Glucagon-like peptide-1 ( GLP-1 ) is secreted by gut enteroendocrine cells. GLP-1 receptor agonists ( GLP-1 RAs) control glucose-related augmentation of insulin and suppress glu-cagon secretion. GLP-lRAs also inhibit gastric emptying, food intake and limit weight gain. In the past decade, significant progresses have been made in the investigation on the effects of GLP-1 RAs on cardiovascular system. The potential advantages of oral small-molecule GLP-1 RAs could improve the application of this class of drugs. This review highlights the multiple cardiovascular profiles of GLP-1 RAs in the treatment of cardiovascular diseases to provide new insights into cardiovascular benefits of GLP-1 RAs.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

Objective: To assess the safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use on different immunization procedures in healthy people aged 9-65 years. Methods: A randomized, blind, positive-controlled clinical study was conducted in March 2015. The eligible residents aged 9-65 were recruited in Dengfeng city and Biyang County, Henan Province. A total of 1 956 subjects were enrolled. The subjects were randomly (1∶1∶1) assigned to 5-dose control group, 4-dose trial group and 5-dose trial group, with 652 subjects in each group. The subjects of 5-dose control group were immunized with control vaccine on days 0, 3, 7, 14 and 28. The subjects of 4-dose trial group were immunized with trial vaccine on days 0, 7 and 21 (2-1-1 phases) and the subjects of 5-dose trial group were immunized with trial vaccine on days 0, 3, 7, 14 and 28. A combination of regular follow-up and active reporting was used to observe local and systemic adverse reactions till 30 days after the first and full immunization, and the incidence rate of adverse reactions in three groups was analyzed and compared. The venous blood was collected before the first immunization, 7 days after the first immunization, 14 days after the first immunization and 14 days after the full immunization. The neutralizing antibody of rabies virus was detected by rapid fluorescent focus inhibition test (RFFIT), and the seropositive conversion rate and geometric mean concentration (GMC) of antibody were calculated. Results: The adverse reaction rates in 5-dose control group, 4-dose trial group and 5-dose trial group were 41.87% (273/652), 35.43% (231/652) and 34.97% (228/652), respectively. The adverse reaction rates of 4-dose trial group and 5-dose trial group were lower than those of the 5-dose control group (P<0.05). The local reactions were mainly pain, itching, swelling and redness in injection site, while the systemic reactions were mainly fever, fatigue, headache and muscle pain. The severity of adverse reactions was mainly mild (level 1), accounting for 85.33% (518/607), 89.02% (373/419) and 88.96% (427/480) of the total number of adverse reactions in each group. At 14 days after the first immunization and 14 days after the full immunization, the antibody positive conversion rates of three groups were all 100%. At 7 days, 14 days after the first immunization and 14 days after the full immunization, the GMCs of three groups were 0.60, 0.72, 0.59 IU/ml, 20.42, 23.99, 24.38 IU/ml and 22.95, 23.52, 24.72 IU/ml, respectively, with no significant difference (P>0.05). Conclusion: The freeze-dried rabies vaccine (Vero-cells) for human use has good safety and immunogenicity when inoculated according to 5-dose and 4-dose immunization procedures.
Humans ; Rabies Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing ; Rabies virus ; Vaccination ; Rabies/prevention & control*

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Talent is one of the basic and strategic supports for building a modern socialist country in all aspects. Since the 1980s, the establishment of forensic medicine major and the cultivation of innovative talents in forensic medicine have become hot topics in higher education in forensic medicine. Over the past 43 years, the forensic medicine team of Shanxi Medical University has adhered to the joint education of public security and colleges, and made collaborative innovation, forming a training mode of "One Combination, Two Highlights, Three Combinations, Four in One" for innovative talents in forensic medicine. It has carried out "5+3/X" integrated reform, and formed a relatively complete talent training innovation mode and management system in teaching, scientific research, identification, major, discipline, team, platform and cultural construction. It has made a historic contribution to China's higher forensic education, accumulated valuable experience for the construction of first-class major and first-class discipline of forensic medicine, and provided strong support for the construction of the national new forensic talent training system. The popularization of this training mode is conducive to the rapid and sustainable development of forensic science, and provides more excellent forensic talents for national building, regional social development and the discipline construction of forensic science.
Humans ; Forensic Medicine/education* ; Aptitude

Proto-Oncogene Proteins c-akt ; TOR Serine-Threonine Kinases ; GTP-Binding Protein alpha Subunits, Gi-Go/metabolism*

