BACKGROUND:Current research has shown that human umbilical cord mesenchymal stem cells and melatonin can both improve ovarian function.However,the protective effect and mechanism of human umbilical cord mesenchymal stem cells combined with melatonin on chemotherapy-induced premature ovarian insufficiency have not been reported.OBJECTIVE:To investigate the protective effect and mechanism of human umbilical cord mesenchymal stem cells combined with melatonin on chemotherapy-induced premature ovarian insufficiency.METHODS:Forty Wistar rats with normal estrous cycle were randomly divided into control group,model group,human umbilical cord mesenchymal stem cell group,melatonin group,and human umbilical cord mesenchymal stem cell+melatonin group,with 8 rats in each group.In addition to the control group,the rat model of premature ovarian insufficiency was constructed by intraperitoneal injection of cisplatin solution.The rats in the human umbilical cord mesenchymal stem cell group and the human umbilical cord mesenchymal stem cell+melatonin group were injected with 1×106 human umbilical cord mesenchymal stem cells in the tail vein at 1,6,and 11 days after modeling,respectively.The rats in the melatonin group and human umbilical cord mesenchymal stem cell+melatonin group were injected intraperitoneally with 10 mg/kg melatonin daily.The changes in body mass and estrous cycle of rats were monitored during treatment.After 14 days of treatment,ELISA was used to detect serum levels of estradiol,follicle stimulating hormone,luteinizing hormone,and anti Mullerian hormone.Ovarian index was calculated.Hematoxylin-eosin staining was performed to observe ovarian histological morphology.Ultrastructure of ovarian granulosa cells was observed by transmission electron microscopy.Western blot assay was conducted to detect the expression of PI3K/AKT/mTOR signaling pathway proteins and LC3 and P62 autophagy proteins in ovarian tissues.RESULTS AND CONCLUSION:(1)Compared with the control group,the body mass of rats in the model group decreased gradually,the estrous cycle was disturbed,and the ovarian index decreased significantly(P＜0.01).The levels of estradiol and anti-Mullerian hormone were decreased(P＜0.01),while the levels of follicle stimulating hormone and luteinizing hormone were increased(P＜0.01).The histological morphology and granulosa cell ultrastructure of ovary were seriously damaged.The protein expressions of p-PI3K/PI3K,p-AKT/AKT,p-mTOR/mTOR,and P62 were significantly decreased(P＜0.01),while the protein expressions of LC3Ⅱ/Ⅰ were significantly increased(P＜0.001).(2)Compared with the model group,the body mass of rats in all treatment groups recovered gradually,the estrous cycle of some rats returned to normal,and the ovarian index was significantly increased(P＜0.01);the levels of estradiol and anti-Mullerian hormone were increased(P＜0.05),while the levels of follicle stimulating hormone and luteinizing hormone were decreased(P＜0.05).The histological morphology and ultrastructure of ovary were significantly improved.The protein expressions of p-PI3K/PI3K,p-AKT/AKT,p-mTOR/mTOR,and P62 were significantly increased(P＜0.001),while the protein expression of LC3Ⅱ/Ⅰ was significantly decreased(P＜0.01).Human umbilical cord mesenchymal stem cell+melatonin group showed more significant improvement in the above indexes.The results suggest that human umbilical cord mesenchymal stem cells combined with melatonin may inhibit ovarian granulosa cell autophagy by upregulating PI3K/AKT/mTOR signaling pathway to treat premature ovarian insufficiency.

