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Objective To explore the effects of chronic stress and stress cessation on hypothalamic appetite regulators in mice,and to explore the stress-dependent mechanism of appetite change.Methods A total of 32 male C57BL/6 mice were randomly divided into control(Ctrl)group(n=16)and chronic unpredictable mild stress(CUMS)group(n=16).The mice in the CUMS group were given CUMS to establish the stress model,and those in the Ctrl group were fed normally.The food intake and weight of mice were recorded.The CUMS model was verified through tail suspension experiments and forced swimming experiments.Eight mice in the Ctrl group and 8 mice in the CUMS group were randomly sacrificed at the 12th week.The Ctrl group was re-grouped into the cessation-control(C-Ctrl)group(n=8),the CUMS group was re-grouped into the cessation-stress(C-CUMS)group(n=8),and the mice were sacrificed at the 15th week.The mRNA and protein levels of appetite-regulating factors,including orexin 1 receptor(OX1R),leptin receptor(LEPR)and agouti-related protein(AgRP)in the hypothalamus,were detected by quantitative polymerase chain reaction and immunochemistry.Results From week 2 to week 11 of stress,the food intake of the mice in the CUMS group was significantly higher than that in the Ctrl group(all P＜0.05),while there was no significant difference in body weight between the 2 groups within 11 weeks(all P＞0.05).Compared with the Ctrl group,the immobility durations of forced swimming and tail suspension of the CUMS group were markedly longer after 11 weeks(both P＜0.01),indicating successful modeling.AgRP and OX1R mRNA expression in the hypothalamus of the CUMS group was significantly increased(both P＜0.01),while LEPR mRNA expression was significantly decreased(P＜0.01);AgRP protein in the hypothalamic arcuate nucleus of the CUMS group was significantly higher than that of the Ctrl group(P＜0.05),and LEPR protein was markedly lower than that of the Ctrl group(P＜0.01).However,after 3 weeks of stress cessation,the C-CUMS group had less food intake and lower body weight than the C-Ctrl group(both P＜0.05).The LEPR mRNA of the C-CUMS group was significantly increased(P＜0.01),while AgRP and OX1R mRNA were not significantly different(both P＞0.05).There was no significant difference in AgRP protein levels between the C-CUMS group and the C-Ctrl group(P＞0.05),while LEPR protein level of the C-CUMS group was significantly higher than that of the C-Ctrl group(P＜0.01).Conclusion CUMS can lead to increased appetite in mice,which may involve the functional regulation of LEPR and AgRP.After the stress cessation,the appetite decreases,which may involve the functional regulation of LEPR.

Objective:To study the effects of aluminum exposure on learning and memory and the expression of nerve growth factor(NGF)in the hippocampus of offspring rats,and to investigate the mechanism by which aluminum impairs learning and memory function.Methods:Forty pregnant Wistar rats were randomly assigned to the Control group(Control),low-dose Al group(Al-L),medium-dose Al group(Al-M)and high-dose Al group(Al-H).The off-spring rats were fed with Al through breast milk from birth to weaning,while the rats in the control group were fed with distilled water.The maternal rats Al-L,Al-M and Al-H groups drank distilled water solution containing 2.0,4.0 and 8.0 g/L AlCl3,respectively.After weaning,the offspring rats in the aluminum exposure group drank distilled water so-lution containing 2.0,4.0 and 8.0 g/L AlCl3 by themselves until the 90th day after birth to establish the offspring rat model of subchronic aluminum exposure.After aluminum exposure,the shuttle box test was used to detect the learning and memory ability of offspring rats,and the body weight of offspring rats and hippocampus were weighed to evaluate the effect of aluminum exposure.The expression of nerve growth factor(NGF)protein in hippocampus of offspring rats was detected by Western blot,and the expression of NGF mRNA in hippocampus of offspring rats was detected by real time RT-PCR.Results:The body weight of offspring rats in Al-H group was significantly lower than that in the other three dose groups.In the shuttle box test,compared with the control group,the active avoidance response and passive avoid-ance response of the offspring rats in the aluminum exposure group showed a downward trend with the increase of alumi-num exposure dose,indicating that the learning and memory ability of the offspring rats in the aluminum exposure group was impaired.Compared with the control group,the NGF protein content and NGF mRNA expression in the hippocam-pus of offspring rats in the aluminum exposure group were significantly decreased.Conclusion:Subchronic aluminum exposure down-regulates the expression of NGF in the hippocampus,which may cause learning and memory impairment in offspring rats.

