Methamphetamine(METH)addiction is a severe and increasingly prevalent neuropsychiatric disorder for which current diagnostic and therapeutic approaches remain limited and predominantly symptom-oriented.Exercise,as a s...Methamphetamine(METH)addiction is a severe and increasingly prevalent neuropsychiatric disorder for which current diagnostic and therapeutic approaches remain limited and predominantly symptom-oriented.Exercise,as a safe,accessible and cost-effective non-pharmacological intervention,has emerged as a promising strategy to ameliorate METH-induced neurotoxicity and addiction-related behaviors.Growing evidence indicates that these benefits are closely linked to the regulation of exercise-induced biomarkers,defined as molecular indicators whose expression or activity is dynamically altered during or after physical activity.This review focuses on the core regulatory role of exercise-induced biomarkers in METH addiction and systematically summarizes their involvement in key neurobiological pathways,outlining molecular pathological mechanisms such as dysregulation of dopamine,glutamate and GABA neurotransmitter systems,neuroinflammation and oxidative stress,and epigenetic remodeling,and emphasizing how these processes converge on changes in candidate biomarkers in the brain and periphery.On this basis,the review describes how exercise modulates neural plasticity,neurotransmitter systems,inflammation and oxidative stress through biomarkers such as brain-derived neurotrophic factor(BDNF),exerkines,inflammatory cytokines,metabolites and noncoding RNAs,with particular attention to neurotrophic and immune-related markers,microRNAs and other epigenetic regulators that can reverse METH-induced synaptic and structural abnormalities and promote recovery of cognitive and emotional functions.Advances in high-throughput omics technologies,including transcriptomics,metabolomics and multi-omics integration,are summarized to illustrate the screening and identification of key exercise-responsive biomarkers.Studies in METH-addicted animal models have revealed differentially expressed genes,signaling pathways(e.g.,PI3K-Akt,mTOR,Wnt)and core nodes such as NFKBIA and CXCL12 that may mediate the protective effects of exercise.The review further discusses the potential of exercisemediated biomarkers as objective indicators for diagnosis,dynamic monitoring of therapeutic efficacy and patient stratification.Multi-gene diagnostic models based on peripheral samples(e.g.,hair follicles,blood)demonstrate how biomarker panels can distinguish non-recovered,almost-recovered and healthy individuals,providing a molecular basis for staging METH use disorder and evaluating the impact of exercise interventions.The temporal dynamics of biomarker changes before and after exercise are highlighted,underscoring the value of longitudinal monitoring of factors such as BDNF,immune-related genes and circulating microRNAs to capture treatment-relevant windows of plasticity.In addition,the underlying molecular basis of exercise as an adjunct therapy and gene-targeted exercise strategies that leverage individual biomarker and gene expression profiles to optimize exercise prescriptions are summarized.Current conceptual and technical challenges are outlined,including heterogeneity of biomarker responses,individual variability,assay sensitivity and specificity,and gaps between preclinical findings and clinical application,together with future directions for integrating exercise with multi-omics,artificial intelligence-assisted biomarker discovery and,prospectively,gene-editing-based interventions.Particular emphasis is placed on the need to standardize exercise protocols,incorporate stage-specific and sex-sensitive designs,and combine exercise with pharmacotherapy and psychosocial rehabilitation in real-world clinical settings across diverse healthcare systems.Overall,this review aims to provide a comprehensive and integrated mechanistic framework and updated theoretical support for the application of exercise-mediated biomarkers in the diagnosis,therapeutic effect monitoring and personalized intervention of METH addiction,and to offer new and clinically relevant insights into the development of precision medicine strategies for substance use disorders.展开更多
