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  • Qing MA, Li LI, Shan-shan ZHU, Qiao-yan WANG, Hao CHEN
    Chinese Journal of Clinical Pharmacology. 2025, 41(17): 2429-2434.
    Objective

    To investigate the clinical efficacy and safety of midazolam injection combined with propofol medium/long-chain fat emulsion target-controlled infusion (TCI) in severely obese patients undergoing laparoscopic sleeve gastrectomy with double-tract anastomosis (LSG-DJB).

    Methods

    Severely obese patients treated in our hospital were randomly assigned by a random number table method to the control group or the treatment group. The control group received propofol medium/long-chain fat emulsion TCI (effect-site concentration 1.2–2.0 μg·mL-1), while the treatment group additionally received midazolam injection (0.03 mg·kg-1 for induction, 0.02 mg·kg-1·h-1 for maintenance). Pain indicators, recovery quality, inflammatory markers, oxidative stress parameters and safety outcomes were compared between the two groups.

    Results

    A total of 179 patients were screened in this study, with 67 cases enrolled in the control group and 68 cases in the treatment group. Three cases dropped out in the control group and four cases dropped out in the treatment group; ultimately, 64 cases in each group completed the study. The pain scores (NRS) at discharge from the operating room were (0.76±0.42) and (0.93±0.28) points for the treatment group and control group, respectively; at 6 hours postoperatively, they were (1.94±0.46) and (2.37±0.82) points, respectively; at 12 hours postoperatively, they were (2.24±0.51) and (2.92±0.71) points, respectively. Compared with the control group, the differences in the above indicators in the treatment group were statistically significant (all P<0.05). The total intraoperative dosage of sufentanil injection were (0.75±0.12) and (0.92±0.15) μg·kg-1 for the treatment group and control group, respectively; the eye-opening time was (10.77±1.48) and (8.39±1.23) min, respectively; the extubation time was (18.68±2.91) and (13.21±2.48) min, respectively; the respiratory recovery time was (16.87±2.25) and (11.93±2.03) min, respectively. Compared with the control group, the differences in the above indicators in the treatment group were statistically significant (all P<0.05). At 24 hours postoperatively, the serum interleukin-6 (IL-6) levels were (72.16±10.28) and (88.32±11.14) ng·L-1 for the treatment group and control group, respectively; tumor necrosis factor-α (TNF-α) levels were (152.47±21.95) and (176.84±25.67) ng·L-1, respectively; C-reactive protein (CRP) levels were (5.63±0.88) and (7.74±0.86) mg·L-1, respectively; malondialdehyde (MDA) levels were (4.82±1.19) and (7.03±1.22) mmol·mL-1, respectively; cortisol (Cor) levels were (31.42±3.27) and (37.75±4.16) μg·dL-1, respectively; superoxide dismutase (SOD) levels were (37.38±5.82) and (23.67±3.59) mmol·mL-1, respectively. Compared with the control group, the differences in the above indicators in the treatment group were statistically significant (all P<0.05). The main adverse drug reactions in the treatment group were hypoxemia, hypotension, delayed recovery, nausea and vomiting; the main adverse reactions in the control group were nausea and vomiting, hypoxemia, and hypotension. The total incidence rates of adverse drug reactions were 54.69% and 42.19% in the treatment group and control group, respectively, with no statistically significant difference (P>0.05).

    Conclusion

    Midazolam injection combined with propofol medium/long-chain fat emulsion TCI provides optimized sedation depth, reduces inflammatory and stress responses, and demonstrates good safety in severely obese patients undergoing LSG-DJB.

  • Ling-wei ZENG, Jing YANG, Chang-yi WANG, Liang LI
    Chinese Journal of Clinical Pharmacology. 2025, 41(17): 2471-2476.
    Objective

    To investigate the effects of fucoxanthin on endothelial cell function in coronary heart disease (CHD) and its mechanism.

