Table of Content

Volume 30 Issue 11
26 November 2025

Previous Issue   

Neural mechanisms of orexin regulating the sleep-wake cycle

HE Chao, LUO Xinwei, YU Qingsong, LI Yadong

2025, 30(11):  1443-1452.  doi:10.12092/j.issn.1009-2501.2025.11.001

Asbtract ( 12 )   PDF (1029KB) ( 5 )  

Related Articles | Metrics

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.

Beyond sleep-wake regulation: roles of orexin in cognition and emotion regulation

LI Yadong, YU Qingsong, HE Chao, WANG Jing

2025, 30(11):  1453-1466.  doi:10.12092/j.issn.1009-2501.2025.11.002

Asbtract ( 6 )   PDF (1328KB) ( 2 )  

Related Articles | Metrics

Orexin, also known as hypocretin, is a neuropeptide crucial for the regulation of sleep–wake states. Emerging evidence indicates that the orexinergic system also plays a pivotal role in cognitive and emotional functions, yet a comprehensive synthesis of these findings is lacking. In this review, we first summarize the neurocircuitry and molecular mechanisms by which the orexinergic system regulates cognition and emotion under physiological conditions. We then focus on how dysfunction of the orexinergic system contributes to cognitive and affective impairments in aging and neurodegenerative diseases. Finally, we discuss the therapeutic potential of targeting the orexinergic system to enhance cognitive and emotional function. We propose that modulating orexinergic system to increase arousal levels represents a key strategy for improving cognition and emotion. Advancing research in this area will deepen our understanding of orexin function and enrich theoretical frameworks linking arousal, cognition, and emotion.

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

2025, 30(11):  1467-1478.  doi:10.12092/j.issn.1009-2501.2025.11.003

Asbtract ( 10 )   PDF (1613KB) ( 2 )  

Related Articles | Metrics

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. 

Mechanisms and pharmacological intervention strategies of insomnia disorder

KOU Liang, XIA Yun, WANG Tao

2025, 30(11):  1479-1490.  doi:10.12092/j.issn.1009-2501.2025.11.004

Asbtract ( 10 )   PDF (1099KB) ( 2 )  

Related Articles | Metrics

Sleep is crucial for human physical and mental health. However, insomnia is one of the most prevalent sleep disorders worldwide and significantly increases the risk of cardiovascular and cerebrovascular diseases, mental illnesses, and neurodegenerative disorders. Researches suggested that hyperarousal may be the final common pathway in the pathophysiology of insomnia. Current intervention strategies for insomnia mainly include cognitive-behavioral therapy and pharmacological treatment. Commonly used medications primarily consist of benzodiazepines and non-benzodiazepine sedative-hypnotics. However, limitations such as tolerance, dependence, and next-day residual effects make these drugs unable to meet clinical treatment needs. Orexin receptor antagonists inhibit the hyperarousal state by blocking orexin receptors, prolonging both rapid eye movement (REM) and non-REM sleep, and promoting natural sleep. With fewer side effects and no addictive potential, they offer new hope for the treatment of insomnia. This article aims to summarize the pathophysiological mechanisms of insomnia and current pharmacological treatment strategies, providing a reference for clinical insomnia management.

Daridorexant: from discovery to clinical application

WANG Zan, WANG Ruiqi, SUN Qingqing, ZHANG Yanan

2025, 30(11):  1491-1499.  doi:10.12092/j.issn.1009-2501.2025.11.005

Asbtract ( 8 )   PDF (1343KB) ( 2 )  

Related Articles | Metrics

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.

