Assessing variability in predictors of adequate follow-up after esophageal food bolus impaction: a retrospective study and literature review.

Amphetamine-type stimulants, mainly including methamphetamine (MA), are the third most widely abused class of drugs globally, posing a significant global public health challenge []. As a synthetic sympathomimetic amine, MA exerts adverse effects on multiple organ systems. Prolonged MA use can lead to strong drug dependence and severe neurotoxic effects. Chronic MA abuse is associated with various psychiatric disorders, such as anxiety, hallucinations, delusions, and reduced volition [,], along with varying degrees of cognitive dysfunction [,,]. MA-induced neuropsychiatric adverse effects are strongly linked to its neurotoxic properties. Chronic MA abuse can lead to shorter neuronal dendritic lengths and a significant increase in the expression of neuronal death and apoptosis-related markers in the human brain [,]. Apoptosis, a well-established form of programmed cell death, plays an important regulatory role in neurotoxic damage caused by MA exposure. In addition, MA-induced cognitive impairment is also closely associated with neuronal apoptosis [,]. MA induces neurotoxicity via mitochondrial dysfunction and apoptosis initiation. Evidence suggests that oxidative products of dopamine cause mitochondrial dysfunction, including respiratory chain disorders, mitochondrial swelling, loss of membrane potential, and decreased phosphorylation ability [,]. In addition, MA exacerbates mitochondrial dysfunction via multiple molecular pathways, such as Glu receptors, ONOO•, proliferator-activated gamma receptor coactivator 1-alpha, and protein kinase C-delta [,,]. The neurotoxicity resulting from mitochondrial dysfunction is primarily mediated by mitochondria-induced apoptosis []. Various studies have reported that MA increases pro-apoptotic protein expression while reducing anti-apoptotic protein expression in rodent brains [,]. This pro-apoptotic shift is largely due to the extensive release of mitochondrial membrane gap proteins such as cytochrome c (Cyt-c) [], which interacts with adaptor protein apoptotic peptidase activating factor 1 (Apaf-1) and pro-caspase-9 to form an apoptosome, leading to caspase cascade activation []. In our previous study, we also found that MA induces caspase cascade activation and apoptosis in the hippocampus, prefrontal cortex, and primary cells of rats []. Mitochondrial dynamics refers to the balance between mitochondrial fission and fusion. Dynamin-related protein 1 (Drp1) is essential for mitochondrial fission [], while mitofusin 1 (Mfn1) initiates the fusion of the outer mitochondrial membrane [], and optic atrophy protein 1 (Opa1) induces endosomal fusion in an Mfn1-dependent manner []. The PINK1/Parkin pathway is a key regulator of mitophagy, vital for preserving mitochondrial function []. Drp1-mediated mitochondrial fission has also attracted attention in behavioral modulation, neurotoxicity, and myocardial toxicity associated with drug abuse []. Transcription factor early growth response 3 (Egr3) can be induced by acute cocaine exposure and has been shown to be a key factor in cocaine induced reward effects and exercise responses []. In addition, the binding of Erg3 to Drp1 increases during cocaine exposure, while knocking down Erg3 expression can weaken cocaine induced mitochondrial fission []. These studies reveal that mitochondrial dynamic changes may be involved in the regulatory mechanisms of drug abuse behavior. For cocaine induced neurotoxicity, cocaine reduces neuronal mitochondrial membrane potential and activates autophagy to produce neurotoxicity, involving mitochondrial dynamics related proteins such as Drp1, Fis1, and Parkin []. Moreover, a drug-related cardiovascular study showed that before any structural changes occur in myocardial tissue, the effect of cocaine on myocardial cells has altered mitochondrial dynamics: its division activity significantly increases while fusion activity significantly decreases []. Recent research has found that MA can cause ultrastructural changes in mitochondrial cristae structure, inner and outer membranes, and matrix, while MA-induced neurodegeneration is significantly associated with specific mitochondrial damage. In addition, after MA exposure, the expression of fission/autophagy related proteins such as Fis1 and Drp1 decreased, while the expression of Pink1 and Parkin increased, all of which occurred synchronously with mitochondrial structural changes [].