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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 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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    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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    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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    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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    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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    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 advance in progesterone therapy for endometrial cancer
    ZHANG Liyi, GUO Zifen
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (2): 230-235.   DOI: 10.12092/j.issn.1009-2501.2024.02.013
    Abstract257)      PDF (631KB)(498)       Save
    Endometrial cancer originates from the endometrium and is one of the common gynecologic malignancies, with its incidence and mortality rate increasing year by year. Although endometrial cancer is more prevalent in the peri- and post-menopausal female population, it has been an evident trend in recent years towards younger patients. For young patients who have not yet given birth but intend to do so, the application of progestins in endometrial cancer treatment has made significant progress in clinical practice. Considering the existence of large individual differences and unclear mechanisms of action in the clinical application of progestins, this paper aims to provide an overview of the current clinical application status, efficacy, hormone resistance, and its mechanisms in the context of hormone therapy.
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    Application of single-cell multi-omics sequencing technology in the study of ischemic stroke
    MENG Qian, WANG Yiwen, CUI Na, BAI Min, YANG Le, DING Yi
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (6): 690-699.   DOI: 10.12092/j.issn.1009-2501.2024.06.011
    Abstract216)      PDF (810KB)(494)       Save
    Ischemic stroke is an acute cerebrovascular disease with high disability and mortality, is the most common cause of death in China. Despite years of research, there are still no biomarkers for stroke, and the molecular mechanisms remain largely unknown. In the past decade, single-cell sequencing technology, as a rapidly developing emerging technology, can conduct high-throughput sequencing of multiple omics including genome, transcriptome, epigenome and proteome at the level of a single cell, providing a new way to discover biomarkers and analyze pathological mechanisms. In this paper, the progress of single-cell multi-omics sequencing technology and its application in the discovery of biomarkers, pathological mechanisms and drug development of ischemic stroke are introduced in detail, in order to provide valuable reference for precision medicine of ischemic stroke.
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    The attenuating and potentiating effects of traditional Chinese medicine in immune checkpoint therapy
    ZHANG Zhipeng, CHEN Ziqi, TIAN Jianhui
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (3): 339-347.   DOI: 10.12092/j.issn.1009-2501.2024.03.013
    Abstract231)      PDF (649KB)(453)       Save
    Immunotherapy has become a global focus in cancer clinical practice and scientific research.In the past two years, PD-1\PD-L1 and CTLA-4 inhibitors, especially Nivolumab, Pembrolizumab, Atezolizumab and Lpilimumab, have been used in non-small cell lung cancer, colon cancer. Promising results have been obtained in malignancies such as melanoma and urinary tract cancer. Traditional Chinese medicine has a long history in China. Modulating immune checkpoints has certain advantages in treating malignant tumors, and it has shown good efficacy in improving its adverse events. This article reviews the role of traditional Chinese medicine in regulating immune checkpoints and improving adverse reactions and its application prospects in immunomodulatory treatment.
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    Progress in perioperative application of tranexamic acid
    WANG Wenli, YAO Yiting, YANG Chun
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (2): 198-206.   DOI: 10.12092/j.issn.1009-2501.2024.02.010
    Abstract266)      PDF (649KB)(427)       Save
    Perioperative bleeding is closely related to the prognosis of patients, and massive blood loss can lead to serious adverse events. Tranexamic acid, a lysine derivative, exerts anti-fibrinolytic effects by competitively blocking lysine binding sites on plasminogen to achieve hemostasis. Perioperative use of tranexamic acid can effectively reduce the risk of bleeding and the need for blood transfusion, and reduce the risk of bleeding related complications and death. At present, the use of tranexamic acid for perioperative hemostasis is increasingly widespread, and it is gradually entering the consensus and guidelines in more surgical fields. In this paper, the mechanism of action, perioperative application and adverse reactions of tranexamic acid were reviewed, and the effectiveness and safety of tranexamic acid in different surgical types were discussed, so as to provide reference for the application and research of tranexamic acid in China.
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    Drug treatment options and research progress of adolescent endometriosis
    HUANG Chunzhi, LIU Qinglan, SU Ran, SUN Nan
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (5): 535-542.   DOI: 10.12092/j.issn.1009-2501.2024.05.008
    Abstract175)      PDF (642KB)(400)       Save
    Endometriosis is a chronic, relapsing disease that requires long-term management. Adolescent endometriosis is a group that can be ignored, and the drug treatment is an important method for long-term management and fertility preservation. There are many kinds of drugs to treat endometriosis, such as NSAIDs, combined oral contraceptives (COC), progesterone, GnRHa. For the drug treatment selection, the characteristics of adolescents should be carefully considered and individualized treatment should be provided. In order to better long-term management, it is necessary to develop new treatments, which can effectively relieve endometriosis without damaging fertility. This review focuses on the drug treatment options and research progress of basic drug treatment for adolescent endometriosis, so as to delay disease progression, reduce adverse reactions, preserve fertility, and improve quality of life.
