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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 Abstract （111）      PDF （835KB）（313）       Knowledge map    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. Related Articles | Metrics

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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 Abstract （404）      PDF （754KB）（283）       Knowledge map    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. Related Articles | Metrics

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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 Abstract （182）      PDF （654KB）（190）       Knowledge map    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. Related Articles | Metrics

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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 Abstract （128）      PDF （624KB）（167）       Knowledge map    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. Related Articles | Metrics

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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 Abstract （122）      PDF （672KB）（155）       Knowledge map    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. Related Articles | Metrics

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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 Abstract （183）      PDF （734KB）（140）       Knowledge map    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. Related Articles | Metrics

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The possibility of phosphodiesterase 4 inhibitors as drug therapy for idiopathic pulmonary fibrosis LI Yating, YUE Hongmei, LIU Miaomiao, XU Jinhui, WU Xingdong, ZHU Haobin Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (7): 818-823.   DOI: 10.12092/j.issn.1009-2501.2023.07.013 Abstract （152）      PDF （620KB）（136）       Knowledge map    Save Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible and typical chronic fibrotic lung disease. In recent years, significant progress has been made in the pathophysiology, clinical diagnosis and treatment of IPF. However, to date, there is still no cure for IPF. The second messenger cyclic adenosine monophosphate (cAMP) inhibits fibroblast proliferation or differentiation into myofibroblasts during the development of IPF. Phosphodiesterase 4 (PDE4) is a major camp-degrading enzyme in lung fibroblasts, which is up-regulated during the progression of fibrosis. PDE4 inhibitors have anti-fibrosis effects in vivo and in vitro in IPF models. In addition, PDE4 is widely involved in inflammatory processes, which are also active in the pathogenesis of IPF. Thus, PDE4 inhibition is a potential therapeutic approach for IPF. This article reviews the pathogenesis of IPF and the physiological function of PDE subtype 4 inhibitors in the treatment of IPF.  Related Articles | Metrics

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Advances in targeted therapy for HER2-positive breast cancer LUO Shiping, ZHANG Jie, YU Yushuai, SONG Chuangui Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (8): 876-886.   DOI: 10.12092/j.issn.1009-2501.2023.08.004 Abstract （231）      PDF （761KB）（136）       Knowledge map    Save Since the beginning of the 21st century, with the continuous development of anti-HER2-targeted drugs, more treatment options have been provided for patients with HER2-positive breast cancer and the survival prognosis has been significantly improved. At present, anti-HER2 targeted drugs mainly include monoclonal antibody drugs such as trastuzumab and pertuzumab, small molecule tyrosine kinase inhibitors such as lapatinib and neratinib, and antibody-drug conjugates such as T-DM1 and T-DXd, which play an extremely important role in different disease processes. The treatment of HER2-positive breast cancer is based on targeted therapy with trastuzumab. Early-stage patients with high risk factors can be treated with intensive targeted therapy to further improve the prognosis, while advanced patients need a reasonable arrangement of targeted therapy to overcome drug resistance and prolong survival. This article will review the current status, the latest research progress and the future prospects of anti-HER2 targeted therapy in different stages of the disease. Related Articles | Metrics

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Advances in venlafaxine-related PK-PD relationship and influencing factors WANG Xin, WU Guodong, AN Ming, LI Gang, LIU Yang Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (7): 788-795.   DOI: 10.12092/j.issn.1009-2501.2023.07.010 Abstract （146）      PDF （879KB）（133）       Knowledge map    Save Venlafaxine (VEN) is a new antidepressant drug that can effectively antagonize the reuptake of serotonin (5-HT) and norepinephrine (NE), compared with other antidepressants, venlafaxine pharmacokinetics/pharmacodynamics (PK-PD) is more regular and has the characteristics of less toxic side effects, fast oral absorption, and high bioavailability. This article reviews the PK-PD modelling of venlafaxine and its quantitative relationship, as well as the factors affecting the process in vivo of venlafaxine, including sex, body weight, individual genotype, liver and kidney function impairment, drug-drug interaction and other related factors. Related Articles | Metrics

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Pathogenic mechanism and research progress of adipocytokines in endometrial cancer MA Yitong, MA Jianhong, GAO Yating, LIU Chang Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (11): 1315-1320.   DOI: 10.12092/j.issn.1009-2501.2023.11.015 Abstract （73）      PDF （621KB）（133）       Knowledge map    Save Endometrial carcinoma (EC) is one of the most common gynecologic tumors, and its incidence and mortality are increasing.The prognosis is usually favorable when the disease is diagnosed at an early stage. However, the prognosis for patients with recurrence and metastasis is relatively poor. As one of the risk factors for EC, the complex and widespread oncogenic role of obesity in EC has been validated, then the oncogenic and pro-carcinogenic mechanisms of adipocytokines secreted by adipose tissue in EC have attracted continuous attention. This review highly summarizes and concludes the previous relevant literature on the role of adipocytokines in endometrial cancer and the progress of research， and elucidates the correlation between adipocytokines and the occurrence risk, stage grading, and long-term prognosis of EC, as well as their signaling pathways and mechanisms of action in the development of EC. All this information will likely contribute to the development of novel molecular markers in EC, the discovery of new therapeutic targets, and the study of related targeted drugs, which may in turn break the current dilemma of early screening, early diagnosis, and treatment of recurrent and metastatic patients in EC in the future, resulting in an improvement of the long-term prognosis of patients with EC. Related Articles | Metrics

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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 Abstract （155）      PDF （851KB）（132）       Knowledge map    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. Related Articles | Metrics

