Ketamine， a non-competitive N-methyl-D-aspartate （NMDA） receptor antagonist， has gained increasing attention for its rapid antidepressant effects in treatment-resistant depression （TRD） and suicidal ideation. Its mechanisms include NMDA receptor blockade， AMPA receptor activation， and upregulation of BDNF/mTOR signaling. Its enantiomers， esketamine and R-ketamine， as well as its metabolites， exhibit differences in efficacy and mechanisms. Intranasal esketamine has been approved in the Europe， United States， and China for TRD， demonstrating rapid efficacy in alleviating depressive symptoms and acute suicidal ideation. In contrast， R-ketamine demonstrates potential for longer-lasting effects and a improved safety profile. This review summarizes recent advances in the pharmacology， pharmacokinetics， and clinical applications of ketamine and its enantiomers in depressive disorders， bipolar disorder， substance use disorders， post-traumatic stress disorder and obsessive-compulsive disorder. Despite ketamine's multifaceted therapeutic potential， safety concerns such as dissociation， cognitive impairment， and abuse liability warrant continued attention.［Funded by Key Project of Natural Science Research for Universities of Anhui Provincial Education Department （number， 2023AH050647）； Anhui Provincial Department of Education Outstanding Young Talent Support Program Project 2022 （number， gxyqZD2022022）］

Objective: human cysteine protease inhibitor S; helicobacter pylori antibody typing; human epidermal growth factor receptor 2 ; gastric cancer; pathological stage; gastric cancer lymph node metastasis Methods: A total of 150 gastric cancer patients admitted to Chaohu Hospital Affiliated to Anhui Medical University for surgery from December 2021 to December 2023 were selected as the study objects. Serum CST4 and HP antibody typing were performed before surgery, and HER2 expression levels in gastric cancer tissues were detected by immunohistochemistry after surgery. The clinicopathological data of gastric cancer patients with different serum CST4, HP antibody types and HER2 expression were compared and the correlation was analyzed. ROC curve was used to compare the predictive value of single and combined detection of serum CST4, HP antibody typing and HER2 expression in lymph node metastasis and TNM staging of gastric cancer. Results: Patients with CST4, HPI and HER2-positive expression had deeper tumor invasion and were more likely to develop distant lymph node metastasis, and TNM stages were more likely to occur in Ⅲ and Ⅳ stages(P<0.05). Meanwhile, patients with CST4 positive expression were more likely to have vascular and nerve invasion(P<0.05). In patients with HPI positive expression, tumors were more likely to occur in the cardia and the bottom of the stomach, and the tumor diameter was larger and vascular invasion was more likely(P<0.05), while HER2 was negatively correlated with the degree of tumor differentiation, and the tumors were more likely to occur in high and secondary differentiation(P<0.05). ROC curve analysis showed that the AUC of single and combined detection of serum CST4, HPI and HER2 expression to predict lymph node metastasis of gastric cancer were 0.780, 0.676, 0.611 and 0.872, respectively(P<0.05). The AUC for TNM stage diagnosis of gastric cancer were 0.762, 0.635, 0.613 and 0.801(P<0.05), respectively. The diagnostic efficiency of combined detection was higher than that of single detection. Conclusion The expression of CST4, HPI and HER2 in serum is closely related to the depth of tumor invasion, lymph node metastasis and TNM stage. The expression of CST4, HPI and HER2 in serum can be used as an important predictor of lymph node metastasis and TNM stage in gastric cancer patients, providing a new idea for clinical diagnosis.

