OBJECTIVE: To observe the clinical efficacy of heat-sensitive moxibustion robot for improving the depressive state of methamphetamine addicts during withdrawal period. METHODS: A total of 60 patients with methamphetamine addiction accompanied with depressive state were randomly divided into an observation group (40 cases, 4 cases dropped out) and a control group (20 cases, 2 cases dropped out). The control group received routine health education and addiction treatment in compulsory isolation drug rehabilitation center. On the basis of the treatment in the control group, in the observation group, the heat-sensitive moxibustion robot was used to locate sensitive points at the Shenque (CV8) and Danzhong (CV17), and dual-point sparrow-pecking moxibustion was delivered for 60 min per session. The moxibustion therapy was performed 4 times in the 1st week, 3 times in the 2nd and 3rd weeks respectively, and 2 times in the 4th week, for 12 times totally. The scores of Hamilton depression scale (HAMD), self-rating depression scale (SDS), visual analogue scale (VAS) for drug craving, Hamilton anxiety scale (HAMA), self-rating anxiety scale (SAS), and Pittsburgh sleep quality index (PSQI) were observed before treatment, at the end of the 2nd and 4th weeks of treatment, and 4 weeks after the treatment completion (follow-up) in the two groups. RESULTS: At each time point after treatment, in the observation group, the HAMD, VAS, HAMA and PSQI scores were decreased compared with those before treatment (P<0.01, P<0.001); at the end of the 4th week of treatment and in follow-up, the SDS and SAS scores were decreased compared with those before treatment (P<0.001, P<0.01). Compared before treatment, there were no significant differences in the above scores at each time point after treatment in the control group (P>0.05). In the observation group, at each time point after treatment, the HAMD and VAS scores were lower than those in the control group (P<0.01, P<0.001, P<0.05); at the end of the 4th week of treatment and in follow-up, the SDS and HAMA scores were lower than those in the control group (P<0.05, P<0.001); at the end of the 4th week of treatment, the PSQI score was lower than that in the control group (P<0.01). CONCLUSION Heat-sensitive moxibustion robot effectively improves depression, anxiety and sleep quality, and reduces drug craving in methamphetamine addicts during withdrawal period.
Humans ; Moxibustion/methods* ; Male ; Adult ; Female ; Methamphetamine/adverse effects* ; Depression/therapy* ; Middle Aged ; Robotics ; Young Adult ; Amphetamine-Related Disorders/psychology* ; Acupuncture Points ; Substance Withdrawal Syndrome/psychology*

This study aimed to explore the roles of microRNAs (miRNAs) in the post-transcriptional regulation of cocaine- and amphetamine-regulated transcript (CART) peptide in the bovine hypothalamus and to screen key regulatory miRNAs. Targetscan was used to predict the potential miRNAs binding to CART 3' untranslated regions (3'UTR). Bioinformatics analysis predicted 7 miRNA binding sites in the bovine CART 3'UTR, which were bta-miR-377, bta-miR-331-3p, bta-miR-491, bta-miR-493, bta-miR-758, bta-miR-877, and bta-miR-381, respectively. Reverse transcription-PCR (RT-PCR) was carried out to determine the endogenous expression of CART and target miRNAs in the bovine hypothalamus. All the 7 target miRNAs and CART were endogenously expressed in the bovine hypothalamus. The dual-luciferase reporter gene assay was employed to detect the targeted binding relationship between CART 3'UTR and target miRNAs obtained from bioinformatics analysis. The dual-luciferase reporter gene assay confirmed that the 3'UTR of CART had a targeted binding relationship with the 7 target miRNAs. Cell experiments were conducted to examine the effects of target miRNAs on the messenger RNA (mRNA) and protein levels of exogenous CART and screen for key regulatory miRNAs. The results of cell experiments showed that the 7 miRNAs downregulated the mRNA level of CART, with bta-miR-491 demonstrating the strongest downregulating effect. Bta-miR-377, bta-miR-331-3p, bta-miR-491, bta-miR-493, and bta-miR-381 downregulated the protein level of CART, with bta-miR-381 exerting the strongest downregulating effect. Animal experiments were conducted to explore the effects of key regulatory miRNAs on the mRNA and protein levels of CART in the hypothalamus and the CART concentration in the serum. The results from animal experiments showed that miR-491 and miR-381 regulated the endogenous expression of CART in the hypothalamus and the concentration in the serum by binding to the CART 3'UTR. These results suggest that miR-491 and miR-381 are the main miRNAs regulating CART expression in the bovine hypothalamus, which can affect serum CART concentration by modulating endogenous CART expression.
Animals ; MicroRNAs/metabolism* ; Cattle ; Hypothalamus/metabolism* ; 3' Untranslated Regions/genetics* ; Nerve Tissue Proteins/metabolism* ; Gene Expression Regulation ; Binding Sites ; Base Sequence ; Computational Biology/methods* ; Cocaine- and Amphetamine-Regulated Transcript Protein

