of the limbic system and hypoactivation of the frontal cortex. The amygdala and orbital frontal cortex (OFC) are two critical regions of the emotion regulation neural systems. METHODS: This study investigated the anatomical basis of abnormal emotion regulation by tracking the fiber tracts connecting the amygdala and OFC. In addition, using dynamic casual modeling on resting-state fMRI data of 20 MDD patients and equivalent controls, we investigated the exact neural mechanism through which abnormal communications between these two nodes were mediated in MDD. KEY RESULTS: The results revealed disrupted white matter integrity of fiber tracts in MDD, suggesting that functional abnormalities were accompanied by underlying anatomical basis. We also detected a failure of inhibition of the OFC on the activity of the amygdala in MDD, suggesting dysconnectivity was mediated through "top-down" influences from the frontal cortex to the amygdala. Following 8 weeks of antidepressant treatment, the patients showed significant clinical improvement and normalization of the abnormal OFC-amygdala structural and effective connectivity in the left hemisphere. CONCLUSIONS & INFERENCES: Our findings suggest that pathways connecting these two nodes may be core targets of the antidepressant treatment. In particular, it raised the intriguing question: Does the reversal of structural markers of connectivity reflect a response to antidepressant medication or activity-dependent myelination following a therapeutic restoration of effective connectivity?

A novel strategy for quantitative analysis of the formulated complex system using chromatographic fingerprints combined with some chemometric techniques.

In this work, a novel strategy based on chromatographic fingerprints and some chemometric techniques is proposed for quantitative analysis of the formulated complex system. Here, the formulated complex system means a formulated type of complicated analytical system containing more than one kind of raw material under some concentration composition according to a certain formula. The strategy is elaborated by an example of quantitative determination of mixtures consist of three essential oils. Three key steps of the strategy are as follows: (1) remove baselines of the chromatograms; (2) align retention time; (3) conduct quantitative analysis using multivariate regression with entire chromatographic profiles. Through the determination of concentration compositions of nine mixtures arranged by uniform design, the feasibility of the proposed strategy is validated and the factors that influence the quantitative result are also discussed. This strategy is proved to be viable and the validation indicates that quantitative result obtained using this strategy mainly depends on the efficiency of the alignment method as well as chromatographic peak shape of the chromatograms. Previously, chromatographic fingerprints were only used for identification and/or recognition of some products. This work demonstrates that with the assistance of some effective chemometric techniques, chromatographic fingerprints are also potential and promising in solving quantitative problems of complex analytical systems.

A Combinational Strategy of Model Disturbance and Outlier Comparison to Define Applicability Domain in Quantitative Structural Activity Relationship.

In order to define an applicability domain for quantitative structure-activity relationship modeling, a combinational strategy of model disturbance and outlier comparison is developed. An indicator named model disturbance index was defined to estimate the prediction error. Moreover, the information of the outliers in the training set was used to filter the unreliable samples in the test set based on "structural similarity". Chromatography retention indices data were used to investigate this approach. The relationship between model disturbance index and prediction error can be found. Also, the comparison between the outlier set and the test set could provide additional information about which unknown samples should be paid more attentions. A novel technique based on model population analysis was used to evaluate the validity of applicability domain. Finally, three commonly used methods, i.e. Leverage, descriptor range-based and model perturbation method, were compared with the proposed approach.

Prediction of retention indices for frequently reported compounds of plant essential oils using multiple linear regression, partial least squares, and support vector machine.

Retention indices for frequently reported compounds of plant essential oils on three different stationary phases were investigated. Multivariate linear regression, partial least squares, and support vector machine combined with a new variable selection approach called random-frog recently proposed by our group, were employed to model quantitative structure-retention relationships. Internal and external validations were performed to ensure the stability and predictive ability. All the three methods could obtain an acceptable model, and the optimal results by support vector machine based on a small number of informative descriptors with the square of correlation coefficient for cross validation, values of 0.9726, 0.9759, and 0.9331 on the dimethylsilicone stationary phase, the dimethylsilicone phase with 5% phenyl groups, and the PEG stationary phase, respectively. The performances of two variable selection approaches, random-frog and genetic algorithm, are compared. The importance of the variables was found to be consistent when estimated from correlation coefficients in multivariate linear regression equations and selection probability in model spaces.

