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Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection

Weibao Song, Hongjuan Zhang, Yu Zhang, Rui Li, Yanxing Han, Yuan Lin, Jiandong Jiang

《医学前沿（英文）》 2021年 第15卷 第3期   页码 404-415 doi: 10.1007/s11684-021-0834-9

摘要： Zika virus (ZIKV) is an emerging pathogen associated with neurological complications, such as Guillain–Barré syndrome in adults and microcephaly in fetuses and newborns. This mosquito-borne flavivirus causes important social and sanitary problems owing to its rapid dissemination. However, the development of antivirals against ZIKV is lagging. Although various strategies have been used to study anti-ZIKV agents, approved drugs or vaccines for the treatment (or prevention) of ZIKV infections are currently unavailable. Repurposing clinically approved drugs could be an effective approach to quickly respond to an emergency outbreak of ZIKV infections. The well-established safety profiles and optimal dosage of these clinically approved drugs could provide an economical, safe, and efficacious approach to address ZIKV infections. This review focuses on the recent research and development of agents against ZIKV infection by repurposing clinical drugs. Their characteristics, targets, and potential use in anti-ZIKV therapy are presented. This review provides an update and some successful strategies in the search for anti-ZIKV agents are given.

关键词： Zika virus     clinical drugs     ZIKV inhibitors     antivirals     repurposing    

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整合药学发展的战略思考

张勇,赵一秀,杨宝峰

《中国工程科学》 2021年 第23卷 第1期   页码 185-192 doi: 10.15302/J-SSCAE-2021.01.022

摘要：

整合药学是以现代药学为基础、随着人类对复杂性疾病认识的日益深刻而提出来的，涉及新药研发、传统医药创新、 临床药学实践、药学学科建设及人才培养等诸多领域。为推进我国整合药学实践的发展，本文运用文献研究、学术交流、专 家咨询等方法，阐明了整合药学理念及内涵，提出了整合药学的未来发展战略。研究指出，要促进现代药学与传统药学的整 合，应建立健全整合用药临床实践指南、鼓励基于整合思维的创新中药研究、规范整合中西药临床应用；推进基于整合药学 的新药研发，应创新整合药物设计思路、开发适应整合药学的药物评价体系、加快建设整合药物的新药研发体系；推进整合 药学的临床实践，应进一步完善以患者为中心的临床用药指导、实现个体化治疗、丰富整合药学临床实践内容、加强整合药 物合理应用；推进整合药学学科建设，应丰富基于整合药学的药学本科理论和实践课程、加强教育培训及专业间协作。整合 药学是现代药学理论和实践的变革与发展，融合药学各相关学科的理论与实践，是构建促进人类健康、完善医疗体系的新型 药学理论和实践体系。

关键词： 整合药学，整合药物，新药研发，药物评价，临床用药指导    

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Small-molecule anti-COVID-19 drugs and a focus on China’s homegrown mindeudesivir (VV116)

《医学前沿（英文）》 doi: 10.1007/s11684-023-1037-3

摘要： The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir–ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir–ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir–ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China’s homegrown anti-COVID-19 drugs.

关键词： COVID-19     antiviral drugs     mindeudesivir    

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Occurrence, distribution and risk assessment of abused drugs and their metabolites in a typical urban

Peng Hu, Changsheng Guo, Yan Zhang, Jiapei Lv, Yuan Zhang, Jian Xu

《环境科学与工程前沿（英文）》 2019年 第13卷 第4期 doi: 10.1007/s11783-019-1140-5

摘要：

We developed a method for determining 11 abused drugs in water and sediment.

METH and EPH were the dominant drugs in water and sediment in Beiyunhe River.

Abuse drugs in Beiyunhe River were mainly from hospitals and sewage effluents.

Abused drugs in the water would not impair the aquatic ecosystem biologically.

关键词： Drugs of abuse     Occurrence     Distribution     Urban river     Environmental risk    

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Chinese expert consensus on oral drugs for the treatment of mature B-cell lymphomas (2020 edition)

《医学前沿（英文）》 2022年 第16卷 第5期   页码 815-826 doi: 10.1007/s11684-021-0891-0

摘要： Oral drugs such as ibrutinib play an important role in the treatment of mature B-cell lymphoma (BCL) due to their reliable efficacy, manageable safety, high accessibility, and convenience for use. Still, no guidelines or consensus focusing on oral drug therapies for BCL is available. To provide a reference of oral agent-based treatment for mature BCL, a panel of experts from the Lymphocyte Disease Group, Chinese Society of Hematology, Chinese Medical Association conducted an extensive discussion and reached a consensus on oral drugs for Chinese BCL patients on the basis of the current application status of oral drugs in China, combined with the latest authoritative guidelines in the world and current research reports. This consensus reviewed the application of oral drugs in the treatment of BCL and the latest research and provided appropriate recommendations on the use of oral drugs for indolent or aggressive BCL patients. With the deepening of research and the development of standardized clinical applications, oral medications will bring better treatment to BCL patients, enabling more patients to benefit from them.

