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  • Xiu-lin GAO, Li-qing ZHANG, Wei-feng LU
    Chinese Journal of Clinical Pharmacology. 2025, 41(1): 60-64.
    Objective

    To investigate the protective effect of astaxanthin (ASTA) on gouty chondrocyte injury induced by monosodium urate crystal (MSU) and its mechanism.

    Methods

    The gout cell model by sodium urate crystals was established. C-28I2 cells were randomly divided into blank group (conventional culture), model group (200 μg·mL-1 MSU), experimental-L group (200 μg·mL-1 MSU+20 μmol·mL-1 ASTA), experimental-H group (200 μg·mL-1 MSU+40 μmol·L-1 ASTA), experimental-H+Vector group (transfected with Vector +200 μg·mL-1 MSU+40 μmol·L-1 ASTA), experimental-H+NLRP3 group (transfected with NLRP3 plasmid +200 μg·mL-1 MSU+40 μmol·L-1 ASTA). Cell counting kit-8 (CCK-8) assay was used to detect the cell proliferation rate; Western blot assay was used to detect the expression of related proteins; the levels of Hyp and GAG were detected by enzyme-linked immunosorbent assay (ELISA).

    Results

    The cell proliferation rate of blank group, model group, experimental-L group and experimental-H group were (100.00±5.40)%, (67.41±4.52)%, (72.69±5.05)% and (81.47±7.73)%, respectively. The above indicators showed statistically significant differences between the model group and the blank group, between the experimental-L, experimental-H groups and the model group (all P<0.05). Nucleotide binding oligomeric domain-like receptor protein 3 (NLRP3) protein expression levels in blank group, model group, experimental-L group, experimental-H group, experimental-H+Vector group and experimental-H+NLRP3 group were 0.44±0.04, 0.86±0.06, 0.72±0.10, 0.52±0.03, 0.51±0.03 and 1.13±0.10, respectively; the expression levels of cleaved Caspase-1 (Cl-caspase-1) protein were 0.33±0.05, 0.73±0.08, 0.61±0.07, 0.42±0.04, 0.39±0.04 and 0.70±0.06, respectively; the mature interleukin (m-IL)-1β protein expression levels were 0.26±0.03, 0.91±0.05, 0.70±0.11, 0.57±0.08, 0.58±0.06 and 0.79±0.08, respectively; the Hyp levels were (1.95±0.22), (3.33±0.25), (2.53±0.18), (2.22±0.21), (2.24±0.20) and (3.25±0.38) μg·mL-1, respectively; the GAG levels were (2.30±0.20), (3.71±0.26), (3.29±0.33), (2.90±0.16), (2.97±0.24) and (3.50±0.34) ng·mL-1, respectively. The above indicators showed statistically significant differences between the model group and the blank group, between the experimental-L, experimental-H groups and the model group, between the experimental-H+NLRP3 group and the experimental-H+Vector group (all P<0.05).

    Conclusion

    Astaxanthin can regulate NLRP3 to play an anti-inflammatory role and has a protective effect on MSU-induced gouty cartilage injury.

  • Xin YANG, Xue-kun CAI, Ze-long WU, An-tao CHEN, Zi-hao CHEN, Xuan XIE, Jia-kang OU, Zhao-qi HUANG
    Chinese Journal of Clinical Pharmacology. 2025, 41(1): 71-75.
    Objective

    To study the expression characteristics of osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK) system and the relationship with fibrosis in myocardial tissues of rats with chronic heart failure.

    Methods

    SD rats were randomly divided into sham-operation group (12 rats) and model group. In sham-operation group, surgical thread was passed through the abdominal aorta without constricting it after laparotomy; in model group, establish the heart failure model by abdominal aorta coarctation. The successful model rats were randomly divided into model 1 week (12 rats), model 2 weeks (11 rats), model 4 weeks (11 rats), model 8 weeks (11 rats) and model 12 weeks groups (11 rats). The end point of the study is at week 12. The contents of hydroxyproline (HYP), total myocardial collagen and collagen volume fraction (CVF) were compaired in all proups. The expression levels of OPG, RANKL and RANK proteins in cardiomyocytes were determined by Western blot.

