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The current research status of the diagnosis and treatment of status epilepticus Youyang QU, Yulan ZHU Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (2): 175-184.   DOI: 10.12092/j.issn.1009-2501.2026.02.005 Abstract （583）   HTML （4）    PDF （1209KB）（12925）       Knowledge map    Save Status epilepticus (SE) is a severe critical condition that poses a great threat to patients. Over the past decade or so, a series of important progress has been made in the research of SE. This article comprehensively refers to the recent domestic and foreign authoritative guidelines, expert consensus, and the latest cutting-edge research results, and describes the latest progress of SE, as well as the current research status of its diagnosis and treatment. It further explores the key challenges faced by SE in current clinical practice and predicts the future development trends, aiming to provide assistance for clinical practice. Table and Figures | Reference | Related Articles | Metrics

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The latest progress in the pathogenesis of multiple sclerosis and drug therapy Yayan SHI, Yu WANG, Wei KUANG, Shouyang YU Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (1): 78-87.   DOI: 10.12092/j.issn.1009-2501.2026.01.009 Abstract （315）   HTML （6）    PDF （908KB）（5434）       Knowledge map    Save Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). As a global health concern, MS manifests with motor symptoms such as muscle weakness and ambulatory dysfunction, along with non-motor symptoms including cognitive impairment, neuropsychological manifestations, and pain. The pathogenesis of MS remains intricate and not fully elucidated. In recent years, pharmacological treatments have remained the first-line therapeutic approach for MS. This review summarizes current understanding of potential pathogenic mechanisms and advances in pharmacotherapeutic interventions for MS, while proposing potential future research directions to provide novel perspectives for investigating the pathogenesis and treatment of this disease. Table and Figures | Reference | Related Articles | Metrics

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Research progress on the pharmacological effects and mechanisms of oxazepam Yiqun WANG, Zhilin WANG, Qingyang LI, Wenjie CEN, Qiaoyuan ZHENG, Zhili HUANG Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (3): 352-361.   DOI: 10.12092/j.issn.1009-2501.2026.03.007 Abstract （658）   HTML （0）    PDF （717KB）（5064）       Knowledge map    Save Oxazepam belongs to the class of medium-to-short-acting benzodiazepine sedative-hypnotic drugs. Its mechanism of action mainly involves regulating the γ-aminobutyric acid A receptor through positive allosteric effects, thereby enhancing the inhibitory neural transmission of γ-aminobutyric acid. Studies have shown that oxazepam has significant efficacy in regulating biological rhythms, improving sleep, and alleviating anxiety. Recent researches have found that this drug can also promote the generation of neurosteroids by binding to mitochondrial translocation proteins, thereby potentially playing a role in the treatment of drug addiction and alcohol dependence. In terms of safety, compared with some long-acting benzodiazepine drugs, oxazepam has a relatively smaller impact on cognitive function, especially in elderly patients, as its metabolic pathway does not rely on cytochrome P450, and there are fewer cases of excessive sedation and drug accumulation, making it safer. When using this drug clinically, it is necessary to fully consider the patient's symptom characteristics and individual condition, comprehensively weigh the pros and cons, and use it in a standardized and reasonable manner. Table and Figures | Reference | Related Articles | Metrics

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Etiology, diagnosis, and current treatment of excessive daytime sleepiness LI Qingyun, HUANG Ke Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (12): 1587-1595.   DOI: 10.12092/j.issn.1009-2501.2025.12.001 Abstract （473）      PDF （735KB）（3317）       Knowledge map    Save Excessive daytime sleepiness (EDS) is a clinical condition characterized by an inability to maintain alertness and wakefulness during the daytime, leading to diminished vigilance, impaired daytime functioning, and increased risks of traffic or occupational accidents. The core pathophysiology involves disrupted sleep architecture and dysfunction of brain arousalpromoting systems, which can stem from diverse etiologies including sleep disorders, systemic diseases, psychiatric disorders, and medication/substance use. Clinically, high-risk populations for EDS include occupational drivers and transportation workers, shift workers, individuals with chronic systemic diseases or psychiatric disorders, and users of sedative substances. Diagnosis of EDS relies on a detailed medical history and sleep/wake cycle assessment, supplemented by subjec‐tive scales (e.g., Epworth sleepiness scale) and ob‐jective tests such as polysomnography (PSG) and the multiple sleep latency test (MSLT). It is crucial to differentiate EDS from fatigue. Currently, there is no universally standardized treatment protocol for EDS. Management focuses on addressing underlying causes and alleviating symptoms, often combined with wake-promoting agents (WPAs) for sufficient therapeutic effect. This article summarizes the etiology, pathophysiological mechanisms, high-risk populations, diagnostic approaches, and current treatment strategies for EDS. It also proposes future research directions to advance standardized clinical management and promote precision medicine in EDS diagnosis and therapy. Related Articles | Metrics

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Research advances in wake-promoting drugs for the treatment of narcolepsy ZHAN Shuqin, ZHANG Huimin, ZHANG Yimeng Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (12): 1615-1624.   DOI: 10.12092/j.issn.1009-2501.2025.12.004 Abstract （462）      PDF （851KB）（3256）       Knowledge map    Save Narcolepsy (NT) is a rare central disorder of hypersomnolence, categorized as type 1 or type 2 depending on whether there is loss of hypothalamic orexinergic neurons. Its core clinical features—excessive daytime sleepiness (EDS) and abnormalities in REM sleep—significantly interfere with patients' educational attainment, work productivity, and activities of daily living. Currently, wake-promoting agents (WPAs) remain the cornerstone of EDS symptom management. This article provides a systematic review of advances over the past decade in the treatment of NT-related EDS with WPAs. Traditional central nervous system stimulants—amphetamine , methyphenidate, modafinil and armodafinil—have the longest history of use, yet research progress on their pharmacological mechanisms and therapeutic optimization has been limited in recent years. Novel WPAs, such as the dopamine and norepinephrine reuptake inhibitor solriamfetol and the histamine H3 receptor antagonist/inverse agonist pitolisant, significantly improve both subjective and objective assessment indices of NT-related EDS by modulating monoaminergic and histaminergic wake-promoting pathways. The gamma-hydroxybutyrate (GHB) prodrug sodium oxybate, which consolidates nocturnal sleep and regulates cataplexy by activating gama-aminobutyric acid_B (GABA_B) receptors and modulating noradrenergic and dopaminergic neuronal activity, has demonstrated equivalent efficacy to conventional formulations while reducing dosing frequency and cardiometabolic burden through its controlled-release and low-sodium formulations. Network meta-analyses indicate that the aforementioned WPAs exhibit favorable therapeutic efficacy in narcolepsy, and all three are recommended as first-line agents for NT-related EDS by domestic and international guideline consensus. Notably, orexin type 2 receptor agonists—the first etiology-targeted therapy—have completed Phase III clinical trials, demonstrating sustained wake-promoting effects and favorable safety profiles in patients with NT1, heralding a breakthrough in pathogenesis-oriented treatment. Related Articles | Metrics

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A novel drug for the treatment of METex14 skipping mutation non-small cell lung cancer—Glumetinib Xiaoyu YIN, Ming LU, Zefang YU, Guoxun PANG Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (3): 420-427.   DOI: 10.12092/j.issn.1009-2501.2026.03.014 Abstract （456）   HTML （0）    PDF （533KB）（2437）       Knowledge map    Save The MET exon 14 (METex14) skipping mutation is an important therapeutic target in non-small cell lung cancer (NSCLC). Glumetinib, a highly selective oral MET inhibitor developed in China, has gained approval in China and Japan for treating locally advanced or metastatic NSCLC harboring the METex14 skipping mutation. Preclinically, glumetinib selectively inhibits c-Met kinase activity and its downstream signaling pathways, demonstrating an inhibition rate exceeding 87.7% against MET-driven tumors. In a pivotal phase II study involving 79 patients with METex14-positive NSCLC, glumetinib treatment yielded an objective response rate (ORR) of 66% and a median progression-free survival (PFS) of 8.5 months. The incidence of grade ≥3 treatment-related adverse events (TRAEs) was 54%, primarily edema, hypoalbuminemia, and transaminase elevations. Treatment discontinuation due to adverse events occurred in only 8% of patients, indicating a manageable safety profile. Glumetinib thus represents a novel and effective therapeutic option for NSCLC patients with METex14 skipping mutations, particularly in managing brain metastases. Its clinical application is expanding to include overcoming drug resistance and exploring combination therapies. This paper aims to concisely review Glumetinib's structural properties, pharmacokinetics, efficacy, safety profile, drug interactions, and potential in combination therapy. Furthermore, it seeks to outline future applications of this drug, providing a valuable reference for clinical medication selection in NSCLC management. Table and Figures | Reference | Related Articles | Metrics

