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    Progress in clinical application of topical anesthesia
    TAO Yijia, YANG Chun, LIU Cunming
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (5): 594-600.   DOI: 10.12092/j.issn.1009-2501.2023.05.015
    Abstract348)      PDF (614KB)(2834)       Save
    Topical anesthesia are being widely used in clinical diagnostic or therapeutic fields such as ophthalmology, ENT, dermatology, urology. It is defined as superficial loss of sensation in mucous membranes or skin, produced by direct application of penetrating local anesthetics. Topical anesthesia has the advantages of simple performance, high safety, quick recovery, which can effectively improve patient's satisfaction. In recent years, more and more attention has been paid to the concept of comfortable diagnosis and treatment. The new drugs and application methods of topical anesthesia are emerging constantly, special attention must be paid to their pharmacological characteristics and possible adverse reactions when using them. This article reviews the research progress of topical anesthesia in clinical application in order to provide reference for clinical practice.
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    Progress on the pathological mechanism and treatment of frostbite 
    ZHANG Li, LIN Xingyao, SHANG Yun, WANG Qiang
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (3): 347-354.   DOI: 10.12092/j.issn.1009-2501.2023.03.014
    Abstract400)      PDF (808KB)(1436)       Save
    Frostbite is a tissue injury that occurs when the body is exposed to extreme cold. Its path-ological mechanism is complex and has not been ful-ly elucidated. In high cold and high altitude areas, outdoor sports people have a high risk of injury, and severe frostbite has high disability and mortality. Ex-ploring the pathological mechanism of frostbite is helpful to determine the treatment methods and timing. At present, the clinical treatment of frostbite is mainly symptomatic treatment, such as drug treatment and surgical treatment, but the curative effect can not meet the clinical needs. Therefore, it is of great significance to seek more efficient drugs or treatment methods. This article reviews the rele-vant research progress in pathophysiological mecha-nism, clinical treatment, cellular and molecular path-ways of frostbite in recent years, in order to provide new ideas for future research and clinical treatment. 
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    Research progress in the treatment of early Alzheimer's disease with lecanemab
    JIN Panpan, LIU Yang, QIU Bo, WU Huizhen
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (2): 207-214.   DOI: 10.12092/j.issn.1009-2501.2024.02.011
    Abstract512)      PDF (672KB)(1139)       Save
    Lecanemab is a new drug used to treat early Alzheimer's disease (AD) with mild cognitive impairment or mild dementia. It is a human anti-Aβ fibril monoclonal IgG1 antibody, which is injected intravenously into the patient, through the blood-brain barrier into the brain, clearing amyloid plaque, thereby slowing the rate of cognitive decline in patients and delaying disease progression. This article reviews the pharmacological studies, clinical studies, safety and limitations of lecanemab, in order to help clinical understand the current research status and existing achievements of this drug.
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    Progress in clinical research on remazolam
    XIN Yuqi, CAO Ya, WANG Yulong
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (10): 1195-1200.   DOI: 10.12092/j.issn.1009-2501.2023.10.014
    Abstract405)      PDF (624KB)(857)       Save
    Benzodiazepines are among the most commonly used drugs in the field of anesthesia. Remazolam is a newly developed ultra-short-acting benzodiazepine, which has the characteristics of rapid onset, rapid recovery, high safety, and less side effects such as hypotension and respiratory depression. The aim of this review is to summarize the progress of pharmacokinetics, clinical pharmacology mechanism of action and clinical application of remazolam.
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    Ferroptosis regulatory signaling pathway and its research progress in related diseases
    ZHANG Liang, LIAO Yongqun, XIA Qinchuan, ZHOU Shitong, LI Xiaoli
    Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (2): 227-234.   DOI: 10.12092/j.issn.1009-2501.2022.02.015
    Abstract1063)      PDF (440KB)(832)       Save
    Ferroptosis is an iron-dependent novel type of programmed cell death. The main features of ferroptosis include lipid reactive oxygen accumulation, iron accumulation and lipid peroxidation. The main mechanisms and signal pathways of ferroptosis are complex and closely related to cystine/glutamate antiporter system, glutathione peroxidase 4, ferroptosis suppressor protein 1, and dihydroorotate dehydrogenase. This review summarizes the current regulatory mechanisms of ferroptosis and discusses the research progress of ferroptosis in tumors, non-alcoholic fatty liver disease, Parkinson's disease, and congestive heart failure.
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    Research progress of the classical TCM formula Huaihua powder 
    CHEN Cheng, DENG Yu, GONG Youlan, ZHANG Zhenming, DUAN Wulei, QING Jun, ZHANG Bo
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (6): 697-704.   DOI: 10.12092/j.issn.1009-2501.2023.06.013
    Abstract373)      PDF (734KB)(789)       Save
    Huaihua powder, a classical TCM formula, was initially recorded in Pu Ji Ben Shi Fang by the prestigious physician Xu Shuwei. It is a classical prescription for treating "chang-feng-zang-du"(chang-feng-xia-xue). Modern research shows that the main components of Huaihua powder are flavonoids, volatile oil, saponins and so on, which have anti-inflammatory, antioxidant, hemostatic, antibacterial, anti-tumor and other pharmacological effects.The clinical application is mostly used for the treatment of ulcerative colitis, radioactive enteritis, hemorrhoid postoperative bleeding and other skin diseases. Its modern clinical application is slightly better than the ancient clinical application. This paper summarized and summarized the chemical composition and analysis method, process research and quality control, modern pharmacology and clinical application, and discussed the material basis and research direction of its efficacy. Based on the research results, combined with the modern pharmacology and clinical application of Huaihua powder, it is recommended to develop the entire pharmacological active ingredients of this classic formula, as well as the main effective ingredients, anti-inflammatory targets, and mechanism of action for the treatment of radiation induced enteritis, allergic purpura, and other skin diseases.
