Mechanism and deterioration pattern of sandstone surrounding rock voiding at bottom of heavy-haul railway tunnel.

This study combines laboratory experiments and discrete element simulation methods to analyze the mechanism and deterioration patterns of sandstone surrounding rock voiding the bottom of a heavy-haul railway tunnel. It is based on previously acquired measurement data from optical fiber grating sensors installed in the Taihangshan Mountain Tunnel of the Wari Railway. By incorporating rock particle wastage rate results, a method for calculating the peak strength and elastic modulus attenuation of surrounding rock is proposed. Research indicates that the operation of heavy-haul trains leads to an instantaneous increase in the dynamic water pressure on the bottom rock ranging 144.4-390.0%, resulting in high-speed water flow eroding the rock. After 1-2 years of operation, the bottom water and soil pressures increase by 526.5% and 390.0%, respectively. Focusing on sandstone surrounding rock with high observability, laboratory experiments were conducted to monitor the degradation stages of infiltration, particle loss, and voiding of rock under the action of dynamic water flow. The impact of water flow on the "cone-shaped" bottom rock deformation was also clarified. The extent of rock deterioration and voiding was determined using miniature water and soil pressure sensors in conjunction with discrete element numerical simulations. The measured rock particle loss was used as a criterion. Finally, a fitting approach is derived to calculate the peak strength and elastic modulus attenuation of surrounding rock, gaining insight into and providing a reference for the maintenance and disposal measures for the bottom operation of heavy-haul railway tunnels.

[Research progress of traditional Chinese medicines as quorum sensing inhibitors in collaboration with antibiotics to inhibit drug-resistant bacteria].

Quorum sensing system regulates the expression of genes related to bacterial growth, metabolism and other behaviors by sensing bacterial density, and controls the unified action of the entire bacterial population. This mechanism can ensure the normal secretion of bacterial metabolites and the stability of the biofilm microenvironment, providing protection for the formation of biofilms and the normal growth and reproduction of bacteria. Traditional Chinese medicine, capable of quorum sensing inhibition, can inhibit the formation of bacterial biofilms, reduce bacterial resistance, and enhance the anti-infection ability of antibiotics when combined with antibiotics. In recent years, the combination of traditional Chinese and Western medicine in the treatment of drug-resistant bacterial infections has become a research hotspot. Starting with the associations between quorum sensing, biofilm and drug-resistant bacteria, this paper reviews the relevant studies about the combined application of traditional Chinese medicines as quorum sensing inhibitors with antibiotics in the treatment of drug-resistant bacteria. This review is expected to provide ideas for the development of new clinical treatment methods and novel anti-infection drugs.

Sleep Deprivation Impairs Human Cognitive Reappraisal Ability: A Randomized Controlled Trial.

Purpose: This study aims to examine the impact of sleep deprivation on individual cognitive reappraisal ability using a standardized behavioral paradigm. Methods: A randomized pretest-posttest control group design was conducted. Thirty-nine participants were eventually enrolled and randomly assigned to receive either the sleep control (SC: n = 17) or the sleep deprivation (SD: n = 22). Both of them were required to perform a standardized behavioral paradigm of measuring cognitive reappraisal ability one time under sleep-rested condition and another time under the condition of different sleep manipulation a week later. Results: Mean valence ratings of SD group were more negative than SC group's (p < 0.05) and mean arousal ratings of SD group were higher than SC group's (p < 0.01). Conclusion: Sleep deprivation may impair individual cognitive reappraisal ability and could potentially undermine the efficacy of cognitive therapy in terms of emotion regulation.

