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  • Meng-fan FENG, Jin-xia YANG, Hong-hao LI, Xue-zhi ZHANG, Wei-wei LI
    Chinese Journal of Clinical Pharmacology. 2025, 41(5): 742-746.

    Olanzapine is a widely used atypical antipsychotic drug (AAPD) with proven efficacy in treating schizophrenia and bipolar disorder. However, it is also associated with the highest risk of metabolic disturbances among antipsychotic medications. Long-term use can significantly increase patients’ blood glucose and lipid levels, leading to adverse effects such as hypertension, diabetes, and obesity. There are multiple strategies to manage antipsychotic-induced obesity. In recent years, significant progress has been made in both clinical and basic research on the use of traditional Chinese medicine (TCM) to treat olanzapine-induced glucose and lipid metabolic disorders. Qi and blood disharmony is identified as the primary pathophysiological mechanism underlying olanzapine-induced drug-induced obesity and metabolic disturbances. Certain TCM monotherapies, herbal compound prescriptions, or acupuncture treatments used for managing obesity and regulating glucose and lipid metabolism have shown varying degrees of efficacy in counteracting olanzapine-induced glucose and lipid metabolic disturbances. This article summarizes the recent research findings on the use of TCM to antagonize olanzapine-induced drug-induced glucose and lipid metabolic disorders and obesity, aiming to provide a reference for the clinical application of treatments for olanzapine-induced metabolic disturbances and the development of new therapeutic agents.

  • Deng-yun CHEN, Yi-bo WU, Kun-bo HUANG, Han-hui ZHANG, Zhi-shan ZHANG, Zhi-peng HONG
    Chinese Journal of Clinical Pharmacology. 2025, 41(5): 671-675.
    Objective

    To investigate the effect of microRNA-183-5p (miR-183-5p) targeting RNA-binding motif single-stranded-interacting protein 1 (RBMS1) on autophagy and migration of breast cancer cells and its mechanism.

    Methods

    Human breast cancer cells MCF-7 were divided into control group, NC inhibitor group (transfected with NC inhibitor) and miR-183-5p inhibitor group (transfected with miR-183-5p inhibitor), miR-183-5p inhibitor+si-NC group (transfected with miR-183-5p inhibitor and empty vector si-NC), miR-183-5p inhibitor+si-RBMS1 group (transfected with miR-183-5p inhibitor and RBMS1 knockdown plasmid si-RBMS1). The expression levels of autophagy and phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) pathway-related proteins in each group were detected by Western blot, and the mobility of cells in each group was detected by scratch test.

    Results

    Control group, NC inhibitor group, miR-183-5p inhibitor group, miR-183-5p inhibitor+si-NC group and miR-183-5p inhibitor+si-RBMS1 group the relative expression levels of light chain 3 Ⅱ (LC3-Ⅱ)/light chain 3 Ⅰ (LC3-Ⅰ) protein were 0.29±0.03, 0.31±0.03, 0.86±0.10, 0.84±0.09 and 0.43±0.05, respectively; the relative expression levels of Beclin-1 protein were 0.18±0.02, 0.20±0.02, 0.74±0.08, 0.78±0.09 and 0.35±0.04, respectively; the relative expression levels of sequestosome-1 (P62) protein were 0.93±0.12, 0.89±0.10, 0.51±0.06, 0.54±0.06 and 0.86±0.10, respectively; the 48 h cell mobility was (62.87±7.26)%, (59.23±6.89)%, (24.13±3.49)%, (26.14±4.72)% and (40.11±5.71)%, respectively; the relative expression levels of phospho- (p-) PI3K/PI3K protein were 0.67±0.12, 0.64±0.10, 0.32±0.06, 0.35±0.06 and 0.74±0.09, respectively. The above indexes of miR-183-5p inhibitor+si-RBMS1 group were compared with those of miR-183-5p inhibitor+si-NC group, and those of miR-183-5p inhibitor group were compared with those of NC inhibitor group, and the differences were statistically significant (all P<0.05).