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer, and any change of miRNAs expression will affect the degree of target regulation, thus affecting intracellular homeostasis. This study verified that miR-186-5p could inhibit the proliferation, migration and invasion of LUAD cells by regulating PRKAA2. METHODS: Previous investigations found that the expression of miR-186-5p was markedly suppressed in LUAD. Bioinformatics method is used to predict the target protein related to ferroptosis downstream and inquire about its expression level in LUAD and its influence on the survival of patients. Double luciferase verified the binding site of PRKAA2 and miR-186-5p. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of PRKAA2. The effects of miR-186-5p of LUAD cells as well as the mechanism by which miR-186-5p inhibits Fer-1's sensitivity to ferroptosis were confirmed by EdU, Transwell, and scratch assays. The effect of miR-186-5p on the amount of reactive oxygen species (ROS) in LUAD cells was discovered using ROS experiment. Malondialdehyde (MDA) and glutathione (GSH) experiments were used to detect the effects of miR-186-5p and PRKAA2 on ferroptosis index of LUAD cells. The concentration of lipid ROS (L-ROS) in LUAD cells were measured using the L-ROS tests to determine the effects of miR-186-5p and PRKAA2. RESULTS: The expression of PRKAA2 is up-regulated, and a high level of PRKAA2 expression was associated with a poor prognosis for patients with LUAD. Overexpression of miR-186-5p decreased the gene and protein expression of PRKAA2. By promoting ferroptosis, miR-186-5p overexpression prevented lung cancer cells from proliferating, invading, and migrating. ROS could be produced in higher amounts in LUAD cells due to miR-186-5p. Overexpression of miR-186-5p and knockdown PRKAA2 up-regulated MDA content and reduced GSH content in LUAD cells, respectively. miR-186-5p could increase the content of L-ROS and promote the ferroptosis sensitivity of LUAD cells by targeting PRKAA2. CONCLUSIONS miR-186-5p promotes ferroptosis of LUAD cells through targeted regulation of PRKAA2, thus inhibiting the proliferation, invasion and migration of LUAD.
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Humans ; Lung Neoplasms/genetics* ; Carcinoma, Non-Small-Cell Lung ; Ferroptosis/genetics* ; Reactive Oxygen Species ; Adenocarcinoma of Lung/genetics* ; MicroRNAs/genetics* ; 3,4-Methylenedioxyamphetamine ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; AMP-Activated Protein Kinases

With the proliferation of synthetic drugs, research on the mechanism of action of addictive drugs and treatment methods is of great significance. Among them, methamphetamine (METH) is the most representative amphetamine synthetic drug, and the treatment of METH addiction has become an urgent medical and social problem. In recent years, the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness, multiple targets, low side effects, low cost, and other characteristics. Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction. Based on the research on METH in recent years, this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.
Humans ; Methamphetamine/adverse effects* ; Drugs, Chinese Herbal/therapeutic use* ; Amphetamine/therapeutic use* ; Behavior, Addictive/drug therapy* ; Amphetamine-Related Disorders/drug therapy*

Drug problem is a major social and public security problem in the world. Drug abuse poses a great threat to economic development, social stability and public health. In recent years, synthetic drugs represented by methamphetamine have surpassed traditional drugs such as morphine, heroin, ketamine and become one of the most abused drugs in the world. In order to solve the problem of drug abuse, it is of great theoretical value and practical significance to carry out all-round and multi-level scientific research on drug-related issues. Based on the current situation of drug abuse, this article reviews research progresses on the epidemiology of methamphetamine abuse, the monitoring technology, the basic researches on toxicity damage, the withdrawal drug screening, the related clinical comorbidity and the testing technologies, comprehensively presenting the development trend of methamphetamine abuse related issues.
Amphetamine-Related Disorders/epidemiology* ; Heroin ; Humans ; Illicit Drugs ; Methamphetamine/adverse effects* ; Substance Abuse Detection

Synthetic cathinones are a class of new psychoactive substances with a structure similar to amphetamine drugs, which can produce excitatory effects similar to drugs such as amphetamine and cocaine after being taken. In recent years, the abuse of synthetic cathinones worldwide has become increasingly serious, posing a serious threat to social security and public health. This article focuses on several common synthetic cathinones, collects their research results in animal autonomous activity experiments and drug dependence model experiments and summarizes their relevant experimental conclusions in animal body temperature regulation, learning and memory, and anxiety, in order to provide data reference and method guidance for the domestic development of related drug research.
Alkaloids/pharmacology* ; Amphetamine ; Animals ; Behavior, Animal ; Illicit Drugs

