Objective The annual incidence of Alzheimer's disease in China is increasing year by year.The herbicide paraquat widely used in early China may be the factor inducing Alzheimer's disease.This study intends to analyze the mechanism of inducing Alzheimer's disease by constructing an animal model of paraquat poisoning.Methods SD rats were fed paraquat,and the integrity of blood-brain barrier was observed by Evans blue staining.The expression level of Aβ42 in brain tissue was detected by Western-blot,and the expression levels of inflammatory cytokines interleukin-1β,tumor necrosis factor-α and inducible isoform of nitric oxide synthase were detected by ELISA.Results Paraquat could significantly increase the expression level of Aβ42 in brain tissue,destroy the integrity of blood-brain barrier,and increase the expression level of GSK-3β in blood-brain barrier.Further results showed that the use of GSK-3β inhibitors significantly alleviated paraquat induced blood-brain barrier damage and Aβ42 levels.Conclusion Paraquat can damage the integrity of the blood-brain barrier by up-regulating GSK-3β,and eventually lead to paraquat entering the brain,which increases the expression level of Aβ42.

Objective:To evaluate the application effect of mini-clinical exercise assessment (Mini-CEX) in clinical teaching of pediatrics of Chinese medicine, further optimize Mini-CEX scale with characteristics of pediatrics of Chinese medicine, and improve teachers' understanding of its connotation.Methods:A total of 50 pediatric clinical practice undergraduates were randomly divided into Mini-CEX group and control group, 25 in each group, with a total of 4 weeks of practice. The application effect of Mini-CEX was evaluated by clinical comprehensive ability assessment, and the students' evaluation on the introduction of Mini-CEX in clinical teaching was understood through questionnaire survey on the recognition, advantages and existing problems of various contents of Mini-CEX. SPSS 17.0 was used for t test and chi-square test. Results:Total scores and sub-item scores of clinical comprehensive ability examination in Mini-CEX group were higher than those in control group ( P < 0.05), and the satisfaction with teaching in Mini-CEX group was significantly higher than that in control group ( P < 0.05). Through the questionnaire, it was found that the students had a high degree of recognition for the items in the improved Mini-CEX scale, and thought it was more suitable for the internship study and effect evaluation of pediatrics of Chinese medicine, especially in the aspects of clinical communication skills and humanistic care. Conclusion:Mini-CEX has many advantages, such as improving the clinical comprehensive ability of undergraduates, teaching effect, flexible teaching methods, objective evaluation methods and focusing on the cultivation of doctor-patient communication skills, which is worthy of clinical promotion.

Abstract Public physical education teaching has adopted modern concepts and approachs of physical training to highlight the importance and effectiveness of physical education in colleges and universities in China. These courses have placed an emphasis on the need to attend to the structural integrity of the human body, optimizing the basic action mode and the efficient transmission of the power chain in motion. From the perspective of curriculum education, it is helpful to update ideas surrounding the public physical education curriculum in colleges and universities to enrich the content of public physical education courses provided by these institutions and to improve the scientific nature of training, while also enhancing the physical fitness of college students and promoting lifelong sports consciousness. However, there is insufficient explanation and implementation of modern physical training concepts and approachs into the teaching and process of public sports in colleges and universities. It will be beneficial to improve its top level design, increase policy support, provide better facilities, strengthen the construction of teachers, actively organize enjoyable physical fitness competitions, enrich the teaching content system and clear on the positioning of college physical education, in order to promote the fundamental tasks of school based physical education and the value of school sports. This is also important to ensure a renewal of the concept of the public physical education curriculum in our country, and encourage reform of the curriculum content, teaching mode and teaching methods, while also highlighting the essential function of physical training.

Objective: To compare difference in stability between two fixation modes in application of three-dimensional (3D) printed coronoid process prosthesis. Methods: 3D coronoid process prosthesis was reconstructed from computed tomography (CT) scanning acquired from volunteers with normal bony architecture of elbow. The prosthesis fixation was simulated using screws with diameter of 2.0 mm and 2.5 mm separately. Finite element analysis (FEA) was conducted at elbow flexion with different angles and the parameters including the maximum equivalent stress and the maximum displacement were evaluated. Results: Compared fixation using screw with the diameter of 2.0 mm and 2.5 mm, the maximum equivalent stress were 56.29 MPa and 39.96 MPa and the maximum displacement were 0.038 0 mm and 0.029 0 mm in 30° flexion of elbow; the maximum equivalent stress were 8.97 MPa and 8.12 MPa and the maximum displacement were 0.006 5 mm and 0.005 8 mm in 90° flexion of elbow; the maximum equivalent stress were 10.03 MPa and 9.32 MPa and the maximum displacement were 0.007 9 mm and 0.006 6 mm in 130° flexion of elbow. The maximum equivalent stress occurs at the junction of head and shaft with in both situations while the value from screw with diameter of 2.5 mm was lower. The displacement was smaller in the screw with diameter of 2.5 mm. Conclusion Compared to screws with the diameter of 2 mm, screw with the diameter of 2.5 mm shows superior stability in the fixation of 3D printed coronoid process prosthesis.