    Conclusion

    Inhibition of miR-183-5p expression can promote autophagy and inhibit cell migration in MCF-7 cells, while down-regulation of RBMS1 has the opposite effect, which is related to the PI3K/Akt/mTOR pathway.

  • Xian LIU, Ru-zhai QIN, Qi CHENG, Xue-yi CHEN, De-ping YI, He-yi HUANG, Zhi-hong XIE, Li-ka YE, Lian DUAN
    Chinese Journal of Clinical Pharmacology. 2025, 41(5): 706-711.
    Objective

    To study the pharmacokinetic profile of oseltamivir phosphate dry syrup in Chinese healthy subjects and to evaluate the bioequivalence and safety of the test formulation (T) and the reference formulation (R) under fasting and fed conditions.

    Methods

    In a randomized, open, two-agent, two-sequence, two-cycle, double-crossover trial design, 36 healthy subjects were enrolled in the fasting and fed groups, respectively, who received a single oral dose of 2.5 g of oseltamivir phosphate dry syrup of either the T or R. The blood concentrations of oseltamivir were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the pharmacokinetic parameters were calculated by using the WinNonlin (8.2) software and evaluated for bioequivalence and safety.

    Results

    Under fasting conditions, the Cmax of oseltamivir of the T and R were (64.40±17.50) and (64.10±20.90) ng·mL-1, AUC0-t were (142.76±43.64) and (151.60±35.10) h·ng·mL-1, AUC0-∞ were (147.67±37.60) and (153.05±35.30) h·ng·mL-1, respectively. Under fed conditions, the Cmax of oseltamivir of the T and R were (47.70±18.30) and (46.90±17.20) ng·mL-1, AUC0-t were (170.52±26.28) and (168.70±24.51) h·ng·mL-1, AUC0-∞ were (173.08±26.50) and (171.30±24.59) h·ng·mL-1, respectively. The 90% confidence intervals for the geometric mean ratios of Cmax, AUC0-t and AUC0-∞ for the T and R fell in the range of 80.00% to 125.00% for both the fasting and fed groups. Adverse drug reaction rates were 27.78% and 44.44% in the fasting and fed groups, respectively.

    Conclusion

    Two kinds of oseltamivir phosphate dry syrups were bioequivalent and had favorable safety profiles in Chinese healthy subjects in both fasted and fed states.

  • Wei ZHAO, Xue-min HAN, Shi-yao SUI, Xiu-ting MEN
    Chinese Journal of Clinical Pharmacology. 2025, 41(5): 631-635.
    Objective

    To observe the influence of propofol injection emulsion combined with esketamine injection on hemodynamics and postoperative recovery quality in elderly patients after lower limb arthroplasty.

    Methods

    The elderly patients undergoing lower limb joint replacement were divided into low-dose group (0.25 mg·kg-1 esketamine), high-dose group (0.50 mg·kg-1 esketamine) and control group (equal volume of 0.9% NaCl) according to the cohort method. Hemodynamics [heart rate (HR), mean arterial pressure (MAP)], postoperative recovery quality scale-15 (QoR-15) scores, dosages of anesthetic drugs, Ramsay sedation score, recovery quality and adverse reactions were compared among the three groups.

