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  • He LI, Yuan-fang JIN, Fang-fang HUANG, Xiao-ling SHOU, Na LI
    Chinese Journal of Clinical Pharmacology. 2025, 41(18): 2645-2649.
    Objective

    To compare the safety and efficacy of two different companies’ sodium hyaluronic acid gels for correcting moderate to severe nasolabial folds, and evaluate the non-inferiority of the test device to the control device.

    Methods

    This study included healthy subjects with the desire for nasolabial fold beauty who visited the hospital from March to August 2019, the subjects were randomly assigned to the test group and the control group at a ratio of 1∶1, and followed up to 12 months after a single injection sodium hyaluronic acid gel. The primary efficacy evaluation index was the effective rate of wrinkle improvement in the bilateral nasolabial area before and 6 months injection. The secondary efficacy evaluation indexes were the Wrinkles Severity Rating Scale (WSRS) scores of wrinkle improvement at different time points by the investigator and the subjects, and the Global Aesthetic Improvement Scale (GAIS) scores.

    Results

    A total of 137 subjects were included per protocol set, with 70 in the test group and 67 in the control group, respectively. Compared with the baseline, the effective rates of improvement of one grade or above in the test group and the control group were 94.29% (66 cases/70 cases) and 94.03% (63 cases/67 cases), respectively, with a difference of 0.26% between the two groups, and the 95% limit of the difference (asymptotic normal) was [-0.08, 0.08], with the lower limit greater the non-inferiority limit of -10%, and the efficacy of the test group was not inferior to that of the control group. At 6 months post-injection, the investigator’s WSRS scores on the left of the test and control groups were (2.13±0.64) and (2.22±0.6) points, respectively, on the right side were (2.23±0.68) and (2.3±0.6) points; the subjects’ WSRS scores on the left were (2.24±0.79) and (2.32±0.84) points, on the right side were (2.18±0.77) and (2.29±0.76) points, respectively. The investigator’s GAIS of the test and control groups that were regarded as improved were 98.57% (69 cases/70 cases) and 97.01% (65 cases/67 cases), respectively; the subjects’ GAIS that were regarded as improved were 88.5% (62 cases/70 cases) and 86.57% (58 cases/67 cases), respectively, and there was no statistically significant difference between the groups all (P>0.05). In addition, there was no significant difference in the incidence of adverse reactions/adverse events between the two groups (P>0.05).

    Conclusion

    The effectiveness of the test group sodium hyaluronate gel for correcting moderate to severe nasolabial folds was not inferior to that of the control. And it has similar safety.

  • Jing ZHAO, Zhi-fei REN, Gao-yan JIA, Guang-yi Zhang
    Chinese Journal of Clinical Pharmacology. 2025, 41(18): 2630-2634.
    Objective

    To study the clinical effect and safety of atosiban acetate injection combined with magnesium sulfate injection in inhibiting uterine contractions in premature delivery.

    Methods

    Patients with threatened preterm delivery were divided into treatment group (treated with atosiban acetate combined with magnesium sulfate) and control group (treated with magnesium sulfate) by random number table method. The 24 h dose magnesium sulfate injection was 30 g and this drug was stopped when uterine contraction was inhibited, the total dose of atosiban acetate injection was ≤ 330 mg and total treatment time should not exceed 48 h. The effects of contraction inhibition, serological indexes, hemodynamics, safety and perinatal outcomes of the two groups were compared.

    Results

    A total of 97 cases were screened in this study, there were 47 cases in control group and 45 cases in treatment group. The treatment group and control group with success rate of fetal protection were 97.78% and 82.98%, the extended gestation time was (26.35±4.12) and (20.04±3.27) d, and the onset time of uterine contraction was (1.58±0.26) and (2.45±0.38) h, and the difference was all statistically significant (all P<0.05). After treatment, the interleukin-6 (IL-6) levels in treatment group and control group were (142.34±15.75) and (182.17±19.43) ng·L-1, respectively. Matrix metalloproteinase inhibitor-1 (TIMP-1) was (135.29±15.42) and (112.48±13.55) pg·mL-1, nitric oxide (NO) was (23.03±2.17) and (28.13±3.01) μmol·L-1; and the difference of the indexes between two groups was statistically significant (P<0.05). After treatment, there were no statistically significant differences in systolic blood pressure (SBP)[(120.07±13.97) vs. (119.28±13.51) mmHg], heart rate (HR)[(93.56±10.82) vs. (93.32±10.65) bpm] and diastolic blood pressure (DBP) [(77.22±9.05) vs. (78.32±9.47) mmHg] between 2 groups (P>0.05). There were no statistically differences in perinatal mortality and incidence of adverse reactions in 2 groups (P>0.05). The incidence of neonatal asphyxia in treatment group and control group was 2.22% and 17.02%, and the incidence of low body weight infants was 2.22% and 14.89%, the difference was statistically significant (P<0.05).

