Objective To investigate the effect of methamphetamine(METH)on production of cytokines in RAW264.7 cells stimulated by lipopolysaccharide(LPS)and to explore the possible mechanism.Methods To study the effect of METH on the production of cytokines by LPS-stimulated RAW264.7 cells,the cells were divided into five groups:blank control group,LPS stimulation group,and three METH intervention groups at different concentrations(20,100,and 200 μmol/L),which were METH/LPS groups.To study the role of the dopamine D3 receptor(D3R)in the process,the D3R antagonist NGB2904 was used,and there were five groups:blank control group,LPS stimulation group,METH/LPS group,NGB2904/LPS group,and NGB2904/METH/LPS group.Cell viability was determined using the MTT assay.The levels of IL-6,IL-10,and TNF-α in the supernatants were determined using ELISA.The expressions of p-ERK1/2 and ERK1/2 were determined by Western blotting.Results Compared with the blank control group,the LPS stimulation group and the METH/LPS group had significantly increased cell viability,IL-6,IL-10,TNF-α,and ERK1/2 phosphorylation(P＜0.05).Compared with the LPS stimulation group,the METH/LPS group showed no obvious change in cell viability(P＞0.05),but significantly decreased levels of IL-6,IL-10,and ERK1/2 phosphorylation(P＜0.05).The inhibitory effect of METH showed a dose-dependent manner,with the highest inhibitory effect at METH 200 μmol/L.Furthermore,after the D3R antagonist was used,the results showed that compared with the LPS stimulation group,the cell activity was not significantly changed(P＞0.05),but the levels of IL-6,IL-10 and ERK1/2 phosphorylation were significantly decreased in the METH/LPS group and the NGB2904/LPS group(P＜0.05).Compared with the METH/LPS group or the NGB2904/LPS group,the levels of IL-6,IL-10 and ERK1/2 phosphorylation were further decreased in the NGB2904/METH/LPS group(P＜0.05).Conclusion METH might inhibit the phosphorylation of ERK1/2,thereby reducing the production of IL-6 and IL-10 in RAW264.7 cells stimulated by LPS.The immunosuppressive effect of METH is similar to the immune effect when D3R is antagonized.

Objective To investigate the effect of methamphetamine(METH)on production of cytokines in RAW264.7 cells stimulated by lipopolysaccharide(LPS)and to explore the possible mechanism.Methods To study the effect of METH on the production of cytokines by LPS-stimulated RAW264.7 cells,the cells were divided into five groups:blank control group,LPS stimulation group,and three METH intervention groups at different concentrations(20,100,and 200 μmol/L),which were METH/LPS groups.To study the role of the dopamine D3 receptor(D3R)in the process,the D3R antagonist NGB2904 was used,and there were five groups:blank control group,LPS stimulation group,METH/LPS group,NGB2904/LPS group,and NGB2904/METH/LPS group.Cell viability was determined using the MTT assay.The levels of IL-6,IL-10,and TNF-α in the supernatants were determined using ELISA.The expressions of p-ERK1/2 and ERK1/2 were determined by Western blotting.Results Compared with the blank control group,the LPS stimulation group and the METH/LPS group had significantly increased cell viability,IL-6,IL-10,TNF-α,and ERK1/2 phosphorylation(P＜0.05).Compared with the LPS stimulation group,the METH/LPS group showed no obvious change in cell viability(P＞0.05),but significantly decreased levels of IL-6,IL-10,and ERK1/2 phosphorylation(P＜0.05).The inhibitory effect of METH showed a dose-dependent manner,with the highest inhibitory effect at METH 200 μmol/L.Furthermore,after the D3R antagonist was used,the results showed that compared with the LPS stimulation group,the cell activity was not significantly changed(P＞0.05),but the levels of IL-6,IL-10 and ERK1/2 phosphorylation were significantly decreased in the METH/LPS group and the NGB2904/LPS group(P＜0.05).Compared with the METH/LPS group or the NGB2904/LPS group,the levels of IL-6,IL-10 and ERK1/2 phosphorylation were further decreased in the NGB2904/METH/LPS group(P＜0.05).Conclusion METH might inhibit the phosphorylation of ERK1/2,thereby reducing the production of IL-6 and IL-10 in RAW264.7 cells stimulated by LPS.The immunosuppressive effect of METH is similar to the immune effect when D3R is antagonized.