关键词： B-cell lymphoma     oral drug     targeted therapy     immunotherapy     COVID-19 pandemic    

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nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleic acid drugs

Vaibhav Mundra, Ram I. Mahato

《化学科学与工程前沿（英文）》 2014年 第8卷 第4期   页码 387-404 doi: 10.1007/s11705-014-1457-3

摘要： There are many challenges in developing efficient and target specific delivery systems of small molecule and nucleic acid drugs. Cell membrane presents one of the major barriers for the penetration of hydrophilic macromolecules across the plasma membrane. Nanocarriers have been designed to enhance their cellular uptake via endocytosis but following their cellular uptake, endosomal escape is the rate limiting step which restricts the value associated with the enhanced uptake by nanocarriers. Viruses are an excellent model for efficient cytosolic delivery by nanocarriers. Viruses exploit intracellular cues to release the genome to cytosol. In this review, we first discuss different endocytic uptake pathways and endosomal escape mechanisms. We then summarize the existing tools for studying the intracellular trafficking of nanocarriers. Finally, we highlight the important design elements of recent virus-based nanocarriers for efficient cellular uptake and endosomal escape.

关键词： nanocarrier     cellular uptake     endosomal release     nucleic acid drug    

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Telomeric impact of conventional chemotherapy

null

《医学前沿（英文）》 2013年 第7卷 第4期   页码 411-417 doi: 10.1007/s11684-013-0293-z

摘要：

The increased level of chromosome instability in cancer cells, leading to aneuploidy and gross chromosomal rearrangements, is not only a driving force for oncogenesis but also can be the Achille’s heel of the disease since many chemotherapies (CT) kill cells by inducing a non-tolerable rate of DNA damage. A wealth of published evidence showed that telomere stability can be more affected than the bulk of the genome by several conventional antineoplasic drugs. These results raise the interesting possibility that CT with genotoxic drugs preferentially target telomeres. In agreement with this view, accelerated shortening of telomere length has been described in blood lineage cells following high-dose CT (stem cell transplantation) or non-myeloablative CT. However, almost nothing is known on the consequences of this shortening in terms of telomere stability, senescence and on the development of second cancers or post-treatment aging-like syndromes in cancer survivors (cognitive defect, fertility impairment, etc.). In this article, we propose: (1) telomeres of cancer cells are preferential genomic targets of chemotherapies altering chromosome maintenance; (2) telomere functional parameters can be a surrogate marker of chemotherapy sensitivity and toxicity; (3) the use of anti-telomere molecule could greatly enhance the sensitivity to standards chemotherapies.

关键词： telomere     antineoplasic drugs     conventional chemotherapies    

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Product identification and toxicity change during oxidation of methotrexate by ferrate and permanganate in water

《环境科学与工程前沿（英文）》 2022年 第16卷 第7期 doi: 10.1007/s11783-021-1501-8

摘要：

• Oxidation of methotrexate by high-valent metal-oxo species was first explored.

关键词： Anticancer drugs     High-valent metal-oxo species     Oxidation kinetics     Reaction mechanisms     Multi-endpoint toxicity    

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Stroke prevention: an update

null

《医学前沿（英文）》 2012年 第6卷 第1期   页码 22-34 doi: 10.1007/s11684-012-0178-6

摘要：

Stroke is a personal, familial, and social disaster. It is the third cause of death worldwide, the first cause of acquired disability, the second cause of dementia, and its cost is astronomic. The burden of stroke is likely to increase given the aging of the population and the growing incidence of many vascular risk factors. Prevention of stroke includes—as for all other diseases—a “mass approach” aiming at decreasing the risk at the society level and an individual approach, aiming at reducing the risk in a given subject. The mass approach is primarily based on the identification and treatment of vascular risk factors and, if possible, in the implementation of protective factors. These measures are the basis of primary prevention but most of them have now been shown to be also effective in secondary prevention. The individual approach combines a vascular risk factor modification and various treatments addressing the specific subtypes of stroke, such as antiplatelet drugs for the prevention of cerebral infarction in large and small artery diseases of the brain, carotid endarterectomy or stenting for tight carotid artery stenosis, and oral anticoagulants for the prevention of cardiac emboli. There is a growing awareness of the huge evidence-to-practice gap that exists in stroke prevention largely due to socio-economic factors. Recent approaches include low cost intervention packages to reduce blood pressure and cheap “polypills” combining in a single tablet aspirin and several drugs to lower blood pressure and cholesterol. Polypill intake should however not lead to abandon the healthy life-style measures which remain the mainstay of stroke prevention.

