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  • Yao-wu CHEN, Zhi-xiang CHEN, Mao-wen WANG, Meng-li JI, Wen ZHANG, Jian-min FAN
    Chinese Journal of Clinical Pharmacology. 2025, 41(8): 1170-1174.
    Objective

    To analyze iron death genes and related pathogenesis in chronic thromboembolic pulmonary hypertension (CTEPH) based on bioinformatics, and to screen potential traditional Chinese medicine (TCM) active ingredients for treating CTEPH through iron death related pathways.

    Methods

    The differentially expressed genes in dataset GSE130391 were analyzed by R language, and the genes related to iron death were obtained from FerrDB database. The intersection of the two genes was selected, and the intersection genes were enriched by Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO). The intersection genes were analyzed by random forest algorithm, and the key genes were obtained. The immune infiltration analysis of GSE130391 was performed by cibesort algorithm. Potential TCM active ingredients were screened by cMAP database, and the binding stability and affinity of TCM active ingredients and key targets were analyzed by molecular docking and molecular dynamics simulation.

    Results

    A total of 878 DEGs were obtained, 264 iron death related genes and 14 intersection genes were obtained from FerrDB database. There were 630 items in GO enrichment analysis, and 13 pathways were enriched by KEGG. Three key genes were obtained by random forest algorithm. Immunoinfiltration analysis showed that dendritic cells and mast cells were inhibited in CTEPH group, and immunoinfiltration correlation showed that mast cells were strongly correlated with M1 macrophages, M1 macrophages were strongly correlated with T cells, and the key gene arachidonic acid 12-lipoxygenase 12R type (ALOX12B) was positively correlated with M2 macrophages. Cytokine signal transduction inhibitor 1 (SOCS1) was negatively correlated with M2-type macrophages. The active ingredients of traditional Chinese medicine were ononanthine and rotensin screened in cMAP database. Molecular docking and molecular dynamics simulation analysis showed that rotensin and ALOX12B had stable binding energy and strong affinity.

    Conclusion

    The therapeutic targets related to iron death in CTEPH are found by bioinformatics method and the active components of Chinese medicine that can be targeted for intervention are screened.

  • Chun-chun FANG, Feng-jie LIANG, Hui-hui SONG, You-hong SHEN, Yu-sheng HE, Xiao-fen LOU
    Chinese Journal of Clinical Pharmacology. 2025, 41(8): 1152-1156.
    Objective

    To study the bioequivalence of two formulations of haloperidol tablets in healthy Chinese subjects.

    Methods

    The randomized, open, single dose, two periods, crossover study design was adopted in the study. Twenty-eight healthy subjects were enrolled under fasting condition and given either test preparation or reference preparation 2 mg respectively in one period. After collecting plasma samples, the plasma concentrations of haloperidol were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated by WinNonlin 8.0 and the bioequivalence was evaluated using the average bioequivalence (ABE) method.

    Results

    The pharmacokinetic parameters of haloperidol of the test preparation or reference preparation were as follow: Cmax were (719.50±378.43) and (703.43±329.63) pg·mL-1, AUC0-t were (1.94×104±6 766.21) and (1.94×104±6 522.79) pg·h·mL-1, AUC0-∞ were (2.31×104±7 693.66) and (2.30×104±7 309.97) pg·h·mL-1. The 90% confidence intervals (CI) of the geometric mean ratio (GMR) were 92.46%-114.76%, 96.70%-108.15%, 96.36%-111.34% for Cmax, AUC0-t and AUC0-∞, respectively, which were within the acceptance criteria of 80.00%-125.00%.

    Conclusion

    The two preparations of haloperidol tablets were bioequivalent in Chinese healthy subjects.

  • Xiao-dan WU, Ya-nan TONG, Ying ZHAN, Wen-wen ZHANG, Zhi-guo WANG, Guo-xu ZHANG
    Chinese Journal of Clinical Pharmacology. 2025, 41(8): 1138-1143.
    Objective

    To investigate the effect of Acorus calamus L. on wound healing of radioactive skin injury in rats based on the mitogen-activated protein kinase (MAPK)/nuclear factor κB (NF-κB) signaling pathway.