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Angelica polysaccharides improve hepatic endoplasmic reticulum stress by inhibiting the expression of GRP78, p-PERK and p-Eif2α in diabetic KK-Ay mice MA Xiankang, YANG Lixia, CUI Yangyang, MI Denghai Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (8): 926-936.   DOI: 10.12092/j.issn.1009-2501.2023.08.009 Abstract （121）      PDF （3112KB）（120）       Knowledge map    Save AIM: To investigate the regulatory mechanism of Angelica polysaccharide on hepatic endoplasmic reticulum stress in diabetic KK-Ay mice. MEHTODS: Forty diabetic KK-Ay mice were randomly divided into model group, metformin group, and angelica polysaccharide high, medium, and low dose groups, with 8 mice in each group. 8 C57BL/6J mice were used as blank control group. The mice were gavaged with 400 mg/kg, 200 mg/kg and 100 mg/kg of angelica polysaccharide in the high, medium and low dose groups, respectively, and 200 mg/kg of metformin hydrochloride in the metformin group, while the normal and model groups were gavaged with equal volume of saline, and fasting blood glucose and body weight were measured weekly. After 4 weeks of gavage, triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were measured in mice serum; RT-PCR was performed to observe the expression of glucose-regulated protein 78 (GRP78), phosphorylated pancreatic endoplasmic reticulum kinase (p-PERK) and phosphorylated α-subunit eukaryotic initiation factor 2 (p-Eif2α) in liver tissues. mRNA expression; Western blot, immunohistochemistry to detect the protein expression of GRP78, p-PERK, p-Eif2α in mouse liver tissues. HE staining: to observe the histopathological changes in the liver. RESULT: Compared with the blank group, the levels of TC, TG and LDL-C were significantly increased (P<0.01) and the levels of HDL-C were significantly decreased (P<0.01) in the model group; compared with the model group, the levels of TC, TG and LDL-C were significantly decreased (P<0.05, P<0.01) and the levels of HDL-C were significantly increased in the metformin group, angelica polysaccharide high and medium dose groups. Compared with the blank group, the expression of GRP78, p-PERK and p-Eif2α in the model group was significantly upregulated (P<0.01), and the expression of GRP78, p-PERK and p-Eif2α in the angelica polysaccharide high, medium and low dose groups was significantly downregulated (P<0.05, P<0.01), and the high dose group had the best effect compared with the model group. Compared with the model group, the mice in the angelica polysaccharide group showed dense liver tissue, reduced vacuole-like degeneration, reduced liver steatosis, gradually aligned hepatocytes, and clear hepatic sinusoidal structure, and the effect was dose-dependent. CONCLUSION: Angelica polysaccharide significantly improved liver injury in diabetic KK-Ay mice, and its mechanism of action may be related to the inhibition of endoplasmic reticulum stress-related proteins and factors GRP78, p-PERK and p-Eif2α expression by Angelica polysaccharide and improvement of endoplasmic reticulum stress. Related Articles | Metrics

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Involvement of intracellular organelle stress, autophagy and ferroptosis in cobalt chloride-induced vascular smooth muscle cell injury LEI Yan, PENG Xiaoyong, DENG Mengsheng, ZHANG Dongdong, ZHU Yingguo, WANG Jianmin, DUAN Zhaoxia, LI Tao, LIU Liangming, YANG Guangming Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (1): 1-10.   DOI: 10.12092/j.issn.1009-2501.2024.01.001 Abstract （92）      PDF （1695KB）（117）       Knowledge map    Save AIM: To investigate the relationship between vascular smooth muscle cell (VSMC) injury, organelle stress response and autophagic cell death (autophagy) and ferroptosis induced by the chemical hypoxia inducer cobalt chloride (CoCl2) through the bioinformatics analysis and in vitro cell experimentation. METHODS: The dataset GSE119226 of VSMC treated with cobalt chloride was acquired from the gene expression database (GEO). The R language was used to investigate the relationship between CoCl2 treatment and organelle stress response (Golgi stress, endoplasmic reticulum stress) and two forms of cell death (ferroptosis and autophagic cell death). With primary cultured rat VSMC (rVSMC) and CoCl2-induced anoxia model, the changes in cell viability were detected by CCK-8 method, and reactive oxygen species (ROS) levels were measured using DCFH-DA method. The expression levels of HIF-1α (a key molecule in hypoxia), Golgi stress markers GM130 and p115, endoplasmic reticulum stress markers GRP78 and CHOP, autophagy markers LC3-II/LC3-I and Beclin1, and ferroptosis markers GPx4 and xCT were detected by Western blot. The effect of inducing or inhibiting organelle stress and cell death on the CoCl2-induced cell damage was also observed. RESULTS: Differentially expressed genes analysis of GSE119226 dataset showed that CoCl2 treatment of VSMCs had significant effects on organelle function and stress response, autophagy and ferroptosis-related genes, in which endoplasmic reticulum stress, protein processing in endoplasmic reticulum, regulation of Golgi to plasma membrane protein transport, autophagy/autophagic cell death, and ferroptosis pathways were remarkably enriched. The results of in vitro experiment showed that compared with normal rVSMC, cell viability was significantly decreased after CoCl2 treatment, as well as HIF-1α protein expression and ROS levels in rVSMCs were increased. In rVSMC treated with CoCl2, the expression levels of Golgi structural proteins GM130 and p115 (reflecting the occurrence of Golgi stress) were decreased, while the markers GRP78 and CHOP (reflecting the occurrence of endoplasmic reticulum stress) were increased. At the same time, CoCl2 treatment also reduced the expression of autophagy markers LC3-II/LC3-I and Beclin1 (indicating the decrease levels of autophagy), while the expression of ferroptosis markers GPx4 and xCT were decreased (indicating the occurrence of ferroptosis). Compared with CoCl2 treatment group, induced Golgi stress, endoplasmic reticulum stress, or ferroptosis could further reduce cell viability, while inhibition of these processes could improve cell viability. On the other hand, increasing the level of autophagy can improve the cell viability. CONCLUSION: Hypoxia induced by cobalt chloride can lead to VSMC injury. Golgi stress, endoplasmic reticulum stress, ferroptosis, and the reduction of autophagy level play an important role in it. Inhibition of organelle stress response and ferroptosis, or increase of autophagy level can improve VSMC injury caused by cobalt chloride. Related Articles | Metrics