关键词： stroke     prevention     vascular risk factors     cerebral infarction     cerebral hemorrhage     anti-thrombotic drugs     carotid endarterectomy    

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Ontological reconstruction of the clinical terminology of traditional Chinese medicine

null

《医学前沿（英文）》 2014年 第8卷 第3期   页码 358-361 doi: 10.1007/s11684-014-0348-9

摘要：

This study proposes the ontological reconstruction of the current clinical terminology of traditional Chinese medicine (TCM). It also provides an overview of preliminary work related to the said reconstruction, including the ontology-based analysis of TCM clinical terminology. We conclude that the ontological reconstruction of TCM clinical terminology provides a proper translation from the idealized organizational model to real-world implementation and to a formalized, shared, and knowledge-based framework.

关键词： ontology     traditional Chinese medicine     clinical terminology    

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Factors related to compliance with oral analgesic treatment of inpatients with chronic pain

null

《医学前沿（英文）》 2015年 第9卷 第3期   页码 374-379 doi: 10.1007/s11684-015-0411-1

摘要：

This study aimed to determine the relationship between the different factors of analgesic therapy and the compliance of chronic pain inpatients. We prospectively investigated 100 consecutive inpatients with non-cancer chronic pain who were hospitalized to receive oral analgesic treatment in the Pain Department of West China Hospital from May 2013 to October 2013. Patients who completed the treatment plan were recorded as good compliance, whereas patients who partly completed or even refused the treatment were recorded as moderate or non-compliance, respectively. A total of 73 (73.7%), 17 (17.1%), and 9 (9.2%) patients showed good, moderate, and non-compliance, respectively. Univariate analyses showed significantly better compliance among farmers, patients educated in college or above, with family income of<3000 CNY, and with severe or moderate pain than those employed and unemployed (P=0.02), patients educated below college (P=0.013), with family income of≥3000 CNY (P=0.025), and with mild pain (P<0.001), respectively. Logistic regression analysis showed that the family income of≥3000 CNY (OR: 2.50, 95%CI: 1.65–4.51, P=0.021) and mild pain (OR: 1.27, 95%CI: 1.03–3.31, P=0.016) were associated with moderate or non-compliance with oral analgesic treatment. In conclusion, the low compliance with oral treatment of analgesics was found in Chinese inpatients with chronic pain and compliance was negatively associated with family income and degree of pain of patients.

关键词： chronic pain     inpatient     oral paregoric drugs     compliance    

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Theoretical insights into influence of additives on sulfamethoxazole crystal growth kinetics and mechanisms

《化学科学与工程前沿（英文）》 2023年 第17卷 第10期   页码 1503-1515 doi: 10.1007/s11705-022-2294-4

摘要： In this work, the influence of the initial chemical potential gradient, stirring speed, and polymer type on sulfamethoxazole (SMX) crystal growth kinetics was systematically investigated through density functional theory (DFT) calculations, experimental measurements and the two-step chemical potential gradient model. To investigate the influence of different conditions on the thermodynamic driving force of SMX crystal growth, SMX solubilities in different polymer solutions were studied. Four model polymers effectively improved SMX solubility. It was further found that polyvinylpyrrolidone (PVP) and hydroxypropyl methyl cellulose (HPMC) played a crucial role in inhibiting SMX crystal growth. However, polyethylene glycol (PEG) promoted SMX crystal growth. The effect of the polymer on the crystal growth mechanisms of SMX was further analyzed by the two-step chemical potential gradient model. In the system containing PEG 6000, crystal growth is dominated by the surface reaction. However, in the system containing PEG 20000, crystal growth is dominated by both the surface reaction and diffusion. In addition, DFT calculations results showed that HPMC and PVP could form strong and stable binding energies with SMX, indicating that PVP and HPMC had the potential ability to inhibit SMX crystal growth.

