孕妇新型冠状病毒肺炎及疫苗的流行病学研究进展

新型冠状病毒肺炎（COVID-19）是一种由新型冠状病毒（新冠病毒）引起的急性呼吸道传染性疾病。由于妊娠期间的生理变化,孕妇易感COVID-19,尤其是新冠病毒变异株流行期间,孕妇不良妊娠结局的发生风险可能更高。目前尚缺乏孕妇接种新冠病毒疫苗（新冠疫苗）的随机临床试验证据,各国关于孕妇接种新冠疫苗的推荐存在差异,这给孕妇COVID-19的防控带来了一定挑战。本文回顾了国内外妊娠期感染新冠病毒的重要研究进展,论述了妊娠期患COVID-19对孕妇、胎儿及婴儿的危害,以及真实世界研究中妊娠期接种新冠疫苗的有效性和安全性等,以期为今后开展孕妇相关研究,制定防控措施提供参考。     

Triptolide: Progress on research in pharmacodynamics and toxicology

Ethnopharmacological relevance

Tripterygium wilfordii Hook. f. (Tripterygium wilfordii), also known as Huangteng and gelsemium elegan, is a traditional Chinese medicine that has been marketed in China as Tripterygium wilfordii glycoside tablets. Triptolide (TP), an active component in Tripterygium wilfordii extracts, has been used to treat various diseases, including lupus, cancer, rheumatoid arthritis and nephritic syndrome. This review summarizes recent developments in the research on the pharmacodynamics, pharmacokinetics, pharmacy and toxicology of TP, with a focus on its novel mechanism of reducing toxicity. This review provides insight for future studies on traditional Chinese medicine, a field that is both historically and currently important.

Materials and methods

We included studies published primarily within the last five years that were available in online academic databases (e.g., PubMed, Google Scholar, CNKI, SciFinder and Web of Science).

Results

TP has a long history of use in China because it displays multiple pharmacological activities, including anti-rheumatism, anti-inflammatory, anti-tumor and neuroprotective properties. It has been widely used for the treatment of various diseases, such as rheumatoid arthritis, nephritic syndrome, lupus, Behcet?s disease and central nervous system diseases. Recently, numerous breakthroughs have been made in our understanding of the pharmacological efficacy of TP. Although TP has been marketed as a traditional Chinese medicine, its multi-organ toxicity prevents it from being widely used in clinical practice.

Conclusions

Triptolide, a biologically active natural product extracted from the root of Tripterygium wilfordii, has shown promising pharmacological effects, particularly as an anti-tumor agent. Currently, in anti-cancer research, more effort should be devoted to investigating effective anti-tumor targets and confirming the anti-tumor spectrum and clinical indications of novel anti-tumor pro-drugs. To apply TP appropriately, with high efficacy and low toxicity, the safety and non-toxic dose range for specific target organs and diseases should be determined, the altered pathways and mechanisms of exposure need to be clarified, and an early warning system for toxicity needs to be established. With further in-depth study of the efficacy and toxicity of TP, we believe that TP will become a promising multi-use drug with improved clinical efficacy and safety in the future.     

真实世界证据与随机对照试验：RCT DUPLICATE项目启动、实施、进展解读与启示（二）

随着医疗大数据的推广与应用,监管机构开始使用非随机化的真实世界证据（RWE）来评估医疗产品的有效性。本文简要介绍了哈佛大学研究团队于2018年发起RCT DUPLICATE项目的最新进展与研究成果,并结合我国医疗服务特点总结了相关研究经验,为国内学者今后开展相关RWE研究提供借鉴。     

Antiarrhythmic efficacy of CPUY102122, a multiple ion channel blocker,on rabbits with ischemia/reperfusion injury