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    Research progress of lactate dehydrogenase A in digestive system tumors and related drugs
    WANG Siyu, LI Jiawei, LI Chenghao, LI Ling, GUO Qingyang, QIU Lu, ZHOU Shiqin, LIU Yongqi
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (4): 445-454.   DOI: 10.12092/j.issn.1009-2501.2023.04.012
    Abstract537)      PDF (1441KB)(765)       Save
    Malignant tumors of digestive system are highly prevalent malignant tumors that seriously threaten human health around the world. At present, the curative efficacy and prognosis of traditional treatment methods cannot reach the expectation, so it is urgent to find new targets for cancer treatment and realize targeted therapy for tumors. Abnormal energy metabolism in tumor  cells is regarded as a hallmark of cancer, and malignant tumor cells absorb glucose through aerobic glycolysis pathway, and obtain a small amount of energy and produce lactate under the catalysis of a series of enzymes. Lactate dehydrogenase A (Lactate dehydrogenase A, LDHA), as a key enzyme in the aerobic glycolysis pathway of tumor cells, plays an important role in the metabolic changes of tumor cells. Studies have demonstrated that LDHA has high expression characteristics in a variety of tumor cells,and its high expression in clinic is often related to the poor prognosis and high metastasis rate of tumors, which is expected to be a new target for cancer therapy. This article reviews the role of LDHA in the development of digestive system tu- mors and the research progress of related drugs.
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    Analysis and verification of the effect of Yi Qi Yang Yin decoction on rheumatoid arthritis
    GUAN Rui, YAO Jiashu, ZHAO Yeyu, ZHENG Jiannan, QI Qing, YU Jing, GAO Mingli
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (1): 26-36.   DOI: 10.12092/j.issn.1009-2501.2024.01.003
    Abstract147)      PDF (5757KB)(737)       Save
    AIM: Yi Qi Yang Yin Decoction (YQYY) has been used to treat patients with rheumatoid arthritis (RA) and achieved good results in clinical applications, but the mechanism still needs to be explored. The purpose was to investigate the mechanism of YQYY in rats with collagen-induced arthritis. METHODS: The possible treatment target and signaling pathway were predicted by bioinformatics and network pharmacology analysis. Elisa,quantitative real-time polymerase chain reaction, and Western Blot were used to verify the mechanism of YQYY in treating RA. RESULTS: FABP4, MMP9 and PTGS2 were the most common predicational therapeutic targets. The results of pathology and CT showed that YQYY could improve ankle swelling, synovitis and bone erosion in CIA rats. Compared with the model group, YQYY or YQYY+MTX can significantly reduce the secretion of CRP, TNF-α, IL-1β and FABP4 in serum of CIA rats (P<0.05 or P<0.01), meanwhile, reduce the mRNA of FABP4, IKKα and p65 in synovial tissue (P<0.01), PPARγ was increased (P<0.01). YQYY could significantly reduce the expression of FABP4, IKKα and pp65 proteins in synovium, and suppress the activate of NF-κB signaling pathway. CONCLUSION: FABP4, MMP9 and PTGS2 may be the targets of YQYY decoction for RA treatment. YQYY can relieve joint symptoms in CIA rats, and regulate inflammation by inhibiting FABP4/PPARγ/NF-κB signaling pathway, playing a role in the treatment of RA. The effect of YQYY combined with MTX was more prominent. This provided experimental evidence for the efficacy of YQYY decoction in clinical practice.
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    Research progress on mechanisms and therapeutic drugs of peroxisome proliferator-activated receptor in treatment of cholestatic liver disease
    WANG Anjing, WANG Yaya, LIANG Xuan, YAN Yajie, SU Jing, LI Caidong
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (7): 796-808.   DOI: 10.12092/j.issn.1009-2501.2023.07.011
    Abstract312)      PDF (851KB)(733)       Save
    Cholestatic liver disease is a common disease that causes bile flow dysfunction due to various reasons. The etiology of cholestatic liver disease is complexed, and therapeutic drugs are extremely limited. To date, ursodeoxycholic acid is the only FDA-approved drug for treating primary biliary cirrhosis, whereas its efficacy is limited to early stage of the disease, therefore novel drugs are urgently needed. Nuclear receptors become therapeutic hotspot target in cholestasis since these receptors play a key role in regulating bile acid homeostasis. Peroxisome proliferator-activated receptor (PPAR) is an important nuclear receptor involved in regulating multiple mechanisms of cholestasis in vivo. It can improve intrahepatic cholestasis by inhibiting bile acid synthesis, reducing bile acid toxicity, affecting the expression of bile acid metabolic enzymes and transporters, and can play an anti-inflammatory, anti-oxidation and anti-fibrosis role. A number of studies have shown that PPAR agonists represented by fibrates alone or in combination can improve liver function indexes, inflammatory factors and fibrosis markers in patients with cholestasis. This review analyzes and summarizes the lastest advances in the molecular mechanism of PPAR as a therapeutic target for cholestasis and drug treatment in development or have been used in clinical.