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New progress in research on novel control strategies for methicillin-resistant staphylococcus aureus infection QIAO Hongliang, DING Ning, DENG Kaihong, LIU Binbin, DONG Chuanjiang, CHEN Xiaobo, ZOU Lili Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (6): 676-687.   DOI: 10.12092/j.issn.1009-2501.2023.06.011 Abstract （152）      PDF （1017KB）（115）       Knowledge map    Save Methicillin-resistant staphylococcus aureus (MRSA) is one of the most common multi-drug resistant bacteria in clinical practice and is known as a "superbug". With the evolution of MRSA resistance mechanisms, it is increasingly difficult to treat MRSA infections with conventional antibiotics. In recent years, novel control strategies for MRSA infections have been developed at various levels. The unique structure of nanomaterials has antimicrobial activity and can also be used as an efficient transport carrier. Photodynamic therapy promotes cellular oxidative stress by light-activated photosensitizer (PS) interacting with molecular oxygen or substrates to generate reactive oxygen species (ROS). The antimicrobial properties of herbal medicines by multiple mechanisms have been widely demonstrated. Immunotherapy has made breakthroughs in the use of immune escape mechanisms, polyvalent vaccines, and mixed antibodies against MRSA. Gene targets represented by the mecA gene are being explored. Novel candidate antibacterial compounds targeting TDRS, especially the Trx system, will be a promising force in the future. In this paper, novel control strategies for MRSA are reviewed and prospected. Related Articles | Metrics

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Clinical application and research progress of antibody drugs conjugation in breast cancer CHEN Keyu, HUANG Yuan, WANG Xiaojia, ZHENG Yabing Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (8): 898-909.   DOI: 10.12092/j.issn.1009-2501.2023.08.006 Abstract （142）      PDF （762KB）（114）       Knowledge map    Save Antibody drug conjugations (ADCs) are a new class of drugs with both targeted specificity and high activity of chemotherapy drugs, which has gradually become a novel generation of therapeutic models with great clinical application prospects. In recent years, ADCs composed of monoclonal antibodies against different tumor cell surface antigens and small molecule potent cytotoxic drugs have shown superior therapeutic effects on recurrent/metastatic breast cancer. This article reviews the clinical application and research progress of ADCs with different molecular targets in the field of breast cancer. Related Articles | Metrics

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Mechanisms of endocrine-resistance and therapeutic breakthroughs in hormone receptor-positive, HER2-negative breast cancer ZHANG Huyunlong, ZHU Xiuzhi, JIN Xi, SHAO Zhimin Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (8): 854-865.   DOI: 10.12092/j.issn.1009-2501.2023.08.002 Abstract （154）      PDF （1473KB）（113）       Knowledge map    Save Breast cancers that are positive for hormone receptor but negative for human epidermal growth factor receptor 2 (abbreviated as HR+/HER2-) account for approximately 60% of total cases. Targeting estrogen signaling is one of the most important therapeutic strategies for HR+/HER2- breast cancer. However, the management of endocrine-resistant HR+/HER2- breast cancer remains a difficult issue in clinical practice. Previous multi-omic analysis and translational research have identified the mechanisms underlying endocrine-resistance including genomic alteration and abnormal epigenetic modification. To overcome endocrine-resistance, we have established a comprehensive and coherent therapeutic strategy.  In addition, several novel therapies have shown promising efficacy in previous clinical trials and will emerge as alternative options for targeting endocrine-resistant HR+/HER2- breast cancer. In this review, we will introduce the mechanisms of endocrine-resistance, explain the current therapeutic strategy for endocrine-resistant HR+/HER2- breast cancer and discuss the possible targeted therapies in the future. Related Articles | Metrics

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Application of population modeling analysis to evaluate the impact of gene polymorphism on drug PK/PD  LIU Lu, SHI Yufei, HE Qingfeng, XU Fengyan, WANG Kun, CAI Weimin, XIANG Xiaoqiang Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (11): 1275-1282.   DOI: 10.12092/j.issn.1009-2501.2023.11.010 Abstract （127）      PDF （705KB）（113）       Knowledge map    Save Polymorphism refers to the simultaneous and frequent existence of two or more discontinuous variants or genotypes or alleles in a biological population, also known as genetic polymorphisms or genes Polymorphism. This gene polymorphism may have a certain degree of influence on the pharmacokinetics and pharmacodynamics of the drug. The study of genomics plays an important role in realizing personalized, patient-oriented precision medicine treatment. Population model analysis is to use a modeling method to quantitatively describe the correlation and variability between pharmacokinetic and pharmacodynamic parameters and individual characteristics and to quantify the impact of covariates. At present, this method has been widely used. This paper systematically introduces the application examples of using the population model approach to assess the effects of genetic polymorphisms on the drug PK/PD. Related Articles | Metrics

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Research progress on therapeutic role of recombinant human soluble thrombomodulin in atherosclerosis ZHAO Lingzhi, HE Yanjun, XIE Jianqin, YOU Chongge Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (7): 832-840.   DOI: 10.12092/j.issn.1009-2501.2023.07.015 Abstract （136）      PDF （722KB）（109）       Knowledge map    Save Atherosclerosis is a multifocal, smoldering, immunoinflammatory disease caused by lipid accumulation. Acute cardio-cerebrovascular disease caused by AS is one of the most serious life threats in the world. Endothelial cell injury, vascular inflammatory stimulation, abnormal lipid metabolism and coagulation disorder are the main pathological mechanisms of AS. Thrombomodulin (TM) is a transmembrane glycoprotein mainly expressed on the surface of endothelium. It plays a key role in maintaining the dynamic equilibrium of the vascular system through its functions of anti-coagulation, anti-inflammation and cell protection. Recombinant human soluble thrombomodulin (rhsTM), a soluble form of human TM containing the extracellular domain of TM, might be effective in the treatment of AS. This review summarizes the structure and function of TM and the mechanism of rhsTM in the treatment of AS. Aiming to provide new ideas for the prevention and treatment of AS.  Related Articles | Metrics

