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Research progress on targeted therapy combined with immune-activating strategies in CLDN18.2-positive gastric cancer NIE Yang, WANG Yue, WEI Jia Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (2): 146-158.   DOI: 10.12092/j.issn.1009-2501.2025.02.001 Abstract （982）      PDF （1213KB）（984）       Knowledge map    Save Claudin 18 isoform 2 (Claudin18.2, CLDN18.2) is a crucial structural protein involved in cell-cell tight junctions. While its expression is limited in normal tissues, it is specifically overexpressed in malignant tumors such as gastric cancer, pancreatic cancer, and esophageal cancer, making it a promising therapeutic target for cancer treatment. Recent advances in CLDN18.2-targeted therapies have been encouraging, and studies suggest that CLDN18.2-positive gastric cancer may possess a unique immune microenvironment. This raises the potential for combining targeted therapies with immune activation to achieve synergistic effects, potentially improving treatment outcomes for patients with advanced gastric cancer. This review will focus on the immune microenvironment characteristics of CLDN18.2-positive gastric cancer and summarize the current research and clinical trial progress in targeted therapies combined with immune activation for this specific cancer type. Related Articles | Metrics

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Advancements and frontiers in targeted therapy for pancreatic cancer DU Nan, WEI Miaoyan, XU Jin Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (2): 183-192.   DOI: 10.12092/j.issn.1009-2501.2025.02.004 Abstract （950）      PDF （762KB）（1792）       Knowledge map    Save The incidence of pancreatic cancer has been increasing each year, and the 5-year survival rate is still around 10%. Diagnosis and treatment strategies are major concerns in the industry. Gene sequencing and multi-omics research have revealed more signal pathways and actionable targets, offering the potential for new targeted therapeutic drugs. However, current drug treatment for pancreatic cancer still relies mainly on chemotherapy, and targeted therapy strategies are not yet fully developed and require further discussion. As basic and translational research in pancreatic cancer advances and precision medicine develops, it is expected that targeted treatment for pancreatic cancer will become more precise and individualized in the future. This article discusses the current progress and frontiers of targeted treatment for pancreatic cancer. Related Articles | Metrics

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Pharmacological effects and clinical evaluation of toludesvenlafaxine in the treatment of depression LI Yumeng, DU Xiaoyu, QIU bo, WU Huizhen Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 419-426.   DOI: 10.12092/j.issn.1009-2501.2025.03.016 Abstract （884）      PDF （954KB）（375）       Knowledge map    Save Depression is a common mental disease. At present, there are poor efficacy and drug-related safety problems in antidepressant treatment. Toludesvenlafaxine, as a new triple reuptake inhibitor (TRIs/SNDRIs), increases the inhibitory effect of dopamine (DA) reuptake on the basis of serotonin (5-HT) and norepinephrine (NE), achieves multi-target synergistic therapy and reduces 5-HT/NE-related adverse drug reactions. This article reviews the basic introduction, preclinical research, clinical efficacy and safety of toludesvenlafaxine, in order to provide more ideas and options for the treatment of depression. Related Articles | Metrics

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Advances in precision diagnosis and treatment of cholangiocarcinoma CHEN Zhenmei, CHEN Jinhong Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (2): 159-170.   DOI: 10.12092/j.issn.1009-2501.2025.02.002 Abstract （724）      PDF （909KB）（1484）       Knowledge map    Save Cholangiocarcinoma (CCA) is a highly aggressive and heterogeneous biliary malignancy characterized by challenges in early diagnosis, limited efficacy of traditional chemotherapy, and poor prognosis. Due to its significant heterogeneity at the genomic, epigenetic, and molecular levels, molecular testing and targeted therapy have become increasingly important in CCA management, forming an integral part of the era of precision oncology. The development of next-generation sequencing (NGS) has advanced research into the molecular subtypes and therapeutic targets of CCA, including FGFR2 fusions/rearrangements, IDH1 mutations, and BRAF mutations. Recently, two phase III clinical trials, TOPAZ-1 and KEYNOTE-966, have established the pivotal role of immunotherapy combined with chemotherapy in advanced CCA. While precision diagnosis and treatment in CCA have shown promising progress, this field remains in its exploratory phase and faces numerous challenges. This review summarizes recent advancements in the diagnosis, molecular targeted therapy, immunotherapy, resistance mechanisms, and the development of novel strategies for CCA.  Related Articles | Metrics

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Current clinical application and research progress of antiplatelet drugs PAN Guanxing, HUANG Pinfang, CHAI Dajun, ZHANG Jing Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (1): 91-99.   DOI: 10.12092/j.issn.1009-2501.2025.01.011 Abstract （679）      PDF （934KB）（744）       Knowledge map    Save Arterial thrombosis is a major cause of death in several cardiovascular diseases (CVDs), including coronary heart disease and stroke. Since platelets play a pivotal role in arterial thrombosis, antiplatelet drug is an important part of the clinical therapy of CVD patients. Currently, the long-term antithrombotic effect of the dual antiplatelet therapy of P2Y12 antagonists combined with aspirin are showed to be effective. And αΙIbβ3 antagonists represented by tirofiban are widely used for antiplatelet therapy in emergency surgery. However, the bleeding risk caused by antiplatelet therapy is a clinical issue that cannot be ignored. In order to provide a reference for further research on antiplatelet drugs, this article reviews the major targets of antiplatelet drugs and the drugs that have been under clinical research in recent years. Related Articles | Metrics

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Characteristics and applications in bioequivalence of physiologically based on pharmacokinetic model WANG Jianxiong, HU Xiao, MIAO Beibei, ZHANG Lan Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (2): 244-250.   DOI: 10.12092/j.issn.1009-2501.2025.02.012 Abstract （616）      PDF （623KB）（879）       Knowledge map    Save Physiologically based pharmacokinetics (PBPK) model is a tool to simulate the process of drug absorption, distribution, metabolism and excretion in vivo. It is widely used in drug research and regulation. In the bioequivalence evaluation of generic drug consistency evaluation and drug production process change,the PBPK model can provide a certain reference and theoretical support for the drug bioequivalence, thereby promoting safer and more economic drug clinical trials. In this paper, the application progress of PBPK model in bioequivalence study will be reviewed in order to provide support for clinical research on drugs in China. Related Articles | Metrics