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    Research progress on antipyretic effect of Chinese medicine
    CHEN Shengfu, LI Xiaolin, WANG Weigang, DU Weize, LI Maoxing
    Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (3): 334-344.   DOI: 10.12092/j.issn.1009-2501.2022.03.014
    Abstract386)      PDF (915KB)(704)       Save
    Fever is a sign of infection and inflammatory diseases in the body. Persistent high fever will lead to cell degeneration, causing multiple organ dysfunction, and seriously affecting brain nerve and tissue function. Although the fever process is common and ordinary, its pathological mechanism involves multiple signaling pathways, such as nuclear transcription factor κB signaling pathway, Toll-like receptor 4 signaling pathway. A large number of studies have shown that traditional Chinese medicine compound and its active components can reduce serum inflammatory factors (TNF-α, IL-1β and IL-6) and hypothalamic thermoregulatory mediators (PGE2, cAMP), inhibit NF-κB signaling pathway, and effectively inhibit the pathological increase of body temperature. This paper summarizes the relevant literature in PubMed and CNKI database, and systematically expounds the active components of traditional Chinese medicine and the antipyretic effect of compound prescription, in order to provide theoretical basis and research ideas for the use of traditional Chinese medicine in the treatment of fever and the excavation of new anti-fever drugs.
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    Progress in the clinical application of the biased μ-opioid agonist oliceridine
    ZHU Changmao, XIE Li, WU Zifeng, WANG Sen, ZHANG Qi, XU Xiangqing, YANG Chun
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (9): 1057-1061.   DOI: 10.12092/j.issn.1009-2501.2024.09.012
    Abstract277)      PDF (596KB)(703)       Save
    Opioid receptors μOR, δOR, κOR and NOPR are all G protein-coupled receptors (GPCRs), which mainly function through G protein and β-arrestin. Recent studies have found that G protein mediates analgesia, while β-arrestin reduces analgesia and is related to the side effects of opioids. Oliceridine is the first biased μOR agonist approved for commerce. It mainly exerts analgesic effect by activating G protein. It has rapid onset of action and reliable analgesic effect. Due to its low activity on β-arrestin, the incidence of side effects is low, comparing to the classic opioid morphine. Oliceridine can be safely used in patients with liver or kidney insufficiency and its metabolite is inactive. This article summarizes the current progress of pharmacological research and clinical application of oliceridine, aiming to provide reference for the clinical practice of oliceridine.
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    Model informed precision dosing of warfarin: China expert consensus report (2022 version)
    ZHANG Jinhua, LIU Maobai, CAI Mingzhi, ZHENG Yingli, LAO Haiyan, XIANG Qian, DU Liping, ZHU Zhu, DONG Jing, ZUO Xiaocong, LI Xingang, SHANG Dewei, CHEN Bing, YE Yanrong, WANG Yuzhu, GAO Jianjun, ZHANG Jian, CHEN Wansheng, XIE Haitang, JIAO Zheng
    Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (11): 1201-1212.   DOI: 10.12092/j.issn.1009-2501.2022.11.001
    Abstract714)      PDF (780KB)(699)       Save
    Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.
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    Research progress of uterine endometrial epithelial cell organoids in the field of reproduction
    CAO Zhiwen, YAN Guijun
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (5): 576-582.   DOI: 10.12092/j.issn.1009-2501.2024.05.013
    Abstract368)      PDF (829KB)(697)       Save
    In recent years, significant progress has been made in the study of endometrial epithelial organoids in the field of reproduction. Traditional two-dimensional cell culture models and animal experiments fail to accurately replicate the three-dimensional structure and physiological functions of the endometrium, limiting the in-depth exploration of its normal physiological mechanisms and related disease mechanisms. Emerging organoid technologies have provided new avenues for research. These organoids, formed by self-organization of stem cells or progenitor cells in a three-dimensional culture system, faithfully recapitulate the characteristics of endometrial glands in situ. Not only can these organoid models mimic the changes in the endometrium at different stages of the menstrual cycle, but they can also simulate the interaction between the fertilized embryo and the endometrium. Moreover, organoid systems have become essential tools for fundamental research in the field of reproduction and for disease research, including studies related to reproductive biology, drug screening and development, disease mechanism exploration, drug action mechanisms, drug combination therapies, and targeted therapies. These studies have provided novel insights and methods for a deeper understanding of the biological properties of the endometrium, its disease mechanisms, and the development of therapeutic strategies for related disorders.
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    PDE4 inhibitors serve as therapeutic targets for pulmonary fibrosis 
    LIU Nanyu, YUE Hongmei, SONG Peipei, WEI Jifang, WEI Yaqian, XIE Yingying, WANG Jiaqi
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (3): 355-360.   DOI: 10.12092/j.issn.1009-2501.2023.03.015
    Abstract544)      PDF (665KB)(677)       Save
    Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal chronic interstitial lung disease characterized by a progressive decline in lung function, and current treatment options are limited. cAMP is one of the most important second messengers and plays a key role in relaxing airway smooth muscle cells and reducing inflammation. Phosphodiesterase (PDE) is a superfamily of enzymes, and PDE4 enzymes dominate 11 PDE super-family enzymes, available in four isoforms-PDE4A, PDE4B, PDE4C and PDE4D, which selectively decompose cAMP, while PDE4 inhibitors increase cAMP levels by preventing cAMP from breaking down, thereby exerting anti-inflammatory, anti-remodeling effects and providing an attractive drug target for the treatment of IPF. This review summarizes knowledge about the association of pulmonary fibrosis with PKE4, as well as emerging preclin-ical studies and clinical trials regarding PDE4 inhibitors.
