Objective To design and synthesize a series of new type four hydrogen quinoline-benzyl/benzimidazole amine derivatives as a potential new inhibitor targeting auxiliary receptor CXCR 4, and determine their inhibitory activities to HIV-1.Methods Based on HIV-1 receptor CXCR4 inhibitors containing three nitrogen structure-activity motif and CCR5 partial hydrophobic pharmacophore , a series of new compounds were designed , synthesized and characterized by 1 HNMR and MS.The inhibitory activities of these compounds were determined using HIV-1 IIIB virus.Results and Conclusion Ten target compounds are synthesized .Four hydrogen quinoline-benzimidazole amine derivatives exhibit good anti-HIV activity(IC50 <1 μmol/L), but four hydrogen quinoline-benzyl amine compounds are less active ((IC50 >8 μmol/L).

BACKGROUND: Ultraviolet light (UVA) has a close relationship with photoaging, and mitochondrial damage is a basis of coil senescence and death.OBJECTIVE: To explore the influence of UVA on the mitochondrial deoxyribonucleic acid of human skin fibroblasts, in addition, to discuss whether transforming growth factor β1 (TGF-β1) could relieve mitochondrial DNA (mtDNA) deletion. DESIGN, TIME AND SETTING: The experiment was performed at Department of Plastic Surgery, the First Affiliated Hospital of Fourth Military Medical University from March 2007 to April 2008.MATERIALS: TGF-β1 was purchased from PerProtech Company; rnitochondrial DNA 4 977 bp primer was synthesized by Shanghai Sangon Biological Engineering Technology & Services Co., Ltd; UVA light was produced by Beijing Optical Instruments Factory; and the ultraviolet radiation meter was provided by Photoelectric Instrument Factory of Beijing Normal University.METHODS: Young adult's fibroblasts were obtained from 12 cases with posthectomy. Then the cells were divided into control,UVA irradiation (30, 60, 90 J/cm~2) groups. The mitochondrial DNA 4 977 bp deletion was detected by semi-quantitative PCR. After that, TGF-β1 with different doses (0.1, 1, 10 βg/L) were used to interfere the cells with UVA 90 J/cm~2 irradiation.MAIN OUTCOME MEASURES: DNA 4 977 bp deletion under different doses cumulative irradiation, as well as the effect of TGF-β1 on mtDNA 4 977bp deletion after irradiates UVA90 J/cm~2 were observed.RESULTS: Mitochondrial DNA 4 977 bp had deleted when irradiated with cumulative dose of 60 J/cm~2 UVA, the deletion was aggravated when the UVA dose arrived at 90 J/cm~2, The absorbance value, PCR electrophoresis and band scanning showed that the deletion of mitochondrial DNA 4 977 bp was reduced after adding TGF-β1 at 2 hours prior to irritation in the large dose (10 μg/L) group. However, the difference between the medium and small dose groups had no obviously significance.CONCLUSION: A certain dose of TGF-β1 (10 μg/L) has protective effect on mtDNA 4 977 bp deletion.