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Expert consensus on the value and strategies of precise drug administration for multi-ethnic populations in China Yuan LIU, Cheng CUI, Miao YU, Wenyu JIN, Yinliang BAI, Yabin DUAN, Cao FANG, Jianchang HE, Yan HE, Hua HUANG, Shixia HUO, Yang JIN, Lin JIANG, Zhe JIANG, Zheng JIAO, Xuejun LI, Xiangyang LI, Hongjian LI, Lihong LIU, Yang LIU, Hongqiang QIU, Feng SUN, Jianjun SUN, Xuechang WANG, Jianhua WANG, Zhenlei WANG, Shijie WEI, Xiaowen YAN, Lei ZHANG, Xuenong ZHANG, Yuxin ZHANG, Jun ZHAO, Jiye YIN, Ru YAN, Xinchun WANG, Dongyang LIU Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (1): 1-13.   DOI: 10.12092/j.issn.1009-2501.2026.01.001 Abstract （435）   HTML （6）    PDF （849KB）（2089）       Knowledge map    Save The level of precision medication for multiple ethnic groups is crucial to the overall health and ethnic unity of our country, and is of vital importance to the realization of "Healthy China 2030" and the development and security of our country. To improve the health level of multiple ethnic groups, this article takes precision medication research as the core, elaborates on its significance in enhancing the rationality and safety of medication, and emphasizes the necessity of precision medication research for ethnic minorities. The aim is to establish a consensus on precision medication research based on the clinical pharmacokinetic and pharmacodynamic variations of multiple ethnic groups, in order to better ensure the efficacy and safety of medication for different ethnic groups. This consensus systematically reviews the general situation of clinical pharmacokinetic and pharmacodynamic variations in multiple ethnic groups, and analyzes the causes and mechanisms of variations from significant influencing factors such as genetic factors, intestinal flora, pathological and physiological states, high-altitude hypoxic environment, and dietary habits. Based on the existing evidence from clinical pharmacokinetics and pharmacodynamics studies of multi-ethnic populations, as well as the latest research techniques (physiologically pharmacokinetic virtual humans) strategies and considerations, the value and strategies of ethnic-specific drug use research are clarified. After thorough discussion, a consensus was reached, providing theoretical basis and practical guidance for the research on precise drug use in multi-ethnic populations. Table and Figures | Reference | Related Articles | Metrics

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Research progress on perioperative management of adult patients with obstructive sleep apnea undergoing upper airway surgery Jing YAN, Ailin LUO, Shiyong LI Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (2): 265-271.   DOI: 10.12092/j.issn.1009-2501.2026.02.014 Abstract （322）   HTML （3）    PDF （516KB）（1979）       Knowledge map    Save Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder, characterized by symptoms related to sleep breathing disturbances, but often comorbid with cardiovascular, respiratory, neurological, metabolic, endocrinic, and other multisystemic conditions. The first-line treatment is continuous positive airway pressure (CPAP) during sleep; for patients who fail CPAP therapy, multilevel's upper airway surgery is an effective alternative treatment option. In the present review, we summarized the progress in preoperative preparation and intraoperative and postoperative management of upper airway surgery based on published literature and expert management experience, especially focusing on the key aspects of perioperative management of upper airway surgery, with the aim of improving perioperative safety and promoting patient recovery. Reference | Related Articles | Metrics

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Diagnosis and management of sleep-related hypermotor epilepsy: an update Feifei ZHAI, Yan HUANG Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (2): 168-174.   DOI: 10.12092/j.issn.1009-2501.2026.02.004 Abstract （439）   HTML （1）    PDF （492KB）（1538）       Knowledge map    Save Sleep-related hypermotor epilepsy (SHE), previously termed nocturnal frontal lobe epilepsy (NFLE), is a focal epilepsy syndrome characterized by hypermotor seizures or asymmetric tonic/dystonic posturing occurring predominantly during sleep. SHE has heterogeneous etiologies, including genetic factors, structural brain lesions, and unknown causes. Although seizures in SHE commonly originate from the frontal lobe, extrafrontal seizure onset zones—such as the insular, temporal, or parietal regions—have also been identified. Clinically, diagnosis largely depends on detailed seizure history and typical ictal video-EEG recordings. However, scalp EEG often fails to provide specific findings due to movement artifacts or deeply localized seizure foci, presenting considerable diagnostic challenges. In terms of treatment, carbamazepine remains the first-line medication, but alternative drugs such as oxcarbazepine, topiramate, lacosamide, and perampanel offer additional therapeutic options. Advances in our understanding of nicotinic acetylcholine receptor (nAChR) involvement in SHE pathogenesis have prompted exploration of receptor-modulating treatments, such as nicotine patches and fenofibrate, though robust clinical evidence remains limited. For patients with drug-resistant SHE and clearly defined focal structural lesions, epilepsy surgery is an effective option, often leading to excellent seizure outcomes. Despite recent progress in diagnosis and management, substantial gaps and challenges persist in the understanding and treatment of SHE, underscoring the need for further research to improve patient outcomes and quality of life. Table and Figures | Reference | Related Articles | Metrics

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Research progress in the intervention of myocardial fibrosis by regulating signal pathways with traditional Chinese medicine Yuanyuan HUANG, Lingzhun WANG Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (3): 372-381.   DOI: 10.12092/j.issn.1009-2501.2026.03.009 Abstract （429）   HTML （3）    PDF （579KB）（1510）       Knowledge map    Save Myocardial fibrosis is a heart disease characterized by abnormal cardiac structure and function, primarily manifested by pathological deposition of the extracellular matrix in myocardial cells. The pathogenesis of this disease is complex and involves multiple biological pathways, which have not yet been fully elucidated. Currently, traditional Chinese medicine (TCM) can intervene in the treatment of myocardial fibrosis by regulating signaling pathways such as TGF-β, MAPKs, PI3K/Akt, Wnt, AMPK, NF-κB, JAK/STAT, and Notch. This article deeply analyzes the potential mechanisms and clinical applications of traditional Chinese compound formulas, single Chinese herbs, and other TCM therapies in the treatment of myocardial fibrosis, providing a scientific basis for optimizing treatment protocols for myocardial fibrosis. By regulating relevant signaling pathways, TCM has shown unique advantages and broad application prospects in the prevention and treatment of myocardial fibrosis. Table and Figures | Reference | Related Articles | Metrics

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Research progress on the mechanism of GLP-1 receptor agonists in the treatment of diabetic nephropathy HUANG Shumin, XIE Baocheng, LIU Guohui Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (12): 1701-1710.   DOI: 10.12092/j.issn.1009-2501.2025.12.014 Abstract （348）      PDF （1345KB）（1322）       Knowledge map    Save Diabetic nephropathy (DN) remains the leading cause of end-stage renal disease (ESRD) worldwide. In recent years, glucagon-like peptide-1 (GLP-1) receptor agonists, a novel class of hypoglycemic agents, have garnered significant attention in the field of diabetology. Emerging evidence suggests these therapeutic agents demonstrate considerable potential in diabetic nephropathy management through multiple pathways, including inflammation modulation, oxidative stress reduction, anti-fibrotic effects, renal hemodynamic improvement, lipid metabolism regulation, and modulation of programmed cell death pathways. This comprehensive review examines the pleiotropic biological functions of GLP-1 receptor agonists and elucidates their multifaceted mechanisms of action in combating diabetic nephropathy progression. Related Articles | Metrics

