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  • Qiu-xiao ZHU, Zi-bo LIU, Lin-yi SHU, Zhi-hua HAO, Hui-yao HAO
    Chinese Journal of Clinical Pharmacology. 2025, 41(23): 3343-3349.
    Objective

    To investigate the promoting effect and mechanism of hyperoside (Hyp) on wound healing in diabetic foot ulcer (DFU) rats by inhibiting the nuclear factor-kappa B (NF-κB) pathway and the Nod-like receptor family Pyrin domain-containing 3 (NLRP3) inflammasome.

    Methods

    A total of 50 SD rats were randomly divided into blank group, model group, metformin group, low-dose experimental group and high-dose experimental group, with 10 rats in each group. Fasting blood glucose (FBG), wound healing rate and transcutaneous oxygen partial pressure (TcpO2) in the tissues surrounding the wounds were measured using a blood glucose meter. Pathological changes in the wound tissues were observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of interleukin (IL)-8, IL-1β, tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP). Western blotting was employed to assess the relative expression levels of matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), NF-κB p65, phosphorylated (p)-NF-κB p65 and NLRP3 proteins.

    Results

    The FBG levels in blank, model, metformin, low-dose experimental and high-dose experimental groups were (5.31±0.91), (22.52±3.18), (11.27±2.35), (13.11±2.67) and (8.76±1.15) mmol·L-1, respectively; the wound healing rates were (76.91±12.30)%, (9.53±1.01)%, (45.26±6.15)%, (39.94±5.47)% and (57.10±9.26)%, respectively; the TcpO2 values were (41.09±8.51), (24.35±4.97), (33.27±5.68), (30.84±3.26), and (37.92±4.14) mmHg, respectively; the serum levels of IL-8 were (15.34±0.39), (41.92±3.12), (26.68±2.28), (30.55±3.27) and (17.95±2.70) ng·L-1, respectively; IL-1β levels were (31.05±4.62), (64.39±7.14), (46.62±5.07), (50.21±3.92) and (39.54±4.25) ng·L-1, respectively; TNF-α levels were (26.95±4.15), (69.74±7.43), (39.85±4.29), (45.08±4.36) and (35.52±2.95) ng·L-1, respectively; and CRP levels were (0.69±0.08), (5.11±0.60), (3.23±0.58), (3.68±0.71) and (1.95±0.30) ng·L-1, respectively; the protein relative expression levels of MMP-9 were 0.23±0.03, 0.99±0.11, 0.62±0.05, 0.74±0.06 and 0.39±0.04, respectively; the MMP-9/TIMP-1 ratios were (22.56±1.23)%, (97.07±5.67)%, (60.18±5.01)%, (70.49±5.98)% and (38.39±4.15)%, respectively; the p-NF-κB p65/NF-κB p65 protein relative expression levels were 0.21±0.02, 1.23±0.10, 0.51±0.04, 0.57±0.06 and 0.33±0.04, respectively; and the NLRP3 protein relative expression levels were 0.25±0.01, 0.93±0.07, 0.72±0.08, 0.80±0.06 and 0.35±0.04, respectively. Statistically significant differences were observed when comparing the model group with the blank group and the low- and high-dose experimental groups with the model group (all P<0.05).

    Conclusion

    Hyp promotes wound healing in DFU rats by inhibiting NF-κB and NLRP3 pathways, reducing inflammation and reducing MMP-9 expression.

  • Bo SU, Bo ZHENG
    Chinese Journal of Clinical Pharmacology. 2025, 41(23): 3415-3420.
    Objective

    To systematically analyze the linear plasmid-related studies published from 1994 to 2023 by using bibliometric methods, and to sort out the research pattern, core forces and development context of this field.

    Methods

    A total of 989 linear plasmid-related literatures indexed in the Web of Science Core Collection were selected as research objects. Bibliometric analysis was carried out from the dimensions of country, institution, journal, author and keyword by using CiteSpace (a literature analysis software) and GraphPad Prism (a graphing software).

    Results

    Linear plasmids were taken as the core research object. The United States and Germany together contributed 53% of the relevant literature, with the USA National Institutes of Health (NIH) ranking first in the number of publications (50 papers). Journal of Bacteriology has published 80 papers on this topic, and German scholar Meinhardt Friedhelm (16 papers) is the core author in this field. Among them,Borrelia burgdorferi is the classic research microorganism, and the research hotspots include comparative genomics, replication and horizontal transfer mechanisms, and gene regulation. In addition, the dissemination of antibacterial drug resistance genes mediated by linear plasmids and the evolution of resistant plasmids have also attracted great attention.