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    Mechanism and treatment of mucous hypersecretion in chronic obstructive pulmonary disease
    ZHANG Ting, SUN Rong, YANG Yong, LIU Weichun, YUAN Yuping, JU Xu, WANG Qian
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (4): 383-391.   DOI: 10.12092/j.issn.1009-2501.2024.04.004
    Abstract298)      PDF (719KB)(387)       Save
    Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease. It has been reported in the literature that COPD patients with chronic airway mucus hypersecretion have more frequent acute exacerbations, more severe lung function decline, and higher hospitalizations and mortality. Therefore, it is particularly critical to understand the pathogenesis of hypersecretion of mucus in chronic obstructive pulmonary disease and find out effective treatment. This article focuses on the structure, significance of airway mucus and the mechanism of hypersecretion of mucus in chronic obstructive pulmonary disease (COPD). In addition, we also summarized drug and non-drug therapy for chronic airway mucus hypersecretion in this article. Drug therapy includes traditional drug therapy, some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy, and non-drug therapy includes smoking cessation, physical therapy and bronchoscopy therapy. We hope that it will provide new ideas and directions for the treatment of mucus hypersecretion in COPD patients.
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    Recent progress of targeting Nrf2-ferroptosis to treat brain injury after ischemic stroke
    LI Mei, LI Qiang
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (2): 188-197.   DOI: 10.12092/j.issn.1009-2501.2024.02.009
    Abstract382)      PDF (973KB)(380)       Save
    Emerging evidences suggest that ferroptosis plays a vital role in the pathophysiological process of brain injury after Ischemic stroke. Accumulating evidence supports  pharmacological inhibition of ferroptosis as a therapeutic target for brain injury after Ischemic stroke through activating nuclear factor erythroid 2-related factor 2 (Nrf2), which transcriptionally controls many key components of the ferroptosis pathway. In this review, briefly describe ferroptosis processes and the roles they play in contributing to brain injury after ischemic stroke in the brain. We then provide a critical overview of the relationship between Nrf2 signalling and ferroptosis. With a focus on discuss how therapeutic modulation of the Nrf2 pathway is a viable strategy to explore in the treatment of ferroptosis-driven brain injury after Ischemic stroke.
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    Network pharmacology-molecular docking analysis and experimental validation to explore the protective mechanism of Mongolian medicine Gaoyou on renal function
    Celimuge, Hudeligen, XU Liang
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (9): 968-978.   DOI: 10.12092/j.issn.1009-2501.2024.09.002
    Abstract156)      PDF (2207KB)(379)       Save
    AIM: To explore the protective mechanism of Mongolian medicine Gaoyou on renal function through network pharmacology molecular docking and animal experiments. METHODS: The effective active components and targets of Gao you acting on acute kidney injury (AKI) and the related targets of AKI disease were obtained by using the relevant database of traditional Chinese medicine. The targets and components were mutually constructed to act on the network, and the signal pathways of drugs and diseases were enriched and analyzed. And the molecular docking validation study was carried out on the pharmacodynamic components with high moderate value in the network and the core action target. On this basis, after establishing the rat model of acute renal injury and giving Gaoyou intervention, the contents of creatinine (CR), urea nitrogen (BUN) and tumor necrosis factor-A (TNF-α), Kidney damage molecule-1 (Kim-1), cystatin C (Cys-C), neutrophil gelatinase related lipid transporter (NGAL) in serum of rats were detected, and renal tissue sections were observed with HE staining to verify the protective effect of Mongolian medicine Gaoyou on renal function of rats with acute renal injury. The predicted signal pathway was verified by Western blot. RESULTS: 40 key targets were obtained by network pharmacology and molecular docking analysis. KEGG and go enrichment analysis were carried out on the key targets. ALB, AKT1, VEGFA, IL-6, CASP3 and other key targets were predicted, and cancer signal pathway, TNF signal pathway, PI3K/AKT signal pathway and other key pathways were predicted. The results of molecular docking showed that the main active components of Gaoyou had good binding activity with related targets. The results of animal experiments showed that Gao you had a good protective effect on renal function, and Cr and BUN were significantly lower than those in the model group (P<0.05). The content of TNF-α decreased significantly (P<0.05). Kim-1, Cys-C and NGAL decreased significantly (P<0.05). HE staining showed that Gao can obviously improve the pathological state of acute renal damage. The expression of AKT1, p-AKT1 and CASP3 in renal tissue of rats with acute renal injury increased (P<0.05). Compared with the model group, the expression of AKT1, p-AKT1 and CASP3 in renal tissue of rats in Gaoyou group decreased significantly (P<0.05). CONCLUSION: Gaoyou can protect the renal function of rats with renal injury through multiple pathways such as anti-inflammatory, antioxidant, antithrombotic, anti apoptotic and so on through the characteristics of multi-component, multi target. Intervention of PKA3/AKT signal pathway and apoptosis factor may be one of its main mechanisms.
