注射用肉毒毒素制剂及其研发进展

肉毒毒素(Botulinum Toxin,BoNT)已成为现代医学最具多用途的治疗药物之一。通过将肉毒毒素注射到特定过度活动的肌肉中,可以阻断神经和肌肉之间的信号传导,引起肌肉的松弛性麻痹,从而达到治疗的功效。从业者应熟悉各类产品的特性,以实现安全有效地使用。除了已经上市的众多肉毒毒素产品外,目前还在开发其他新型制剂,这些产品将会进一步扩大肉毒毒素的适用范围,以及给患者提供更多的选择。     

温病学理论指导下的新型冠状病毒肺炎诊治刍议

基于温病学理论,探讨新型冠状病毒肺炎的中医病因病机与诊治思路。温病学说源于明清之前的历代中医理论积累,经过长期的温热病防治实践而形成,其对于外感热病(包括烈性传染病)的病因病机、证治方药有着较为系统的论述,近年来在我国的新发传染病防治中发挥出积极的作用。温瘟相通,瘟疫病因多为热毒疫邪,表现为热证阳证,可按温病学中的卫气营血或三焦辨证分期论治,或治以吴又可、庞安时等的经方验方,这些因、机、证、治理论可试用于新型冠状病毒肺炎的中医诊疗。且肺与大肠相表里,胃肠道也是新型冠状病毒侵袭或繁殖的部位,采用中医清热通下之法,使邪从肠道而出,可能是减轻体内病毒感染与肺脏炎症的一种途径。     

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.     

延续护理干预对慢性乙型肝炎患者抗病毒治疗依从性的影响观察

目的:分析延续护理干预对慢性乙型肝炎患者抗病毒治疗依从性的影响。方法:研究选取2017年1月~2017年12月某院肝二病区收治的112例乙型肝炎患者和2018年1月~2018年12月收治的98例乙型肝炎病毒患者作为研究对象,所有患者均进行抗病毒治疗,回顾性分析患者的病历资料。将2017年收治的112例患者作为常规组实施常规护理,将2018年收治的98例患者的作为研究组实施延续性护理,比较两组的护理效果。结果:研究组的治疗依从率为93.88%(92例),远高于常规组的77.68%(87例),两组数据比较存在统计学意义(P<0.05)。结论:延续性护理措施可以有效提高慢性乙型肝炎抗病毒治疗的依从性,可以在临床中推广使用。     

Evaluation of protection induced by a dengue virus serotype 2 envelope domain III protein scaffold/DNA vaccine in non-human primates

We describe the preclinical development of a dengue virus vaccine targeting the dengue virus serotype 2 (DENV2) envelope domain III (EDIII). This study provides proof-of-principle that a dengue EDIII protein scaffold/DNA vaccine can protect against dengue challenge. The dengue vaccine (EDIII-E2) is composed of both a protein particle and a DNA expression plasmid delivered simultaneously via intramuscular injection (protein) and gene gun (DNA) into rhesus macaques. The protein component can contain a maximum of 60 copies of EDIII presented on a multimeric scaffold of Geobacillus stearothermophilus E2 proteins. The DNA component is composed of the EDIII portion of the envelope gene cloned into an expression plasmid. The EDIII-E2 vaccine elicited robust antibody responses to DENV2, with neutralizing antibody responses detectable following the first boost and reaching titers of greater than 1:100,000 following the second and final boost. Vaccinated and naïve groups of macaques were challenged with DENV2. All vaccinated macaques were protected from detectable viremia by infectious assay, while naïve animals had detectable viremia for 2–7 days post-challenge. All naïve macaques had detectable viral RNA from day 2–10 post-challenge. In the EDIII-E2 group, three macaques were negative for viral RNA and three were found to have detectable viral RNA post challenge. Viremia onset was delayed and the duration was shortened relative to naïve controls. The presence of viral RNA post-challenge corresponded to a 10–30-fold boost in neutralization titers 28 days post challenge, whereas no boost was observed in the fully protected animals. Based on these results, we determine that pre-challenge 50% neutralization titers of >1:6000 correlated with sterilizing protection against DENV2 challenge in EDIII-E2 vaccinated macaques. Identification of the critical correlate of protection for the EDIII-E2 platform in the robust non-human primate model lays the groundwork for further development of a tetravalent EDIII-E2 dengue vaccine.