[Estimation of Early Postmortem Interval of Asphyxial Death Rats at Different Ambient Temperatures by GC-MS-Based Metabolomics].

ABSTRACT: Objective To establish the orthogonal partial least square （OPLS） model for the estimation of early postmortem interval （PMI） of asphyxial death rats in four ambient temperatures based on gas chromatography-mass spectrometry （GC-MS） metabolomics. Methods The 96 rats were divided into four temperature groups （5 ℃, 15 ℃, 25 ℃ and 35 ℃）. Each temperature group was further divided into 3 h, 6 h, 12 h and 24 h after death, and 6 other rats were taken as the control group. The cardiac blood was collected at the set time points for the four temperature groups and 0 h after death for the control group for the metabolomics analysis by GC-MS. By OPLS analysis, the variable importance in projection （VIP）>1 and the result of Kruskal-Wallis test P<0.001 were used to screen out the differential metabolite related to PMIs in the cardiac blood of rats of different temperature groups. Then OPLS regression models of different temperature groups were established with these metabolites. At the same time, a prediction group for investigating the prediction ability of these models was set up. Results Through the analysis of OPLS, 18, 15, 24 and 30 differential metabolites （including organic acids, amino acids, sugars and lipids） were screened out from the rats in groups of 5 ℃, 15 ℃, 25 ℃ and 35 ℃, respectively. The prediction results of the four temperature group models showed that the prediction deviation of 5 ℃ model was larger than that of other groups. The prediction results of other temperature groups were satisfactory. Conclusion There are some differences in the changes of metabolites in cardiac blood of rats at different ambient temperatures. The influence of ambient temperature should be investigated in the study of PMI estimation by metabolomics, which may improve the accuracy of PMI estimation.

Relationship between Blood Acetaldehyde Concentration and Psychomotor Function of Individuals with Different ALDH2 Genotypes after Alcohol Consumption.

ABSTRACT: Objective To explore the change rules of blood ethanol and blood acetaldehyde concentration, the impairment of psychomotor functions of different acetaldehyde dehydrogenase （ALDH） 2 genotype individuals after alcohol consumption and the relationship among them. Methods The ALDH2 genotypes in seventy-nine healthy volunteers were obtained by SNaPshotTM method, then divided into ALDH2*1/*1 （wild type） and ALDH2*1/*2 （mutant type） group. After volunteers consumed 1.0 g/kg of alcohol, blood ethanol concentration and blood acetaldehyde concentration at a series of time points before and after alcohol consumption and psychomotor functions, such as, visual selective response time, auditory simple response time and tracking experiment were detected. Biphasic alcohol response questionnaires were collected. Results After alcohol consumption, ALDH2*1/*2 group's blood ethanol and blood acetaldehyde concentration reached the peak earlier than ALDH2*1/*1 group. Its blood acetaldehyde concentration was higher than that of ALDH2*1/*1 group, 1-6 h after alcohol consumption. The psychomotor functions, such as visual selective response time and auditory simple response time in ALDH2*1/*2 group were more significantly impaired than those in ALDH2*1/*1 group after alcohol consumption. There was no statistical significance between the two groups in excitement or sedation reactions （P>0.05）. Pearson correlation coefficient test showed that blood acetaldehyde concentration was related with psychomotor function. Conclusion There are significant differences between the psychomotor function of ALDH2 wild type and mutant type individuals after alcohol consumption estimated to be related to the difference in blood acetaldehyde concentration after alcohol consumption.

[Correlation of Genetic Polymorphism, Alcoholic Beverage Type and Ethanol Metabolism].

OBJECTIVES: To explore the effects of ADH1B and ALDH2 gene polymorphism and type of alcoholic beverage on ethanol metabolism, to provide data support for cases involving the interpretation of ethanol metabolism or back calculation of blood ethanol concentration in forensic practice. METHODS: A total of 81 volunteers were selected. The genotypes of ADH1B, ADH1C and ALDH2 were obtained by a multiplex SNaPshot genotyping method. Each subject was administered with 1.0 g/kg of alcohol. About 1 mL venous blood was collected before and after the alcohol consumption at 30 min, 45 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h and 8 h, respectively. The concentrations of ethanol and acetaldehyde in blood were determined by headspace gas chromatography. The peak times of blood ethanol concentration （Tmax）, the peak mass concentrations of ethanol （Cmax）, the area under curve （AUC） of ethanol （AUCethanol）, AUCacetaldehyde and ethanol elimination rates （ß） were calculated. In order to eliminate the influence of ADH1C, the ADH1C*1/*1 carriers were grouped based on the genotype of ADH1B and ALDH2. The data of each group were evaluated by one-way analysis of variance and pairwise comparison tests were performed by least significant difference method. The gene interactions were evaluated by two-way analysis of variance. Each parameter of three kinds of alcoholic beverage （white wine, red wine and beer） among groups was analysed by variance analysis with randomized block design. RESULTS: There were no differences in the value of Tmax and Cmax between the groups with different ADH1B and ALDH2 genotype. The differences in the values of AUCethanol, ß and AUCacetaldehyde among some groups carrying different ADH1B and ALDH2 genotype had statistical significance, while no significant difference was observed in these parameters when one individual taking same dose of different alcoholic beverage type. CONCLUSIONS: The ethanol metabolism is associated with the related gene polymorphism, which is barely affected by alcoholic beverage type.