    Results

    In this study, 39 cases were enrolled in the low-dose group, 40 cases in the high-dose group and 42 cases in the control group. The HR of patients in low-dose group, high-dose group and control group immediately after operation (T1) was (76.39±5.77), (77.16±5.24) and (73.21±4.79) beat·min-1, respectively; MAP values were (85.11±5.22), (85.21±5.37) and (82.79±4.86) mmHg, respectively; at 15 min after operation, the HR of T2 were (78.36±5.11), (78.24±5.02) and (80.67±4.57) beat·min-1; the MAP were (85.75±5.11), (85.39±4.97) and (87.93±3.67) mmHg, respectively; the QoR-15 scores 24 h after operation were (108.19±10.29), (109.56±10.12) and (99.66±10.21) points, respectively; the dosage of propofol were (220.66±25.19), (211.66±27.88) and (283.37±26.28) mg, respectively; the dosage of remifentanil were (2.37±0.42), (2.24±0.38) and (2.89±0.35) mg, respectively; Ramsay sedation scores were (1.56±0.27), (1.61±0.22) and (1.58±0.24) points at T0; and (3.18±0.33), (3.29±0.34) and (2.67±0.29) points at T3, respectively. Compared with the control group, there were statistically significant differences in the above indexes between the low-dose group and the high-dose group (all P<0.05), while there were no statistically significant differences in the above indexes between the low-dose group and the high-dose group (all P>0.05). Adverse drug reactions included respiratory depression, nausea/vomiting, dizziness, restlessness, hypotension, etc. The total incidence of adverse drug reactions were 2.56% (1 case /39 cases) in the low-dose group, 15.00% (6 cases/40 cases) in the high-dose group, and 26.19% (11 cases /42 cases) in the control group. The total incidence of adverse drug reactions of low-dose group was significantly lower than the control group, and the difference was statistically significant (P<0.05).

    Conclusion

    The application of propofol combined with esketamine can reduce the intraoperative dosages of propofol and remifentanil in elderly patients undergoing knee arthroplasty, enhance the sedation effect, improve the hemodynamics, and promote the postoperative recovery.

  • Qi CHEN, Qun-yi PENG, Yan HAN, Li-de WU
    Chinese Journal of Clinical Pharmacology. 2025, 41(5): 681-685.
    Objective

    To study the effect of tazemetostat on the stemness of diffuse large B-cell lymphoma and the related mechanism of action.

    Methods

    OCI-LY3 cells were divided into blank group, tazemetostat group and microRNA-378a-3p (miR-378a-3p) mimics group. Blank group cell conventional culture; tazemetostat group was treated with 5 μmol·L-1 tazemetostat; miR-378a-3p mimics group was transfected with miR-378a-3p mimics. The relative expression level of miR-378a-3p was detected by fluorescence in situ hybridization. mRNA expression levels of dryness related factors were detected by quantitative real time polymerase chain reaction; the expression of signal pathway-related proteins was detected by Western blot.

    Results

    The relative expression levels of miR-378a-3p in blank group and tazemetostat group were 1.00±0.14 and 0.52±0.08, respectively, the difference was statistically significant (P<0.001). The relative expression of octamer binding transcription factor 4 mRNA in blank group, tazemetostat group and miR-378a-3p mimics group were 1.00±0.16, 0.21±0.06 and 0.49±0.08, respectively; the relative expression of sex determining region Y box protein 2 mRNA were 1.00±0.09, 0.39±0.05 and 0.85±0.11, respectively; the relative expression of Nanog homeobox mRNA were 1.00±0.13, 0.17±0.03 and 0.65±0.10, respectively; the relative expressions of Kruppel like factor 4 mRNA were 1.00±0.10, 0.28±0.05 and 0.86±0.14, respectively; the relative expressions of Yes associated protein were 1.00±0.19, 3.46±0.52 and 2.14±0.36, respectively; the relative expression of transcriptional coactivator with PDZ-binding motif protein were 1.00±0.14, 1.90±0.35 and 1.51±0.33, respectively. The above indexes of tazemetostat group were compared with those of blank group, and the above indexes of miR-378a-3p mimics group were compared with those of tazemetostat group, the differences were statistically significant (P<0.001, P<0.05).

    Conclusion

    Tazemetostat can inhibit the stemness of OCI-LY3 cells by down-regulating the level of miR-378a-3p, which may be achieved through the Yes associated protein/transcriptional coactivator with PDZ-binding motif signaling pathway.

  • Xian-da XIE, Dai-rong TANG, Qin ZOU, Xiang-wen CHEN, Zhe CHEN, Xiong YAN, Xiang-ping LIAO
    Chinese Journal of Clinical Pharmacology. 2025, 41(5): 636-640.
    Objective

    To investigate the clinical effect of cinacalcet in the treatment of secondary hyperparathyroidism (SHPT) in patients undergoing hemodialysis for chronic kidney disease (CKD).