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Targeting the cGAS-STING pathway for the treatment of ischemic stroke  QIAN Qingfang, LI Wenjing, LI Qiang Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (5): 690-694.   DOI: 10.12092/j.issn.1009-2501.2025.05.013 Abstract （615）      PDF （770KB）（515）       Knowledge map    Save Ischemic stroke is a devastating neurological disease worldwide, with high global burden. The microglial activation-driven neuroinflammation plays a critical role in pathophysiology of ischemic stroke. After the ictus of brain ischemic attack, cytosolic double-stranded DNA (dsDNA) released by necrotic neuronal cells is a potential damage-associated molecular pattern (DAMP) to activate cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. cGAS-STING signaling pathway has emerged as a key player in microglial activation, sterile neuroinflammation, and cell death following ischemic stroke. Targeting this pathway holds promise for developing novel therapeutics that effectively mitigate neuroinflammation, prevent cell death, and enhance patient outcomes. In this review, we first outline the principal elements of the cGAS-STING signaling cascade, then discusses the pivotal role of the cGAS-STING pathway in ischemic stroke. Then, we outline selective small-molecules modulators that function as cGAS-STING inhibitors and summarize their mechanisms to treat Ischemic stroke. Finally, we discuss key limitations of the current therapeutic paradigm and generate possible strategies to overcome them.  Related Articles | Metrics

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Current status and progress of targeted therapy for hepatocellular carcinoma CHEN Zhiwen, WANG Longrong, WANG Lu Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (2): 171-182.   DOI: 10.12092/j.issn.1009-2501.2025.02.003 Abstract （607）      PDF （763KB）（686）       Knowledge map    Save Hepatocellular carcinoma, as a common malignant tumor, remains a serious global health problem. Traditional methods such as surgical resection and chemotherapy have limited effects in improving the prognosis of advanced hepatocellular carcinoma. With the deepening of research into molecular mechanisms, targeted therapy has become an important direction for the treatment of hepatocellular carcinoma. In this review, we summarize the main targeted drugs and associated therapeutic strategies for hepatocellular carcinoma, aiming to provide references and evidence for future related research. Related Articles | Metrics

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The mechanism and application prospects of mitochondrial quality control in osteoarthritis WANG Liang, DENG Yinshuan, QU Tao, DA Chaoming, HE Yunfei, LIU Rui, NIU Weimin, YAN Weishun, CHEN Zhen, LI Shuo, YANG Zhiyun, GUO Binbin, LAI Xueqian Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (2): 282-288.   DOI: 10.12092/j.issn.1009-2501.2025.02.016 Abstract （584）      PDF （615KB）（910）       Knowledge map    Save Osteoarthritis (OA) is a common joint disease in clinical practice, and cartilage damage is a typical pathological change. The pathogenesis of OA is complex, and various adverse factors can lead to the occurrence of OA. Mitochondria are important organelles within cells and play important roles in cellular physiological and pathological activities. Mitochondrial quality control is an important regulatory mechanism in the body to maintain normal mitochondrial structure and function, mainly including mitochondrial biogenesis, mitochondrial dynamics, mitochondrial autophagy, mitochondrial oxidative stress, and other forms. The imbalance of mitochondrial quality control in chondrocytes is closely related to the occurrence and development of osteoarthritis, and regulating the balance of mitochondrial quality control is a potential therapeutic point for osteoarthritis. The author reviewed relevant research literature in recent years to provide a review of the relationship between mitochondrial quality control and the occurrence and development of osteoarthritis, in order to provide new ideas and directions for the research and diagnosis and treatment strategies of osteoarthritis. Related Articles | Metrics

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Clinical efficacy of Tirellizumab combined with lenvatinib in the treatment of advanced liver cancer WU Yuanyuan, LI Chenlu, CHEN Yan, CAO Mengda, SHAO Hua Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 392-397.   DOI: 10.12092/j.issn.1009-2501.2025.03.012 Abstract （534）      PDF （642KB）（361）       Knowledge map    Save AIM: To investigate the efficacy and safety of checkpoint inhibitor lenvatinib combined with Tirelizumab in the treatment of advanced hepatocellular carcinoma (HCC). METHODS: A retrospective analysis was performed on 52 patients with advanced HCC treated with Renvatinib, tirellizumab or their combination from January 2021 to December 2022 in Zhongda Hospital Affiliated to Southeast University, with disease progression, death and intolerance as endpoints. Efficacy was assessed according to RECIST 1.1 criteria and follow-up was conducted up to June 2023. The main endpoints of the study were objective response rate (ORR), disease control rate (DCR), progression-free survival, PFS) and security. RESULTS: The combination therapy significantly improved ORR and mPFS in patients compared with tirelizumab or lenvatinib monotherapy. Compared with single tirellizumab or lenvastinib, there was no significant difference in the adverse reactions associated with the combination treatment, suggesting that the combination of the two was generally well tolerated and the side effects are controllable. CONCLUSION: Lonvastinib combined with tirelizumab is more effective in the treatment of HCC, can significantly prolong PFS, and is generally well tolerated, which may be a potential treatment for advanced HCC. Related Articles | Metrics

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Research progress on the addictivity and neurotoxicity of ketamine ZI Zhian, ZHAO Tingyi, WANG Gongwu, CAO Jun Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (9): 1233-1242.   DOI: 10.12092/j.issn.1009-2501.2025.09.010 Abstract （533）      PDF （676KB）（51）       Knowledge map    Save As a new type of rapid antidepressant, ketamine has provided a new approach for the treatment and research on the pathological mechanism of major depressive disorder. However, the addictive potential and neurotoxicity of ketamine have become issues that cannot be ignored in clinical medication. This article briefly introduces the relevant research progress on ketamine addiction and neurotoxicity mechanisms at home and abroad, hoping to provide a reference for the rational development and utilization of ketamine. Related Articles | Metrics

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Research on the application of machine learning algorithms in anticancer drug response prediction TAN Yanchen, WANG Wenwen, XIA Jielai, LI Chen Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (2): 200-208.   DOI: 10.12092/j.issn.1009-2501.2025.02.006 Abstract （484）      PDF （958KB）（1136）       Knowledge map    Save With the continuous development of genomics and precision medicine, targeted therapy and immunotherapy targeting biomarkers have ushered in a new era of anti-tumor therapy. However, due to the heterogeneity of tumor cells and the variability of tumor microenvironment, there are still significant differences in response to the same drug even in patient populations with the same biomarker enrichment. By combining omics data with drug sensitivity algorithms, the response of anti-tumor drugs can be predicted and transformed into personalized diagnosis and treatment strategies required for precision medicine, which is expected to improve the effectiveness of anti-tumor drugs in clinical treatment. Currently, machine learning is one of the commonly used modeling algorithms for predicting the response of anti-tumor drugs. However, due to differences in input data and algorithm construction methods, there is currently a lack of comprehensive literature review in this field. Therefore, this article provides a review of machine learning algorithms for predicting anti-tumor drug responses, summarizing publicly available cell genome characterization datasets, machine learning algorithms, and evaluation indicators in drug response prediction, as well as the current situation and challenges faced in clinical applications, in order to provide methodological references for the main research problems and potential solutions of machine learning algorithms in the field of drug response prediction. Related Articles | Metrics

