OBJECTIVE To investigate the effect of bs-5-YHEDA iron chelating peptide combined with semaglutide on the cognitive ability and pathological characteristics of D-Gal-induced Alzheimer's disease(AD) model mice. METHODS Forty mice were randomly divided into 5 groups, namely the healthy control group, PBS group, bs-5-YHEDA iron chelating peptide group, combined treatment group and positive control group, with 8 mice in each group, half of each sex. Except for the healthy control group, D-galactose was injected to induce the AD mice model for 6 weeks. For 3 consecutive weeks starting from the 4th week, the bs-5-YHEDA iron chelating peptide group was injected with bs-5-YHEDA(1 mg·mL–1) once every other day at 200 µL in the tail vein; the bs-5-YHEDA iron chelating peptide(1 mg·mL–1) and semaglutide(25 nmol·kg–1·d–1) were given alternately once a day in the combination treatment group; the positive control group was given memantine(3.3 mg·kg–1·d–1) by gavage every other day. The healthy control group and PBS group were injected with the equal dose of PBS. At the end of treatment, the learning memory ability of mice was detected by the Morris water maze method, whole brain and whole blood were dissected, and pathological changes in hippocampal region were observed by HE staining, and Aβ expression and Tau protein phosphorylation levels were detected by immunohistochemistry, enzyme-linked immunosorbent assay and immunoblotting. RESULTS In the Morris water maze spatial exploration experiment, the differences in the number of times the mice traversed the platform, the ratio of swimming distance to the target quadrant, and the time ratio were statistically significant in each group(P<0.05); compared with the PBS group, the ratio of swimming distance to the target quadrant increased in the combined treatment group, and the differences were statistically significant(P<0.05). The results of HE staining showed that compared with the healthy control mice, the hippocampal area in the PBS group showed reduced levels of pyramidal cells, disorganized arrangement, cell edema, and deep staining of nuclei consolidation. Cellular disorganization, deep staining of nuclei and apoptosis in the hippocampus were significantly improved in each treatment group after drug treatment. Immunohistochemistry and Western blotting results showed that the Aβ expression levels and Tau protein phosphorylation levels were significantly higher in the PBS-administered mice compared with the healthy control mice, and the Aβ expression levels and Tau protein phosphorylation levels were reduced in each group after drug treatment, with statistically significant differences(P<0.01 or P<0.001 ). CONCLUSION The combination of bs-5-YHEDA iron chelating peptide and semaglutide can effectively improve the learning and memory ability and pathological characteristics of AD mice, but from the results of immunohistochemistry and immunoblotting experiments, the improvement of pathological characteristics of AD mice in the combination treatment group is not obvious compared with the single bs-5-YHEDA iron chelating peptide group, suggesting that there may be a threshold effect of our designed dual-target combination treatment on the cognitive improvement of AD mice, and the optimization and validation of the effect of multi-target combination treatment need further study.

Objective To explore the effective chemical components of Fuzhenghuaxian decoction and its mechanism of action in the treatment of liver fibrosis based on UPLC-Q-TOF-MS combined with network pharmacology and experimental verification.Methods UPLC-Q-TOF-MS/MS technology was used to analyze the active components of Fuzhenghuaxian decoction.The potential targets and mechanisms of FZHXD were analyzed from the aspects of pharmacokinetics,target information,GO enrichment and KEGG Pathway.FZHXD was used to verify the key pathways and targets screened by network pharmacology in mice with liver fibrosis induced by carbon tetrachloride(CCl4),and further improve the accuracy of its prediction results.Results A total of 35 effective chemical components were identified,mainly saponins and organic acids.Through network pharmacology screening,669 drug targets,440 common targets,5 core targets and 11 key active ingredients were obtained.The main signal transduction pathways were predicted to be PI3K-Akt,FOXO,NF-κB signaling pathway,etc.In vivo experiments confirmed that FZHXD improved liver fibrosis in mice through PI3K/AKT,FOXO and NF-κB signaling pathways.Conclusion Fuzhenghuaxian decoction has the characteristics of multi-pathway and multi-target in anti-liver fibrosis by down-regulating PI3K,AKT,NF-κB and up-regulating FOXO.

