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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.

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.

Objective To examine the influence of gender difference on the reperfusion delay in patients with ST-elevation myocardial infarction (STEMI).Methods A total of consecutive 325 patients with STEMI were analyzed admitted in the 306 Hospital of PLA from Jan.2011 to Dec.2015.Patients were divided into two groups:male group (n=268) and female group (n=57).The clinical data and the time intervals including symptom onset to first medical contact (So-to-FMC),transfer delay (FMC-to-D),FMC to balloon dilatation (FMC-to-B),activation delay and door to balloon (D-to-B) time were compared between different gender groups,and the prognosis was observed.Results The overall median of pre-hospital delay was 125 minutes.The median of prehospital delay time (male 119.5min vs.female 160.0min) and So-to-FMC time (male 69.5min vs.female 100.0min) were longer in female than in male patients,but no statistical difference existed (P＞0.05) between the two groups in pre-hospital delay,So-to-FMC,FMC-to-B,D-to-B and total ischemia time.Compared with male patients,female patients were more likely to have additional comorbidities,such as hypertension and diabetes mellitus,and lower rate of smoking (P＜0.05).However,the incidence of major adverse cardiac and cerebrovascular events (MACCE) showed no significant difference between female and male patients at 30-day (male 5.22％ vs.female 5.26％) and I-year (male 10.82％ vs.female 8.77％) follow-up (P＞0.05).Conclusion The influence of gender on reperfusion delay is gradually weakening.

Objective To compare the clinical efficacy and safety of nilotinib and imatinib as frontline therapy in newly diagnosed patients with chronic myeloid leukemia in chronic phase ( CML-CP ) . Methods Until December 31st 2016, 18 patients using nilotinib and 83 using imatinib were recruited in our study.The efficacy and safety of two groups were evaluated .Results A total of 101 patients with CML-CP included 18 receiving nilotinib and 83 imatinib.The optimal response rates at 3, 6, 12 and 18 months in nilotinib and imatinib group were 88.9%(16/18) vs 57.3%(47/82) (P=0.012), 82.4%(14/17) vs 55.7%(44/79) (P=0.041), 9/12 vs 63.9% (39/61) (P=0.460), 6/9 vs 68.9% (31/45) (P=0.896) respectively.The optimal response rates by 3 months in low sokal risk group on nilotinib and imatinib were 9/9 vs 76.5%(26/34) (P=0.107), in intermediate and high sokal risk group were 7/8 vs 45.2%(14/31) (P=0.032).At the end of follow-up, the rate of major molecular response (MMR) in nilotinib group was 72.2%, which was higher than 56.6% in imatinib group (P=0.021).The rate of complete cytogenetic response ( CCyR ) in nilotinib group was 100%, which was higher than 71.1% in imatinib group (P =0.002).Progression free survival (PFS) rates in nilotinib and imatinib groups were 94.4%and 98.8%(P=0.019) respectively; whereas event free survival (EFS) rates were 88.9% and 48.2%(P=0.045).The incidence of drug related adverse reactions in nilotinib and imatinib was similar with only minor proportion of grade 3/4 adverse reactions .Conclusions Nilotinib achieves a deeper molecular response in a shorter time than imatinib in newly diagnosed patients with CML-CP, especially in patients with high risk outcome .Good safety is obtained in both groups so as to ensure a long-term administration and improving prognosis .

Objective:To investigate the purification of antibacterial effective fraction of Syringae folium by macroporous resins. Methods:Static adsorption and desorption tests were carried out to screen the macroporous resins. The desorption experiment was per-formed on the selected D101 resin to optimize the separation process. The effects of resin amount, diameter length ratio, elution flow rate, elution solution concentration and volume were studied. Results:The optimal conditions were as follows:the elution solution was 55% ethanol, the adsorption flow rate was 1 BV·h-1 , the elution flow rate was 5 BV·h-1 , 6 BV 25% ethanol was used to eliminate impurity and 8 BV 55% ethanol was used to elute to obtain the effective fraction. Conclusion: The content of antibacterial effective component is above 65% after purified by D101 resin, indicating that the present method is suitable for large-scale preparation of anti-bacterial effective fraction of Syringae folium.

Objective To assess the health status of rodent laboratory animals by pathological diagnosis, our lab has being take apart in investigating the quality of laboratory animals in Beijing area for years and offer some advices for standardized breeding to ensure accurate results of scientific research.This paper focuses on the analysis of laboratory rodent samples that collected in October 2014.Methods We collected the heart, liver, spleen, lung, kidney, large intestine and small intestine, and put these organs into 10%Calcium formaldehyde solution for fixation, and then prepared into two different sections for optical microscopy observation including all paraffin specimens stained with H&E and the frozen sections stained with Oil Red-O and PAS.Results The vast majority of laboratory rodents were up to standard, but there still a problem in individual units.The main problem is liver and lung disease.The rate of Hepatocyte swellingis 6%(mouse), 2.5% (rat), 8.2% (guinea pig), moreover part of them were lipidosis, according to Oil Red-O stain.the mainly problem of lung is congestion ,edema and Interstitial pneumonia ,the detectable rate of pulmonarydiseases is 15.5%(guinea pig).Conclusions The vast majority of laboratory rodents were pathologically diagnosed as healthy animals.The liver disease may be caused by improper feeding.And disease of lung may led by haze, unqualified bedding and low temperature.