    Conclusion

    Atosiban acetate injection combined with magnesium sulfate injection can effectively inhibit uterine contraction, reduce inflammation, improve vascular endothelial function, regulate serum TIMP-1 expression, and improve perinatal outcomes in patients with threatened preterm delivery, with good safety and no significant effects on hemodynamics.

  • Fang ZHAO, Shu-chen LI, Jing-jing LIU, Feng-lei YIN, Jing LIU, Bo YANG, Juan WANG
    Chinese Journal of Clinical Pharmacology. 2025, 41(18): 2599-2604.
    Objective

    To investigate the efficacy and safety of zanubrutinib capsules-rituximab injection-lenalidomide capsules(ZR2) in the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

    Method

    Patients with R/R DLBCL were divided into control group and treatment group according to a random number table. The control group received rituximab injection 375 mg·m-2 by intravenous infusion on day 1 of the treatment cycle, and orally took lenalidomide capsules 25 mg once daily from day 1 to day 14 of the cycle. The treatment group received oral zanubrutinib capsule 160 mg twice daily from day 1 to day 21 of the cycle, in addition to the treatment given to the control group. Both groups were treated in 21-day cycles for a total of 6 cycles. The clinical efficacy, immune environment-related indicators, inflammation-related indicators, angiogenesis and metabolism-related indicators, rogression-free survival (PFS) and overall survival (OS) were compared between the two groups.

    Results

    In control group, 2 cases were lost to follow-up and 1 case withdrew, resulting in 40 cases actually included; in treatment group, 3 cases were lost to follow-up, resulting in 40 cases actually included. After treatment, the disease control rates (DCR) of the control group and the treatment group were 60.00% and 82.50%, respectively; cluster of differentiation 3 positive T lymphocyte (CD3+) were (62.17±8.23)% and (67.29±7.95)%, respectively; cluster of differentiation 4 positive T lymphocyte (CD4+)/cluster of differentiation 8 positive T lymphocyte (CD8+) were 1.44±0.36 and 1.65±0.47, respectively; T helper 17 cell (Th17) were (1.37±0.34)% and (1.62±0.46)%, respectively; natural killer cell (NK) were (22.47±3.69)% and (24.86±4.12)%, respectively; tumor necrosis factor-alpha (TNF-α) were (23.35±6.28) and (19.62±5.31) pg·mL-1, respectively; soluble interleukin-2 receptor (sIL-2r) were (621.74±134.89) and (539.48±116.83) U·mL-1, respectively; lactate dehydrogenase (LDH) were (278.64±56.84) and (251.37±48.43) U·L-1, respectively; beta-2-microglobulin (β2-MG) were (1.86±0.87) and (1.49±0.74) mg·L-1, respectively; the PFS rates were 22.50% and 52.50%, respectively; the OS rates were 45.00% and 67.50%, respectively. The differences in the above data between the two groups of patients were statistically significant (all P<0.05). The total incidence of adverse drug reactions in the control group and the experimental group were 67.50% (27 cases/40 cases) and 77.50% (31 cases/40 cases) respectively, with no statistically significant difference, (P>0.05).

    Conclusion

    ZR2 regimen can improve the tumor immune microenvironment, suppress inflammatory responses and tumor angiogenesis in patients with R/R DLBCL, thereby leadingto higher DCR and improved long-term survival benefits, without increasing the risk of treatment-related adverse events.

  • Yun LI, Bo ZHENG, Lan-qing CUI, Xiu-zhen ZHANG, Yun-jian HU, Yu-fen JIN, Shi-yang PAN, Wei GUO, Feng ZHAO, Yun-song YU, Xuan CAI, Wen-en LIU, De-hua LIU, Ying FEI, Jia-yun LIU, Feng-yan PEI, Ling MENG, Ping JI, Jin TANG, Lei ZHU, Kai-su PAN, He-ping XU, Jian-dong ZHANG, Feng XUE, Shan WANG, Yao-yao LIU, Wei ZHONG
    Chinese Journal of Clinical Pharmacology. 2025, 41(18): 2551-2566.
    Objective

    To investigate the gram-positive coccus resistance in nationwide tietiary hospitals, understand the trend of antimicrobial resistance and provide scientific data for the rational use of antibiotis.