Posttraumatic administration of a sub-anesthetic dose of ketamine exerts neuroprotection via attenuating inflammation and autophagy.

As a complex disease, traumatic brain injury (TBI) can result in long-term psychiatric changes and sensorimotor and cognitive impairments. The TBI-induced loss of memory and long-term cognitive dysfunction are related to mechanistic factors including an increased inflammatory response, autophagy, edema, and ischemia. Many published studies have offered evidence for the neuroprotective effects and anti-inflammatory properties of ketamine for TBI patients. Nonetheless, there is a limited understanding of the accurate mechanism that underlies the potential neuroprotective effects of ketamine. Herein, it can be shown that posttraumatic administration of ketamine at a sub-anesthetic dose (10mg/kg ketamine, every 24h up to 7days) can prevent the TBI-induced production of IL-6 and TNF-α, attenuate deficits of dendrites and spines and exert beneficial effects on memory and behavior. Moreover, studies show that ketamine may activate the mTOR signaling pathway by p-mTOR induction to down-regulate the expression of crucial autophagic proteins such as LC3 and Beclin-1. According to these findings, ameliorating secondary brain injury and anti-inflammatory properties is closely related to the neuroprotection of ketamine, which supports the use of ketamine as a potential therapy for patients with TBI to alleviate functional deficits.

Mediating effects on health-related quality of life in adults with osteoporosis: a structural equation modeling.

UNLABELLED: Participants with physical limitation and high degree of pain had poor mental and physical health-related quality of life. In addition, the more support and exercise that the participants had, the more likely they were to report better health-related quality of life. INTRODUCTION: Osteoporosis is a public health threat worldwide. The aim of this study is to examine the effects of individual demographics, disease characteristics, and social support on health-related quality of life (HrQoL) of adults with osteoporosis. Most psychosocial studies focused on the relationships but not the specific construct of social support on HrQoL. METHODS: In a correlational design, face-to-face, structured interviews were employed to collect information. Study questionnaires included a demographic sheet, the modified Social Support Inventory, and the Short-Form 36 scales on a convenience sample of 161 individuals recruited from four outpatient centers. Using the structural equation modeling approach, all relationships among factors, mediators, and HrQoL were analyzed. RESULTS: The mean duration of osteoporosis was longer than 5 years. Participants who exercised more than three times per week had greater HrQoL than individuals who exercised less frequently. Participants with physical limitation and high degree of pain had poor mental and physical HrQoL. The more support that the participants perceived, the more likely they were to report better HrQoL. The best fitted structural equation modeling (SEM) model included individual demographics and physical function, and social support as significant predictors on HrQoL, with informational support and physical function acting as mediators in those relationships. Moreover, this structural model explained 35, 42, and 40 % of the variance on activity of daily living (ADL), physical, and mental health-related quality of life. CONCLUSIONS: The more informational support that individuals have, the more likely they were to report better HrQoL. Individuals with osteoporosis who have lower pain and more exercise are considered having better HrQoL. Further longitudinal research will help clarify the direction of these relationships.

Cultivation of recombinant Escherichia coli to achieve high cell density with a high level of penicillin G acylase activity.

A mutant strain of E. coli EP1 harbouring pGL-5 was employed to develop a process for producing penicillin G acylase (PGA). In comparison with different carbon sources in the medium, it was found that the specific levels of PGA activity obtained in the glucose medium were the lowest. which was likely due to catabolic repression. Phenylacetic acid (PAA) was previously reported to be an regulatory inducer for PGA production, whereas in this study, the addition of PAA repressed both cell growth and enzyme expression. In a fed-batch culture, the increase of specific PGA activity followed the pattern of the cell concentration during the early to middle cell growth phase. With application of pure oxygen aeration and an appropriate medium design, the cell concentration reached 162 (g wet weight/l), which was 2.4 times higher compared to that of the original operation, and a specific PGA activity of 37 (IU/g wet weight) was achieved after 12 h of cultivation.

Physical linkage of a human immunoglobulin heavy chain variable region gene segment to diversity and joining region elements.

Antibody genes are assembled from a series of germ-line gene segments that are juxtaposed during the maturation of B lymphocytes. Although diversification of the adult antibody repertoire results in large part from the combinatorial joining of these gene segments, a restricted set of antibody heavy chain variable (VH), diversity (DH), and joining (JH) region gene segments appears preferentially in the human fetal repertoire. We report here that one of these early-expressed VH elements (termed VH6) is the most 3' VH gene segment, positioned 77 kilobases on the 5' side of the JH locus and immediately adjacent to a set of previously described DH sequences. In addition to providing a physical map linking human VH, DH, and JH elements, these results support the view that the programmed development of the antibody VH repertoire is determined in part by the chromosomal position of these gene segments.