A novel 16-gene alternative mRNA splicing signature predicts tumor relapse and indicates immune activity in stage I-III hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a lethal disease with high relapse and dismal survival rates. Alternative splicing (AS) plays a crucial role in tumor progression. Herein, we aim to integratedly analyze the relapse-associated AS events and construct a signature predicting tumor relapse in stage I-III HCC. Methods: AS events of stage I-III HCC with tumor relapse or long-term relapse-free survival were profiled to identify the relapse-associated AS events. A splicing network was set up to analyze the correlation between the relapse-associated AS events and splicing factors. Cox regression analysis and receiver operating characteristic curve were performed to develop and validate the relapse-predictive AS signature. Single-sample gene set enrichment analysis (ssGSEA) and the ESTIMATE algorithm were used to assess the immune infiltration status of the HCC microenvironment between different risk subgroups. Unsupervised cluster analysis was conducted to assess the relationship between molecular subtypes and local immune status and clinicopathological features. Results: In total, 2441 ASs derived from 1634 mRNA were identified as relapse-associated AS events. By analyzing the proteins involved in the relapse-associated AS events, 1573 proteins with 11590 interactions were included in the protein-protein interaction (PPI) network. In total, 16 splicing factors and 61 relapse-associated AS events with 85 interactions were involved in the splicing network. The relevant genes involved in the PPI network and splicing network were also analyzed by Gene Ontology enrichment analysis. Finally, we established a robust 16-gene AS signature for predicting tumor relapse in stage I-III HCC with considerable AUC values in all of the training cohort, testing cohort, and entire cohort. The ssGSEA and ESTIMATE analyses showed that the AS signature was significantly associated with the immune status of the HCC microenvironment. Moreover, four molecular subgroups with distinguishing tumor relapse modes and local immune status were also revealed. Conclusion: Our study built a novel 16-gene AS signature that robustly predicts tumor relapse and indicates immune activity in stage I-III HCC, which may facilitate the deep mining of the mechanisms associated with tumor relapse and tumor immunity and the development of novel individualized treatment targets for HCC.

Subtrochanteric Osteotomy in Direct Anterior Approach Total Hip Arthroplasty.

Subtrochanteric osteotomy of the femur (STO) is a valuable corrective procedure in hip surgeries. However, STO in traditional posterolateral approach usually encounters complications such as postoperative dislocation, bone non-union, and prosthesis failure. Some relevant pathologies and mechanisms have been identified, but there is sparse evidence for verification. The aim of this video in orthopaedic technique is to test our hypothesis of STO in direct anterior approach to total hip arthroplasty in a complicated hip surgery, and to further illustrate the rationality, reproducibility, and superiority of STO in this minimally invasive and enhanced-recovery approach by presenting a standardized and systemic protocol, as well as operational pearls and pitfalls.

Direct Anterior Approach in Crowe Type III-IV Developmental Dysplasia of the Hip: Surgical Technique and 2 years Follow-up from Southwest China.

OBJECTIVES: To summarize our pioneering surgical practice and clinical outcome of Crowe type III-IV developmental dysplasia of the hip (DDH) with a direct anterior approach total hip arthroplasty in a single teaching hospital in Southwest China. METHODS: Fourteen patients (15 hips) diagnosed with Crowe type III-IV developmental dysplasia of the hip were involved in this single-center retrospective study between 2016 and 2018. A comprehensive surgical procedure, including preoperative planning and algorithms for leg length equalization, intraoperative stepwise soft tissue release, bone defect reconstruction, and an innovative subtrochanteric osteotomy, was described. Furthermore, advancements in intraoperative CT guidance, computer navigation, and nerve monitoring were available for specific demands. The short-term clinical outcome was evaluated at the endpoint of follow-up by three patient-reported functional scales (Harris, WOMAC, and SF-12 scores), and objective data collected at the clinic, including functional recovery (muscle strength of hip flexor and abductor, correction of the pelvic tilt, leg length discrepancy, and limp), radiographic analysis, and complication occurrence. RESULTS: The intraoperative variables were carefully recorded. The mean operating times in Crowe type III and IV groups were 115.8 min and 156.2 min, and the median blood loss volumes were 520.5 mL and 810.2 mL, respectively. The general changes in the Harris, SF-12, and WOMAC scores of the two groups were 46.2, 8.7 and 134.3, respectively, at a mean follow-up of 25.4 months. Enhanced recovery of hip abductor muscle strength was identified in 85.7% of the population at the third postoperative month. The equalization of leg length and correction of the pelvic tile were observed at the sixth postoperative month, with a 36-mm decrease in leg length discrepancy. No radiographic evidence of the loosening or migration of the components was observed. A self-innovated subtrochanteric shortening osteotomy was performed in five patients, and they healed after 6 months. Specific complications included two cases of distal femoral cracks and one case of a periprosthetic fracture needing internal fixation. Two patients received a late iliotibial band release at the 3rd month postoperatively due to progressive genu valgum. No records of infection, dislocation, nerve palsy, bone non-union, or revision surgery were identified. DISCUSSION: The direct anterior approach total hip arthroplasty showed potential advantages, including optimum component positioning, improved hip stability, steerable complication rate, and enhanced functional recovery with Crowe type III-IV DDH. The short-term outcome is comparable to that of the traditional posterolateral approach.