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    Effects of the proliferation, migration and apoptosis of AHVAC-Ⅰ on gastric cancer MKN-28 cells
    HUANG Xiaomei, ZHI Hui, CHEN Hao, LU Linming, ZHU Xiaoqun, WANG Lizhen, ZHOU Jue, PANG Jinjin, XU Jinliang
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (3): 270-276.   DOI: 10.12092/j.issn.1009-2501.2024.03.004
    Abstract128)      PDF (1799KB)(377)       Save
    AIM: To investigate the effects of agkis-trodon halys venom anti-tumor component Ⅰ (AHVAC-Ⅰ) on the biological behavior of gastric cancer MKN-28 cells. METHODS: Gastric cancer MKN-28 cells were treated with the experimental concentrations (5, 10, 15 μg/mL) of AHAVC-Ⅰ for 24 h.Cell proliferation and toxicity assay (cell counting kit-8, CCK-8) was used to detect the inhibition rates of the cells in different concentrations of AHVAC-Ⅰ. The migration ability of the cells was evaluated by wound-healing and Transwell assay. The apoptosis were observed by laser confocal microscopy with annexin V-mCherry/DAPI double staining, and the apoptosis rates were analyzed by flow cytometry with annexin V-FITC/PI double fluorescence staining. The protein level of Caspease-3 was determined by Western blot. RESULTS: Compared with normal control group, the results of AHVAC-Ⅰ concentration groups showed that with the increase of AHVAC-Ⅰ concentration, the proliferative activity of MN-28 cells decreased gradually (P<0.01), the cell migration ability decreased gradually (P<0.01), and the cell apoptosis rate increased (P<0.05). The expression of apoptosis-related protein Caspease-3 was up-regulated (P<0.01). CONCLUSION: AHVAC-Ⅰ inhibits proliferation and migration of gastric cancer MSN-28 cells and induces apoptosis.
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    Expert consensus on the diagnosis and treatment of insomnia in specified populations
    CHEN Guihai, DENG Liying, DU Yijie, HUANG Zhili, JIANG Fan, JIN Furui, LI Yanpeng, LIU Chunfeng, PAN Jiyang, PENG Yanhui, SU Changjun, TANG Jiyou, WANG Tao, WANG Zan, WU Huijuan, XUE Rong, YANG Yuechang, YU Fengchun, YU Huan, ZHAN Shuqin, ZHANG Hongju, ZHANG Lin, ZHAO Zhengqing, ZHAO Zhongxin
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 841-852.   DOI: 10.12092/j.issn.1009-2501.2024.08.001
    Abstract221)      PDF (795KB)(357)       Save
    Clinicians need to focus on various points in the diagnosis and treatment of insomnia. This article prescribed the treatment protocol based on the unique features, such as insomnia in the elderly, women experiencing specific physiological periods, children insomnia, insomnia in sleep-breathing disorder patients, insomnia in patients with chronic liver and kidney dysfunction. It provides some reference for clinicians while they make decision on diagnosis, differentiation and treatment methods.
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    Role of heterotrimer G protein in podocyte injury
    LIU Can, DAI Enlai, DING Zhaoran, DUAN Shuwen, WANG Xiaohui
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (2): 177-187.   DOI: 10.12092/j.issn.1009-2501.2024.02.008
    Abstract156)      PDF (721KB)(335)       Save
    GPCRs are the largest membrane protein receptor superfamily in the human body, with more than 800 isoforms, and approximately 35% of Food and Drug Administration-approved and marketed drugs currently target GPCRs for the treatment of a wide range of diseases, for heart failure (beta-adrenergic receptors), peptic ulcer (histamine receptors), prostate cancer (gonadotropin receptors), hypertension (adrenergic and angiotensin receptors), pain (opioid receptors), and bronchial asthma (beta2-adrenergic receptors) examples. Although the number of GPCRs is enormous, the signaling proteins downstream of them are limited, heterotrimeric G proteins (GPs) are key proteins that signal GPCRs, translate extracellular stimuli into intracellular responses by coupling to GPCRs and initiate multiple signaling events via downstream cascades. Podocytes are an important component of the glomerular filtration barrier, and their damage is a central event in proteinuria formation and progressive glomerulosclerosis. This article reviews the regulation of GPs, their signaling and their role in podocyte injury to provide a theoretical basis for scientific research and clinical treatment of this disease.
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    Research progress of molecular docking in screening anti-cervical cancer drugs
    WANG Dan, ZHANG Wenyan, LUO Renjie, CHEN Yuanjing, HAN Xue, QU Bo, FENG Shifang, NIE Xiazi, LIU Huiling
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 955-960.   DOI: 10.12092/j.issn.1009-2501.2024.08.018
    Abstract199)      PDF (568KB)(329)       Save
    Cervical cancer is one of the most common gynecological malignant tumors,the five-year survival rate decreased significantly in the case of lymph node metastasis and distant metastasis,so the development of new anti-cervical cancer drugs is of great significance for the treatment of cervical cancer.Molecular docking technology is one of the most commonly used research methods in computer aided drug design,which is widely used in screening the effective components of drugs, finding the targets of drugs acting on tumors and exploring the mechanism of antineoplastic drugs. This paper reviews the molecular docking technology in the screening of anti-cervical cancer drugs,the determination of anti-tumor targets and the mechanism of anti-cervical cancer,in order to provide more sufficient theoretical basis for the screening of anti-cervical cancer drugs and new drug research and development.