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Research progress on postoperative sleep disorders in orthopedic surgery patients Wenxin ZHAO, Xingyu XIONG, Wen TAN, Yuanyuan WANG, Zhengxiu SUN, Yongao LIN, He LIU, Junli CAO Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (2): 281-288.   DOI: 10.12092/j.issn.1009-2501.2026.02.016 Abstract （402）   HTML （1）    PDF （646KB）（1297）       Knowledge map    Save Sleep is a natural cyclical physiological phenomenon with profound implications for the human body. Adequate postoperative sleep quality not only promotes bodily repair and maintains physiological balance but also plays an irreplaceable role in improving cognitive function, regulating emotions, and expediting postoperative recovery. However, postoperative patients commonly experience a decline in sleep quality, particularly prevalent among orthopedic surgery patients. This article aims to facilitate the postoperative recovery of orthopedic surgery patients by addressing postoperative sleep quality issues. It provides a comprehensive review of the epidemiology, mechanisms, risk factors, impact on prognosis, and prevention and treatment measures of postoperative sleep disorders in orthopedic surgery patients, offering new insights and clinical practice references for preventing postoperative sleep disorders. Table and Figures | Reference | Related Articles | Metrics

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Research progress on dopamine and norepinephrine reuptake inhibitors for the treatment of excessive daytime sleepiness ZHANG Bin, XIN Qianqian, HUANG Haokang Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (12): 1632-1639.   DOI: 10.12092/j.issn.1009-2501.2025.12.006 Abstract （433）      PDF （1305KB）（1266）       Knowledge map    Save Excessive daytime sleepiness (EDS) is characterized by failure to maintain wakefulness and alertness, with a compelling need to sleep and may even fall asleep involuntarily. It is often accompanied by deficits in attention and memory, impairs daily functioning, and poses safety risks. Dysregulation of monoaminergic arousal pathways-particularly noradrenergic and dopaminergic systems—is closely implicated. Although several commonly used agents act via monoamine reuptake inhibition, only solriamfetol, a selective dopamine-norepinephrine reuptake inhibitor (DNRI), currently has clear evidence supporting efficacy for EDS associated with narcolepsy and obstructive sleep apnea (OSA). As a selective dopamine and norepinephrine reuptake inhibitor (DNRI), solriamfetol exerts its wake-promoting effects by blocking the corresponding transporters, thereby increasing monoamine levels in the synaptic cleft. Results from multiple clinical trials indicate that solriamfetol significantly improves patients' subjective sleepiness scores and objective ability to maintain wakefulness, with an overall favorable safety profile and no observed rebound sleepiness or withdrawal reactions. Real-world studies further confirm the feasibility of its long-term use. Against the backdrop of the mechanism of action and clinical application of monoamine reuptake inhibitors, this article focuses on reviewing the pharmacological characteristics of solriamfetol and its clinical research progress in both approved and investigational indications, aiming to provide evidence-based references for personalized wake-promoting treatment strategies in patients with EDS as a core phenotype. Related Articles | Metrics

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The development of wake-promoting agents: past, present and future WU Huijuan, ZHAO Zhongxin Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (12): 1606-1614.   DOI: 10.12092/j.issn.1009-2501.2025.12.003 Abstract （389）      PDF （908KB）（1255）       Knowledge map    Save Wake-promoting agents (WPAs) are a class of drugs that primarily excite the cerebral cortex, with effects including promoting wakefulness, increasing alertness, enhancing attention, improving cognitive function, and reducing fatigue. The use of WPAs can be traced back hundreds of years, with traditional commonly used WPAs including caffeine and amphetamine stimulants. However, the contradictions between their efficacy and tolerability (such as drug dependence and cardiovascular side effects), as well as the clinical limitations of insufficient efficacy for excessive daytime sleepiness (EDS) in specific etiologies (such as narcolepsy), have driven the development of novel WPAs. Compared to traditional drugs, novel WPAs such as modafinil, solriamfetol, and pitolisant have become important breakthroughs in this field due to their safety advantages. The discovery of orexin receptor agonists has also opened new directions for WPA development. This article reviews the past, present, and future of WPA development, aiming to provide a reference basis for formulating individualized treatment plans in clinical practice. Related Articles | Metrics

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Comparative study on the efficacy of hengglinide and pioglitazone in the treatment of type 2 diabetes mellitus complicated with metabolic fatty liver disease  HU Jing, LIANG Yanru, QI Ruiqian, DU Jing Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (12): 1683-1691.   DOI: 10.12092/j.issn.1009-2501.2025.12.012 Abstract （363）      PDF （740KB）（1241）       Knowledge map    Save AIM: To observe the efficacy and safety of two regimens, namely, hengglinide combined with metformin and pioglitazone combined with metformin, in treating patients with type 2 diabetes mellitus (T2DM) complicated with metabolic fatty liver disease (MAFLD). METHODS: Patients with T2DM complicated with MAFLD were randomly divided into experimental group (44 cases) and control group (43 cases). The experimental group was given oral hengglinide tablets (10 mg once a day) combined with metformin (500 mg twice a day), while the control group was given pioglitazone (15 mg twice a day) combined with metformin (500 mg twice a day). The observation period was 12 weeks. Glucose and lipid metabolism, Body mass index (BMI), waist-hip ratio (WHR), waist hip ratio (Whtr), liver function and liver hardness (1iver stiffness measurement, LSM), controlled attenuation index (CAP) and other indicators were compared, and the above data were compared between the two groups after treatment, and the incidence of adverse drug reactions was observed.RESULTS: (1) The BMI of the experimental group and the control group decreased after treatment, but the decrease in the experimental group was greater. The WHR of the experimental group and the control group decreased compared with that before treatment, and the amplitude of the experimental group was greater. The waist height in the experimental group decreased significantly compared with that before treatment, but there was no significant change in the control group.(2) Fasting glucose (FPG), HbA1-glycosylated hemoglobin (HbAlc) and insulin resistance index of steady-state model (HOMA-IR) in the experimental group and the control group all decreased after treatment, but the decrease in the experimental group was even greater. (3) Total cholesterol (TC) and Triglyceride (TG) in the experimental group and the control group decreased after treatment, but there was no statistical difference between the two groups after treatment. Low density lipoprotein cholesterol (LDL-C) in the experimental group and the control group decreased after treatment, especially in the experimental group. High density lipoprotein cholesterol (HDL-C) in the experimental group increased after treatment, and the difference was statistically significant, while there was no difference in the control group before and after treatment. (4) Alanine transaminase (ALT), aspartate aminotransferase (AST) and Gamma-glutamyltransferase (GGT) in the experimental group and the control group all decreased after treatment, especially in the experimental group. LSM and CAP in the experimental group and the control group decreased after treatment, especially in the experimental group. (5) The total incidence of adverse drug reactions was 34.09% (15 cases /44 cases) in the experimental group and 13.95% (6 cases /43 cases) in the control group (all P<0.05). CONCLUSION: Compared with pioglitazone combined with metformin, hengglinide combined with metformin has better effects on glucose and lipid metabolism, obesity, liver function and liver hardness in patients with T2DM complicated with MAFLD, it may be a more comprehensive treatment choice for T2DM complicated with MAFLD. Related Articles | Metrics

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Daridorexant: from discovery to clinical application WANG Zan, WANG Ruiqi, SUN Qingqing, ZHANG Yanan Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (11): 1491-1499.   DOI: 10.12092/j.issn.1009-2501.2025.11.005 Abstract （1146）      PDF （1343KB）（1148）       Knowledge map    Save Insomnia is a common sleep-wake disorder characterized by difficulty in falling asleep or maintaining sleep, accompanied by daytime dysfunction, which severely affects patients' physical and mental health, quality of life, and social functioning. Traditional first-line medications for insomnia, such as benzodiazepines, have limited utility due to their side effects, including addiction, drug tolerance, and daytime functional impairment. Central nervous system hyperarousal is one of the core pathophysiological mechanisms of insomnia. The orexin system has garnered significant attention for its key role in regulating and maintaining wakefulness, and suppressing arousal has emerged as a novel therapeutic strategy for insomnia. Daridorexant, as a new dual orexin receptor antagonist, significantly improves nighttime sleep and daytime function without altering sleep architecture by simultaneously blocking orexin type 1 and type 2 receptors, and it exhibits a favorable safety profile. Currently, daridorexant has been approved for marketing in China. This article reviews the research journey of daridorexant, covering aspects from drug discovery, pharmacological properties, and clinical development to its safety, efficacy, and clinical application, thereby providing evidence for the use of this novel anti-insomnia agent. Related Articles | Metrics