Objective To explore the effective chemical components of Fuzhenghuaxian decoction and its mechanism of action in the treatment of liver fibrosis based on UPLC-Q-TOF-MS combined with network pharmacology and experimental verification.Methods UPLC-Q-TOF-MS/MS technology was used to analyze the active components of Fuzhenghuaxian decoction.The potential targets and mechanisms of FZHXD were analyzed from the aspects of pharmacokinetics,target information,GO enrichment and KEGG Pathway.FZHXD was used to verify the key pathways and targets screened by network pharmacology in mice with liver fibrosis induced by carbon tetrachloride(CCl4),and further improve the accuracy of its prediction results.Results A total of 35 effective chemical components were identified,mainly saponins and organic acids.Through network pharmacology screening,669 drug targets,440 common targets,5 core targets and 11 key active ingredients were obtained.The main signal transduction pathways were predicted to be PI3K-Akt,FOXO,NF-κB signaling pathway,etc.In vivo experiments confirmed that FZHXD improved liver fibrosis in mice through PI3K/AKT,FOXO and NF-κB signaling pathways.Conclusion Fuzhenghuaxian decoction has the characteristics of multi-pathway and multi-target in anti-liver fibrosis by down-regulating PI3K,AKT,NF-κB and up-regulating FOXO.

Objective:To study the use of three-dimensional computer reconstruction in diagnosis and treatment of hilar cholangiocarcinoma.Methods:A retrospective analysis of clinical data was conducted on patients with hilar cholangiocarcinoma admitted to the Department of General Surgery, the First Affiliated Hospital of the University of Science and Technology of China from January 1, 2017 to July 31, 2019. The classification of hilar cholangiocarcinoma, vascular invasion and surgical resectability were determined by preoperative three-dimensional reconstruction. These data were then compared with the findings obtained during operations, by comparing with the three-dimensional reconstruction technology findings in classification of hilar cholangiocarcinoma, vascular invasion, and hilar extent of biliary and vasculature involvement.Results:Of 65 patients included in this study, there were 35 males and 30 females, with an age of (60.35±10.70) years. After operation, these 65 patients were classified into type I ( n=7), type II ( n=4), type III ( n=14), and type IV ( n=40) using the Bismuth classification. The accuracy rates of preoperative three-dimensional reconstruction for hilar cholangiocarcinoma classification, portal vein invasion, hepatic artery invasion, and diagnosis of hilar cholangiocarcinoma vasculature involvement were 90.7% (59/65), 90.7% (59/65), 86.1% (56/65) and 80.0% (52/65) respectively. Conclusions:The three-dimensional computer reconstruction technology could visually and accurately display the shape and spatial extent of hilar cholangiocarcinoma. It has an important clinical use in accurately diagnosing hilar cholangiocarcinoma preoperatively.

Objective To explore the diagnostic value of dual syringe and dual-channel direct multi-slice computed tomography venography(MSCTV) for lower extremity deep venous obstructive disease.Methods 100 patients highly suspected deep vein thrombosis by clinic wereunderwent dual syringe and dual-channel direct MSCTV.The original data processed with technology of subtraction,and put into workstation and reconstructed with maximum intensity projection(MIP),multiplanar reformation(MPR) and volume rendering (VR).Images of deep venous obstructive lesions were analysed and graded.All patients were underwent DSA in one week.Results Direct MSCTV showed that the reconstructed images and the vascular contrast were very clear.In the evaluation of deep venous,excellent proportion was 95 ％ for the inferior vena cava,94 ％ for the common iliac vein,95 ％ for the external iliac vein,95.5 ％ for the femoral vein,96.5％ for the popliteal vein and 92 ％ for the low leg vein.Direct MSCTV displayed complete and regular vein in 8 normal patients,92 cases displayed different parts and different degrees of thrombosis.On original axial images,eccentric filling defect of vascular were showed (there were 64 multiple vein occlusion cases and 28 solitary obstruction cases).The occlusion locations in deep venous were as following:3 in the inferior vena cava,67 in the common iliac vein,28 in the external iliac vein,50 in the femoral vein,26 in the popliteal vein,89 in the anterior tibial vein,35 in the posterior tibial vein and 5 in the peroneal vein.There were 7 normal patients and 93 patients with different parts and different degrees of thrombosis.Conclusion Direct MSCTV can accurately show deep vein thrombosis,which image is clear and reliable for displaying the scope and extent of lesions of the vascular and whether the collateral circulation established.Direct MSCTV has a significant clinical value in diagnosing the thrombotic disease of deep vein obstructive lesions.