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    Research progress on the regulation of endometriosis by PI3K/Akt signaling pathway and the intervention effect of traditional Chinese medicine
    LI Quanyang, HAO Yafang, WU Guotai, WANG Ruiqiong
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (5): 501-511.   DOI: 10.12092/j.issn.1009-2501.2024.05.004
    Abstract189)      PDF (1158KB)(324)       Save
    Endometriosis (Endometriosis, EMs) is a disease caused by abnormal colonization of the endometrial stroma or glands to sites other than the coated mucosa of the uterine cavity. Phospholipid inositol 3 kinase (phosphoinositide 3-kinase, PI3K)/protein kinase B (protein kinase B, Akt) signaling pathway is involved in the process of focal blood vessel formation, cell autophagic apoptosis, migration and invasion, and is one of the classic pathways regulating the pathological characteristics of EMs. The characteristics of multi-component, multi-target and multi-pathway of TCM have significant advantages in the treatment of EMs. Some TCM active components and TCM compounds can interfere with the PI3K/Akt signaling pathway, thus inhibiting the treatment of endometriotic tissues, reducing pain and alleviating fibrotic lesions. By explaining the connection between the key targets of PI3K/Akt signaling pathway and EMs, this paper summarizes and summarizes the research status of EMs by regulating PI3K/Akt signal pathway in home and abroad, aiming to provide a new perspective and idea for the use of traditional Chinese medicine and compound to treat EMs.
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    Research progress of pharmacologic therapy in obstructive sleep apnea
    WU Xingdong, YUE Hongmei, ZHU Haobin, LIU Miaomiao, LI Yating, XU Jinhui
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (2): 215-229.   DOI: 10.12092/j.issn.1009-2501.2024.02.012
    Abstract474)      PDF (1349KB)(312)       Save
    Obstructive sleep apnea (OSA) is a common sleep disordered breathing disorder. As a major global public health problem, untreated OSA can lead to a variety of adverse health outcomes, including various cardiovascular and cerebrovascular diseases, metabolic disorders, and psychiatric disorders such as anxiety and depression. Traditional OSA therapies such as positive airway pressure (PAP), weight loss, oral?appliance, upper airway surgery, and postural therapy focus on the anatomical factors of OSA. However, the pathogenesis of OSA is heterogeneous, and non-anatomical factors also play an important role in most patients. Although there is no drug with exact efficacy for the treatment of OSA, with the deepening understanding of the pathophysiological mechanism of OSA, more and more clinical studies are devoted to the study of drug treatment of OSA and its complications, and a series of results have been achieved. The following is a review of the relevant studies on drug treatment of OSA in recent years, hoping to provide literature support and theoretical basis for future research on drug treatment of OSA.
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    Research progresses of nonsense-mediated mRNA decay in tumorigenesis and cancer therapy
    WANG Yuhui, WANG Jingpeng, CHEN Bei, WANG Yaru, LI Tangliang
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 930-936.   DOI: 10.12092/j.issn.1009-2501.2024.08.010
    Abstract224)      PDF (815KB)(312)       Save
    Nonsense-mediated mRNA decay (NMD) is a highly conserved post-transcriptional regulatory mechanism in eukaryotic cells. NMD can recognize and degrade abnormal transcripts containing premature termination codons (PTC) to prevent the translation of C-terminal truncated proteins. Furthermore, NMD could degrade a subset of normal gene transcripts and thus fine-tune gene expression. NMD is essential for cell fate determination, stress response, as well as animal development. In this review, we briefly discussed the functional and molecular mechanisms of NMD pathway activation and inhibition in tumorigenesis, cancer progression and therapy. Current studies indicate that NMD factor mutations can lead to a variety of human tumors. Interestingly, inhibition of NMD factors can activate DNA damage response and inhibit the expression of oncogenic factors, thereby killing cancer cells. This review may provide new perspectives for the biological mechanism and therapeutic strategy of human tumors.
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    Research progress of miRNA in ulcerative colitis
    LIU Xuan, FENG Cuijuan, WANG Yiqiang, LI Fang
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 917-929.   DOI: 10.12092/j.issn.1009-2501.2024.08.009
    Abstract161)      PDF (977KB)(307)       Save
    Ulcerative colitis (UC) is a chronic immune-mediated disease characterized by diffuse mucosal inflammation and clinical symptoms of abdominal pain, diarrhea, mucopurulent bloody stool and tenesmus. Due to its complex etiology, difficult treatment and poor prognosis, UC has been listed as one of the modern refractory diseases by the World Health Organization. MicroRNAs (microRNAs) regulate various biological processes such as cell growth, differentiation, and development by regulating gene expression. Studies have shown that miRNA is involved in the pathogenesis of UC through various pathways such as intestinal mucosal barrier homeostasis disorder, intestinal flora imbalance and excessive differentiation of immune cells, and is expected to become a new target for clinical treatment of UC. In order to better understand the role of miRNA in the pathogenesis of UC and provide new research directions for the treatment of UC, this article reviews the correlation between miRNA and the pathogenesis of UC, the potential of miRNA as a biomarker of UC, and the treatment strategies of miRNA in UC in recent years.
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    Progress in the potential therapeutic mechanism of mesenchymal stem cell-derived exosomes for liver fibrosis
    ZHAO Tingting, LI Junfeng, ZHANG Liting
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (4): 475-480.   DOI: 10.12092/j.issn.1009-2501.2024.04.017
    Abstract267)      PDF (888KB)(307)       Save
    Liver fibrosis is pathological in most chronic liver diseases. Exosomes secreted by mesenchymal stem cells (MSCs) can regulate liver fibrosis through mechanisms such as inhibition of inflammatory response and proliferation of activated hepatic stellate cells, regulation of immune cells and metabolism. Therefore, MSC-derived exosomes can be used as a cell-free therapy for chronic liver disease, expanding new ideas for the treatment of chronic liver disease. Recent researches on MSC-derived exosomes in the treatment of liver fibrosis are reviewed in this article.