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Frontier explorations: New progress in wakefulness regulation mechanisms and its implications for new drug development WANG Zan, WANG Ruiqi, ZHANG Yanan, CAI Lijia, SUN Qingqing Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (12): 1596-1605.   DOI: 10.12092/j.issn.1009-2501.2025.12.002 Abstract （457）      PDF （1414KB）（1125）       Knowledge map    Save Sleep-wake regulation is a core physiological process dominated by widely distributed neural circuits in the brain. In recent years, with the development of optogenetics and chemogenetics technologies, researchers have not only improved their understanding of the functions of multiple classic regulatory brain regions (such as the reticular activating system, thalamus, hypothalamus, and basal forebrain) but also successively identified and verified a series of novel sleep-wake regulatory nuclei. These studies have simultaneously revealed the regulatory roles of various neurotransmitters, including histamine (HA), dopamine (DA), orexin, γ-aminobutyric acid (GABA), and norepinephrine (NE), in the sleep-wake process, laying a theoretical foundation for deciphering the mechanisms of sleep-wake-related neural circuits. This article systematically reviews the research progress on the neural mechanisms of sleep-wake regulation, explores its intervention targets, and provides a theoretical basis for the development of novel wake-promoting drugs. Regarding therapeutic targets, drugs such as histamine H3 receptor antagonists (e.g., pitolisant), dopaminergic modulators (e.g., modafinil, solriamfetol), orexin type 2 receptor agonists (e.g., TAK-861), GABA B receptor agonists (e.g., sodium oxybate), and NE reuptake inhibitors (e.g., AXS-12) have shown broad clinical application prospects in promoting wakefulness. Although the development of wake-promoting drugs still faces challenges such as hepatotoxicity, significant individual differences in efficacy, and lack of long-term safety data, with the deepening understanding of the mechanisms of sleep-wake-related circuits, precise intervention strategies targeting specific neurotransmitter systems are expected to open up new avenues for the treatment of sleep-wake disorders. Related Articles | Metrics

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Therapeutic advances in small-molecule drugs for moderate-to-severe ulcerative colitis Furui WANG, Tian HUANG, Wenli JIANG, Zenan HU Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (3): 392-399.   DOI: 10.12092/j.issn.1009-2501.2026.03.011 Abstract （425）   HTML （6）    PDF （2129KB）（1106）       Knowledge map    Save Ulcerative colitis (UC) is a chronic non-infectious inflammation primarily affecting the colon and rectum, characterised by continuous inflammation and ulceration of the intestinal mucosal layer. In recent years, with deepening research into the pathogenesis of UC, treatment strategies have progressively shifted towards precision targeted therapy at the molecular level. Small-molecule drugs, owing to their distinct advantages such as convenient administration, lack of immunogenicity, and short half-life, demonstrate significant potential in the treatment of moderate-to-severe UC. This review summarises therapeutic advances in small-molecule drugs for moderate-to-severe UC, focusing on representative compounds and their clinical trial outcomes in recent years. Table and Figures | Reference | Related Articles | Metrics

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Effect of Dan-Lou tablets on the pharmacokinetics and pharmacodynamics of atorvastatin in high-fat diet-fed rats Ke ZHANG, Ziting LI, Fofo JIANG, Feng ZHAO, Yinling MA, Guoxun PANG Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (3): 324-336.   DOI: 10.12092/j.issn.1009-2501.2026.03.004 Abstract （293）   HTML （0）    PDF （2285KB）（971）       Knowledge map    Save AIM: To investigate the effects of Dan-Lou tablets (DLT) on the pharmacokinetics and pharmacodynamics of atorvastatin (ATV) in hyperlipidemic rats, and provide theoretical basis for clinical combination therapy of Chinese and Western medicines in dyslipidemia management. METHODS: A high-fat diet-induced hyperlipidemic rat model was established. Following single and multiple oral administrations of DLT at clinical equivalent doses combined with ATV, plasma concentrations of ATV and its active metabolites were quantified using LC-MS/MS with multiple reaction monitoring (MRM) mode. Pharmacokinetic parameters were calculated through non-compartmental analysis. Pharmacodynamic evaluations included serum lipid profiles (TC, TG, HDL-C, LDL-C) and histopathological examination of hepatic tissue. RESULTS: Pharmacokinetic analysis revealed that compared with ATV monotherapy, DLT co-administration increased AUC0-24h by 160.63% and 50.96% in normal and model groups, respectively, with corresponding Cmax elevations of 27.95% and 7.93%. Pharmacodynamically, the combination therapy demonstrated superior effects with 29.89% body weight reduction versus 12.48% in ATV monotherapy group. Significant improvements were observed in lipid profiles: TC, TG and LDL-C decreased by 38.2%, 41.7% and 52.4% respectively, while HDL-C increased by 28.6% (all P<0.01). Hepatic histopathology showed remarkable reduction of lipid droplet accumulation in combination group compared to monotherapy. CONCLUSION: DLT significantly enhances systemic exposure of ATV in hyperlipidemic conditions by altering its pharmacokinetic profile. These findings suggest that when combining DLT with ATV in clinical practice, therapeutic efficacy and potential adverse reactions should be closely monitored, with particular attention to adjusting ATV dosing regimens to mitigate potential drug interaction risks. Table and Figures | Reference | Related Articles | Metrics

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Research progress on pharmacological mechanism of traditional Chinese medicine targeting type 2 diabetes related pathways Ying ZHOU, Juntong LIU, Qingfeng WANG, Yufeng YANG, Yan SHI Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (4): 500-508.   DOI: 10.12092/j.issn.1009-2501.2026.04.009 Abstract （360）   HTML （2）    PDF （800KB）（965）       Knowledge map    Save Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease characterized by hyperglycemia. Traditional Chinese medicine has the characteristics of overall regulation, syndrome differentiation and treatment, multi-target and multi-mechanism regulation, and has great potential in the treatment of T2DM. Recent studies have shown that, effective components and compound of traditional Chinese medicine regulate AMP-activated protein kinase (AMPK), nuclear transcription factor-κB (NF-κB), transforming growth factor-β (TGF-β), mitogen-activated protein kinases (MAPK), Phosphoinositol 3-kinase (PI3K) / protein kinase B (Akt), nuclear factor-erythroid 2 related factor 2 (Nrf2), wingless type MMTV integration site family (Wnt) / β-catenin, and other signaling pathways. It can inhibit the apoptosis of islet β cells, promote the proliferation of islet β cells, improve islet function, reduce oxidative stress and inflammatory response, inhibit liver gluconeogenesis, and improve insulin resistance (IR), thus playing a role in the treatment of T2DM. This paper summarizes and analyzes the research progress of the effective components of traditional Chinese medicine and compound intervention in T2DM and the mechanism of related pathways, in order to provide a new direction and reference for the treatment of T2DM. Table and Figures | Reference | Related Articles | Metrics

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Clinical research advances in the treatment of immune thrombocytopenia with hetrombopag in combination therapy Shuangmiao JIANG, Huaijun ZHU, Danying LI Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (3): 382-391.   DOI: 10.12092/j.issn.1009-2501.2026.03.010 Abstract （356）   HTML （1）    PDF （497KB）（950）       Knowledge map    Save Immune thrombocytopenia (ITP) is an acquired autoimmune disease involving multiple mechanisms, which leads to platelet destruction and macrocytosis and impaired platelet production, mainly manifested as decreased platelet levels and a tendency to bleed, which seriously affects the quality of life and prognosis of patients. Treatment of ITP aims to increase platelet count (PLT), reduce the incidence of fatal bleeding, and improve quality of life. To improve efficacy, reduce adverse reactions and the advent of thrombopoietin receptor agonists (TPO-RAs) prompted a shift in ITP treatment to combination therapy. Hetrombopag is a novel oral second generation small molecule, non-peptide TPO-RAs that binds to the transmembrane domain of thrombopoietin receptor (TPO-R), stimulates megakaryocyte proliferation and differentiation, and promotes platelet production. Hetrombopag combined with other drugs (glucocorticoid, rhTPO and cyclosporine A) in the treatment of ITP can achieve multi-target treatment, through the integration of different drug mechanisms of action, can more comprehensively intervene in the pathogenesis of ITP, so as to improve the therapeutic effect, so this article reviews the clinical research progress of hetrombopag combination in the treatment of ITP. Table and Figures | Reference | Related Articles | Metrics

