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  • Jie LIU, Hua JIN, Jie DU, Xuan BAO
    Chinese Journal of Clinical Pharmacology. 2025, 41(22): 3241-3247.

    Cardiac fibrosis is a common pathological basis for a variety of cardiovascular diseases, and its core feature is cardiac fibroblast overactivation and extracellular matrix deposition, which ultimately leads to cardiac structural remodeling. Studies have shown that mitochondrial dysfunction is an important driver of the occurrence and development of cardiac fibrosis. Mitochondrial quality control is a set of precise dynamic regulatory systems in cells, involving mitochondrial dynamics, mitochondrial biogenesis and mitochondrial autophagy, which are responsible for maintaining mitochondrial homeostasis. Traditional Chinese medicine has the advantages of multiple pathways, multiple targets and small toxic side effects, and shows great potential in regulating mitochondrial quality control and treating cardiac fibrosis. Based on this, this paper systematically reviews the relationship between mitochondrial quality control and cardiac fibrosis and the mechanism of traditional Chinese medicine to regulate mitochondrial quality control in the treatment of cardiac fibrosis, aiming to provide a theoretical basis and new targets for the clinical treatment of cardiovascular diseases.

  • Yu-han ZHAO, Ning ZHANG, Jun CHEN, Wei-gen XIONG, Xiao-fang TAN
    Chinese Journal of Clinical Pharmacology. 2025, 41(22): 3234-3240.
    Objective

    To investigate the prevalence and associated influencing factors of potentially inappropriate medications (PIM) in elderly hospitalized patients with ischemic stroke, and to construct a risk prediction model for this population. This study aimed to provide decision support for identifying high-risk patients and ensuring rational clinical medication use.

    Methods

    Retrospective analysis was performed on the medical records of elderly hospitalized patients with ischemic stroke admitted to our hospital from January 2021 to December 2023. The 2023 version of the Beers Criteria was adopted to assess PIM. Univariate and multivariate Logistic regression analyses were applied to identify risk factors associated with PIM, and the optimal model was ascertained via the Akaike information criterion (AIC) followed by nomogram development. The discriminative ability, calibration, and clinical utility of the model were evaluated systematically.

    Results

    A total of 1 797 patients were included, among whom 866 (48.19%) had PIM, involving 1 756 PIM episodes. Multivariate Logistic regression analysis revealed that female gender, number of medications≥10 types, National Institutes of Health Stroke Scale (NIHSS) score of >5 points, personal history of cerebral infarction, type 2 diabetes mellitus, coronary heart disease, and atrial fibrillation were independent risk factors for PIM (P<0.05, P<0.001). Validation of the nomogram model showed an area under curve (AUC) of the receiver operating characteristic of 0.73. The Hosmer-Lemeshow goodness-of-fit test showed a P-value >0.05, meaning the model fit well, and there was good agreement between the calibration curve and the ideal curve. Clinical decision curve analysis (DCA) demonstrated that when the threshold probability ranged from 15% to 87%, the model achieved a high net benefit, confirming its clinical practical value.

    Conclusion

    The constructed nomogram model exhibits good discriminative ability, calibration, and clinical applicability. It can accurately predict the risk of PIM in elderly patients with ischemic stroke, facilitating early clinical risk identification and targeted intervention implementation.

  • Ju-xian ZHAO, Shuan-jun ZHANG, Wen LI, Cai-hong WANG, Hui-wen WANG
    Chinese Journal of Clinical Pharmacology. 2025, 41(22): 3270-3276.

    Elderly patients with hip fracture have a high incidence of perioperative neurocognitive disorders (PND), poor prognosis and high resource consumption. Remazolam has the pharmacokinetic advantages of esterase metabolism, predictable recovery and hemodynamic friendliness, and can be quickly reversed by flumazenil, making it suitable for people with advanced age, insufficient organ reserve or high risk of cognitive complications. Recent studies have shown that remazolam can reduce the level of postoperative inflammatory markers, improve early cognitive function and reduce the incidence of delirium, while retaining good hemodynamic stability and controllable recovery characteristics. The underlying mechanism involves the inhibition of excessive activation of microglia and neuroinflammatory response, reduction of systemic inflammatory response, reduction of stress and pain intensity, and reduction of cerebral hypoperfusion events and other pathways to produce neuroprotective effects. Therefore, this paper integrates the latest evidence of the molecular mechanism, pharmacological characteristics and clinical application of remazolam in the prevention and treatment of perioperative neurocognitive disorders in elderly patients with hip fracture, and emphasizes its potential value in optimizing perioperative anesthesia management of elderly hip fracture. It is expected to provide a theoretical basis for future high-quality, multi-center, long-term follow-up clinical research, and provide reference for individualized perioperative strategy formulation and PND prevention and treatment.