Objective To examine the sex differences in prescribing patterns of psychotropic drugs and drug-induced side effects in schizophrenia patients in China. Methods Using the same design and a standardized protocol as in 2002 and 2006, the cross-sectional survey was conducted from July to August, 2012 in 45 psychiatric hospitals/centers in 10 provinces and municipalities in China. Inpatients and outpatients with schizophrenia were consecutively screened for eligibility for this study. Sociodemographic characteristics and prescription pattern were collected by using a modified questionnaire for the study. Data comparisons between male and female were performed with univariate analysis. Multiple logistic regression analysis was employed to determine the gender differences in prescription pattern and drug-induced side effects. Results The sample consisted of 2 260 male and 1 979 female patients. Univariate analyses showed that male patients were younger than female patients(t=5.398), having an earlier age at onset(t=5.662), higher percentage of being employed(χ2=31.597), and more negative symptoms(χ2=10.814)and aggressive behavior (χ2=5.816), more likely to receive clozapine (23.9%(472/1 979) vs. 28.5%(645/2 260),χ2=11.955), higher antipsychotic doses(476 mg vs. 514 mg,F=14.003), less use of antidepressants (7.9%(156/1 979) vs. 6.0%(136/2 260),χ2=5.722)and benzodiazepines(23.9%(472/1 979)vs. 20.0%(451/2 260),χ2=9.396), more frequent tardive dyskinesia(1.3%(25/1 979)vs. 2.1%(47/2 260),χ2=4.212)and less weight gain(11.0%(218/1 979)vs. 7.7%(173/2 260),χ2=14.233)and prolactin elevation(3.2%(63/1 979)vs. 1.7%(39/2 260),χ2=9.548;all P<0.05). In multivariate analyses, greater rate of clozapine use (OR=1.268,P=0.001), less rate of benzodiazepines use(OR=0.841,P=0.025) and antidepressants(OR=0.78,P=0.045),higher rate of tardive dyskinesia(OR=1.879,P=0.014)and less weight gain (OR=0.669,P=0.001) and prolactin elevation (OR=0.527,P=0.003) were independently associated with the male sex. Conclusion Gender is one of the independent contributors to psychotropic prescription pattern and side effects of antipsychotics in Chinese schizophrenia patients. Gender differences should be given more attention in research and clinical practice.

Objective To examine the sex differences in prescribing patterns of psychotropic drugs and drug-induced side effects in schizophrenia patients in China. Methods Using the same design and a standardized protocol as in 2002 and 2006, the cross-sectional survey was conducted from July to August, 2012 in 45 psychiatric hospitals/centers in 10 provinces and municipalities in China. Inpatients and outpatients with schizophrenia were consecutively screened for eligibility for this study. Sociodemographic characteristics and prescription pattern were collected by using a modified questionnaire for the study. Data comparisons between male and female were performed with univariate analysis. Multiple logistic regression analysis was employed to determine the gender differences in prescription pattern and drug-induced side effects. Results The sample consisted of 2 260 male and 1 979 female patients. Univariate analyses showed that male patients were younger than female patients(t=5.398), having an earlier age at onset(t=5.662), higher percentage of being employed(χ2=31.597), and more negative symptoms(χ2=10.814)and aggressive behavior (χ2=5.816), more likely to receive clozapine (23.9%(472/1 979) vs. 28.5%(645/2 260),χ2=11.955), higher antipsychotic doses(476 mg vs. 514 mg,F=14.003), less use of antidepressants (7.9%(156/1 979) vs. 6.0%(136/2 260),χ2=5.722)and benzodiazepines(23.9%(472/1 979)vs. 20.0%(451/2 260),χ2=9.396), more frequent tardive dyskinesia(1.3%(25/1 979)vs. 2.1%(47/2 260),χ2=4.212)and less weight gain(11.0%(218/1 979)vs. 7.7%(173/2 260),χ2=14.233)and prolactin elevation(3.2%(63/1 979)vs. 1.7%(39/2 260),χ2=9.548;all P<0.05). In multivariate analyses, greater rate of clozapine use (OR=1.268,P=0.001), less rate of benzodiazepines use(OR=0.841,P=0.025) and antidepressants(OR=0.78,P=0.045),higher rate of tardive dyskinesia(OR=1.879,P=0.014)and less weight gain (OR=0.669,P=0.001) and prolactin elevation (OR=0.527,P=0.003) were independently associated with the male sex. Conclusion Gender is one of the independent contributors to psychotropic prescription pattern and side effects of antipsychotics in Chinese schizophrenia patients. Gender differences should be given more attention in research and clinical practice.