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Shikonin restrains TGF-β1/Smad signaling pathway to improve renal fibrosis Tao WANG, Xiaowen CHENG, Zhirui ZHANG, Hao JIAO Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (1): 48-54.   DOI: 10.12092/j.issn.1009-2501.2026.01.005 Abstract （266）   HTML （3）    PDF （3268KB）（925）       Knowledge map    Save AIM: To explore the effect of shikonin (SK) in the treatment of renal fibrosis in mice. METHODS: C57BL/6 mice were randomly divided into sham group, UUO group, shikonin low-dose group (5 mg·kg?1·d?1) and high-dose group (20 mg·kg?1·d?1), with 8 mice in each group. Mice in the experimental group were given different concentrations of shikonin, sham group and UUO group were given equal volume of normal saline, continuous intervention for 10 days. Serum urea nitrogen (BUN), creatinine (Cr) and uric acid (UA) levels were detected by automatic differentiation analyzer, serum inflammatory factors IL-6, IL-1β and TNF-α levels were detected by enzyme-linked immunosorbent assay (ELISA), and renal tissue damage and collagen deposition were detected by HE staining, Masson staining and qRT-PCR. Use protein blotting to detect the expression levels of TGF-β1, p-Smad2, Smad2, p-Smad3, Smad3. RESULTS: Compared with the sham group, the levels of inflammatory factors, renal function indexes, fibrosis-related proteins and TGF-β1/Smad signaling pathway proteins in UUO group were significantly increased (P<0.05), and the degree of renal fibrosis was aggravated. Compared with UUO group, the levels of inflammatory factors, renal function indexes, fibrosis-related proteins and TGF-β1/Smad signaling pathway proteins in the SK group were significantly decreased, and the degree of renal fibrosis was improved, and the improvement was more obvious in the SK high-dose group, with statistical significance (P<0.05). CONCLUSION: Shikonin may alleviate renal inflammation and fibrosis by inhibiting the TGF-β1/Smad signaling pathway, improve renal function and kidney injury status, and play a role in alleviating the progression of renal fibrosis. Table and Figures | Reference | Related Articles | Metrics

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Research progress of traditional Chinese medicine in the prevention and treatment of diabetic nephropathy based on intestinal flora and branched-chain amino acids Liya SUN, Jiaxin LI, Guiyan SUN, Zhichao CHEN, Qingfeng WANG, Yufeng YANG, Yan SHI Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (4): 527-535.   DOI: 10.12092/j.issn.1009-2501.2026.04.012 Abstract （237）   HTML （0）    PDF （749KB）（918）       Knowledge map    Save Diabetic nephropathy is characterized by progressive impairment of glomerular filtration and elevated blood glucose levels, ultimately leading to end-stage renal failure. It is one of the primary causes of end-stage renal disease worldwide. The gut microbiota plays a significant role in diabetic nephropathy, and branched-chain amino acids (BCAAs), as metabolites of the gut microbiota, are key regulators of energy support, nutrient sensing, neurotransmitter synthesis, and cell signaling. They serve as critical biomarkers in the development of diabetic nephropathy. Traditional Chinese Medicine (TCM) can prevent and treat diabetic nephropathy by improving gut microbiota function, maintaining its balanced homeostasis, and alleviating BCAAs metabolic disorders. This article primarily explores the roles of gut microbiota and BCAAs in diabetic nephropathy, as well as the research progress of TCM in preventing and treating diabetic nephropathy by regulating gut microbiota and BCAAs metabolism. The aim is to provide new insights with TCM characteristics for the prevention and treatment of diabetic nephropathy. Table and Figures | Reference | Related Articles | Metrics

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Research progress on the treatment of type I hypersensitivity reactions via different epinephrine administration routes Jiarui CHEN, He ZHANG, Haili ZHANG, Yi CHENG, Chunyan LIU, Meng LI, Nan LIU, Zengming WANG, Hui ZHANG, Aiping ZHENG Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (3): 400-408.   DOI: 10.12092/j.issn.1009-2501.2026.03.012 Abstract （315）   HTML （3）    PDF （960KB）（913）       Knowledge map    Save Epinephrine is the first-line drug for treating type I hypersensitivity reactions and can effectively alleviate symptoms such as hypotension, erythema, urticaria, and angioedema, while also inhibiting the further release of allergic mediators. Intramuscular administration of epinephrine ensures rapid absorption and efficacy, and both epinephrine injection vials and auto-injectors are available on the market, providing timely treatment in emergency situations. To enhance the convenience of drug administration and improve patient compliance, new routes of administration for epinephrine are being explored, including liquid nasal sprays, powder nasal sprays, sublingual formulations, and inhalers. This article summarizes the advantages and limitations of currently available and under-researched epinephrine formulations with different routes of administration and predicts future research directions and priorities. Table and Figures | Reference | Related Articles | Metrics

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Drug research based on dual orexin receptor intervention in sleep-wake disorders: A bidirectional regulatory strategy from antagonists to agonists TANG Jiyou, HUANG Weiwei, ZHAO Mengke Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (11): 1467-1478.   DOI: 10.12092/j.issn.1009-2501.2025.11.003 Abstract （645）      PDF （1613KB）（873）       Knowledge map    Save There are obvious limitations in the traditional treatments for sleep-wake disorders like insomnia and excessive daytime sleepiness (EDS). The development of dual orexin receptor antagonists (DORAs) and orexin receptor agonists (ORAs), which target the orexin system, has introduced a revolutionary bidirectional regulatory strategy in this field. This article systematically reviews the progress in the research and clinical studies of these two classes of drugs. DORAs (e.g., suvorexant, lemborexant and daridorexant) promote sleep in a physiological manner by antagonizing both orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R), effectively improving sleep initiation and maintenance. They offer notable advantages, including the preservation of normal sleep architecture, minimal next-day residual effects, and a low risk of dependence, making them particularly valuable for elderly patients and those with neurodegenerative disease-associated insomnia. Conversely, ORAs (e.g., TAK-861) exert wake-promoting effects by activating OX2R, significantly alleviating core symptoms of daytime sleepiness and cataplexy, thereby representing a breakthrough in the etiological treatment of narcolepsy type 1. However, their clinical translation still faces challenges: DORAs exhibit interindividual pharmacokinetic variability and CYP3A4-mediated drug interactions, while ORAs require careful monitoring of potential safety concerns, such as neurological and urological side effects. DORAs and ORAs mark the advent of a new era in the precise and targeted modulation of sleep-wake disorders. Future directions include the development of novel formulations, the exploration of biased agonists, and the integration of precision medicine.  Related Articles | Metrics

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Advances in the pathogenesis of diffuse large B-cell lymphoma and its immunotherapy ZHANGXIAO Yangzi, ZHU Yongfu, MEI Dan Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (12): 1711-1721.   DOI: 10.12092/j.issn.1009-2501.2025.12.015 Abstract （224）      PDF （1159KB）（821）       Knowledge map    Save Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous and aggressive hematologic malignancy that poses significant challenges in clinical practice due to its tendency for relapse and difficulty in achieving lasting remission. Tumor immunotherapy has shown considerable therapeutic potential for DLBCL by stimulating or reconstructing the body's immune system to recognize and eliminate tumor cells. The evolution of immunotherapy, from early monoclonal antibodies to bispecific/multispecific antibodies, chimeric antigen receptor (CAR) therapy, and more recently oncolytic viruses and gene therapies, has provided DLBCL patients with a broader range of treatment options. With ongoing research into the immunopathological mechanisms of DLBCL and its tumor microenvironment, new immunotherapies are expected to further enhance treatment efficacy and improve patient outcomes. This paper reviews the immunopathological mechanisms of DLBCL and the advancements in immunotherapy for this condition. Related Articles | Metrics