7,8-Dihydroxyflavone exacerbates arsenic trioxide-induced cardiomyocyte toxicity and mitochondrial respiratory dysfunction

GUO Dandan, HANG Pengzhou, ZHAO Jing, ZHU Hua

2025, 30(11):  1500-1507.  doi:10.12092/j.issn.1009-2501.2025.11.006

Asbtract ( 12 )   PDF (2035KB) ( 4 )  

Related Articles | Metrics

AIM: To investigate the effects of 7,8-dihydroxyflavone (DHF) on arsenic trioxide (ATO)-induced cardiomyocyte cytotoxicity and mitochondrial dysfunction, as well as the underlying mechanisms. METHODS: HL-1 and H9c2 cardiomyocyte cell lines were used to establish an ATO-induced cell injury model, followed by DHF intervention. Cell morphology was observed under a light microscope, cell viability was assessed using the MTT assay, and cell survival rate was evaluated via Calcein-AM staining. Mitochondrial respiratory function (including basal respiration, maximal respiration, and reserved respiratory capacity) was measured using a high-resolution mitochondrial respirometry system. The protein expression levels of AKT, HO-1, and Nrf2 were detected by Western blot. RESULTS: ATO (5, 10 μmol/L) induced damage of and impaired mitochondrial respiratory function in HL-1 cells. DHF intervention further exacerbated ATO-induced HL-1 cell damage and mitochondrial dysfunction. In H9c2 cells, ATO (5 μmol/L) inhibited survival and reduced cell viability, while DHF treatment aggravated these detrimental effects, suppressed mitochondrial respiration, which was associated with increased phosphorylated AKT and HO-1 protein expression, and decreased Nrf2 expression. CONCLUSION: DHF exacerbates ATO-induced cardiomyocyte cytotoxicity and mitochondrial respiratory dysfunction.

Establishment and function of a mouse model of renal tubular epithelial cell-specific FXR gene knockout 

LIU Zhaofeng, LI Ling, NA Shufang, YUE Jiang, YE Qifa

2025, 30(11):  1508-1515.  doi:10.12092/j.issn.1009-2501.2025.11.007

Asbtract ( 6 )   PDF (2085KB) ( 2 )  

Related Articles | Metrics

AIM: To investigate the effect of FXR gene knockout on the kidney of mice. METHODS: Renal tubular epithelial cell-specific FXR gene knockout mice were constructed based on the cre-loxp system. qRT-PCR was used to detect the mRNA transcription level of FXR in kidney, western blot and immunofluorescence were used to detect the expression of FXR protein in kidney, hematoxylin-eosin staining and periodate sherff staining were used to observe the kidney morphology of mice, and transmission electron microscopy was used to observe the tubule morphology under ultrastructure. Renal function was assessed by testing Scr, BUN, and urine NAG. RESULTS: The mRNA transcription level and protein expression level of FXR in the renal tubular epithelial cells were decreased after specific knockout of FXR in mice, and there were obvious vacuolization in the renal tubules. The levels of SCr and BUN in the serum were not significantly changed, but the level of NAG in urine was increased. CONCLUSION: The mouse model of FXR gene knockout in renal tubular epithelial cells has been successfully established, and FXR knockout leads to vacuolization of renal tubular epithelial cells and impairment of renal function.

Effects of AAVC-I on proliferation and migration of human oral squamous cell carcinoma SCC4 and Cal27 cells through ERK1/2/MAPK signaling pathway

WEI Lingjie, ZHANG Mingyu, TAO Zhihao, WANG Mengyu, YAN Jingjing, WANG Xinyi, CHAI Lin

2025, 30(11):  1516-1523.  doi:10.12092/j.issn.1009-2501.2025.11.008

Asbtract ( 5 )   PDF (2757KB) ( 2 )  