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    Immunologic characteristics and management and prospects of targeted biological therapy in adults with severe asthma
    SUN Ao, WANG Jingluan, LIU Wenjuan, REN Dunqiang, LIU Xiaojing
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (4): 415-422.   DOI: 10.12092/j.issn.1009-2501.2024.04.008
    Abstract236)      PDF (645KB)(293)       Save
    Severe asthma stands as a formidable contributor to both mortality and morbidity of patients suffering asthma, casting substantial social and economic shadows on communities. As our understanding of asthma's pathophysiology deepens, a beacon of hope emerges in the form of biological targeted therapies, offering a promising avenue for the management of this challenging condition. These therapies, by precisely inhibiting or modulating pivotal molecules in the inflammatory cascade, offer potential benefits in symptom alleviation, lung function enhancement, and risk reduction of acute exacerbations. They signify a paradigm shift in severe asthma treatment. Within the confines of this article, we embark on a systematic exploration of the immunological underpinnings that define severe asthma. By delving into the intricacies of the immune system's role in exacerbating this condition, we aim to offer a comprehensive assessment of both the current landscape and the future prospects of biological therapies. Our objective is to provide a scientifically robust and valuable reference that can guide the individualized treatment of patients grappling with severe asthma.
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    Progress in the application of non-peptide gonadotropin-releasing hormone antagonist in the treatment of uterine fibroid
    ZHENG Yunxi, YI Xiaofang, XU Congjian
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (5): 482-487.   DOI: 10.12092/j.issn.1009-2501.2024.05.001
    Abstract266)      PDF (603KB)(286)       Save
    Non-peptide gonadotropin-releasing hormone antagonist (GnRH-antagonist) is a highly efficient and selective antagonist of GnRH receptor. The oral preparations (Elagolix, Relugolix and Linzagolix) had been approved for listing abroad. It shows efficacy in reducing the size of uterine fibroid and controlling heavy bleeding. Appropriate combination of‘add-back’therapy could improve the safety in medical application and patient compliance. Compared with other hormonal pharmaceuticals, oral GnRH-antagonists showed promising prospects in the treatment of uterine fibroid.
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    Stains: recent research progress for endometriosis
    QIN Xian, WANG Qian, HOU Jia, XU Dongmei
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (5): 488-494.   DOI: 10.12092/j.issn.1009-2501.2024.05.002
    Abstract259)      PDF (580KB)(283)       Save
    Defined as a common gynecologic endocrine disease, endometriosis is characterized by the presence of endometrium outside of the uterus cavity, affecting about 10% to 15% of reproductive-aged women worldwide.Moreover, Asian women tend to have a nine-fold increased risk of endometriosis compared with their white counterparts in Europe and the United States. Endometriosis not only causes chronic pelvic pain, dysmenorrhea, painful sex and other pain symptoms, but also leads to infertility, pushing the patients into a state of fatigue, high sensitivity and anxiety, thus reducing their quality of life. As the aging of Chinese population intensifies and the women's childbearing age delays, it is highly urgent to find solutions to those gynecological endocrine diseases such as endometriosis, which hamper women's fertility. In recent years, studies have shown that patients with endometriosis have abnormal serum lipid metabolism and an increased risk of cardiovascular diseases. At the same time, as a type of cholesterol-lowering drug, statins can inhibit the progression of endometriosis at the cellular and animal levels. Also, a few clinical studies have exhibited that statins exert a positive effect on the treatment of endometriosis. Therefore, this article aims to review the researches regarding the relationship between endometriosis and the cardiovascular disease, as well as the research progress of statin therapy on endometriosis based on the level of cells, animals and human beings. 
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    Advances in clinical research of CAR-T immunotherapy for systemic rheumatic diseases
    LI Zhi, ZHANG Mengying, ZHU Chuanmiao, MAO Li, PENG Hui
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (8): 937-946.   DOI: 10.12092/j.issn.1009-2501.2024.08.011
    Abstract209)      PDF (743KB)(279)       Save
    Systemic rheumatic disease is a kind of autoimmune disease which is caused by the dysfunction of autoimmune cells and the damage of multiple systems and organs. Traditional immunosuppressants play an important role in the treatment of systemic rheumatic diseases, but there are still a considerable number of refractory systemic rheumatic diseases that do not respond well to traditional immunosuppressant therapy, and new therapeutic methods need to be explored. Chimeric antigen receptor T cell therapy (CAR-T) immunotherapy was initially used for the treatment of malignant hematological diseases and has shown good efficacy. Recently,CAR-T immunotherapy has also achieved remarkable efficacy in refractory systemic lupus erythematosus. It brings new hope for the treatment of systemic rheumatic diseases. This article summarizes the progress of clinical application of CAR-T immunotherapy in systemic rheumatic diseases in recent years, aiming to enhance clinicians' cognition of CAR-T immunotherapy and promote the further development of CAR-T immunotherapy in systemic rheumatic diseases.