Objective The purpose of this study was to investigate the effect of methamphetamine （MA） on spatial learning and memory and the role of tetrahydropalmatine （THP） in MA-induced changes in these phenomena in mice. ...Objective The purpose of this study was to investigate the effect of methamphetamine （MA） on spatial learning and memory and the role of tetrahydropalmatine （THP） in MA-induced changes in these phenomena in mice. Methods Male C57BL/6 mice were randomly divided into eight groups, according to different doses of MA, different doses of THP, treatment with both MA and THP, and saline controls. Spatial learning and memory were assessed using the Morris water maze. Western blot was used to detect the expression of extracellular signal-regulated protein kinase （ERK） in the mouse prefrontal cortex （PFC） and hippocampus. Results Repeated MA treatment significantly increased the escape latency in the learning phase and decreased the number of platform site crossings in the memory-test phase. ERK1/2 expression was decreased in the PFC but not in the hippocampus of the MA-treated mice. Repeated THP treatment alone did not affect the escape latency, the number of platform site crossings or the total ERK1/2 expression in the brain. Statistically significantly shorter escape latencies and more platform site crossings occurred in MA＋THP-treated mice than in MA-treated mice. Conclusion Repeated MA administration impairs spatial learning and memory in mice, and its co-administration with THP prevents this impairment, which is probably attributable to changed ERK1/2 expression in the PFC. This study contributes to uncovering the mechanism underlying MA abuse, and to exploring potential therapies.展开更多
Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic ...Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.展开更多
为探究考虑心理因素影响下我国城市潜在MaaS(Mobility as a Service)用户的套餐选择行为与支付意愿的影响因素,综合考虑了受访者个人属性、心理属性与套餐属性3个方面,分别在北京和大连开展了RP与SP调查。在此基础上,构建了结构方程模...为探究考虑心理因素影响下我国城市潜在MaaS(Mobility as a Service)用户的套餐选择行为与支付意愿的影响因素,综合考虑了受访者个人属性、心理属性与套餐属性3个方面,分别在北京和大连开展了RP与SP调查。在此基础上,构建了结构方程模型和离散选择模型,对受访者的MaaS套餐选择行为和支付意愿进行了定性与定量研究。研究结果显示:个人属性方面,北京样本中男性和收入为1万~2万元对MaaS套餐选择行为有显著正面影响;本科教育水平和家中儿童数为2个及以上有显著负面影响;大连样本中本科及以上教育水平、家中老人数为2个及以上、收入2万元及以上、工作有弹性等因素对MaaS套餐选择行为有显著正面影响;年龄在36~60岁、家中有私家车、家中有儿童等因素有显著负面影响。心理属性方面,行为态度对MaaS套餐选择行为具有显著影响,其中北京受访者表现尤为明显;套餐属性方面,套餐价格、公共交通次数及共享单车次数对MaaS套餐选择行为均有显著影响。支付意愿方面,北京和大连受访者对出租车和网约车支付意愿均最高,每增加一公里出租车或网约车均愿为套餐多花费1元。研究结果可为我国未来MaaS套餐的设计与推广提供理论支撑。展开更多
Aim p53 up-regulated modulator of apoptosis （PUMA） is a known apoptosis inducer; however its role in microglial survival remains poorly understood. In addition to the classical transcription factor p53, microRNA- ...Aim p53 up-regulated modulator of apoptosis （PUMA） is a known apoptosis inducer; however its role in microglial survival remains poorly understood. In addition to the classical transcription factor p53, microRNA- 143 （miR-143） is involved in PUMA expression at the post-transcriptional level. Furthermore, they identify unique roles of miR-143/PUMA in mediating microglial survival via the regulation of apoptosis and autophagy interplay. Results Blockage of autophagy accelerated methamphetamine-induced apoptosis, whereas the induction of autoph- agy attenuated the decrease in microglial survival. Moreover, anti-miR-143-dependent PUMA up-regulation re- versed the methamphetamine-induced decrease in microglial survival via the regulation of apoptosis and autophagy. The in vivo relevance of these findings was confirmed in mouse models, which demonstrated that the microinjection of anti-miR-143 into the hippocampus ameliorated the methamphetamine-induced decrease in microglia as well as that observed in heterozygous miR-143 ^＋/- mice. Conclusion These findings provided new insight for the specific contributions of miR-143/PUMA to microglial survival in the context of drug abuse.展开更多