BackgroundAssisted reproductive technology is increasingly mature and widely used in clinic. As more and more newborns are born with assisted reproductive technology， the health problems of these newborns also need more attention. ObjectiveTo investigate the effects of assisted reproductive technology on newborn physique and autistic behavior， and to raise the attention of autistic behavior of assisted reproductive children. MethodsFrom the medical record information system， 588 assisted reproduction newborns （assisted reproduction group） born in the obstetrics department of Chaohu Hospital of Anhui Medical University from August 2018 to August 2019 were selected as the study objects. From the medical records information system， 600 newborns born naturally in the obstetrics department in the same period of time were selected as the control group. The basic information of all newborns was collected， including the mother's age and years of education， sex， gestational age， birth weight and birth length， and they were assessed by the Clancy Autism Behavior Scale （CABS） at 3 years of follow-up. ResultsThe educational years of mothers in assisted reproduction group were longer than those in control group ［（12.04±1.96） years vs. （11.34±2.90） years， t=-4.887， P<0.01］， gestational age and birth weight of assisted reproduction group were lower than those of control group ［（38.68±2.56） weeks vs. （39.53±2.91） weeks， t=5.315， P<0.01； （3 273.27±720.39） g vs. （3 158.29±701.74） g， t=2.792， P<0.05］. There was no significant difference in birth length between the two groups ［（49.97±5.94） cm vs. （50.07±6.08） cm， t=-0.287， P>0.05］. At the age of three， the weight and height of the assisted reproduction group were both lower than those of the control group ［（16.16±2.53）kg vs.（16.96±1.67）kg， t=6.393， P<0.01， （95.81±4.50）cm vs.（97.47±7.49）cm， t=4.626， P<0.01］. Respectively， 6 （1.00%） and 15 （2.55%） children with autism were detected in the control group and assisted reproduction group， and the difference was statistically significant （χ²=4.113， P<0.05）. ConclusionAssisted reproductive technology may affect the physical and neurological development of children. ［Funded by Outstanding Young Talents Support Program of Anhui Education Department （number， gxyqZD2022022）］

ObjectiveTo systematically review the effect of high-intensity interval training (HIIT) on executive function for healthy children and adolescents, and delineate the factors related to the intervention outcome. MethodsLiterature about the effect of HIIT on executive functions for healthy children and adolescent was retrieved from Web of Science, PubMed, Cochrane, Embase, Google Scholar, and CNKI, up to July 31st, 2023. The methodological quality was evaluated using the Physiotherapy Evidence Database (PEDro) scale, and relevant data were systematically reviewed. ResultsFifteen researches were included, from nine countries, comprising 13 randomized controlled trials with the scores of PEDro scale from five to eight, involving 17 021 participants aged six to 18 years. They were published mainly from 2016 to 2023. The primary factors related to the intervention outcome were the age of participants, HIIT intervention programs, and work-to-rest ratio. HIIT significantly improved working memory and inhibitory control in healthy children, while it was limited for adolescents. ConclusionHIIT can significantly improve inhibitory control and working memory in healthy children. Key factors related to the intervention outcomes include the age of participants and the specifics of the HIIT program, etc.

OBJECTIVE To explore the relationship between the ANKK1 rs1800497 polymorphism and atypical antipsychotic drug-induced metabolic syndrome （MS）. METHODS Totally 94 patients with schizophrenia were included， and ANKK1 rs1800497 genotypes of patients were detected by micro-fluorescence immunoassay； social demographic information， clinical characteristics and other data were collected. The χ2 test was used to compare the correlation between the sex of patients and the occurrence of MS， and the correlation between gene polymorphism and the occurrence of MS and its risk factors.RESULTS Totally 94 patients included 24 cases （25.53%） of GG， 51 cases （54.26%） of GA and 19 cases of AA （20.21%）. Among them， there were 45 cases （47.87%） of MS， and the incidence of MS in male was higher than that in female （P＜0.05）. Genotype analysis showed that ANKK1 rs1800497 polymorphism was not associated with MS （P＝0.452）. ANKK1 rs1800497 A allele was significantly associated with hyperglycemia （χ2＝4.379， P＝0.036）， while it was not related to abdominal obesity， hypertension， high level of TG and low level of HDL-C （P＞0.05）， suggesting that for patients with schizophrenia， allele A was a relative risk factor for inducing hyperglycemia [OR＝2.008，95%CI（1.039， 3.881）]. CONCLUSIONS ANKK1 rs1800497 polymorphism has no correlation with the induction of MS by atypical antipsychotics， while the schizophrenia patients with A allele are more likely to induce hyperglycemia. The incidence of MS in male patients is significantly higher than that in female patients.

