Aldehyde dehydrogenase 2-associated changes in pharmacokinetics, locomotor function and peripheral glutamic acid and gamma-aminobutyric acid levels during acute alcohol intoxication in male mice.

The insufficiency of human aldehyde dehydrogenase 2 (ALDH2) has been consistently associated with high blood acetaldehyde levels and impaired locomotor function during acute alcohol intoxication. The ALDH2-associated change in peripheral glutamic acid (Glu) and gamma-aminobutyric acid (GABA) levels and its correlation with pharmacokinetics and psychomotor function remain unclear. In this study, ALDH2*2 mice were used to build an acute alcohol intoxication model after intraperitoneal administration. The blood ethanol and acetaldehyde concentrations were analyzed to generate concentration-time curves at two doses of alcohol (2.0 and 4.0 g/kg). The dose of 4.0 g/kg was selected in accordance with the preliminary behavioral evaluation result to perform the following behavioral tests (e.g. the rotarod test, the open field test, and the Y-maze test), so as to assess locomotor activity, anxiety and cognitive ability. Plasma Glu and GABA levels were determined through enzyme-linked immunosorbent assays. The results suggested that the ALDH2*2 mice had highly accumulated acetaldehyde levels, impaired locomotor activity and anxiety-like emotion but unimpaired cognitive function, compared to the wild type (WT) mice. The plasma Glu level and the ratio of Glu/GABA in the alcohol-treated WT and ALDH2*2 groups decreased from 2 to 5 h after intraperitoneal administration, whereas the GABA level did not change significantly. The blood alcohol concentration in the WT and ALDH2*2 mice was positively correlated with plasma Glu level, whereas the blood acetaldehyde level was found as the opposite. We speculate that the decline degree of Glu/GABA ratio could be associated with psychomotor retardation and needs to be further investigated.

Assessment of the forensic application of 50 Y-STR markers in a large pedigree.

Short tandem repeats on the Y chromosome (Y-STRs), characterized by paternal inheritance, are valuable in forensic practice. Notably, the potential application of Y-STRs in pedigrees should be drawn upon, especially in China's surname-concentrated natural villages. The study focused on 50 Y-STRs, including 13 rapidly mutating (RM) Y-STRs that largely constitute the current Y-STR commercial kits, and determined the differences in these Y-STRs between branches in a large pedigree and the discriminatory power of these haplotypes in different units for male relatives. As indicated in the results, 14 inconsistencies were observed at 9 Y-STRs between 10 father-son pairs. In addition, these 50 Y-STR haplotypes discriminated 10 out of 47 father-son pairs, 106 of 148 cousin pairs, 70 of 119 uncle-nephew pairs, 17 of 39 brother pairs, and 14 out of 33 grandfather-grandson pairs in a large pedigree. The RM Y-STR set is able to differentiate close male relatives in a large pedigree.

A 9-year retrospective study of poisoning-related deaths in Southwest China (Sichuan).

Poisoning is an increasing and significant burden that causes morbidity and mortality worldwide. In this retrospective study, poisoning-related cases that occurred in 19 cities and prefectures in Sichuan, Southwest China, between 2010 and 2018 were collected from the West China Forensic Medical Center of Sichuan and Public Security Bureaus. A total of 782 poisoning-related deaths were recorded, and their demographic characteristics, season of death, type of poison, and manner and cause of death were analysed. Of these cases, the victims were predominantly male (65.3%), and the 21∼50-year-old age group included the most victims (63.2%). The rural incidence was 71%. The most common poisoning agent was pesticide (40%), followed by toxic gases (32%), and there were cases of poisoning by poisonous animals and plants that are not common in other regions of China. The predominant manner of poisoning death was accident (50%), followed by suicide (38.3%) and homicide (5.0%). In this study, relevant information on poisoning-related cases was collected and compared with the poisoning data from other areas of China and foreign countries to provide guidance for the formulation of public health policies in Sichuan, Southwest China.

Metabolic effects of repeated ketamine administration in the rat brain.

Ketamine is a popular recreational drug used in club and dance music settings. Evidence suggests that chronic or repeated ketamine use could induce neurological and psychological harm, while the mechanisms underlying ketamine's effects on the nervous system are still unclear. The aim of this study was to explore the metabolic changes that occur in the prefrontal cortex (PFC), hippocampus (Hip) and striatum of rats with repeated ketamine exposure and withdrawal intervention and to identify the potential metabolic pathways influenced by ketamine. An untargeted ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS)-based metabolomics method coupled with multivariate and univariate statistical analysis was applied to analyze the metabolic profiles of the PFC, Hip, and striatum and to identify metabolite alterations. The pathway analysis tool in MetaboAnalyst was subsequently applied for pathway predictions. A total of 79, 54 and 58 changed metabolites were identified in the PFC, Hip and striatum, respectively, after repeated ketamine exposure. Pathway analysis indicated that purine metabolism and glycerophospholipid metabolism were the main pathways disturbed by ketamine in all three brain regions. After one week of withdrawal intervention, most changed metabolites in the Hip and striatum had been restored to control levels, while the metabolite alterations in the PFC were persistent. These results revealed that repeated ketamine exposure significantly changed purine metabolism and glycerophospholipid metabolism in the PFC, Hip and striatum, which might be involved in the neurotoxic effects of ketamine. Additionally, this study also identified that the PFC, rather than the Hip or striatum, was more likely to be the target region of the long-term effects of ketamine.