    Methods

    The cell experiment section divided the human coronary artery endothelial cells (HCAEC) into blank group, ox-LDL group (40 μg·mL-1), fucoxanthin group (ox-LDL+25 μmol·L-1 fucoxanthin) and miR-483-3p inhibitor group (transfected with miR-483-3p inhibitor+ox-LDL+25 μmol·L-1 fucoxanthin). The expression levels of miR-483-3p and pyroptosis related proteins NLR family pyrin domain containing 3 (NLRP3) were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting (WB), respectively. The animal experiment section divided the rats into control group, model group (constructed CHD model), experimental group (modeling +30 mg·kg-1 fucoxanthin) and inhibitor group (modeling+transfection of miR-483-3p inhibitor+30 mg·kg-1 fucoxanthin). The relative expression levels of miR-483-3p, endothelium-related factors and pyroptosis related proteins NLRP3 were detected by RT-qPCR, enzyme-linked immunosorbent assay (ELISA) and Western blot, respectively.

    Results

    In cell experiment, the relative expression levels of miRNA-483-3p in cells of blank group, ox-LDL group, fucoxanthin group and miR-483-3p inhibitor group were 1.00±0.11, 0.39±0.07, 0.74±0.06 and 0.22±0.03, respectively; NLRP3 protein relative expression levels were 0.39±0.02, 1.03±0.07, 0.52±0.04 and 0.85±0.10, respectively. ox-LDL group was compared with blank group, fucoxanthin group was compared with ox-LDL group, miR-483-3p inhibitor group was compared with fucoxanthin group, the above indicators all showed statistically significant differences. (all P<0.001). In animal experiments, the relative expression levels of miR-483-3p in control group, model group, experimental group and inhibitor group were 1.00±0.12, 0.51±0.06, 0.70±0.08 and 0.31±0.04, respectively; nitric oxide (NO) levels were (46.93±3.18), (20.21±2.43), (36.13±4.87) and (24.43±1.60) μmol·L-1, respectively; the NLRP3 protein relative expression levels were 0.29±0.04, 0.97±0.09, 0.56±0.09 and 0.86±0.08, model group was compared with control group, experimental group was compared with model group, inhibitor group was compared with experimental group, the above indicators all showed statistically significant differences. (all P<0.001).

    Conclusion

    Fucoxanthin can up-regulate miR-483-3p to improve endothelial cell pyroptosis and relieve CHD inflammatory response.

  • Zhi-guang LIU, Xue-zhong WANG, Ya-long DU
    Chinese Journal of Clinical Pharmacology. 2025, 41(17): 2453-2458.
    Objective

    To investigate the effects of baicalein combined with 5-fluorouracil (5-FU) on the proliferation, apoptosis and migration of H446 cells, and to explore the sensitization mechanism.

    Methods

    Lung cancer H466 cells were allocated into blank, control, experimental and combination groups. The blank group was treated with 10 μmol·L-1 dimethyl sulfoxide, the control group with 20 μmol·L-1 baicalein, the experimental group with 20 μmol·L-1 5-FU, and the combination group with 10 μmol·L-1 baicalein plus 10 μmol·L-1 5-FU. Cell viability was determined using the cell counting kit-8 assay. Apoptosis and reactive oxygen species (ROS) levels were analyzed by flow cytometry. Cell migration was evaluated with Transwell assays, and alterations in mitogen-activated protein kinase (MAPK) pathway protein expression were examined by Western blotting.

