Objective:To analyze the effect of depressive state on Alzheimer's disease(AD)mice,3xTg-AD mice were stimulated with chronic social frustration stress(CSDS)and chronic mild unpredictable stress(CUMS),to estab-lish an early AD-induced depression mouse model,and to detect cognitive and behavioral changes,activation of micro-glia in the hippocampus and neuronal loss.Methods:Three-month-old mice were subjected to 8-day stress stimulation alternately,the depressive state of the mice was evaluated by behavior,the evaluation criteria were formulated,and the cognitive behavior was detected and analyzed,and the hippocampal brain tissue sections were stained with immunofluo-rescence to observe the deposition of β-amyloid(Aβ)and the aggregation of microtubule-associated protein(tau),mi-croglia activation and neuronal loss.Results:Depression-related behavioral results showed that the CSDS+CUMS group had depression-related phenotypes.Cognitive-behavioral testing showed that the new object recognition index of the mice in the CSDS+CUMS group was significantly reduced(P＜0.05),and the Morris water maze showed that the spatial memory ability of the CSDS+CUMS group was significantly reduced(P＜0.05),but there was no obvious fear memory loss in the CSDS+CUMS group in the conditioned fear experiment.The results of immunofluorescence staining showed that Aβ deposition appeared in the hippocampus at 4 months of age,the activated microglia increased(P＜0.001),and a certain degree of neuronal loss appeared in the CSDS+CUMS group(P＜0.001);At 8 months of age,the CSDS+CUMS group showed tau protein aggregation early.Conclusion:We established a model of AD-induced de-pression in AD mice,in which 3xTg-AD mice experienced early decline in learning memory and increased AD-related pathological deposition of neurons in the hippocampus,accompanied by microglial activation and neuronal loss.

AIM:To investigate the therapeutic effect of raddeanin A(RA)on prostate cancer xenograft mouse model,and to explore its potential mechanisms.METHODS:(1)Western blot analysis was used to investigate the effects of different concentrations(0,0.5,1,2 and 4 μmol/L)of RA on the expression of programmed cell death li-gand 1(PD-L1)protein in prostate cancer cell lines PC-3,DU145 and RM-1.(2)Thirty C57BL/6J mice were randomly divided into blank group,low-dose RA group,and high-dose RA group,with 10 mice in each group.The mice in low-and high-dose RA groups were intraperitoneally injected with 2 and 4 mg/kg RA continuously for 24 d,respectively.Mouse body weight was recorded,and tumor volume and weight were measured.Immunohistochemistry experiments were con-ducted to detect the expression of Ki67 and PD-L1 proteins in mouse tumor tissues.Flow cytometry was used to determine the percentages of CD8+T cells,CD4+T cells and regulatory T cells(Treg),as well as the levels of interferon-γ(IFN-γ)and granzyme B(GzmB)in tumor tissues.RESULTS:Treatment with RA significantly reduced the expression of PD-L1 in PC-3,DU145 and RM-1 cells(P<0.05 or P<0.01).In vivo experiments showed that RA treatment led to significant decreases in tumor volume and weight(P<0.05 or P<0.01).Additionally,the expression levels of Ki67 and PD-L1 in tu-mor tissues were significantly reduced(P<0.05 or P<0.01).Furthermore,RA treatment significantly increased the per-centages of CD8+T cells and CD4+T cells within mouse tumors,elevated the levels of IFN-γ and GzmB,and reduced the number of activated Treg(P<0.05 or P<0.01).CONCLUSION:The RA exhibits potent inhibitory effects on tumor growth in a prostate cancer xenograft mouse model.Its mechanism may be associated with the inhibition of PD-L1 expres-sion,increased infiltration of tumor-infiltrating T cells,and suppression of Treg.