    Results

    The contents of HYP in sham-operation, model 1 week, model 2 weeks, model 4 weeks, model 8 weeks and model 12 weeks group were (0.25±0.04), (0.37±0.05), (0.45±0.04), (0.60±0.05), (0.82±0.10) and (1.03±0.07) μg·mg-1; the total myocardial collagen contents were (1.87±0.31), (2.73±0.38), (3.36±0.31), (4.47±0.37), (6.08±0.74) and (7.67±0.49) μg·mg-1; the CVF were (1.95±0.23)%, (2.40±0.25)%, (3.65±0.25)%, (5.43±0.29)%, (6.97±0.36)% and (9.38±0.49)%; the relative expression levels of OPG protein were 0.64±0.07, 0.80±0.07, 1.02±0.07, 1.32±0.11, 2.13±0.12 and 2.84±0.16; the relative expression levels of RANKL protein were 0.71±0.08, 1.06±0.07, 1.53±0.07, 2.62±0.12, 4.46±0.14 and 6.11±0.16; the relative expression levels of RANK protein were 0.30±0.05, 0.45±0.05, 0.63±0.06, 0.98±0.07, 1.43±0.10 and 1.63±0.10. With the extention of time, the above indexs of all model groups were significantly higher than those in the sham-operation group (all P<0.05). There were positive linear correlation between the relative expression levels of OPG, RANKL, RANK protein and the levels of CVF and total contents in cardiomyocytes of rats with chronic heart failure (all P<0.01).

    Conclusions

    In the process of chronic heart failure, the expression of OPG/RANKL/RANK axis is obviously enhanced, in which the up-regulation of RANKL level is most obvious. The expression level of OPG/RANKL/RANK is positively correlated with CVF and total myocardial collagen content.

  • Hao WANG, Qing-qing LIU
    Chinese Journal of Clinical Pharmacology. 2025, 41(1): 36-39.
    Objective

    To investigate the effect of subanesthetic dose esketamine hydrochloride injection combined with midazolam injection on hip replacement in elderly patients.

    Methods

    The elderly patients undergoing hip replacement were divided into control group and treatment group. The control group was given 0.02 mg·kg-1 midazolam injection; the treatment group was given 0.02 mg·kg-1 midazolam injection combined with 0.25 mg·kg-1 esketamine hydrochloride injection. Anesthesia (sedation, analgesic effect), hemodynamic indexes, and safety evaluation.

    Results

    There were 90 cases in the treatment group and 90 cases in the control group. The scores of sedation in the treatment group and the control group were (1.54±0.28) and (1.67±0.35) points, respectively; the scores of pain simulation at 2 h after operation were (3.16±0.47) and (3.38±0.59) points, respectively; at the end of the operation, the mean arterial pressure of the treatment group and the control group were (83.06±2.47) and (82.15±2.94) mmHg, respectively; the heart rate were (82.04±3.25) and (80.75±3.32) time·min-1, respectively, and the difference was statistically significant (all P<0.05). The total incidence of adverse drug reactions in the treatment group and the control group was 8.89% (8 cases /90 cases) and 13.33% (12 cases /90 cases), respectively, with no statistical significance (P>0.05).

    Conclusion

    The subanesthetic dose of esketamine hydrochloride injection combined with midazolam hydrochloride injection can effectively stabilize the hemodynamic level of the body and reduce postoperative pain in elderly patients with hip replacement with good safety.

  • Hong WANG, Lu-fan SHEN, Rui-ling MA, Ming-shuang HOU, Hong-ying LÜ, Guan-jun JIA, Lin YI
    Chinese Journal of Clinical Pharmacology. 2025, 41(1): 121-126.

    Hypertensive nephropathy is one of the common chronic kidney diseases in China, the morbidity and mortality are increasing year by year, which seriously endangers the physical and mental health of patients. Traditional Chinese medicine believes that human is an organic whole, the five viscera and six organs are closely related in physiology and pathology, based on the theory of “holistic concept”, the application of Chinese medicine in the treatment of hypertensive nephropathy can effectively improve kidney function and reduce the occurrence of adverse reactions. Therefore, based on the theory of “five viscera in one”, this paper summarizes the etiology and pathogenesis of hypertensive nephropathy and the treatment of hypertensive nephropathy from the five aspects of liver, heart, spleen, lung and kidney, aiming to provide new ideas for the prevention and treatment of kidney disease by traditional Chinese medicine.

  • Zi-qiao CHEN, Xia CHEN
    Chinese Journal of Clinical Pharmacology. 2025, 41(1): 137-142.