Related Articles | Metrics

AIM: To investigate whether the antitumor component I of Agkistrodon venom can inhibit the proliferation and migration of human oral squamous cell carcinoma SCC4 and Cal27 cells and whether it inhibits their proliferation and migration through the ERK1/2/MAPK signaling pathway. METHODS: After different concentrations of AAVC-I (0, 2.5, 5, 10, 20, 40 μg/mL) were applied to human oral squamous cell carcinoma SCC4 and Cal27 cells for 24 hours, the cell proliferation ability was detected by CCK-8 and EDUC-488 experiments. Cell apoptosis was detected by flow cytometry, cell invasion ability was detected by Transwell assay, cell migration ability was detected by scratch assay, and expression of related proteins in MAPK signaling pathway was detected by Western blot assay. RESULTS: After different concentrations of AAVC-I (0, 2.5, 5, 10, 20, 40 μg/mL) were treated on human oral squamous cell carcinoma SCC4 and Cal27 cells for 24 hours, the experimental group was compared with the normal control group. With the increase of AAVC-I concentration, the proliferation, invasion and migration ability of SCC4 and Cal27 cells of human oral squamous cell carcinoma gradually weakened, and the percentage of apoptosis gradually increased. The expression levels of MEK1 and ERK1/2 in MAPK signaling pathway did not change significantly. However, phosphorylated MEK1 and phosphorylated ERK1/2 decreased with the increase of drug concentration. Its expression level was down-regulated.CONCLUSION: AAVC-I can inhibit the proliferation, invasion and migration of human oral squamous cell carcinoma SCC4 and Cal27 cells, and the mechanism of its inhibition may be closely related to ERK1/2/MAPK signaling pathway.

Clinical efficacy and influence factors about intra-patient variation of tacrolimus concentration in children with nephrotic syndrome

CHANG Zhao, ZHOU Yuxue, ZHANG Shengnan, LV Meng

2025, 30(11):  1524-1529.  doi:10.12092/j.issn.1009-2501.2025.10.009

Asbtract ( 4 )   PDF (950KB) ( 0 )  

Related Articles | Metrics

AIM: To explore the intra-patient variation of tacrolimus concentration in children with nephrotic syndrome, evaluate clinical efficacy and analyze the factors, in order to provide reference for promoting rational drug use in children. METHODS: Sixty-four children with nephrotic syndrome were followed up in our hospital from January 2021 to November 2023. Basic information, medication orders, tacrolimus concentration and CYP3A5*3 polymorphism were collected. Evaluate the clinical efficacy and analyze the factors affecting tacrolimus concentration intra-patient variation. RESULTS: Tacrolimus initial dose was 0.01-0.14 mg·kg-1·d-1. C0 was (4.42±3.03) ng/mL, only 15.63% of children in the target concentration. After medication adjustment, children in target concentration up to 62.07%. 50% and 52.17% of children reach the target concentration respectively at 3 and 6 months. The coefficient of variation (CV) about all Tac-C0 was 37.75%±16.16%. The overall remission rate was 89.58%. The CV of children with non-remission was significantly higher (P<0.05). Tac-C0-CV was affected by CYP3A5*3 polymorphism and age (P<0.05). CONCLUSION: Children with high CV have poor clinical efficacy. The Tac-C0-CV in children with nephrotic syndrome is affected by CYP3A5*3 and age. TDM and genotype testing should be paid more attention in order to adjust the medication.

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

2025, 30(11):  1530-1535.  doi:10.12092/j.issn.1009-2501.2025.11.010

Asbtract ( 7 )   PDF (914KB) ( 1 )  

Related Articles | Metrics

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.

Median effective dose (ED50) of sugammadex combined with glycopyrrolate and neostigmine in reversing muscle relaxation during intraoperative neurophysiological monitoring

JIN Jingxing, MEI Fengmei, ZHAO Jinbing, ZENG Qiong

2025, 30(11):  1536-1540.  doi:10.12092/j.issn.1009-2501.2025.11.011

Asbtract ( 9 )   PDF (888KB) ( 1 )  