In Vitro-In Vivo Predictive Dissolution-Permeation-Absorption Dynamics of Highly Permeable Drug Extended-Release Tablets via Drug Dissolution/Absorption Simulating System and pH Alteration.

Each of dissolution and permeation may be a rate-limiting factor in the absorption of oral drug delivery. But the current dissolution test rarely took into consideration of the permeation property. Drug dissolution/absorption simulating system (DDASS) valuably gave an insight into the combination of drug dissolution and permeation processes happening in human gastrointestinal tract. The simulated gastric/intestinal fluid of DDASS was improved in this study to realize the influence of dynamic pH change on the complete oral dosage form. To assess the effectiveness of DDASS, six high-permeability drugs were chosen as model drugs, including theophylline (pKa1 = 3.50, pKa2 = 8.60), diclofenac (pKa = 4.15), isosorbide 5-mononitrate (pKa = 7.00), sinomenine (pKa = 7.98), alfuzosin (pKa = 8.13), and metoprolol (pKa = 9.70). A general elution and permeation relationship of their commercially available extended-release tablets was assessed as well as the relationship between the cumulative permeation and the apparent permeability. The correlations between DDASS elution and USP apparatus 2 (USP2) dissolution and also between DDASS permeation and beagle dog absorption were developed to estimate the predictability of DDASS. As a result, the common elution-dissolution relationship was established regardless of some variance in the characteristic behavior between DDASS and USP2 for drugs dependent on the pH for dissolution. Level A in vitro-in vivo correlation between DDASS permeation and dog absorption was developed for drugs with different pKa. The improved DDASS will be a promising tool to provide a screening method on the predictive dissolution-permeation-absorption dynamics of solid drug dosage forms in the early-phase formulation development.

Correlation Between Brain Activation Changes and Cognitive Improvement Following Cognitive Remediation Therapy in Schizophrenia: An Activation Likelihood Estimation Meta-analysis.

BACKGROUND: Several studies using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have indicated that cognitive remediation therapy (CRT) might improve cognitive function by changing brain activations in patients with schizophrenia. However, the results were not consistent in these changed brain areas in different studies. The present activation likelihood estimation (ALE) meta-analysis was conducted to investigate whether cognitive function change was accompanied by the brain activation changes, and where the main areas most related to these changes were in schizophrenia patients after CRT. Analyses of whole-brain studies and whole-brain + region of interest (ROI) studies were compared to explore the effect of the different methodologies on the results. METHODS: A computerized systematic search was conducted to collect fMRI and PET studies on brain activation changes in schizophrenia patients from pre- to post-CRT. Nine studies using fMRI techniques were included in the meta-analysis. Ginger ALE 2.3.1 was used to perform meta-analysis across these imaging studies. RESULTS: The main areas with increased brain activation were in frontal and parietal lobe, including left medial frontal gyrus, left inferior frontal gyrus, right middle frontal gyrus, right postcentral gyrus, and inferior parietal lobule in patients after CRT, yet no decreased brain activation was found. Although similar increased activation brain areas were identified in ALE with or without ROI studies, analysis including ROI studies had a higher ALE value. CONCLUSIONS: The current findings suggest that CRT might improve the cognition of schizophrenia patients by increasing activations of the frontal and parietal lobe. In addition, it might provide more evidence to confirm results by including ROI studies in ALE meta-analysis.