    Conclusion

    Over the past 30 years, research on linear plasmids has evolved from sequence analysis to functional mechanism exploration, and has continuously integrated new technologies. However, the current research still has limitations such as insufficient breadth and depth. In the future, international cooperation should be strengthened to conduct in-depth research on linear plasmids, which can provide theoretical support for the formulation of drug resistance prevention and control strategies and the development of new antibacterial drugs.

  • Xiu-zhen DI, Xiao-hui WANG, Hua SUN, Nan BAI
    Chinese Journal of Clinical Pharmacology. 2025, 41(23): 3399-3407.

    Hyperuricemia (HUA) is a metabolic disorder characterized by abnormally elevated serum uric acid levels, with a rising prevalence worldwide. The potential hazards of HUA and its precise intervention strategies have emerged as a central focus in clinical medicine research. Current research indicates that HUA is closely associated with various systemic diseases, such as cardiovascular and renal diseases. Its pathogenic mechanisms involve multiple pathways, such as oxidative stress, inflammatory factor activation, and urate crystal deposition. However, the treatment of HUA patients with comorbid cardiovascular or renal diseases—particularly those with asymptomatic hyperuricemia (AH)—remains highly controversial. Existing clinical guidelines show significant regional variations, European and American guidelines favor a conservative monitoring approach, while Asian guidelines advocate for earlier intervention. Therefore, to establish the long-term clinical benefits for HUA patients, there is an urgent need for evidence-based medical support through large-scale prospective cohort studies and randomized controlled trials (RCTs). These studies will provide a more reliable foundation for standardized clinical management.

  • Li-li LIU, Fang LI, Li-li HA, Dong LI, Man-ru REN, Yu ZHOU
    Chinese Journal of Clinical Pharmacology. 2025, 41(23): 3426-3429.

    Acetylcysteine is a commonly used clinical drug, and its free thiol group can break the disulfide bond (S-S) in the glycoprotein peptide chain in sputum, thereby reducing sputum viscosity and promoting sputum excretion. It is an endogenous substance. When conducting bioequivalence studies, it is necessary to fully consider and design aspects such as the research type, dosage, blood collection point design, bioequivalence evaluation, etc., and fully evaluate the impact of endogenous acetylcysteine on bioequivalence evaluation. This article integrates the pharmacokinetic (PK) characteristics of acetylcysteine granules along with the bioequivalence research conducted on its generic version prior to domestic marketing. Through this approach, it comprehensively explores the general design requirements and key considerations for conducting bioequivalence studies on this product.

  • Shou-fang KONG, Yi-yuan CAI, Xiang-qian XU, Hui YUAN
    Chinese Journal of Clinical Pharmacology. 2025, 41(23): 3321-3327.
    Objective

    To observe the clinical efficacy and safety of anlotinib hydrochloride capsules combined with standard chemotherapy (cisplatin for injection+paclitaxel injection) in the treatment of patients with recurrent and metastatic cervical cancer.

    Methods

    The patients with recurrent and metastatic cervical cancer were divided into treatment group and control group according to the treatment methods. In control group, paclitaxel injection (175 mg·m-2, infused within 3 hours) and cisplatin for injection (infusion time≥1 h) were intravenously infused. In treatment group, based on the treatment in control group, anlotinib hydrochloride capsules (12 mg qd) were orally administered. Both groups were continuously treated for 4 courses. The clinical efficacy, tumor marker levels, tumor angiogenesis-related indicators, quality of life, short-term prognosis of the two groups were compared, and the safety was evaluated.