    Hemophilia is a rare monogenic inherited coagulation factor deficiency disease, which begins in early childhood, and severe patients often have a history of spontaneous bleeding or joint muscle bleeding, requiring long-term frequent transfusion of clotting factor. This article reviews the clinical development process of bispecific antibody drug EMICIZUMAB and two gene therapies ROCTAVIAN and HEMGENIX for the corresponding hemophilia subtypes, so as to summarize the strategies for rare disease drug development and the key elements of gene therapy drug development, and to provide reference for the development of similar drugs in similar indications in the future.

  • Yu-shan NING, Tao-hua SUN, An-jin CHEN, Rong WEI
    Chinese Journal of Clinical Pharmacology. 2025, 41(1): 96-99.

    The active ingredient of WINREVAIR, sotatercept-csrk, is a recombinant activin receptor IIA-Fc (ActRIIA-Fc) fusion protein that improves pro-proliferation (ActRIIA/Smad2/3-mediated) and anti-proliferation (BMPRII/Smad1/5/8-mediated) signals, thereby regulating vascular proliferation. In March 2024, WINREVAIR was approved by the U.S. Food and Drug Administration for the treatment of pulmonary arterial hypertension (PAH) in adults. Clinical studies have shown that WINREVAIR can improve exercise capacity and reduce the incidence of all-cause death or clinical worsening of PAH by 84%. Common adverse drugreactions include headache, epistaxis, rash, etc.

  • Zhao-yue LIU, Hui-fang YAN, Shan-shan JIN
    Chinese Journal of Clinical Pharmacology. 2025, 41(1): 16-20.
    Objective

    To observe the clinical efficacy and safety of dexamethasone injection combined with tranexamic acid injection in the treatment of patients with hyperfibrinolysis caused by bleeding after prostatic hyperplasia.

    Methods

    Patients with hyperfibrinolysis caused by hemorrhage after prostatic hyperplasia were randomly divided into control group and treatment group. The control group was given 1 g·d-1 tranexamic acid intravenously. On the basis of the control group, the treatment group was given dexamethasone 10 mg, intravenous injection, q12 h. Both groups were treated continuously for 5 days. The clinical efficacy, coagulation factor level, quality of life (QOL) score, international prostate symptom score (IPSS), and safety were compared between the two groups.

    Results

    In the treatment group, 52 cases were enrolled, 2 cases fell off, and finally 50 cases were included in the statistical analysis. In the control group, 51 cases were enrolled, 1 case fell off, and finally 50 cases were included in the statistical analysis. After treatment, the total effective rates of treatment group and control group were 94.00% (47 cases /50 cases) and 72.00% (36 cases /50 cases), respectively, and the difference was statistically significant (P<0.05). After treatment, the partial thromboplastin time of treatment group and control group were (35.12±4.38) and (49.14±5.61)s; the prothrombin time were (12.78±1.67) and (16.10±1.94) s; D-dimer levels were (350.42±25.90) and (380.90±37.10) μg·L-1; QOL scores were (1.16±0.37) and (2.26±0.78) points, IPSS were (4.48±1.22) and (16.12±3.67) points, respectively. The differences of above indexes were statistically significant between two groups (all P<0.05). The adverse drug reactions of two groups were mainly abdominal pain, anemia and headache. The incidences of total adverse drug reactions in treatment group and control group were 6.00% and 16.00%, respectively, without statistical significance (P>0.05).

    Conclusion

    Dexamethasone injection combined with tranatemylic acid injection has a definitive clinical efficacy in the treatment of patients with bleeding induced hyperfibrinolytic hyperplasia after prostatic hyperplasia, which can significantly improve the coagulation function of patients, relieve symptoms, without increasing the incidence of adverse drug reactions.

  • Si-qi KONG, Juan CHUAN, Jin-tian LI, Jian-qing LIANG, Yi ZHANG
    Chinese Journal of Clinical Pharmacology. 2025, 41(1): 100-104.

