Tree peony seed oil alleviates hyperlipidemia and hyperglycemia by modulating gut microbiota and metabolites in high-fat diet mice.

With the changes of people's lifestyle, hyperlipidemia and hyperglycemia which were induced from a diet high in both fat and sugar have become serious health concerns. Tree peony seed oil (PSO) is a novel kind of edible oil that shows great potential in the food industry because of its high constituent of unsaturated fatty acids. Based 16S rRNA and gut untargeted metabolomics, this study elucidated that the mechanism of PSO regulating blood glucose (Glu) and lipids. The impact of PSO on gut microbiota balance and gut metabolites of mice with a high-fat diet (HFD) was evaluated. The findings indicated that PSO decreased HFD mice's body weight and fat accumulation, ameliorating the levels of blood lipid, reduced liver fat vacuole levels. What's more PSO modulated the proportion of gut microbiota in HFD mice and enhanced the abundance of probiotics. Furthermore, untargeted metabolomic analysis revealed that PSO not only impacted the generation of short-chain fatty acids (SCFAs) by gut microorganism and altered metabolic pathway but exerted influence on secondary bile acids (BA), amino acid metabolism, and various other metabolites. These results suggested that PSO has the potential function for mitigating HFD-induced hyperlipidemia and hyperglycemia by regulating gut microbiota and host metabolism.

Geometries and stabilities of chromium doped nitrogen clusters: mass spectrometry and density functional theory studies.

Metal-doped nitrogen clusters serve as effective models for elucidating the geometries and electronic properties of nitrogen-rich compounds at the molecular scale. Herein, we have conducted a systematic study of VIB-group metal chromium (Cr) doped nitrogen clusters through a combination of mass spectrometry techniques and density functional theory (DFT) calculations. The laser ablation is employed to generate CrNn+ clusters. The results reveal that CrN8+ cluster exhibits the highest signal intensity in mass spectrometry. The photodissociation experiments with 266 nm photons confirm that the chromium heteroazide clusters are composed of chromium ions and N2 molecules. Further structural searches and electronic structure calculations indicate that the cationic CrN8+ cluster possesses an X shaped geometry with D2 symmetry and exhibits robust stability. Molecular orbital and chemical bonding analyses demonstrate the existence of strong interactions between Cr+ cation and N2 ligands. The present findings enrich the geometries of metal doped nitrogen clusters and provide valuable guidance for the rational design and synthesis of novel transition metal nitrides.

A general numerical model of leukocyte adhesion in microchannels.

Leukocyte adhesion on the vascular endothelium plays an important role in human immune system and reflects the physiological condition of a human body. In this paper, a generally implementable dynamic adhesion model based on the length limit of microvilli was developed to explore the behavior of a suspended leukocyte's adhesion process under microchannel shear flow. Simulations showed that the whole adhesion process can be divided into cell sedimentation, preliminary adhesion and stable dynamic adhesion stages. The cell tumbling kinetics, cell deformation, cell adhesion area and adhesion force were studied under the conditions of various bond strength, cell membrane surface tension, inlet flow velocity and cytoplasmic viscosity. Results showed that the bond strength affects the cell tumbling behaviors differently by changing the adhesion force. The cell with lower membrane surface tension induces a larger adhesion area, and eventually results in a greater adhesion and a lower cell tumbling velocity. The flow velocity changes cell velocity through the flow viscous force during the whole adhesion process. The cytoplasmic viscosity affects adhesion mainly in the preliminary adhesion stage by changing the cell deformation rate but has slight effect on the stabilized dynamic adhesion on cells. This study provides a simple theoretical basis to further clarify the mechanism of cell behaviors under stress and adhesion and becomes one of the prerequisites for study of tissue inflammation, wound healing, and disease treatments.

Population pharmacokinetics of clozapine and its primary metabolite norclozapine in Chinese patients with schizophrenia.

AIM: To develop a combined population pharmacokinetic model (PPK) to assess the magnitude and variability of exposure to both clozapine and its primary metabolite norclozapine in Chinese patients with refractory schizophrenia via sparse sampling with a focus on the effects of covariates on the pharmacokinetic parameters. METHODS: Relevant patient concentration data (eg, demographic data, medication history, dosage regimen, time of last dose, sampling time, concentrations of clozapine and norclozapine, etc) were collected using a standardized data collection form. The demographic characteristics of the patients, including sex, age, weight, body surface area, smoking status, and information on concomitant medications as well as biochemical and hematological test results were recorded. Persons who had smoked 5 or more cigarettes per day within the last week were defined as smokers. The concentrations of clozapine and norclozapine were measured using a HPLC system equipped with a UV detector. PPK analysis was performed using NONMEM. Age, weight, sex, and smoking status were evaluated as main covariates. The model was internally validated using normalized prediction distribution errors. RESULTS: A total of 809 clozapine concentration data sets and 808 norclozapine concentration data sets from 162 inpatients (74 males, 88 females) at multiple mental health sites in China were included. The one-compartment pharmacokinetic model with mixture error could best describe the concentration-time profiles of clozapine and norclozapine. The population-predicted clearance of clozapine and norclozapine in female nonsmokers were 21.9 and 32.7 L/h, respectively. The population-predicted volumes of distribution for clozapine and norclozapine were 526 and 624 L, respectively. Smoking was significantly associated with increases in the clearance (clozapine by 45%; norclozapine by 54.3%). The clearance was significantly greater in males than in females (clozapine by 20.8%; norclozapine by 24.2%). The clearance of clozapine and norclozapine did not differ significantly between Chinese patients and American patients. CONCLUSION: Smoking and male were significantly associated with a lower exposure to clozapine and norclozapine due to higher clearance. This model can be used in individualized drug dosing and therapeutic drug monitoring.