Objective:To explore the mechanism of Yiqi Yangyin decoction in the treatment of thyroid cancer by means of network pharmacology and molecular docking technique.Meth-ods:the chemical constituents of 10 kinds of Yiqi Yangyin decoction were searched by HERB database,the active components were screened by PubChem and SwissADNE,and the action targets of active components were predicted by Swisstargetprediction.The disease targets after operation of thyroid cancer were obtained by searching the databases of GeneCards,OMIM,Dis-GeNET and DrugBank.The intersection target of drug and disease was obtained by Venny2.1.0 platform,the intersection target protein interaction network was constructed by String database,and the core target protein was screened by Cytoscape3.9.1,the drug-active ingredient-target network map was constructed by Cytoscape3.9.1,and the key active components were obtained;the enrichment analysis of GO and KEGG was carried out using Metascape database;and the molecular docking verification of key targets and key components was carried out.Results:157active components of Yiqi Yangyin decoction were obtained,and 507targets of active compo-nents were predicted,1817 targets of thyroid cancer-related diseases and 154targets of drug-disease intersection were obtained.The key target genes of SRC,HSP90AA1,PIK3R1,PIK3CA and AKT1 were obtained by PPI analysis.Quercetin,kaempferol and luteolin were the key active components.Molecular docking showed that the key targets and key active components had good affinity.KEGG enrichment analysis showed that cancer pathway,PI3K-Akt pathway and HIF-1 pathway were the key pathways of drug action.Conclusion:Yiqi Yangyin decoction can play a therapeutic role in anti-inflammation,anti-tumor and improving tissue microenvironment with multi-components,multi-targets and multi-pathways.

Objective: BMI may play a protective role in reducing the mortality rate of patients with chronic obstructive pulmonary disease (COPD), but its effect on acute exacerbation of COPD remain unclear. Methods: Subjects were selected from the COPD patients registration system established in 2014 in Pudong new district, Shanghai. COPD patients from 8 communities were selected by cluster sampling and follow up was conducted prospectively for 18 months. Basic information and BMI were obtained from baseline survey, and acute exacerbations were collected during follow-up. The association between BMI and risk of acute exacerbation was evaluated by using multiple negative binomial regression. Results: Among 328 community COPD patients, 295 who completed the follow up were included in the analysis, in whom 96.3% (284/295) were mild COPD patients. During the follow-up, 11.1% (33/295) of the patients reported acute exacerbation. The results of multiple negative binomial regression suggested that, the risk for acute exacerbation decreased with the increase of BMI (IRR=0.85, 95%CI:0.73-0.98), overweight patients with BMI ≥25.0 kg/m² (IRR=0.36, 95%CI:0.13-0.91) or moderate BMI (T₂ vs. T₁, IRR=0.31, 95%CI:0.11-0.77) had lower risk for acute exacerbation compared with the patients with normal or low BMI. BMI had a linear correlation with the risk of acute exacerbation. Conclusion: The risk for acute exacerbation in patients with mild or moderate COPD in communities decreased with the increase of BMI, and being overweight might be a protective factor for the acute exacerbation of COPD.
Body Mass Index ; China/epidemiology* ; Disease Progression ; Humans ; Overweight/complications* ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive/complications*

Objective To investigate the expression of elastin and collagen in heart of rats with chronic heart failure and their related proteases. Methods Sprague-Dawley rat model of chronic heart failure was made by intraperitoneal injection of doxorubicin hydrochloride. Examination of cardiac function by echocardiography. ELISA and immunohistochemistry were used to detect brain natriuretic peptide ( BNP) , and Masson staining was used to detect myocardial fibrosis. The mRNA levels of elastin, I /IH collagen were detected by Real-time PCR and the expression levels of elastin, I/IH collagen, Matrix metalloproteinase (MMP)-2 and MMP-9 were detected by Western blotting. Results Compared with the control group, the heart function of rats in the model group decreased, the BNP content in serum increased, the expression of BNP in myocardial tissue was strongly positive, and the mRNA and protein expression of elastin decreased. Nevertheless, the mRNA and protein expression of I / IH collagen increased. At the same time, both MMP-2 and MMP-9 protein expression levels increased in model rat heart. Conclusion Heart failure leads to decreased expression of elastin, I /IH collagen expression increased, and the MMP-2 and MMP-9 may be involved in the regulation of this process.