Psychoactive substances abusing may induce neuron-specific adaptation and lead to physical and psychological dependence.Moreover,psychoactive substances have toxicological actions to cause physical damages.It has been reported that DNA methylation,acting as an epigenetic modification,may be one of the mechanisms involved in these adaptive changes and physical damages.This review shows a general introduction to the molecular mechanism of DNA methylation,and expounds the pharmacological and toxicological effects of some psychoactive substances on DNA methylation,including ethanol,methamphetamine,morphine,and cocaine.

Phosphodiesterase-4 ( PDE4 ) has been one of the most popular drug targets during recent years due to its critical role in the control of intracellular cyclic adenosine monophos-phate ( cAMP ) concentration and downstream signal transduc-tion. PDE4 is widely distributed in the central nervous system ( CNS) with different expression levels of its four subtypes. Re-cent data indicate that altered PDE4 expression and/or activity is relevant to multiple CNS disorders, such as depression, memory deficiency, drug dependence, and neural lesion. Selective PDE4 inhibitors exhibit therapeutic effects on these disorders and might be a promising pharmacotherapy. The paper highlights recent re-search progress in the roles of PDE4 in CNS function, and dis-cusses the prospects of PDE4 as a novel therapeutic target for CNS disorders.

Approach-avoidance conflict(AAC)refers to the internal conflict that individuals experi-ence when faced with conflicting approach or avoidance thoughts.It reveals some characteristics of mental disorders,such as anxiety,depression,and addiction represented by excessive tendencies of approach or avoidance.The function of the cortico-limbic-striatal system influences behavioral choices at the neural level during the onset of AAC,and the development of related behavioral paradigms that can better represent AAC behaviors is critical to evaluating the efficacy of drugs and guiding the development of new drugs.This paper summarizes the neural mechanisms,behavioral paradigms,and applications in behavioral pharmacology related to AAC behaviors from the perspective of psychopharmacology with a view to providing new perspectives and methods for the diagnosis and treatment of related neuro-psychiatric disorders.

OBJECTIVE：To i nvestigate the clini cal ch aracteristics of anaphylactic shock induced by piperacillin and its compound preparation ，and to provide reference for prevention and treatment of the severe ADR. METHODS ：A case of anaphylactic shock induced by piperacillin and sulbactam were analyzed in our hospital ，meanwhile ADR literatures about piperacillin alone and its compound preparation-induced anaphylactic shock were collected from Medline ，CNKI，Wanfang database and VIP during the inception to Jul. 2020. Gender and age of patients ，allergic history ，primary disease and treatment ，skin test ， administration route and dosage of piperacillin and its compound preparation ，occurrence time and main manifestations of anaphylactic shock ，treatment measure and prognosis were analyzed ，then prevention and treatment suggestions were put forward. RESULTS：The patient in this case was transferred to the ICU after partial hepatectomy. The use of piperacillin and sulbactam to prevent postoperative infection caused anaphylactic shock. A total of 28 literatures about anaphylactic shock induced by piperacillin and its compound preparations were collected from the database （involving 28 patients）. Among totally 29 patients，there were 12 male and 17 female；the majority of patients were 50-59 years old （6 cases，20.69％）. Three patients had allergic history （food， latex gloves ，etc.），and most of the primary diseases were infectious diseases or the drug used in perioperative period. Skin tests were carried out in 22 patients（75.86％）before medication and the results were negative. The possible allergenic drugs of 27 cases which were administered by intravenous route included piperacillin ，piperacillin sulbactam and piperacillin tazobactam. The dosage was different according to the primary disease and severity. 14 patients（55.56％）developed anaphylactic shock within 5 minutes after drug exposure. The main symptoms were systemic allergic reaction ，mainly involving the circulatory system. Except for two death cases ，the other patients ’symptoms were relieved after treatment. CONCLUSIONS ：Allergic history and skin test results may have limitation in predicting anaphylactic shock induced by piperacillin and its compound preparation. Close monitoring needs to be taken in patients during these medications. Rescue therapy should be prepared in advance and countermeasures need to be carried out promptly in case of anaphylactic shock.

This paper elucidates the connotation and extension of the concept of "impending illness" from the perspective of logic. The connotation of impending illness refers to the intermediate state between health （not yet sick） and disease （already sick）， characterized by the initial instability of yin and yang or a low-level balance of yin and yang as its internal mechanism， and mild dysfunctions in physiological， psychological， and social functions as its manifestations. The extension of impending illness includes latent disease status and pre-disease status. By adopting a creative hermeneutic approach to explore the deep-seated connotations of impending illness， this paper systematically analyzes the concept of impending illness from five levels： the existential level， the intentional level， the implicational level， the situational level， and the necessitational level， arguing that impending illness represents the unity of ambiguity and precision， the deviation of the human body system from homeostasis within a certain range， and an important component of the improvement of the traditional Chinese medicine health management system. Thoroughly explicating and clarifying the concept of "impending illness" can provide theoretical references for the study of transitional states between health and disease and the improvement of the traditional Chinese medicine health management system.

Objective: : To investigate the relationship between the expression of RUNX1 isoforms and the clinical curative effect and the prognosis of acute leukemia (AL), in order to provide valuable experimental data for the individualized treatment, MRD (minimal residual disease) monitoring and prognosis prediction of AL. Methods: AL patients with primary treatment (PT, n=88) and recrudescence (RC, n=10) that treated at the Department of Hematology of Affiliated Hospital of Guangdong Medical University from April, 2012 to April, 2013 were included in this study. Real-time PCR was used to examine the mRNA expression of RUNX1 isoforms (RUNX1a and RUNX1b/c) in PT patients, RC patients and controls (non-malignant hematological disease patients).The changes in mRNA expression of RUNX1a and RUNX1b/c in patients before and after the chemotherapy were also observed. Results： ： (1)The expression levels of RUNX1a mRNAinAML andALL PT group andAML RC group was significantly higher than those of control group (P<0.05); The expression level of RUNX1a mRNAinAMLPT group was increased compared withALLPT group (P<0.05). (2) The expression levels of RUNX1a and RUNX1b/c mRNAinAML andALL patients at initial treatment were significantly higher than those after complete remission (CR) (P<0.05). (3) By comparing the expression levels of RUNX1a and RUNX1b/c mRNA at initial diagnosis, there was no significant difference between 6-month death group and survival group, CR group and NCR (non-complete remission) group after first cycle of chemotherapy, or the high leukocyte group and non-high leukocyte group (all P>0.05).The expression level of RUNX1a mRNA in AML-ETO positive group was higher than that of negative group (P<0.05). (4) The expression levels of RUNX1a and RUNX1b/c mRNA in patients with acute leukemia decreased with the increasing chemotherapy cycle, and significantly increased when had a relapse, which may even succeed the initial level.Conclusion: RUNX1a isoforms participate in the pathogenesis of acute leukemia, and isrelated to the relapse ofAML. The expression levels of RUNX1a and RUNX1b/c mRNAare related to the clinical efficacy that can be used as an indicator of curative effect, but have no significant correlation with the prognosis of the disease.Dynamic monitor of theexpression levels of RUNX1a and RUNX1b/c isomers can be used as an effective indicator of MRD monitoring after chemotherapy, which can be used to evaluate the efficacy and identify the risk of recurrence at early stage.