Related Articles | Metrics

AIM: To investigate the median effective dose (ED50) of low-dose sugammadex combined with glycopyrrolate and neostigmine in reversing muscle relaxation during intraoperative neurophysiological monitoring. METHODS: Thirty six patients with ASA grade II or III, aged between 18 and 80 years, were selected for elective resection of tumors in the cerebellopontine angle region under general anesthesia in our hospital, BMI 20-30 kg/m2. Anesthesia induction was administered with 0.60 mg/kg rocuronium bromide, and tracheal intubation was performed after TOF was 0. During the operation, muscle relaxation was maintained by pumping rocuronium bromide. When performing neurophysiological monitoring, the pumping of rocuronium bromide was stopped, TOF recovery to T2 appearance, the initial dose of sugammadex was 1 mg/kg combined with 4 μg/kg of glycopyrrolate and 0.02 mg/kg of neostigmine. An effective dose can be induced electrophysiological waveforms within 3 minutes. Otherwise, it is ineffective. The next patient is recommended to use 20% of the initial dose as a gradient to increase or decrease adjacent doses,the study ends until 8 dose inflection points are reached. Using SPSS 20 software, using Probit regression mode lto calculate ED50 and 95% confidence interval (95%CI). record HR and MAP before administration (T0) and 1 minute (T1), 3 minutes (T2), and 5 minutes (T3) after use, and intraoperative awareness, body movement rate, satisfaction with electrophysiological monitoring. RESULTS: A total of 36 patients were included in the analysis, and the Probit regression model calculated  ED50 1.338 mg/kg, 95%CI 0.838-1.786 mg/kg. The hemodynamics remained stable After administration, and the satisfaction rate of the neuroelectrophysiological monitoring doctor was 4.5±0.4. There was no intraoperative awareness or occurrence of body movements. CONCLUSION: Low dose sugammadex combined with glycopyrrolate and neostigmine can reverse muscle relaxation during intraoperative neurophysiological monitoring, with ED50 1.338 mg/kg and 95%CI 0.838-1.786 mg/kg.

Pharmacovigilance of antibody drugs: Bayesian network practice

CAO Shang, RAO Yuqing, DONG Chenglong, LI Ziwei, KAN Hongwei

2025, 30(11):  1541-1549.  doi:10.12092/j.issn.1009-2501.2025.11.012

Asbtract ( 6 )   PDF (880KB) ( 1 )  

Related Articles | Metrics

Pharmacovigilance is a critical measure to ensure drug safety, particularly challenging in the context of antibody drugs-complex macromolecular biologics, which due to their intricate adverse reaction monitoring and management needs. As a causal analysis tool grounded in probabilistic inference, Bayesian networks offer significant advantages in handling complex data relationships and uncertainties. Focusing on the characteristics of antibody drugs, including high target specificity, patterns of adverse reactions, and immunogenicity, this paper explores how to integrate multi-source data using Bayesian networks. Furthermore, it provides a preliminary investigation into the feasibility of causal inference and risk prediction for adverse events under conditions of variable missingness and complex interactions. The study aims to offer both a reference and methodological foundation for pharmacovigilance research on antibody drugs.

Advances in the study of the pathological role of salivary gland epithelial cells in Sj?gren's syndrome

TIAN Jiexiang, QI Wenxia, WANG Gang, YAN Yanfeng, WANG Zhandong, WEI Yong, LIU Hailong, ZHANG Yuanyuan

2025, 30(11):  1550-1558.  doi:10.12092/j.issn.1009-2501.2025.11.013

Asbtract ( 10 )   PDF (860KB) ( 1 )  

Related Articles | Metrics

Sjgren's syndrome (SS) is an autoimmune disease characterized by exocrine gland dysfunction. Currently, although the pathogenesis of SS has not been fully elucidated, more and more studies have shown that salivary epithelial cells play an important role in the pathogenesis of salivary gland damage in SS, and that blocking the activation of salivary epithelial cells and restoring their normal physiological function may be able to improve the secretory function of salivary glands. In this paper, the pathological mechanism of salivary gland epithelial cells in desiccation syndrome will be elaborated in depth from four aspects, including the pathological structural changes of the salivary glands in SS, the death pattern of salivary gland epithelial cells, their communication with immune cells, and the common signaling pathways.