  • Zhi-wei LIU, Zi-ru DAI, Xin-zhong LI, Shuang TANG, Dong-sheng SUN, Min Wang, Hang XIAO, Wen-lan LI, Gui-bo SUN
    Chinese Journal of Clinical Pharmacology. 2025, 41(22): 3255-3261.

    As a multi-target tyrosine kinase inhibitor, sorafenib is the core therapeutic drug for advanced hepatocellular carcinoma, renal cell carcinoma and differentiated thyroid cancer. However, its cardiotoxicity significantly limits clinical application, mainly manifests in hypertension, myocardial ischemia, heart failure, arrhythmia, and thrombosis/hemorrhage events, which seriously affect the patient’s prognosis. This paper deeply explores the molecular mechanisms of sorafenib inducing cardiotoxicity, including key pathways such as oxidative stress and mitochondrial dysfunction, autophagy imbalance, ribonucleic acid binding motif protein 20 (RBM20) mediated gene splicing abnormalities, calcium homeostasis imbalance and myocardial electrophysiological abnormalities; at the same time, a systematic summary of clinical prevention and treatment strategies, covering monitoring and intervention measures for adverse reactions such as hypertension and heart failure, as well as research progress in experimental therapeutic drugs.

  • Ya-yun WANG, Tian-peng HE, Long-fei GUO
    Chinese Journal of Clinical Pharmacology. 2025, 41(22): 3248-3254.

    Sepsis-induced cardiomyopathy is a common cardiovascular complication among septic patients, which significantly increases mortality rates. Ferroptosis is an iron-dependent form of regulated cell death characterized by increased lipid reactive oxygen species (ROS), which causes lipid peroxidation and cell membrane damage. Increasing evidence has highlighted a significant link between ferroptosis and sepsis-induced cardiomyopathy, in which traditional Chinese medicine (TCM) exhibits promising therapeutic potential. This article reviews the mechanism of ferroptosis and current advances in the use of TCM active ingredients and formulated preparations to target ferroptosis in treating sepsis-induced cardiomyopathy, aiming to offer new perspectives for clinical management.

  • Bo SU, Bo ZHENG
    Chinese Journal of Clinical Pharmacology. 2025, 41(22): 3200-3205.
    Objective

    To comparatively analyze the molecular characteristics of linear plasmids in Enterococcus avium, clarify the global transmission trajectory of linear plasmids in Enterococcus, and explore the genetic stability of linear plasmids in different host strains through subculture of transconjugants, thereby providing a theoretical basis for the prevention and control of clinically drug-resistant bacteria.

    Methods

    The minimum inhibitory concentrations (MICs) of vancomycin against Enterococcus avium ZB195, three recipient strains (Enterococcus avium 07H170, Enterococcus faecalis FA2-2, and Enterococcus faecium BM4105RF), and their corresponding transconjugants were determined using the broth microdilution method. Whole-genome sequencing of strain ZB195 was performed to characterize its plasmid features. Linear plasmid sequences from 18 global Enterococcus faecium strains isolated between 2000 and 2019 were collected, and phylogenetic trees and Bayesian evolutionary trees were constructed using MAFFT, IQtree, and BEAST software. The global transmission trajectory was simulated with SpreaD3 software. The genetic stability of linear plasmids in different host strains was evaluated through a 15-day subculture experiment without antibiotic selection pressure.

