Misuse of the psychostimulant methamphetamine (METH) could induce serious hepatotoxicity. Our previous study revealed the effects of luteolin on alleviating METH-induced hepatotoxicity, however, the detailed mechanisms have not been elucidated. In this study, rats were orally pretreated with 100 mg/kg luteolin or sodium dodecyl sulfate water, and then METH (15 mg/kg, intraperitoneal [i.p.]) or saline was administered. Histopathological and biochemical analyses were used to determine the alleviative effects of luteolin. Based on the RNA-sequencing data, METH induced 1859 differentially expressed genes (DEGs) in comparison with the control group, which were enriched into 11 signaling pathways. Among these DEGs, 497 DEGs could be regulated through luteolin treatment and enriched into 16 pathways. The p53 signaling pathway was enriched in both METH administered and luteolin pretreated rats. Meanwhile, luteolin significantly suppressed METH-induced elevation of p53, caspase9, caspase3, cleaved caspase3, the ratio of Bax/Beclin-2, as well as autophagy-related Beclin-1, Atg5, and LC3-II. Luteolin also relieved METH-induced hepatotoxicity by decreasing inflammation factors, including TNF-α, IL-1β, and IL-18. Moreover, the levels of PI3K, p-Akt, and the normalized ratio of p-Akt/Akt declined after METH administration, whereas luteolin pretreatment failed to reverse these effects. Our results suggest that luteolin alleviates METH-induced hepatic apoptosis, autophagy, and inflammation through repressing the p53 pathway. It further illustrates the protective mechanisms of luteolin on METH-induced hepatotoxicity and provides a research basis for clinical treatment.

Electric bicycles (e-bikes) and bicycles in large Chinese cities have recently witnessed substantial growth in ridership. According to related accident trends, this study analyzed characteristics and spatial distribution in the period when e-bike-related accidents rapidly increased to propose priority measures to reduce accident casualties. For e-bike- and bicycle-related accident data from the Guangzhou Public Security Traffic Management Integrated System, linear regression was used to examine the trends in the number of accidents and age-adjusted road traffic casualties from 2011 to 2021. Then, for the period when e-bike-related accidents rapidly increased, descriptive statistics were computed regarding rider characteristics, illegal behaviors, road types, collision objects and their accident liability. One-way analysis of variance (ANOVA) followed by Bonferroni's multiple comparison test. P < 0.05 was considered statistically significant. Finally, the density distribution of accidents was presented, and Moran's I (MI) was used for assessing spatial autocorrelation. Hotspots were identified based on an optimized hotspot analysis tool. Between 2011 and 2021, the number of accidents and casualty rate (per 100,000 population) increased for e-bikes but decreased for bicycles. After 2018, e-bike-related accidents increased rapidly, and bicycle-related accidents plateaued. Accident hotspots were concentrated in central city areas and suburban areas close to the former. Three-quarters of accidents occurred in motorized vehicle lanes. Most occurred on roads without physically segregated nonmotorized vehicle lanes. More than three-fifths of the accidents involved motor vehicles with at least four wheels. The prevalence (per 100 people) of casualties among e-bike rider victims and cyclist victims accounted for 92.0 % and 96.5 %, respectively. A total of 71.6 % of e-bike-related accidents involved migrant workers. Riding in motorized vehicle lanes was the most common illegal behavior. Although e-bike-related and bicycle-related accidents presented similar characteristics, the sharp increase in e-bike-related accidents requires attention. To improve e-bike safety, governments should develop appropriate countermeasures to prevent riders from riding on motorways, such as improving road infrastructure, adjusting the driver's license system and addressing priority control areas.

The patient was an 88-year-old woman with a 10-year history of hypertension. She was suspected to have been hit by a car. At the time of the event, she was conscious and able to stand on her own and had no obvious injuries. She was sent home, but she lapsed into unconsciousness and was nonresponsive after 2 hours. She was sent to the hospital, and her heartbeat and breathing stopped. After half an hour of rescue attempts, her heartbeat did not recover, and she was declared dead. During the autopsy, a small subcutaneous hemorrhage was observed below the right knee joint. No obvious internal organ injuries or bone fractures were observed. The deceased also had mild atherosclerosis in the coronary arteries and an old cerebral infarction in the right cerebellum. The tissue histopathological tests showed distinct fat embolism in multiple organs, including the brain, lungs, kidneys, liver, and pancreas. A postmortem blood biochemistry test of the heart blood showed that the levels of low-density lipoprotein, cholesterol, triglycerides, and free fatty acids in the blood were increased, and the level of C-reactive protein was elevated. According to the autopsy results, the direct cause of death was multiorgan fat embolism. This case suggests that aging, hypertension, and hyperlipidemia may be risk factors for nontraumatic fat embolism under stressful conditions.

Methamphetamine (METH) is a major psychostimulant drug of abuse worldwide, and its neurotoxicity has been studied extensively. In addition to neurotoxicity, METH can also induce hepatotoxicity. The underlying mechanism of intestinal microorganisms in METH-induced hepatotoxicity remains unclear. In this study, mice have received antibiotics intragastrically or PBS once each day for 1 week, followed by METH or saline. The antibiotics attenuated METH-induced hepatotoxicity as evidenced by histopathological observation and biochemical analysis; furthermore, they alleviated METH-induced oxidative stress. The effect of antibiotics on METH-induced hepatotoxicity was investigated using RNA-sequencing (RNA-seq). The RNA-seq results demonstrated that antibiotics could regulate 580 differentially expressed genes (DEGs), of which 319 were upregulated after METH treatment and then downregulated with antibiotic pretreatment and 237 were first downregulated after METH administration and then upregulated after antibiotic pretreatment, in addition to 11 upregulated and 13 downregulated ones simultaneously in METH and antibiotic-pretreated groups. RNA-seq analyses revealed that TLR4 is one of the hub genes. Western blot analysis indicated that antibiotics inhibited the increase of TLR4, MyD88 and Traf6 induced by METH. This research suggests that antibiotics may play an important role in preventing METH-induced liver injury by regulating oxidative stress and TLR4/MyD88/Traf6 axis, though further investigation is required.

Sudden Death from Ischemic Heart Disease While Driving: Cardiac Pathology, Clinical Characteristics, and Countermeasures - Article abstract #929212