    Methods

    A rat model of radioactive skin injury was induced by the radionuclide irradiation, the successful model rats were randomly divided into the model group, the control group, and the experimental -H, -M, -L groups with 12 rats in each group, and another 12 normal rats were taken as the normal group. Experimental-H, -M, -L goups was applied with Acorus calamus L. 600, 400, 200 g·kg-1, respectively. Control group was applied with triethanolamine cream 400 g·kg-1 on rat wounds; normal and model groups were treated with 0.9% NaCl. Six groups were treated once a day for 45 days. The healing rate of wounds was compared among the six groups. The levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in serum and hydroxyproline (HYP) in wound tissue were measured by enzyme linked immunosorbent assay. The protein levels of IL-1β, IL-6, TNF-α, mitogen-activated protein kinase (p38) and nuclear factor κB p65 subunit (p65) were detected by Western blot.

    Results

    The wound healing rates of experimental-H, -M, -L groups, control group and model group were (70.24±3.17)%, (62.41±4.52)%, (49.89±4.61)%, (50.35±2.44)% and (29.42±4.23)%, respectively. The levels of IL-1β in experimental-H, -M, -L groups, control group, model group and normal group were (41.22±2.98), (52.35±1.69), (61.32±2.74), (45.26±3.12), (79.24±5.64) and (28.85±2.11) pg·L-1; the levels of IL-6 were (25.68±1.65), (32.55±2.64), (51.23±2.34), (32.32±1.56), (61.12±2.35) and (18.88±1.12) pg·L-1; the levels of TNF-α were (62.38±5.66), (73.56±4.52), (88.63±5.68), (68.33±4.32), (112.48±6.52) and (55.21±3.89) pg·L-1; the levels of HYPs of (3.77±0.41), (3.51±0.26), (2.98±0.39), (3.62±0.37), (2.21±0.48) and (4.22±0.55) μg·mg-1; the relative expression levels of IL-1β were 0.31±0.04, 0.43±0.07, 0.60±0.03, 0.51±0.04, 0.69±0.06 and 0.11±0.07; the relative expression levels of IL-6 were 0.50±0.03, 0.60±0.04, 0.69±0.04, 0.62±0.07, 0.83±0.08 and 0.28±0.06; the relative expression levels of TNF-α were 0.49±0.06, 0.61±0.03, 0.73±0.06, 0.59±0.04, 0.83±0.05 and 0.28±0.04; the phosphorylated p38/p38 ratios were 0.46±0.06, 0.56±0.04, 0.67±0.03, 0.56±0.05, 0.84±0.04 and 0.34±0.08; the phosphorylated p65/p65 ratios were 0.37±0.06, 0.54±0.03, 0.63±0.04, 0.47±0.05, 0.79±0.04, and 0.32±0.06, respectively. Compared with model group, the above indexes in the experimental-H, -M groups were statistically significant (all P<0.05).

    Conclusion

    Acorus calamus L. can promote the healing of radioactive skin injury in rats, inhibit the inflammation level of the wound tissue, and promote collagen deposition, and its mechanism may be related to the regulation of MAPK/NF-κB pathway.

  • Xin-yi MA, Pan-pan XIE, Zhi-xing CHEN, Xi WENG, Ai-xin SHI
    Chinese Journal of Clinical Pharmacology. 2025, 41(8): 1164-1169.
    Objective

    To establish a pharmacodynamic model of sodium-glucose transporter 2 inhibitors (SGLT-2i) in order to evaluate the efficacy characteristics of the drugs.

    Methods

    A model-based meta-analysis was used. By searching randomized controlled trials of SGLT-2i monotherapy in patients with type 2 diabetes (T2DM) in databases, the change in glycosylated hemoglobin (HbA1c) from baseline was used as the efficacy indicator. The pharmacodynamic models of SGLT-2i and placebo were constructed, and the covariates were screened to determine the factors affecting the drug’s efficacy.

    Results

    A total of 39 studies were included, involving 96 trial groups, 8 534 participants, and 13 drugs (dapagliflozin, canagliflozin, empagliflozin, ipragliflozin, luseogliflozin, ertuglilfozin, enavogliflozin, henagliflozin, licogliflozin, sotagliflozin, bexagliflozin, janagliflozin and tofogliflozin). The time-effect relationships of the drug group and the placebo group were consistent with the Emax model, and fasting plasma glucose baseline had an effect on the pharmacodynamic parameters of SGLT-2i.

    Conclusion

    The final model can describe the pharmacodynamic characteristics of the drug and placebo groups, and there is a significant association between FPB baseline and drug efficacy.