This study compared the efficacy and safety of tiotropium bromide inhalation powder (spiriva) and doxofylline oral tablet (doxofylline) in the treatment of chronic obstructive pulmonary disease (COPD). A multi-center, randomized, double-blind, double-dummy, parallel-controlled study involved 127 eligible stable moderate to severe COPD patients treated with inhaled tiotropium dry powder (18 μg/day) or oral doxofylline tablets (0.2 g/time, 2 times a day) for 12 and 24 weeks. Before and after treatment for 12 weeks and 24 weeks, respectively, pulmonary function, 6-min walking distance and dyspnea index were recorded. The results showed that in both tiotropium group and doxofylline groups, after 12-week treatment, FEV(1), FEV(1)/FVC% and 6-min walk distance were significantly higher than those before the medication, while dyspnea index decreased as compared with that before treatment. After 24-week treatment, a slight improvement in the measures was observed as compared with that of 12-weeks treatment, but the difference was not statistically significant. With both 12-week and 24-week treatment, the effect of tiotropium was slightly better than that of doxofylline tablets, with the difference being statistically insignificant. The major adverse events in the tiotropium group and doxofylline group were observed in 9 cases (9.9%) and 12 cases (12.9%), respectively, and no statistically significant difference was found between them. We are led to conclude that both tiotropium at 18 μg a day and doxofylline tablets at 0.2 g/day (two times a day) are effective and safe for the treatment of COPD.

This study compared the efficacy and safety of tiotropium bromide inhalation powder (spiriva) and doxofylline oral tablet (doxofylline) in the treatment of chronic obstructive pulmonary disease (COPD).A multi-center,randomized,double-blind,double-dummy,parallel-controlled study involved 127 eligible stable moderate to severe COPD patients treated with inhaled tiotropium dry powder (18 μg/day) or oral doxofylline tablets (0.2 g/time,2 times a day) for 12 and 24 weeks.Before and after treatment for 12 weeks and 24 weeks,respectively,pulmonary function,6-min walking distance and dyspnea index were recorded.The results showed that in both tiotropium group and doxofylline groups,after 12-week treatment,FEV1,FEV1/FVC％ and 6-min walk distance were significantly higher than those before the medication,while dyspnea index decreased as compared with that before treatment.After 24-week treatment,a slight improvement in the measures was observed as compared with that of 12-weeks treatment,but the difference was not statistically significant.With both 12-week and 24-week treatment,the effect of tiotropium was slightly better than that of doxofylline tablets,with the difference being statistically insignificant.The major adverse events in the tiotropium group and doxofylline group were observed in 9 cases (9.9％) and 12 cases (12.9％),respectively,and no statistically significant difference was found between them.We are led to conclude that both tiotropium at 18 μg a day and doxofylline tablets at 0.2 g/day (two times a day) are effective and safe for the treatment of COPD.

Objective To set up a three-dimensional finite element model (FEM) to investigate biomechanics of point contact locking plate (PC-LP) fixating femoral shaft fractures. Methods One intact fresh adult cadaveric femur was scanned by CT at 1 mm interval. Then, the data of CT were utilized to establish three-dimensional FEM by using software Mimics and PRO/E and simulate the different clini-cal loading conditions. The changes of theoretical stress of femur and PC-LP were analyzed under flexion, axial compression and torsion loads. Results (1) Under four-point bending load, the distribution of femur stress was in uniformity, with the largest stress of the PC-LP focused on the edge. (2) Under axial compression load of 250 N, the largest stress of the femur was focused on the screw holes on beth distal ends, with the largest stress of the PC-LP focused on the middle screw holes. (3) Under the torsion load cused on the middlepart and the middle screw holes. Conclusions Under the four-point bending, ax-ial compression and torsion loads, the distribution of femur stress is in uniformity, when the largest stress of the PC-LP focuses on edge or the middle screw holes, while that of the PC-LP on two screw holes of proximal or distal ends.