The ezrin-radixin-moesin (ERM) proteins are a family of membrane-associated proteins known to play roles in cell-shape determination as well as in signaling pathways. We have previously shown that amphetamine decreases phosphorylation levels of these proteins in the nucleus accumbens (NAcc), an important neuronal substrate mediating rewarding effects of drugs of abuse. In the present study, we further examined what molecular pathways may be involved in this process. By direct microinjection of LY294002, a PI3 kinase inhibitor, or of S9 peptide, a proposed GSK3β activator, into the NAcc core, we found that phosphorylation levels of ERM as well as of GSK3β in this site are simultaneously decreased. These results indicate that ERM proteins are under the regulation of Akt-GSK3β signaling pathway in the NAcc core. The present findings have a significant implication to a novel signal pathway possibly leading to structural plasticity in relation with drug addiction.
Amphetamine ; Animals ; Glycogen Synthase Kinases ; Humans ; Membrane Proteins ; Microinjections ; Negotiating ; Neurons ; Nucleus Accumbens ; Phosphorylation ; Phosphotransferases ; Plastics ; Proto-Oncogene Proteins c-akt ; Rats ; Reward ; Signal Transduction ; Street Drugs ; Substance-Related Disorders

BACKGROUND: Liquid chromatographyetandem mass spectrometry (LC-MSMS) for simultaneous analysis of multiple microbial secondary metabolites (MSMs) is potentially subject to interference by matrix components. METHODS: We examined potential matrix effects (MEs) in analyses of 31 MSMs using ultraperformance LC-MSMS. Twenty-one dust aliquots from three buildings (seven aliquots/building) were spiked with seven concentrations of each of the MSMs (6.2 pg/µl–900 pg/µl) and then extracted. Another set of 21 aliquots were first extracted and then, the extract was spiked with the same concentrations. We added deepoxy-deoxynivalenol (DOM) to all aliquots as a universal internal standard. Ten microliters of the extract was injected into the ultraperformance LC-MSMS. ME was calculated by subtracting the percentage of the response of analyte in spiked extract to that in neat standard from 100. Spiked extract results were used to create a matrix-matched calibration (MMC) curve for estimating MSM concentration in dust spiked before extraction. RESULTS: Analysis of variance was used to examine effects of compound (MSM), building and concentration on response. MEs (range: 63.4%–99.97%) significantly differed by MSM (p < 0.01) and building (p < 0.05). Mean percent recoveries adjusted with DOM and the MMC method were 246.3% (SD = 226.0) and 86.3% (SD = 70.7), respectively. CONCLUSION: We found that dust MEs resulted in substantial underestimation in quantifying MSMs and that DOM was not an optimal universal internal standard for the adjustment but that the MMC method resulted in more accurate and precise recovery compared with DOM. More research on adjustment methods for dust MEs in the simultaneous analyses of multiple MSMs using LC-MSMS is warranted.
2,5-Dimethoxy-4-Methylamphetamine ; Calibration ; Dust ; Mass Spectrometry ; Methods

Phentermine is a sympathomimetic amine, like amphetamine, which is one of the most often prescribed drugs for weight loss. Although exact mechanism of phentermine causing psychosis is still not clear, numerous reports already showed that phentermine can induce psychosis. Psychotic symptoms are generally resolved once the medications are stopped. In contrast, we present a case of a 25-years-old Asian female patient who developed psychotic symptoms repeatedly after phentermine administrations. This case suggests that phentermine can cause psychotic episodes repeatedly, resulting in chronic occupational and social impairment. Therefore, a precautious measure such as government regulations for physicians prescribing and an education for patients taking phentermine are urgently needed.
Amphetamine ; Asian Continental Ancestry Group ; Education ; Female ; Government Regulation ; Humans ; Phentermine ; Psychotic Disorders ; Recurrence ; Weight Loss

To explore the mechanism for changes in brain microstructure in long-term abstinent from methamphetamine-dependence by using the diffusion tensor imaging (DTI).
 Methods: A total of 26 patients with long-term abstinent methamphetamine-dependence, whose abstinence time more than 14 months, and 26 normal controls all underwent cognitive executive function tests and DTI scans. We used voxel-based analysis to compare the fractional anisotropy (FA) and mean diffusivity (MD) to obtain the abnormal brain regions of DTI parameters between the two groups. Spearman correlation analysis was used to explore the correlation between FA, MD of the brain regions with abnormal parameters and cognitive executive function tests.
 Results: There were no statistical differences in the cognitive executive function tests between the two groups (P>0.05). Compared with the normal control group, the long-term abstinent from methamphetamine-dependence group showed the decreased FA in the right precuneus, right superior frontal gyrus, right calcarine, left inferior temporal gyrus and the increased MD in the right triangular part of inferior frontal gyrus, right precuneus, right posterior cingulate, right middle temporal gyrus, bilateral middle occipital gyrus, left superior parietal lobule, and lobule VIII of cerebellar hemisphere. The MD values of the right middle temporal gyrus in the long-term abstinent group were negatively correlated with the number of completions within 60 seconds (r=-0.504) and within 120 seconds (r=-0.464) .
 Conclusion: The DTI parameters in multiple brain regions from the methamphetamine-dependence patients are still abnormal after a long-term abstinence. DTI can provide imaging evidence for brain microstructural abnormalities in long-term abstinent from methamphetamine-dependence.
Amphetamine-Related Disorders ; Anisotropy ; Brain ; Diffusion Tensor Imaging ; Humans ; Methamphetamine