The relapse of methamphetamine (meth) is associated with decision-making dysfunction. The present study aims to investigate theimpact of different emotions on the decision-making behavior of meth users. We used 2 (gen...The relapse of methamphetamine (meth) is associated with decision-making dysfunction. The present study aims to investigate theimpact of different emotions on the decision-making behavior of meth users. We used 2 (gender: male, female) × 3 (emotion:positive, negative, neutral) × 5 (block: 1, 2, 3, 4, 5) mixed experiment design. The study involved 168 meth users who weredivided into three groups: positive emotion, negative emotion and neutral emotion group, and tested by the emotional IowaGambling Task (IGT). The IGT performance of male users exhibited a decreasing trend from Block 1 to Block 3. Female methusers in positive emotion had the best performance in IGT than females in the other two groups. In positive emotion, the IGTperformance of female meth users was significantly better than that of men. Female meth users in positive emotion had betterdecision-making than those in negative or neutral emotion. Female meth users in positive emotion had better decision-makingperformance than males in positive emotion. In negative and neutral emotions, there was no significant gender difference indecision-making.展开更多
目的探讨慢性自发性荨麻疹(CSU)患者血清Mas相关G蛋白偶联受体成员X2(MRGPRX2)、白细胞介素-6(IL-6)及IL-24的水平在发病中的意义。方法收集2023年9月—2023年12月就诊于徐州医科大学附属医院的CSU患者75例,作为病例组,并根据病情严重...目的探讨慢性自发性荨麻疹(CSU)患者血清Mas相关G蛋白偶联受体成员X2(MRGPRX2)、白细胞介素-6(IL-6)及IL-24的水平在发病中的意义。方法收集2023年9月—2023年12月就诊于徐州医科大学附属医院的CSU患者75例,作为病例组,并根据病情严重程度分为轻度组、中度组、重度组,完成荨麻疹活动评分(urticaria activity score,UAS7)与慢性荨麻疹生活质量问卷评分(chronic urticaria quality of life questionnaire,CU-Q2oL);另选取60例健康者作为对照组。比较各组血清MRGPRX2、IL-6及IL-24水平,分析其与UAS7、CU-Q2oL得分的相关性。结果病例组血清MRGPRX2、IL-6及IL-24水平均高于对照组(P<0.05),CSU患者血清MRGPRX2、IL-6水平升高与其病情严重程度呈正相关(r=0.531,P<0.05;r=0.462,P<0.05),但IL-24水平升高与CSU患者病情严重程度无显著相关性(r=0.015,P>0.05)。经logistic回归分析显示,血清中MRGPRX2、IL-6、IL-24水平升高均是CSU发生的独立危险因素(P<0.05)。经受试者操作特征(ROC)曲线分析结果显示,血清中MRGPRX2、IL-6、IL-24水平3项指标联合预测的曲线下面积(AUC)高于单独指标(P<0.05)。结论血清MRGPRX2、IL-6及IL-24水平在CSU患者血清中呈高表达,且血清MRGPRX2、IL-6与其病情严重程度相关,三者联合检测CSU发生的效能优于各指标单独检测。展开更多
基金supported by grants from The National Natural Science Foundation of China(82472611)The“14th Five Year Plan”Scientific Research and Innovation Team of Chengdu Sport University(23CXTD02)Sports Medicine Key Laboratory of Sichuan Province/Key Laboratory of Sports Medicine,General Administration of Sport of China(2025-A028)。
文摘Methamphetamine(METH)addiction is a severe and increasingly prevalent neuropsychiatric disorder for which current diagnostic and therapeutic approaches remain limited and predominantly symptom-oriented.Exercise,as a safe,accessible and cost-effective non-pharmacological intervention,has emerged as a promising strategy to ameliorate METH-induced neurotoxicity and addiction-related behaviors.Growing evidence indicates that these benefits are closely linked to the regulation of exercise-induced biomarkers,defined as molecular indicators whose expression or activity is dynamically altered during or after physical activity.This review focuses on the core regulatory role of exercise-induced biomarkers in METH addiction and systematically summarizes their involvement in key neurobiological pathways,outlining molecular pathological mechanisms such as dysregulation of dopamine,glutamate and GABA neurotransmitter systems,neuroinflammation and oxidative stress,and epigenetic remodeling,and emphasizing how these processes converge on changes in candidate biomarkers in the brain and periphery.On this basis,the review describes how exercise modulates neural plasticity,neurotransmitter systems,inflammation and oxidative stress through biomarkers such as brain-derived neurotrophic factor(BDNF),exerkines,inflammatory cytokines,metabolites and noncoding RNAs,with particular attention to neurotrophic and immune-related markers,microRNAs and other epigenetic regulators that can reverse METH-induced synaptic and structural abnormalities and promote recovery of cognitive and emotional functions.Advances in high-throughput omics technologies,including transcriptomics,metabolomics and multi-omics integration,are summarized to illustrate the screening and identification of key exercise-responsive biomarkers.Studies