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    Clinical features, risk factors and treatment of type 2 diabetes mellitus in patients with acute exacerbation of chronic obstructive pulmonary disease
    WANG Xiaochuan, WANG Hanchao, YAO Yu, LI Li, HE Gaoyan, LI Bo, ZHU Tao
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (4): 392-400.   DOI: 10.12092/j.issn.1009-2501.2024.04.005
    Abstract246)      PDF (707KB)(263)       Save
    AIM: To investigate the clinical features of acute exacerbation chronic obstructive pulmonary disease (AECOPD) of complicated with type 2 diabetes mellitus (T2DM) , and analyze the related clinical features and risk factors. METHODS: This was a single-center cross-sectional study. From March 2020 to January 2023, 479 hospitalized patients with AECOPD in the department of respiratory and critical care medicine, Suining Central Hospital were included. There were 215 patients in AECOPD group and 60 patients in AECOPD with T2DM group. The collected variables included demographic data, complications, blood routine, infection index, random blood glucose, blood gas analysis and lung function. The adoption rate and constituent ratio of the basic description classification data were expressed as mean standard deviation for the normal distribution measurement data and median interquartile range for the skew distribution measurement data. T-test was used for normal distribution and non-parameter test was used for non-normal distribution. The categorical variables were tested by chi-square test. Rank sum test was used for rank variable data. Binary logistic regression model was used to investigate the independent factors associated with T2DM in patients with AECOPD. Finally, the results of logistic regression were verified and visualized by nomogram, validation curve, ROC curve and DCA curve. P<0.05 was a significant statistical difference. RESULTS: Univariate analysis showed that there were significant differences in body mass index (BMI), essential hypertension, coronary heart disease, atrial fibrillation (AF), pulmonary function (GOLD stage), blood neutrophil (NS), blood lymphocyte (LYM), arterial blood gas PaCO2, Alanine transaminase (ALT) and random blood glucose (RBG) between the two groups (P<0.05). The binary logistic regression model (C-index=0.847) was constructed with the above 10 variables, the results showed that BMI (OR=1.309), Af (OR=8.188), LYM counts (OR=0.474), PaCO2 (OR=1.082) and RBG (OR=1.434) were independently associated with type 2 diabetes in patients with AECOPD (all P>0.05). The results of logistic regression were verified and visualized by Nomogram and its-associated ccurves. The MAE and AUC curves were 0.021 and 0.847 respectively, indicating that the model had good prediction consistency and accuracy. The DCA curve showed that Nomogram's risk threshold ranged from 0.01 to 0.99, suggesting that nomogram's model had better clinical predictive value. CONCLUSION: Our results showed that increased BMI, PaCO2 and random glucose, decreased blood lymphocyte, and atrial fibrillation is an independent clinical feature of AECOPD with T2DM. These results suggest that the immune function of patients with AECOPD and T2DM are more severely impaired and more likely to be accompanied by atrial fibrillation, which is a potential cause of poor prognosis in these patients. Meanwhile, this conclusion needs to be further verified in multicenter study with large sample size.
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    Effects of remimazolam on early postoperative cognitive function in elderly patients with hip fracture
    DUAN Gongchen, WU Jimin, XU Qiaomin, JIANG Jianxin, LAN Haiyan, ZHANG Xutong, YUAN Kaiming, LI Jun
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (2): 146-153.   DOI: 10.12092/j.issn.1009-2501.2024.02.004
    Abstract300)      PDF (749KB)(262)       Save
    AIM: To evaluate the effect of remimazolam on early postoperative cognitive function in elderly patients with hip fracture based on a randomized controlled trial. METHODS: A total of 106 elderly patients, aged 65-90 years, ASA grade Ⅱ or Ⅲ, who underwent hip fracture surgery under combined spinal-epidural anesthesia in the Sixth Affiliated Hospital of Wenzhou Medical University from December 2022 to June 2023 and met the inclusion criteria, were selected and randomized into remimazolam group (group R) and propofol group (group P) according to the random number table, with 53 cases in each group. Patients in group P received a slow intravenous injection of propofol at a dose of 0.3-0.5 mg/kg (injection time of 1min), followed by a pump infusion at 0.5-3 mg·kg-1·h-1 for maintenance. In group R, intraoperative sedation was maintained by remimazolam at 0.1-0.3 mg·kg-1·h-1 after a loading dose of 0.05 mg/kg (injection time of 1min). The pump infusion rate were adjusted by maintaining MOAA/S score at 3-4 and BIS value at 75-85, and stopped administering sedatives while suturing the incision. MOAA/S score, MAP, HR, RR, SpO2 and BIS values were recorded before sedation (T0), 5 (T1), 10 (T2), 15 (T3), 30 (T4) and 60 (T5) min after sedation and at the end of surgery. The emergence time, intraoperative amnesia, the incidence of postoperative delirium (POD) and delayed neurocognitive recovery (DNR) within 7 days after operation, and the occurrence of adverse events during perioperative observation were recorded. RESULTS: Compared with T0, the BIS and MOAA/S scores of the two groups at T1-T5 were significantly decreased, and the MAP and HR of the two groups at T1-T6 were significantly lower (P<0.05). Compared with group P, group R showed higher MAP at all time points from T1 to T6 (all P<0.05), shorter emergence time (6.6±1.8 vs. 7.7±2.2 min, P<0.05), less decline in Hopkins Verbal Learning Test scores on postoperative day 7 (3.9±3.9 vs. 6.2±4.6, P<0.05), lower incidence of postoperative delirium and DNR (7.5% vs. 28.3%,5.7% vs. 20.8%, P<0.05), higher incidence of intraoperative amnesia (52.8% vs. 28.3%, P<0.05) lower incidence of hypotension and bradycardia (15.1% vs. 37.7%, 5.6% vs. 22.6%, P<0.05), and fewer frequent use of vasoactive drugs (P<0.05). CONCLUSION: Application of remimazolam for perioperative sedation in elderly patients with hip fracture can provide effective sedation and stable hemodynamic, with little effect on early neurocognitive function, and overall safety higher than propofol.