Objective:To explore the application effect of coaching technique in respiratory function exercise of patients with chronic obstructive pulmonary disease (COPD) in stable stage.Methods:Using the convenient sampling method, a total of 40 COPD patients in stable stage who were treated in Geriatric and Respiratory Departments of 3 provincial hospitals in Hangzhou were selected as the research objects from August 2018 to June 2019. They were given a six-month breathing intervention based on coaching techniques by trained health coaches. COPD Self-Efficacy Scale (CSES) and COPD Assessment Test (CAT) were used to evaluate self-efficacy and quality of life of patients before and after intervention. The awareness and implementation of respiratory function exercise were compared before and after intervention.Results:After6 months of intervention, compared with those before intervention, the score of awareness and implementation of respiratory function exercise of patients increased, and the differences were statistically significant ( P<0.05) . After the intervention, the score of CSES increased and the scores of CAT decreased, and the differences were statistically significant compared with those before the intervention ( P<0.05) . Conclusions:The application of coaching technique in the respiratory function exercise of COPD patients in stable period has a certain effect, which can improve the awareness and implementation of patients with respiratory function exercise and improve their sense of self-efficacy and quality of life.

Clinical data of 23 children with atrial septal defect and pulmonary valvular stenosis admitted in Dalian Children′s Hospital during March 2015 to March 2018 were retrospectively analyzed. Twenty patients were treated with percutaneous closure of atrial septal defect through femoral vein first, then transthoracic echocardiography-guided balloon pulmonary valvuloplasty was performed; while 3 patients had no balloon pulmonary valvuloplasty after percutaneous closure of atrial septal defect. Patients were followed up by transthoracic echocardiography and all were doing well. The transvalvular pressure fell under 35 mmHg (1 mmHg=0.133 kPa) [(19.5±1.9)mmHg] in all patients, which was significantly lower than that before treatment [(62.0±7.8 mmHg)] (t=28.92, P<0.01). During follow-up, no residual shunt of atrial septal defect was found; and mild pulmonary regurgitation occurred in 3 cases. The study indicates that combined percutaneous treatment with transthoracic echocardiography guidance is effective and safe for children with atrial septal defect and pulmonary valvular stenosis. The pulmonary artery stenosis of some patients can be alleviated, after closuring of the atrial septal defect.

Objective To investigate the efficacy and safety of percutaneous patent ductus arteriosus (PDA) closure via femoral vein solely under transesophageal echocardiography guidance.Methods From May 2014 to May 2015,28 patients(13 boys,15 girls) were selected in Dalian Children's Hospital Affiliated to Dalian Medical University with PDA closure via the femoral vein under transesophageal echocardiography guidance,with mean age (3.5 ± 2.6)years and mean body weight (16.0 ± 6.5) kg.The mean diameter of PDA was (7.1 ± 3.9) mm.Patients were all treated by percutaneous PDA closure solely by transesophageal echocardiography via the femoral vein.The effect of the procedures was evaluated by echocardiography.The transthoracic echocardiography,chest X-ray film,cardiogram at 1 month,3 months and 6 months after procedure were followed up.Results Twenty-seven cases were successfully treated with percutaneous PDA closure via the femoral vein solely under transesophageal echocardiography guidance,while 1 patient was closed by surgical closure with on-pump beating-heart because PDA occluder strayed into the left pulmonary artery on 1-month follow-up.The procedural time was (48.5 ±8.7) min.The mean diameter of PDA occluder was (8.2 ± 4.1) mm.Twenty-seven patients survived without peripheral vascular injury or complications such as residual shunt,arrhythmia and cardiac perforation.One patient was transformed to surgical closure.Hospitalization time was (2.5 ± 0.5) days.At one month follow-up,no complications such as residual shunt or pericardial effusion occurred.Conclusion Transesophageal echocardiography guided percutaneous PDA closure via the femoral vein approach is safe and effective without the damage from radiation and contrast agents,and aviods the use of femoral artery puncture.

