Nowadays the pathogenesis of early-onset depression is still uncertain. Only SSRIs are currently approved for clinical use as antidepressants in children and adolescents, indicating that 5-HT is the most important neurotransmitter involved in the dis-ease. Current studies with regard to central 5-HTergic system in early-onset depression mainly focus on 5-HT synthesis deficien-cy, 5-HT transportation dysregulation, as well as the earlier mat-uration of 5-HT system than norepinephrine system. 5-HT precur-sor tryptophan malabsorption and dysregulation of 5-HT synthesis can contribute to 5-HT deficiency. Moreover, the 5-HTTLPR low-expressing genotypes may increase the risk of early-onset de-pression. It is necessary to make preclinical and clinical studies more widely and deeply about the effect of central 5-HTergic sys-tem in early-onset depression in future.

Objective To observe the effects of kidney-tonifying therapy on spatial learning, memory abilities and ultrastructure of hippocampal dentate gyrus ( DG ) cells of kidney deficiency rats induced by sexual intemperance. Methods SD rats with low reproductive capacity were caused by continuously mating for 6 months, and then were randomly divided into 5 groups, namely model group, low- and high-dose of Liuwei Dihuang pills (LDP) groups (in the dosage of 4.8, 9.6 g·kg-1·d-1), low-and high-dose of Jingui Shenqi pills (JSP) group (in the dosage of 5.2, 10.4 g·kg-1·d-1), 8 rats in each group. Except the model group, the other groups were respectively given with the corresponding medication. SD rats aged 2 months served as the normal control group. After treatment for 30 continuous days, the learning and memory abilities of rats were examined by Morris Water Maze. The cell ultra structure of hippocampal dentate gyrus was observed by transmission electron microscopy. Results The results of the place navigation test of Morris water maze showed that the escape latency of rats was prolonged obviously in the model group compared with that of the normal control group (P<0.01), and the escape latency of rats in the medication groups was shorter than the kidney deficiency model group (P<0.05 or P<0.01). The results of spatial probe test showed that the residence time in the former hidden platform quadrant and its surrounding area was significantly shortened in the model group compared with that of the normal control group ( P<0.01) , but was prolonged after medication of high-dose JSP ( P<0.05 or P<0.01 compared with that of the model group). Under the electron microscope, the cell ultra structure lesions of hippocampal dentate gyrus were much relieved in the high-dose LDP group, and high-dose JSP group as compared with those of the model group. Conclusion ( 1) Long-term sexual intemperance can impair spatial learning and memory abilities and causes the cell ultra structure lesions of hippocampal dentate gyrus of rats. (2) The kidney-tonifying therapy can significantly alleviate the spatial learning and memory disturbance and the cell ultra structure lesions of hippocampal dentate gyrus induced by sexual intemperance. ( 3) There are not significant differences between the two kidney-tonifying therapies in improving spatial learning and relieving cell ultra structure lesions. The effect of JSP on improving spatial memory abilities is better than that of LDP.