  • Shan ZHOU, Hao LIU, Mei-juan KONG, Bei-pei KANG, Lu BAI, Ke ZHOU, Jia-yun LIU
    Chinese Journal of Clinical Pharmacology. 2025, 41(8): 1144-1151.
    Objective

    To analyze the antimicrobial sensitivity against clinical isolates in the first affiliated hospital of air force medical university in the past three years.

    Methods

    The nonduplicate clinical isolates were collected in 2021—2023, identification and drug sensitivity test were performed by using VITEK2-compact automatic bacteria identification system. The data was analyzed using WHONET 5.6 software and interpreted according to the Clinical and Laboratory Standards Institute (CLSI) 2023 breakpoints.

    Results

    A total of 20 536 clinical isolates were collected, of which 28.78% were gram-positive, 58.64% were gram-negative, 11.94% were fungi and 0.64% were anaerobe. The prevalence of methicillin-resistant strains in Staphylococcus aureus and coagulase-negative Staphylococcus were 49.11% and 73.06%, respectively. No Staphylococcus resistant to vancomycin, linezolid, or tigecycline was detected. The resistance rates of Enterococcus faecium to most antimicrobial agents were much higher than Enterococcus faecalis. 8 strains of vancomycin-resistant Enterococcus faecium were isolated, and a few linezolid-resistant strains were identiffed in both species. The prevalence of penicillin-susceptible Streptococcus pneumoniae (PSSP) was 95.85%. The resistance rate to carbapenems was 0.2% to 12.8% in Enterobacterales species, and the detection rate of carbapenem-resistant Enterobacteriaceae (CRE) was 6.6%, with Klebsiella pneumoniae accounting for 66.53%. The resistance rates of Acinetobacter spp to imipenem and meropenem were 75.3% and 76.7%, respectively. Meanwhile, the rates of Pseudomonas aeruginosa were 22.9% and 19.9% respectively.

    Conclusion

    The antimicrobial resistance of clinical isolates in our hospital is still serious. All relevant departments should strengthen the monitoring of bacterial resistance in order to curb the development and spread of bacterial resistance.

  • Jin-fen LI, Jun-jiang ZHU, Yuan-yuan LIU, Ji LUO, Xu-hui LIANG, Jian-ying XIAO
    Chinese Journal of Clinical Pharmacology. 2025, 41(8): 1126-1131.
    Objective

    To investigate the protective effect of icariin on recurrent spontaneous abortion (RSA) mice and its potential mechanism.

    Methods

    Female CBA/J mice were randomly divided into control group (mated with male BALB/c mice), model group (modeling mating with male DBA/2 mice), experimental-L group (after modeling, 25.00 mg·kg-1 icariin was given by intragastric administration), experimental-H group (50.00 mg·kg-1 icariin was given by intragastric administration after modeling), positive group (2.6 mg·kg-1 desdrogesterone was given by intragastream after modeling), uterine tissue was collected after 14 days of treatment for follow-up experiments. Embryo absorption rate was observed and recorded. The levels of interleukin (IL) -4 and interferon γ (IFN-γ) were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of Foxp3 and Toll-like receptor 4 (TLR4) were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Western blot assay was used to detect the expression of TLR4 and phosphorylated nuclear transcription factor-κB (p-NF-κB) protein.

    Results

    The absorption rates of mouse embryos in control group, model group, experimental-L group, experimental-H group and positive group were 7.37% (7 cases/95 cases), 37.33% (28 cases/75 cases), 20.93% (18 cases/86 cases), 13.79% (12 cases/87 cases) and 12.22% (11 cases/90 cases), respectively; IL-4 expression levels were (33.84±5.71), (10.71±2.34), (16.86±1.13), (26.91±3.04) and (19.56±1.79) pg·mL-1, respectively; the expression levels of IFN-γ were (25.97±1.40), (63.38±5.39), (47.23±6.78) (34.80±4.08) and (29.61±3.25) pg·mL-1, respectively; the relative expression levels of Foxp3 mRNA were 1.00±0.07, 0.57±0.05, 0.72±0.06, 0.90±0.05 and 0.66±0.06, respectively; the relative expression levels of TLR4 mRNA were 1.00±0.10, 2.32±0.17, 1.78±0.14, 1.40±0.08 and 2.05±0.26, respectively; the relative expression levels of TLR4 protein were 0.31±0.05, 0.90±0.11, 0.68±0.05, 0.55±0.05 and 0.79±0.10, respectively; the relative expression levels of p-NF-κB protein were 0.27±0.02, 0.82±0.13, 0.66±0.04, 0.42±0.05 and 0.75±0.09, respectively. The above indicators in the model group compared with the control group, the experimental-L and experimental-H groups were compared with the model group, and the differences were statistically significant (all P<0.05).