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    Effects of Chinese patent medicine for activating blood circulation on cardiac repair after myocardial infarction
    CHEN Xi, LI Yongjun
    Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (6): 680-688.   DOI: 10.12092/j.issn.1009-2501.2022.06.012
    Abstract266)      PDF (509KB)(649)       Save
    Myocardial infarction (MI) is a cardiovascular disease with high morbidity and mortality, which seriously endangers human health. Poor ways of repair after MI may damage people's life quality, therefore scientists have been committed to exploring the way of myocardial repair after MI to strive for a better prognosis of these patients. Chinese patent medicines for blood circulation activation have a long history of use in treatment of MI, where they have been shown to attenuate myocardial injury after MI and promote cardiac repair with multiple targets, links and pathways. This review focuses on a few representative Chinese patent medicines for MI and summarizes their pharmacological effects and clinical research in cardiac repair following MI, effectively providing scientific foundation on treating MI with Chinese patent medicines.
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    Research progress on immunotherapy for triple-negative breast cancer
    HE Lihua, ZHU Xiuzhi, JIANG Yizhou
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (8): 842-853.   DOI: 10.12092/j.issn.1009-2501.2023.08.001
    Abstract777)      PDF (754KB)(647)       Save
    Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It is highly aggressive, easy to relapse, and chemotherapy remains its mainstay treatment due to the lack of therapeutic targets. In recent years, many advances have been made in the development of immunotherapy for TNBC. This review summarizes the primary modalities of immunotherapy for TNBC, including immune checkpoint inhibitors, adoptive immune cell therapy, tumor vaccines and oncolytic virus. We present the latest research progress on each treatment from the perspective of clinical study and fundamental research, while introducing the potential predictive biomarkers and resistance mechanisms of immunotherapy for TNBC.
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    Research progress in plasma concentration monitoring of rivaroxaban
    YU Qiaoling, ZHAI Weiwei, LIU Ping, QIU Bo, WU Huizhen
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (7): 809-817.   DOI: 10.12092/j.issn.1009-2501.2023.07.012
    Abstract375)      PDF (654KB)(646)       Save
    Rivaroxaban, a novel oral anticoagulant drug, is widely prescribed in clinical practice. Rivaroxaban offers predictable pharmacokinetic and pharmacodynamic properties, a lowprobability of drug-drug and food-drug interactions. Compared with warfarin, rivaroxaban does not require continuous therapeutic monitoring and can be administered in fixed doses.However,in certain emergency clinical situations, such as bleeding, acute stroke, acute kidney injury, prior to urgent surgery and in the suspected accumulation of durg, plasma concentration monitoring of rivaroxaban is necessary and important for patients. Existing studies proved that there were significant individual variability and wide range in the plasma rivaroxaban concentration, which increased the risk of clinical use. Therefore, Data in the degree of rivaroxaban concentration may provide recommendations for the clinical application to promote medication safety and individuality in the future. This article collected the latest literatures and case reports related to research progress of rivaroxaban plasma concentration monitoring, and Summarized influencing factors, monitoring methods, so as to provide a basis for further study on rational use of rivaroxaban in clinical.
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    Progress of medical treatment of coronary heart disease
    CHANG Shufu
    Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (4): 405-408.   DOI: 10.12092/j.issn.1009-2501.2022.04.008
    Abstract663)      PDF (298KB)(632)       Save
    Coronary heart disease (CHD) treatment methods are changing rapidly, and new drugs are constantly entering the clinic. Antiplatelet drugs are the basis for the treatment of CHD, but there are currently no new drugs that can challenge the status of aspirin and P2Y12 receptor inhibitors. Inflammation is the mechanism of the occurrence and development of CHD, and anti-inflammatory treatment is just beginning, and further exploration is still needed. This paper aims to summarize the progress of drug treatment for CHD and provide a new perspective for clinical practice.
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    Pharmacokinetic interaction study between sorafenib and dapagliflozin in rats
    HE Xueru, LI Ying, MA Yinling, FU Yuhao, XUN Xuejiao, DONG Zhanjun
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (5): 498-507.   DOI: 10.12092/j.issn.1009-2501.2023.05.003
    Abstract241)      PDF (1822KB)(616)       Save
    AIM: To explore the pharmacokinetic interactions between sorafenib and dapagliflozin in rats and to provide some theoretical basis for the rational clinical use of the two drugs. METHODS: An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) method was developed for the simultaneous determination of sorafenib and dapagliflozin. Male SD rats were randomly divided into 5 groups (6 rats in each group), including 100 mg/kg sorafenib group, 0.5 mg/kg dapagliflozin group, 1 mg/kg dapagliflozin group, and 100 mg/kg sorafenib combined with 0.5 mg/kg dapagliflozin group and 100 mg/kg sorafenib combined with 1 mg/kg dapagliflozin group, for sorafenib and dapagliflozin drug interaction study. All samples were analyzed using a validated UPLC/MS/MS method, and the main pharmacokinetic parameters were calculated by compartment model. RESULTS: 1 mg/kg dapagliflozin increased the Cmax, AUC0-t and AUC0-∞ of sorafenib by 52.5%, 38.1% and 37.7%, respectively, and 0.5 mg/kg dapagliflozin increased the AUC0-t and AUC0-∞ of sorafenib by 36.3% and 36.3%. CONCLUSION: Pharmacokinetic interactions may exist between sorafenib and dapagliflozin, active surveillance for treatment and toxicity should be required when the two drugs combined together in clinical practice.