    Methods

    Patients who underwent hemodialysis for CKD and had SHPT were divided into the control group and the treatment group according to the cohort method. The control group was treated with 0.25 μg of calcitriol capsules once a day via oral administration. On this basis, the treatment group was treated with 25 mg of cinacalcet tablets once a day via oral administration. Patients in both groups were treated for 12 weeks. Clinical efficacy, parathyroid volume, parathyroid function [serum phosphorus, serum calcium, alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH)], and cardiovascular function [creatine kinase-MB (CK-MB), hypersensitive troponin Ⅰ (hs-cTnⅠ) and myoglobin (MYO)]were compared between the two groups. Safety was evaluated.

    Results

    Sixty-two cases were enrolled in the treatment group and fifty-eight cases in the control group. After treatment, the total effective rates in the treatment group and the control group were 93.55% (58 cases/62 cases) and 77.59% (45 cases/58 cases), with statistically significant difference (P<0.05). After treatment, serum phosphorus levels in the treatment group and the control group were (1.31±0.16) and (1.50±0.34) mmol·L-1; serum calcium levels were (2.63±0.91) and (2.25±0.72) mmol·L-1; ALP levels were (83.28±8.40) and (126.46±12.39) U·L-1; iPTH levels were (215.32±16.69) and (307.65±20.14) pg·mL-1. The differences were statistically significant (all P<0.05). After treatment, the length of the parathyroid gland in the treatment group and the control group were (0.58±0.10) and (0.77±0.19) cm; width were (0.34±0.08) and (0.45±0.16) cm; thickness were (0.25±0.05) and (0.33±0.15) cm; volume were (0.82±0.15) and (1.13±0.22) cm3. The differences were statistically significant (all P<0.05). After treatment, serum CK-MB levels in the treatment group and the control group were (4.18±0.73) and (6.53±1.26) ng·mL-1; hs-cTnⅠ levels were (0.04±0.01) and (0.07±0.03) ng·mL-1; MYO levels were (70.69±9.41) and (112.39±12.60) ng·mL-1. The differences were statistically significant (all P<0.05). The adverse drug reactions in the treatment group and the control group mainly included nausea and vomiting, increased blood pressure, and myalgia. The total incidence of adverse drug reactions in the treatment group and the control group were 8.06 % (5 cases / 62 cases) and 22.41% (13 cases / 58 cases), respectively, and the difference was statistically significant (P<0.05).

    Conclusion

    Cinacalcet is effective in the treatment of SHPT in patients undergoing hemodialysis for CKD. It can reduce parathyroid gland volume, maintain calcium and phosphorus metabolism, and protect cardiovascular function, with high safety.

  • Jia FANG, Ya XIE
    Chinese Journal of Clinical Pharmacology. 2025, 41(5): 616-620.
    Objective

    To observe the clinical efficacy of nilapalil toluene sulfonate capsules, bevacizumab injection, and their combination therapy for ovarian cancer, and to assess their impact on serum biomarkers and ovarian blood flow parameters.

    Methods

    Ovarian cancer patients were divided into three groups according to a cohort methods: Control A group, control B group, and combined group. Control A group received nilapalil toluene sulfonate capsules, 300 mg once daily for 21 days per cycle. Control B group received bevacizumab injection 7.5 mg·kg-1, administered every 3 days for 21 days per cycle. The combined group received both nilapalil toluene sulfonate capsules and bevacizumab injection following the same regimen as the control groups. All groups underwent 4 cycles of treatment. Clinical efficacy, serum tumor biomarkers, ovarian blood flow parameters, adverse drug reactions, and patient survival were compared across the three groups.