    Results

    For the first time, this study identified a linear plasmid in the genome of Enterococcus avium ZB195, which harbors the vancomycin resistance vanA gene and was capable of horizontal transfer to three recipient strains. Sequence alignment showed that the linear plasmid of ZB195 had the highest sequence identity with that of Enterococcus faecium AA708 from Japan, and phylogenetic analysis confirmed that they were most closely related. Simulation of global transmission trajectories revealed that the linear plasmid in Enterococcus was first detected in Japan in 2000, and then gradually spreaded to China, the United States, Norway, Denmark, India and other countries. Passage experiments indicated that the linear plasmid exhibited the highest stability in Enterococcus avium hosts.

    Conclusion

    The linear plasmids detected in Enterococcus strains in China may have originated from the horizontal transmission of Enterococcus faecium from Japan. Moreover, after transferring to Enterococcus avium, these plasmids can form better host adaptability. This suggests that it is necessary to strengthen cross-regional monitoring of linear plasmids in Enterococcus to curb the global spread of drug-resistant genes.

  • Jing-jing LIU, Li-ping WU, Ning-ning DU
    Chinese Journal of Clinical Pharmacology. 2025, 41(22): 3178-3184.
    Objective

    To observe the clinical efficacy of dulaglutide injection combined with letrozole tablets in the treatment of obese polycystic ovary syndrome (PCOS) infertility patients.

    Methods

    Obese infertility patients with PCOS were divided into control group and treatment group according to medication regimen. The control group was given letrozole tablets 5 mg orally, once a day for 3 months on the basis of conventional treatment; the treatment group was given dulaglutide injection 1.5 mg, subcutaneous injection once a week, and letrozole tablets were treated with the same method as the control group for 3 months. The clinical efficacy, glucose metabolism characteristics, visceral fat, body composition and the occurrence of adverse drug reactions were compared between the two groups.

    Results

    42 patients were included in the treatment group and 38 in the control group. After treatment, the total effective rate of treatment group and control group was 90.48% (38 cases /42 cases) and 73.68% (28 cases /38 cases), the difference was statistically significant (P<0.05). After treatment, the fasting plasma glucose (FPG) of the treatment group and the control group were (4.37±0.85) and (4.84±0.81) mmol·L-1, respectively; glycosylated hemoglobin (HbA1c) were (4.84±0.82)% and (5.25±0.88)%, respectively; homeostasis model assessment for insulin resistance (HOMA-IR) were 2.45±0.41 and 2.73±0.48, respectively; visceral fat mass were (687.19±97.29) and (739.37±105.24) g, respectively; visceral fat volume were (751.21±106.34) and (821.82±112.64) cm3, respectively; visceral fat area were (143.29±27.88) and (156.39±25.26) cm2, respectively; body mass index (BMI) were (32.04±3.65) and (34.33±3.56) kg·m-2, respectively; waist-hip ratio (WHR) were 0.96±0.22 and 1.10±0.25, respectively; body fat percentage were (31.43±4.87)% and (34.37±4.54)%, respectively. The differences of the above indexes between the two groups were statistically significant (P<0.05, P<0.01). The main adverse drug reactions in the treatment group were nausea, vomiting, and loss of appetite, while no obvious adverse reactions occurred in the control group. There was no statistically significant difference in the total incidence of adverse reactions between the two groups (P>0.05).

    Conclusion

    Dulaglutide injection combined with letrozole tablets has significant clinical efficacy in the treatment of obese PCOS infertility patients, which can regulate the level of glucose and lipid metabolism, visceral fat content and body composition, reduce insulin resistance, and has certain safety.

  • Feng-chao HAN, Kun-long TANG, Yan-nan DAI, Xia-qing GAO
    Chinese Journal of Clinical Pharmacology. 2025, 41(22): 3221-3227.
    Objective

    To study the mechanism of mangiferin alleviating liver injury induced by high-fat and high-sugar diet in obese rats based on oxidative stress signaling pathway.

