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

This study focused on the separation, characterization, content determination, and antiviral efficacy research on colloidal particles with different sizes in Maxing Shigan Decoction(MXSG). The mixed colloidal phase of MXSG was initially separated into small colloidal particle segment(S), medium colloidal particle segment(M), and big colloidal particle segment(B) using ultrafiltration. Further fine separation was performed using size-exclusion chromatography. Dynamic light scattering(DLS) and transmission electron microscopy(TEM) were employed to characterize the size and morphology of the separated colloidal particles. UPLC-MS/MS was used to determine the content of ephedrine, amygdalin, glycyrrhizic acid, and the EDTA complexometric titration was used to measure the calcium(Ca~(2+)) content in different colloidal phases. Finally, a respiratory syncytial virus(RSV) infection mouse model was established using intranasal administration. The experimental groups included a blank group, a model group, a ribavirin group, an MXSG group, an S group, an M group, and a B group. Oral administration was given for treatment, and pathological changes in mouse lung tissue and organ indices were evaluated. The results of the study showed that the distribution of ephedrine, amygdalin, glycyrrhizic acid, and Ca~(2+) content was not uniform among different colloidal segments. Among them, the B segment had the highest proportions of the three components, except for Ca~(2+), accounting for 46.35%, 53.72%, and 92.36%, respectively. Size-exclusion chromatography separated colloidal particles with uniform morphology in the size range of 100-500 nm. Compared to the S and M segments, the B segment showed an increased lung index inhibition rate(38.31%), spleen index, and thymus index in RSV-infected mice, and it improved the infiltration of inflammatory cells and lung injury in the lung tissue of mice. The complex components in MXSG form colloidal particles of various sizes and morphologies through heating, and small-molecule active components such as ephedrine, amygdalin, glycyrrhizic acid, and Ca~(2+) participate in the assembly to varying degrees. The main material basis for the antiviral effect of MXSG is the colloidal particles with certain particle sizes formed by the assembly of active components during the heating process.
Mice ; Animals ; Amygdalin/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Glycyrrhizic Acid/analysis* ; Ephedrine/analysis* ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Antiviral Agents/pharmacology*

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

OBJECTIVE: To evaluate the antidiarrheal effect of ethanol extract of Glycyrrhiza uralensis Fisch root (GFR) in vivo and jejunal contraction in vitro. METHODS: In vivo, 50 mice were divided into negative control, positive control (verapamil), low-, medium- and high-dose GFR (250, 500, 1,000 mg/kg) groups by a random number table, 10 mice in each group. The antidiarrheal activity was evaluated in castor oil-induced diarrhea mice model by evacuation index (EI). In vitro, the effects of GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) on the spontaneous contraction of isolated smooth muscle of rabbit jejunum and contraction of pretreated by Acetylcholine (ACh, 10 µmol/L) and KCl (60 mmol/L) were observed for 200 s. In addition, CaCl₂ was accumulated to further study its mechanism after pretreating jejunal smooth muscle with GFR (1 and 3 g/L) or verapamil (0.03 and 0.1 µmol/L) in a Ca²⁺-free-high-K⁺ solution containing ethylene diamine tetraacetic acid (EDTA). RESULTS: GFR (500 and 1,000 mg/kg) significantly reduced EI in castor oil-induced diarrhea model mice (P<0.01). Meanwhile, GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) inhibited the spontaneous contraction of rabbit jejunum (P<0.05 or P<0.01). Contraction of jejunums samples pretreated by ACh and KCl with 50% effective concentration (EC₅₀) values was 1.05 (0.71-1.24), 0.34 (0.29-0.41) and 0.15 (0.11-0.20) g/L, respectively. In addition, GFR moved the concentration-effect curve of CaCl₂ down to the right, showing a similar effect to verapamil. CONCLUSIONS GFR can effectively against diarrhea and inhibit intestinal contraction, and these antidiarrheal effects may be based on blocking L-type Ca²⁺ channels and muscarinic receptors.
Mice ; Rabbits ; Animals ; Antidiarrheals/adverse effects* ; Jejunum ; Glycyrrhiza uralensis ; Castor Oil/adverse effects* ; Calcium Chloride/adverse effects* ; Diarrhea/drug therapy* ; Plant Extracts/adverse effects* ; Verapamil/adverse effects* ; Muscle Contraction