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Research progress of epigenetics in the pathogenesis of depression ZHANG Yao, ZOU Manshu, HAN Yuanshan, WANG Yuhong Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 517-525.   DOI: 10.12092/j.issn.1009-2501.2025.04.010 Abstract （476）      PDF （924KB）（941）       Knowledge map    Save Depression is a mental disease with increasing prevalence worldwide, which seriously endangers human health with high disability rate and high suicide rate. Epigenetics is an emerging genetic theory in the 21st century. Its main research content is to regulate the process of gene transcription or translation and affect its function and characteristics without changing the DNA sequence. These include DNA methylation, histone modification, chromatin remodeling and non-coding RNA regulation. The nervous system is susceptible to changes in the activity of epigenetic modifiers, and an increasing number of studies have shown that genetics and environment play an important role in the development of depression. This review will focus on the epigenetic mechanisms of depression. Related Articles | Metrics

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Research progress on the resistance mechanism of anti-angiogenesis targeted drugs in the treatment of colorectal cancer  JIANG Haitao, XU Yangxian Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (2): 193-199.   DOI: 10.12092/j.issn.1009-2501.2025.02.005 Abstract （473）      PDF （589KB）（802）       Knowledge map    Save Colorectal cancer (CRC) is one of the most common malignancies worldwide, although anti-angiogenic targeted agents such as bevacizumab have shown significant efficacy in the treatment of metastatic CRC, however, the emergence of drug resistance is still a key obstacle affecting the success rate of treatment and survival of patients. This article reviews the progress of anti-angiogenesis targeted drugs in the treatment of CRC, the mechanism of drug resistance and how to solve the problem of drug resistance.  Related Articles | Metrics

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SAS macro tool for pharmacokinetic parameter estimation based on non-compartmental models ZHANG Li, LOU Donghua Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (5): 608-621.   DOI: 10.12092/j.issn.1009-2501.2025.05.004 Abstract （447）      PDF （706KB）（647）       Knowledge map    Save AIM: To develop a SAS macro tool for calculating pharmacokinetic (PK) parameters using non-compartmental analysis (NCA) that is applicable to various routes and frequencies of drug administration. METHODS: By incorporating the principles of NCA PK parameter calculations, the structure of the SAS macro program is designed and programmed. The usage of the macro program is demonstrated through simulated examples. RESULTS: Based on NCA, this study programmed a SAS macro using SAS macro language to calculate both single-dose and steady-state complete PK parameters. It supports three modes of drug administration: extravascular, intravenous infusion, and intravenous bolus injection, as well as four algorithms for calculating area under the curve (AUC). By comparing with authoritative calculation software, the results were found to be highly consistent across various calculation scenarios, with more accurate calculations for the time of first measurable concentration (Tlag). CONCLUSION: The %M_CREATE_PK_PARAMETERS macro is a SAS macro that supports comprehensive PK parameter calculations in NCA, providing an accurate, efficient, and flexible solution for PK parameter estimation with broad application prospects. Related Articles | Metrics

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Clinical research progress of efgartigimod in the treatment of generalized myasthenia gravis LIU Shu, SUN Chunhui, TAN Zhirong, XING Man Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (5): 714-720.   DOI: 10.12092/j.issn.1009-2501.2025.05.017 Abstract （447）      PDF （742KB）（497）       Knowledge map    Save Myasthenia gravis (MG) is a chronic autoimmune disease that causes partial or systemic skeletal muscle weakness and fatigue. Efgartigimod is an antibody fragment targeting the Fc receptor in newborns, which clears pathogenic immunoglobulin G antibodies through a unique mechanism. Efgartigimod is used to treat systemic myasthenia gravis safely and efficiently, which can significantly improve muscle strength and quality of life for patients. This article reviews pharmacological, clinical research, and safety of efgartigimod, in order to providing reference for its clinical treatment in systemic myasthenia gravis (gGM). Related Articles | Metrics

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Research progress on targeted drug delivery strategies in inflammatory lung diseases LI Xiaonan, LI Yang, XU Zhangxi, KANG Shuzhen, KONG Li, ZHANG Zhiping Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 313-324.   DOI: 10.12092/j.issn.1009-2501.2025.03.003 Abstract （432）      PDF （946KB）（786）       Knowledge map    Save Inflammatory lung diseases are currently a major challenge threatening human health and life. Imbalanced inflammation and excessive inflammation can lead to tissue damage and trigger the occurrence and development of systemic diseases. Anti-inflammatory treatment is of vital importance for improving patient survival and quality of life. In recent years, significant progress has been made in the exploration and research of drug targeting strategies, effectively addressing issues such as slow onset, low bioavailability, and rapid in vivo clearance rates during drug delivery. Drug targeting can increase local drug concentrations, reduce dosing frequency, and mitigate side effects. This review primarily elaborates on the classification and characteristics of inflammatory lung diseases. It comprehensively reviews targeted drug delivery strategies for inflammatory lung diseases from three perspectives: local targeting, passive targeting, and active targeting. Furthermore, it discusses the prospects and challenges of drug targeted therapy for lung diseases, potentially providing new research and application ideas for the targeted treatment of inflammatory lung diseases. Related Articles | Metrics