[Recent advances in drug dissolution/permeation synchronous evaluation technologies based on physiological characteristics of gastrointestinal tract].

Pharmacokinetic behavior of orally administrated formulations involves dissolution and absorption in the gastrointestinal tract (GIT), which is required for the systemic effects of a drug. The dissolution and subsequent penetration through the intestinal epithelia is a vital step toward in vivo bioavailability. A lot of effort has been devoted to the study of physiological characteristics of GIT by means of in vitro dissolution methods or in vitro permeation methods. Moreover, drug dissolution/permeation synchronous evaluation technology could be employed to predict the process of drug dissolution and absorption by the combination of dissolution apparatus and permeation apparatus. Better prediction tools are priority in the critical path initiative of US Food and Drug Administration. The studies and applications of the drug dissolution/permeation synchronous evaluation technology are attracting more and more attention each year. However, there is no systematic review on the theoretical basis and the recent development. Therefore, in this review, we will give an overview on the physiological basis and theoretical basis of the drug dissolution/permeation synchronous evaluation technology, as well as their recent advances of this kind of equipments at home and abroad. Moreover, we have also compared their advantages and disadvantages, and the applicable scopes. With hope that the critical path study will promote the development of innovative drug research and development, and improve the druggability.

[Progress on studies of impact on CYP450 enzymes activity of traditional Chinese medicine by Cocktail probe substrates approach].

Cocktail probe substrates approach is a fast, sensitive and high through put method to determine cytochrome P450 enzymes activity. It has been widely used to screen early drug development, analyze drug metabolism types and confirm the metabolism pathways, study drug-drug interactions, optimize clinical regimen, evaluate post marketing drugs and help liver/kidney pathological studies. This article reviewed characteristics of Cocktail probe substrates, focused on the application to traditional Chinese medicine to CYP450 system as follows: the metabolic pathway research of Chinese herb active ingredients; processing way and compatibility of medical herbs affect CYP450; find out the metabolic characteristic of Chinese patent medicine, study in pharmacy of national minority; do research in liver protective effect of traditional Chinese medicine and evaluate traditional Chinese medicine syndromes in animal models. This article make a summary of existing research results and also make a comparison of cocktail probe substrates approach application to western medicine and Chinese medicine.

[Research and Application of the ICP-MS Detection Technology for the Content of Nb and Ta in Geochemical Sample].

In order to provide the test analysis technology to support the exploration and development of niobium and tantalum resource, based on the special chemical properties of Nb and Ta in geochemical sample, we studied the detection methods for the content of Nb and Ta in geochemical sample by using inductively coupled plasma mass spectrometry (ICP-MS). The results show that the sample dissolution and instrumental parameter of ICP-MS, especially the former have significant influence? on detection results. Therefore, optimizing important parameters of sample dissolution is the key of the detection technology. The optimal parameters are that the weight of sample is 50 mg; the dosage of HF acid is 15 mL; the concentration of nitric acid and tartaric acid in the sample solution is 2% and 1.5%, respectively; the validity period of detection for sample solution ≤1 d. The detection method has been validated by the national geochemistry standard reference material. The precise and exaction of method meet the required of industry standards. The detection limits of method for Nb and Ta are 1.05 and 0.13 µg · g(-1), respectively. The experiment proved that the ICP-MS detection methods, which using certain preparation process of sample solutions, is suitable for accurate and rapid determination of Nb and Ta in geochemical sample, especially geochemical survey samples which with a large amount and low content of Nb and Ta.