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    A novel antibody-drug conjugate: disitamab vedotin
    YIN Xiaoyu, LU Ming, YU Zefang, PANG Guoxun
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (11): 1315-1320.   DOI: 10.12092/j.issn.1009-2501.2024.11.015
    Abstract159)      PDF (673KB)(260)       Save
    Antibody drug conjugates (ADCs) are a new class of anti-tumor drugs in which linkers in the structure link cytotoxic drugs to monoclonal antibodies and release cytotoxic drugs to tumors. Disitamab vedotin (RC48) is a new antibody-drug conjugate independently developed in China. It targets the HER2 protein on the surface of tumors, it has both antibody targeting and small molecule drug killing, and can accurately recognize and kill tumor cells. Compared with traditional HER2-targeted drugs, disitamab vedotin has a wider therapeutic window and less toxicity to normal tissues. Currently, disitamab vedotin for injection has been approved by the National Medical Products Administration (NMPA) for use in patients with HER2 overexpression (HER2 immunohistochemical results of 2+ or 3+) who have locally advanced or metastatic gastric cancer (including gastroesophageal junction adenocarcinoma) and have received at least two types of systemic chemotherapy. Additionally, it is indicated for patients with locally advanced or metastatic urothelial carcinoma who have previously undergone platinum-containing chemotherapy and exhibit HER2 overexpression, specifically 2+ or 3+ immunohistochemical results. In this paper, we will review the structural characteristics, mechanism of action and clinical trials of disitamab vedotin and look forward to the clinical application prospects of this drug.
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    Rapid health technology assessment of dienogest in the treatment of endometriosis
    GUO Hua, LIU Lanlan, HUANG Chunzhi, SUN Nan, REN Yanli
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (5): 512-519.   DOI: 10.12092/j.issn.1009-2501.2024.05.005
    Abstract237)      PDF (616KB)(259)       Save
    AIM: To rapidly evaluate the effectiveness, safety and economy of dienogest in the treatment of endometriosis so as to provide evidence-based reference for clinical drug selection and decision. METHODS: Retrieved from PubMed, Embase, Cochrane Library, CNKI, SinoMed, Wanfang and health technology assessment (HTA) organization websites, HTA report, systematic review/Meta-analysis and pharmacoeconomic study were included during the inception to Sep 2023. Data extraction and quality evaluation were carried out for the literature that met the inclusion and exclusion criteria, and the research results were summarized and analyzed qualitatively. RESULTS: Nine systematic review/Meta-analyses, and 2 pharmacoeconomic studies were included. The quality of Meta-analysis literatures was low, and the quality of economic research was good. In terms of effectiveness, compared with no treatment, dienogest can significantly reduce postoperative recurrence rate, VAS score, and improve pregnancy rate and effective rate; Dienogest has similar therapeutic effects in terms of recurrence rate as GnRHa and COC; With regard to recurrence rate and pregnancy rate, dienogest is superior to danazol, gestrinone, and mifepristone. In terms of safety, compared with placebo, the incidence of vaginal bleeding and headache was significantly increased with dienogest, and there was no difference in bone loss; The incidence of vaginal bleeding caused by dienogest was significantly higher than that of GnRHa, but the incidence of hot flashes and bone loss was lower. In terms of economy, dienogest has a more cost-effective advantage comparing with GnRHa, but does not have economic benefits comparing with COC. CONCLUSION: Dienogest has good effectiveness and safety in the treatment of endometriosis, and economically superior to GnRHa, but inferior to COC.
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    Progress in researches for perampanel in the treatment of comorbidities of epilepsy
    CHEN Sirui, LI Junqiang, DANG Xiaoli, WANG Tiancheng
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (3): 354-360.   DOI: 10.12092/j.issn.1009-2501.2024.03.015
    Abstract245)      PDF (575KB)(251)       Save
    Sleep disorder, migraine, cognitive and behavioral disorders, anxiety and depression are common comorbidities of epilepsy. The comorbidity rate of epilepsy patients is eight times that of the general population, which affects the prognosis and quality of life of epilepsy patients. Perampanel (PER), as a third-generation antiseizure medication, has shown promising clinical research and application in the treatment of comorbidities in epilepsy. PER can improve the total sleep time, sleep latency and sleep efficiency of patients with epilepsy comorbid sleep disorder. PER also shows good efficacy in reducing seizure and migraine attacks of patients with epilepsy comorbid migraine. Meanwhile, the impact of PER on overall cognitive characteristics is neutral, with no systematic cognitive deterioration or improvement, but behavioral changes are one of the most common adverse events related to PER. For patients with comorbid anxiety and depression, PER does not exacerbate the anxiety and depression of epilepsy patients, and the severity of anxiety and depression in some patients will improve. This article will review the mechanism of action and clinical treatment research progress of PER on comorbidities of epilepsy.