    Methods

    Forty SD rats were divided into blank control group (NC) (raised normally and given the same amount of normal saline), model group (fed with high-fat and high-sugar diet and given the same amount of normal saline), the mangiferin administration group (MGF) (fed with high-fat and high-sugar diet), and mangiferin administration+miR-195-3p mimics group (MGF+miR-195-3p mimics) (fed with high-fat and high-sugar diet and administered 40 mg·kg-1 mangiferin suspension, in addition, recombinant lentiviruses containing miR-195-3p mimics were injected into the tail vein), with 10 rats in each group. After treatment, body mass, visceral fat mass and liver coefficient were measured, blood glucose, blood lipid, aminotransferase, liver glycogen and oxidative stress related factors were detected by kit, and histopathological status of liver was detected by hematoxylin-eosin (HE) staining. Real-time quantitative fluorescence polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect the levels of miR-195-3p, and protein Western blot (WB) was used to detect the expression levels of nuclear factor erythroidderived 2-like 2 (Nrf2) and heme oxygenase-1 (HO-1).

    Results

    After different treatment, the liver coefficients of NC group, Model group and MGF group were (2.20±0.29)%, (3.11±0.40)% and (2.75±0.32)%, respectively. Insulin was (310.63±38.06), (426.59±55.35) and (378.57±42.81) ng·L-1; glutamic pyruvic transaminase was (55.17±6.11), (137.57±17.45) and (106.85±12.66) U·L-1, respectively. The liver glycogen was (21.64±2.98), (7.96±1.03) and (15.52±2.16) mg·g-1, respectively. The malondialdehyde levels in Model group, MGF group and MGF+miR-195-3p mimics group were (9.63±1.22), (7.79±0.91) and (9.11±1.16) mmol·g-1, respectively, super oxide dismutase was (110.42±14.57), (251.36±36.26) and (181.45±20.95) U·g-1, and Nrf2 mRNA was 1.00±0.12, 1.97±0.20, 1.29±0.15, respectively. The mRNA of HO-1 was 1.00±0.14, 2.84±0.35 and 1.81±0.29, respectively. Comparison of Model group with NC group, MGF group with Model group and MGF+miR-195-3p mimics group with MGF group showed statistically significant differences in the above indexes (all P<0.05).

    Conclusion

    Mangiferin can reduce liver injury and regulate glucose and lipid metabolism in obese rats, and its mechanism may be related to the down-regulation of miR-195-3p expression and activation of Nrf2/HO-1 signaling pathway.

  • Qing-lian MA, Qin TIAN, Yan ZHANG, Jing YANG
    Chinese Journal of Clinical Pharmacology. 2025, 41(21): 3075-3082.
    Objective

    To explore the effects of geniposide on insulin resistance and oxidative stress damage in polycystic ovary syndrome (PCOS) rats by regulating the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1) signaling pathway.

    Methods

    A PCOS model was induced by gavage of letrozole for 21d and rats were randomly assigned into blank group (not modeled +normal saline), model group (modeled +normal saline), low-dose geniposide group (modeled+400 mg·kg-1 geniposide by gavage), high-dose geniposide group (modeled+800 mg·kg-1 geniposide by gavage), positive control group (modeled+0.34 mg·kg-1 ethinylestradiol and cyproterone by gavage) and high-dose geniposide+ML385 group (modeled+800 mg·kg-1 geniposide by gavage+30 mg·kg-1 ML385 by by intraperitoneal injection), with 10 rats in each group. The levels of fasting blood glucose (FBG) and fasting insulin (FINS) were measured by blood glucose meter and enzyme-linked immunosorbent assay (ELISA) and then homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. The levels of serum sex hormones and inflammatory were detected by ELISA and ovarian tissue oxidative stress index levels were detected by test kit, hematoxylin-eosin (HE) staining was used to measure the number of cystic follicles in rat ovarian tissue. TdT-media duTP nict end labeling (TUNEL) method was used to measure apoptosis of rat ovarian granulosa cells. Moreover, Western blot (WB) was used to detect apoptosis and Nrf2/HO-1 signaling pathway related protein expression in ovarian tissues.