Pilot study on efficacy of reduced cathartic bowel preparation with polyethylene glycol and bisacodyl.

AIM: To evaluate the efficacy of reduced cathartic bowel preparation with 2 L polyethylene glycol (PEG)-4000 electrolyte solution and 10 mg bisacodyl enteric-coated tablets for computed tomographic colonography (CTC). METHODS: Sixty subjects who gave informed consent were randomly assigned to study group A, study group B or the control group. On the day prior to CTC, subjects in study group A were given 20 mL 40% wt/vol barium sulfate suspension before 3 mealtimes, 60 mL 60% diatrizoate meglumine diluted in 250 mL water after supper, and 10 mg bisacodyl enteric-coated tablets 1 h before oral administration of 2 L PEG-4000 electrolyte solution. Subjects in study group B were treated identically to those in study group A, with the exception of bisacodyl which was given 1 h after oral PEG-4000. Subjects in the control group were managed using the same strategy as the subjects in study group A, but without administration of bisacodyl. Residual stool and fluid scores, the attenuation value of residual fluid, and discomfort during bowel preparation in the three groups were analyzed statistically. RESULTS: The mean scores for residual stool and fluid in study group A were lower than those in study group B, but the differences were not statistically significant. Subjects in study group A showed greater stool and fluid cleansing ability than the subjects in study group B. The mean scores for residual stool and fluid in study groups A and B were lower than those in the control group, and were significantly different. There was no significant difference in the mean attenuation value of residual fluid between study group A, study group B and the control group. The total discomfort index during bowel preparation was 46, 45 and 45 in the three groups, respectively, with no significant difference. CONCLUSION: Administration of 10 mg bisacodyl enteric-coated tablets prior to or after oral administration of 2 L PEG-4000 electrolyte solution enhances stool and fluid cleansing ability, and has no impact on the attenuation value of residual fluid or the discomfort index. The former is an excellent alternative for CTC colorectum cleansing.

Role of carotid baroreflex and sympathetic responses in the push-pull effect: a simulation study.

BACKGROUND: The push-pull maneuver (PPM) can lead to loss of consciousness in pilots of high-performance aircraft. This paper presents a mathematical model for the simulation of carotid baroreflex function and sympathetic responses during PPM. METHODS: The previous model was first modified by incorporating a submodel of the carotid baroreflex and then validated by comparing the simulation results with experimental data. Then the role of the carotid baroreflex was evaluated by varying the time delay and gain of the baroreflex independently during PPM and control runs, and the influence of different PPM profiles on sympathetic efferent activities were predicted. RESULTS: Model outputs suggest that the effects of carotid baroreflex regulation with different time delays and gain factors on the push-pull effect (PPE) are almost the same as those on the control run. Meanwhile, simulation of sympathetic responses indicates that the frequency of spikes in the efferent sympathetic nerves increases with higher magnitude and longer duration of -Gz exposure, as well as with higher magnitude of +Gz exposure. However, the effect of changed sympathetic responses may be alleviated when transferred to baroreflex effectors. CONCLUSION: The simulation results support that the carotid baroreflex and sympathetic responses might have little specific influences on the PPE. It also suggests that the limited range of G alteration and transition rate should be considered when using tilting experiments to investigate sympathetic response to PPE. The limitation of the present model due to the lack of sufficient data on the contribution of different peripheral vascular beds and their myogenic response is discussed.

Cortical thinning in patients with recent onset post-traumatic stress disorder after a single prolonged trauma exposure.

Most of magnetic resonance imaging (MRI) studies about post-traumatic stress disorder (PTSD) focused primarily on measuring of small brain structure volume or regional brain volume changes. There were rare reports investigating cortical thickness alterations in recent onset PTSD. Recent advances in computational analysis made it possible to measure cortical thickness in a fully automatic way, along with voxel-based morphometry (VBM) that enables an exploration of global structural changes throughout the brain by applying statistical parametric mapping (SPM) to high-resolution MRI. In this paper, Laplacian method was utilized to estimate cortical thickness after automatic segmentation of gray matter from MR images under SPM. Then thickness maps were analyzed by SPM8. Comparison between 10 survivors from a mining disaster with recent onset PTSD and 10 survivors without PTSD from the same trauma indicates cortical thinning in the left parietal lobe, right inferior frontal gyrus, and right parahippocampal gyrus. The regional cortical thickness of the right inferior frontal gyrus showed a significant negative correlation with the CAPS score in the patients with PTSD. Our study suggests that shape-related cortical thickness analysis may be more sensitive than volumetric analysis to subtle alteration at early stage of PTSD.