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Research progress in vaccine for breast cancer  LI Mengxi, ZHANG Kejing, XIA Fan Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (8): 918-925.   DOI: 10.12092/j.issn.1009-2501.2023.08.008 Abstract （240）      PDF （704KB）（109）       Knowledge map    Save Breast cancer was the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%) in 2020. Breast cancer ranks first among malignant tumors in the world, seriously threatening women's health. Due to continuously enrichment of treatment methods for breast cancer, patients' prognosis have been greatly improved. The emergence of vaccines is an important treatment method to promote the development of human health. For cancer therapy, preventive vaccines have been popularized for kinds of tumor with specific incentives, such as cervical cancer caused by HPV infection. At present, the causative factors of breast cancer are still unclear, and it is still difficult to develop preventive vaccines against breast cancer. In recent years, a variety of therapeutic vaccines have emerged in the field of breast cancer treatment. When patient completed comprehensive treatment, vaccine is used to stimulate body immune system to recognize tumor cell-specific antigens, thereby reducing the recurrence rate as much as possible. Most of these vaccines are currently aimed at more malignant triple-negative breast cancer and HER2-positive breast cancer. This article will focus on the research progress of several therappeutic vaccines. Related Articles | Metrics

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Molecular mechanism of artesunate attenuates the release of proinflammatory cytokines from macrophages LIAO Mengling, WANG Yan, LUO Jing, WANG Nuoyan, HUA Ling, ZHANG Yu, DENG Fei, YUAN Yue, ZHOU Jun, ZHOU Hong Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (9): 969-978.   DOI: 10.12092/j.issn.1009-2501.2023.09.002 Abstract （114）      PDF （1437KB）（109）       Knowledge map    Save AIM: Lipopolysaccharide (LPS) on the cell membrane of gram negative bacteria is closely related to the occurrence and development of severe acute pancreatitis (SAP). Local and systemic monocyte/macrophages play an important role in the inflammatory process of SAP. Artesunate (AS) was reported to protect rats with severe acute pancreatitis by reducing the release of proinflammatory cytokines. This study further explored the molecular mechanism of anti-inflammatory effect of AS. METHODS: The release of proinflammatory cytokines in the supernatant were studied by enzyme-linked immunosorbent assay. Then, the mRNA expressions of PI3K-III and its key molecules in signaling pathway were detected by real-time quantitative PCR. Finally, the phosphorylation levels of PI3K-III were detected by Western blot. RESULTS: AS could significantly inhibit the release of proinflammatory cytokines from mouse macrophage induced by LPS. Autophagy inhibitor 3-methyladenine (3-MA) could significantly inhibit the release of TNF-α from mouse macrophages induced by LPS; LPS significantly increased the mRNA expression of PI3K-III and its key molecules in mouse peritoneal macrophages (PMs). Finally, AS could significantly inhibit the increase of PI3K-III phosphorylation induced by LPS in PMs. CONCLUSION: The anti-inflammatory mechanism of AS is closely related to the inhibition of PI3K-III phosphorylation. Related Articles | Metrics

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Analysis of 197 cases of pentoxifylline injection and exploring supervision mode of rational drug use in hospitals CHEN Qun, ZHU Heping, YUAN Xiaolong Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (8): 948-953.   DOI: 10.12092/j.issn.1009-2501.2023.08.011 Abstract （94）      PDF （622KB）（107）       Knowledge map    Save AIM: To analyze and evaluate the use of pentoxifylline injection in a hospital, and explore effective supervision mode, so as to provide some reference for clinical rational drug use. METHODS: A total of 197 inpatients with pentoxifylline injection who were discharged from October 2021 to June 2022 were randomly selected from HIS system. Referring to drug-label and collecting evidence-based medical evidence to judge the rationality of use of pentoxifylline injection in the hospital. RESULTS: Among the 197 medical records extracted, 140 medical records were unreasonable, accounting for 71.07% of the total medical records. Among them, 111 cases (79.29%) were no indication for use, 13 cases (9.29%) were off-label, 2 cases (1.43%) were inappropriate for indications, 13 cases (9.29%) were inappropriate for usage and dosage, and 1 case (0.71%) was inappropriate for solvent. CONCLUSION: The irrational use of pentoxifylline injection in this hospital is serious. It is necessary to standardize its clinical application through the intervention of smart pharmacy management mode, improving system, strengthening medication education and other ways.  Related Articles | Metrics

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Treatment progress of triple positive breast cancer FU Xiaoyu, KONG Deguang, LI Juanjuan Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (8): 866-875.   DOI: 10.12092/j.issn.1009-2501.2023.08.003 Abstract （131）      PDF （589KB）（102）       Knowledge map    Save Triple positive breast cancer overexpress ER (estrogen receptor), PR and HER2 (human epidermal growth factor receptor 2, HER2), accounting for about 50%-60% of the HER2 positive breast cancer patients. Based on the data from clinical trials, the crosstalk between the ER signaling pathway and the HER2 signaling pathway in triple-positive breast cancer may weaken the efficacy of anti-HER2 therapy and endocrine therapy, and this feature has attracted widespread attention. Emerging evidence shows that while blocking HER2 signaling pathway, together with enhancing blocking of ER signaling pathway, such as anti-HER2 dual-targeting + endocrine therapy ± CDK4/6 inhibitors, could effectively overcome drug resistance, and improve the efficacy. Predictive biomarkers including Ki67, intrinsic subtypes, and multi-gene assay, which have the potential benefit for personalized treatment. Related Articles | Metrics

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Drug-induced dysphagia risk in elder people——A pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) database JIA Boying, ZHOU Shuang, WAN Liyan, ZHOU Ying, CUI Yimin Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (10): 1109-1120.   DOI: 10.12092/j.issn.1009-2501.2023.10.004 Abstract （86）      PDF （1139KB）（100）       Knowledge map    Save AIM: To evaluate the risk of drug-related dysphagia in elder people based on the FDA Adverse Event Reporting System (FAERS). METHODS: We collected the reports of dysphagia in elder people (Age≥65) from 2004 quarter 1 through 2022 quarter 2 of FAERS by Open Vigil 2.1 database. The reported odds ratio (ROR) and the proportional reported ratio (PRR) were calculated to detect the adverse reaction signal of drug-induced dysphagia in elder people. Signal generation standard of ROR: number of reports≥3 with the lower limit of 95% confidence interval (CI) of the ROR value>1, PRR≥2 and c2≥4, which indicates positive signal. RESULTS: A total of 51, 590 reports (including 13,197 dysphagia events and 1,395 drug) were considered, and 350 positive signal drugs were detected. The Median age of the included patients was 75 years,and there were more females than males. Positive signal drugs are mainly concentrated on nervous system ［n=99, ROR 2.17(1.97-2.39)］ , alimentary tract and metabolism ［n=47, ROR 1.44(1.25-1.66)］, cardiovascular system ［n=42, ROR 1.30(1.22-1.39)］, anti-infectives for systemic use ［n=27, ROR 1.44(1.29-1.61)］. CONCLUSION: Drug-induced dysphagia risk are widespread according to the FAERS. It is recommended that multidisciplinary teams should assess the swallowing status of potients when selecting drugs. For elderly patients with high risk of swallowing, priority should be given to drugs with negative signals of dysphgia. When the preferred  drugs fail to meet the clinical need, it is recommended to select drug with lowe risk.Simultaneous clinical need to supervise the application of drugs in the process to prevent the occurrence of dysphagia events. Related Articles | Metrics