    Results

    After 24 h of incubation, cell viability in blank, control, experimental and combination groups were (114.34±2.88)%, (79.87±3.48)%, (57.66±1.82)% and (40.31±2.73)%, respectively; the corresponding apoptosis rates were (14.47±1.36)%, (33.94±4.33)%, (49.20±3.82)% and (49.17±2.13)%; and cell migration rates were (8.43±1.94)%, (11.25±1.55)%, (26.74±3.31)% and (68.83±4.32)%. Compared with control group, the above indexes of experimental group and combined group were significantly increased, and combined group were significantly higher than experimental group (all P<0.01). After adding ROS scavenger NAC to combination group, the apoptosis rates of blank group, control group, experimental group, combination group and combination group+NAC were (7.82±0.94)%, (12.31±2.13)%, (33.48±4.92)%, (52.42±3.17)% and (30.39±2.72)%, respectively; the cell migration rates were (4.36±0.54)%, (4.92±0.71)%, (31.43±3.14)%, (52.64±5.26)% and (27.61±3.52)%, respectively. Compared with combined group, the above indexes of combined group+NAC were significantly decreased (all P<0.01). The relative expression levels of p-JNK protein in blank, experimental, control, combination and combination group+NAC were 0.78±0.05, 0.70±0.04, 0.73±0.03, 0.98±0.02 and 0.73±0.05, respectively; the relative expression levels of p-p38 were 0.56±0.02, 0.51±0.03, 0.60±0.04, 0.76±0.06 and 0.54±0.03, respectively; the relative expression levels of p-ERK were 0.34±0.03, 0.30±0.04, 0.28±0.04, 0.18±0.03 and 0.33±0.05, respectively. The relative expression levels of p-JNK and p-p38 protein in combination group were significantly higher than those in control group, and the relative expression levels of p-ERK protein were significantly lower (all P<0.01); the relative expression levels of p-JNK and p-p38 low protein in combined group+NAC were significantly decreased, while the relative expression levels of p-ERK protein were significantly increased (all P<0.01).

    Conclusion

    The combination of baicalein and 5-FU can enhance the inhibitory effect on proliferation, induce apoptosis, and suppress migration in H446 cells by upregulating ROS levels, activating the JNK and p38 pathways, and inhibiting the ERK pathway.

  • Yu-guo ZHU, Rui-ya SU, Sheng GUO
    Chinese Journal of Clinical Pharmacology. 2025, 41(17): 2477-2482.
    Objective

    To investigate the effects of total alkaloids of Aconitum carmichaelii on myocardial function in rats and its underlying mechanisms.

    Methods

    SPF-grade Wistar rats were randomly assigned into five groups (n=10 each): blank group (0.9% NaCl), control group (isoproterenol 10 mg·kg-1), experimental-L group (2.72 g·kg-1 total alkaloids of A. carmichaelii), experimental-M group (3.68 g·kg-1), and experimental-H group (4.98 g·kg-1). All groups were gavaged once daily for 5 consecutive days. Thirty minutes after the last injection, T-wave amplitude on electrocardiogram was recorded. An isolated heart perfusion model was established to evaluate cardiac function and myocardial contractility. Myocardial cell activity and malondialdehyde content were measured, and real-time quantitative PCR was used to detect mRNA expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1α), B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax).

    Results

    The T-wave amplitudes for the experimental -L, -M, -H groups, blank group and control group were (0.17±0.07), (0.29±0.05), (0.37±0.04), (0.30±0.07) and (0.36±0.04) mV, respectively; the myocardial cell activities were (0.46±0.05), (0.44±0.08), (0.35±0.07), (0.45±0.06) and (0.33±0.05) Abs, respectively; the while malondialdehyde contents were (2.56±0.28), (2.55±0.26), (2.86±0.28), (2.49±0.34) and (2.83±0.25) mmol·mL-1, respectively; the relative mRNA expression levels of Pgc-1α were 0.49±0.05, 0.41±0.07, 0.27±0.05, 0.48±0.06 and 0.35±0.05, respectively; the relative mRNA expression levels of Bax were 1.10±0.08, 1.25±0.09, 1.36±0.07, 1.09±0.09 and 1.33±0.07, respectively; the relative mRNA expression levels of Bcl-2 were 0.58±0.06, 0.51±0.05, 0.44±0.04, 0.56±0.08 and 0.45±0.03, respectively. Compared with the experimental -M, -H groups and blank group, the above indexes of the experimental -L group were statistically significant (all P<0.05).