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    Research progress in population pharmacokinetics of rituximab
    LI Mengxue, HE Jie, YU Xiaxia, HU Linlin, SHAO Hua
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (4): 468-474.   DOI: 10.12092/j.issn.1009-2501.2023.04.015
    Abstract513)      PDF (638KB)(613)       Save
    Rituximab, a chimeric human-mouse monoclonal antibody, has been used as a first-line treatment for CD20+ B-cell non-Hodgkin lymphoma in combination with chemotherapy. It is also used for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and immunemediated nephropathy. The clinical therapeutic effect of rituximab is significant. However, individual pharmacokinetics vary greatly, which bring some uncertainties to the efficacy and safety of clinical application, individualized treatment is needed to improve the rationality of its medication. Currently, studies on the optimization of rituximab administration regimen using population pharmacokinetics have been reported. Our paper reviewed the research progress in population pharmacokinetics of rituximab, aiming to provide reference to formulate an individualized dosing scheme of rituximab and realize precise administration for domestic patients.
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    Progress on anti-tumor mechanisms of Ganoderma lucidum active ingredients
    LV Yujiao, ZHOU Shuting, WANG Lina, SHEN Mingmei, LIU Yongchao
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 947-954.   DOI: 10.12092/j.issn.1009-2501.2024.08.012
    Abstract257)      PDF (712KB)(613)       Save
    Malignant tumors are one of the main causes of death from chronic diseases in China, and their incidence and mortality rates show an increasing trend year by year. Advanced non-surgical treatment of malignant tumors is an important means of improving patients' prognosis and enhancing their quality of life. The traditional Chinese medicine Ganoderma lucidum has anti-tumor effects and plays a role in the treatment of many malignant tumors. In this paper, a systematic review of the effects of Ganoderma lucidum active ingredients on tumors has been conducted at home and abroad in the past five years to explore the anti-tumor mechanism of Ganoderma lucidum active ingredients and to lay a theoretical foundation for the application of Ganoderma lucidum active ingredients in clinical practice.
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    Pharmacology and clinical evaluation of vericiguat in the treatment of heart failure
    LIU Ping, QIU Bo, WU Huizhen
    Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (2): 212-218.   DOI: 10.12092/j.issn.1009-2501.2022.02.013
    Abstract902)      PDF (1896KB)(606)       Save
    Vericiguat is a soluble guanylate cyclase stimulator, acting on nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway. Vericiguat can improve the sensitivity soluble guanylate cyclase sensitivity to nitric oxide, stimulate soluble guanylate cyclase without relying on nitric oxide, leading to increased formation of cyclic guanosine monophosphate , which results in multi-dimensional protection effects for the heart. It provides a new therapeutic approach for patients with heart failure. This review provides an overview of mechanism, preclinical studies, pharmacokinetics, clinical efficacy, drug-drug interactions and limitations of vericiguat.
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    Research progress on CXC chemokines and their receptors and pulmonary fibrosis
    CHEN Feng, LI Long, WANG Jie, LIU Shengfei
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (5): 583-589.   DOI: 10.12092/j.issn.1009-2501.2024.05.014
    Abstract185)      PDF (665KB)(597)       Save
    Pulmonary fibrosis (PF) is a common, persistent, irreversible, fatal chronic lung disease with a median survival of 2-4 years after diagnosis. It is characterized by excessive extracellular matrix deposition and scarring in the lungs, leading to functional failure, severe respiratory problems and even death. Numerous studies have shown that CXC chemokines and their receptors play important roles in PF and other desmoplastic disorders. Several studies have shown that chemokines may become new targets for the treatment of many diseases. Here, we review the role of key CXC chemokines and their receptors in PF to provide a reference for the treatment of PF.
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    Application of quantitative pharmacology in vaccine research and de-velopment: overview and prospect 
    MA Guangli, ZHANG Jing
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (3): 315-322.   DOI: 10.12092/j.issn.1009-2501.2023.03.010
    Abstract344)      PDF (1748KB)(595)       Save
    This article introduces the mechanism including antigen presentation, adjuvant, lymphatic system and the characteristics of vaccine, and then summarizes the key applications of core pharmaco-metrics approaches including QSP, PK/PD, dose re-sponse analysis, MBMA, in dose-response, preclini-cal and clinical translation, and correlation be-tween biomarkers and efficacy of vaccines. It is ex-pected that the successful application of model in-formed drug development can promote model in-formed vaccine development so that pharmaco-metrics makes its due contributions to the develop-ment of safer, more effective and more controlla-ble vaccine products.
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    Regulatory mechanism of LDLR and research progress of its related diseases and drugs
    LI Miao, YU Qinwei, JIANG Zhenzhou, ZHANG Luyong,
    Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (8): 946-954.   DOI: 10.12092/j.issn.1009-2501.2022.08.014
    Abstract913)      PDF (519KB)(585)       Save
    Cholesterol is an important lipid component in the body, which not only participates in the formation of cell membranes, but also is the raw material for the synthesis of bile acids and steroid hormones. Low density lipoprotein receptor (LDLR) is involved in cholesterol metabolism and plays an important role in maintaining the cholesterol homeostasis of organism cells. The expression of LDLR is precisely regulated by transcription, post-transcription and post-translation, and the imbalance of ldlr expression will lead to the occurrence and development of many diseases. In this paper, the molecular regulation mechanism of LDLR, the damage of target organs caused by the imbalance of LDLR expression and the research and development progress of drugs targeting LDLR are reviewed, which provides theoretical basis for further understanding of the progress of diseases related to lipid metabolism disorder and new insights for developing drugs targeting LDLR with more effective and less side effects.