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Precision medication analysis based on the detection of neurological and psychotropic drug gene polymorphisms in 36 patients using MALDI-TOF-MS technology Yanan CHEN, Yaru YANG, Chen JIANG, Feng YAO, Ke WANG, Renpeng ZHOU, Yingjie ZHAO, Wei HU Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (3): 344-351.   DOI: 10.12092/j.issn.1009-2501.2026.03.006 Abstract （310）   HTML （0）    PDF （1676KB）（788）       Knowledge map    Save AIM: To detect and analyze the polymorphism of related drug genes in patients treated with neurological and psychiatric drugs, and to explore the clinical value of gene detection for neurological and psychiatric drugs, so as to provide basis for precision drug use. METHODS: Stroma-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was employed to detect genes related to neurological and psychiatric drugs in 36 patients admitted to the department of psychology and sleep medicine at the second affiliated hospital of Anhui medical university between February 2024 and September 2024. The polymorphisms of drug-metabolizing enzyme genes (CYP2D6 and CYP2C19) and target genes (FKBP5, SACM1L, MDGA2, HTR1A, and HTR2A) were analyzed. Based on the results of gene polymorphism, precision drug use analysis was conducted. RESULTS: Among the 36 patients, the mutation frequency of the CYP2D6*4 gene was the lowest at 0.00%, while that of the CYP2C19*2 gene was the highest at 44.4%. Regarding drug target gene polymorphisms, the AC genotype of MDGA2 had the highest frequency at 38.3%, the GG genotype of SACM1L was the most frequent at 63.8%, and the GG genotype of FKBP5 was prevalent at 61.1%. Additionally, the CG and GG genotypes of HTR1A both had the highest frequencies at 47.2%, and the GG genotype of HTR2A was the most common at 55.6%. For patients with the CYP2D6*10/*10 and CYP2C19*2/*2 genotypes, drug metabolism and clearance may be reduced. It is recommended to lower the dose and regularly monitor blood drug concentration in these patients. CONCLUSION: The polymorphism of genes related to neurological and psychotropic drugs is closely linked to patients' responses to these medications. Providing precision medication guidance based on genetic testing results for these drugs holds significant clinical value. Table and Figures | Reference | Related Articles | Metrics

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Progress of B lymphocytes in the pathogenesis of primary Sjogren's syndrome ZHANG Guohua, WANG Zhandong, QI Wenxia, ZHANG Qiqi, TIAN Jiexiang, ZHANG Yanying, GUO Chao, WANG Yongfeng Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (12): 1722-1728.   DOI: 10.12092/j.issn.1009-2501.2025.12.016 Abstract （223）      PDF （808KB）（756）       Knowledge map    Save Primary Sjogren's syndrome (pSS) is a chronic systemic autoimmune disease characterized by extensive infiltration of lymphoplasmacytic cells, leading to progressive damage of the salivary and lacrimal glands, which in turn triggers and oral and ocular dryness. During this pathologic process, abnormal proliferation of CD4+T cells and B cells becomes a distinctive feature of pSS histopathology. Although it was thought in the past that T cells play a dominant role in the autoimmune response, while B cells are mainly responsible for the production of autoantibodies. Recent studies have shown that B cells play a more complex and critical role in the pathologic process of pSS. In this paper, we will comprehensively explore the multiple roles of B lymphocytes in the pathogenesis of pSS in terms of their involvement in the production of antibodies to pSS, homing of lymphocytes, formation of ectopic germinal centers and B-cell survival and proliferative factors, and different subpopulations of B lymphocytes, highlighting their potential application value in the future diagnosis and treatment of pSS. Related Articles | Metrics

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Mg2+/quercetin-loaded alginate hydrogel exerts immunomodulatory effects by suppressing neutrophil inflammation and oxidative stress YANG Fan, JIN Liang, CHEN Luyang, LI Lan, ZHOU Haifeng, WU Jing Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (12): 1640-1647.   DOI: 10.12092/j.issn.1009-2501.2025.12.007 Abstract （277）      PDF （2097KB）（748）       Knowledge map    Save AIM: To overcome the limitations of sodium alginate hydrogel (SAH), including its slow degradation and limited bioactivity in wound healing applications, we developed a functionalized hydrogel (SAQM) incorporating Mg2? and quercetin (Que). We further conducted a systematic evaluation of its roles and underlying molecular mechanisms in modulating neutrophil-mediated inflammatory responses and oxidative stress. METHODS: SAH and SAQM were prepared via ionic crosslinking induced by CaCl2. Morphology was characterized by SEM, mechanical properties were analyzed via rheometry, and component release was quantified using ICP-AES/UV spectrophotometry. In vitro evaluation employed a dHL60 neutrophil model stimulated with LPS. Inflammatory markers and NF-kB pathway activation were assessed by RT-qPCR and Western blot, while ROS generation was measured via flow cytometry. RESULTS: In vitro experiments demonstrated sustained release of Mg2+ and Que from SAQM. SEM and rheological analyses revealed comparable gelation and microstructure between SAQM and SAH, but SAQM showed significantly reduced swelling and enhanced degradation rates. Biocompatibility studies confirmed negligible cytotoxicity toward neutrophils. In LPS-induced inflammation, SAQM markedly suppressed pro-inflammatory cytokine expression and ROS production. Compositional analysis indicated Mg2+ primarily mediated anti-inflammatory effects, while Que contributed to antioxidant activity. Notably, SAQM treatment inhibited LPS-induced activation of the canonical NF-kB pathway, suggesting its anti-inflammatory mechanism involves NF-kB suppression. CONCLUSION: SAQM combines improved degradability with dual anti-inflammatory and antioxidant properties, representing a promising immunomodulatory hydrogel dressing for clinical applications. Related Articles | Metrics

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New antipsychotic drug KarXT Xin LIU, Xiaolin LIU, Yanan ZHOU, Jinguo ZHAI Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (3): 428-432.   DOI: 10.12092/j.issn.1009-2501.2026.03.015 Abstract （444）   HTML （4）    PDF （428KB）（737）       Knowledge map    Save At present, antipsychotic drugs mainly act on dopamine receptors, but the improvement of negative symptoms and cognitive symptoms is limited. There are extrapyramidal adverse reactions, metabolic syndrome, endocrine disorders and other adverse reactions, which some patients can not tolerate. KarXT (trade name Cobenfy), a novel antipsychotic drug approved by the FDA for the treatment of schizophrenia in adults, acts on M1 and M4 muscarinic acetylcholine receptors (mAChR). The results of current clinical trials have shown that KarXT can improve the positive symptoms, negative symptoms and cognitive impairment of schizophrenia, and the adverse reactions are mainly gastrointestinal symptoms. This article reviews the latest literature on the pharmacological mechanism, pharmacokinetics, clinical evaluation, and safety of KarXT. Reference | Related Articles | Metrics

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Therapeutic effect of emodin on cholestatic liver injury in mice based on CYP7A1 / FXR / SHP pathway Weichen WANG, Yaping MA, Meng WANG, Qinglin LI, Hui CHENG Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (2): 204-212.   DOI: 10.12092/j.issn.1009-2501.2026.02.008 Abstract （221）   HTML （1）    PDF （3811KB）（651）       Knowledge map    Save AIM: To investigate the therapeutic effect of emodin on cholestatic liver injury in mice. METHODS: C57BL/6J mice were subcutaneously injected with ethinyl estradiol (EE) for 7 consecutive days to establish a cholestasis model. The changes of body weight and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GT) and total bilirubin (TBIL) were detected. HE (hematoxylin-eosin) staining and MASSON staining were used to evaluate the effects on liver and other organs. After the efficacy was determined by animal model administration experiment, the human normal liver cell L02 was induced by lithocholic acid (LCA) to construct a cholestatic cell model. The CCK-8 method was used to detect the median lethal dose (IC50) by LCA intervention for 24 hours to determine the modeling concentration. Through emodin intervention for 24 h, the survival rate of each group was detected to determine the concentration of emodin. The survival rate of emodin on liver cells after LCA modeling was detected and evaluated. By detecting the changes of liver injury index related enzymes ALT, AST levels and oxidative stress related enzymes glutathione (GSH), serum superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species(ROS) levels in each group of L02 cells, the mechanism of emodin in anti-cholestasis by improving oxidative stress was evaluated. Western blot was used to detect the protein expression of Cholesterol 7α-hydroxylase (CYP7A1), Farnesol X receptor (FXR) and small heterodimer partner (SHP) in the liver of mice. RESULTS: Emodin significantly improved the body weight change and liver index of mice, reduced the levels of ALT, AST, γ-GT and TBIL in serum, improved the trend of liver lesions, and inhibited liver damage. Improving the survival rate of L02 cells improved the survival state of cells, reduced the changes of ALT and AST levels and improved cell damage. It also changed the level of oxidative stress by increasing GSH and SOD levels and reducing MDA and ROS levels. In addition, emodin significantly increased FXR and SHP in the liver of mice and decreased the protein expression level of CYP7A1. CONCLUSION: Emodin can play a protective role in cholestatic liver injury, and its mechanism may be through inhibiting oxidative stress injury and regulating bile acid synthesis and metabolism through FXR / CYP7A1 / SHP pathway. Table and Figures | Reference | Related Articles | Metrics