    Conclusion

    Lower doses of Aconitum carmichaelii total alkaloids positively influence ECG T-wave amplitude, cardiac function, and myocardial contractility, improve myocardial cell activity, and reduce oxidative stress, whereas high doses exert cardiotoxic effects.

  • Dong-xia LÜ, Fan ZHANG, Xin GAO, Hang-xing ZHANG, Guo-xu WANG, Zhi RAO, Yu-hui WEI
    Chinese Journal of Clinical Pharmacology. 2025, 41(17): 2496-2502.
    Objective

    To investigate the effect of Gardenia jasminoides Ellis (Zhi-zi) in alleviating the hepatotoxicity induced by its constituent, genipin, which is called the "self-detoxification" effect, and to explore its mechanism through targeted metabolomics and integrated network pharmacology.

    Methods

    Male mice of the Kunming breed were randomly divided into three groups (n=8) including blank group, control group and experimental group. Blank group was administered a blank solvent 0.5% carboxymethyl cellulose (CMC-Na) by gavage; control group was administered genipin by gavage at a dose of 100 mg·kg-1·d-1, and experimental group was administered 100 mg·kg-1·d-1 genipin and 520 mg·kg-1·d-1 Zhi-zi aqueous extract powder by gavage. After 28 days of continuous administration, serum biochemical indicators were measured using an automated biochemical analyzer, liver tissue pathology was examined using hematoxylin and eosin (HE) staining, and differential metabolites were quantified and analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for targeted metabolomics analysis. The targets associated with active compounds in Zhi-zi, genipin, and liver damage were predicted separately. Finally, the results of metabolomics and network pharmacology were integrated to screen the potential targets related to the self-detoxification effect of Zhi-zi.

    Results

    The alanine transaminase (ALT) levels in experimental group, control group and blank group were (35.75±8.50), (53.00±14.43) and (37.38±3.11) U·L-1, respectively; the aspartate transaminase (AST) levels were (123.38±31.40), (146.50±19.73) and (115.75±17.44) U·L-1, respectively. Compared with control group, experimental group showed significant decrease in ALT levels, with statistically significant difference (P<0.05). Compared with control group, the AST levels in experimental group showed no statistically significant difference (P>0.05). Targeted metabolomics identified 8 characteristic endogenous metabolites including fumaric acid, isocitric acid, maleic acid, ornithine, aminocaproic acid, isoLCA, pipecolic acid and pyrrole-2-carboxylic acid, and the metabolic pathways induced by these 8 differentially expressed metabolites were primarily associated with arginine biosynthesis and the tricarboxylic acidcycle (TCA) metabolic pathways.

    Conclusion

    Zhi-zi can improve the metabolic disorders of endogenous metabolites in the liver caused by genipin by affecting the arginine biosynthesis and the TCA metabolic pathway, and improve inflammation and oxidative stress by acting on the corresponding targets to alleviate the hepatic injuries caused by genipin and exerting the self-detoxification effect.

  • Meng-zhen LI, Da-wei HE, Yan-ming HAO, Chong LI, Yi YIN
    Chinese Journal of Clinical Pharmacology. 2025, 41(17): 2446-2452.
    Objective

    To investigate the effect and of hydrogen sulfide (H2S) on the osteogenic differentiation of osteoblast precursor cells (MC3T3-E1) by regulating the polarization of macrophages (RAW264.7).