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Real-world study of ceftazidime-avibactam in the treatment of multidrug-resistant gram-negative bacterial infections JIANG Daoli, CHOU Xiaohua, LIU Zhidong, LI Wei, ZHANG Bo, XU Sang, TAN Defei, FANG Yi, LV Dongmei, WANG Tao Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (9): 1008-1017.   DOI: 10.12092/j.issn.1009-2501.2023.09.006 Abstract （95）      PDF （750KB）（99）       Knowledge map    Save AIM: To describe and evaluate the clinical characteristics, treatment management and clinical outcomes of ceftazidime-avibactam (CZA) in the treatment of patients with multidrug-resistant gram-negative bacterial (MDR-GNB) infections. METHODS: A retrospective cohort study was performed on patients hospitalized in the Affiliated Hospital of Xuzhou Medical University from September 2019 to December 2021. Adult patients who received CZA for ≥ 72 hours consecutively were eligible for inclusion. The primary outcome was clinical failure, defined as a composite of 30-day all-cause mortality, microbiological failure and/or failure to resolve or improve signs and symptoms of infection during treatment with CZA. RESULTS: A total of 198 patients with MDR-GNB infections were described and evaluated, including 132 in the carbapenem-resistant Enterobatceriaceae (CRE) cohort and 66 in the Pseudomonas spp. cohort. The main infection sites were lung infection (92.42%), abdominal infection (10.61%), and intracranial infection (10.61%), among which 63 patients (31.82%) were positive for blood culture. Clinical failure, 30-day all-cause mortality and microbiological failure occurred in 61(30.81%), 33(16.67%) and 11(5.56%) patients, respectively. Body mass index (BMI), acute physiology and chronic health evaluation scoring system (APACHE Ⅱ) and polymicrobial infections were positively associated with clinical outcome failure ［adjusted OR 1.109, 95%CI 1.017,1.209; adjusted OR 1.071, 95%CI 1.015,1.129; adjusted OR 2.844, 95%CI 1.391,5.814］, however, initiation of CZA within 48 hours of admission was protective (adjusted OR 0.424, 95%CI 0.205, 0.879). A total of 15 patients had adverse reactions possibly related to CZA, including 2 cases of rash, 6 cases of nausea and vomiting, and 7 cases of antibiotic-related diarrhea. CONCLUSION: CZA can be used to treat infections caused by a range of MDR-GNB, including Pseudomonas spp. and CRE. Related Articles | Metrics

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Mechanism of Pingxiao capsule promoting breast cancer apoptosis through AKT1/β-catenin signal based on network pharmacology CHEN Hongxiao, LIU Su, JIN Le, ZHANG Huihui, ZHANG Lei, CHEN Zhaolin Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (12): 1321-1330.   DOI: 10.12092/j.issn.1009-2501.2023.12.001 Abstract （179）      PDF （5786KB）（97）       Knowledge map    Save AIM: To explore the potential mechanism of action of Pingxiao capsule in the treatment of breast cancer. METHODS: TCMSP, TCM-ID, GeneCards and other databases were used to screen the related targets of Pingxiao capsule and breast cancer. Cytoscape software builds drug-target-disease networks. R software was used for GO and KEGG analysis. Autodock Vina and Pymol software were used for molecular docking and visualization of Pingxiao capsule active ingredients and core targets. Core targets were analyzed by R software survival package, and genes closely related to overall survival time were screened out. Cell viability was detected by CCK-8 method. Flow cytometry was used to detect cell apoptosis. The protein expression levels of p-AKT1, β-catenin and cyclinD1 were detected by Western blot. RESULTS: A total of 194 drug targets were screened, 1612 disease targets were identified, 127 intersection targets were identified by Venn diagram, and 20 core targets were TB53, AKT1, TNF, CASP3, etc. GO analysis was mainly related to oxidative stress response, cell regulation of chemical reaction and other biological activities. KEGG analysis was mainly related to PI3K-AKT signaling pathway, TNF signaling pathway, IL-17 signaling pathway and other pathways. Molecular docking results showed that the active constituents were well combined with the core targets AKT1, MAPK1 and RELA. Cell experiments showed that quercetin (40, 80, 120 μmol/L) promoted apoptosis of breast cancer cells. Western blot analysis showed that the protein expressions of p-AKT1, β-catenin and cyclinD1 decreased with different concentrations of quercetin treated for 48h. CONCLUSION: Network pharmacology and cell experiments confirmed that Pingxiao capsule may exert its anti-breast cancer effect by regulating AKT1/β-catenin signaling pathway.  Related Articles | Metrics

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Paraventricular thalamic nucleus nerve pathways involved in general anesthesia wakefulness and sleep wakefulness GU Yunfei, CHEN Suheng, YU Kaihua, BAO Zhenxing, LI Yulan Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (12): 1436-1440.   DOI: 10.12092/j.issn.1009-2501.2023.12.015 Abstract （96）      PDF （557KB）（94）       Knowledge map    Save The paraventricular thalamic nucleus (PVT) is a key nucleus involved in wakefulness. PVT plays an important role in normal sleep-wake regulation, but its role may vary during anesthesia depending on the stage of anesthesia. This article will review the role of PVT in sleep and anesthesia based on its wakefulness function neural pathways. Related Articles | Metrics