Liver transplantation for recurrent posthepatectomy malignant hepatic angiomyolipoma: a case report.

Hepatic angiomyolipomas (AMLs) are typically benign tumors containing varying amounts of smooth muscle cells, adipose tissue, and vessels, and are commonly found in the kidney and occasionally in the liver. The preoperative diagnosis of hepatic AML is primarily made from imaging and fine-needle aspiration biopsy results, though limited experience for such diagnoses can result in misdiagnosis. Some uncommon features of hepatic AML have been reported in the literature without an objective or qualitative consensus. As the majority of cases are benign, conservative treatment of AMLs is recommended. However, in rare cases, liver transplantation has been implemented. Only five cases of malignant hepatic AML have been reported. We report a rare case of recurrent posthepatectomy malignant hepatic AML that was misdiagnosed as liver cancer in a 37-year-old woman, which was treated by liver transplantation. The imaging and pathologic findings are presented in order to provide a more concise description to aid in future diagnoses.

Prediction of protein structural classes based on feature selection technique.

The prediction of protein structural classes is beneficial to understanding folding patterns, functions and interactions of proteins. In this study, we proposed a feature selection-based method to accurately predict protein structural classes. Three datasets with sequence identity lower than 25% were used to test the prediction performance of the method. Through jackknife cross-validation, we have verified that the overall accuracies of these three datasets are 92.1%, 89.7% and 84.0%, respectively. The proposed method is more efficient and accurate than other existing methods. The present study will offer an excellent alternative to other methods for predicting protein structural classes.

Comparison of scaled-average, population, and individual bioequivalence on 2 tablets of pitavastatin calcium: a 3-period, reference-replicated, crossover study in healthy Chinese volunteers.

BACKGROUND: Pitavastatin, a fully synthetic ß-hydroxy-ß-methylglutaryl-coenzyme A reductase inhibitor, is potent for the treatment of primary hyperlipidemia and mixed dyslipidemia. Recently, the original product and some generic products of pitavastatin calcium have become available in China. However, the intrasubject variability and interchangeability of this newly developed generic product and the branded innovator product have rarely been investigated in the Chinese population. PURPOSE: The aim of this study is to develop and compare the scaled-average, population, and individual bioequivalence (BE) of pitavastatin calcium tablets in healthy Chinese volunteers. This study will be used to allow for the interchangeability (switchability and prescribability) of the 2 products in clinical medication in China. METHODS: A single-dose, reference-replicated, 3-period crossover BE study was conducted in 36 healthy male volunteers. Plasma samples were collected before and after oral administration of 2-mg test or reference tablets. A LC-MS/MS method was used to determine the concentration of pitavastatin calcium. A noncompartmental method was used to investigate the pharmacokinetic parameters. The ANOVA and 90% CIs of ln(AUC0-t) and ln(Cmax) were used for statistical analysis of scaled-average BE. A nonparametric test (Wilcoxon signed rank test) was performed to Tmax. The analyses of population BE and individual BE were used to assess the switchability and prescribability of the 2 products. FINDINGS: Thirty-six volunteers were enrolled in this clinical research; 33 volunteers completed the 3 treatment periods. The mean (SD) relative bioavailability calculated from the ratios (T/R) of AUC0-t was 101.3% (19.7%). The mean ln(AUC0-t) and ln(Cmax) were 98.64 (90% CI, 93.44-104.13) and 98.68 (90% CI, 91.88-105.99) within previously stipulated ranges recommended by the US Food and Drug Administration and the China Food and Drug Administration (CFDA). The intrasubject %CVs of AUC0-t and Cmax were 12.0% and 18.0% for the reference tablet and 13.0% and 17.0% for the test tablet. No significant differences were found among Tmax (0.742 ± 0.276, 0.674 ± 0.202, and 0.689 ± 0.226, respectively) for reference tablet 1, reference Supplemental Table II in the online version at 10.1016/j.clinthera.2014.06.21, and test tablet by a Wilcoxon test (P > 0.05). For ln(AUC0-t) and ln(Cmax), the statistical test-reference ratios were 99.13% and 98.95%, respectively. After inspecting the results for reference and mixed scaling, all the upper confidence limits were <0; therefore, population and individual BE were given. IMPLICATIONS: In the healthy Chinese males, the generic and branded name tablets of pitavastatin calcium are bioequivalent at the rate and extent of absorption after a comparison of scaled-average, population, and individual BE and thus may be used interchangeably. Both the formulations are generally well tolerated. Chinese Clinical Trial identifier: ChiCTR-TTRCC-13003973.