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Radix angelica sinensis and astragalus mongholicus extract mediating the Jagged1/Notch1 pathway to inhibit fibroblast transdifferentiation and resist radiation induced myocardial fibrosis LI Wen, JIANG Hugang, WANG Xinqiang, LI Yingdong, LIU Kai, ZHAO Xinke Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (2): 209-215.   DOI: 10.12092/j.issn.1009-2501.2025.02.007 Abstract （423）      PDF （2873KB）（303）       Knowledge map    Save AIM: To study the mechanism of action of radix angelica sinensis and astragalus mongholicus extract (RAS-AM) in inhibiting fibroblast transdifferentiation (CMT) and preventing radiation-induced myocardial fibrosis (RIMF) via the Jagged1/Notch1 pathway. METHODS: Sixty male Wistar rats were randomly divided into blank group, model group, benazepril hydrochloride group, low dose RAS-AM group, medium dose RAS-AM group, and high dose RAS-AM group, with 10 rats in each group. Except for the blank group, all other groups were induced with high-energy radiation at a dose of 38 Gy to establish RIMF models. The blank group and the model group received sterile distilled water by gavage, and the other groups received medication for 4 weeks of intervention: benazepril hydrochloride group (1.0 mg·kg-1·d-1), low dose RAS-AM group (150 mg·kg-1·d-1), medium dose RAS-AM group (300 mg·kg-1·d-1), and high dose RAS-AM group (600 mg·kg-1·d-1). The general condition of rats, the ultrastructure of myocardial tissue were observed using electron microscopy, changes in myocardial tissue fibers using Masson staining, and  CMT related protein Vimentin and α-SMA expression using immunohistochemical staining techniques. ELISA was used to detect serum inflammatory factors IL-6 and TNF-α in rats. The levels of cTnI and ST2, and the expression of Jagged1 and Notch1 were detected by Western blot. RESULTS: Compared with the blank group, the model group rats exhibited symptoms such as mental fatiguem anorexiam and loose stools; The arrangement of some myofibrils in the myocardium is disordered, with dissolution and breakage of myofibrilsm abnormal Z-line structure in some partsm disordered mitochondrial arrangement, rupture of mitochondrial membranem, and rupture or disappearance of mitochondrial ridge structure in some parts. A large amount of collagen fibers proliferate and deposit in the myocardium, and the fibrotic area significantly increases (P<0.01); The expression of myocardial tissue Vimentin α-SMA protein increased (P<0.05), while the expression of Jagged1 and Notch1 proteins decreased (P<0.05); serum IL-6 and TNF-α, the expression of inflammatory factors such as cTnI and ST2 increased (P<0.05). compared with the model group, the RAS-AM and benazepril hydrochloride groups showed varying degrees of improvement in general conditions; the pathological changes of myocardial ultrastructure have been improved, and myocardial fibrosis has been alleviated; The area of collagen fibers significantly decreased (P<0.01); Myocardial tissue Vimentin α-SMA protein expression decreased (P<0.05), while Jagged1 and Notch1 expression increased (P<0.05); Serum IL-6 and TNF-α, The expression of inflammatory factors such as cTnI and ST2 decreased (P<0.05). CONCLUSION: RAS-AM may alleviate RIMF by intervening in the Jagged1/Notch1 pathway to inhibit CMT. The specific mechanism still needs further investigation.  Related Articles | Metrics

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Optimizing the dosing regimen of aripiprazole microspheres by population pharmacokinetic modeling and simulation MENG Qingheng, HAN Zhihui, LEI Qi, CHEN Bin, YIN Xia, HU Haitang, LIU Hongxia, ZHENG Qingshan, XU Ling, HUANG Qin Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 493-500.   DOI: 10.12092/j.issn.1009-2501.2025.04.007 Abstract （402）      PDF （2366KB）（340）       Knowledge map    Save AIM: To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere (LZMT05) using plasma concentration data from two clinical trials. METHODS: Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05, and a population pharmacokinetic (PopPK) model was developed. The therapeutic window was defined as the steady-state trough-to-peak concentration range (94.0-534 ng/mL) of oral aripiprazole. Multiple clinical scenarios were simulated to identify the optimal regimen. RESULTS: A one-compartment model with dual first-order absorption and first-order elimination characterized LZMT05 pharmacokinetics. Covariates like sex and CYP2D6 genotype were integrated into the final model. Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 every 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations. CONCLUSION: The PopPK-guided optimized LZMT05 regimen maintained drug exposure within the therapeutic window, suggesting favorable efficacy and safety. Related Articles | Metrics

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Research and application of personalized treatment of severe infection patients with Meropenem based on TDM WANG Wenjuan, LU Peiyuan, YANG Xiaotong, CHEN Li, ZHAO Yinzhi, YUAN Yuan Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (12): 1329-1336.   DOI: 10.12092/j.issn.1009-2501.2024.12.002 Abstract （396）      PDF （634KB）（291）       Knowledge map    Save Severe infection is a significant threat to patient safety and survival. As the main treatment for hospital acquired infections, meropenem is limited in its effectiveness due to the emergence of drug resistance, especially after long-term use of antibiotics. Therefore, optimizing the efficacy of antibiotics such as meropenem and avoiding microbial resistance has become an urgent issue to be addressed. Therapeutic drug monitoring (TDM), as an important tool for achieving personalized drug administration, is increasingly recognized as an important strategy for optimizing antibiotic concentration, avoiding treatment failure and toxicity in critically ill patients and patients with renal insufficiency. By reviewing the current application status, pharmacokinetics, and TDM guidance of meropenem, clinical references are provided for the treatment of critically ill patients and patients with renal insufficiency, and guidance and support are provided for optimizing antibiotic treatment. Related Articles | Metrics

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Clinical study on model-guided vancomycin plasma concentration monitoring YUAN Shixuan, LV Ziyan, YANG Yong, CHEN Lu, ZHANG Lijuan Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (12): 1344-1352.   DOI: 10.12092/j.issn.1009-2501.2024.12.004 Abstract （393）      PDF （1232KB）（214）       Knowledge map    Save AIM: The purpose of this paper is to study whether the precise administration of vancomycin under the guidance of the model can achieve better clinical treatment effect by implementing the precise medication model in Sichuan Provincial People's Hospital, so as to promote its wide application in practice. METHODS: A prospective cohort study was conducted. The experimental group was patients who used the Model-informed Precision Dosing to determine the vancomycin dosing regimen, and the control group was patients who only decided the vancomycin dosing regimen based on the existing diagnosis and treatment process. Two sets of data were matched to compare whether there were significant differences between the two groups of patients in the TDM steady-state trough concentration or the steady-state AUC compliance ratio, and to evaluate the application value of the model software. RESULTS: According to the inclusion and exclusion criteria, the steady-state blood concentration data of vancomycin in a total of 280 patients were used for analysis. The final result of the experiment was that the number of people in the experimental group was 10, and the compliance rate was 62.50%. There were 64 cases in the control group, and the compliance rate was 24.24% (P=0.002). CONCLUSION: The study found that the model-guided precise dosing regimen can more accurately control the blood concentration of vancomycin in patients, and significantly improve the patient's steady-state trough concentration compliance rate. Therefore, it is recommended to increase the research on the program and promote its wide application in clinical practice.  Related Articles | Metrics

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Progress of macrophage regulation mechanism in acute renal injury DUAN Yuxin, ZHANG Yanni, BAI Yi, YU Jinyao, SUN Jiayi, WANG Zejie, LI Ling, YE Qifa Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (1): 110-117.   DOI: 10.12092/j.issn.1009-2501.2025.01.013 Abstract （364）      PDF （1264KB）（385）       Knowledge map    Save Acute kidney injury (AKI) is a syndrome characterized by rapid decline in renal excretory function. Its pathogenesis is still unclear. Studies have shown that macrophages are major players in AKI inflammation, regulating tissue damage and regeneration repair. During AKI inflammation, macrophages can be activated into different functional phenotypes through molecular and signaling pathways, regulate different molecules and signaling pathways, and determine the progression of AKI. In this paper, the activation of macrophages and the molecular signaling pathways involved in the regulation of AKI in the past five years are reviewed, and the mechanism of action of macrophages in AKI is determined, which provides ideas for the study of macrophages as therapeutic targets. Related Articles | Metrics