BACKGROUND:Current research has shown that human umbilical cord mesenchymal stem cells and melatonin can both improve ovarian function.However,the protective effect and mechanism of human umbilical cord mesenchymal stem cells combined with melatonin on chemotherapy-induced premature ovarian insufficiency have not been reported.OBJECTIVE:To investigate the protective effect and mechanism of human umbilical cord mesenchymal stem cells combined with melatonin on chemotherapy-induced premature ovarian insufficiency.METHODS:Forty Wistar rats with normal estrous cycle were randomly divided into control group,model group,human umbilical cord mesenchymal stem cell group,melatonin group,and human umbilical cord mesenchymal stem cell+melatonin group,with 8 rats in each group.In addition to the control group,the rat model of premature ovarian insufficiency was constructed by intraperitoneal injection of cisplatin solution.The rats in the human umbilical cord mesenchymal stem cell group and the human umbilical cord mesenchymal stem cell+melatonin group were injected with 1×106 human umbilical cord mesenchymal stem cells in the tail vein at 1,6,and 11 days after modeling,respectively.The rats in the melatonin group and human umbilical cord mesenchymal stem cell+melatonin group were injected intraperitoneally with 10 mg/kg melatonin daily.The changes in body mass and estrous cycle of rats were monitored during treatment.After 14 days of treatment,ELISA was used to detect serum levels of estradiol,follicle stimulating hormone,luteinizing hormone,and anti Mullerian hormone.Ovarian index was calculated.Hematoxylin-eosin staining was performed to observe ovarian histological morphology.Ultrastructure of ovarian granulosa cells was observed by transmission electron microscopy.Western blot assay was conducted to detect the expression of PI3K/AKT/mTOR signaling pathway proteins and LC3 and P62 autophagy proteins in ovarian tissues.RESULTS AND CONCLUSION:(1)Compared with the control group,the body mass of rats in the model group decreased gradually,the estrous cycle was disturbed,and the ovarian index decreased significantly(P＜0.01).The levels of estradiol and anti-Mullerian hormone were decreased(P＜0.01),while the levels of follicle stimulating hormone and luteinizing hormone were increased(P＜0.01).The histological morphology and granulosa cell ultrastructure of ovary were seriously damaged.The protein expressions of p-PI3K/PI3K,p-AKT/AKT,p-mTOR/mTOR,and P62 were significantly decreased(P＜0.01),while the protein expressions of LC3Ⅱ/Ⅰ were significantly increased(P＜0.001).(2)Compared with the model group,the body mass of rats in all treatment groups recovered gradually,the estrous cycle of some rats returned to normal,and the ovarian index was significantly increased(P＜0.01);the levels of estradiol and anti-Mullerian hormone were increased(P＜0.05),while the levels of follicle stimulating hormone and luteinizing hormone were decreased(P＜0.05).The histological morphology and ultrastructure of ovary were significantly improved.The protein expressions of p-PI3K/PI3K,p-AKT/AKT,p-mTOR/mTOR,and P62 were significantly increased(P＜0.001),while the protein expression of LC3Ⅱ/Ⅰ was significantly decreased(P＜0.01).Human umbilical cord mesenchymal stem cell+melatonin group showed more significant improvement in the above indexes.The results suggest that human umbilical cord mesenchymal stem cells combined with melatonin may inhibit ovarian granulosa cell autophagy by upregulating PI3K/AKT/mTOR signaling pathway to treat premature ovarian insufficiency.

Objective To compare the effect of nursing students acting as social volunteers to participate in gerontological nursing practice teaching with traditional practice teaching mode, and promote the reform of teaching mode in nursing practice. Methods Students of two classes from department of nursing, medical college of Wuhan University of Science and Technology were selected as research objects. In class one nursing students acted as social volunteers to participate in gerontological nursing practice teaching (the experimental group), In class two nursing students took practice in geriatric wards according to traditional practice mode(the control group). The practice effect was compared between two groups. Results The average final grade of the experimental group was 86.50, and 78.51 in the control group. Ridit analysis revealed that, setting class one as the experimental group, R=0.796 8,95% confidence interval was 0.715 1-0.878 4, in the control group, R =0.500 0. The investigation showed that the experimental group and the control group were different in moral elevation aspect, teaching level, capability improving aspect and employment promotion aspect, the difference was significant (P<0.01). Conclusions The mode of nursing students acting as social volunteers to participate in gerontological nursing practice teaching has advantage over traditional practice teaching, and it can gain satisfying teaching effect.

BACKGROUND:Buyang HuanwuDecoction is commonly used in clinical medicine in treatment of intracerebral hemorrhage. Previous studies have been found that it has excelent neuroprotective effect, can efficiently inhibit the apoptosis of nervecels. Autophagic activity is closely related to apoptosis of nerve cels. CXCR4-PI3K autophagy signaling pathway has been verified in clinic. However, the effect of Buyang HuanwuDecoction is poorly understood. There is no study on Beclin-1 in the neuroprotective studies ofBuyang HuanwuDecoction.
OBJECTIVE:To explore the effects ofBuyang HuanwuDecoction on CXCR4-PI3K autophagy signaling pathway and Beclin-1 in rats with cerebral hemorrhage and related mechanisms.
METHODS:According to Rosenberg method, a rat model of cerebral hemorrhage was replicated and intragastricaly administeredBuyang HuanwuDecoction. Western blot assay was used to measure Beclin-1 protein. Immunohistochemical method was utilized to detect the expression of PI3K, AKT, stromal cel derived factor 1 and CXCR-4 protein. TUNEL assay was applied to identify apoptosis.
RESULTS AND CONCLUSION:(1) After administration,Buyang HuanwuDecoction could reduce the number of neuronal apoptosis in rats with intracerebral hemorrhage, up-regulate the expression of Beclin-1, PI3K, AKT, stromal cel derived factor 1, and CXCR-4 protein, and exert neuroprotective effect. (2)Buyang HuanwuDecoction could activate CXCR4-PI3K autophagy signal transduction pathway, both to stimulate autophagy and to regulate autophagy state, can inhibit apoptosis, and exert cerebral protective effect.