Objective: To investigate the status of insomnia, Internet addiction, and depressive symptoms among medical students and to analyze the effect of Internet addiction on insomnia and the mediating role of depressive symptoms, in order to provide a basis for the development of targeted interventions and measurements for medical students. Methods: A stratified whole group sampling method was used to select full-time college students from three medical universities in Anhui Province. The Chinese version of Insomnia Severity Index (ISI), Internet Addiction Test (IAT) scale and 9-item Patient Health Questionnaire (PHQ-9) were used to evaluate the symptoms of insomnia, Internet addiction and depressive in students. A multivariate Logistic regression analysis was used to explore the factors influencing insomnia among medical students and to analyze the relationship between insomnia with Internet addiction and depressive symptoms, respectively. Results: The overall rate of Internet addiction was 49.5%, depressive symptoms was 39.5%, insomnia was 18.6%. High academic stress, and the presence of surrounding people diagnosed with COVID-19 were associated with a higher risk of insomnia ( P <0.05). The higher the level of Internet addiction (mild, OR =2.60; moderate/severe, OR =4.21) and depression. (mild, OR =6.35; moderate/severe, OR =19.32), the higher the risk of insomnia. Mediated effect analysis showed that Internet addiction had a direct predictive effect ( β =0.02, P <0.05) on insomnia and also indirectly affected insomnia through depression (indirect effect=0.07，95% CI =0.06-0.08). Conclusion The detected rates of insomnia, Internet addiction and depressive symptoms are high among medical students in Anhui Province, and Internet addiction and depressive symptoms are risk factors for insomnia, which should be given more attention and appropriate interventions when necessary to improve their physical and mental health.

Objective: Excessive daytime sleepiness (EDS) and insomnia symptoms are common in patients with major depressive disorder (MDD), which might lead to a poor prognosis and an increased risk of depression relapse. The current study aimed to investigate the prevalence, and sociodemographic and clinical correlates of EDS and insomnia symptoms among adolescents with MDD. Methods: The sample of this cross-sectional study included 297 adolescents (mean age=15.26 years; range=12–18 years; 218 females) with MDD recruited from three general and four psychiatric hospitals in five cities (Hefei, Bengbu, Fuyang, Suzhou, and Ma’anshan) in Anhui Province, China between January and August, 2021. EDS and insomnia symptoms, and clinical severity of depressive symptoms were assessed using Epworth sleepiness scale, Insomnia Severity Index, and Clinical Global Impression-Severity. Results: The prevalence of EDS and insomnia symptoms in adolescents with MDD was 39.7% and 38.0%, respectively. Binary logistic regression analyses showed that EDS symptoms were significantly associated with higher body mass index (odds ratio [OR]=1.097, 95% confidence interval [CI]=1.027–1.172), more severe depressive symptoms (OR=1.313, 95% CI=1.028–1.679), and selective serotonin reuptake inhibitors use (OR=2.078, 95% CI=1.199–3.601). And insomnia symptoms were positively associated with female sex (OR=1.955, 95% CI=1.052–3.633), suicide attempts (OR=1.765, 95% CI=1.037–3.005), more severe depressive symptoms (OR=2.031, 95% CI=1.523–2.709), and negatively associated with antipsychotics use (OR=0.433, 95% CI=0.196–0.952). Conclusion EDS and insomnia symptoms are common among adolescents with MDD. Considering their negative effects on the clinical prognosis, regular screening and clinical managements should be developed for this patient population.