    Conclusion

    Icariin may play a protective role in improving RSA immune response by inhibiting TLR4/NF-κB pathway.

  • Ding-cai MA, Mao-mao WANG, Zhe WANG, Yu-gui ZHANG, Ting LIU, Fei-yun GAO, Yan-jun WANG, Zhuan-hong ZHANG, Yue-feng LI
    Chinese Journal of Clinical Pharmacology. 2025, 41(8): 1191-1195.

    Surgery, chemoradiotherapy are the conventional methods of clinical treatment of tumor, due to adverse reactions, drug resistance and other problems, the prognosis and survival are poor. Due to its characteristics of stable action with little toxic side effects and multi-channel and multi-target comprehensive regulation, traditional Chinese medicine has been widely concerned and recognized in anti-tumor. Autophagy and apoptosis are two ways of programmed cell death, and the interaction between autophagy and apoptosis is crucial to the overall fate of cancer cells. The balance between autophagy and apoptosis contains the theory of Yin and Yang in traditional Chinese medicine, and has become an effective strategy for clinical treatment of cancer. This study summarized the mechanism of the signaling pathway involved in the regulation of autophagy and apoptosis balance and thus effectively inhibited the pathological process of tumors, in order to provide pharmacological basis and scientific reference for the development and clinical application of traditional Chinese medicine anti-tumor drugs.

  • Hua-wei LI, Li ZHANG, Ji-liang WANG, Qing-qing SHEN, Li-jie LIU
    Chinese Journal of Clinical Pharmacology. 2025, 41(8): 1096-1101.
    Objective

    To explore the mechanism of prasugrel (PRAS) in alleviating oxidative stress of myocardial ischemia reperfusion (IR) by inducing pyroptosis of rat cardiomyocytes based on nuclear factor erythroid derived 2-like 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) signaling pathway.

    Methods

    SD rats were randomly divided into sham operation group (only the heart was exposed, no IR model was constructed, and the same amount of normal saline was injected into the stomach), model group (IR rat model was constructed, and the stomach was given an equal amount of 0.9% NaCl), the experimental-L group (model group rats were intragastric with 5 mg·kg-1 PRAS), the experimental-M group (model group rats were intragastric with 10 mg·kg-1 PRAS), and experimental-H group (model group rats were intragastric with 15 mg·kg-1 PRAS). The serum levels of myocardial injury markers and oxidative stress factors were detected by enzyme-linked immunosorbent assay. The relative expression levels of pyroptosis-related proteins and Nrf2/HO-1/NQO1 signaling pathway-related proteins in myocardial tissue were detected by Western blot.

    Results

    The contents of cardiac troponin Ⅰ (cTnⅠ) in sham operation group, model group, experimental-L group, experimental-M group and experimental-H group were (264.52±39.04), (558.40±101.68), (477.65±64.33), (429.71±75.94) and (313.84±52.26) pg·mL-1, respectively; the creatine kinase isoenzyme (CK-MB) levels were (0.68±0.11), (2.76±0.45), (1.92±0.27), (1.53±0.23) and (1.11±0.19) U·L-1, respectively; the levels of malondialdehyde (MDA) were (4.05±0.68), (10.12±1.74), (8.44±1.26), (6.79±1.05) and (5.47±1.02) nmol·L-1, respectively; the relative expression levels of nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) were 1.00±0.14, 2.16±0.32, 1.72±0.25, 1.54±0.28 and 1.28±0.21, respectively; the relative expression levels of Nrf2 were 1.00±0.15, 0.32±0.04, 0.39±0.05, 0.61±0.10 and 0.80±0.13, respectively. The above indexes of model group were compared with those of sham-operation group, and those of experimental-L, experimental-M and experimental-H groups were compared with those of model group (P<0.05, P<0.01, P<0.001).

    Conclusion

    PRAS may resist oxidative stress and reduce pyroptosis and apoptosis of myocardial cells by activating Nrf2/HO-1/NQO1 signaling pathway, thereby alleviating IR injury and protecting cardiac function.