    Method

    All the clinical isolates were collected from 18 hospitals and the minimal inhibitory concentrations (MICs) were tested using agar/broth dilution method recommended by Clinical and Laboratory Standards Institute (CLSI) in central laboratory.

    Results

    A total of 2 311 pathogenic gram-positive coccus from 18 tertiary hospitals in 18 cities nationwide over the period from July 2023 to June 2024 were studied. Based on the MIC results, the prevalence of methicillin resistant Stapylococcus aureus (MRSA) and methicillin resistant Stapylococcus epidermidis (MRSE) were 30.6% and 76.3%, respectively. No vancomycin insensitivitive Staphylococcus was detected. Stapylococcus aureus were 100% susceptible to linezolid and teicoplanin. Antibiotic resistance rates of Enterococcus faecalis and Enterococcus faecium to ampicillin were 0.6% and 89.1%, respectively. 18 strains of vancomycin-resistant Enterococcus (VRE) were detected, all of which was Enterococcus faecium. The detection rate of VRE among Enterococcus faecium was 5.5%. The prevalence of penicillin non-susceptible Streptococcus pneumoniae (PNSSP) was 9.9% based on non-meningitis and parenteral administration criterion, while for cases of oral penicillin, the rate was 73.1%, showing similar to last time. The resistance rates of Streptococcus pneumoniae from children to cephalosporins, macrolides and clindamycin were slightly higher than those of adults and the elderly, while there were no statistic significant differences of resistance rates of Stapylococcus aureus, Stapylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium and Streptococcus pneumoniae among various groups such as different departments, ages, or specimen sources (all P>0.05).

    Conclusion

    The detection rate of MRSA has continued to decline, while the detection rate of VRE has been on the rise. This situation requires continuous monitoring.

  • Cai-xia YIN, Lei ZENG, Lei-zhao HUANG, Hua-you LI
    Chinese Journal of Clinical Pharmacology. 2025, 41(18): 2588-2593.
    Objective

    To investigate the clinical efficacy and safety of finerenone tablets combined with losartan potassium capsules in the treatment of patients with chronic kidney disease (stage 1-3) and non-diabetic immunoglobulin A (IgA) nephropathy.

    Method

    Patients with chronic kidney disease (stage 1-3) and non-diabetic IgA nephropathy were divided into control group and treatment group according to different drug treatment plans. Control group was treated with losartan potassium capsules at an initial dose of 50 mg·time-1, once a day, for 3 months. Treatment group was treated with finerenone tablets at an initial dose of 20 mg·time-1, once a day, for 3 months, and combined with losartan potassium capsules, dose same as control group. The clinical efficacy and levels of renal function indexes, immunoglobulin indexes, complement indexes and inflammatory factors were compared between the two groups. The safety was evaluated.

    Results

    A total of 96 cases were enrolled in this study. Among them, 47 cases were included in control group and 49 cases were included in treatment group. After treatment, the total effective rates in control group and treatment group were 82.98% (39 cases/47 cases) and 97.96% (48 cases/49 cases), and the treatment group was significantly higher (P<0.05). After treatment, glomerular filtration rates (eGFR) in control group and treatment group were (87.29±16.30) and (95.72±18.53) mL·min-1·1.73 m-2; 24 h urine protein levels were (0.69±0.14) and (0.48±0.10) g·24 h-1; urinary albumin-to-creatinine ratios (UACR) were (32.96±6.38) and (26.57±5.49) mg·mmol-1; blood urea nitrogen (BUN) levels were (12.68±2.24) and (11.15±2.17) mmol·L-1; serum creatinine (SCr) levels were (122.39±24.73) and (108.45±21.94) μmol·L-1; cystatin c (CysC) levels were (2.74±0.51) and (2.31±0.48) mmol·L-1; IgA levels were (2.18±0.46) and (1.73±0.39) g·L-1; complement (C) 3 levels were (0.95±0.18) and (1.14±0.22) g·L-1; C4 levels were (1.27±0.25) and (1.53±0.29) g·L-1; C1q levels were (0.19±0.05) and (0.23±0.06) g·L-1; interleukin (IL)-2 levels were (16.83±4.32) and (12.18±3.75) ng·L-1; IL-6 levels were (10.25±2.04) and (7.22±1.43) ng·L-1; high-sensitivity C-reactive protein (hs-CRP) levels were (0.52±0.16) and (0.40±0.11) mg·L-1. The differences in above indicators between treatment group and control group were statistically significant (all P<0.05). Adverse drug reactions in control group included dizziness, orthostatic hypotension, gastrointestinal reactions, skin rashes and hyperkalemia. Adverse drug reactions in treatment group included dizziness, orthostatic hypotension, gastrointestinal reactions and hyperkalemia. The total incidence rates of adverse reactions in treatment group and control group were 12.77% (6 cases/47 cases) and 14.29% (7 cases/49 cases), showing no statistically significant difference (P>0.05).