    Methods

    RAW264.7 cells were divided into four groups (n=10 in each group), including control group (untreated), M1 induction group [added with 100 ng·mL-1 lipopolysaccharide (LPS)], M2 induction group (added with 20 ng·mL-1 interleukin-4+20 ng·mL-1 interleukin-10, IL-4+IL-10), GYY4137 intervention group (H2S donor GYY4137 100 μmol·L-1). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the mRNA and protein expression levels of M1 macrophage related factors including tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β) and inducible nitric oxide synthase (i-NOS) and M2 macrophage related factors including interleukin-10 (IL-10), arginase-1 (Arg-1) and mannose receptor (CD206), and to verify the effect of polarization induction and the intervention of GYY4137; cell counting kit-8 (CCK-8) was used to detect the activity of RAW264.7 cells treated with GYY4137 at different concentrations for 24 h and 72 h (6 wells in each group). The expression levels of Arg-1 and CD206 in control group and GYY4137 group (100 μmol·L-1) were detected by flow cytometry (n=10 in each group). MC3T3-E1 cells were divided into four groups (n=10), which were blank group (without osteogenic induction medium), osteogenic control group (with osteogenic induction medium), co-culture group (co-cultured with RAW264.7 cells Transwell) and GYY4137 pretreatment co-culture group (co-cultured with 100 μmol·L-1 GYY4137 pretreated RAW264.7 cells). The mRNA expression levels of osteogenic related genes including Runt-related transcription factor 2 (Runx-2), osteopontin (OPN), bone morphogenetic protein-2 (BMP-2) and bone sialoprotein (BSP) mRNA were detected by RT-qPCR; alkaline phosphatase (ALP) staining and alizarin red staining were used to detect osteogenic differentiation.

    Results

    The relative expression levels of TNF-α mRNA in control group, M1 induction group and GYY4137 intervention group were 1.56±0.22, 16.49±3.56 and 0.57±0.11, respectively; the relative expression levels of IL-1β mRNA were 1.06±0.24, 3.37±0.76 and 1.43±0.34, respectively. The above indexes in M1 induced group were significantly higher than those in control group, and the above indexes in GYY4137 intervention group were significantly lower than those in M1 induced group (all P<0.001). The relative expression levels of Arg-1 mRNA in GYY4137 group and control group were 1.38±0.36 and 0.91±0.12, respectively; the relative expression levels of CD206 mRNA were 17.43±2.84 and 1.14±0.21, respectively; the relative expression levels of CD206 protein were 0.89±0.25 and 0.20±0.04, respectively; the relative expression levels of i-NOS protein were 0.72±0.19 and 0.25±0.07, respectively; the relative expression levels of Arg-1 were 28.65±3.21 and 12.31±2.15, respectively; the relative expression levels of CD206 were 31.24±2.89 and 10.8±1.98, respectively. The above indexes in GYY4137 intervention group were significantly higher than those in control group, and the differences were statistically significant (P<0.05, P<0.001). The relative expression levels of Runx-2 mRNA in GYY4137 pretreatment and co-culture groups were 3.21±0.45 and 1.56±0.22, respectively; the relative expression levels of OPN mRNA were 2.89±0.38 and 1.43±0.19, respectively; the relative expression levels of BMP-2 mRNA were 3.56±0.52 and 1.67±0.25, respectively; the relative expression levels of BSP mRNA were 2.98±0.41 and 1.51±0.20, respectively. The above indexes in GYY4137 pretreatment co-culture group were significantly higher than those in co-culture group, and the differences were statistically significant (all P<0.05). The OD values of ALP in GYY4137 pretreatment co-culture group and osteogenic control group were (0.89±0.12) and (0.56±0.08) μm2, respectively; the areas of alizarin red stained calcium nodules were (2 865.32±215.67) and (1 568.45±189.32) μm2, respectively; the above indexes of GYY4137 pretreatment co-culture group were significantly higher than those of osteogenic control group, and the differences were statistically significant (all P<0.05).

    Conclusion

    100 μmol·L-1 GYY4137 can enhance the osteogenic differentiation of MC3T3-E1 cells by promoting the polarization of RAW264.7 cells to M2 macrophages, up regulating the expression of osteogenic related genes.

  • Xiao-feng LI, Shou-yuan YANG, Xi-xiang LI, Hui-rong XI, Ya-li ZHOU
    Chinese Journal of Clinical Pharmacology. 2025, 41(17): 2534-2538.