    Results

    A total of 31 patients in control A group, 28 patients in control B group, and 41 patients in the combined group were included. After treatment, the total effective rates for control A group, control B group, and the combined group were 70.97% (22 cases/31 cases), 71.43% (20 cases /28 cases) and 92.68% (38 cases /41 cases), respectively. The combined group showed a significantly higher effective rate compared to both control A group and control B group (all P<0.05). After treatment, the serum levels of carcinoembryonic antigen (CEA) in control A group, control B group, and the combined group were (15.26±2.33), (14.89±2.34) and (9.74±1.21) μg·L-1, respectively; and the pulsatility index (PI) were 1.35±0.24, 1.39±0.21 and 1.82±0.32, respectively. The combined group showed significant differences in these parameters compared to both control A group and control B group (all P<0.05). Adverse drug reactions in control A group mainly included gastrointestinal reactions, hair loss, and proteinuria; control B group had gastrointestinal reactions, hair loss, and muscle pain; and the combined group experienced gastrointestinal reactions, hair loss, proteinuria, and muscle pain. The overall adverse drug reaction rates in control A group, control B group, and the combined group were 25.81% (8 cases /31 cases), 25.00% (7 cases /28 cases) and 26.38% (11 cases /41 cases), respectively, with no significant difference between the groups (all P>0.05). After 12 months of follow-up, the survival rates for control A group, control B group, and the combined group were 70.97% (22 cases /31 cases), 67.86% (19 cases /28 cases) and 90.24% (37 cases /41 cases), respectively. The survival rate of the combined group was significantly higher than that of control A group and control B group (all P<0.05).

    Conclusion

    The combination of nilapalil toluene sulfonate capsules and bevacizumab injection in the treatment of ovarian cancer effectively reduces serum biomarker levels, improves ovarian blood flow parameters, has a low incidence of adverse drug reactions, high safety, and significantly improves patient survival.

  • Yao-yao LIU, Feng XUE, Yun LI
    Chinese Journal of Clinical Pharmacology. 2025, 41(5): 646-653.
    Objective

    To evaluate the in vitro antibacterial activity of cefteram against common clinically isolated bacteria in the past three years.

    Methods

    The clinical isolates were collected and the minimal inhibitory concentration (MICs) were determined by the microdilution method.

    Results

    A total of 484 pathogenic bacteria over the period 2021-2023 were studied. The results show that cefteram has good antibacterial activity against Streptococcus spp other than penicillin-resistant Streptococcus pneumoniae (MICs of penicillin ≥ 2 mg·L-1), MIC90 value of cefteram was less than or equal 1 mg·L-1, and the susceptibility rate was 100.0%, which was similar to penicillin, slightly better than cefpodoxime, better than cefuroxime, cefixime, cefaclor and cefalexin. Against gram-negative bacteria, cefteram also showed better antibacterial activity, especially against β-lactamase (ESBLs) negative Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Haemophilus influenzae, and Moraxella catarrhalis. The MIC90 value of cefteram was ≤ 2 mg·L-1, and the susceptibility rate was 100.0%. Especially for Hemophilus influenzae, cefteram was better than all comparator agents, were comparable to cefpodoxime, better than cefuroxime, cefaclor and cefalexin. For Peptostreptococcus spp., cefteram was comparable to cefuroxime, better than all compared agents.

    Conclusion

    Cefteram had a wide and balanced antibacterial against clinical isolatied of gram-negative bacteria, gram-positive bacteria and anaerobic bacteria in China in recent years. Cefteram also showed better antibacterial activity, especially against penicillin intermediate and ampicillin-resistant Hemophilus influenzae, and is a good variety among oral cephalosporins.

  • Jia HE, Dong-yan KONG
    Chinese Journal of Clinical Pharmacology. 2025, 41(5): 701-705.
    Objective

    To study the effect and mechanism of galangin in improving depression-like behavior in vascular dementia (VD) mice through microRNA-134 (miRNA-134).

    Methods

    Seventy C57BL/6J mice were randomly divided into sham group (0.9% NaCl), model group (0.9% NaCl), low-dose group (25 mg·kg-1 galangin), medium-dose group (50 mg·kg-1 galangin), high-dose group (100 mg·kg-1 galangin), and mimic NC group (100 mg·kg-1 galangin and mimic NC 15 nmol), miRNA-134 mimic group (100 mg·kg-1 galangin and miRNA-134 mimic 15 nmol). The degree of depression was detected by tail suspension test and forced swimming test; the level of corticosterone was detected by enzyme-linked immunosorbent assay; the level of miRNA-134 was detected by quantitative real time polymerase chain reaction; the apoptosis rate of brain tissue cells was detected by TdT-mediated dUTP nick-end labeling; and the level of synaptic plasticity related protein was detected by Western blot.

