Objective:To explore the effects of intrahippocampal injection of ferroptosis inducer Erastin on depressive- and anxiety-like behavior and the expression of ferroptosis-related proteins in rats.Methods:Forty 6-week-old healthy male Sprague-Dawley rats were randomly divided into five groups ( n=8/group): Control group, Erastin low-dose(200 ng/μL) group, Erastin medium-dose(400 ng/μL) group, Erastin high-dose group(600 ng/μL) and lipopolysaccharide (LPS, 10 μg/L) group.After the intrahippocampal injection of Erastin(2.5 μL per side), body weight, and behavioral tests, including sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and elevated plus maze (EPM), were performed to evaluate depressive- and anxiety-like phenotypes from the fourth day after injection.The levels of ferroptosis-related proteins and mRNA, including glutathione peroxidase 4 (GPX4), cyclo-oxygenase 2 (COX2), ferritin heavy polypeptide 1 (FTH1), long-chain fatty acyl-CoA synthetase 4 (ACSL4), solute carrier family 7 member 11 (SLC7A11) were measured using real-time quantitative PCR and Western blot analysis.SPSS 22.0 software was used for statistical analysis.One-Way ANOVA was used for multi-group comparison, and LSD was used for further pound-wise comparison. Results:(1)Body weight and behavioral tests: there were no statistically significant differences in baseline body weight and behavioral tests in these groups ( F=0.02-1.15, all P>0.05). After intrahippocampal injection, compared with the control group, medium-dose Erastin induced depression-like behaviors in rats more significantly, as indicated by reduced bodyweight ((245.20±5.24)g, (267.45±13.16)), sucrose preference in SPT ((32.14±8.51)%, (68.17±13.67)%), central time in OFT ((6.01±2.57)s, (16.49±7.21)s), percentage of time in open arm in EPM ((5.00±3.83)%, (19.63±5.91)%) and increased immobility time in FST ((37.00±7.58)s, (12.50±5.51)s) and percentage of time in closed arm in EPM ((89.43±4.77)%, (59.96±9.91)%), and there were statistically significant differences in these groups (all P<0.05). (2)The expression of ferroptosis-related indicators: after intrahippocampal injection, the expression of mRNA ( F=2.23, 8.37, 2.91, 7.60, 3.16, all P<0.05) and protein ( F=3.31, 40.13, 8.52, 3.70, 70.79, all P<0.05) of FTH1, GPX4, SLC7A11, COX2 and ACSL4 in hippocampus were statistically significant differences in the 5 groups.The mRNA and protein levels of FTH1, GPX4 and SLC7A11 in Erastin medium-dose group were lower than those in the control group (all P<0.05), while the mRNA and protein levels of COX2 and ACSL4 were higher than those in the control group (all P<0.05). Conclusion:Intrahippocampal microinjection of Erastin(400 ng/μL) can induce ferroptosis in hippocampus of rats and can also induce depressive-like behaviors in rats.

Depression is a common psychiatric disorder characterized by low mood with complex pathophysiological mechanisms and poor effect of pharmacological treatment.The animals were placed in greater sensory, physical and/or social stimuli than those of the standard feeding environment, so that they can obtain positive plasticity and adaptability.Environmental enrichment(EE) is a common intervention to improve brain function in laboratory.A large number of studies have shown that EE had significant ameliorative effects on various animal models of depression, but the mechanisms have not been yet fully understood with outcome heterogeneity in ethology.There was no universally accepted and unified paradigm and standard for EE due to its multi-dimensionality and complexity.Therefore, it is necessary to improve the structural components and implementation steps of EE by integrating the existing data.Combined with recent studies on animal models of depression, this paper reviewed the anti-depression mechanism of EE from promoting hippocampal neurogenesis, reducing neuroinflammation, regulating neuroendocrine and affecting epigenetic modifications, in order to provide new ideas for mechanisms research and treatment of depression.As the rise of precision medicine and individualized medicine brings human growing interest in exploring the sources and mechanisms of inter-individual differences and intra-group effects of depression, it will be a challenge to translate EE to the human society in a rational way.

Objective To investigate the efficacy and safety of capecitabine in the treatment of colorectal cancer. Methods Totally 160 elderly patients with stageⅣcolorectal cancer were enrolled in this study. After first-line combined chemotherapy,80 patients were treated with capecitabine monotherapy(maintenance group)and another 80 cases were not(control group). The survival rate was analyzed by Kaplan-Meier curve and the efficiency and incidence of adverse events were compared. Results (1) The Kaplan-Meier curve suggested that the difference between two groups was statistically significant(P<0.05).(2)The response rate of maintenance group was significantly higher than that of control group (P < 0.05). (3)The incidence of adverse events during capecitabine monotherapy was lower than that during combined chemotherapy(P < 0.05).(4)The incidence of adverse reactions during capecitabine monotherapy was similar to that of control group(P > 0.05). Conclusion Capecitabine monotherapy in patients with stage Ⅳ colorectal cancer after combined chemotherapy has a longer median PFS than those without maintenance but similar adverse reactions ,which was worthy of clinical promotion.

As a common psychiatric disorder, the etiology and pathogenesis of depression are complex and not yet fully elucidated.The diagnosis of depression mainly depends on the patients’ medical history, clinical symptoms and related examinations.Identification of biomarkers will provide important clues for the specific diagnosis and targeted treatment of depression.In addition to the widely recognized neurotransmitter dysregulation, hypothalamus-pituitary-adrenal axis hyperactivity, neuroplasticity, and neuro-inflammation theory, oxidative stress is also involved in the pathogenesis of depression in multiple ways.Many studies showed that the heat shock protein 70(HSP70)levels will increase in early stage to cope with the stress in patients with depression.However, lower HSP70 levels are often correlated with more severe depressive symptoms.HSP70 may be involved in depression through multiple pathways of oxidative stress, glucocorticoid receptors, neuroinflammation and neuroplasticity.Furthermore, increasing HSP70 expression results in significant improvement in depression-like behavior in animals.Thus, HSP70 possesses potential value as an early warning marker for depression as well as a therapeutic target.