    Digestive system diseases is a common clinical disease with high incidence, which is seriously threatening human health and has become the main cause of the global social disease burden. Therefore, prevention and treatment of digestive system diseases is of great significance to reduce the medical burden. Traditional Chinese medicine has achieved good curative effect in the treatment of digestive system related diseases. Glycyrrhizae Radix has the effects of tonifying spleen and reinforcing qi, relieving pain and so on. According to the relevant literature at home and abroad, the active ingredients of Glycyrrhizae Radix and its compound are effective in preventing and treating diseases related to the digestive system. This article reviewes the research progress of Glycyrrhizae Radix in the prevention and treatment of esophageal diseases, stomach diseases, liver diseases, colon diseases, pancreas and other diseases, and provides thinking for the further study of Glycyrrhizae Radix and its compound in the prevention and treatment of digestive system diseases, which is conducive to the wider therapeutic effect of glycyrrhiza and its compound in clinic.

  • Jia-qing CHANG, Wei-wei ZHAO, Li-li MA, Hai-chao JU, Jia-shu YANG, Xin-ping WANG, Xi-ping XING
    Chinese Journal of Clinical Pharmacology. 2025, 41(16): 2324-2329.
    Objective

    To explore the roles of oxidative stress and apoptosis in the renal deficiency and blood stasis type oligoasthenozoospermia(OAS) model, and to investigate the mechanism of the intervention by the Qi-supplementing, Blood-activating and Essence-nourishing formula.

    Methods

    The rat model of renal deficiency and blood stasis type oligoasthenozoospermia was established by intragastric administration of Gentiana macrophylla polysaccharides (GTW). The rats were randomly divided into the model group, the levocarnitine group, the low, medium and high doses of the Qi-supplementing, Blood-activating and Essence-nourishing formula groups; another 8 rats were randomly selected as the normal control group. The levocarnitine group was intragastrically administered 1.8 mL·kg-1 levocarnitine oral liquid; the low, medium and high doses of the Qi-supplementing, Blood-activating and Essence-nourishing formula groups were given 7.87, 15.75 and 31.50 g·kg-1,respectively; the blank group and the model group were intragastrically administered the same amount of 0.9% NaCl. All 6 groups of rats were administered the drugs once daily and continuously for 28 days. The general conditions of the rats were observed; the testicular and epididymal indices were measured; the sperm quality was detected; the pathological morphology of the testicular tissue was observed by hematoxylin-eosin staining (HE); the activity of reactive oxygen species (ROS), catalase (CAT) and superoxide dismutase (SOD) in the testicular tissue was detected by enzyme-linked immunosorbent assay (ELISA); the mRNA expression levels of Caspase-3, Bcl-2 and Bax in the testicular tissue were detected by real-time fluorescence quantitative polymerase chain reaction (q-PCR).