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*

BACKGROUND: Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise approaches in asthmatic children, there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years. This study aimed to compare the safety and efficacy of salmeterol/fluticasone (SFC) vs. montelukast (MON), or combination of montelukast and fluticasone (MFC) in children and adolescents aged 4 to 18 years with bronchial asthma. METHODS: A systematic search was conducted in MEDLINE, EMBASE, the Cochrane Library, China BioMedical Literature Database, Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, and Wanfang for randomized controlled trials (RCTs) published from inception to May 24, 2021. Interventions are as follows: SFC vs. MON, or combination of MFC, with no limitation of dosage or duration. Primary and secondary outcome measures were as follows: the primary outcome of interest was the risk of asthma exacerbation. Secondary outcomes included risk of hospitalization, pulmonary function, asthma control level, quality of life, and adverse events (AEs). A random-effects (I2 ≥ 50%) or fixed-effects model (I2 < 50%) was used to calculate pooled effect estimates, comparing the outcomes between the intervention and control groups where feasible. RESULTS: Of the 1006 articles identified, 21 studies met the inclusion criteria with 2643 individuals; two were at low risk of bias. As no primary outcomes were similar after an identical treatment duration in the included studies, meta-analysis could not be performed. However, more studies favored SFC, instead of MON, owing to a lower risk of asthma exacerbation in the SFC group. As for secondary outcome, SFC showed a significant improvement of peak expiratory flow (PEF)%pred after 4 weeks compared with MFC (mean difference [MD]: 5.45; 95% confidence interval [CI]: 1.57-9.34; I2 = 95%; P = 0.006). As for asthma control level, SFC also showed a higher full-controlled level (risk ratio [RR]: 1.51; 95% CI: 1.24-1.85; I2 = 0; P < 0.001) and higher childhood asthma control test score after 4 weeks of treatment (MD: 2.30; 95% CI: 1.39-3.21; I2 = 72%; P < 0.001) compared with MFC. CONCLUSIONS: SFC may be more effective than MFC for the treatment of asthma in children and adolescents, especially in improving asthma control level. However, there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma. Further research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs. PROSPERO REGISTRATION NUMBER CRD42019133156.
Acetates ; Administration, Inhalation ; Adolescent ; Adrenal Cortex Hormones/therapeutic use* ; Albuterol/therapeutic use* ; Anti-Asthmatic Agents/therapeutic use* ; Asthma/drug therapy* ; Child ; Cyclopropanes ; Drug Therapy, Combination ; Fluticasone/therapeutic use* ; Humans ; Quinolines ; Salmeterol Xinafoate/therapeutic use* ; Sulfides

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

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

To systematically review the efficacy and safety of Liujunzi Decoction combined with Western medicine in the treatment of stable chronic obstructive pulmonary disease(COPD). Three English databases and four Chinese databases were systematically searched from the database establishment to April 1, 2020. We screened randomized controlled trial(RCT) according to the pre-determined inclusion and exclusion criteria, then extracted data. Methodological quality of included studies was assessed with Cochrane bias risk evaluation tool. Data were analyzed by using RevMan 5.3. A total of 401 articles were retrieved and finally 17 RCTs were included in this study, involving 1 447 patients, and the overall quality of the included studies was not high. Meta-analysis showed that, in reducing traditional Chinese medicine symptom score, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing the grade of modified medical research council(mMRC), Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing COPD assessment test(CAT) score, Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone. In delaying the decline of forced expiratory volume in one second(FEV_1) or % in the expected value, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In delaying the decline of ratio of FEV_1 to forced vital capacity(FEV_1/FVC), Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone, but there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing acute exacerbation rate, there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. On the other outcome measures of Liujunzi Decoction combined with other Western medicine, Meta-analysis could not be conducted and conclusions due to the inclusion of only one study. In terms of the occurrence of adverse reactions, some studies did not mention, so the safety of Liujunzi Decoction combined with Wes-tern medicine could not be determined in this paper. Due to the limitations of the quality and quantity of inclu-ded studies, the efficacy of Liujunzi Decoction combined with Western medicine for COPD still needs more high-quality studies for confirmation, and its safety needs to be further verified.
Administration, Inhalation ; Bronchodilator Agents/therapeutic use* ; Drug Combinations ; Drugs, Chinese Herbal ; Humans ; Medicine ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Salmeterol Xinafoate/therapeutic use*