Effect of molecular weight of polyethylene glycol on pharmacokinetics of baicalin / 药学学报

The aim of this study was to investigate the effects of polyethylene glycol (PEGs) with different molecular weights (MW: 400, 1 000, 4 000) on the pharmacokinetics of baicalin, and preliminarily analyze its mechanism. Rats were gavaged with baicalin (168 mg·kg-1) + aqueous solution or baicalin + PEGs solution and plasma samples were collected from 0 to 24 h after administration. The concentration of baicalin and its main metabolite baicalein 6-O-β-D-glucuronide (B6G) were determined at different time points by UPLC-MS/MS, and the pharmacokinetic parameters were calculated with DAS 3.0 software. The results showed that PEGs with different molecular weights could effectively increase the AUC0-t of baicalin and B6G, increase the Cmax, and prolong the t1/2, effectively increasing the concentration of baicalin and B6G in vivo. The mechanism may be by promoting the activity of uridine diphosphate glucuronosyl-transferases 1A8 (UGT1A8) and 1A9 (UGT1A9), thereby increasing the transformation rate of baicalin and B6G. The rate of metabolism of B6G was faster than that of baicalin, suggesting that PEGs had a higher affinity for UGT1A8, and PEG400 had the most significant effect. The purpose of this study was to provide a basis for the clinical safe use of baicalin and other flavonoids and the design of new dosage forms with the participation of PEGs. The animal experiment protocol in this study was approved by the Experimental Animal Ethics Committee of Guizhou Medical University.

Investigation of Effect of Polyethylene Glycol 400 on Pharmacokinetics and Anti-inflammatory Effect of Baicalin Based on UPLC-MS/MS and Molecular Docking Techniques / 中国实验方剂学杂志

Objective:To investigate the effects of polyethylene glycol 400 （PEG400） on the pharmacokinetics and anti-inflammatory effect of baicalin， and to preliminarily explore the anti-inflammatory effects of baicalin and its main metabolite baicalein 6-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucuronide （B6G） by molecular docking. Method:Rats were randomly divided into two groups with water and PEG400 as the dissolving matrix， and rats were administrated the equal dose of baicalin aqueous solution （baicalin+water group） and baicalin PEG400 solution （baicalin+PEG400 group）. After the plasma samples were processed at different time periods， the concentrations of baicalin and B6G in rat plasma were determined by ultra performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and pharmacokinetic parameters were processed by DAS 3.2.2 software. Mice were randomly divided into a blank group （normal saline， 20 mL·kg^-1）， aspirin group （dose of 0.2 g·kg^-1）， baicalin/baicalin+PEG400 high and low dose （3.0， 1.5 g·kg^-1） groups， after continuous administration for 7 days， the mouse ear swelling and foot swelling models were established， and the swelling degree and swelling inhibition rate were calculated. Result:The pharmacokinetic study showed that compared with baicalin+water group， the plasma concentrations of baicalin and B6G increased after administration of baicalin PEG400 solution， and the area under the curve （AUC_0-<italic>_t</italic>） increased by 2.36， 1.97 times， and the peak concentration （<italic>C</italic>_max） increased by 2.12， 1.65 times， respectively. The results of mouse ear and foot swelling inflammation models showed that the anti-inflammatory effect was enhanced after intragastric administration of baicalin PEG400 solution. In addition， molecular docking results showed that baicalin and B6G could site bind to multiple target proteins ［tumor necrosis factor （TNF）-<italic>α</italic>， interleukin （IL）-6， IL-1<italic>β</italic>， prostaglandin E₂ （PGE₂） and nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B）］ with higher affinity， which was superior to the positive drug aspirin. Conclusion:PEG400 can increase the plasma concentration of baicalin and its main metabolite B6G， and enhance the anti-inflammatory effect. Baicalin and B6G can form strong hydrogen bonds with various inflammatory factors and of nuclear transcription factors， it is speculated that baicalin and B6G jointly play an anti-inflammatory role.

Study on epidemic factors of varicella outbreak under high varicella vaccine coverage / 中华疾病控制杂志

Objective To explore the epidemic factors of varicella transmission under high varicella vacince coverage, assess the vaccine effectineness of one dose of varicella vaccine, so as to provide scientific basis for controlling the varicella outbreak and optimizing the varicella immunization strategy. Methods A 1 ∶〗2 paired case-control study of a varicella outbreak was conducted in a primary school in central region of Jiangsu Province in 2018. Analysis of varicella epidemic factors was performed using conditional logistic stepwise regression. Results This outbreak lasted for 14 days. A total of 45 students were infected with varicella, of which 71.1% were breakthrough cases. The fever, rash degree and disease course of breakthrough cases were all relatively mild compared with those without immune history (all P5 years and the initial immunization age <15 months were potential risk factors for breakthrough cases. The overall vaccine effectiveness of one dose of varicella vaccine was 77.9%(95% CI: 53.3%-92.1%). The fever, severity of the rash and the course of the disease were all milder than those without the history of immunization (all P<0.05). Conclusions The clinical symptoms of the breakthrough cases are relatively mild, and one dose of varicella vaccine is insufficient to control the outbreak of varicella with limited vaccine effectiveness. Two doses of varicella immunization strategy is recommended.