This study reported two women with extreme obesity who underwent metabolic surgery due to their mutations in leptin receptor (LEPR).Genomic DNA was extracted from the anticoagulant blood samples of the two patients and their parents.A panel of genes related to metabolic diseases or whole exon sequencing was screened and the results were confirmed by Sanger sequencing.This is the first time that these three mutations in LEPR were reported.Two patients complained insatiety and early-onset obesity since childhood at clinics.Patient 1 was a 39-year-old woman with height 150 cm,weight 130 kg,and BMI 57.8 kg/m2.Serum leptin level was 156.4 μg/L.A homozygous mutation of c.2317G＞T was found in exon 15 of LEPR gene in patient 1,which was descended from her father and mother respectively.Patient 2 was a 37-year-old woman with height 158 cm,weight 167 kg,and BMI 67 kg/m2.Serum leptin level was 193.4 μg/L.Genetic analysis showed compound heterozygous mutations of c.1482delT and c.1892C ＞ A.Her father showed heterozygous c.1482delT mutation,and her mother carried heterozygous c.1892C ＞ A mutation.Two patients all underwent metabolic surgery with body weight reduction of about 22 kg and 40 kg respectively after first six months.However,the follow-up studies showed that the body weight of patient 1 rebounded to pre-surgery level in two years and patient 2 did not further lose weight in the following six months.

Based on the review of existed references,research methods and experiences of ethnographic studies of Chinese medicine in the UK,this article proposed several suggestions on the social scientific studies of Chinese medicine abroad under the background of the "Belt and Road":studies should be more pragmatic in order to take the role of think tank;multi-discipline studies are encouraged to take the advantages of professional subjects;multi-cultures should be respected and local conditions should be taken into consideration to achieve conversational communication and all-win interest consortium;qualitative research should be more emphasized to present more ethnographic work for analytical studies;historical studies should be paid attention to in order to get dynamic trends.

AIM: To observe the inhibitory effect of recombinant human endostatin (rhES) on plaque angio-genesis, and to explore the regulatory mechanism of Dll4 /Notch pathway in the anti-angiogenic effect of rhES.METH-ODS: Male Wistar rats were randomized into 3 groups: normal control group (N group), atherosclerotic model group (AS group), and rhES treated group (AS +rhES group).The rats in N group were fed a normal diet, while the remaining 2 groups were established to atherosclerotic rat model via high-cholesterol diet, intraperitoneal injection of vitamin D3 and aor-tic balloon injury.The rats in AS +rhES group received intraperitoneal injection of rhES.The blood total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), interleukin-1 (IL-1) and troponin I (TnI) were measured.The atherosclerotic abdominal aortas were taken for pathological observation.Immu-nohistochemical staining was used to measure the density of neovessels in the plaques, which were marked by CD31.The protein levels of Dll4 and Notch1 in the aortas were analyzed by Western blot.RESULTS: The levels of blood TC, TG, LDL-C, CRP and IL-1 in AS group and AS +rhES group were much higher than those in N group (P <0.05), and no sta-tistical difference between AS group and AS +rhES group was observed.The expression of CD31 in AS group was the high-est among all groups.Compared with AS group, the density of neovessels in the plaques of AS +rhES group decreased sig-nificantly (P <0.05).The protein expression of Dll4 and Notch1 in AS group was lower than that in N group (P <0.05). Compared with AS group, the protein expression of Dll4 and Notch1 increased significantly (P <0.05).CONCLUSION:rhES has the ability to inhibit plaque angiogenesis in rats.The activation of Dll4 /Notch pathway may be the mechanism of rhES in inhibiting plaque angiogenesis.