Objective:To study the effects of aluminum exposure on learning and memory and the expression of nerve growth factor(NGF)in the hippocampus of offspring rats,and to investigate the mechanism by which aluminum impairs learning and memory function.Methods:Forty pregnant Wistar rats were randomly assigned to the Control group(Control),low-dose Al group(Al-L),medium-dose Al group(Al-M)and high-dose Al group(Al-H).The off-spring rats were fed with Al through breast milk from birth to weaning,while the rats in the control group were fed with distilled water.The maternal rats Al-L,Al-M and Al-H groups drank distilled water solution containing 2.0,4.0 and 8.0 g/L AlCl3,respectively.After weaning,the offspring rats in the aluminum exposure group drank distilled water so-lution containing 2.0,4.0 and 8.0 g/L AlCl3 by themselves until the 90th day after birth to establish the offspring rat model of subchronic aluminum exposure.After aluminum exposure,the shuttle box test was used to detect the learning and memory ability of offspring rats,and the body weight of offspring rats and hippocampus were weighed to evaluate the effect of aluminum exposure.The expression of nerve growth factor(NGF)protein in hippocampus of offspring rats was detected by Western blot,and the expression of NGF mRNA in hippocampus of offspring rats was detected by real time RT-PCR.Results:The body weight of offspring rats in Al-H group was significantly lower than that in the other three dose groups.In the shuttle box test,compared with the control group,the active avoidance response and passive avoid-ance response of the offspring rats in the aluminum exposure group showed a downward trend with the increase of alumi-num exposure dose,indicating that the learning and memory ability of the offspring rats in the aluminum exposure group was impaired.Compared with the control group,the NGF protein content and NGF mRNA expression in the hippocam-pus of offspring rats in the aluminum exposure group were significantly decreased.Conclusion:Subchronic aluminum exposure down-regulates the expression of NGF in the hippocampus,which may cause learning and memory impairment in offspring rats.

Objective:To investigate the association between exposures of seven classic phthalate metabolites and fertility among preconception women before pregnancy.Methods:Based on the preconception cohort, a nested case-control study was carried out. Preconception couples who were recruited from Shanghai Jiading District Maternal and Child Health Hospital from 2016 to 2020 with intention to conception were selected. A total of 100 women whose time to pregnancy (TTP) >12 months were selected as the case group, and 151 women with the TTP≤12 months were randomly selected as control group. The single and joint effects on fertility of phthalate metabolites were analyzed by the comparison between the two groups via the multivariate binary logistic regression model, and the weighted quantile sum regression model.Results:There were significant differences in mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-carboxmethyl)-hexyl phthalate (MCMHP), the sum of the detected concentrations of MEHP, MCMHP, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-carboxypentyl) phthalate (∑DEHP), and the sum of the detected concentrations of the seven phthalate metabolites (∑PAE) exposure levels between the case group and control group ( P=0.005, P<0.001, P=0.001, P=0.007). As shown by the multivariate binary logistic regression model, women with MEHP, MCMHP, ∑DEHP, ∑PAE at the highest quartile level were found to have significantly increased risk of infertility compared with women at the lowest quartile level (a OR=2.40, 95% CI: 1.12-5.15, P=0.025; a OR=7.74, 95% CI: 3.14-19.08, P<0.001; a OR=4.35, 95% CI: 1.93-9.79, P<0.001; a OR=2.04, 95% CI: 0.96-4.34, P=0.044). The weighted quantile sum regression model demonstrated that the exposure to seven phthalate metabolite mixtures in preconception was associated with an increased risk of infertility ( P<0.05). Among the seven phthalate metabolites, MCMHP had the largest contribution weight (61.7%). Conclusion:Women of childbearing age should avoid the exposure to phthalates in the environment when preparing for conception, such as to reduce the consumption of highly processed foods and foods packaged with plastic/polyvinyl chloride materials to promote fertility.