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    Progress of pharmacotherapy for heart failure
    PENG Juan, FAN Linlin, LI Ranyi, LI Xiaoyu, LV Qianzhou, ZOU Yunzeng
    Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (4): 373-381.   DOI: 10.12092/j.issn.1009-2501.2022.04.004
    Abstract515)      PDF (521KB)(577)       Save
    Heart failure is the terminal stage of all kinds of heart diseases. Despite the use of a variety of traditional drug standard treatment, the prognosis is still not ideal, and there is an urgent need for the update and improvement of new drugs and treatment methods. In recent years, angiotensin receptor-enkephalase inhibitors (Sacubitril/Valsartan), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), soluble guanoside cyclase agonists (Vericiguat) and myocardial myosin activators omecamtiv mecarbil have been developed successively. SGLT2 inhibitors can improve ventricular load, reduce fibrosis and affect myocardial metabolism. sGC agonists play an anti-heart failure role by enhancing l-ARg-No-SGC-CGMP signaling pathway, improving myocardial and vascular function, reversing ventricular hypertrophy and fibrosis, slowing ventricular remodeling, and reducing ventricular afterload through systemic and pulmonary vasodilation. In addition, fineridone, a novel salt corticosteroid receptor antagonist, has also been reported in clinical studies in the field of heart failure. Therefore, it is the direction and hope for the development of heart failure in the future to select appropriate drugs for different types of patients with heart failure and carry out individualized treatment according to the optimized process of heart failure.
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    Mechanism of tyrosine kinase 2 inhibitors in treatment of plaque psoriasis and their progress in clinical trials 
    SHEN Jiaqing, LIU Yi
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (3): 323-330.   DOI: 10.12092/j.issn.1009-2501.2023.03.011
    Abstract292)      PDF (1286KB)(575)       Save
    As a chronic, immune-mediated in-flammatory disease, plaque psoriasis has a great burden of disease and influences on patient's physi-cal and mental health. In the past decade, plaque psoriasis treatment with biological agents achieved breakthrough development, while oral drugs with promising efficacy and safety are yet to be met. By cell signal transduction, the Janus kinase-signal transducer and activator of transcription pathway plays an important role in numerous immune-relat-ed diseases. Tyrosine kinase 2 (TYK2), a member of the JAK family, can impact on plaque psoriasis by regulating signaling and functional responses down-stream of IL-12, IL-23, IFN. Deucravacitinib, a highly selective TYK2 inhibitor, has finished its phase 3 clinical trials and shown its efficacy and safety in treatment of plaque psoriasis. Several kinds of TYK2 inhibitors are under research and develop-ment at the moment. In this review, we demon-strate roles of JAK-STAT pathway and TYK2 in plaque psoriasis as well as updates on ongoing and recently completed trials of TYK2 inhibitors. 
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    Mechanism of action and research progress of vaccine adjuvants
    ZHANG Li, LU Chang, AN Minghui, WANG Mengmeng, ZONG Xiaoyu, YU Lin, RAN Zhuo-ling, SONG Jing, LI Huijie, GONG Jian
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (7): 785-791.   DOI: 10.12092/j.issn.1009-2501.2024.07.008
    Abstract316)      PDF (831KB)(563)       Save
    Vaccines are among the most effective measures for preventing infectious diseases and play a crucial role in controlling the spread of these diseases. Adjuvants, serving as auxiliary components in vaccines, are indispensable in the vaccine development process. Ideal adjuvants not only enhance the immune response, enabling the body to achieve optimal protective immunity but also play important roles in reducing the dosage of immunogens and lowering vaccine production costs. To meet the demands of novel vaccines, many new types of adjuvants have been developed. However, there is still a lack of adjuvants that are safe, effective, easy to prepare, highly pure, and suitable for a variety of vaccines in clinical settings. This article categorizes adjuvants and summarizes their mechanisms of action and characteristics, focusing on traditional aluminum salt adjuvants and more modern lipid-based and nucleic acid-based adjuvants. The summary is based on a computer search of databases including PubMed, Embase, The Cochrane Library, CNKI (China National Knowledge Infrastructure), VIP Database, and Wanfang Database, using English search keywords such as Adjuvants, Vaccine, Vaccine Adjuvant, aluminum salts, MF59, AS03, Toll-like receptor agonist, etc., and corresponding Chinese search terms. The aim is to provide references for the development and application of adjuvants.
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    Research progress of JAK/STAT signaling pathway in the intervention of diabetic microvascular complications
    LI Tao, YANG Lixia, GAO Bo, LI Qin, SONG Shuang
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (12): 1415-1421.   DOI: 10.12092/j.issn.1009-2501.2023.12.012
    Abstract188)      PDF (685KB)(552)       Save
    Diabetic microvascular complications are the main reason for the high mortality of diabetic patients. There is still a great shortage of existing therapeutic drugs, so there is an urgent need for more effective new drugs. Janus kinase/signal transducer and activator of transcription (JAK/STAT) is involved in the progression of diabetic microvascular complications, which can be improved by regulating this pathway. Therefore, this article reviews the progress of JAK/STAT in diabetic microvascular complications (diabetic kidney disease, diabetic retinopathy, diabetic peripheral neuropathy), and summarizes the potential drugs that intervene JAK/stat to improve diabetic microvascular complications in recent years from three aspects of therapeutic drugs, preclinical drugs, and traditional Chinese medicine, in order to provide ideas for drug development and treatment of diabetic microvascular complications.