ObjectiveToestablisharatmodelofatherosclerosiscombinedwithsyndromeofintermingledphlegm and blood stasis , to observe the inflammatory reactions and the treatment effect of prescription ( Danlou tablet ) on the rat model.Methods Thirty-two healthy male SD rats were randomly and equally divided into four groups , namely, normal control group, model control group, atorvastatin group (ATV group), and Danlou group (DLP group).The normal control group was given basic forage , while other three groups were given high fat forage plus intraperitoneal injection of vitamin D 3 and balloon injury of the left common carotid artery to build rat atherosclerosis model combined with syndrome of intermingled phlegm and blood stasis , and then received intragastric administration of saline , atorvastatin suspension and Danlou tablets suspension for 4 weeks, respectively.After intervention, both serum lipid and hs-CRP, IL-6, TNF-α, and LP-PLA2 levels were determined by ELISA , pathological alterations in the thoracic aorta was analyzed using HE staining , the expressions of IL-6, TNF-αand LP-PLA2 mRNA in the thoracic aorta tissue were assessed by real-time fluorescent quantitativePCRtechnology.Results ①Comparedwiththenormalcontrolgroup,thereweresignificantincreasesin serum TC, LDL-C, hs-CRP, IL-6, TNF-α, and LP-PLA2 levels (P<0.05 for all) and decrease of serum HDL-C levels in the model group (P<0.05).The expressions of IL-6, TNF-α, and LP-PLA2 mRNA in the rat aorta were significantly increased ( P<0.05 for all ) .In the model control group , HE staining showed altered arrangement of aortic endothelial cells, irregular intimal thickening , broadened subendothelial space , and accumulation of foam cells and lipid deposition , forming typical atherosclerotic plaques .② Compared with the model control group , the ATV and DLP groups showed significantly decreased serum TC , LDL-C, hs-CRP, IL-6, TNF-α, and LP-PLA2 levels ( P<0.05 for all) as well as the expressions of IL-6, TNF-α, and LP-PLA2 mRNA in the thoracic aorta (P<0.05 for all).There were no significant differences between the ATV and DLP groups (P>0.05).There were also reduced aortic intimal hyperplasia , macrophage infiltration and plaque area compared with those of the model group .Conclusions Rat model of atherosclerosis combined with syndrome of intermingled phlegm and blood stasis can be established by high fat diet feeding combined with the intraperitoneal injection of vitamin D 3 and balloon injury of carotid artery .The prescription ( Danlou tablet ) can inhibit the inflammatory reaction and ameliorate atherosclerotic changes in the rat models .

Objective To investigate the molecular mechanisms of effect of glycogen synthase kinase -3beta( GSK3β) on proliferation of human osteosarcoma cells .Methods Normal osteoblast hFO and osteosarcoma cell lines were examined for GSK 3βexpression and activity by Western blot and in vitro kinase assay ( NIRKA) . The effects of small molecule GSK3βinhibitors on cell proliferation and apoptosis were examined .Depletion of en-dogenous GSK3βby GSK 3βsiRNA detected the expression and phosphorylation of p 27 and its downstream cy-clinD1-CDK-Rb pathway factor by Western blot .Human osteosarcoma cell xenografts ,in athymic mice model , were treated with DMSO as control or with GSK 3βinhibitor SB-216763 or AR-A014418 by intraperitoneal in-jection,3 times a week.The tumor growth and body weight were observed in nude mice .Results Osteosarcoma cell lines showed increased GSK 3βexpression and decreased serine 9 phosphorylation compared with normal oste-oblast cells.Inhibition of GSK3βresulted in attenuated cell proliferation and increased apoptosis in most osteosar-coma cell lines in vitro and in vivo in MG 63 xenografts in rodents but not in hFOB cells .We decreased endoge-nous GSK3b activity,tumor growth was inhibited in SB216763,AR -A014418 group compared with control group.There was statistical significance(P<0.05).GSK3βinhibition in osteosarcoma cells was associated with decreased p27 expression, Rb expression and phosphorylation level of decline , CDK2, 4, 6 protein level de-creased,the upregulation of cyclin D1 expression but the phosphorylation level of no effect .Conclusion In this research,we demonstrate that deregulated GSK 3βsustains osteosarcoma cells survival through modulation of p27and cyclinD1-CDK-Rb pathway.The result will open up a potential target for clinical treatment of osteosar -coma.

Objective To observe the pathophysiological change of right heart remodeling model of beagle dogs caused by tricuspid regurgitation. Methods Six beagle dogs were separated to TR group and sham operation group randomly and equally. The anterior and posterior leaflets of tricuspid valve of beagle dogs from TR group were cut off under direct vision on the beating heart. The echocardiography data were measured pre-operation and post-operation 3, 6, 12 months respectively and autopsy results were acquired after the sacrifice of two animals who had been raised for 18 months. Results The operation was successful and survival 100%. The weight of TR group increased, and the echocardiography showed right atrium and ventricle enlargement and right heart dysfunction. The autopsy of TR group found myocardial fibrosis , liver cirrhosis and ascites. All of the results indicated the occurrence of right heart remodeling and right heart failure. There is no significant difference in sham operation group before or after operation. Conclusion The myocardial fibrosis is one of the pathological basis of right heart remodeling.