    Results

    The testicular indices of the blank group, model group, low, medium and high doses of the Qi-supplementing, Blood-activating and Essence-nourishing formula group, and the levocarnitine group were (0.83±0.09)%, (0.55±0.10)%, (0.55±0.07)%,(0.71±0.12)%,(0.81±0.08)%, and (0.67±0.07)%, respectively; the epididymal indices were (0.36±0.05)%, (0.24±0.03)%, (0.25±0.04)%, (0.28±0.02)%,(0.35±0.06)%, and (0.28±0.03)%,respectively; the sperm concentrations were (24.11±11.64, 4.65±2.48, 6.75±3.81, 11.60±7.78, 21.72±7.81, 23.22±8.80)×106 sperm·mL-1, respectively; the sperm motility was (86.93±12.00)%, (33.46±16.13)%, (53.01±21.71)%, (63.15±24.35)%, (79.97±10.22)%, and (75.83±25.05)%, respectively; the ROS intensity was 597 926.11±87 518.20, 925 239.02±95 539.79, 846 676.84±64 867.76, 784 277.73±81 354.32, 658 228.04±82 768.68, and 725 740.12±87 846.36, respectively; the CAT activity was (1.40±0.11), (0.56±0.09), (0.77±0.11), (0.95±0.13), (1.15±0.12), and (1.03±0.11) U·mgprot-1, respectively; the SOD activity was (2.41±0.07), (1.65±0.05), (1.79±0.33), (1.90±0.04), and (2.21±0.05), and (2.06±0.04) U·mgprot-1, respectively. the relative expression levels of Bcl-2 mRNA were 1.00±0.04, 0.26±0.02, 0.39±0.04, 0.49±0.02, 0.87±0.02, and 0.66±0.05, respectively; the relative expression levels of Bax mRNA were 1.00±0.05, 1.78±0.07, 1.50±0.04, 1.39±0.02, 1.12±0.04, and 1.27±0.04, respectively; the relative expression levels of Caspase-3 mRNA were 1.00±0.03, 1.95±0.06, 1.81±0.03, 1.68±0.03, 1.18±0.07, and 1.49±0.08, respectively. The above-mentioned indicators of the model group compared with the blank group, the high-dose group compared with the model group, and the L-carnitine group except for the epididymal index compared with the model group, all showed statistically significant differences (P<0.05,P<0.01).

    Conclusion

    Oxidative stress and cell apoptosis play multiple regulatory roles in the sperm quality and testicular damage of OAS rats. The Qi-supplementing, activating blood, and tonifying essence formula may improve the sperm quality and testicular function of rats by inhibiting oxidative stress and cell apoptosis.

  • Shu-yang HU, Yan XU, Liang XU
    Chinese Journal of Clinical Pharmacology. 2025, 41(16): 2263-2268.
    Objective

    To observe the clinical efficacy and safety of finerenone tablets combined with dapagliflozin tablets in the treatment of elderly diabetic nephropathy (DN).

    Methods

    Elderly patients with DN in hospital were divided into treatment group and control group. The patients in control group were treated with oral dapagliflozin tablets once a day in the morning, with a dose of 5 mg each time, while the patients in the treatment group were combined with finerenone tablets on the basis of control group, and adjusted according to the estimated glomerular filtration rate (eGFR) levels of patients. Serum creatinine (SCr), blood urea nitrogen (BUN), 24 h urine protein quantification, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-cRP), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and clinical efficacy were compared between groups of patients, and the safety was evaluated.

    Results

    A total 90 patients were enrolced; 45 in treatment group and 45 in control group. After treatment, the SCr levels in treatment group and control group were (127.63±10.28) and (140.27±11.95) μmol·L-1, BUN levels were (11.45±3.57) and (18.62±3.29) mmol·L-1, 24 h urine protein quantification levels were (99.28±11.42) and (117.92±12.00) mg·24 h-1, IL-6 levels were (12.32±2.15) and (16.41±3.50) ng·L-1, TNF-α levels were (31.68±10.52) and (43.09±11.83) ng·L-1, hs-cRP levels were (6.08±1.20) and (9.56±1.57) ng·L-1, TC levels were (4.49±0.55) and (4.83±0.72) mmol·L-1, TG levels were (2.57±0.63) and (2.79±0.48) mmol·L-1, LDL-C levels were (2.71±0.63) and (3.06±0.45) mmol·L-1 respectively, and the above indicators in treatment group were significantly lower than those in control group, with statistically significant differences (all P<0.05). The total clinical effective rate in treatment group was 93.34% (42 cases/45 cases), and that in control group was 75.56% (34 cases/45 cases), with statistically significant difference (P<0.05). The adverse drug reactions in treatment group were hypotension, hypoglycemia, acute kidney injury, hyperkalemia and pruritus, and the adverse drug reactions in control group included hypoglycemia, acute kidney injury and hyperkalemia. The total incidence rates of adverse drug reactions in treatment group and control group were 22.22% (10 cases/45 cases) and 8.89% (4 cases /45 cases) respectively, without statistically significant difference (P>0.05).