Development of the mechanism of cationic imbalance in secondary spinal cord injury and potential intervention drugs

ZHOU Mingjun, SANG Xue, CHANG Jingwen, LIU Fang, TAO Yu, FAN Fangtian

2025, 30(11):  1559-1568.  doi:10.12092/j.issn.1009-2501.2025.11.014

Asbtract ( 7 )   PDF (915KB) ( 1 )  

Related Articles | Metrics

Spinal cord injury (SCI) is an impairment caused by direct or indirect external forces acting on the spine, resulting in a sensory-motor dysfunction in corresponding segments. Spinal cord injury can be divided into primary SCI and secondary SCI according to the occurrence sequences and progression mechanism. Secondary SCI is a phenomenon of further aggravation of the extent of SCI caused by the development of pathophysiological processes due to the initial damage of the spinal cord. Secondary SCI includes cell death after SCI, such as loss of neurons, gliosis, inflammatory response, changes in the immune microenvironment, spinal cord edema, ischemia and hypoxia, etc. These factors interact to exacerbate the SCI by causing further changes to the function and structure of the spinal cord neurons. Cationic imbalance, for example, is one of the important factors that affect the process of secondary SCI. There are some common ions in the central nervous system, such as sodium, potassium and calcium, in which concentration variation can cause changes in neuronal excitability and further aggravate the SCI level. Besides, concentration variation of some common ions in the central nervous system, such as sodium, potassium and calcium, is found to cause changes in neuronal excitability and further aggravate the SCI level. The concentration of potassium ions in the extracellular fluid increases when SCI occurs, leading to a decrease in neuronal excitability, which affects neuronal function and structure. In secondary SCI, the increased concentration of sodium ions can enhance neuronal excitability, which exacerbates SCI level. In conclusion, cationic imbalance is closely related to secondary SCI, and can further aggravate the SCI level after injury. Treatment of cation imbalance may become an important strategy in the management of secondary SCI. This paper summarizes the changes and effects of common cations in neurons in secondary SCI, and introduces the relevant drug research progress to provide further theoretical basis for the pathogenesis and treatment of SCI.

Research progress of targeted nanoparticles in the treatment of cervical cancer

HAN Xue, WANG Dan, LIU Huiling

2025, 30(11):  1569-1577.  doi:10.12092/j.issn.1009-2501.2025.11.015

Asbtract ( 5 )   PDF (799KB) ( 4 )  

Related Articles | Metrics

Cervical cancer is one of the most common gynecological malignancies, which seriously threatens women's life and health. Traditional treatment methods are still mainly surgery and chemotherapy, these methods have improved the overall prognosis of cervical cancer patients, there are still many problems such as tumor recurrence and drug resistance. In recent years, with the development of nanotechnology, targeted nanoparticles can not only improve the solubility, stability and biodistribution of drugs, but also achieve minimally invasive drug release. It is a new type of drug targeted delivery system with great therapeutic potential. This article summarizes the latest research progress of nano-targeted drug delivery systems in the field of cervical cancer treatment, and looks forward to the challenges and development directions in this field.

Discussion on the key points of clinical trials for FDA-approved CAR-T cell therapy products

PENG Siqi, HAN Jinghong

2025, 30(11):  1578-1584.  doi:10.12092/j.issn.1009-2501.2025.11.016

Asbtract ( 11 )   PDF (665KB) ( 1 )  

Related Articles | Metrics

As a groundbreaking advancement in cancer immunotherapy, chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized treatment options for patients with hematologic malignancies. Based on the Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell Products Guidance for Industry, this study systematically analyzes key clinical trial data from seven FDA-approved CAR-T products as of 2024. The analysis provides detailed discussion on several pivotal aspects including single-arm trial design and control settings, recommended dosing strategies, as well as safety and efficacy evaluation methodologies. While CAR-T therapy has demonstrated remarkable clinical success, future development directions encompass expansion into solid tumors, exploration of novel targets, advancement of universal CAR-T technologies, optimization of combination therapies, and integration of emerging technologies such as artificial intelligence, all of which will collectively drive the high-quality development of the CAR-T industry.