in METH-addicted animal models have revealed differentially expressed genes,signaling pathways(e.g.,PI3K-Akt,mTOR,Wnt)and core nodes such as NFKBIA and CXCL12 that may mediate the protective effects of exercise.The review further discusses the potential of exercisemediated biomarkers as objective indicators for diagnosis,dynamic monitoring of therapeutic efficacy and patient stratification.Multi-gene diagnostic models based on peripheral samples(e.g.,hair follicles,blood)demonstrate how biomarker panels can distinguish non-recovered,almost-recovered and healthy individuals,providing a molecular basis for staging METH use disorder and evaluating the impact of exercise interventions.The temporal dynamics of biomarker changes before and after exercise are highlighted,underscoring the value of longitudinal monitoring of factors such as BDNF,immune-related genes and circulating microRNAs to capture treatment-relevant windows of plasticity.In addition,the underlying molecular basis of exercise as an adjunct therapy and gene-targeted exercise strategies that leverage individual biomarker and gene expression profiles to optimize exercise prescriptions are summarized.Current conceptual and technical challenges are outlined,including heterogeneity of biomarker responses,individual variability,assay sensitivity and specificity,and gaps between preclinical findings and clinical application,together with future directions for integrating exercise with multi-omics,artificial intelligence-assisted biomarker discovery and,prospectively,gene-editing-based interventions.Particular emphasis is placed on the need to standardize exercise protocols,incorporate stage-specific and sex-sensitive designs,and combine exercise with pharmacotherapy and psychosocial rehabilitation in real-world clinical settings across diverse healthcare systems.Overall,this review aims to provide a comprehensive and integrated mechanistic framework and updated theoretical support for the application of exercise-mediated biomarkers in the diagnosis,therapeutic effect monitoring and personalized intervention of METH addiction,and to offer new and clinically relevant insights into the development of precision medicine strategies for substance use disorders.
基金supported by grants from the Ministry of Science and Technology of China (2009 DFA 31080)the National Natural Science Foundation of China (30973365)
文摘Objective The purpose of this study was to investigate the effect of methamphetamine （MA） on spatial learning and memory and the role of tetrahydropalmatine （THP） in MA-induced changes in these phenomena in mice. Methods Male C57BL/6 mice were randomly divided into eight groups, according to different doses of MA, different doses of THP, treatment with both MA and THP, and saline controls. Spatial learning and memory were assessed using the Morris water maze. Western blot was used to detect the expression of extracellular signal-regulated protein kinase （ERK） in the mouse prefrontal cortex （PFC） and hippocampus. Results Repeated MA treatment significantly increased the escape latency in the learning phase and decreased the number of platform site crossings in the memory-test phase. ERK1/2 expression was decreased in the PFC but not in the hippocampus of the MA-treated mice. Repeated THP treatment alone did not affect the escape latency, the number of platform site crossings or the total ERK1/2 expression in the brain. Statistically significantly shorter escape latencies and more platform site crossings occurred in MA＋THP-treated mice than in MA-treated mice. Conclusion Repeated MA administration impairs spatial learning and memory in mice, and its co-administration with THP prevents this impairment, which is probably attributable to changed ERK1/2 expression in the PFC. This study contributes to uncovering the mechanism underlying MA abuse, and to exploring potential therapies.
基金supported by the National Natural Science Foundation of China,No.81971246 (to TM)Opening Foundation of Jiangsu Key Laboratory of Neurodegeneration,Nanjing Medical University,No.KF202204 (to LZ and SF)。
文摘Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.