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Mechanism of neuroprotective effect of ginsenoside Rg1 regulating Epac1/Rap1 signaling pathway in rats with ischemic stroke WANG Kun, XU Peipei, ZHOU Lanlan, LU Sheng Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (7): 721-727.   DOI: 10.12092/j.issn.1009-2501.2023.07.001 Abstract （235）      PDF （1891KB）（93）       Knowledge map    Save AIM: To investigate the neuroprotective effect of ginsenoside Rg1 on rats with ischemic stroke and to investigate its mechanism of action. METHODS: Eighty-four SPF-grade SD male rats at about 13 weeks of age were randomly divided into 7 groups (n=12): sham-operated group, model group, Rg1 low-dose group, Rg1 medium-dose group, Rg1 high-dose group, Epac1 agonist group, and Epac1 inhibitor group. The model group, Rg1 low, medium and high dose groups, Epac1 agonist group and Epac1 inhibitor group were all used to establish a permanent focal cerebral ischemia rat model. Rats in the Rg1 low, medium and high dose groups were treated with 60, 120 and 240 μmol/L Rg1 administered by gavage at a fixed time every morning. The rats in the Epac1 agonist and Epac1 inhibitor groups were administered intraperitoneally at a fixed time each morning with a concentration of 1.0×104 μmol/L for the Epac1 agonist 8-CPT and 1.0×105 μmol/L for the inhibitor ESI-09. After two weeks of continuous administration, the rats in each group were decapitated. The brain infarct volume, number of intact neurons, oxidative damage index, apoptosis, and protein expression levels of NOX2, Epac1, Rap1, and caspase3 in each group of rats were detected by TTC staining, Nissler staining, TUNEL staining, microenzyme labeling, and Western blotting method, respectively. RESULTS: Compared with the sham-operated group, the brain infarct volume of rats in the model group and Epac1 agonist group was significantly larger, the number of intact neurons in brain tissue was significantly reduced, the oxidative damage of neurons in brain tissue was significantly aggravated, the apoptosis rate of neuronal cells was significantly higher, and the expression of NOX2, Epac1, Rap1, and caspase3 was significantly higher, with statistically significant differences (P<0.05); compared with the model group, the brain infarct volume was significantly reduced in the Rg1 low, medium and high dose groups and Epac1 inhibitor group, the number of intact neurons in brain tissue was significantly increased, the apoptosis rate of neuronal cells was significantly reduced, and the expression of NOX2, Epac1, Rap1 and Caspase3 was significantly reduced, and the differences were statistically significant (P<0.05). CONCLUSION: Ginsenoside Rg1 can regulate the Epac1/Rap1 signaling pathway after ischemic stroke and attenuate the oxidative stress of brain neurons, thus reducing neurological impairment and exerting a protective effect on neuronal cells. Related Articles | Metrics

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Emodin reduces the injury of glomerular mesangial cells in lupus nephritis by targeting forkhead protein K2 through miR-96-5p SHI Shanhong, LIN Weiyuan, ZHANG Jiequn, ZHENG Yanling Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (12): 1331-1338.   DOI: 10.12092/j.issn.1009-2501.2023.12.002 Abstract （95）      PDF （2544KB）（92）       Knowledge map    Save AIM: To investigate the injury of emodin (EMO) in reduce of glomerular mesangial cells (MCs) in lupus nephritis by targeting forkhead protein K2 (FOXK2) through miR-96-5p. METHODS: The contents of 24 h urine protein, serum urea nitrogen (BUN) and serum creatinine (Scr) in MRL/faslpr mice (lupus nephritis group) and MRL/MPJ mice (control group) were detected. MCs were separated, purified and divided into: MCs group (MCs without any treatment), L-EMO group (MCs treated with 10 μmol/L Emodin), M-EMO group (MCs treated with 25 μmol/L Emodin), H-EMO group (MCs treated with 50 μmol/L Emodin), H-EMO+miR-96-5p-NC group (MCs treated with 50 μmol/L Emodin and transfected with miR-96-5p-NC), and H-EMO+miR-96-5p-minic group (MCs treated with 50 μmol/L Emodin and transfected with miR-96-5p-minic). Double luciferase report experiment was used to verify the targeting relationship between miR-96-5p and FOXK2. The real-time quantitative fluorescent polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-96-5p. Western blot was used to detect the expression of FOXK2 and apoptosis related proteins. The enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors in MCs. cell count kit 8 (CCK-8) was used to determine the activity of MCs. Annexin-V FITC/PI double staining was used to detect apoptosis of MCs. RESULTS: Compared with the control group, 24 h urinary protein content, serum BUN and Scr levels in the lupus nephritis group were significantly increased (P<0.05). Compared with the MCs group, the miR-96-5p expression, interleukin1β (IL-1β), interleukin6 (IL-6), tumor necrosis factor-α (TNF-α), A450 value and B-lymphoblastoma-2 (Bcl-2) protein in the L-EMO group, M-EMO group and H-EMO group were significantly decreased (P<0.05), the FOXK2 level, cell apoptosis rate, Bcl-2 related X gene (Bax), aspartate specific cysteine proteinase-3 (cleaved Caspase-3) protein levels were significantly increased, respectively (P<0.05), the effect of Emodin was dose-dependent. Compared with the H-EMO group and H-EMO+miR-96-5p-NC group, H-EMO+miR-96-5p-minic group obviously increased the miR-96-5p expression, inflammatory factor levels, A450 value and Bcl-2 protein level (P<0.05), and obviously decreased FOXK2 level and cell apoptosis rate (P<0.05). CONCLUSION: EMO can reduce the injury of lupus nephritis MCs by down-regulating miR-96-5p and then up-regulating FOXK2. Related Articles | Metrics

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Pharmacological  and clinical evaluation of Dorzagliatin in the treatment of type 2 diabetes DU Xiaoyu, LI Yumeng, WU Huizhen, QIU Bo Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (10): 1177-1183.   DOI: 10.12092/j.issn.1009-2501.2023.10.012 Abstract （108）      PDF （639KB）（92）       Knowledge map    Save Dorzagliatin is a new dual action allosteric systemic glucokinase agonist (GKA), which can simultaneously activate the glucokinase (GK) in the pancreas and liver, promote insulin secretion and liver glycogen conversion in patients with type 2 diabetes, and improve pancreatic islets β-Cell function and insulin resistance simultaneously stimulate intestinal GK to regulate the secretion of Glucagon-like peptide-1 to play multiple hypoglycemic effects. As the first marketed GKA drug, it provides a new therapeutic approach for patients with type 2 diabetes. This article reviews the mechanism of action, pharmacokinetics, Drug interaction, clinical research and safety of Dorzagliatin. Related Articles | Metrics