【Objective】 To investigate the role of dopamine D3 receptor deficiency in depression-like behavior in perimenopausal depression and to explore the role of dopamine D3 receptor in the pathogenesis of perimenopausal depression. 【Methods】 Based on the perimenopausal depression animal model， RT-PCR was used to study the changes of D3 receptor mRNA in the nucleus accumbens （NAc） in mice. Furthermore， dopamine D3 receptor knockout （D3RKO） mice and wild type （WT） mice of the same genetic background were used， respectively. Forced swim test （FST） and tail suspension test （TST） were used to assess depressive-like behavior in mice. 【Results】 D3 receptor mRNA in the NAc decreased significantly in perimenopause （P<0.05）. Chronic immobilization stress （CIS） induced the decrease of D3 receptor mRNA in young mice （P<0.05）. CIS induced a further decrease of D3 receptor mRNA in perimenopausal mice （P<0.05）. The immobility in the FST was significantly prolonged in perimenopausal D3RKO mice， compared with perimenopausal WT mice （P<0.05）. The immobility in both FST and TST was significantly prolonged in perimenopausal D3RKO mice， compared with young D3RKO mice （P<0.05）. No significant difference was found between the groups of the WT mice （P>0.05）. 【Conclusion】 Dopamine D3 receptor in the NAc is significantly decreased during perimenopause. Obvious decrease or deficiency of dopamine D3 receptors may be involved in the regulation of perimenopausal depression.

【Objective】 To explore the effect of Lactobacillus rhamnosus on postpartum depression （PPD） and its potential mechanism. 【Methods】 The mouse model of PPD was established by using dexamethasone sodium phosphate during pregnancy. At the end of adaptive feeding， 50 pregnant female mice were randomly divided into low-dose group （group Ⅰ）， high-dose group （Group Ⅱ）， positive control group （Group Ⅲ）， model control group （Group IV）， and blank control group （Group Ⅴ）. The mice in Group Ⅰ and Group II were given Lactobacillus rhamnosus 1×10⁷ and1×10⁸CFU（kg·d）. The mice in Group Ⅲ were given 1.8 mg /（kg·d） paroxetine， and the mice in Groups IV and V were given the same amount of normal saline for 4 weeks. The 24-hour food consumption test， open field test and sugar water consumption test were used to detect the behavior of mice in each group. The concentrations of 5-hydroxytryptamine （5-HT）， norepinephrine （NE）， and dopamine （DA） were determined by RP-HPLC. The changes in Enterococcus faecalis， Bifidobacterium， Lactobacillus and Escherichia coli in the cecum of mice were detected by Real-time fluorescence quantitative PCR （RT-qPCR）. 【Results】 Before modeling， there were no significant differences in food intake， weight change rate， open field moving distance and speed， and percentage of sugar consumption among the groups （P>0.05）. After modeling， there was no significant difference in food intake or weight change rate among the five groups， but the open field moving distance， moving speed and percentage of sugar preference were significantly reduced （P<0.05）. After intervention with Lactobacillus rhamnosus， compared with Group Ⅳ， the depression-like behavior in Group Ⅰ and Group Ⅱ mice was improved； the weight change rate， open field moving distance and speed， percentage of sugar preference， and monoamine neurotransmitter concentration in Group I and Group Ⅱ were significantly increased compared with those in Group Ⅳ （P<0.05）， while Enterococcus faecalis， Escherichia coli and lactobacillus were significantly decreased （P<0.05）， and Bifidobacterium had an upward trend， but without significant difference. There was no significant change in food intake. 【Conclusion】 Lactobacillus rhamnosus can improve the depression-like behavior， affect monoamine neurotransmitters in mice， and regulate intestinal flora， which provides a new direction for studies on postpartum depression.

Objective To explore the effect of psychosomatic therapy on pain management in patients with gynecological malignant tumor, and to provide theoretical basis for improving the quality of pain management. Methods A total of 156 patients with gynecological malignant tumors were selected and 75 cases from August to November in 2015 were as the control group and 75 cases from December 2015 to March 2016 were as the intervention group. The control group received routine care in the wards, and the intervention group received psychosomatic therapy based on relaxation, image guidance, music therapy and personalized psychological counseling on the basis of routine nursing. The pain evaluation indexes of the two groups were compared. Results The number of the mild, moderate and severe pain in the intervention group were 56, 19, and 0, respectively, and 37, 41 and 3 in the control group, respectively. The difference between the 2 groups was statistically significant (Z=5.751, P<0.05). The number of the invalid, mild, obvious, complete remission of patients with cancer pain in the intervention group were 8, 14, 25, 28, respectively, and 18, 27, 21, 15 in the control group, respectively. The difference between the 2 groups was statistically significant (Z=2.081, P<0.05). The influence degree of pain on sleep was (4.96 ± 1.26) points in the intervention group and (5.72 ± 1.32) points in the control group, the difference was statistically significant (t=3.638, P<0.05). The satisfaction degree of pain control was (3.39 ± 1.15) points in the intervention group and (2.94 ± 0.74) points in the control group, and the difference was statistically significant (t=2.931, P<0.05). In the intervention group, 81.33％ (61/75) of one drug controlled pain program was used, which was higher than 64.20％ (52/81) of the control group (χ2=5.727, P<0.05). Conclusions Psychosomatic therapy can effectively relieve the pain of patients with gynecologic malignant tumor, and has guiding significance for the management of patients with cancer pain.