    Conclusion

    The clinical efficacy of fenelidone tablets combined with losartan potassium capsules in treatment of chronic kidney disease (stage 1-3) with non-diabetes IgA nephropathy is more significant than that of losartan potassium capsule alone. It can significantly increase eGFR, lower urine protein level, improve renal function and immune function and alleviate micro-inflammation, with good safety.

  • Peng-cheng DOU, Sheng CHANG, Rui-ping SONG, Jiao-jiao ZUO, Zhuang-zhuang FENG, Xin-yi CHEN, Xiao-long WANG, Jin SHU
    Chinese Journal of Clinical Pharmacology. 2025, 41(18): 2679-2684.

    The high morbidity and mortality of gastric cancer seriously affect and threaten the public's life and health. Precancerous lesions of gastric cancer (PLGC) is a key stage in the process of gastric mucosal carcinogenesis, and it is also a "golden turning point" before the formation of gastric cancer. Early and effective intervention has become an important way and research focus for the prevention and control of gastric cancer. Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) signaling pathway is involved in a variety of biological processes such as inflammatory response, angiogenesis, autophagy level and apoptosis. Studies have confirmed that this pathway is abnormally activated in PLGC and can promote the malignant progression of the disease to gastric cancer by regulating a variety of pathways, which can be used as a potential target and effective way for the prevention and treatment of PLGC. In recent years, traditional Chinese medicine has achieved many research results in delaying or even reversing PLGC by targeting the PI3K/Akt signaling pathway. Based on the PI3K/Akt signaling pathway, this paper systematically expounds the role of this signaling pathway in PLGC and the research progress of traditional Chinese medicine intervention, in order to provide reference for the clinical treatment of this disease and drug development and application.

  • Fei-fei LIU, Dong LIU, Dong LI, Yu-zhu WANG
    Chinese Journal of Clinical Pharmacology. 2025, 41(18): 2692-2696.

    The research and development of combination chemical drug occupy an important position in the development of new drugs and generic drugs. Two or more active ingredients are often formulated into combined preparations for development based on clinical needs, the mechanism of drug action and actual clinical effects. In the research and development of combined chemical drugs, clinical pharmacology research serves as a crucial bridge connecting the theories of drug research and development and the practical application in clinical practice. Based on regulations and guidelines, this article explores the application of clinical pharmacology research in the research and development of combined pharmaceutical preparations by integrating research and development cases, clinical practice and literature research.

  • Xin-ying LIU, Fang FANG, Yuan-yuan GU, Yan-li MENG, Yu-yan GUO, Jun ZUO, Yu LONG, Yuan-qi GUO
    Chinese Journal of Clinical Pharmacology. 2025, 41(18): 2674-2678.

    Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by persistent airflow limitation. Its pathogenesis is complex and involves multiple pathological processes such as oxidative stress, inflammatory response and apoptosis. The mitogen-activated protein kinase (MAPK) signaling pathway plays a significant role in regulating cell growth, proliferation, differentiation and apoptosis. Modern research has confirmed that traditional Chinese medicine can exert therapeutic effects on COPD by intervening in the MAPK signaling pathway. This article reviews the regulatory mechanism of the MAPK signaling pathway on COPD and the intervention effect of traditional Chinese medicine on COPD in recent years, aiming to provide research basis for the development of new traditional Chinese medicine and the clinical application of traditional Chinese medicine in the treatment of COPD.

  • Ting LIU, Rui-long LÜ, Zhuan-hong ZHANG, Yu-gui ZHANG, Ding-cai MA, Er-dan XIN, Yu-jing SUN, Fen-yu DOU, Meng-na CHAI, Yue-feng LI
    Chinese Journal of Clinical Pharmacology. 2025, 41(18): 2639-2644.
    Objective

    To explore the mechanism by which processed Radix Hedysari and vinegar-processed Rhizoma Curcumae inhibit angiogenesis in colitis-associated colorectal cancer (CAC).