This study was aimed to explore five Chinese medicine components or ingredients from Qu-Shi Hua-Y u Decoction (QSHYD) with uniform design method and screen ingredients assembling of Chinese medicine BZL pre-scription in order to verify its therapeutic effect on experimental fatty liver rats. High-fat diet was used in the estab-lishment of fatty liver rat models. Five effective ingredients (i.e., chlorogenic acid, geniposide, curcumin, polydatin and polysaccharide of Atractylodes macrocephala Koidz) of QSHYD were used as study subjects. Uniform design was applied in the grouping design. The intragastric administration was given for four weeks. The screening index was the content of liver triglyceride (TG). The ingredients assembling of Chinese medicine BZL prescription was screened through uniform design and regression analysis. The same fatty liver animal model was used in the comparison be-tween QSHYD and rosiglitazone. The TG content in liver tissues of rats and serum ALT activity were detected. The pathological changes of liver tissues were observed (HE stain and oil red O stain) with Ridit analysis to verify its therapeutic effect. The results showed that through screening, the regression equation was Y = 15.083X1 + 5.321X2- 5.186X3 - 16.157X4 + 9.35X5 + 17.667X3X4 - 8.422X1X2 - 6.617X3X5 + 16.571 (X1: chlorogenic acid, X2:polydatin, X3: polysaccharide of Atractylodes macrocephala Koidz, X4: geniposide, X5: curcumin). According to this equation, the best TG reducing effect occurred when the chlorogenic acid (X1), polysaccharide of Atractylodes macrocephala Koidz (X3), and geniposide (X4) were the maximum dosage. It showed that the best combination in inhibiting TG content in liver tissues was X3, X4 and X1 (i.e. BLZ prescription). Among fatty liver rat mod-els induced with same high-fat diet, the screened Chinese medicine ingredient BZL prescription can obviously reduce its TG content in liver tissues and serum ALT activity ( P < 0 . 01 ) . It obviously improved the fatty degen-eration of rat's liver. It was concluded that ingredients assembling of Chinese medicine BZL prescription screened through uniform design can obviously prevent and treat fat deposition and injury of the liver among rat models induced by high-fat diet .

Objective To determine the characteristics of early cognitive dysfunction and N300 event-related potentials(ERPs)in patients with acute cerebral infarction(ACI).Methods Thirty patients with ACI and thirty normal healthy elderly people were studied.The two groups were examined with a picture recognition test and EEG waveforms were recorded.The ERPs were analysed statistically.The mini-mental state examination(MMSE) was used to evaluate cognitive function,and the results were correlated with the ERPs. Results The average MMSE scores of the ACI and control groups were significantly different.Reaction times(RTs)in the picture recognition test were(798.63±49.32)ms in the ACI group and(765.21±35.67)ms in the control group,a difference significant at the 5% confidence level.The average accuracy rates,(59.75±8.45)%and(65.26±9.28)%,were also significantly different.Average N300 ERPs the in the ACI group were significantly lower than those in the control group,and the average latencies were significantly longer.Both latency and amplitude in the ACI group showed a linear correlation with MMSE scores. Conclusion The ERPs of ACI patients have some clinical significance,and can be used as a scale-based assessment of cognitive function.

BACKGROUND: Long-term sustained release naltrexone has been reported in clinical application near one year that it can improve emotional state and relieve addiction; therefore, the effect of long-term sustained release naltrexone on memory restoration at neuropsychology level were explored. OBJECTIVE: To observe the effect of long-term sustained release naltrexone on memory ability of opioid addicts. DESIGN, TIME AND SETTING: A contrast observational study was performed at Drug Rehabilitation Centers of Wuhan, Changde, Zhengzhou, and Jiangyang between October and December 2006. Healthy controls were tested in Shenzhen Hospital of Peking University in October 2006. PARTICIPANTS: A total of 88 males with opioid addicts were divided into naltrexone group (n=35), compulsory detoxification group (n=26), and non-treatment group (n=27). Another 22 healthy subjects were considered as the controls. METHODS: At 6-12 months before testing, naltrexone (3.1 g) was subcutaneously implanted into bilateral abdominal wall in the naltrexone group; patients in the compulsory detoxification group underwent completely compulsory detoxification for 6 months, and the examination results, including diamorphine, methadone, and buprenorphine in urine, were negative on the immediately testing day. Event related potential and its wave form were recorded from the opioid addicts in the three groups and from healthy controls who finished semantic recognition between new and old words using portable-type event related potential working system. MAIN OUTCOME MEASURES: Correct rate and response time of semantic memory; latency and amplitude of language related potential-N400. RESULTS: ①There were significant differences in correct rate and response time between three expedmental groups and healthy control group (P ＜ 0.001 ); in addition, correct rate was significantly increased, and response time was significantly shortened in the naltrexone group compared to compulsory detoxification group and non-treatment group (P＜ 0.05). ② N400 latency in the three experimental groups was significantly longer than healthy control group (P ＜ 0.01), while N400 amplitude in the naltrexone group was increased, which was no significant difference compared to healthy control group (P> 0.05) but was significant difference compared to compulsory detoxification group and non-treatment group (P ＜ 0.01). CONCLUSION: Long-term sustained release naltrexone can effectively improve neural function and enhance semantic memory of the opioid addicts.