Objective:To investigate the association between exposures of seven classic phthalate metabolites and fertility among preconception women before pregnancy.Methods:Based on the preconception cohort, a nested case-control study was carried out. Preconception couples who were recruited from Shanghai Jiading District Maternal and Child Health Hospital from 2016 to 2020 with intention to conception were selected. A total of 100 women whose time to pregnancy (TTP) >12 months were selected as the case group, and 151 women with the TTP≤12 months were randomly selected as control group. The single and joint effects on fertility of phthalate metabolites were analyzed by the comparison between the two groups via the multivariate binary logistic regression model, and the weighted quantile sum regression model.Results:There were significant differences in mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-carboxmethyl)-hexyl phthalate (MCMHP), the sum of the detected concentrations of MEHP, MCMHP, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-carboxypentyl) phthalate (∑DEHP), and the sum of the detected concentrations of the seven phthalate metabolites (∑PAE) exposure levels between the case group and control group ( P=0.005, P<0.001, P=0.001, P=0.007). As shown by the multivariate binary logistic regression model, women with MEHP, MCMHP, ∑DEHP, ∑PAE at the highest quartile level were found to have significantly increased risk of infertility compared with women at the lowest quartile level (a OR=2.40, 95% CI: 1.12-5.15, P=0.025; a OR=7.74, 95% CI: 3.14-19.08, P<0.001; a OR=4.35, 95% CI: 1.93-9.79, P<0.001; a OR=2.04, 95% CI: 0.96-4.34, P=0.044). The weighted quantile sum regression model demonstrated that the exposure to seven phthalate metabolite mixtures in preconception was associated with an increased risk of infertility ( P<0.05). Among the seven phthalate metabolites, MCMHP had the largest contribution weight (61.7%). Conclusion:Women of childbearing age should avoid the exposure to phthalates in the environment when preparing for conception, such as to reduce the consumption of highly processed foods and foods packaged with plastic/polyvinyl chloride materials to promote fertility.

Atherosclerosis (AS) is a chronic and progressive arterial disease. It is an important cause of the occurrence and development of cardiovascular and cerebrovascular diseases. With the development of Traditional Chinese Medicine (TCM), TCM has many advantages in the therapy of AS, with less adverse reactions. Studies have shown that TCM can resist AS, and the mechanism mainly belongs to regulating lipid metabolism, anti-lipid peroxidation, anti-inflammation, anticoagulation, and protecting the structure and function of vascular endothelial cells. The mechanism of TCM for AS is warranted to be studied systematically, and the chemical components need to be further clarified.

Objective: To investigate the efficiency and safety of domestic tyrosine kinase inhibitor (TKI) dasatinib (Yinishu) as second-line treatment for patients with chronic myeloid leukemia in chronic phase (CML-CP). Methods: A retrospective analysis of clinical data of CML-CP patients who received domestic dasatinib as second-line treatment in the CML collaborative group hospitals of Hubei province from March 2016 to July 2018 was performed. The optimal response rate, the cumulative complete cytogenetic response (CCyR), the cumulative major molecular responses (MMR), progression free survival (PFS), event free survival (EFS) and adverse effects (AEs) of the patients were assessed at 3, 6 and 12 months of treatment. Results: A total of 83 CML-CP patients were enrolled in this study. The median follow-up time was 23 months. The optimal response rates at 3, 6 and 12 months in 83 CML-CP patients treated with dasatinib were 77.5% (54/71), 72.6% (61/75) and 60.7% (51/69), respectively. By the end of follow-up, the cumulative CCyR and MMR rates were 65.5% (55/80) and 57.1% (48/73), respectively. The median time to achieving CCyR and MMR was 3 months. During follow-up time, the PFS rate was 94.0% (79/83) and the EFS rate was 77.4% (65/83). The most common non-hematological AEs of dasatinib were edema (32.5%), rash itching (18.1%) and fatigue (13.3%). The common hematological AEs of dasatinib were thrombocytopenia (31.3%), leukopenia (19.3%) and anemia (6.0%). Conclusion Domestic dasatinib was effective and safe as the second-line treatment of CML-CP patients and it can be used as an option for CML-CP patients.