    Results

    The patients (n=125) were divided into control group (n=64) and treatment group (n=61). After treatment, the disease control rate (DCR) was 67.19% (43 cases/64 cases) in control group and 83.61% (51 cases /61 cases) in treatment group; the objective response rate (ORR) were 23.44% (15 cases /64 cases) and 40.98% (25 cases /61 cases), respectively; the median progression-free survival (PFS) were 6.40 and 11.31 months, respectively; and the median overall survival (OS) were 10.22 and 16.13 months, respectively. All the aforementioned indicators in treatment group were statistically significantly different from those in control group (all P<0.05). After treatment, the squamous cell carcinoma antigen levels in control group and treatment group were (2.80±0.53) and (2.56±0.47) ng·mL-1, respectively; the carcinoembryonic antigen levels were (3.09±0.62) and (2.85±0.45) μg·L-1, respectively; the carbohydrate antigen 19-9 levels were (21.08±3.04) and (19.59±2.72) U·mL-1, respectively; the cytokeratin 19 fragment antigen 21-1 levels were (26.09±3.44) and (24.63±3.01) μg·L-1, respectively; the vascular endothelial growth factor receptor levels were (461.93±97.86) and (415.74±101.87) pg·mL-1, respectively; the platelet-derived growth factor receptor levels were (69.68±12.15) and (64.87±11.39) pg·mL-1, respectively; the physiological condition scores were (18.66±4.04) and (21.49±4.15) points, respectively; the social/family situation scores were (17.16±4.03) and (19.57 ± 4.15) points, respectively; the functional status scores were (14.64±2.99) and (16.36±3.81) points, respectively; and the emotional state scores were (16.89±3.32) and (18.46±5.19) points, respectively. All the above-mentioned indicators in treatment group had statistically significant differences from those in control group (all P<0.05). No statistical significant difference in adverse drug reactions was observed between the two groups (P>0.05).

    Conclusion

    Anlotinib combined with the standard chemotherapy regimen has a remarkable efficacy in treating patients with recurrent and metastatic cervical cancer. It can reduce the levels of tumor markers in patients, inhibit tumor angiogenesis, improve their quality of life and short-term prognosis, and is highly safe.

  • Dong-bo WANG, Lei XU, Juan FENG, Wu-lin WEN, Yan-ru LI, Xiao-sheng WANG, Jin TIAN, Ya-jie JIA, Qing HAO, Xiu-li ZHAO, De-min HAN
    Chinese Journal of Clinical Pharmacology. 2025, 41(23): 3447-3450.
    Objective

    Decentralized clinical trials (DCT) have shown a rapid growth trend in recent years due to their advantages such as being geographically unrestricted, enhancing research efficiency, and reducing research costs. The United States has a significant development advantage in this field, with a clear concentration trend. China is still in its infancy in this area, lacking practical experience and summaries. This study takes the "Multicenter Prospective Open Randomized Controlled Clinical Study on the Early Intervention of Lianhua Qingwen Granules in Acute Pharyngitis Patients" as an example, and through the implementation of DCT digital management based on the internet platform, it sorts out and summarizes the key links in conducting DCT, explores the technical aspects and applicable fields of DCT in China, and provides practical references for accelerating the resolution of the bottlenecks in promoting DCT.

  • Yu ZHOU, Fang-hua HUANG, Tao SUN
    Chinese Journal of Clinical Pharmacology. 2025, 41(23): 3374-3381.

    The ICH S1B(R1) guideline addendum, adopted by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) in August 2022, introduces a comprehensive Weight of Evidence (WoE)-based approach into the traditional framework for drug carcinogenicity risk assessment. This method aims to conduct an integrated analysis by incorporating multiple key factors to evaluate whether the two-year rat carcinogenicity study can provide additional valuable information for human carcinogenicity risk assessment. Consequently, under certain circumstances, the two-year rat carcinogenicity study may be waived, allowing resources to be focused on more scientific, mechanism-based carcinogenicity assessments. This transformation is grounded in scientific advances since the release of ICH S1B in 1997, retrospective analyses of drug databases, and an international prospective study, confirming that the WoE approach can adequately assess risks in specific contexts and aligns with the 3R principles (Replacement, Reduction, Refinement) aimed at reducing animal use. The addendum emphasizes a systematic evaluation of factors such as target biology, secondary pharmacology, histopathology from long-term toxicity studies, hormonal effects, genotoxicity, and immunomodulation, encouraging a mechanism-driven risk assessment strategy. However, its implementation faces scientific and procedural challenges, and there may be disagreements between regulatory authorities and applicants regarding WoE conclusions. Promoting practical application requires early communication, standardized documentation submission, and international experience sharing. Although current implementation experience is limited and both regulators and industry remain cautious, coordinated efforts by the ICH Implementation Working Group (IWG) and accumulating case studies are expected to advance WoE-based carcinogenicity assessment, optimize drug development processes, reduce unnecessary animal testing, and foster the safe and ethical development of innovative drugs.