  • Quan-yang LI, Ya-fang HAO, Guo-tai WU, Li-dong DU, Rui-qiong WANG
    Chinese Journal of Clinical Pharmacology. 2025, 41(8): 1108-1113.
    Objective

    To establish an animal model of polycystic ovary syndrome (PCOS) characterized by kidney deficiency and blood stasis, and to evaluate its efficacy.

    Methods

    SD rats were randomly divided into normal group, PCOS group, model group and formula counter-evidence group, with 10 rats in each group. The normal group was given 1 mg·kg-1 1% sodium carboxymethyl cellulose daily by intragastric administration; PCOS group was given 1 mg·kg-1 letrozole daily by intragastric administration; on the basis of PCOS group, the model group was injected subcutaneously with 0.6 mg·kg-1 epinephrine hydrochloride solution daily for 2 weeks from day 21. On the basis of the model group, the formula counter-evidence group was given 12.51 g·kg-1 Zhu’s Tiaojing decoction daily for 2 weeks from the 21st day. After 35 days of intervention, the indexes of ovarian index, testosterone, vitamin D and whole blood low shear rate were compared.

    Results

    The ovarian indexes of normal, PCOS, model and formula counter-evidence groups were (6.39±0.58)×10-4, (5.32±0.71)×10-4, (5.05±0.29)×10-4 and (8.17±0.65)×10-4; testosterone concentrations were (7.10±0.97), (9.22±0.43), (9.06±1.21) and (7.73±0.76) nmol·L-1; vitamin D levels were (1 850.98±227.95), (986.10±152.50), (1 220.67±64.35) and (1 598.20±294.75) pg·mL-1; whole blood low shear rates were (13.00±1.79), (13.37±0.54), (16.38±1.51) and (11.43±2.77) mPa·s, respectively. The above indexes in the model group were statistically significant compared with the formula counter-evidence group and the normal group (all P<0.05).

    Conclusion

    Letrozole combined with epinephrine hydrochloride can stably replicate the PCOS rat model with kidney deficiency and blood stasis syndrome.

  • Hui-na ZHANG, Min YU, Wei GU, Li-ping HOU, Li-rong CHENG
    Chinese Journal of Clinical Pharmacology. 2025, 41(8): 1114-1118.
    Objective

    To observe the protective effect of resveratrol on kidney of diabetic rats through lipid metabolism pathway.

    Methods

    The SD rats were randomly divided into control group, model group and experimental -L, -M, -H groups. The control group was fed with normal feed, while the other four groups were all based on high-fat and high-sugar feed feeding + intraperitoneal injection of streptozotocin to establish diabetic rat models. After successful modeling, the control group and the model group were given the same amount of normal saline, while the experimental-L, -M, -H groups were given 5, 25, 50 mg·kg-1 concentration of resveratrol once a day, and were given continuous gavage for 10 weeks. Kidney function levels [cystatin C (Cys-C), serum creatinine (SCr), blood urea nitrogen (BUN)]were determined by enzyme-linked immunosorbent assay. The expressions of peroxissome proliferator-activated receptor γ (PPARγ), fatty acid- binding protein (FABP1), peroxisomal acyl-coenzyme A oxidase 1 (ACOX) 2 and ACOX1 were detected by Western blot.

    Results

    The Cys-C levels of experimental -M, -H groups, control group, model group were (1.85±0.15), (1.39±0.11), (0.78±0.11) and (2.42±0.32) mg·L-1; SCr levels were (55.74±7.02), (48.15±6.97), (32.41±4.22) and (68.15±8.48) μmol·L-1; BUN levels were (10.37±1.02), (9.41±0.87), (7.12±1.12) and (14.48±2.45) mmol·L-1; the relative expression levels of PPARγ protein were 0.74±0.08, 0.92±0.10, 1.22±0.15 and 0.39±0.05; the relative expression levels of FABP1 protein were 0.64±0.08, 0.81±0.07, 0.98±0.09 and 0.30±0.05; the relative expression levels of ACOX2 protein were 0.59±0.06, 0.72±0.07, 0.85±0.13 and 0.27±0.05; the relative expression levels of ACOX1 protein were 0.58±0.06, 0.67±0.05, 0.78±0.06 and 0.24±0.03. The differences of above indexes were statistically significant between the experimental-M, -H groups and control group and the model group (all P<0.05).

    Conclusion

    Resveratrol may play a protective role on kidney of diabetic rats by regulating lipid metabolism pathway.