Objective:To observe the effect of combining robot-assisted gait training (RAGT) with task-oriented training (TOT) on the walking ability of children with dyskinetic cerebral palsy (DCP).Methods:Sixty DCP children were randomly divided into a conventional intervention group, an RAGT group, and a combined intervention group, each of 20. All of the children received conventional rehabilitation therapy, while the RAGT and combined intervention groups were additionally provided with RAGT, and RAGT combined with TOT, respectively. Before the experiment and after 12 and 24 weeks of treatment, the subjects′ walking ability was evaluated using the 10-metre walk test (10MWT), and the D energy zone (standing position) and the E energy zone (walking, running and jumping) of the Gross Motor Function Measurement-88 (GMFM-88) instrument.Results:After 12 and 24 weeks of treatment, the average 10MWT speed and D and E energy zone scores of all three groups had improved significantly. After 24 weeks the combined group′s averages on all three measures were significantly better than those of the other two groups.Conclusion:RAGT combined with TOT and conventional rehabilitation training significantly improves the walking ability of DCP children.

Objective To investigate the mechanism mediating the regulatory effect of lncRNA MAGI2-AS3 on cisplatin(DDP)resistance in non-small cell lung cancer(NSCLC).Methods MAGI2-AS3 and miR-1269a expression levels were detected by qRT-PCR in DDP-sensitive lung cancer cell lines(A549 and H1299)and their resistant counterparts(A549/DDP and H1299/DDP).In A549 and H1299 cells with MAGI2-AS3 silencing and A549/DDP and H1299/DDP cells overexpressing MAGI2-AS3,the effects of 20 μmol/L DDP on cell viability and apoptosis were examined with CCK-8 assay,colony formation assay,flow cytometry and Western blotting,and the changes in epithelial-mesenchymal transition(EMT)were assessed with wound healing and Transwell assays.The interaction between MAGI2-AS3,miR-1269a and PTEN was predicted using GEPIA,StarBase and miRDB and verified with luciferase reporter gene assay and radioimmunoprecipitation(RIP)assay.A miR-1269a mimic and pcDNA3.1-PTEN plasmid were used to perform the rescue assay.Results MAGI2-AS3 expression was significantly downregulated in lung cancer tissues(P<0.05)in association with a poor prognosis(P<0.05).In the two DDP-resistant lung cancer cell lines,MAGI2-AS3 expression was significantly lowered as compared with the sensitive cells.Silencing MAGI2-AS3 significantly enhanced cell viability and promoted EMT of A549 and H1299 cells irrespective of DDP treatment,and also decreased DDP-induced apoptosis of the cells.In A549/DDP and H1299/DDP cells,MAGI2-AS3 overexpression strongly repressed cell viability and EMT irrespective of DDP treatment and promoted DDP-induced cell apoptosis.Luciferase reporter gene and RIP assays confirmed the binding of MAGI2-AS3 with miR-1269a and the binding of miR-1269a with 3'-UTR domain of PTEN.The rescue assay demonstrated that MAGI2-AS3 acted as a sponge for miR-1269a to promote PTEN expression and downregulate AKT phosphorylation,thus inhibiting EMT and promoting DDP-induced apoptosis of A549/DDP cells.Conclusion MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.

Objective To investigate the mechanism mediating the regulatory effect of lncRNA MAGI2-AS3 on cisplatin(DDP)resistance in non-small cell lung cancer(NSCLC).Methods MAGI2-AS3 and miR-1269a expression levels were detected by qRT-PCR in DDP-sensitive lung cancer cell lines(A549 and H1299)and their resistant counterparts(A549/DDP and H1299/DDP).In A549 and H1299 cells with MAGI2-AS3 silencing and A549/DDP and H1299/DDP cells overexpressing MAGI2-AS3,the effects of 20 μmol/L DDP on cell viability and apoptosis were examined with CCK-8 assay,colony formation assay,flow cytometry and Western blotting,and the changes in epithelial-mesenchymal transition(EMT)were assessed with wound healing and Transwell assays.The interaction between MAGI2-AS3,miR-1269a and PTEN was predicted using GEPIA,StarBase and miRDB and verified with luciferase reporter gene assay and radioimmunoprecipitation(RIP)assay.A miR-1269a mimic and pcDNA3.1-PTEN plasmid were used to perform the rescue assay.Results MAGI2-AS3 expression was significantly downregulated in lung cancer tissues(P<0.05)in association with a poor prognosis(P<0.05).In the two DDP-resistant lung cancer cell lines,MAGI2-AS3 expression was significantly lowered as compared with the sensitive cells.Silencing MAGI2-AS3 significantly enhanced cell viability and promoted EMT of A549 and H1299 cells irrespective of DDP treatment,and also decreased DDP-induced apoptosis of the cells.In A549/DDP and H1299/DDP cells,MAGI2-AS3 overexpression strongly repressed cell viability and EMT irrespective of DDP treatment and promoted DDP-induced cell apoptosis.Luciferase reporter gene and RIP assays confirmed the binding of MAGI2-AS3 with miR-1269a and the binding of miR-1269a with 3'-UTR domain of PTEN.The rescue assay demonstrated that MAGI2-AS3 acted as a sponge for miR-1269a to promote PTEN expression and downregulate AKT phosphorylation,thus inhibiting EMT and promoting DDP-induced apoptosis of A549/DDP cells.Conclusion MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.