Mathematical modeling of the push-pull effect for various acceleration profiles and countermeasures.

BACKGROUND: The push-pull maneuver (PPM) can lead to loss of consciousness in pilots of high-performance aircraft. Modeling of the physical and physiological aspects of this phenomenon should allow improved countermeasures. METHODS: A structurally based mechanistic computer model was developed to incorporate dynamic carotid baroreflex responses and detailed modeling of vessel segments for different anatomic regions. The model was used to predict the effect of the PPM on cardiovascular responses and the protection afforded by extended coverage anti-G suits (ECGS) and neck pressure. RESULTS: The model was validated by comparing the simulation results with previously published experimental data obtained during centrifuge and tilt-table studies. Simulations of various PPM acceleration profiles indicated that +Gz tolerance was reduced in the presence of higher +Gz levels prior to the push phase, more -Gz levels during the push phase, and prolongation of the push phase. On the other hand, the onset rate for the two phases had only minor effects on +Gz tolerance. Model output suggested that improved protection could be provided by an ECGS with minimal inflation delay and a multilevel pressure schedule in which the leg bladders inflated to a higher pressure than the abdominal bladder. Modeling application of a 100-mmHg neck pressure during the push phase partly inactivated the carotid baroreflex, but induced only a small increase in tolerance. CONCLUSIONS: Mathematical modeling and simulation showed that +Gz tolerance for the PPM might be increased by improving the design and inflation schedule of the ECGS.

Cardiovascular changes of conscious rats after simulated microgravity with and without daily -Gx gravitation.

This study was designed to test the hypothesis that postsuspension cardiovascular manifestation in conscious rats after a medium-term (28-day) tail suspension (SUS) is hypertensive and tachycardiac and can be prevented by a countermeasure of daily 1-h dorsoventral (-G(x)) gravitation provided by standing (STD). To assess associated changes in cardiovascular regulation, blood pressure (BP) and heart rate (HR) variability were analyzed by spectral analysis computed by parametric autoregressive (AR) method and by nonlinear recurrence quantification analysis (RQA) and approximate entropy (ApEn) measure. The results showed that conscious SUS rats manifested hypertensive and tachycardiac response before and after being released from suspension compared with the controls, and the countermeasure of 1 h/day -G(x) prevented the hypertensive response. Auto- and cross-spectral analysis and transfer function analysis did not show significant changes in cardiovascular variability. However, SUS decreased the three RQA indexes [recurrence percentage (RC%), determinism percentage (DT%), and the longest diagonal line (L(max))] of systolic BP, whereas STD alleviated these changes. ApEn values of HR data sets were significantly higher in the SUS and SUS + STD groups compared with those of the control group before and after release from suspension. The present study has demonstrated that daily -G(x) for as short as 1 h is sufficient to prevent postsuspension cardiovascular alteration in conscious rats after a medium-term SUS. Nonlinear measures, but not spectral analysis, might provide promising data to estimate the overall changes in cardiovascular autonomic regulation due to microgravity exposure.

Mathematical modeling of high G protection afforded by various anti-G equipment and techniques.

BACKGROUND: It is difficult to assess how different combinations of recently developed anti-G protective equipment will affect +Gz tolerance and central hemodynamics during high G solely by centrifuge experiments. In this paper we report a mathematical model simulating the effects of various combinations on human circulatory response and +Gz tolerance, and its validation with published centrifuge data. METHODS: A structurally based mechanistic model incorporating cardio-pulmonary function, as well as a more detailed modeling of vessel segments for different anatomic regions, was established to simulate hemodynamic responses during high-G exposure and the protection afforded by various protective modalities, such as tilt-back seats, extended coverage anti-G suits (ECGS), and positive pressure breathing for +Cz (PBC). RESULTS: There were 43 pairs of human data from centrifuge trials and model outputs under the same or similar conditions that were compared. This comparison indicated that in 86% of cases the differences were less than 15%. From the model outputs, the best combinations which satisfied different protective needs, such as protection to +9 Gz, +10 Gz, and +12 Gz, respectively, could be discovered. They also suggested that while the combined protection of ECGS with PBG may be expressed as a simple addition of the two effects, the combined effect of the tilt-back seat with ECCGS and/or PBG seemed to be better fitted by a synergistic model. CONCLUSIONS: Comparisons with published centrifuge data have suggested the validity and confidence of the model developed. The benefits and limitations of the model for future high-G physiology and protection are discussed.

