Major depressive disorder is a mental illness characterized by depressed mood, lack of engagement in pleasurable activities, anhedonia, and cognitive-behavioral disorders. Currently, traditional pharmacological treatments for depression have a delayed therapeutic onset and low treatment effectiveness. (2R, 6R)-HNK, as a key metabolite of ketamine, can not only exert rapid and lasting antidepressant effects but also has no side effects such as hallucination and addiction caused by ketamine, which has potential clinical application values. Studies have found that the antidepressant effect of (2R, 6R)-HNK is closely related to the regulation mechanism of glutamate receptor and synaptic plasticity. Besides, the changes of downstream signaling pathways include the upregulation of brain-derived neurotrophic factor (BDNF) expression, dephosphorylation of eukaryotic elongation factor 2 (eEF2), and activation of the mammalian target of rapamycin (mTOR) play a key role in the antidepressant process of the drug. Understanding the molecular mechanisms underpinning (2R, 6R)-HNK's antidepressant effects will be invaluable for the identification of targets, which will drive the development of novel, effective, next-generation pharmacotherapies for the treatment of depression.

ObjectiveTo provide a basis for human enteroviruses prevention and control by monitoring the enterovirus （EV） and its main virus types. MethodsSamples of hand-foot-and-mouth disease， herpetic angina and fever clinic patients in Dapeng New District of Shenzhen from 2016 to 2022 were tested for EV with real-time polymerase chain reaction （PCR）. To identify the isolates of EV， VP1 genes of EV were amplified with nested reverse transcription PCR， and then sequenced.A geneticphylogenetic tree was constructed based on the VP1 gene. ResultsAmong the 1 124 suspected hand-foot-and-mouth disease cases， 740 （65.84%） tested EV positive. Coxsackievirus A6 （CVA6） and Coxsackievirus A16 （CVA16） were the main two serotypes with regular cycle trends. Of the 137 suspected herpetic angina cases， 88 （64.23%） were EV positive， with Coxsackievirus A4 （CVA4） and CVA16 as the dominant serotypes. Among 428 respiratory infection specimens， 71 （16.59%） were EV positive. Coxsackievirus A4 （CVA4） was the predominant serotype which caused herpetic angina and respiratory infection. The epidemic EV isolates CVA6 from Shenzhen had a close genetic relationship with isolates in China’s mainland. ConclusionThe main serotypes EV CVA6 and CVA16 which caused hand-foot-and-mouth disease exhibit cyclical trends . The risk of EV transmitted from abroad is low， but their genetic variation and virulence change should be monitored continuously. In addition， the monitoring of dominant isolates CVA4 which cause herpetic angina and respiratory infection should be strengthened.

ObjectiveTo determine the pathogenic characteristics and genotype of two outbreaks of herpangina in children in Dapeng New District， Shenzhen， in May 2021. MethodsA total of five throat swabs from children in the two outbreaks of herpangina were collected and examined for common enteroviruses by real-time PCR. The VP1 region was further amplified by nested RT-PCR. The CLUSTAL W program in MEGA7 software was used to conduct the alignment and reconstruct a phylogenetic tree. ResultsThe pathogen causing the 2 cluster outbreaks of herpangina was coxsackievirus A4 （CVA4）. The sequences of CVA4 VP1 genes revealed that a nucleotide identity of 92% between the strains in the two outbreaks. The three CVA4 strains isolated in kindergarten A had the closest phylogenetic relationship with that isolated in Shenzhen in 2018（MN840533）， with the nucleotide identity of 98.11%. The two strains in kindergarten B had the closest phylogenetic relationship with CVA4 strain isolated in Sichuan in 2018（MW178763）， with the nucleotide identity of 97.88%. The phylogenetic tree showed that all five CVA4 strains in this study belonged to the C2 genotype. ConclusionThe C2 genotype of CVA4 is the causative agent in both outbreaks of herpangina.