文摘为探究考虑心理因素影响下我国城市潜在MaaS(Mobility as a Service)用户的套餐选择行为与支付意愿的影响因素,综合考虑了受访者个人属性、心理属性与套餐属性3个方面,分别在北京和大连开展了RP与SP调查。在此基础上,构建了结构方程模型和离散选择模型,对受访者的MaaS套餐选择行为和支付意愿进行了定性与定量研究。研究结果显示:个人属性方面,北京样本中男性和收入为1万~2万元对MaaS套餐选择行为有显著正面影响;本科教育水平和家中儿童数为2个及以上有显著负面影响;大连样本中本科及以上教育水平、家中老人数为2个及以上、收入2万元及以上、工作有弹性等因素对MaaS套餐选择行为有显著正面影响;年龄在36~60岁、家中有私家车、家中有儿童等因素有显著负面影响。心理属性方面,行为态度对MaaS套餐选择行为具有显著影响,其中北京受访者表现尤为明显;套餐属性方面,套餐价格、公共交通次数及共享单车次数对MaaS套餐选择行为均有显著影响。支付意愿方面,北京和大连受访者对出租车和网约车支付意愿均最高,每增加一公里出租车或网约车均愿为套餐多花费1元。研究结果可为我国未来MaaS套餐的设计与推广提供理论支撑。
文摘Aim p53 up-regulated modulator of apoptosis （PUMA） is a known apoptosis inducer; however its role in microglial survival remains poorly understood. In addition to the classical transcription factor p53, microRNA- 143 （miR-143） is involved in PUMA expression at the post-transcriptional level. Furthermore, they identify unique roles of miR-143/PUMA in mediating microglial survival via the regulation of apoptosis and autophagy interplay. Results Blockage of autophagy accelerated methamphetamine-induced apoptosis, whereas the induction of autoph- agy attenuated the decrease in microglial survival. Moreover, anti-miR-143-dependent PUMA up-regulation re- versed the methamphetamine-induced decrease in microglial survival via the regulation of apoptosis and autophagy. The in vivo relevance of these findings was confirmed in mouse models, which demonstrated that the microinjection of anti-miR-143 into the hippocampus ameliorated the methamphetamine-induced decrease in microglia as well as that observed in heterozygous miR-143 ^＋/- mice. Conclusion These findings provided new insight for the specific contributions of miR-143/PUMA to microglial survival in the context of drug abuse.
基金supported by grants from the National Social Science Foundation of China(19BGL230)the Key Project of Social Science Planning in Jiangxi Province(23JY01).
文摘The relapse of methamphetamine (meth) is associated with decision-making dysfunction. The present study aims to investigate theimpact of different emotions on the decision-making behavior of meth users. We used 2 (gender: male, female) × 3 (emotion:positive, negative, neutral) × 5 (block: 1, 2, 3, 4, 5) mixed experiment design. The study involved 168 meth users who weredivided into three groups: positive emotion, negative emotion and neutral emotion group, and tested by the emotional IowaGambling Task (IGT). The IGT performance of male users exhibited a decreasing trend from Block 1 to Block 3. Female methusers in positive emotion had the best performance in IGT than females in the other two groups. In positive emotion, the IGTperformance of female meth users was significantly better than that of men. Female meth users in positive emotion had betterdecision-making than those in negative or neutral emotion. Female meth users in positive emotion had better decision-makingperformance than males in positive emotion. In negative and neutral emotions, there was no significant gender difference indecision-making.
文摘目的探讨慢性自发性荨麻疹(CSU)患者血清Mas相关G蛋白偶联受体成员X2(MRGPRX2)、白细胞介素-6(IL-6)及IL-24的水平在发病中的意义。方法收集2023年9月—2023年12月就诊于徐州医科大学附属医院的CSU患者75例,作为病例组,并根据病情严重程度分为轻度组、中度组、重度组,完成荨麻疹活动评分(urticaria activity score,UAS7)与慢性荨麻疹生活质量问卷评分(chronic urticaria quality of life questionnaire,CU-Q2oL);另选取60例健康者作为对照组。比较各组血清MRGPRX2、IL-6及IL-24水平,分析其与UAS7、CU-Q2oL得分的相关性。结果病例组血清MRGPRX2、IL-6及IL-24水平均高于对照组(P<0.05),CSU患者血清MRGPRX2、IL-6水平升高与其病情严重程度呈正相关(r=0.531,P<0.05;r=0.462,P<0.05),但IL-24水平升高与CSU患者病情严重程度无显著相关性(r=0.015,P>0.05)。经logistic回归分析显示,血清中MRGPRX2、IL-6、IL-24水平升高均是CSU发生的独立危险因素(P<0.05)。经受试者操作特征(ROC)曲线分析结果显示,血清中MRGPRX2、IL-6、IL-24水平3项指标联合预测的曲线下面积(AUC)高于单独指标(P<0.05)。结论血清MRGPRX2、IL-6及IL-24水平在CSU患者血清中呈高表达,且血清MRGPRX2、IL-6与其病情严重程度相关,三者联合检测CSU发生的效能优于各指标单独检测。