Inhibition by N'-nitrosonornicotine of the catalytic activity of glutamate dehydrogenase in alpha-ketoglutarate amination.

The effect of N'-nitrosonornicotine (NNN), one of the tobacco-specific nitrosamines, on the catalytic activity of glutamate dehydrogenase (GLDH) in the alpha-ketoglutarate amination, using reduced nicotinamide adenine dinucleotide as coenzyme, was studied by a chronoamperometric method. The maximum reaction rate of the enzyme-catalyzed reaction and the Michaelis-Menten constant, or the apparent Michaelis-Menten constant, were determined in the absence and presence of NNN. NNN remarkably inhibited the bio-catalysis activity of GLDH, and was a reversible competitive inhibitior with K(i), estimated as 199 micromol l(-1) at 25 degrees C and pH 8.0.

Effectiveness of daily short-duration standing in preventing post-suspension cardiovascular dysfunction in rats assessed by cardiovascular signal analysis.

The aim of the present study was to clarify whether simulated microgravity-induced post-suspension cardiovascular deconditioning in rats could be prevented by daily short-duration standing (STD). Three groups of rats were used as subjects to perform the experiments. Compared to a control group of male Sprague-Dawley rats (CON), a group of rats with tail-suspension (SUS) for 28 d was used to simulate cardiovascular deconditioning due to microgravity. Another group of tailed-suspended rats with daily STD for 1 h was used to provide -GX (dorso-ventral) gravitational loading as countermeasure. In addition to hemodynamic changes to head-up tilt, blood pressure variability (BPV) signals were also analyzed by spectral and nonlinear analysis. The results showed 1) Blood pressure immediately decreased after head-up tilt in all three groups. After several minutes, blood pressure could restore to the initial condition in both CON and SUS+STD group, but the recovery process was slower in the latter group. In contrast, the recovery process was the slowest in the SUS group and could not restore to the initial level completely. 2) In frequency domain, power spectra has similar pattern in CON and SUS+STD group. However, they are quite different in the SUS group in that spectra peak is obvious increased in very low frequency and spectra is narrower and higher in high frequency.

Multiplex detection of mutations in clinical isolates of rifampin-resistant Mycobacterium tuberculosis by short oligonucleotide ligation assay on DNA chips.

A new approach, short-oligonucleotide-ligation assay on DNA chip (SOLAC), is developed to detect mutations in rifampin-resistant Mycobacterium tuberculosis. The method needs only four common probes to detect 15 mutational variants of the rpoB gene within 12 h. Fifty-five rifampin-resistant M. tuberculosis isolates were analyzed, resulting in 87.3% accuracy and 83.6% concordance relative to DNA sequencing.

Oligonucleotide ligation assay-based DNA chip for multiplex detection of single nucleotide polymorphism.

An oligonucleotide ligation assay-based DNA chip has been developed to detect single nucleotide polymorphism. Synthesized nonamers, complementary to the flanking sequences of the mutation sites in target DNA, were immobilized onto glass slides through disulfide bonds on their 5' terminus. Allele-specific pentamers annealed adjacent to the nonamers on the complementary target DNA, containing 5'-phosphate groups and biotin labeled 3'-ends, were mixed with the target DNA in tube. Ligation reactions between nonamers and pentamers were carried out on chips in the presence of T4 DNA ligase. Ligation products were directly visualized on chips through enzyme-linked assay. The effect of G:T mismatch at different positions of pentamers on the ligation were evaluated. The results showed that any mismatch between pentamer and the target DNA could lead to the decrease of ligation, which can be detected easily. The established approach was further used for multiplex detection of mutations in rpoB gene of rifampin-resistant Mycobacterium tuberculosis clinical isolates.