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Unraveling the molecular mechanisms of modified Er-Miao-San (MEMS) in acute gouty arthritis: a multidisciplinary integration of network pharmacology, molecular docking, and experimental validation Xiaomian LIU, Ying LIU, Wenjing TU, Shuo ZHANG, Gaoyan ZHU, Yuyan CUI, Xiaoyu CUI, Yixuan YANG, Xiaobing LI, Hongtao GUO, Dong LI, Xiaojuan HE Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (3): 313-323.   DOI: 10.12092/j.issn.1009-2501.2026.03.003 Abstract （227）   HTML （1）    PDF （4925KB）（647）       Knowledge map    Save AIM: To investigate the therapeutic efficacy and potential mechanisms of modified Er Miao-San (MEMS) in the treatment of Acute Gouty Arthritis (AGA). METHODS: Network pharmacology, molecular docking, and molecular dynamics simulations were used to validate the interactions between the active components of MEMS and the targets associated with AGA. An AGA model was established in rats by injecting 25 mg/kg of monosodium urate (MSU) suspension into the right ankle joint. Treatment efficacy was evaluated by measuring ankle joint swelling, gait scores, and inflammation indices. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of TNF-α, IL-6, IL-1β, IL-17, MDA, SOD, and GSH in AGA rats. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the ankle joint synovial tissue, and Western blotting (WB) was used to analyze the protein levels of NLRP3 and STAT3 in the synovial tissue. RESULTS: Network pharmacology analysis identified quercetin, β-sitosterol, stigmasterol, and wogonin as the core active components in MEMS for the treatment of AGA. The key therapeutic targets of MEMS in treating AGA include TNF, STAT3, IL-6, and IL-1β. The core active components exhibited strong binding affinity and stable conformations with these targets. The key targets were predominantly enriched in signaling pathways, including NOD-like receptors, IL-17, and TNF. In vivo experiments demonstrated that MEMS effectively reduced ankle joint swelling, improved gait scores, alleviated synovial cell proliferation, neutrophil infiltration, and capillary congestion in AGA rats. It also lowered the serum levels of TNF-α, IL-1β, IL-6, IL-17, and MDA, while increasing the levels of SOD and GSH. Furthermore, MEMS downregulated the expression of NLRP3 and STAT3 proteins in the synovial tissue. CONCLUSION: MEMS alleviates inflammation and oxidative stress in AGA rats, exerting anti-inflammatory and antioxidative effects. Its mechanism of action may be associated with the modulation of inflammation factor levels via the inhibition of the STAT3/NLRP3 signaling pathway. Table and Figures | Reference | Related Articles | Metrics

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Analysis of the dispute judgment on 21593 suspicious and unexpected serious adverse reaction reports ZHONG Wei, YAN Shuaishuai, WU Kechang, ZHANG Jing, HE Huiyu, LI Chonghao, WANG Zhiqiang, ZHU Hua Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (11): 1530-1535.   DOI: 10.12092/j.issn.1009-2501.2025.11.010 Abstract （272）      PDF （914KB）（627）       Knowledge map    Save AIM: To provide a reference for high-quality and efficient manage gement of suspicious and unexpected serious adverse reaction (SUSAR) reports and to reduce the safety risks to subjects. METHODS: A total of 21 593 SUSAR reports submitted by sponsors to our hospital's drug clinical trial institution from July 2020 to June 2023 were collected. The analysis focused on the discrepancies and reasons between the sponsor's pharmacovigilance (PV) department and the investigators regarding the assessment of the causality between serious adverse events (SAEs) and the investigational drugs. RESULTS: 10 977 (50.8%) of the SUSAR reports received reported that the relevance judgment was disputed. Among those reports, the researchers considered them relevant to the investigatory drug, while the sponsor considered them irrelevant, with a total of 10 931 reports (99.6%). Among the causes of SAE given by sponsor, 4 760 (31.6%) reports were related to drug combination, 4 366 (29.0%) reports were related to prior medical history and concurrent diseases, and 4 862 (32.3%) reports were related to study disease, age, radiotherapy, surgery or surgical history, infection, own condition and chemotherapy. There were 1 077 reports (7.1 percent) for which no reason was given. CONCLUSION: In the current SUSAR reporting process, the pharmacovigilance (PV) department commissioned by the sponsor demonstrates a clear bias toward classifying serious adverse events (SAEs) as unrelated during relevance assessment. To address this issue, it is imperative to strengthen regulatory oversight of SUSAR reporting, standardize roles, responsibilities, and authority boundaries among stakeholders in the reporting process. This approach aims to ensure comprehensive coverage of SUSAR reports while enhancing accountability awareness and safety supervision capabilities across all parties involved, ultimately safeguarding the maximum protection of trial subjects' safety. Related Articles | Metrics

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Gut microbiota and colorectal cancer: advances from pathogenic mechanisms to therapeutic interventions Wei LIU, Wei ZHANG Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (7): 937-947.   DOI: 10.12092/j.issn.1009-2501.2026.07.010 Abstract （105）   HTML （3）    PDF （4108KB）（611）       Knowledge map    Save Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, and its incidence has shown a steadily increasing trend in recent years. Clinical investigations and experimental evidence from animal models have established a strong association between the gut microbiota and CRC. The gut microbiota functions as a key regulatory factor in the initiation and progression of CRC, primarily through shaping the local immune and inflammatory microenvironment, producing metabolites with either tumor-suppressive or tumor-promoting activities, and secreting genotoxic substances, among other mechanisms, thereby driving CRC development. Meanwhile, the gut microbiota can also modulate the sensitivity of CRC to chemotherapy and immunotherapy through multiple pathways. This review aims to explore specific microbial taxa closely related to CRC onset, progression, and treatment, with a particular focus on the gut microbiota–mediated pathogenic mechanisms of CRC and currently effective therapeutic strategies. Ultimately, this work seeks to advance understanding of the deeper interplay between the gut microbiota and CRC, while providing novel perspectives for improving therapeutic efficacy in CRC. Table and Figures | Reference | Related Articles | Metrics

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Progress in the study of interleukin-17A-mediated signaling network regulating airway remodeling in asthma Zhiwang WANG, Yue ZHANG, Ping QUAN, Yue ZHAO, Bei TIAN, Haijing DUAN, Ruiqiong WANG Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (1): 88-95.   DOI: 10.12092/j.issn.1009-2501.2026.01.010 Abstract （313）   HTML （0）    PDF （1001KB）（609）       Knowledge map    Save Asthma is an immune inflammatory disease. Repeated inflammatory responses cause "damage-repair" to reshape the airway structure (known as "airway remodeling"), and airway remodeling is the main cause of irreversible reduction in lung function in asthma patients. Interleukin-17A (IL-17A), as a special subtype of IL-17, plays a key regulatory role in the pathological changes of airway remodeling, such as airway inflammation, goblet cell (GC) metaplasia, high expression of mucin (Muc), and smooth muscle (ASM) thickening in asthma. Therefore, IL-17A regulation of the signal network related to airway remodeling in asthma has become a new research hotspot in recent years. This article reviews the mechanism of IL-17A regulating airway remodeling in asthma from the perspective of signal networks such as retinoic acid-related orphan receptor γt (RORγt), signal transducer and activator of transcription 3 (STAT3), transforming growth factor-β1 (TGF-β1), nuclear factor-κB (NF-κB), and p38 mitogen-activated protein kinase (p38 MAPK), providing a theoretical basis for the study of the mechanism of airway remodeling in asthma and the development of new drugs. Table and Figures | Reference | Related Articles | Metrics