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Advances and future research prospects in regulatory policies for clinical trials of artificial intelligence medical devices LIANG Hao, WANG Shun, CUI Cheng, SONG Ling, SUN Ailin, LI Man, QIAO Jie, SONG Chunli, LI Haiyan, ZHAO Yangguang, LI Haiyan, ZHANG Chenguang, LIU Dongyang Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 427-431.   DOI: 10.12092/j.issn.1009-2501.2025.03.017 Abstract （359）      PDF （581KB）（2607）       Knowledge map    Save Artificial intelligence (AI) has emerged as a cutting-edge technology leading the future and is a key engine for China's development. In the innovation and research of medical devices, AI has provided critical support in the areas of intelligent diagnostic assistance, intelligent therapeutic assistance, intelligent monitoring, life support, et al. Machine learning-enabled device software functions (ML-DSFs) have become an essential component of many medical devices. Recently, the United States Food and Drug Administration (FDA) released a draft guidance titled " Marketing Submission Recommendations for a Predetermined Change Control Plan for Artificial Intelligence/Machine Learning (AI/ML)-Enabled Device Software Functions (Draft). " that aimed to provide a forward-looking approach to foster the development of ML medical devices. By supporting iterative updates through modifications, this approach ensures the continuous safety and effectiveness of the devices. This guidance represents the latest in regulatory direction and is especially beneficial for enhancing the quality and efficiency of clinical trials for AI products. Therefore, we plan to provide a detailed introduction and interpretation of the guidance, with the aim of learning from international advanced regulatory concepts and experiences to promote the development of ML-DSFs with more profound international influence. Related Articles | Metrics

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Mechanism of doxorubicin/copper complex induced cuproptosis in hepatocellular carcinoma cells LIU Jing, LEI Guojie, CAO Jinghao, YU Lingyan, DU Jing, WANG Ying Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (1): 1-10.   DOI: 10.12092/j.issn.1009-2501.2025.01.001 Abstract （356）      PDF （5391KB）（341）       Knowledge map    Save AIM: To explore the mechanism of doxorubicin/copper (DOX/Cu) complex induced copper death in hepatocellular carcinoma cells. METHODS: Human hepatocellular carcinoma cell line Huh7 was treated with DOX/Cu 0, 2.5, 4, 7.5, 10 and 12.5 μmol/L. The cell viability was detected by CCK-8 method. The cell proliferation level was observed by laser microscopy and proliferation kit. The cell invasion ability was determined by cell scratch assay. The flow cytometry was used to detect intracellular reactive oxygen species (ROS) and copper ion levels. And the western blot was used to detect intracellular iron-sulfur cluster proteins expression levels. RESULTS: With the increase of DOX/Cu concentration, cell viability, cell proliferation and invasion ability decreased gradually. The copper ion chelating agent (TTM) can significantly restore the effects of DOX/Cu on cell viability. After DOX/Cu treatment, intracellular copper ion and ROS levels related to coproptosis were significantly increased, accompanied by the loss of iron-sulfur cluster proteins. CONCLUSION: DOX/Cu can inhibit hepatocellular carcinoma cells through cuproptosis. Related Articles | Metrics

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Progress in the pharmacological effects of naringin on cardiovascular diseases LIU Dan, MIAO Jiawei, TAN Zihao, HE Chunyao, ZHAO Mingzhu, HE Xiuzhen Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (2): 272-281.   DOI: 10.12092/j.issn.1009-2501.2025.02.015 Abstract （351）      PDF （832KB）（554）       Knowledge map    Save Naringin is a flavonoid compound with a wide range of biological and pharmacological activities, which can be used in treating tumor, diabetes, neurodegenerative diseases, cardiovascular diseases, metabolic syndrome, etc. Among them, the application of naringin in cardiovascular diseases has attracted the attention of many researchers. This article mainly reviews the role of naringin in cardiovascular disease (regulating blood lipids, anti atherosclerosis, lowering blood pressure, inhibiting myocardial hypertrophy, anti myocardial infarction, protecting myocardial ischemia/reperfusion injury, reducing myocardial ischemia/reperfusion injury and improving pulmonary arterial hypertension), the protective effect on cardiotoxicity, and the signal pathways in cardiovascular disease (PI3K-Akt-mTOR, p-eNOS/p-Akt/p-ERK, miR-126/GSK-3 β/β-Catenin), clinical trials, etc. This paper is expected to review the current research status of naringin in cells and animal models so as to reveal its clinical application prospects and provide reference for further research in related fields. Related Articles | Metrics

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Advances in diagnosis, treatment and management of hypertriglyceridemia in pregnancy LI Zhimin, LI Shiran, XIE Jingxian, ZHANG Jiao, LI Pengfei, ZENG Siyu, YANG Yong Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (12): 1380-1388.   DOI: 10.12092/j.issn.1009-2501.2024.12.008 Abstract （350）      PDF （655KB）（536）       Knowledge map    Save Hypertriglyceridemia (HTG) during pregnancy may cause serious complications such as acute pancreatitis, gestational diabetes mellitus, and preeclampsia, especially the high mortality rate of maternal acute pancreatitis is of concern.The physiologic increase in triglyceride (TG) levels during pregnancy poses a challenge for the diagnosis of HTG, there are no diagnostic criteria for pregnant women. The management of HTG in pregnancy remains focused on early screening and a scientifically based fat-restricted diet. Omega-3 fatty acid therapy may be considered for those who cannot be controlled after strict dietary restriction and lifestyle changes, and fibrates may be  used in late pregnancy when the benefits outweigh the risks, as appropriate, and plasma exchange may be a safe and effective option for extremely severe patients. TG levels in early pregnancy are associated with maternal postpartum and neonatal prognosis. Further studies on pharmacologic treatments and management for HTG in pregnancy are expected. Related Articles | Metrics

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Research progress of empagliflozin in the treatment of type 2 diabetes mellitus and cardiovascular and renal benefits LIU Zihan, DU Wenyu, GUO Caihui, WANG Zhi, LI Ying, DONG Zhanjun Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 412-418.   DOI: 10.12092/j.issn.1009-2501.2025.03.015 Abstract （350）      PDF （952KB）（1340）       Knowledge map    Save Type 2 diabetes mellitus (T2DM) is an insulin resistance disease. Improving insulin resistance and controlling blood glucose are the main means of clinical treatment for T2DM. Empagliflozin is a highly selective sodium-dependent glucose transporters (SGLT)2 inhibitor, which is independent of insulin. It can effectively control blood glucose levels, reduce blood pressure and body weight, protect heart and kidney function, reduce the rehospitalization rate and the risk of death in patients with heart failure (HF), and does not increase the risk of hypoglycemia. Empagliflozin can be used alone or in combination with other hypoglycemic drugs to control blood glucose. This article reviews the mechanism of action, clinical benefits, and combination with other drugs of empagliflozin, aiming to provide reference for the clinical use of empagliflozin. Related Articles | Metrics