    Results

    The suspension time of the sham group, the model group and the high-dose group were (105.32±15.22), (185.32±24.62) and (112.65±15.08) s, respectively; the swimming time were (86.52±13.25), (152.32±22.22) and (96.22±16.35) s respectively; the levels of corticosterone were (32.65±5.02), (86.62±14.32) and (48.52±5.55) ng·L-1, respectively; the levels of miRNA-134 were 1.00±0.12, 2.32±0.35 and 1.21±0.18, respectively. The apoptosis rates of the sham group, model group, high group, mimic NC group and miRNA-134 mimic group were (5.32±0.62)%, (62.33±8.65)%, (14.32±1.78)%, (15.85±2.22)% and (43.21±7.05)%, respectively; synaptophysin protein levels were 1.00±0.18, 0.32±0.05, 0.88±0.12, 0.82±0.11 and 0.30±0.05, respectively; the postsynaptic density protein-95 protein levels were 1.00±0.14, 0.61±0.07, 0.72±0.09, 0.70±0.08 and 0.45±0.06, respectively. The above indexes in the model group were compared with those in the sham group, those in the high-dose group were compared with those in the model group, and those in the miRNA-134 mimic group were compared with those in the mimic NC group, and the differences were statistically significant (all P<0.05).

    Conclusion

    Galangin may improve the depression-like behavior of VD mice by inhibiting the expression of miRNA-134, improving synaptic plasticity and inhibiting cell apoptosis.

  • Dan-feng WANG, Jian-gang LÜ, Lan SUN
    Chinese Journal of Clinical Pharmacology. 2025, 41(5): 641-645.
    Objective

    To observe the clinical efficacy and safety of recombinant epidermal growth factor (rhEGF) gel combined with gelatin sponge application under ear endoscopy in the treatment of traumatic tympanic membrane perforations.

    Methods

    Patients with traumatic tympanic membrane perforations were divided into control group and treatment group using cohort method. The control group received intravenous infusion of clindamycin phosphate injection (0.9 g, once daily). The treatment group received rhEGF gel (1 drop per dose, twice daily) combined with gelatin sponge application under ear endoscopy. Both groups received treatment for 1 week. The clinical efficacy, inflammatory markers [white blood cell count (WBC), C-reactive protein (CRP)], hearing status, and safety were compared between the two groups.

    Results

    A total of 37 patients in the control group and 43 patients in the treatment group were enrolled. The overall treatment efficacy in the treatment and control groups were 95.35% (41 cases /43 cases) and 78.38% (29 cases/37 cases), respectively, with statistically significant difference (P<0.05). After treatment, the WBC levels in the treatment and control groups were (7.74±1.47) and (10.68±1.64) × 10·L-1, respectively; the CRP levels were (3.37±0.97) and (6.35±1.01) pg·mL-1, respectively; the air conduction hearing thresholds were (25.64±2.13) and (29.68±2.24) dB HL, respectively; and the air-bone conduction gap were (6.54±1.24) and (12.36±2.47) dB, respectively. The treatment group showed statistically significant differences in all these indicators compared to the control group (all P<0.05). The adverse drug reactions in the treatment group, the main adverse drug reaction was infection, while in the control group mainly included infection and re-perforation. The incidence of adverse drug reactions in the treatment and control groups were 4.65% (2 cases /43 cases) and 10.81% (4 cases /37 cases), respectively, with no significant difference (P>0.05).

    Conclusion

    The clinical efficacy of treating patients with traumatic tympanic membrane perforation by combining rhEGF gel with absorbable gelatin sponge patch is better than that of conservative treatment. It has a low incidence of adverse drug reactions and high safety.