    Results

    The FBG levels in the low-dose geniposide group, high-dose geniposide group, positive control group, high-dose geniposide+ML385 group and control group, as well as the model group were (6.87±0.42), (5.21±0.28), (5.03±0.31), (8.32±0.51), (4.90±0.35) and (8.56±0.54) mmol·L-1, respectively; FINS were (16.13±1.62), (10.46±1.37), (10.21±1.51), (20.67±1.82), (9.82±1.14) and (21.45±2.05) mIU·L-1, respectively; HOMA-IR were 4.93±0.48、2.42±0.53、2.28±0.36、7.64±0.72、2.14±0.31 and 8.16±0.67, respectively; follicle-stimulating hormone (FSH) levels were (5.14±0.56), (7.49±0.62), (7.62±0.71), (2.95±0.54), (7.83±0.76) and (2.71±0.43) IU·L-1, respectively; the superoxide dismutase (SOD) levels were (42.91±3.22), (56.45±4.16), (58.02±3.98), (32.16±2.85), (59.73±4.35) and (30.84±2.74) U·mg prot-1, respectively. The relative protein expression levels of Nrf2 were 0.67±0.08, 1.10±0.12, 1.12±0.13, 0.26±0.07, 1.13±0.14 and 0.24±0.06, respectively; HO-1 were 0.61±0.07, 1.06±0.08, 1.08±0.10, 0.18±0.05, 1.09±0.11 and 0.16±0.04, respectively. The malondialdehyde (MDA) levels were (2.47±0.33), (1.39±0.21), (1.30±0.19), (3.38±0.42), (1.21±0.26) and (3.62±0.47) nmol·mg prot-1, respectively. The number of ovarian antral follicles was 9.60±0.74, 4.30±0.57, 4.10±0.71, 14.20±0.98, 3.90±0.65 and 15.10±1.13, respectively. The ovarian granulosa cell apoptosis index was (16.27±1.16)%, (7.48±0.91)%, (7.19±0.76)%, (23.86±1.23)%, (6.94±0.85)% and (25.31±1.42)%, respectively. Compared blank group with the control group; compared model group with low-dose geniposide group, high-dose geniposide group and positive control group; compared low-dose geniposide group with high-dose geniposide group and compred high-dose geniposide group with high-dose geniposide+ML385 group, the differences of above indexes were all statistically significant (all P<0.05).

    Conclusion

    Geniposide can alleviate insulin resistance and oxidative stress damage in PCOS rats, possibly by activating the Nrf2/HO-1 signaling pathway.

  • Chang-yu XIA, Jia ZHOU, Ru-li FENG, Yan YAN, Lei HUANG
    Chinese Journal of Clinical Pharmacology. 2025, 41(21): 3001-3006.
    Objective

    To analyze the species distribution and antimicrobial resistance profiles of Acinetobacter baumannii complex (ABC) isolates from a Grade A tertiary hospital in Beijing (2017-2024), providing evidence for clinical microbiological identification and antimicrobial therapy.

    Methods

    ABC isolates were collected from the hospital’s antimicrobial resistance surveillance network. Species identification was performed by mass sectrometry and susceptibility testing was analyzed using WHONET 5.6. Statistical comparisons of resistance rates were performed with SPSS 26.0 (chi-square test).

    Results

    Among 2 752 non-repetitive ABC isolates,Acinetobacter baumannii (ABA) accounted for 91.75%, followed by Acinetobacter pittii (APT, 6.90%) and Acinetobacter nosocomialis (ANO, 1.31%). Sputum and urine were the predominant specimen types, with ABA and APT frequently isolated from bloodstream infections. The resistance profile varied statistically significantly defferences across the bacterial species for all 12 common antimicrobials (all P<0.05). Among these, ABA demonstrated the highest resistance rates, ANO showed an intermediate profile, and APT was the most susceptible. Specifically, ABA exhibited resistance rates exceeding 80% to β-lactam antibiotics, including piperacillin/tazobactam, ceftazidime, imipenem and meropenem. In contrast, ANO showed resistance rates of 30%-50%, and APT only 10%-30% to the same agents. Resistance profiles between ABA and ANO differed statistically significantly except for trimethoprim-sulfamethoxazole and minocycline (all P>0.05). The single Acinetobacter calcoaceticus isolate was only resistant to doxycycline and trimethoprim-sulfamethoxazole, while remaining susceptible to all other β-lactam and fluoroquinolone agents tested.

    Conclusion

    ABC species exhibit distinct clinical distributions and resistance patterns, emphasizing the need for accurate species identification and ongoing resistance surveillance to guide appropriate empirical therapy.