Objective We aimed to establish and evaluate a rat model of post-infectious irritable bowel syndrome(PI-IBS)with the pattern of liver depression and spleen deficiency coupled with dampness.Methods First,200 rats were randomly divided into the normal group,the infection group,the infection+stress group,the infection+stress+external dampness group,and the acetic acid+stress group(n=40 rats per group)for eight weeks.The rats were treated with Trichinella spiralis infection,chronic restraint stress,an artificial high-humidity climate,and/or acetic acid enema.Weight growth rate,24-hour food intake and water intake,and the fecal moisture percentage were recorded.The open field test and the sucrose consumption test were used to determine the behavioral characteristics of rats in each group.The abdominal withdrawal reflex(AWR)test was used to determine visceral sensitivity.The contents of 5-hydroxytryptamine(5-HT)and aquaporin 4(AQP4)in colon tissue were detected by ELISA.Results Compared with the normal group,the weight growth rate of rats in the infection+stress+external dampness group and the acetic acid+stress group was lower from Week 1 to Week 8 of modeling.The 24-hour food intake of rats in the infection+stress+external dampness group and the infection+stress group was lower than that in the normal group from Week 2 to Week 8 of modeling.At the end of week 2 of modeling,the 24-hour water intake of rats in the infection+stress+external dampness group,the acetic acid+stress group,and the infection+stress group was lower than that in the normal group.The fecal moisture percentage of rats in the infection+stress+external dampness group was higher than that in the normal group at the end of Week 1,6,and 8(P＜0.05).At the end of Week 4 of modeling,the total distance in the open field test in the infection+stress+external dampness group and the acetic acid+stress group was shorter than that in the normal group.The sugar preference rate in the infection+stress+external dampness group was lower than that in the normal group at the end of 1,4,and 8 weeks and lower than that in the acetic acid+stress group at the end of Week 4 and 8(P＜0.05).The AWR scores of rats in the infection+stress+external dampness group were higher than those in the normal group after week 1 at 60 and 80 mmHg(1 mmHg≈0.133 kPa),after Week 4 at 40,60,and 80 mmHg,and after Week 6 and 8 at 20,40,and 80 mmHg(P＜0.05).At the end of Week 2 and 4,a large number of inflammatory cells were infiltrated in the colonic mucosa of the intervention groups,and the inflammation score was higher than that of the normal group(P＜0.05).At the end of weeks 6 and 8,the inflammatory cell infiltration in the intestinal mucosa of the intervention groups was not obvious,and the colonic mucosa returned to normal.At the end of weeks 6 and 8,the 5-HT content was higher in the infection+stress group,the infection+stress+external dampness group,and the acetic acid+stress group than in the normal group(P＜0.05).After Week 4,the AQP4 content was lower in the infection+stress+external dampness group and the acetic acid+stress group than that in the normal group(P＜0.05).After week 6,compared to the normal group,the AQP4 content was lower in all groups except for the acetic acid+stress group,and the AQP4 content in the infection+stress+external dampness group was lower than that in the acetic acid+stress group.After week 8,only in the infection+stress+external dampness group the AQP4 content was lower than in the normal group(P＜0.05).Conclusion The combination of Trichinella spiralis infection,chronic restraint stress,and an artificial high-humidity climate can be used to prepare a relatively stable and reliable rat model of PI-IBS with the pattern of liver depression and spleen deficiency with dampness.

AIM:To establish and evaluate a colonoids model of intestinal barrier dysfunction with irritable bowel syndrome(IBS).METHODS:The colonic recess of 20～22 g male C57BL/6 mice were isolated and cultured in ma-trix glue to proliferate and differentiate into 3D hollow spheres with colonic epithelioid structure.The following experi-ments were carried out:(1)Colonoids and colonic tissues of mice were detected by immunofluorescence to identify colo-noids.(2)Fluorescein isothiocyanate dextran 4(FD4)evaluated the epithelial barrier function of colonoids.(3)To ex-plore the changes in the epithelial barrier of colonoids induced by interferon-γ(IFN-γ)at different concentrations and time points.FD4 and HE staining were used to evaluate the barrier function.RT-qPCR was used to detect the mRNA expres-sion of occludin and zonula occludens-1(ZO-1)in tight junctions of colonoids.Immunofluorescence was used to detect the distribution and localization of occludin and ZO-1 proteins.RESULTS:(1)The expression of EdU proliferation and in-testinal epithelial cell lineage markers in colonoids was consistent with that in mouse colonic tissues.(2)In the control group,FD4 did not infiltrate the colonoids lumen,but FD4 significantly infiltrated the colonoids lumen induced by ethyl-ene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid(EGTA).(3)From 18 h,the IFN-γ at 60,100,200 and 240 ng/mL could significantly infiltrate into the cavity of colonoids(0.033,0.032,0.042 and 0.001),and the barri-er injury of colonoids could be seen by HE staining.After 18 h,all concentrations of IFN-γ could significantly decrease the mRNA expression of occludin and ZO-1,and the fluorescence of occludin and ZO-1 decreased significantly(P<0.05).CONCLUSION:(1)The cultured organoids are colonoids with complete epithelial barrier.(2)IFN-γ could in-duce the decrease of the transcriptional levels of occludin and ZO-1 in the tight junction of colonoids,the decrease of the expression of corresponding proteins,and the change of localization and distribution,thus increasing the epithelial perme-ability of colonoids.This model is highly consistent with the pathophysiological state of IBS colonic mucosal barrier dys-function,which provides a new tool and method for studying the direction of colonic mucosal barrier dysfunction in IBS.