[Synthesis and luminescence properties of Mg2Y8Si6O26 : Ce3+, Mn2+ phosphor].

Mg2Y8Si6O26 : Ce3+, Mn2+ phosphor was synthesized by the high temperature solid-state reaction, and the structure and luminescence properties were characterized by X-ray diffraction (XRD) and fluorescence spectrophotometer. The XRD pattern demonstrated that the synthetic material belongs to the hexagonal phase of Mg2Y8Si6O26 crystal without detectable impurity and space group P6(3)/m. The excitation and emission spectrum showed that there exist two lattice positions for Ce3+ in Mg2Y8Si6O26 crystal and their luminescence properties were compared. There are two emission peaks at 400 and 600 nm in the emission spectra under excitation at 286 nm, which come from Ce3+ and Mn2+ emission, respectively. It was demonstrated that there exists energy transfer between Ce3+ and Mn2+. The white light can be achieved by changing Mn2+ concentration. It can be used as a potential single-phased white phosphor excited by ultraviolet light.

[Synthesis and upconversion luminescence properties of BaIn6 Y2O13 : Yb3+, Er3+].

BaIn6 Y2O13 phosphors with different doping concentrations of Yb3+ and Er3+ were prepared via the high temperature solid-state reaction method. XRD data showed that BaIn6 Y2O13 phosphors belong to hexagonal system and the introduction of doping agent Yb3+ and Er3+ did not change the lattice structure of the host. The upconversion emission spectrum and power were measured by 971 nm LD laser with different excitation powers and the energy efficiencies of the samples were calculated. The obtained data showed that the ratio of green power to red power kept decreasing with the increase in doping agent concentration when the excitation density remains constant, increasing with the increase in the excitation density at the same concentration of doping agent. The analyses revealed that the former was attributed to the increasing cross relaxation between Er3+ ions, while the latter came from the raise of the energy transfer between Yb3+ and Er3+ ions and the excited state absorption of Er3+ ions due to the higher excitation density. With the increase in the excitation density, at the beginning the green luminescence power was proportional to the square of the excitation power, which agrees with the reported result. The maximum values of the fluorescence efficiencies of the samples were obtained as 0.38% (the doping concentrations of Yb3+ and Er3+ are 3%, 1%)and 0.06% (the doping concentrations of Yb3+ and Er3+ are 9%, 3%). It can be attributed to the long lifetime of 4 I13/2 energy level so it can gather a large number of electrons and reduce the population of ground state, resulting in lower pump efficiency.

Using over-represented tetrapeptides to predict protein submitochondria locations.

