Objective:To screen and identify the potential targets of carthamin against sepsis by studying the characteristics of carthamin.Methods:The pharmacological parameters and molecular characteristics of carthamin were analyzed with the aid of Traditional Chinese Medicine Systems Pharmacology (TCMSP). The targets of carthamin were screened by SwissTargetprediction (a website providing compound target prediction) and Drug Repositioning and Adverse drug Reaction via Chemical-Protein Interactome (DRAR-CPI). The anti-sepsis targets were selected from the three databases of Online Mendelian Inheritance in Man (OMIM), Comparative Toxicogenomics Database (CTD) and Therapeutic Targets Database (TTD). The targets of carthamin screened by the two websites and disease targets selected from the three databases were matched to screen the targets of carthamin against sepsis. The anti-sepsis potential targets of carthamin were identified by molecular docking software.Results:The oral bioavailability of carthamin was 41.15%, the drug-likeness was 0.24, and the rotational bond number was 1, which indicated that carthamin was well absorbed by oral administration and showed good drug formation. A total of 115 potential targets of carthamin were screened by SwissTargetprediction and DRAR-CPI; 149 disease targets were found from OMIM, CTD and TTD databases; 115 target proteins of carthamin screened by the two websites were matched with the disease targets , and 10 target proteins were found to be both molecular targets and disease targets. The 10 target proteins were coagulation factor Ⅸ (F9), adenosine A1 receptor (ADORA1), nitric oxide synthase 2 (NOS2), mitogen activity protein kinase 1 (MAPK1), cathepsin G (CTSG), neutrophil elastase (ELANE), protein C (PROC), lipocalin 2 (LCN2), glucose-6-phosphate dehydrogenase (G6PD) and prostaglandin endoperoxidase 2 (PTGS2). Molecular docking software analysis showed that carthamin had the ability to bind to the above 10 target proteins, which were potential targets of carthamin against sepsis. Carthamin could interact with the key amino acid residues of the targeted proteins, so as to play the corresponding efficacy.Conclusion:Carthamin combines with the targets could reduce the tissues and organs damage of sepsis by regulating CTSG, ELANE and LCN2, reduce inflammatory response of sepsis by regulating ADORA1, PTGS2, NOS2, MAPK1 and mediating PROC and F9 to inhibit clotting, and improve oxidative stress, reduce the incidence of sepsis by regulating G6PD, finally, prevented and treated sepsis.

Serum p-amyloid peptide(Aβ)40 and Ap42 levels in patients with type 2 diabetes mellitus (T2DM)and atherosclerosis(AS)were detected by ELISA.The results showed that serum Ap40 level in T2DM group was significantly higher than that in the control group[(274.70±159.51 vs 162.63±87.58)pg/ml,P<0.05],especially in the diabetic patients accompanied with AS[(616.95±195.13)pg/m],P<0.01].Serum Ap40 level in simple AS group was also higher than that in control group[(318.52± 188.65)pg/ml,P<0.05].These results suggest that Ap40 is a risk factor of T2DM complicated with AS.However,there was no difference in serum Ap42 levels among various groups.

Objective To explore the expressions of miR-221 and miR-222 in papillary thyroid carcinoma (PTC),and relativi-ties with clinical pathological features.Methods Samples from patients of PCT (43 cases),nodular golter(21 cases),and para-carcinoma thyroid tissues(14 cases),78 cases in total (from 06/2015 to 05/2016,Shaanxi Provincial People’s Hospital) were collected.Real time-PCR tests were carried out,then analyzed in relation to clinical pathology features,and statistical a-nalysis was used to evaluate the results.Results The expressions of miR-221 and miR-222 were significantly higher in PTC (11.54±3.37,10.67±2.45)than in nodular golter (3.21±1.12,2.89±1.23)and normal thyroid tissue (2.02±0.76, 1.98±0.34)(t=3.62,3.25;3.27,3.01,all P<0.05),which were significantly related with Regional lymph node metasta-sis,tumor invasion coated,distant metastasis and clinical stage (P<0.05),while not related with the gender,age,or size of the tumor of the patients (P>0.05),and no differences were found in nodular golter and in normal thyroid tissue (t=0.91, 0.79,P>0.05).Conclusion miR-221 and miR-222 could be considered as a specific molecular marker of PTC,may play an important role in the diagnosis and treatment on PTC.

Objective To observe the biological activities of human doppel(Dpl) protein transiently expressed and Dpl-like protein PrP?32-121 on a human neuroblastoma cell line SH-SY5Y.Methods Recombinant mammalian expression plasmids containing human PRND gene and truncated PrP?32-121 fragment were generated by PCR.The expression and location of Dpl and PrP?32-121 post-transfection were observed by IFA.The cytotoxicity was measured by MTT analysis.Cellular apoptosis was investigated by flow cytometry and Western blot.Results Both Dpl and PrP?32-121 protein were expressed and mainly located on the cell membrane.Remarkable cytotoxicity was detected on SH-SY5Y cells after 24 h transfection.Meanwhile,more Annexin V/PI positively-stained cells as well as lower levels of cellular pro-caspase-3 and Bel-2 were detected in the cells receiving Dpl and PrP?32-121 expressing plasmids.Conclusion Dpl protein transiently expressed and PrP?32-121 can lead to the similar neural cytotoxicity,probably triggering the cell apoptosis program.