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Recent research progress of Menin inhibitors in NPM1-mutated acute myeloid leukemia YU Xiaoda, LI Jiajing, WANG Anan, GUO Jiangang, LIU Bei Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 533-540.   DOI: 10.12092/j.issn.1009-2501.2025.04.012 Abstract （347）      PDF （999KB）（287）       Knowledge map    Save The nucleophosmin 1 (NPM1) mutation is one of the most frequent subtypes in acute myeloid leukemia (AML). Under the conditions of FLT3-internal tandem duplications (FLT3-ITD) and/or DNMT3A co-mutations or adverse cytogenetics, the originally favorable prognosis will deteriorate. In recent years, studies have found that multiple endocrine neoplasia protein (Menin) inhibitors targeting Menin-KMT2A complex can downregulate the overexpression of leukemia causing genes HOX (homeotic gene) and MEIS1 (myeloid ecotropic viral integration site 1) in NPM1-mutated AML, demonstrating remarkable anti-leukemia activity. This article aims to review the mechanism and clinical research of Menin inhibitors, novel small molecule targeted drugs in NPM1-mutated AML, as well as the resistance mechanism of Menin inhibitors, hoping to provide promising approaches for the subsequent treatment of NPM1-mutated AML patients.  Related Articles | Metrics

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Analysis of the efficacy and influencing factors after the First 131I treatment after surgery for differentiated thyroid cancer TAO Shaoneng, GE Junliang, YANG Jiwen, CHEN Xiaolei, YIN Weili, WANG Yingying, LIU Xiaocen Chinese Journal of Clinical Pharmacology and Therapeutics    2024, 29 (12): 1435-1440.   DOI: 10.12092/j.issn.1009-2501.2024.12.014 Abstract （346）      PDF （718KB）（122）       Knowledge map    Save AIM: To explore the therapeutic efficacy and influencing factors of differentiated thyroid cancer (DTC) after the first postoperative 131I treatment. METHODS: We retrospectively analyzed the clinical data of 116 DTC patients treated with 131I　for the first time after thyroid cancer surgery in the Department of Nuclear Medicine of the First Affiliated Hospital of Wannan Medical College, analysed their therapeutic efficacy, and Univariate and multivariate Logistic analyses were performed for the factors that may affect the efficacy of the treatment, respectively, and established ROC curves to analyse the diagnostic and ER efficacy of those with psTg and TTR that had a significant effect on the multifactorial Logistic analyses. RESULTS: In DTC patients who were followed up 3-9 months after the first postoperative 131I treatment, 69.0% (80/116) achieved ER. Univariate analysis revealed no statistical significance between ER and NER groups in terms of age, gender, TSH, TgVR, maximum tumour diameter, presence of lymph node metastasis, bilaterality of tumour, multifocality and clinical stage (P>0.05). While 131I dose, nsTg, psTg, TgV and TTR（Tg/TSH ratio） were statistically significant (P<0.05). The results of multifactorial Logistic analysis showed that psTg and TTR were independent risk factors for the first 131I treatment after DTC, with a psTg OR of 5.950 (95% CI 1.437-24.639, P<0.05) and a TTR OR of 4.137 (95%CI 1.073-15.947, P<0.05). The best threshold value of psTg for ROC curve analysis to predict the efficacy of the first postoperative 131I treatment for DTC was 8.935 μg/L, with a sensitivity of 80.6%, a specificity of 83.6%, and a Yuden's index of 0.64. And the best threshold value of TTR for predicting the efficacy of the first postoperative 131I treatment for DTC was 125.72 ng/mIU, with a sensitivity, specificity of 80.6% and 91.2%, and the Yuden index was 0.618. psTg and TTR areas under the curve were 0.839 and 0.833, respectively. psTg<8.935 μg/L patients achieved ER after 3-9 months of follow-up in DTC patients (67/74, 90.5%). psTg>8.935 μg/L patients achieved ER (13/42, 30.95%). Correspondingly TTR<125.72 ng/mIU achieved ER (65/72, 90.2%). psTg>125.72 ng/mIU achieved ER (15/44, 34.1%). CONCLUSION: The efficacy of the first 131I treatment after surgery for differentiated thyroid cancer is significant. psTg and TTR are independent risk factors for the first 131I treatment after DTC and have an important predictive value of efficacy. Related Articles | Metrics

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Engineered bacteria modulate tumor-associated macrophages to enhance immunotherapy WANG Long, WANG Yuchen, GUO Yilin, WU Jinhui Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 297-312.   DOI: 10.12092/j.issn.1009-2501.2025.03.002 Abstract （345）      PDF （1338KB）（1811）       Knowledge map    Save The immunosuppressive tumor microenvironment significantly limits the efficacy of immunotherapy. Tumor-associated macrophages (TAMs), the most abundant immune cells in the tumor microenvironment, often exhibit an immunosuppressive M2 phenotype, contributing to this immunosuppressive landscape. Modulating TAMs to adopt anti-tumor phenotypes can enhance immunotherapy outcomes and inhibit tumor progression.In recent years, tumor immunotherapy leveraging engineered bacteria has garnered considerable attention. Bacteria possess the ability to target tumors, preferentially colonizing tumor regions, and contain abundant pathogen-associated molecular patterns that effectively activate TAMs within the immunosuppressive tumor environment. This activation enhances the tumoricidal and clearance capabilities of TAMs. With the rapid advancements in synthetic biology, engineered bacteria have emerged as a potent therapeutic modality for immunotherapy, leading to increased focus on the regulation of TAMs by engineered bacteria.This paper first outlines clinical studies on targeted TAMs therapy and engineered bacteria-based tumor therapy. It then reviews recent advancements in bacterial regulation of TAMs, detailing how engineered bacteria enhance TAM recruitment, improve TAM phagocytosis, and remodel TAM phenotypes. Modulating TAMs with engineered bacteria presents a promising therapeutic strategy and introduces a novel approach in tumor immunotherapy. Related Articles | Metrics