    Non-small cell lung cancer (NSCLC) constitutes the largest portion of lung cancer overall, with high incidence and mortality rates. Apoptosis, is a hot focus in the clinical treatment of NSCLC, its main pathways include the extrinsic death receptor pathway, intrinsic mitochondrial apoptosis pathway and endoplasmic reticulum stress pathway, collectively regulating the cellular apoptosis process. Traditional Chinese medicine (TCM) has significant efficacy in the treatment and prognosis of NSCLC, with advantages such as boosting the body’s resistance and less adverse drug reactions. Studies have shown that various individual Chinese herbal medicines and compound formulas can treat NSCLC through the apoptosis pathway, alleviating the adverse drug reaction of radiotherapy and chemotherapy. Based on this, this article summarizes recent domestic and international literature, focusing on apoptosis, to summarize the research progress of TCM in treating NSCLC by regulating apoptosis, aiming to provide reference for clinical treatment for NSCLC.

  • Ying SUN, Xin SONG, Jia WANG, Yan-fang HOU, Qun FU, Qi ZHANG, Jie LAI, Tao GENG, Chang-xin LI, Jia-hui HUO, Ying ZHANG, Yan WENG
    Chinese Journal of Clinical Pharmacology. 2025, 41(1): 1-5.
    Objective

    To compare the effects of different doses of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet in the treatment of cough variant asthma (CVA) and the improvement of airway function and inflammatory factors.

    Methods

    Elderly patients with cough variant asthma were randomly divided into group A and group B. Both groups of patients received budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet. Group A was given budesonide and formoterol fumarate powder for inhalation(Ⅱ), 2 inhalation per time, twice a day; Group B was given budesonide and formoterol fumarate powder for inhalation, 4 inhalation per time, twice a day; budesonide fumatrol inhalation powder mist for continuous treatment for 6 months, and montelukast sodium tablet 10 mg once a day for at least 3 months. The nighttime cough scores of the two groups were compared before treatment and after treatment. The percentage of forced expiratory volume in one second (FEV1) in the predicted value, the maximum mid expiratory flow (MMEF), the fractional exhaled nitric oxide (FeNO), interleukin-5 (IL-5) and eosinophils were compared between the two groups. The incidence of adverse drug reactions and the recurrence rate within 1 year were compared between the two groups.

    Results

    A total of 45 cases were enrolled in both the group A and the group B. At 9 months after treatment, the nocturnal cough scores of the group A and the group B were (0.93±0.42) and (0.65±0.29) points, respectively; the percentage of FEV1 in the predicted value were (97.75±9.67)% and (100.93±11.06)%, respectively; the MMEF values were (2.81±1.04) and (3.08±1.09) L·s-1, respectively; the FeNO values were (18.94±9.75) and (15.94±7.96) ppb, respectively; the IL-5 levels were (10.88±7.06) and (8.11±5.56) pg·mL-1, respectively. The above indicators in group B showed statistically significant differences compared to group A (all P<0.05). The total incidence of adverse drug reactions in group A and group B were 8.89% (5 cases/45 cases) and 13.33% (6 cases/45 cases), respectively. The recurrence rates was 15.56% (7 cases/45 cases) and 13.33% (6 cases/45 cases), respectively. There was no statistically significant difference in the above indicators between group B and group A (all P>0.05).

    Conclusion

    For elderly patients with CVA, higher dose of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet can better improve cough symptoms, reduce the level of airway hyperresponsiveness and inflammatory factors, reduce the recurrence rate, and the patients are well tolerated.

  • Wei ZHOU, Yue-zhen HE, Yan-ling LIU
    Chinese Journal of Clinical Pharmacology. 2025, 41(1): 116-120.

    Drug-induced liver injury (DILI) is a common adverse drug reactions in clinical practice, with complex pathophysiological process, the pathogenesis has not been fully elucidated, and lack of objective and specific diagnostic methods and treatment, so the prevention and treatment of DILI has attracted extensive attention from scholars. In recent years, the intestinal flora has become a research hotspot in the field of DILI, and the intestinal flora causes or exacerbates DILI by damaging the intestinal mucosal barrier, affecting the metabolites of the intestinal flora and mediating the immune response, and the gut-liver axis is an important pathway for the intestinal flora to participate in the occurrence of DILI, regulating intestinal flora is practicable in the treatment of DILI. This article reviews the characteristics of intestinal flora in DILI patients, and to explore the possible mechanisms of intestinal flora participating in the pathogenesis of DILI through the gut-liver axis, summarizes the latest progress of intervention in the treatment of DILI by intestinal flora, in order to provide references for the screening of the diagnostic targets of DILI and its prevention and treatment from the perspective of intestinal flora.