Objective To observe the biological activities of human doppel (Dpl) protein transiently expressed and Dpl-like protein PrPΔ32-121 on a human neuroblastoma cell line SH-SY5Y. Methods Recombinant mammalian expression plasmids containing human PRND gene and truncated PrPΔ32-121 fragment were generated by PCR. The expression and location of Dpl and PrPΔ32-121 post-transfection were observed by IFA. The cytotoxicity was measured by MTT analysis. Cellular apoptosis was investigated by flow cytometry and Western blot. Results Both Dpl and PrPΔ32-121 protein were expressed and mainly located on the cell membrane. Remarkable cytotoxicity was detected on SH-SY5Y cells after 24 h transfection. Meanwhile, more Annexin V/PI positively-stained cells as well as lower levels of cellular pro-caspase-3 and Bel-2 were detected in the cells receiving Dpl and PrPΔ32-121 expressing plasmids. Conclusion Dpl protein transiently expressed and PrPΔ32-121 can lead to the similar neural cytotoxicity, probably triggering the cell apoptosis program.

OBJECTIVE: To evaluate the clinical effect of sublingual immunotherapy with dust mite for allergic rhinitis. METHOD: The symptom score of 188 patients with dust mite allergic rhinitis were recorded before and after treatment for six months, a year, and compare the treatment effects. RESULT: Symptom scores of 188 patients were decreased after treatment than before, the symptoms of treatment were improved significantly after six months, symptoms were improved more significantly after one year, the difference was significant (P<0.01). CONCLUSION Sublingual immunotherapy with dust mite is a safe and effective treatment for allergic rhinitis, and it is worthy of promotion.
Administration, Sublingual ; Adolescent ; Adult ; Allergens ; administration & dosage ; immunology ; Animals ; Antigens, Dermatophagoides ; administration & dosage ; immunology ; Child ; Child, Preschool ; Desensitization, Immunologic ; Female ; Humans ; Immunotherapy ; Male ; Middle Aged ; Mites ; immunology ; Pyroglyphidae ; immunology ; Rhinitis, Allergic, Perennial ; immunology ; therapy ; Young Adult

Objective:To investigate the relationship between mental resilience and quality of life in patients with Parkinson ′s disease and provide basis for paying attention to the mental health of this group. Methods:A total of 190 in patients with Parkinson ′s disease (PD) were selected from April to July 2017 in the First Affiliated Hospital of Dalian Medical University. The general data questionnaire, Mental Resilience Scale and 39-Item Quality of Life (QOL) Questionnaires were used to investigate among the patients. Results:The mental resilience score of PD patients was 48.0 (29.8, 62.2) points and the quality of life score was 56.0 (27.8, 82.0) points. There was a significant negative correlation between mental resilience and quality of life score ( r value was -0.538, P<0.01). Multivariate linear regression analysis showed that with the increase of psychological elasticity score, the score of quality of life decreased ( b value was -0.002, P<0.001). Conclusions:The mental resilience and quality of life of PD patients are both at a low level, the improvement of mental resilience is beneficial to improve their quality of life.

Objective: To describe bullying victimization of middle school students in Dalian and associated factors, so as to provide scientific basis for campus bullying prevention. Methods: The stratified cluster sampling method was used to select 2 540 middle school students from urban and rural areas in Dalian, who were investigated with campus bullying victimization and related factors. Results: The reported rate of campus bullying victimization among middle school students in Dalian was 25.11%. The rates of physical violence (5.99%, 3.66%) and verbal violence(24.93%, 15.87%) of male students were higher than that of female students( χ 2=6.56, 27.94, P <0.05). The rates of verbal violence (22.84%, 16.25%) and emotional neglect(16.84%, 13.18%) of junior high school students were higher than those of high school students( χ 2=14.21, 5.44, P < 0.05 ). The rates of physical violence(6.07%, 3.55%), verbal violence(24.58%, 16.05%) and emotional neglect(18.88%, 12.06 %) of rural students were higher than those of urban students( χ 2=7.72, 24.81, 19.64, P <0.05). Male students, junior high school students and rural students suffered more severe campus bullying than female students, high school students and urban students( Z =3.46, 3.75, 5.89, P <0.01). The structural equation model showed that academic performance (path coefficient -0.003) and father s education (path coefficient -0.004 ) have a direct negative effect on campus bullying behavior, while mother s education (indirect action coefficient -0.000 8), height(indirect action coefficient -0.000 3), father s education (indirect action coefficient -0.000 3) and weight (indirect action coefficient 0.000 2) indirect effects on campus bullying through academic performance. Conclusion The prevalence of campus bullying victimization among middle school students in Dalian is relatively high, which worths further attention to. Rural students, junior high school students and boys are more likely to suffer campus bullying. Improving academic performance might be beneficial for campus bullying prevention.