BackgroundThe antiarrhythmic potential of a novel multichannel blocker CPUY102122 (CY22) was investigated in the present study.MethodsThe effect of CY22 on rapid delayed rectifier potassium channel current (I_Kr) was studied using whole-cell patch clamp techniques in Chinese Hamster Ovary cells stably expressing human Ether-à-go-go-Related Gene. We further evaluated the antioxidant effects of CY22 and demonstrated the reversal of connexin down-regulation in the development of cardiac ventricular arrhythmias, which was produced using coronary ligation/reperfusion in rabbits. CY22 and Amiodarone were administered 30 min prior to the procedure. Next, electrocardiograms were recorded, protein expression of left ventricular Connexin43 (Cx43), non-phosphorylation-Cx43 (np-Cx43), Rac-1 and gp-91[phox] were assayed using Western blot analysis, microstructural changes in the myocardium were observed and redox system activity was assayed.ResultsCY22 inhibited I_Kr in a concentration-dependent manner with IC₅₀ value of 2.8 ± 0.8 μmol/L. CY22 treatment significantly decreased T-wave amplitude and QTc arrhythmic scores and ameliorated the shape of the infarcted myocardium compared to the model group. CY22 decreased the serum levels of creatine kinase, lactate dehydrogenase, and myocardial levels of malondialdehyde, as well as increased superoxide dismutase activity. Cx43 expression in the left ventricle was significantly increased by CY22 treatment, which significantly decreased np-43 expression, Rac-1 activity and gp-91[phox] protein expression.ConclusionsThese results indicated that CY22 has both antiarrhythmic and cardiovascular protective effects partly by blocking I_Kr, the production of antioxidants and protection of Cx43.     

Hepatotoxicity mechanisms of isoniazid: A mini‐review

Isoniazid (INH) is an antituberculosis drug associated with idiosyncratic liver injury in susceptible patients. INH‐induced hepatotoxicity remains a significant clinical problem, but the underlying mechanisms are still unclear, despite the growing evidence that INH and/or its major metabolite, hydrazine, play an important role in hepatotoxicity. Copyright © 2015 John Wiley & Sons, Ltd.     

细胞色素P450靶向抗肿瘤药物研发进展

细胞色素P450酶能催化各种内源性及外源性化合物的代谢,与多种肿瘤的发生发展有着密切关系,因此细胞色素P450酶靶向药物的研制已成为肿瘤治疗的新的研究方向之一,其中肿瘤特异性表达细胞色素P450酶成为研究热点。综述细胞色素P450酶靶向抗肿瘤药物研发进展,并介绍细胞色素P450 2W1及其靶向药物的研究近况。     

雷公藤甲素对ERα蛋白介导的人乳腺癌MCF-7细胞增殖抑制的影响

目的：研究雷公藤甲素对激素依赖性人乳腺癌细胞MCF-7增殖的抑制作用及可能的机制。方法：MTT法检测雷公藤甲素对MCF-7细胞增殖的抑制作用,Hoechst染色法检测其对细胞凋亡的影响,Western blotting法观察雷公藤甲素对雌激素受体（ER）α蛋白表达的影响。结果：雷公藤甲素对MCF-7细胞增殖有显著的抑制作用,并且呈现良好的时效和量效关系,雷公藤甲素能有效诱导MCF-7细胞凋亡,并且对ERα具有明显的下调作用。结论：雷公藤甲素能抑制人乳腺癌细胞MCF-7增殖并且诱导其凋亡,其诱导MCF-7细胞凋亡的作用机制可能与其下调ERα的表达有关。     

大黄蒽醌类药物影响大黄素在Caco-2细胞中的摄取吸收行为

目的：通过对大黄素在Caco-2细胞中摄取吸收的定量来考察其他游离大黄蒽醌类药物对大黄素吸收的影响。方法：建立了结合荧光检测器的高效液相色谱法用以检测Caco-2细胞中的大黄素的摄取量并初步探讨大黄素的吸收特性。结果：大黄素的吸收被芦荟大黄素、大黄素甲醚显著地抑制。结论：利用游离大黄总蒽醌中的其他成分与大黄素合理配伍用药或许可以有效的减少大黄中大黄素的毒性，提高中药大黄的安全性和有效性。