    Methods

    Sixty SPF-grade C57BL/6J mice were randomly divided into six groups (A-F), A: Blank control; B: Model group [Azoxymethane (AOM)/Dextran sodium sulfate (DSS) AOM/DSS group]; C: Sulfasalazine group; D: Fried Astragalus group; E: Fried Astragalus-Vinegar Curcuma (4∶1) group; F: Curcuma zedoaria group. Each group contained 10 mice. A CAC mouse model was induced using combined AOM and DSS. Simultaneously, each treatment group received intervention, the blank group received 0.9% sodium chloride solution. The experiment concluded after 17 weeks of intervention. Collagen fiber area expression in colon tissues was assessed using Masson’s trichrome staining. Microvascular density in colon tissues was determined via immunohistochemistry. Serum vascular endothelial growth factor(VEGF) and nitric oxide(NO) levels were measured using enzyme linked immunosorbent assay(ELISA). Key proteins in the phosphatidylinositol-3-kinase/ protein kinase B(PI3K/AKT) pathway and VEGF expression were detected by Western blotting (WB).

    Results

    After 17 weeks of pharmacological intervention, the microvessel counts in the blank group, model group, sulfasalazine group, honey-fried Radix Hedysari-vinegar-processed Rhizoma Curcumae (4:1) group, honey-fried Radix Hedysari group, and vinegar-processed Rhizoma Curcumae group were (23.20±4.21), (73.60±13.52), (44.80±2.78), (33.40±6.31), (41.60±3.36), and (47.80±7.29), respectively. The serum VEGF concentrations were (83.03±24.13), (153.61±18.69), (115.08±11.43), (87.03±25.24), (91.33±32.37), and (101.93±19.74) pg·mL-1, respectively. The serum NO levels were (28.46±5.91), (40.62±2.28), (30.62±6.54), (29.18±5.37), (30.87±5.30), and (32.29±3.43) μmol·L-1, respectively. Compared with the blank group, the model group exhibited significant increases in the collagen fiber staining area and microvessel density in colonic tissue, markedly elevated serum VEGF and NO levels, and significantly enhanced phosphorylation of PI3K, AKT, and mTOR as well as upregulated VEGF expression in colonic tissue. In comparison with the model group, the honey-fried Radix Hedysari-vinegar-processed Rhizoma Curcumae (4∶1) group, honey-fried Radix Hedysari group, and vinegar-processed Rhizoma Curcumae group demonstrated significant reductions in the collagen fiber area and microvessel count in colonic tissue, decreased serum VEGF and NO concentrations, and markedly suppressed phosphorylation of PI3K, AKT, and mTOR along with downregulated VEGF expression in colonic tissue (P<0.05 or P<0.01).

    Conclusion

    The combined use of processed Radix Hedysari and vinegar-processed Rhizoma Curcumae exerts a better anti-CAC effect than the single herb. Its mechanism is closely related to regulating the expressions of key proteins in the PI3K/AKT signaling pathway, thereby inhibiting angiogenesis in colitis-associated colorectal cancer.

  • Bo SU, Bo ZHENG
    Chinese Journal of Clinical Pharmacology. 2025, 41(18): 2635-2638.
    Objective

    To sequence a vancomycin-resistant Enterococcus faecium and analyze the vanM gene cluster carried on its plasmid as well as the genes conferring advantage in nutrient utilization.

    Method

    The broth microdilution method was used to perform drug susceptibility tests on strain 15P371 and its transconjugant J15P371. Subsequently, whole-genome sequencing was conducted using Nanopore technology for both strains, followed by analysis of the resistant plasmid sequences. Bacterial growth experiments were carried out to verify the advantage in intestinal nutrient utilization.

    Results

    Strain 15P371 is a vancomycin-resistant strain carrying 6 copies of the vanM gene cluster. Its transconjugant J15P371 can tolerate a higher concentration of vancomycin but only harbors 3 copies of the vanM gene cluster. Genes conferring advantage in intestinal N-acetylgalactosamine utilization are present on the resistant plasmid.

    Conclusion

    In vanM-type vancomycin-resistant strain, the copy number of resistance genes is variable during conjugative transfer. The plasmid carrying genes with advantage in N-acetylgalactosamine utilization confer growth advantage to the host bacteria.