    Conclusion

    Compared with dapagliflozin tablets, the combined use of finerenone tablets for elderly DN can better improve the renal function, and regulate the lipid metabolism, with good safety.

  • Shun ZENG, Yi-tao LIN, Hao ZHOU, Ying PAN, Miao YU
    Chinese Journal of Clinical Pharmacology. 2025, 41(16): 2269-2274.
    Objective

    To analyze the effect of urapidil sustained release capsules combined with finasteride tablet in the treatment of benign prostatic hyperplasia with lower urinary tract symptoms.

    Methods

    Patients with benign prostatic hyperplasia accompanied by lower urinary tract symptoms were included and randomly divided into treatment group and control group. Both groups received basic treatment with finasteride tablets, 5 mg each time, once daily, orally. The treatment group was treated with urapidil sustained release capsules, with an initial dose of 30 mg per day. If the patient’s clinical symptoms did not improve within 1-2 weeks, the dose could be gradually increased to 60 mg per day, with a maximum dose not exceeding 60 mg per day, twice a day, orally. Control group did not receive additional treatment. Compare the improvement of symptoms, quality of life, urodynamic indicators, laboratory indicators, clinical efficacy and evaluate safety between two groups.

    Results

    A total of 45 patients in treatment group and control group were included respectively. Ten patients withdrew from the study due to lost to follow-up or personal factors during the study, 5 patients in each groups. Finally, a total of 80 patients completed the study, 40 patients in treatment group and 40 patients in control group. The total effective rate of treatment group was 95.00% (38 cases/40 cases), while that of control group was 80.00% (32 cases/40 cases), which was statistically significantly higher in treatment group than in control group (P<0.05). After treatment, the international prostate symptom score (IPSS) of treatment group and control group were (10.52±0.98) and (13.79±1.05) points; the prostate quality of life score (QoL) were (2.01±0.77) and (2.51±0.52) points, above indicators in treatment group were statistically significantly lower than those in control group (all P<0.05). After treatment, post-void residual urine volume (PVR) levels of treatment group and control group were (31.60±3.75) and (35.79±3.24) mL, respectively; the average urinary flow rates (AER) were (16.88±1.46) and (14.37±1.22) mL·s-1, respectively; the maximum urinary flow rates (Qmax) were (24.09±2.03) and (21.96±2.77) mL·s-1, respectively. The PVR level in treatment group was statistically significantly lower than that in control group, while the AER and Qmax levels were statistically significantly higher than those in the control group (all P<0.05). After treatment, the prostate-specific antigen (PSA) levels in treatment group and control group were (0.51±0.09) and (0.74±0.10) ng·L-1, respectively; the numbers of red blood cells in urine sediment were (37.41±3.06) and (40.25±3.22) cells per HP, respectively, and the above indicators in treatment group were statistically significantly lower than those in control group (all P<0.05). After treatment,the testosterone (T) levels in treatment group and control group were (974.05±16.87) and (929.78±16.77) ng·mL-1, respectively; the estradiol (E2) levels were (136.47±10.55) and (127.58±10.35) pg·mL-1, respectively. The above indicators in treatment group were significantly higher than those in control group (all P<0.05). The main adverse drug reactions in both groups were gastrointestinal discomfort, headache, etc. The incidence of adverse drug reactions in treatment group was 12.50% (5 cases/40 cases), while in control group was 5.00% (2 cases/40 cases). There was no statistically significant difference between the two groups (P>0.05).

    Conclusion

    Patients with benign prostatic hyperplasia accompanied by lower urinary tract symptoms were treated with combination therapy of urapidil sustained-release capsules and finasteride tablet, which improved their urodynamic indicators and clinical symptoms, restored their sex hormone levels, improved their treatment efficacy and quality of life.