The mitochondrion is a key organelle of eukaryotic cell that provides the energy for cellular activities. Correctly identifying submitochondria locations of proteins can provide plentiful information for understanding their functions. However, using web-experimental methods to recognize submitochondria locations of proteins are time-consuming and costly. Thus, it is highly desired to develop a bioinformatics method to predict the submitochondria locations of mitochondrion proteins. In this work, a novel method based on support vector machine was developed to predict the submitochondria locations of mitochondrion proteins by using over-represented tetrapeptides selected by using binomial distribution. A reliable and rigorous benchmark dataset including 495 mitochondrion proteins with sequence identity ≤25% was constructed for testing and evaluating the proposed model. Jackknife cross-validated results showed that the 91.1% of the 495 mitochondrion proteins can be correctly predicted. Subsequently, our model was estimated by three existing benchmark datasets. The overall accuracies are 94.0, 94.7 and 93.4%, respectively, suggesting that the proposed model is potentially useful in the realm of mitochondrion proteome research. Based on this model, we built a predictor called TetraMito which is freely available at http://lin.uestc.edu.cn/server/TetraMito.

[Preparation and up-conversion luminescence dynamic process of Yb3+/ Er3+ co-doped BaGd2ZnO5].

Yb3+/Er3+ co-doped BaGd2 ZnO5 phosphors were prepared by using the sol-gel method. The up-conversion luminescence powers and efficiencies were measured under different excitation densities. The obtained data showed that the green luminescence power was proportional to the second-order of that of the excitation power under the lower excitation density and linearly in the higher one. The up-conversion mechanism under different excitation power was described by a rate equation. Yb3+/ Er3+ co-doped BaGd2 ZnO5 was excited by 971 nm LD laser with a square wave signal modulation and the rise and decay processes of green up-conversion luminescence were measured. In a low excitation condition, the rate equation of the energy level 4S3/2 for Er3+ ions was used to fit the green rise and decay processes in order to fix the relevant parameters, and confirm that the population of 4S3/2 energy level of Er3+ ion mainly came from the energy transfer from Yb3+ to Er3+.

Study on dissolution and absorption of four dosage forms of isosorbide mononitrate: level A in vitro-in vivo correlation.

The objective of the present study was to develop a novel in vitro system to simulate the process of dissolution and permeation of oral solid dosage forms in vivo, and to establish a correlation between in vitro permeation and in vivo absorption that could predict the bioavailability (BA) and bioequivalence (BE) of congeneric products. The in vitro dissolution and absorption kinetics of four dosage forms of isosorbide mononitrate (ISMN) were evaluated by the USP basket/paddle system and drug dissolution/absorption simulating system (DDASS). The corresponding pharmacokinetic study was performed in beagle dogs. A comparative study was carried out between the classical and the novel method to estimate the effectiveness of the modified DDASS in simulating the course of dissolution and absorption in vivo. Indeed, the correlation coefficients of in vitro dissolution and in vivo absorption obtained from DDASS and dogs were higher. Moreover, a higher level A in vitro-in vivo correlation (IVIVC) between DDASS permeation and dog absorption was established, with correlation coefficients of 0.9968, 0.9872, 0.9921, and 0.9728. The DDASS method was more accurate at modeling the process of dissolution and absorption in vivo for both immediate-release (IR) and sustained-release (SR) dosage forms of ISMN.

[Nitric oxide is involved in the modulation of central respiratory rhythm].

This experiment was expected to test whether nitric oxide (NO) exerted significant effect on the central respiratory rhythm. Experiments were performed on in vitro brainstem slice preparations from neonatal rats. These preparations include the medial region of the nucleus retrofacialis (mNRF); a part of pre-Bötinger complex, ventral respiratory group (VRG) and dorsal respiratory group (DRG). Respiratory-related burst activities were recorded from hypoglossal nerve rootlets before and during superfusion of the slice preparation with L-Arginine (L-Arg), sodium nitroprusside (SNP) or 7-nitro indazole (7-NI, an inhibitor of NO synthase). After perfusion with L-Arg and SNP, there was no significant change in respiratory rhythmical discharge activity (RRDA), but 7-NI decreased the integral amplitude of burst and inspiratory time. These results indicate that NO may take part in the inspiratory off-switching mechanism and that it also modulates the amplitude of respiratory-related bursts.