The prospective study of association between C-reactive protein and hypertension in community population / 中华预防医学杂志

<p><b>OBJECTIVE</b>The aim was to explore the association between high-sensitivity C-reactive protein level at baseline and hypertension in follow-up periods in a Chinese cohort.</p><p><b>METHODS</b>We analyzed data from a cohort established in "Prevention of metabolic syndrome and multi-metabolic disorders in Jiangsu province" in April 2000. A follow-up investigation was carried out for those whose follow up time met 5 years in June 2006. A total of 2035 persons completed investigation and hs-CRP was tested. Subjects with normal baseline blood pressure were classified into four groups(514, 498, 515 and 508 subjects in each group) according to quartiles of hs-CRP level (<1.3, 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L). The relationship between the risk of hypertension and baseline level of hs-CRP were analyzed using Cox proportional hazards regression model.</p><p><b>RESULTS</b>The median of follow up time was 6.39 years among the 2035 subjects (926 males and 1109 females). Hypertension incidence was 2378/100 000 person-years, 2942/100 000 person-years, 3693/100 000 person-years and 4390/100 000 person-years in hs-CRP < 1.3, 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L groups respectively. Compared to the group of hs-CRP < 1.3 mg/L, the relative risk (RR) (95%CI) of hypertension in groups of hs-CRP 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L was 1.22 (0.87-1.72), 1.43 (1.03-2.00), 1.70 (1.21-2.41) respectively, adjusted for sex, age, baseline blood pressure, BMI, smoking, alcohol drinking, physical activity and family history of myocardial infarction and diabetes.When stratified by quartiles of baseline blood pressure, the incidence of hypertension in each group increased with level of hs-CRP.In the group whose baseline SBP < 110 mm Hg (1 mm Hg = 0.133 kPa) , compared to the group of hs-CRP < 1.3 mg/L, RR (95%CI) were 2.24 (1.32-4.03), 2.57 (1.57-4.57) and 3.57 (2.54-5.90) in hs-CRP 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L groups respectively.In the group whose baseline DBP < 65 mm Hg, RR (95%CI) were 1.78 (1.03-3.24), 2.74 (1.63-4.93) and 4.13 (2.35-7.27) respectively.</p><p><b>CONCLUSION</b>Inflammation was an important process in the development of hypertension.</p>

A prospective study on the association between dyslipidemia and hypertension / 中华流行病学杂志

Objective To discuss the risks of hypertension development with relation to the level of lipid variables among populations who had normal blood pressure at baseline study. Methods In April 2000, under the support of project "prevention of metabolic syndrome and multi-metabolic disorders in Jiangsu province", a cohort study was performed to obtain the baseline data among 8685 persons from age 34 to 74. In June of 2006, a follow-up investigation was carried out among those who had been in the study for 5 years after the baseline study started. 2603 persons who met the selection criteria and showed normal blood pressure during baseline study, were recruited in this investigation. The interval from the baseline to the follow-up studies was 6.38 years on average. Relationship between the risk of developing hypertension and the baseline level of lipid variables were analyzed. Results Relations between baseline lipid levels and the incidence of hypertension during the follow-up was discovered. In gender and age adjusted model, the lipid variables were all associated with hypertension(Wend test, P<0.01). In multivariable-adjusted model, HDL-C [aRR=0.71 (95%CI: 0.61-0.99)], non-HDL-C [αRR=1.28 (95%CI: 1.14-1.83)], TC/HDL-C ratio[aRR=1.41 (95%CI: 1.25-2.03)] and TG [αRR=1.49(95%CI: 1.30-2.13)] were again associated with hypertension (trend test, P<0.05). Even the αRR was much weakened after the baseline SBP, DBP were adjusted with Cox model, the significant relation of hypertension to HDL-C, TC/HDL-C ratio and TG still existed. Excluding the two factors of obesity (BMI≥28) and diabetes which had been recognized in marked linking with hypertension, lipid variables were still associated with hypertension. Conclusion Dyslipidemia might occur before being hypertensive. Hypertension was associated with HDL-C, TC/HDL-C and TG or even exclusion of obesity, diabetes and factors of smoking and drinking or baseline level of SBP, DBP were adjusted.

Analysis on 60 Pollution Accidents of Municipal Water Distribution Network and Secondary Water Supply System / 环境与健康杂志

To understand the characteristics and causes of the pollution accidents of municipal water distribution network and secondary water supply system.Data on the pollution accidents of municipal water distribution network and secondary water supply system having occurred in recent 20 years were collected and analyzed. The main pollution type of municipal water distribution network and secondary water supply system was biological pollution,the amount of which took 73.3% of the total accidents.The pollution accidents mainly occured in schools or colleges and residential buildings offered by some enterprises to their members and families with an occurrence rate of 11.7%,besides residential quarters,enterprises and institutions.The main links of pollution were observed in municipal water distribution system(51.7%)and water storage tanks high and low lying(43.3%).The main causes of pollution accidents were the leakage and breakage facilities and mislink between the water pipes and sewage pipes, which resulted in formation of negative pressure.Siphonage and sewage flowing backward,in addition the poor sanitary protection facilities polluted by sewage and rubbish. It was the top priorities to establish special legal system,to enhence the preventive sanitary inspection