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Network pharmacological analysis of berberine inhibiting breast cancer cell proliferation and in vitro cell validation#br# ZHANG Huihui, JIN Le, LIU Su, CHEN Hongxiao, CHEN Zhaolin, TANG Liqin Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 332-338.   DOI: 10.12092/j.issn.1009-2501.2025.03.005 Abstract （337）      PDF （1702KB）（171）       Knowledge map    Save AIM: To explore the mechanism of berberine on breast cancer cells based on network pharmacology and in vitro cell experiments. METHODS: Firstly, berberine and breast cancer were taken as the research objects, the intersection targets of the two were screened by VEEN diagram, GO function and KEGG enrichment analysis were performed by R language, and molecular docking and visualization were carried out by Autodock Vina and Pymol software. Then, berberine treated breast cancer MCF-7 cells for 24 h, and then in vitro cell experiments were performed. CCK-8 was used to detect cell viability, Edu and plate cloning were used to detect cell proliferation and cloning, and apoptosis was detected by An-nexin V-FITC/PI double staining and Western blot. Laser confocal and CETSA were used to verify the binding effect of berberine and AKT1 protein. RESULTS: The results of network pharmacology showed that berberine had a good binding to the core targets AKT1, AKT2 and MAPK3. Berberine (20, 40, 80 μmol/L) significantly inhibited the proliferation and cloning ability of MCF-7 cells in a concentration-dependent manner (P<0.05, P<0.01). The results of laser confocal and CETSA experiments showed that berberine and AKT1 had a binding effect, and the stability of the two was enhanced after the combination. CONCLUSION: Berberine inhibits MCF-7 cell proliferation and induces apoptosis in human breast cancer cells by targeting binding to AKT1 protein. Related Articles | Metrics

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Research progress on advanced therapeutic approaches and emerging technologies in the drug treatment of refractory thyroid cancer CHEN Hongdan, HUANG Yinde, LI Chong Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 325-331.   DOI: 10.12092/j.issn.1009-2501.2025.03.004 Abstract （334）      PDF （845KB）（382）       Knowledge map    Save Poorly differentiated and advanced thyroid cancers are characterized by high malignancy, progress rapidly, and resistance to radiotherapy and chemotherapy. These characteristics pose significant challenges, severely limiting effective treatment options. Various kinase inhibitors have been used in the treatment of refractory thyroid cancer were used accompanying by the carcinogenic mechanisms' studies investigating in thyroid cancer, such as Dabrafenib (BRAF inhibitor), Trametinib (MEK inhibitor), Vandetanib (RET inhibitor), Lenvatinib (VEGF inhibitor), and multi-target kinase inhibitors. However, drug resistance remains an inevitable issue, significantly limiting the efficacy and application of kinase inhibitors. Therapeutic approaches such as immunotherapy, redifferentiation strategies for thyroid cancer, radiopharmaceutical conjugates, and the application of nanotechnology are currently in the clinical research stage, requiring further clarification of their efficacy. Comprehensive understanding of therapeutic strategies and available treatment combinations for refractory thyroid cancer is of paramount importance in the diagnosis and treatment of thyroid cancer. Therefore, this article reviews technologies and methods for treating refractory thyroid cancer, focusing on chemotherapy, molecular targeted therapy, immunotherapy, and radiopharmaceutical therapy, aiming to provide a reference for selecting treatment strategies for refractory thyroid cancer. Related Articles | Metrics

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Expert consensus on the model informed precision dosing of tacrolimus in patients receiving anti-rejection therapy CHEN Bing, ZUO Xiaocong, LI Xingang, SHANG Dewei, ZHOU Peijun, DING Junjie, XIANG Xiaoqiang, QIU Xiaoyan, WANG Zhuo, LI Xiaoyu, ZHANG Yi, ZHAO Wei, WANG Yuzhu, GAO Jianjun, JIAO Zheng Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 433-445.   DOI: 10.12092/j.issn.1009-2501.2025.04.001 Abstract （332）      PDF （844KB）（1261）       Knowledge map    Save There is significant inter-individual variation of pharmacokinetics and pharmacodynamics in patients receiving tacrolimus (TAC) for anti-rejection therapy, which cause the rejection or toxic action. Based on results of therapeutic drug monitoring and pathophysiological index of transplant patients, the individualized dosing regimen can be designed and adjusted by using model informed precision dosing (MIPD). The patients' clinical outcome can be improved. In the consensus, the different methods of MIPD used for patients received TAC for anti-rejection therapy were introduced, which can be used for the designing and adjusting doing regimen, predicting adverse drug reaction, improving medication adherence and economics during therapy. Related Articles | Metrics

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Research progress of Pinellia ternata and its active ingredients in cardiovascular diseases SONG Min, DIAO Tingting, WANG Yichao, LIU Luyi, QI Qiqi, BI Jingjing, ZHU Nailiang, QIAO Xinrong Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (2): 251-264.   DOI: 10.12092/j.issn.1009-2501.2025.02.013 Abstract （331）      PDF （1237KB）（1905）       Knowledge map    Save Cardiovascular diseases (CVD) are chronic disease with high morbidity and mortality in the world. Pinellia ternata is a traditional Chinese medicinal herb and has the effects on drying dampness, resolving phlegm, lowering symptoms, stopping vomiting and relieving swelling. In recent years, researches showed that Pinellia ternata and its active ingredients (β- sitosterol, baicalin, baicalein, quercetin) had significant effects in the treatment of cardiovascular diseases. This review summarized and analyzed the role and mechanism of Pinellia ternata and its active ingredients in cardiovascular diseases, which provided a theoretical basis for its clinical application. Related Articles | Metrics

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Research progress on mechanism of action of Chaenomeles speciosa Nakai in the treatment of rheumatoid arthritis bone restruction CAO Jun, ZHOU Yanlin, AI Zhengwen, LI Shigang Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 404-411.   DOI: 10.12092/j.issn.1009-2501.2025.03.014 Abstract （320）      PDF （800KB）（463）       Knowledge map    Save Rheumatoid arthritis is an autoimmune disease characterized by progressive bone destruction, with joint swelling caused by synovial inflammation in the early stage, and joint deformity caused by cartilage and bone destruction occurring in the middle and late stages as inflammation develops, resulting in a 75% disability and deformity rate within three years, and the prevention and treatment of RA bone and joint destruction is of urgency, and it is therefore of great significance to search for effective drugs to treat RA bone destruction. Studies have shown that wrinkled skin papaya can treat RA bone destruction, but the composition and mechanism of action are unknown, so this review aims to provide an overview of the mechanism of action of the effective active ingredients in wrinkled skin papaya for the treatment of rheumatoid arthritis bone destruction, and to provide a basis and direction for the development of novel formulations of traditional Chinese medicines for anti-RA bone destruction. Related Articles | Metrics