Objective : The differences of cognitive impairment between children with attention deficit hyperactivity disorder (ADHD) and normal children were compared , the influencing factors of cognitive impairment of children with ADHD were analyzed . Methods : A total of 133 children with ADHD were selected as the ADHD group , and 117 normal children were recruited as the control group . The severity of the subjects ′ clinical symptoms was assessed using the Swanson , Nolan , & Pelham Rating Scale⁃Fourth Edition ( SNAP⁃IV) and the Weiss Functional Impairment Rating Scale . The degree of cognitive functional impairment of subjects was assessed using the MATRICS cognitive suite (MCBB) , and the executive function impairment of the subjects was assessed by the Behavior Rating Inventory of Executive Function ( BRIEF) . The differences in cognitive functional impairment of the two groups were compared . The children with ADHD were further divided into three groups according to their clinical phenotype and age , respectively , and the differences of cognitive impairment among the three groups were compared . The influencing factors of the degree of cognitive impairment in children with ADHD were analyzed by multiple linear regression . The improvement of methylphenidate sustained⁃release tablets on cognitive and executive functional impairment in children with ADHD was observed . Results : The scores of SNAP⁃IV , Weiss Functional Impairment Rating Scale , connection test and BRIEF of ADHD patients were significantly higher than those of normal controls (P < 0. 05) . The scores of symbol coding test and maze test of ADHD patients were significantly lower than those of normal controls (P < 0. 05) . The score of symbol encoding test in children with ADHD⁃HI was significantly higher than that in ADHD⁃I and ADHD⁃C groups (P < 0. 05) , and the total BRIEF score of ADHD⁃C was significantly higher than that in ADHD⁃I and ADHD⁃HI groups (P < 0. 05) . With the increase of age , the score of connection test of ADHD children gradually decreased , while the scores of symbol coding test and maze test gradually increased (P < 0. 05) . The results of multiple linear regression analysis showed that age was the influencing factor of ADHD children ′s score in the connection test , symbol coding test and maze test (P < 0. 05) ; the scores of SNAP⁃IV and Weiss Functional Impairment Rating Scale were the influencing factors of BRIEF score of ADHD children (P < 0. 05) . After methylphenidate treatment , the scores of connection testand BRIEF significantly decreased (P < 0. 001) , while the scores of symbol coding test and maze test significantly increased (P < 0. 001) . Conclusion The younger the age and the more serious the clinical symptoms related to ADHD suggest that the cognitive impairment of children with ADHD is more serious . After methylphenidate treatment , the degree of cognitive and executive impairment in children with ADHD are improved .

Aim To investigate the effect of esketamine(ESK)on lipopolysaccharide(LPS)-induced damage to HT22 cells(mouse hippocampal neuron cells)and the underlying mechanism. Methods After ESK pretreatment for 2 h and then LPS treatment for 24 h, Western blot was used to detect high mobility group box-1(HMGB1), long chain acyl CoA synthetase 4(ACSL4), prostaglandin-endoperoxide synthase 2(PTGS2), transferrin receptor 1(TFR1), ferroportin(FPN)and ferritin expression. ELISA was used to detect the expression of inflammatory protein interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α). DHE fluorescent was probed to detect the changes in intracellular reactive oxygen species(ROS). MDA kit was used to detect intracellular lipid oxidation levels. FerroOrange fluorescent was probed to detect intracellular divalent iron ion levels. Electron microscopy was used to observe the changes in mitochondrial ultrastructure. Results Compared with the normal group, the levels of ROS, lipid peroxidation and Fe

Objective: To investigate the effects of embryonic inflammation on the hippocampal synaptosomal-associated protein 25(SNAP-25) level and cognitive function in middle-aged. Methods: During gestational days 15-17, the CD-1 maternal mice received a daily intraperitoneal injection of lipopolysaccharides(LPS, 50 μg/kg) or the equal volume of normal saline, and the corresponding offspring were regarded as LPS group and CON group respectively. At the age of young(3-month-old) and middle-aged(15-month-old), the spatial learning and memory ability was assessed using Morris water maze(MWM), and the expression of hippocampal SNAP-25 protein was detected by immunohistochemical method and Western blot. Results: Compared with the 3-month CON group, the 15-month CON group had longer swimming distance(P<0.01), lower swimming distance percentage(P<0.01) in the target quadrant, and higher hippocampal subregions(CA1, CA3, DG) SNAP-25 levels(P<0.01). The same results were obtained in 15-month LPS group compared with 15-month CON group in learning and memory phase(P<0.05), and higher hippocampal subregions(CA1, DG) SNAP-25 levels(P<0.01). Pearson correlation analysis indicated that the hippocampal CA1 and CA3 subregions SNAP-25 level was positively correlated with the swimming distance, but negatively correlated with the percentage of swimming distance in the target quadrant. Conclusion Embryonic inflammation can accelerate the impairment of spatial learning and memory and the increase of hippocampal CA1 and CA3 subregions SNAP-25 protein in middle-aged CD-1 mice, and there may be a correlation between them.