Objective To investigate the relationship of obesity and vascular endothelial growth factor (VEGF)and the clinicopathological characteristics and prognosis of breast cancer.Methods From Jan.2013 to Dec.2015,147 breast cancer patients were treated at the Department of Breast Surgery in Jiangsu University Affiliated People's Hospital.The clinical factors such as BMI,clinicopathological data and survival prognosis were collected.The chi-square test was used to analyze the association between factors and obesity.Log-rank test and COX regression analysis were performed to make univariate and multivariate analysis.The Oncomine and Kaplan Meier plotter were employed to assess the expression of VEGF in breast cancer and its association with survival prognosis of breast cancer patients.Results The median follow-up time was 40 (ranging from 12 to 58) months.Obesity was associated with tumor size(x2=11.009,P=0.001),and there was no significant correlation between axillary lymph node status,hormone receptor and Her-2 expression.The results of single factor analysis suggested that obesity and axillary lymph node status significantly affected the breast cancer patients OS (P=0.035,P=0.038)and RFS (P=0.035,P=0.036)).Cox multivariate regression analysis results suggested that obesity could be considered as an independent prognostic factor of breast cancer:P=0.051,HR=3.849 (95％ CI:0.995-14.895);Oncomine database analysis found that VEGF was relatively high in breast cancer tissue compared to that in adjacent tissues.Kaplan Meier plotter analysis results showed better overall survival (OS)and recurrence free survival (RFS)in patients with low expression of VEGF in breast cancer tissues.Conclusions Obesity is an adverse prognostic factor in breast cancer patients,and may be associated with elevated VEGF.Weight control may improve the prognosis of breast cancer patients.

Objective To investigate the effects of artesunate combined with arsenic trioxide (ATO) on the proliferation and apoptosis of NB4 cells.Methods The NB4 cells were treated with different concentrations of artesunate and arsenic trioxide respectively for 48 h.The cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) method.The cells were divided into 4 groups:control group,artesunate group,arsenic trioxide group,and the combination of artesunate and arsenic trioxide group.The cell cycle and apoptosis were detected by flow cytometry (FCM).The protein expression levels of Bcl-2 and Bax were detected by Western blot.Results The MTT results showed that compared with the control group,the proliferation inhibition rates of 0.25,0.50,1.00,2.00,4.00 μmol/L artesunate group (19.26％ ± 3.59％,36.53％ ± 2.67％,61.32％ ± 2.50％,70.30％ ± 3.15％,86.92 ± 0.02％) significantly increased (P＜0.05);the proliferation inhibition rates of 1,2,4,8,16 μmol/L arsenic trioxide group (12.69％ ± 2.43％,64.26％ ± 2.02％,85.10％ ± 2.67％,92.06％ ± 2.21％,93.67％ ± 3.36％) significantly increased (P＜0.05);and the proliferation inhibition rate (40.17％ ± 5.49％ vs.32.23％ ± 3.52％) of combination of artesunate and arsenic trioxide group significantly higher than the arsenic trioxide group (P＜0.05).Compared with the arsenic trioxide group,the percentage of G0/G1 phase cells (74.20％ ± 1.43％ vs.66.14％ ± 1.78％),the apoptosis rate (58.00％ ± 2.41％ vs.34.57％ ± 1.22％),and the expression level of Bax protein (1.35 ± 0.09 vs.1.13 ± 0.09) in the combination of artesunate and arsenic trioxide group significantly increased (P＜0.05),the expression level of Bcl-2 protein (0.45 ± 0.09 vs.1.03 ± 0.10) in the combination of artesunate and arsenic trioxide group significantly decreased (P＜0.05).Conclusions Artesunate can significantly enhance the proliferation inhibition and apoptosis induced by arsenic trioxide on NB4 cells.The possible mechanism of proliferation inhibition and apoptosis of NB4 cells by artesunate combined with arsenic trioxide may be related to reduce the expression of anti-apoptotic protein Bcl-2 and increase the expression of apoptotic protein Bax.