关键词： insoluble drugs     polymer     inhibition crystallization     crystal growth kinetics     DFT calculations    

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The clinical impact of tricuspid regurgitation in patients with a biatrial orthotopic heart transplant

《医学前沿（英文）》 2023年 第17卷 第3期   页码 527-533 doi: 10.1007/s11684-022-0967-5

摘要： In this study, we aim to elucidate the clinical impact and long-term course of tricuspid regurgitation (TR), taking into account its dynamic nature, after biatrial orthotopic heart transplant (OHT). All consecutive adult patients undergoing biatrial OHT (1984−2017) with an available follow-up echocardiogram were included. Mixed-models were used to model the evolution of TR. The mixed-model was inserted into a Cox model in order to address the association of the dynamic TR with mortality. In total, 572 patients were included (median age: 50 years, males: 74.9%). Approximately 32% of patients had moderate-to-severe TR immediately after surgery. However, this declined to 11% on 5 years and 9% on 10 years after surgery, adjusted for survival bias. Pre-implant mechanical support was associated with less TR during follow-up, whereas concurrent LV dysfunction was significantly associated with more TR during follow-up. Survival at 1, 5, 10, 20 years was 97% ± 1%, 88% ± 1%, 66% ± 2% and 23% ± 2%, respectively. The presence of moderate-to-severe TR during follow-up was associated with higher mortality (HR: 1.07, 95% CI (1.02–1.12), p = 0.006). The course of TR was positively correlated with the course of creatinine (R = 0.45). TR during follow-up is significantly associated with higher mortality and worse renal function. Nevertheless, probability of TR is the highest immediately after OHT and decreases thereafter. Therefore, it may be reasonable to refrain from surgical intervention for TR during earlier phase after OHT.

关键词： orthotopic heart transplant     tricuspid regurgitation     clinical impact     biatrial heart transplantation    

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Obesity-related glomerulopathy: pathogenesis, pathologic, clinical characteristics and treatment

null

《医学前沿（英文）》 2017年 第11卷 第3期   页码 340-348 doi: 10.1007/s11684-017-0570-3

摘要：

In light of the rapid increase in the number of obesity incidences worldwide, obesity has become an independent risk factor for chronic kidney disease. Obesity-related glomerulopathy (ORG) is characterized by glomerulomegaly in the presence or absence of focal and segmental glomerulosclerosis lesions. IgM and complement 3 (C3) nonspecifically deposit in lesions without immune-complex-type deposits during ORG immunofluorescence. ORG-associated glomerulomegaly and focal and segmental glomerulosclerosis can superimpose on other renal pathologies. The mechanisms under ORG are complex, especially hemodynamic changes, inflammation, oxidative stress, apoptosis, and reduced functioning nephrons. These mechanisms synergize with obesity to induce end-stage renal disease. A slow increase of subnephrotic proteinuria (<3.5 g/d) is the most common clinical manifestation of ORG. Several treatment methods for ORG have been developed. Of these methods, renin–angiotensin–aldosterone system blockade and weight loss are proven effective. Targeting mitochondria may offer a novel strategy for ORG therapy. Nevertheless, more research is needed to further understand ORG.

关键词： obesity-related glomerulopathy     pathogenesis     pathologic     clinical characteristics    

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标题 作者 时间 类型 操作

Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection

Weibao Song, Hongjuan Zhang, Yu Zhang, Rui Li, Yanxing Han, Yuan Lin, Jiandong Jiang

期刊论文

整合药学发展的战略思考

张勇,赵一秀,杨宝峰

期刊论文

Small-molecule anti-COVID-19 drugs and a focus on China’s homegrown mindeudesivir (VV116)

期刊论文

Occurrence, distribution and risk assessment of abused drugs and their metabolites in a typical urban

Peng Hu, Changsheng Guo, Yan Zhang, Jiapei Lv, Yuan Zhang, Jian Xu

期刊论文

Chinese expert consensus on oral drugs for the treatment of mature B-cell lymphomas (2020 edition)

期刊论文

nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleic acid drugs

Vaibhav Mundra, Ram I. Mahato

期刊论文

Telomeric impact of conventional chemotherapy

null

期刊论文

关于联合国开发总署（UNDP）医农药工业在全球竞争中的技术升级研讨会介绍

李正名

期刊论文

Product identification and toxicity change during oxidation of methotrexate by ferrate and permanganate in water

期刊论文

Stroke prevention: an update

null

期刊论文

Ontological reconstruction of the clinical terminology of traditional Chinese medicine

null

期刊论文

Factors related to compliance with oral analgesic treatment of inpatients with chronic pain

null

期刊论文

Theoretical insights into influence of additives on sulfamethoxazole crystal growth kinetics and mechanisms

期刊论文

The clinical impact of tricuspid regurgitation in patients with a biatrial orthotopic heart transplant

期刊论文

Obesity-related glomerulopathy: pathogenesis, pathologic, clinical characteristics and treatment

null

期刊论文