Objective:To investigate the relationship between metabolic syndrome and 1-year poor outcome in elderly patients with acute cerebral infarction (ACI).Methods:The clinical data of elderly patients with ACI admitted to Renqiu Kangjixintu Hospital from January 2014 to November 2018 were selected and divided into metabolic syndrome group (931 cases) and non-metabolic syndrome group (1 851 cases). The clinical data of the two groups of elderly patients with ACI were compared, and the effect of metabolic syndrome on poor outcome (modified Rankin scale>2 scores) of elderly patients with ACI in 1 year was analyzed by multivariate Logistic regression.Results:The proportion of female, hypertension, diabetes, hyperlipidemia, coronary heart disease, smoking, excessive alcohol consumption and antiplatelet drug use in the metabolic syndrome group were higher than those in the non-metabolic syndrome group: 52.74%(491/931) vs. 32.58%(603/1 851), 79.16%(737/931) vs. 64.29% (1 190/1 851), 42.32% (394/931) vs. 6.43% (119/1 851), 17.19% (160/931) vs. 11.62% (215/1 851), 18.90% (176/931) vs. 14.10% (261/1 851), 62.73% (584/931) vs. 50.89% (942/1 851), 3.73% (69/931) vs. 1.61% (15/1 851), 19.23% (179/931) vs. 15.51% (287/1 851), the levels of body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), fasting plasma glucose (TG), total cholesterol (TC), platelet (PLT), fibrinogen (FIB), fall score were higher than those in non-metabolic syndrome group: 26.67 (25.31, 28.60) kg/m 2 vs. 23.30 (21.48, 24.91) kg/m 2, (167.17 ± 22.96) mmHg (1 mmHg = 0.133 kPa) vs. (164.21 ± 24.90) mmHg, (87.06 ± 13.10) mmHg vs. (85.76 ± 12.99) mmHg, (7.33 ± 2.64) mmol/L vs. (5.35 ± 1.38) mmol/L, (2.12 ± 1.51) mmol/L vs. (1.13 ± 0.78) mmol/L, (4.97 ± 1.31) mmol/L vs. (4.65 ± 0.99) mmol/L, 213.00 (179.00, 256.00) × 10 9/L vs. 203.00 (172.00, 241.00) × 10 9/L, 3.07 (2.63, 3.52) g/L vs. 2.94 (2.55, 3.37) g/L, (6.12 ± 1.70) scores vs. (5.93±1.74) scores, the levels of age, high density lipoprotein cholesterol (HDL-C), homocysteine (Hcy) and pressure ulcer score were lower than those of non-metabolic syndrome group: (69.29 ± 6.96) years vs. (71.28 ± 7.66) years, (0.98 ± 0.34) mmol/L vs. (1.31 ± 0.88) mmol/L, (18.93 ± 13.07) mmol/L vs. (21.66 ± 16.39) mmol/L, (18.55 ± 2.42) vs. (19.02 ± 2.43), with statistical significance ( P<0.05). After 1-year follow-up, the proportion of poor outcomes in the metabolic syndrome group was higher than that in the non-metabolic syndrome group: 21.70%(202/931) vs. 18.69% (346/1 851), with statistical significance ( P<0.05). Multivariate Logistic regression analysis showed that age, stroke, national institutes of health stroke scale (NIHSS) score at admission, systolic blood pressure, Hcy, pressure ulcer score, fall score, metabolic syndrome were independent risk factors for poor outcome of ACI in 1 year ( OR = 1.056, 1.309, 1.138, 1.005, 1.006, 0.882, 1.076 and 1.285; 95% CI 1.040 to 1.072, 1.037 to 1.652, 1.097 to 1.180, 1.000 to 1.010, 1.000 to 1.013, 0.834 to 0.933, 1.004 to 1.152 and 1.001 to 1.657; P<0.05). Conclusions:Multiple risk factors for stroke are closely related to poor outcome of ACI in the elderly. And metabolic syndrome is an independent risk factor for poor outcome of ACI in the elderly in 1 year.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Objective To investigate the epidemiological characteristics of Salmonella infection in foodborne diseases in Shanxi Province, and to provide a scientific basis for the prevention and control of Salmonella infection. Methods Automatic microbial biochemical identification system was used to identify Salmonella , and descriptive epidemiological methods were used to analyze the characteristics of Salmonella infections in foodborne diseases in Shanxi Province from 2016 to 2021. Results The basic information of 10 037 cases of foodborne diseases and their Salmonella detection results were analyzed. The detection rate of Salmonella was 5.25%, and the main serotype was Salmonella enteritidis (209/522). The positive detection rate of Salmonella in the 0-10 years old age group was the highest (6.04%), and the difference was statistically significant (χ²= 19.23, P = 0.01). The positive detection rate of Salmonella in kindergarteners was the highest at 10.71%, and there was a significant difference in the positive detection rate among different occupations (χ²= 43.31, P < 0.05). The detection rate of bulk foods (5.16%) was higher than that of pre-packaged foods (3.70%), and the difference was statistically significant (χ²= 4.43, P = 0.04). Cases involving food stores had a higher Salmonella detection rate (9.54%), and the peak period of Salmonella infection was from May 24 to August 23. Conclusion The incidence of Salmonella infection in foodborne diseases is high in summer and autumn. Foods in food stores and bulk foods are more likely to cause Salmonella infection. Supervision and management of food stores should be strengthened, and special attention should be paid to children in kindergartens during the epidemic peak.