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    Research progress on pathogenesis and potential therapeutic target of sarcopenia obesity 
    GUO Yixun, GUAN Xiaoyin, WANG Bo, WEI Yingda, ZHANG Yan, LIN Jianhua
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (3): 341-346.   DOI: 10.12092/j.issn.1009-2501.2023.03.013
    Abstract343)      PDF (631KB)(548)       Save
    Sarcopenia obesity (SO), a specific dis-ease with co-occurrence of obesity and sarcopenia, is shown clinically as abnormal accumulation of fat, decreased mass and strength of muscle, and in-creased risk of incidence and mortality of other chronic diseases. Currently, there exist various defi-nitions and diagnoses about SO in the various re-gions of the world. Its prevalence in populations el-evates in an age-dependent manner. This article summarized the possible pathogenesis of SO from the view of chronic inflammation, oxidative stress, insulin resistance, and Hippo pathway, subsequent-ly listed and analyzed potential pharmacological targets (fibroblast growth factor, CD44, adiponec-tin, etc) involved in treating SO, in order to provide new ideas for clinical diagnosis, treatment of SO pa-tients and research and development of innovative drugs.
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    Human body networks mechanisms of melatonin and its clinical applications
    SHAO Mingkun, LIU Rong, SUN Pin, GUAN Shui, LIAO Bingcan, LI Sha, CONG Tao, LIANG Kai, MA Hui, SUN Changkai
    Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (9): 1031-1040.   DOI: 10.12092/j.issn.1009-2501.2022.09.010
    Abstract838)      PDF (2524KB)(540)       Save
    Melatonin is mainly an endogenous indoleamine hormone with many physiological functions. Melatonin not only plays an important role in the treatment of sleep disorders, but also plays an important role in the treatment of nervous system diseases, cancer, cardiovascular diseases, and bone diseases. In this paper, the human body networks mechanisms and the clinical applications of melatonin were summarized to provide reference for exploring the focus and direction of further clinical application research.
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    Research progress on drug treatment and drug resistance mechanism of gastrointestinal stromal tumors
    ZHAO Quanming, YANG Mandou, HU Yibo, SU Youtong, PU Li, ZHANG Yu, LI Wenliang
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (1): 82-89.   DOI: 10.12092/j.issn.1009-2501.2024.01.009
    Abstract316)      PDF (835KB)(537)       Save
    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) are the cornerstone of GIST therapy, but mutations in resistance genes pose many problems for treatment, especially the heterogeneity of KIT resistance mutations. In recent years, with the release of a number of GIST related drug research and experimental results, the great potential of targeted therapy, immunotherapy and combination therapy to treat GIST in different directions has been revealed, providing more therapeutic directions for GIST. This article will review the experimental research and future direction in recent years.
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    Platelet-endothelial aggregation receptor 1 and its mediated signalling pathway Advances in the study of the role of platelets and endothelial cells
    LI Ruoning, GUO Zhanli, WANG Yuan, SUN Jianjun
    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (4): 438-444.   DOI: 10.12092/j.issn.1009-2501.2023.04.011
    Abstract401)      PDF (1248KB)(525)       Save
    Platelet-aggregation  receptor 1 (PEAR1) is a transmembrane receptor identified in 2005 and expressed mainly on platelets and endothelial cells. PEAR1 is a receptor protein that contacts platelets with each other and plays an important role in platelet activation and aggregation. Endothelial cells play an important role in maintaining vascular tone and vascular repair, and PEAR1 regulates the process of tumourigenesis and development by affecting their proliferation and associated neovascularisation. In recent years, PEAR1 has gradually been recognized as a potential target for anti-thrombotic drugs. This review focuses on elucidating the mechanisms of platelet endothelial aggregation receptor 1 and related signaling pathways in platelets and endothelial cells, and provides new ideas for the study of drug therapy for tumour-associated thrombosis.
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    Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (3): 357-.  
    Abstract112)      PDF (227KB)(519)       Save
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    Research progress of anesthesia-related neural network in depth of anesthesia monitoring
    DING Jiahui, ZHOU Yu, YUAN Tianjie, XIA Junming, LI Wenxian, HAN Yuan
    Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (12): 1400-1407.   DOI: 10.12092/j.issn.1009-2501.2022.12.010
    Abstract410)      PDF (513KB)(519)       Save
    Improper control of depth of anesthesia is not only detrimental to the rapid and stable recovery of anesthesia, but also affects the postoperative outcome of patients. Therefore, accurate control of anesthesia depth is an urgent clinical and scientific problem in the field of anesthesiology. At present, different algorithm models derived from electroencephalogram (EEG) signals are used to monitor the depth of anesthesia, but they cannot meet the requirements of anesthesiologists to accurately evaluate the depth of anesthesia. In recent years, the research on the mechanism and modulation of anesthesia-related neural network suggests that it has potential value as a method to monitor depth of anesthesia. Anesthesia-related neural networks mainly include sleep-wake circuit, thalamic-cortical circuit and corticocortical network. A thorough understanding of the neural network involved in the loss of consciousness caused by anesthesia will guide the depth of anesthesia monitoring more accurately and provide possibility for improving the quality of clinical anesthesia resuscitation.