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Research progress on the related treatment of progressive myoclonic epilepsy DANG Yangbin, LIANG Yuxin, WANG Tiancheng Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (10): 1184-1194.   DOI: 10.12092/j.issn.1009-2501.2023.10.013 Abstract （93）      PDF （738KB）（91）       Knowledge map    Save Progressive myoclonic epilepsy (PME) is a rare epileptic syndrome closely associated with genetic factors. The disease is primarily inherited in an autosomal recessive manner, although there are rare cases that demonstrate autosomal dominant or mitochondrial inheritance. Common clinical features include myoclonus, multiple seizure types, and progressive decline in neurological and cognitive function. PME typically manifests in late childhood or adolescence but can occur at any age. It accounts for approximately 1% of epileptic syndromes among children and adolescents worldwide. In recent years, in addition to antiseizure medications, numerous non-pharmacological treatments have emerged, including dietary therapy, neuromodulatory therapy, immunomodulatory therapy, enzyme replacement therapy, gene therapy, etc. This article aims to review the research progress in the treatment of PME. Related Articles | Metrics

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Research progress of FLT3 inhibitors and drug resistance mechanisms in acute myeloid leukemia WU Tingkai, REN Chongchong, ZHANG Wanwan, LIU Bei Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (1): 90-98.   DOI: 10.12092/j.issn.1009-2501.2024.01.010 Abstract （75）      PDF （714KB）（91）       Knowledge map    Save The FMS-like tyrosine kinase 3 (FLT3) gene mutation is the most common genetic mutation in acute myeloid leukemia (AML) and is associated with poor prognosis. Various targeted inhibitors have been developed for FLT3 mutations and have shown promising clinical efficacy. However, the emergence of resistance poses new challenges for targeted therapy in AML. This article provides an overview of the pathological and prognostic role of FLT3 mutations in AML, the current research progress on commonly used FLT3 inhibitors (type I and type II), the mechanisms of FLT3 inhibitor resistance, and strategies for overcoming resistance. Related Articles | Metrics

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Exploring the mechanism of elemene synergistic bortezomib against multiple myeloma by ROS-NF-κB-p38MAPK pathway ZHU Ruifang, GUO Dongkai, ZHI Hui, JIANG Yiguo, ZHANG Yueling, QIAN Xiaoping, JI Shiliang Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (11): 1219-1226.   DOI: 10.12092/j.issn.1009-2501.2023.11.003 Abstract （103）      PDF （2908KB）（90）       Knowledge map    Save AIM: To investigate the mechanism of elemene synergistic bortezomib against multiple myeloma based on ROS-NF-κB-p38MAPK signaling pathway. METHODS: CCK-8 assay was used to detect cell activity. Nude mice were randomly divided into control group, bortezomib (BTZ) group, elemene (ELE) group and combination group. Each group was treated with BTZ, ELE and BTZ combined with ELE, respectively. Tunel staining was performed to observe the apoptosis of tumor tissues. The expressions of Caspase-3, Bcl-2, NF-κB and p38 MAPK were detected by Western Blot. Cell cycle, apoptosis and reactive oxygen species (ROS) expression were detected by flow cytometry using human myeloma U266 cells. RESULTS: When 4.0 μmol/L ELE combined with 50 nmol/L BTZ treated U266, the cell activity was significantly reduced compared with that of NC, BTZ and ELE groups (P<0.05). The tumor volume of nude mice in BTZ group, ELE group and combined group was significantly reduced compared with the control group (P<0.05), and the combined group was the smallest. Tunel staining results showed that the apoptosis level in the control group was lower than that in the BTZ group, ELE group and the combined group (P<0.05), and the combined group had the lowest apoptosis level. Compared with the control group, the expressions of Caspase-3 and p38 MAPK in BTZ group, ELE group and combination group were significantly increased, while the expression of Bcl-2 was significantly decreased. The apoptosis level and expression of ROS in BTZ group, ELE group and the combined group was significantly increased compared with the control group (P<0.05). CONCLUSION: ELE can enhance the role of BTZ in promoting apoptosis of myeloma cells, which may be achieved by regulating ROS/NF-κB/p38 MAPK signaling pathway to enhance the level of apoptosis of tumor cells to achieve anti-tumor effect. Related Articles | Metrics

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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 Abstract （98）      PDF （649KB）（90）       Knowledge map    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. Related Articles | Metrics

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Effects of Ginkgo biloba extract on renal injury in rats with experimental renal failure through miR-145/FOXO1 axis LI Shixu, LI Linyun, WANG Xin, LI Ke, BIAN Hua Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (7): 728-735.   DOI: 10.12092/j.issn.1009-2501.2023.07.002 Abstract （131）      PDF （2100KB）（89）       Knowledge map    Save AIM: To investigate the effect of Ginkgo biloba extract (GBE) on kidney injury in rats with chronic renal failure (CRF) and its potential molecular mechanism. METHODS: SD rats were given 5/6 nephrectomy to construct CRF models and divided into model group, GBE group (100 mg/kg), GBE+Agomir-NC group, and GBE+Agomir-145 group, 12 per group; another 12 were selected as the sham group, with only the kidney exposed and no nephrectomy. Rats in the GBE group were given GBE 100 mg/kg gavage daily, once a day, for 4 consecutive weeks; rats in the GBE+Agomir-NC group and GBE+Agomir-145 group were given GBE 100 mg/kg gavage daily, and then Agomir-NC and Agomir-145 were injected via the tail vein every 3 days for 4 weeks; the sham group and the model group were given the same amount of normal saline by gavage and injection through the tail vein respectively. The general state of the rat was observed, and the renal function indicators [24 h urine microalbumin (24 h UAlb), blood urea nitrogen (BUN), blood creatinine (SCr)] and oxidative stress indicators [malonaldehyde (MDA), Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)] were detected, Masson staining was used to observe the fibrosis of kidney tissue, real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the mRNA expression levels of microRNA-145 (miR-145), transforming growth factor-β1 (TGF-β1) and forkhead box O1 (FOXO1) in renal tissue, Western blot was used to detect the protein levels of TGF-β1 and FOXO1 in kidney tissue. RESULTS: The general state of CRF rats improved significantly after GBE intervention, the body weight, renal tissue SOD and GSH-Px activities, and FOXO1 mRNA and protein levels were significantly higher than those in the model group (P<0.05); the 24 h UAlb, serum BUN, SCr and renal tissue MDA levels, the relative area of renal interstitial fibrosis, and renal tissue miR-145, TGF-β1 mRNA and protein levels were significantly lower than those in the model group (P<0.05); and on the basis of GBE intervention, up-regulating the expression of miR-145 could significantly weaken the protective effect of GBE on renal injury in CRF rats (P<0.05). CONCLUSION: GBE can alleviate kidney damage in CRF rats, and its mechanism of action may be related to down-regulation of miR-145, up-regulation of FOXO1 expression, and inhibition of renal fibrosis. Related Articles | Metrics