[The application of evaluation tools for criminal responsibility in forensic psychiatric expertise].

Criminal responsibility is divided into three types: full criminal responsibility, diminished criminal responsibility and criminal irresponsibility in China. In forensic psychiatric expertise, doctors often have different opinions about the responsibility in a given case because of lacking objective criteria. The evaluation of criminal responsibility is always unresolved problem in forensic psychiatric expertise. Application of these evaluation tools in forensic psychiatric expertise were reviewed in this article. The value of the tools were still controversial in the reliability and validity, but it is clear that these tools have the positive roles in ensuring the standardization and the uniformity of the forensic investigation.

[Population pharmacokinetics research of clozapine in Chinese schizophrenic patients].

The goal of this study is to investigate the population pharmacokinetics of oral given clozapine in Chinese schizophrenic patients and to identify possible relationships between population parameters and covariates including demography factors and CYP1A2 genetic polymorphism, so as to create the population pharmacokinetics model to guide individual clinical delivery. Details of drug dosage history, sampling time and concentration of 626 data points from 183 patients were collected retrospectively. The 183 patients were randomly allocated either to the index group (n = 168) or to the validation group (n = 15). Population pharmacokinetic data analysis was performed using the nonlinear mixed-effects model (NONMEM) program on the index group. The values of apparent clearance (CL/F), apparent volume of distribution (V/F) and the constant of absorption rate were estimated. A number of covariates including demographic index, coadministration of other drugs and CYP1A2 genotypes were evaluated statistically for their influence on these parameters. The final population model related clearance with day-dose/BSA (DBSA) and smoke habit (SMOK). Predictive performance of the final model evaluated with the validation group showed insignificant bias between observed and model predicted concentrations. Typical value of CL/F (non-smoking group), V/F and the constant of absorption rate were 28.5 L x h(-1) (5.05%), 1 290 L (16.7%) and 2.26 h(-1) (fixed), inter-patient variability (CV) in CL/F and V/F was) 42.2% and 10.0%, respectively. It was observed that the values of CL/F in the two smoking groups were higher than that in the non-smoking group. The residual variability (SD) between observed and model-predicted concentrations was 45.8 microg x L(-1).

Reliability and validity of the Chinese version of the Calgary Depression Scale for Schizophrenia.

OBJECTIVE: The aim of the present study was to determine the reliability and validity of the Chinese version of the Calgary Depression Scale for Schizophrenia (CDSS-C) in schizophrenia patients. METHOD: One hundred and one inpatients from four mental health units who met DSM-IV criteria for schizophrenia were enrolled. The Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HDRS-24), Simpson-Augus Rating Scale (SAS), and Barnes Acathisia Rating Scale (BARS) were administered by the first rater, whereas the CDSS-C was assessed by a second independent rater. RESULTS: The internal consistency (Cronbach's alpha = 0.80) and the inter-rater reliability (kappa coefficient >0.79) were good. The test-retest reliability was high (r = 0.927). The scale had good construct validity, with statistically significant correlations with the HDRS-24, G6 item (depression) of PANSS, and significant weak correlations with the general psychopathology subscale of PANSS. The CDSS-C showed no correlation with the positive and negative subscale of PANSS, the SAS and the BARS. CONCLUSION: The Chinese version of CDSS is a valid and reliable instrument for the assessment of depression in schizophrenia.

Scales for evaluating depressive symptoms in Chinese patients with schizophrenia.

There have been few studies evaluating depressive symptoms in Chinese patients with schizophrenia. Thus, we planned to compare the diagnostic validity of 4 commonly used assessment scales for depression in schizophrenia in China. The association between different depression scales and between depression scales and negative symptoms were also studied. The study population consisted of 101 inpatients meeting the DSM-IV criteria for schizophrenia. Depression in the study subjects was defined by the DSM-IV criteria for a major depressive episode. The negative subscale of the PANSS was used to assess the negative symptoms in schizophrenia. The following 4 depression scales were assessed for their diagnostic validity as measures of depressive disorder in schizophrenia: the Calgary Depression Scale for Schizophrenia (CDSS), the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Rating Scale for Depression (HAM-D), and the depression subscale of the PANSS (PANSS-D). The depression scales were found to be highly intercorrelated with each other. Of the 4 depression scales studied, only CDSS can discriminate between depression and a PANSS negative symptoms subscale score or negative item scores. The areas under the receiver operating characteristic curves of the CDSS, HAM-D, MARDS, and PANSS-D were 0.954, 0.881, 0.828, and 0.897, respectively. The area under the receiver operating characteristic curve of the CDSS was significantly greater than those of the HAM-D, the MARDS, and the PANSS-D. Our study suggests that the CDSS may provide optimal assessment of depression in patients with schizophrenia.