Objective To investigate the effects and relations of carvedilol on heart rate turbulence and secretion of sympathetic nerve in patients with myocardial infarction. Methods Sixty-six patients selected with acute myocardial infarction were randomized to enroll into experimental group ( n = 33 ) treated with earvedilol and control group( n = 33 ) treated with metoprolol for 12 months follow-up treatment. The concenrrarions of plasma norepinephrine(NE) and epinephrine (E) and 24 hour Holter monitoring were messured respectively before the treatment ,after 6 months and 12 months; and new cardiac events were supervised for all cases. Quantification of heart rate turbulenee(HRT) were carried out by computer analyzing two factors: turbulence onset(TO) and turbulence slope(TS) from the data of 24 hour Holter monitoring. NE,E,TO,TS and the occurrence rate of new cardiac events were compared between two groups and in different times of treatment. The correlation between TO,TS and NE,E was analysed. Results Before the treatment, there was no significant differences between two groups to the comparisons of NE,E,TO and TS(P＞0.05). After treating 6 and 12 months, NE, E and TO of experimental group were all lower than control group's significantly, accordingly TS were all higher(P＜0.05). By comparing 3 times( before,after 6 and 12 months of treatment), NE, E and TO of two groups dropped, meanwhile TS rose; experimental group showed significant changes( P＜0.05 ), but control group showed no significant differences(P＞0.05 ). The occurrence rate of new cardiac events of experimental group was lower than control group's significantly (P＜0.05 ).There was significant correlation between NE, E and TO, TS (P＜0.05 ). Conclusion Carvedilol treatment can block the secretion of sympathetic nerve after myocardial infarction and prevent the occurrences of new cardiac events significantly; the changes of the secretion of sympathetic nerve can play an important role for heart rate turbulence (HRT) ,the changes of HRT would be hopeful to predict new cardiac events alter myocardial infarction.

Objective To study the effects of carvedilol on the stability of plasma catecholamine in patients with post-acute myocardial infarction during consecutive periods. Methods Thirty-slx patients selected with acute myocardial infarction were randomized to experimental group treated with the nonselective beta-blocker earvedilol( n=18) and control group treated with the selective beta-blocker metoprolol(=18) for 12-months follow-up. In the two groups,the concentrations of plasma norepinephrine and epinephrine were measured before the treatment and after 2 months,4 months,6 months,8 mouths,10 months and 12 months and new cardiac events were supervised. Results After the treatment, in each point of periods, experimental group showed lower concentrations of plasma norepinephrine and epinephrine statistically than control group(P<0.05) ,and a stable dynamic change during 12 months of treat-ment( P>0.05 ) ;the occurrence rate of new cardiac events was lower significantly in experimental group than in con-trol group(P<0.05). Conclusion Carvedilol can decrease the spillover of sympathetic nerve, control more stably cardiac sympathetic nerve activity and then decrease more sharply the occurrence rate of new cardiac events in pa-tients with acute myocardial infarction than metoprolol.