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    Advances in the study of ω-3 PUFA in heart failure
    YU Jiling, ZHANG Jing, DENG Yifan, HE Shenghu
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (2): 236-240.   DOI: 10.12092/j.issn.1009-2501.2024.02.014
    Abstract191)      PDF (566KB)(248)       Save
    Free fatty acids, as important energy metabolism substrates for the heart, play an important role in various cardiovascular diseases; ω-3 PUFA, as an important branch of free fatty acids, has been confirmed by more and more researches to be closely related to cardiovascular diseases. Heart failure, as a common cardiovascular problem, seriously affects people's quality of life. Studies have shown that ω-3 PUFA plays a significant role in the development of heart failure. In this paper, we try to review the metabolism, pathogenesis and therapeutic significance of ω-3 PUFA in heart failure.
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    Progress in the application of AIT in allergic airway diseases
    WANG Linlin, MA Yuan, CHEN Zhihong, JI Haiying
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (4): 427-431.   DOI: 10.12092/j.issn.1009-2501.2024.04.010
    Abstract185)      PDF (536KB)(248)       Save
    Allergen specific immunotherapy (AIT) is to identify the patient's allergen, give the patient repeated exposure to the allergen extract, and gradually increase the concentration and dose until the target maintenance dose is reached, so that the patient can develop tolerance to the allergen, which is the only treatment that can regulate the pathogenesis of allergic diseases and change its natural course. In recent years, domestic and foreign scholars have made great progress in the clinical practice and research field of AIT. This article reviewed the relevant progress of the mechanism, efficacy and drug administration of AIT.
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    Research progress of dalpiciclib in treatment of breast cancer
    DU Caiying, QUAN Xianghua, SUN Caihong, YUAN Haidan
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (6): 715-720.   DOI: 10.12092/j.issn.1009-2501.2024.06.014
    Abstract163)      PDF (632KB)(248)       Save
    As the first domestically originated cell cycle protein-dependent kinase 4/6 inhibitor, dalpiciclib has been approved by the State Drug Administration for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer in combination with fulvestrant or aromatase inhibitors. This article focuses on the progress of dalpiciclib research in breast cancer, summarizing the drug's mechanism of action, phase I-III clinical trials, and drug safety issues.
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    Mechanism of Dahuangtang pellets in regulating podocyte autophagy of diabetic nephropathy mice through AMPK/mTOR/ULK1 signaling pathway 
    SU Beibei, YANG Lixia, LIANG Yonglin, ZHU Xiangdong, YANG Xia, XUE Chunxia, ZHANG Pu, PEI Xiaoli
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (3): 260-269.   DOI: 10.12092/j.issn.1009-2501.2024.03.003
    Abstract162)      PDF (6320KB)(240)       Save
    AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II/LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P<0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK/mTOR/ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli.
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    Research progress on physiological and pathological functions of salt-inducible kinase and its inhibitors
    LIN Xinyue, WANG Yanyan, BIAN Hongsheng, YU Shuang, HUANG Lili
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (11): 1306-1314.   DOI: 10.12092/j.issn.1009-2501.2024.11.014
    Abstract148)      PDF (743KB)(235)       Save
    The salt-inducible kinase (SIK) family includes three isoforms, SIK1, SIK2 and SIK3, which are the main regulators of physiological and pathological processes and participate in the regulation of glucose and lipid metabolism, tumor, inflammation, depression, sleep-wake and circadian rhythm. SIK inhibitor has become a candidate drug for the treatment of a variety of diseases, and is especially expected to become a potential new drug for the treatment of nervous system diseases, such as sleep disorders, circadian rhythm disorders, and depression. This review summarizes the regulation and mechanism of three isoforms of SIK and their upstream and downstream signaling pathways in the above physiological and pathological processes. It also reviews the recentstudies of SIK inhibitors. 
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    Research progress on material basis and mechanism of Hedyotis Diffusa-Scutellaria Barbata Herb Pair in the treatment of gastric cancer
    ZHANG Xiaowei, WANG Nan, DAI Mengge, LIU Ruijuan, MA Ting
    Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (7): 831-840.   DOI: 10.12092/j.issn.1009-2501.2024.07.014
    Abstract203)      PDF (1074KB)(231)       Save
    Gastric cancer is one of the most common malignant tumors in the digestive system, which often occurs in middle-aged and elderly people. Traditional Chinese medicine recognizes gastric cancer as a kind of tumor characterized by fluid deficiency, heat accumulation and the growing binding of toxins in the stomach. It is commonly treated with heat-clearing and detoxifying drugs in clinical practice. Hedyotis diffusa-Scutellaria barbata herb pair (HS) has the effects of clearing heat and detoxifying, promoting blood circulation, resolving carbuncle and expulsing boil, anti-inflammatory and analgesic, which are consistent with the etiology and pathogenesis of gastric cancer, therefore, it can be used for the treatment of gastric cancer. Modern pharmacological researches have confirmed that HS can play an anti-gastric cancer role by inducing cell apoptosis, inhibiting cell proliferation, inhibiting angiogenesis, improving immune microenvironment and down-regulating telomerase activity. Herein, this review summarizes the active ingredients and related mechanism responsible for the anti-gastric cancer effect of HS, which will provide the theoretical basis for its clinical use and the development of new drugs against gastric cancers.
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