  • Chen-yang ZHAO, Shuang LU
    Chinese Journal of Clinical Pharmacology. 2025, 41(23): 3438-3446.

    Gene therapy drugs based on adeno-associated virus (AAV) have become the most widely used viral vectors for in vivo gene therapy in clinical applications. Until July 2025, nine AAV-based gene therapy drugs have been approved globally, with many more in research or clinical trials. This article analyzes the basic characteristics, adverse reactions, and risk management strategies of AAV gene therapy drugs, aiming to provide valuable insights for risk assessment and mitigation in this field.

  • Jia-qing WANG, Cui-cui YANG, Xing-huan DING, En-shan FENG
    Chinese Journal of Clinical Pharmacology. 2025, 41(23): 3430-3437.
    Objective

    Efgartigimod, as a novel FcRn inhibitor, can improve neuromuscular transmission in patients with generalized myasthenia gravis (gMG) by accelerating the degradation of pathogenic IgG antibodies. Although clinical trials have confirmed its efficacy and good tolerability, its safety profile in the real-world setting requires comprehensive evaluation. This study utilized data from the U.S. FDA Adverse Event Reporting System (FAERS) to investigate and assess potential adverse event (AE) signals associated with Efgartigimod. The aim was to evaluate its real-world safety characteristics and provide evidence for clinical safe medication use and risk monitoring.

    Methods

    Reports listing Efgartigimod as the primary suspected drug were extracted from Q1 2020 to Q4 2023. After deduplication and terminology standardization, disproportionality analysis was conducted using three methods: Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM), to identify significant signals at both the System Organ Class (SOC) and Preferred Term (PT) levels. Important Medical Events (IMEs) were also screened.

    Results

    A total of 788 individual case safety reports involving 13 551 AEs were included. At the SOC level, the strongest signals were for nervous system disorders (ROR=5.12) and neoplasms (ROR=4.78). At the PT level, multiple strong signals were identified, including myasthenic crisis (ROR=2 269.29), bulbar paralysis (ROR=275.64), and thymoma (ROR=170.02). IME analysis further confirmed these events as high-priority safety concerns.

    Conclusion

    This study identified several potential new safety signals for Efgartigimod in the neurological, oncological, and immunological domains, suggesting that clinicians should remain vigilant about adverse reactions related to these organ systems and providing a basis for further targeted safety research.

  • Jia-ying ZHU, De-yu FU, Yu-xiu ZHAO, Yu-long MA, Bo-ying CAO, Xiao-zhe CHEN, Si-yu SUN, Bo LU
    Chinese Journal of Clinical Pharmacology. 2025, 41(23): 3408-3414.
    Objective

    To investigate the mechanism of professor Fu Deyu’s core prescription, Danyu Hemai Granules (DYHMG), in treating hypertension using network pharmacology, and to conduct preliminary validation through molecular docking technology.

    Methods

    Active components and targets of Danyu Hemai Granules were screened with traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), traditional Chinese medicine integrated database (TCMID), and HERB database. Hypertension-related targets were retrieved from GeneCards and OMIM. Intersection targets were identified, and protein-protein interaction (PPI) networks were constructed via STRING. The "Herb-Active Component-Target-Disease" network was visualized using Cytoscape to identify core targets. GO and KEGG pathway enrichment analyses were performed with Metascape. Finally, molecular docking validation was performed between key active components and core targets.

    Results

    A total of 127 active ingredients and 312 targets of DYHMG, and 5 251 hypertension-related targets were identified, resulting in 229 common targets. Analysis suggested DYHMG exerts its antihypertensive effects primarily through active ingredients such as quercetin, kaempferol, luteolin, beta-sitosterol, stigmasterol, and wogonin. These ingredients acted on core targets including signal transducer and activator of transcription 3 (STAT3), RAC-alpha serine/threonine-protein kinase (AKT1), and estrogen receptor alpha (ESR1). Key pathways involved were lipid and atherosclerosis, the HIF-1 signaling pathway, insulin resistance, calcium signaling pathway, cAMP signaling pathway, MAPK signaling pathway, necroptosis, the renin-angiotensin system (RAS), and efferocytosis pathways.

    Conclusion

    Danyu Hemai Granules exhibits the characteristics of multi-component, multi-target, and multi-pathway in the treatment of hypertension. This study can provide ideas for the in-depth research on Danyu Hemai Granules in the treatment of hypertension and offer a scientific basis for its rational clinical application.