BACKGROUNDThe mechanisms underlying diabetic encephalopathy are largely unknown, and no effective treatments are available. Catalpol has received much attention due to its numerous biological effects, especially in neuroprotective studies. The aim of this study was to investigate the effects of catalpol on cognitive functions in diabetic rats and the underlying mechanisms.

METHODSA rat model of diabetes was established by streptozotocin injection, followed by intraperitoneal infusion of catalpol after 10 weeks. Two weeks later, the Morris water maze was used to test the spatial learning performance. Nissl staining was performed to evaluate the morphological changes in the hippocampus. Expression of protein kinase Cγ (PKCγ) and caveolin-1 (Cav-1) in the hippocampus were assessed by reverse transcription PCR and Western blotting. Activities of anti-oxidative enzymes such as glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) and levels of malonaldehyde (MDA) were measured using commercial kits.

RESULTSSignificant hippocampal neuronal injury was observed in rats with streptozotocin-induced diabetes. Moreover, cognitive dysfunction was associated with markedly increased oxidative stress in the brain. Catalpol treatment significantly attenuated cognitive deficits, neuronal damage, and oxidative stress in the brain of diabetic rats. Biochemical analyses showed that catalpol reversed the down-regulation of PKCγ and Cav-1 expression in the diabetic rats.

CONCLUSIONSSpatial memory in diabetic rats is associated with the expression of PKCγ and Cav-1. Catalpol treatment markedly attenuated oxidative stress, reversed the alteration of PKCγ, Cav-1 and spatial memory deficits.

Animals ; Caveolin 1 ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; physiopathology ; Hippocampus ; drug effects ; metabolism ; Iridoid Glucosides ; therapeutic use ; Male ; Neuroprotective Agents ; therapeutic use ; Oxidative Stress ; drug effects ; Protein Kinase C ; metabolism ; Rats ; Spatial Memory ; drug effects ; physiology

OBJECTIVE： To prepare puerarin microemulsion with phase Ⅰ metabolic regulation （R-PR-ME） and to study pharmacokinetic characteristics of rats in vivo. METHODS： R-PR-ME and Puerarin microemulsion without metabolic regulation （NR-PR-ME） were prepared by Shah method. Pseudo-ternary phase diagram was used to optimize microemulsion formula using drug loading amount as index. The particle size and PDI of microemulsion were characterized by using a laser particle size analyzer. Rats were used as animal models， and HPLC method was used to determine the blood concentration of puerarin before and 5， 10， 15， 20， 30， 45， 60， 90， 120， 180， 240， 360， 480， 600 min after intragastric administration of R-PR-ME， NR-PR-ME and puerarin suspension （PR-SP） at puerarin dosage of 120 mg/kg. The pharmacokinetic parameters were calculated by using DAS 2.0 software. SPSS 19.0 software was used for statistical analysis. The relative bioavailability of R-PR-ME was calculated with NR-PR-ME as reference preparation. RESULTS： The formula of R-PR-ME included that oleoyl polyoxyl-6 glyserides （oil phase）-polysorbate 20 （emulsifier）-glycerides （co-emulsifier） mass ratio of 2 ∶ 4 ∶ 4； drug-loading amount of 67.50 mg/g， particle size was （22.59±0.53） nm （n＝3） and PDI was 0.182±0.017 （n＝3）. The formula of NR-PR-ME included that soybean oil （oil phase）-polysorbate 80 （emulsifier）- glycerol （co-emulsifier） mass ratio of 1 ∶ 4.5 ∶ 4.5， drug-loading amount of 61.32 mg/g， particle size of （15.45±1.06） nm（n＝3） and PDI of 0.156±0.012 （n＝3）. Pharmacokinetic parameters of R-PR-ME， NR-PR-ME and PR-SP included that AUC0-600 min were （134.187±37.152）， （65.145±18.762） and （49.623±12.143） μg·min/mL； cmax were （1.316±0.306）， （1.082±0.294） and （0.425±0.106） μg/mL； MRT were （155.068±33.204）， （100.264±27.683）， （60.524±14.086） min； t1/2β were （365.880±101.250）， （283.280±80.940）， （80.063±21.189） min （n＝6）， respectively. Compared with PR-SP， AUC0-600 min， cmax， MRT and t1/2β of R-PR-ME and NR-PR-ME were increased significantly （P＜0.05 or P＜0.01）. Compared with NR-PR-ME， AUC0-600 min， MRT and  t1/2β of R-PR-ME were more higher （P＜0.05）. The relative bioavailability of of R-PR-ME was 205.98％. CONCLUSIONS： R-PR-ME is prepared successfully with high drug-loading amount， and can significantly increase the bioavailability of puerarin in rats， compared with PR-SP and NR-PR-ME.