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Uridine cytidine kinase 2's function in tumors and the ongoing research on its inhibitors Jiawei ZHANG, Xuehan MA, Enhao XIAO, Simiao FAN, Danyang LIU Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (3): 362-371.   DOI: 10.12092/j.issn.1009-2501.2026.03.008 Abstract （290）   HTML （1）    PDF （2821KB）（563）       Knowledge map    Save Uridine cytidine kinase 2 (UCK2) is the rate-limiting enzyme in the pyrimidine salvage synthesis pathway. Recent studies have shown that UCK2 is overexpressed in a variety of tumors and is associated with poor prognosis. In addition to its catalytic function as a kinase, UCK2 also plays a non-catalytic role in cellular signal transduction. UCK2 can not only support the rapid proliferation of tumor cells by catalyzing nucleotide synthesis, but also regulate various signaling pathways, thereby affecting the occurrence and development of tumors. Therefore, UCK2 is a promising target for cancer therapy, and it is of great clinical significance to explore its role in tumorigenesis and development and the development of related inhibitors. Now, the UCK2 inhibitors mainly include two categories: one is based on nucleotide analogs, which are competitive inhibitors of this enzyme’s catalytic function, and the other is based on non-competitive inhibitors that target the catalytic function of signal transduction. In addition, based on the database and molecular docking, we explore the molecules that may interact with UCK2 and their binding ability with UCK2. In conclusion, this review summarizes the roles and mechanisms of UCK2 in cancer, and the progress in the development of compounds that inhibit the biological functions of UCK2 and the mechanisms. Table and Figures | Reference | Related Articles | Metrics

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Research progress on ciliated cells and pulmonary diseases: from basic science to clinical applications Lele ZHANG, Guodong ZANG, Wei ZHANG Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (7): 1001-1008.   DOI: 10.12092/j.issn.1009-2501.2026.07.016 Abstract （102）   HTML （2）    PDF （2683KB）（551）       Knowledge map    Save Ciliated cells, as crucial structural and functional units in pulmonary tissue, are predominantly distributed in airway epithelium. They participate in maintaining normal respiratory system functions through their unique ultrastructure and play pivotal roles in preserving airway immune homeostasis and regulating local immune responses. Recent advancements in ciliated cell research have progressively elucidated their developmental processes, physiological functions, damage-repair mechanisms, and associations with various pulmonary and systemic diseases. This review comprehensively summarizes current research progress regarding the biological characteristics of ciliated cells, their functional roles in pulmonary pathophysiology, and therapeutic implications in respiratory disorders. Furthermore, we propose future research directions aiming to provide novel insights for disease prevention/treatment strategies and promote the translation of basic research findings into clinical applications. Table and Figures | Reference | Related Articles | Metrics

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Current application of P-value: challenges and optimization strategies Zhiwei LIU, Shuqing CHEN, Youjun CHEN, Yiming LI, Fangrong YAN, Yang ZHAO, Hua SUN, Haitang XIE, Ling WANG Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (2): 240-246.   DOI: 10.12092/j.issn.1009-2501.2026.02.011 Abstract （282）   HTML （4）    PDF （541KB）（538）       Knowledge map    Save The P-value (based on the frequentist school of thought) is an important tool in statistics for testing the null hypothesis, representing the probability of observing the current or more extreme results when the null hypothesis is true. Although P-values are widely used to determine the statistical significance of research findings (e.g., P<0.05, P<0.01), their abuse and misuse have sparked numerous controversies. This article reviews the importance and limitations of P-values in scientific research and clinical trials, including their sensitivity to sample size, the misleading nature of binary classification, and their inability to objectively reflect clinical significance, among other issues. Additionally, it explores supplementary and optimized methods, such as confidence intervals, effect sizes, and Bayesian statistics. Based on existing consensus and controversies, recommendations for the rational use of P-values are proposed, emphasizing the integration of multiple statistical indicators to enhance the rigor and reproducibility of scientific inferences, while recognizing the core role of P-values in controlling error rates and making group comparisons. Looking ahead, it advocates repositioning P-values as an indicator of the "compatibility" with the null hypothesis and applying them in conjunction with other methods to avoid simplistic binary classification. Reference | Related Articles | Metrics

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Study on the effect of ZiYin RunZao (ZYRZ) pill on the inflammation and function of submandibular gland in mice with Sjögren's syndrome Wenxia QI, Gang WANG, Yanfeng YAN, Jiexiang TIAN, Hailong LIU, Yong WEI, Jia WANG Chinese Journal of Clinical Pharmacology and Therapeutics    2026, 31 (2): 196-203.   DOI: 10.12092/j.issn.1009-2501.2026.02.007 Abstract （238）   HTML （1）    PDF （1464KB）（514）       Knowledge map    Save AIM: To investigate the effect of ZiYin RunZao (ZYRZ) pill on the inflammation and function of submandibular gland in mice modeled with Sj?gren's syndrome. METHODS: Forty 8-week-old NOD/Ltj mice were randomly divided into five groups: model group, western medicine group, and the high, middle and low dosage groups of ZYRZ, with eight mice in each group. Another 8 ICR mice were blank group. The intervention was started after 1 week of acclimatization feeding. In the high, medium and low dose groups, 1.78, 0.89 and 0.45 mg/kg of ZYRZ pills were administered by gavage, respectively; in the western medicine group, 60 mg/kg of hydroxychloroquine was administered; and in the blank group and the model group, equal amounts of sterile distilled water were administered by gavage once a day for eight consecutive weeks. The body weight and water intake of the mice were monitored at weeks 0, 2, 4, 6 and 8. At the end of the intervention, mice submandibular gland and serum were taken, and the histopathology of submandibular gland was observed by HE staining; the levels of inflammatory cytokines IFN-γ, IL-10, and TNF-α were detected in serum by ELISA; the levels of AQP5 and M3R mRNA were detected in submandibular gland by RT-qPCR; the levels of AQP5 and M3R mRNA in submandibular gland were detected in submandibular gland by Western blot; and the levels of AQP5 and M3R mRNA in submandibular gland were detected in submandibular gland by RT-qPCR. AQP5, M3R protein expression; immunohistochemistry to detect the level of AQP5 protein expression in the submandibular gland tissue of mice. RESULTS: Compared with the normal group, mice in the model group showed no significant changes in body weight, significantly increased water intake (P<0.05), significantly higher expression of IFN-γ and TNF-α in serum of mice (P<0.05), and significantly lower expression of IL-10 (P<0.05); significantly lower expression of mRNA and protein of AQP5 and M3R (P<0.05); compared with the model group, the western blot and the ZYRZ Pill in high school and the western blot were detected in the submaxillary gland tissues of mice; immunohistochemical method was used to detect the expression level of AQP5 in the submaxillary gland tissues. Compared with the model group, mice in the western medicine group and the high school dose group of ZYRZ consumed significantly less water (P<0.05), the expression of IFN-γ and TNF-α in serum was significantly reduced (P<0.05), the expression of IL-10 was significantly elevated (P<0.05), and the expression of AQP5, M3R mRNA, and protein was significantly elevated (P<0.05). CONCLUSION: ZYRZ pill can reduce the inflammatory reaction of submandibular gland in mice with Sj?gren's syndrome model and improve the secretion function of submandibular gland. Table and Figures | Reference | Related Articles | Metrics

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Neural mechanisms of orexin regulating the sleep-wake cycle HE Chao, LUO Xinwei, YU Qingsong, LI Yadong Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (11): 1443-1452.   DOI: 10.12092/j.issn.1009-2501.2025.11.001 Abstract （580）      PDF （1029KB）（500）       Knowledge map    Save The orexin (hypocretin) system is a hypothalamus-specific neuropeptidergic network that integrates metabolic, emotional, and environmental cues to regulate sleep-wake states. By activating arousal-promoting nuclei and inhibiting sleep-promoting regions through widespread downstream circuits, it plays a crucial role in the initiation and maintenance of wakefulness. Orexin system also plays a crucial role in regulation of rapid eye movement sleep. Loss of orexin function is closely associated with narcolepsy, characterized by fragmented wakefulness and emotionally triggered cataplexy. This review summarizes the current advances in the neural mechanisms underlying orexin-mediated regulation of the sleep-wake cycle, aiming to provide a theoretical basis for precision interventions in sleep disorders. Related Articles | Metrics