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Establish and implement a pre-prescription system for outpatient based on Six Sigma DMAIC model WANG Lin, YU Jianguo, LI Xiao, LUAN Jiajie Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (7): 780-787.   DOI: 10.12092/j.issn.1009-2501.2023.07.009 Abstract （116）      PDF （929KB）（88）       Knowledge map    Save AIM: The pre-prescription system of outpatient was established and implemented based on six sigma DMAIC model to ensure the safety of drug use and promote rational of drug use. METHODS: The rules database was made scientifically and precisely, according to DMAIC model of Six Sigma--define, measure, analyze, improve and control. The pre-prescription system of our hospital was established and improved,through adopting the prescription review mode of interception and Intervention.And the process management was continued to optimize. RESULTS: The rule-making of pre-trial system for outpatient prescription in our hospital was reasonable, and the rate of clinical approval and acceptance was high. After the system audit, the average rate of doctor's revision was 76.32%, and the average rate of Pharmacist's intervention was 63.23%, the effective rate and qualified rate of pharmacist intervention were 97.23% and 96.87%, respectively. CONCLUSION: Based on Six Sigma DMAIC model, the pre-trial system for outpatient prescription was established and implemented, which improved the level of rational drug use, effectively ensured the safety of drug use, and improved the satisfaction of patients. Related Articles | Metrics

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Research progress of biomarkers related to the efficacy of HER2 positive breast cancer XIANG Yimei, ZHANG Ningning, HUANG Yuxin, ZENG Xiaohua Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (8): 887-897.   DOI: 10.12092/j.issn.1009-2501.2023.08.005 Abstract （137）      PDF （702KB）（88）       Knowledge map    Save Breast cancer is the most commonly diagnosed cancer and the main cause of cancer deaths among women worldwide. HER2 positive breast cancer accounts for 15% of all breast cancer. This subtype of breast cancer is highly invasive and has a very poor prognosis. With the development of anti-HER2 targeted therapy, the prognosis of these patients has been improved. However, some patients have poor response to the anti-HER2 therapy. Therefore, it is necessary to select biomarkers that can predict the therapeutic effect for improving the efficacy of these patients. This article describes the research progress of HER2 positive biomarkers for breast cancer, focusing on biomarkers related to the efficacy of targeted therapy, in order to provide some reference for future clinical optimization of targeted therapy. Related Articles | Metrics

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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 Abstract （81）      PDF （685KB）（88）       Knowledge map    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. Related Articles | Metrics

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Trimethylamine N-oxide: the potential target for osteoporosis treatment ZHAO Yangting, CHEN Chongyang, PAN Binjing, LV Xiaoyu, LIU Jingfang Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (10): 1161-1167.   DOI: 10.12092/j.issn.1009-2501.2023.10.010 Abstract （91）      PDF （1078KB）（87）       Knowledge map    Save Trimethylamine N-oxide (TMAO) is an intestinal flora metabolite produced in the liver by the oxidation of trimethylamine (TMA) by hepatic enzymes. Recently, it has been found that plasma TMAO levels play an important role in the development and progression of osteoporosis. This review has presented the physiological functions and metabolic processes of TMAO, and its effects on the development and progression of osteoporosis through oxidative stress and inflammation. Plasma TMAO levels are influenced by diet as well as medications, which provides a new perspective and target for the treatment and prevention of osteoporosis. Related Articles | Metrics

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Research progress of nuclear factor erythroid 2-related factor 2 in pulmonary fibrosis WANG Jie, LI Long, CHEN Feng, LIU Shengfei Chinese Journal of Clinical Pharmacology and Therapeutics    2023, 28 (9): 1067-1072.   DOI: 10.12092/j.issn.1009-2501.2023.09.014 Abstract （87）      PDF （577KB）（82）       Knowledge map    Save Pulmonary fibrosis is a common chronic interstitial lung disease. It is characterized by excessive deposition of extracellular matrix and remodeling of lung tissue structure, resulting in severe impairment of lung function. The cause of its pathogenesis is still unclear. Therefore, it is urgent to explore its pathogenesis and find new targets to combat pulmonary fibrosis. Studies have shown that nuclear factor erythroid 2-related factor 2 can maintain the body's redox homeostasis by regulating antioxidant genes and combining antioxidant response components, thereby protecting tissues and cells from oxidative stress. In recent years, many studies have proved that nuclear factor erythroid 2-related factor 2 can play an anti-fibrotic role by alleviating oxidative stress, inhibiting macrophage polarization, activating autophagy, inhibiting ferroptosis, and blocking epithelial-mesenchymal transition. This paper provides a brief review of the association and research progress of nuclear factor erythroid 2-related factor 2 with pulmonary fibrosis, with the aim of providing a new direction for the precise treatment of pulmonary fibrosis. Related Articles | Metrics

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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 Abstract （88）      PDF （631KB）（81）       Knowledge map    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. Related Articles | Metrics