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    New progress in research and application of fenneridone
    CHENG Kuan
    Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (4): 450-456.   DOI: 10.12092/j.issn.1009-2501.2022.04.016
    Abstract598)      PDF (410KB)(513)       Save
    Aldosterone is a mineralocorticoid hormone produced by the adrenal cortex, which acts on receptors in the distal and collecting tubules of the nephron, causing reabsorption of sodium and secretion of potassium. Aldosterone can promote inflammatory response and lead to myocardial remodeling and fibrosis. Aldosterone acts through mineralocorticoid receptor (MR), which is mainly expressed in heart, kidney and blood vessels. Excessive activation of MR can cause endothelial dysfunction, fibrinolysis disorder, oxidative stress, cardiovascular and renal fibrosis, and eventually lead to organ injury, dysfunction and even organ failure. Mineralocorticoid receptor antagonist (MRA) can achieve cardiorenal protection by inhibiting inflammation and fibrosis caused by MR activation. The novel nonsteroidal MRA fenneridone can effectively block MR with its high selectivity and bring definite cardiac and renal protective effects.
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    Progress of hypertension pharmacological treatment
    LIU Guijian, CHENG Kuan, ZHU Wenqing, GE Junbo
    Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (4): 446-449.   DOI: 10.12092/j.issn.1009-2501.2022.04.015
    Abstract740)      PDF (295KB)(512)       Save
    Hypertension is a common cardiovascular disease. Chinese guidelines for the management of hypertension, the global practice guidelines for hypertension of the International Hypertension Society (ISH) and the guidelines for the treatment of adult hypertension drugs of the World Health Organization have been issued successively, which play an important role in guiding the clinical medication of hypertension. Calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), angiotensin receptor neprilysin inhibitor (ARNI), thiazide diuretics and β-receptor blockers are commonly used in clinical antihypertensive drugs. The goal of hypertension drug control, the application timing of hypertension drugs, the selection of combined medication scheme, the drug selection of hypertension complicated with other diseases, and the medication of gestational hypertension are all problems that clinicians need to master.
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    Progress and prospect of inhaled biological agents in asthma
    LI Guanghui, HUANG Jing, ZHU Min, ZHAO Rui, WAN Yakun, CHEN Zhihong
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (4): 406-414.   DOI: 10.12092/j.issn.1009-2501.2024.04.007
    Abstract390)      PDF (904KB)(508)       Save
    More than 300 million people worldwide suffer from asthma, and the incidence is increasing year by year. As one of the most common chronic diseases, asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity. With the in-depth study of physiological and pathological mechanisms, therapeutic small molecule and hormone drugs have been introduced to control and treat most patients, but about 5%-10% of patients still suffer from various subtypes of difficult to control and treat asthma, that is, severe asthma. In the past decade, with the rapid development of biopharmaceutical research, protein and antibody have become the key drugs for the treatment of severe asthma with high efficacy, high specificity and high safety. However, biological drugs are usually administered by injection, they cannot be noninvasive and directly delivered into the lung to quickly absorb and take effect. Therefore, there is an urgent need for the introduction of inhaled biologics with quick effectiveness, convenience, economy and safety in clinical. The review summarizes the existing small molecule, hormone and biological therapy drugs, and summarizes the development of inhalable biological agents of asthma, and analyzes the future prospects of the inhalable biological drugs, which is designed to deepen the perception of the direction of the inhalable biological drugs research, and update the information of the field, in order to provide reference for the development of more inhalable biologics.
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    Advances of VEGF signalling pathway in hepatocellular carcinomar invasion and metastasis and therapy
    LAN Xueling, HUANG Yanni, ZHU Minmin, MA Ping, DONG Min
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (6): 707-714.   DOI: 10.12092/j.issn.1009-2501.2024.05.013
    Abstract206)      PDF (664KB)(507)       Save
    The development of hepatocellular carcinoma (HCC) is closely related to the formation of tumour blood vessels. VEGF-mediated angiogenesis is a major driver of the immune escape response in tumours. VEGF binds to vascular endothelial growth factor receptor2 (VEGFR2) on endothelial cells, promoting endothelial cell proliferation and migration, inducing vascular changes in HCC, and thus promote the growth of hepatocellular carcinoma cells. Anti-VEGF and its receptor-targeted molecular drugs are currently effective new treatments for HCC. Monoclonal antibodies against VEGF and small-molecule tyrosine kinase inhibitors targeting VEGF have been shown to block its angiogenic activity, alleviate the inhibitory effect of the tumour microenvironment, and ultimately achieve tumour regression. This article provides a review of the research progress of VEGF/VEGFR inhibitors in HCC treatment.
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    Research progress in pharmacological and non-pharmacological treatments of hypertension
    XU Jianfei, LIN Li
    Chinese Journal of Clinical Pharmacology and Therapeutics    2022, 27 (4): 433-441.   DOI: 10.12092/j.issn.1009-2501.2022.04.013
    Abstract906)      PDF (473KB)(504)       Save
    Hypertension is the most common chronic non-communicable disease in the world and the most important risk factor for cardiovascular and cerebrovascular diseases. At present, the control rate of hypertension treatment standard is less than 50%, and it is still not effectively managed to a large extent. Despite numerous clinical studies and trials over the past four decades, the progress of new antihypertensive drugs has not been satisfactory. This review discusses recent advances in pharmacological and non-pharmacological treatments for patients with hypertension, and may provide new options for clinical hypertension treatment in the future.
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