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Research progress on the role of macrophage polarization in cardiovascular diseases CUI Hanyu, HU Changping Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 548-555.   DOI: 10.12092/j.issn.1009-2501.2025.04.014 Abstract （310）      PDF （699KB）（1693）       Knowledge map    Save As phagocytic innate immune cells, macrophages interact with various tissue types and play an important role in immune defense, inflammatory response and tissue remodeling. Macrophages participate in the occurrence and development of disease by polarizing into classically activated M1 type and substitutively activated M2 type, or more complex phenotypes, when the tissue microenvironment changes. This paper focused on the application of macrophage polarization in cardiovascular diseases, and introduces macrophage origin and activation to propose the relationship between macrophage polarization and cardiovascular diseases. Then, the strategies for targeted macrophage therapy were proposed to provide an important theoretical basis for improving the inflammatory state of cardiovascular diseases. Related Articles | Metrics

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Effects of branched-chain and aromatic amino acids on type 2 diabetes mellitus and the progress ZHANG Mengli, WU Fangfang, TAN Zhien, OU Min, LIU Lingjie, LU Na, QIAO Liya, YANG Xiaonan Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 526-532.   DOI: 10.12092/j.issn.1009-2501.2025.04.011 Abstract （306）      PDF （1193KB）（564）       Knowledge map    Save Type 2 diabetes mellitus is a metabolic disease characterized by high blood sugar levels. Traditionally, amino acids are primarily viewed as the basic building blocks for proteins and peptide synthesis. However, in recent years, amino acids have gained increased attention as signaling molecules that play crucial roles in the maintenance and regulation of metabolic homeostasis. It has been found that there is a close correlation between the metabolism of branched-chain and/or aromatic amino acids and the occurrence or development of type 2 diabetes mellitus. Furthermore, there have been successive reports on the regulation mechanism involved. This article will focus on the metabolic processes, mechanisms and clinical value of branched-chain and aromatic amino acids in type 2 diabetes mellitus. It will also summarize and provide an outlook on the current state of amino acid metabolism in the treatment of diabetes mellitus, with the aim of offering new ideas for the treatment of type 2 diabetes mellitus. Related Articles | Metrics

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SPP1 expression in SMARCA4-deficient non-small cell lung cancer and its relationship with PD-L1 WU Juan, HUANG Xi, LI Jiajia, WEI Yuqing, ZHANG Liqing, YU Yongmei, LU Zhiwei, ZHANG He Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 477-486.   DOI: 10.12092/j.issn.1009-2501.2025.04.005 Abstract （304）      PDF （1297KB）（1326）       Knowledge map    Save AIM: To analyze the expression of secreted phosphoprotein 1 (SPP1) and programmed cell death-ligand 1 (PD-L1) in SMARCA4-deficient non-small cell lung cancer, and to provide a scientific basis for the study of the follow-up treatment of this rare pathological type of lung cancer. METHODS: The clinical and pathological characteristics of 12 patients with this disease were analyzed retrospectively, and the patients were divided into two groups of adenocarcinomas and poorly differentiated carcinomas according to their morphological characteristics, and the relationship between the expression of SPP1 and PD-L1 was analyzed in the two groups. RESULTS: SPP1 expression was detected in all patients and Its expression level was significantly higher in the poorly differentiated carcinoma group compared with the adenocarcinoma group (P=0.015); PD-L1 expression was found in 6/7 patients (5 cases were not measured), compared with the adenocarcinoma group,PD-L1 was also highly expressed in the poorly differentiated carcinoma group (P=0.048) and the PD-L1 difference between the two groups suggested that the results were similar to those of SPP1. CONCLUSION: SMARCA4-deficient non-small cell lung cancer has high positive expression of SPP1 and PD-L1. It was more pronounced in patients with poorly differentiated carcinoma. There may be a positive correlation between SPP1 and PD-L1 expression in SMARCA4-deficient non-small cell lung cancer and the mechanism of the correlation needs to be further verified in subsequent studies. Related Articles | Metrics

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Clinical effects of tirofiban and butylphthalide combined with stent thrombectomy in the treatment of patients with acute cerebral infarction in the ultra time window TU Hanming, XU Guoqiang, CHEN Yongkang Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 398-403.   DOI: 10.12092/j.issn.1009-2501.2025.03.013 Abstract （302）      PDF （694KB）（405）       Knowledge map    Save AIM: To investigate the clinical effects of tirofiban and butylphthalide combined with stent thrombectomy in the treatment of patients with acute cerebral infarction in the ultra-time window. METHODS: A total of 100 patients with ACI beyond time window admitted to our hospital from January 2021 to January 2023 were randomly grouped into the control group (50 cases, treated with stent thrombectomy) and the study group (50 cases, treated with tirofiban and butylphthalide combined with stent thrombectomy), clinical data of patients were collected, and the clinical efficacy, blood lipid levels, coagulation function, neurological function, quality of life, and incidence of adverse reactions were compared between the two groups. RESULTS: Compared with the control group, the total effective rate of the study group obviously increased (P<0.05). Before treatment, there was no obvious difference between the two groups in triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer (D-D), fibrinogen (FIB), NIHSS score and Barthel index scale (BI) score of patients with ACI beyond time window (P>0.05). After treatment, the TG, TC, LDL-C, FIB, D-D, and NIHSS score of ACI patients in both groups decreased (P<0.05), while HDL-C, PT, APTT, and BI score increased (P<0.05), and the above indicators improved more obviously in the study group (P<0.05). There was no obvious difference in the total incidence of adverse reactions between the two groups (P>0.05). CONCLUSION: The combination of tirofiban and butylphthalide with stent thrombectomy in the treating ACI beyond time window has a definite effect, which can improve the blood lipid level, coagulation function and neurological function of patients, and help to improve the quality of life of patients, with good safety. Related Articles | Metrics

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Drug resistance of tyrosine kinase inhibitors in renal cell carcinoma QIAN Hanxu, ZHAO Yaxuan, YANG Yang, ZHANG Yin Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (1): 100-109.   DOI: 10.12092/j.issn.1009-2501.2025.01.012 Abstract （301）      PDF （1823KB）（434）       Knowledge map    Save Tyrosine kinase inhibitors (TKIs) are the key agent in the treatment of renal cell carcinoma (RCC) so far. Drugs such as sunitinib and sorafenib showed significant benefits RCC patients, however, the adverse effect, drug efficacy and drug resistance limited the use of these therapy. Especially the drug resistant issue brings up a big challenge for clinical practice, and the mechanisms underlying are still poorly understood. In recent years, new therapies have been combined with TKIs to improve the treatment outcome. Immunotherapy, combination therapy with other TKIs, targeted nanoparticle delivery, and drug modification are widely studied to improve the efficacies of TKIs and regain the sensitivity. In this review, we summarizes the current understanding of TKI drug resistance and the approaches to regaining drug sensitivity. Related Articles | Metrics