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  • Jing-han ZHANG, Tao ZUO, Lei ZHAO
    Chinese Journal of Clinical Pharmacology. 2025, 41(16): 2386-2392.

    The treatment of posterior segment diseases has always been a challenge in the field of ophthalmology. How to overcome obstacles in drug delivery and improve the bioavailability of drugs in the posterior segment of the eye is one of the most challenging aspects in the field of drug research. The innovation of drug delivery routes and dosage forms, as well as breakthroughs in drug development, have brought new hope for the delivery of drugs in the posterior segment of the eye. This article reviews three aspects of innovative drug delivery routes for subretinal drug delivery, suprachoroidal drug delivery, and vitreous cavity implantation, innovative drug delivery form design for nano-formulations and exosomal formulations, and innovative drug development for intraocular injections, topical drops, and oral drugs, with the aim of providing new strategies for the treatment of diseases of the posterior segment of the eye.

  • Jiao-jiao ZUO, Rui-ze WANG, Wen-ting WANG, Rui-ping SONG, Peng-cheng DOU, Xin-yi CHEN, Zhuang-zhuang FENG, Jin SHU
    Chinese Journal of Clinical Pharmacology. 2025, 41(16): 2393-2400.

    Precancerous lesions of gastric cancer (PLGC) are considered as a high-risk factor for the development of gastric cancer. Existing studies have confirmed that hypoxia inducible factor-1α (HIF-1α) plays a key role in the progression of PLGC. HIF-1α promotes the malignant transformation of PLGC by regulating various cellular processes, including angiogenesis, aerobic glycolysis, autophagy, cell proliferation, and apoptosis. Traditional Chinese medicine (TCM) has been shown to modulate the HIF-1α signaling pathway and inhibit these pathological processes, thereby intervening in the development of PLGC. This review will focus on the mechanisms by which HIF-1α mediates PLGC and summarize the potential applications of TCM in the prevention and treatment of PLGC, aiming to provide a clear molecular framework for TCM intervention in PLGC and offer theoretical support and research directions for the development of innovative HIF-1α-targeted Chinese medicines.

  • Yan-yan CHAI, Yao SHENG, Dan-qun JIN, Wen-jia TONG, Yun WANG, Fang DENG
    Chinese Journal of Clinical Pharmacology. 2025, 41(11): 1501-1505.
    Objective

    To observe the clinical efficacy and safety of ferulic acid piperazine tablets combined with continuous renal replacement therapy in the treatment of children with acute renal failure.

    Methods

    Children with acute renal failure were randomly divided into control group and treatment group. Both groups were given basic treatment, based on which, the control group was given continuous renal replacement therapy; the treatment group was given piperazine ferulate tablets 100 mg per time, orally, tid, on the basis of control group. Two groups were treated for 2 weeks. The clinical efficacy, renal function, levels of renal injury markers and safety were compared between the two groups.

    Results

    Treatment group was enrolled 85 cases, 2 cases dropped out, and 83 cases were finally included in the statistical analysis. Control group was enrolled 84 cases, 3 cases dropped out, and 81 cases were finally included in the statistical analysis. After treatment, the total effective rates of treatment and control groups were 92.77% (77 cases/83 cases) and 81.48% (66 cases / 81 cases) with statistically significant difference (P<0.05). After treatment, the serum creatinine levels of treatment and control groups were (120.35±17.12) and (148.12±20.03) μmoL·L-1; the blood urea nitrogen levels were (12.29±2.14) and (15.64±3.01) μmoL·L-1; the β2-microglobulin levels were (1.87±0.25) and (2.14±0.39) mg·L-1; the 24-h urinary protein quantification were (0.94±0.31) and (1.24±0.47) g·24 h-1; N-acetyl-β-D-glucosidase contents were (17.03±2.98) and (20.36±3.51) U·L-1; the renal injury molecule 1 contents were (1.62±0.27) and (2.09±0.32) μg·L-1; the neutrophil gelatinase-associated lipid transport protein contents were (50.36±8.13) and (59.23±10.14) μg·L-1, respectively, and the differences were all statistically significant (all P<0.05). The adverse drug reactions of treatment group were nausea, vomiting and abdominal distension, while those in the control group were dizziness, nausea and vomiting. The total incidences of adverse drug reactions in the treatment and control groups were 7.23% and 4.94% without significant difference (P>0.05).

    Conclusion

    Ferulic acid piperazine tablets combined with continuous renal replacement therapy have definitive clinical efficacy in the treatment of children with acute renal failure, which can significantly improve the renal function of children, reduce renal injury, without increasing the incidence of adverse drug reactions.

  • Chun-hua CHEN, Gui-xin SUN
    Chinese Journal of Clinical Pharmacology. 2025, 41(11): 1506-1510.
    Objective

    To observe the clinical efficacy and safety of zoledronic acid concentrate injection combined with alendronate sodium tablets in the treatment of elderly postmenopausal patients with type 2 diabetes mellitus (T2DM) complicated with osteoporosis (OP).

    Methods

    Elderly postmenopausal T2DM patients with OP were divided into control group and treatment group using random number table method. The control group was given oral alendronate sodium tablets, 10 mg per dose, once daily (qd), for a course of 1 year; the treatment group, based on the control group, received additional treatment with zoledronic acid concentrate injection, 5 mg per dose, once a year, via intravenous infusion, for a course of 1 year. The clinical efficacy, pain levels at different time points, bone density before and after treatment, bone metabolism indicators before and after treatment and safety were compared between two groups.

    Results

    A total of 5 cases were lost during this study, with the final number of patients in the control and treatment groups being 38 cases and 42 cases, respectively. After treatment, the overall effective treatment rates were 84.21% (32 cases/38 cases) for the control group and 97.62% (41 cases /42 cases) for the treatment group, with statistically significant difference (P<0.05). The visual analogue scale (VAS) pain scores for the treatment group after 6 months and 1 year of treatment were (5.62±0.70) and (5.02±0.68) points, respectively, which were significantly lower than the control group’s (6.06±0.75) and (5.65±0.70) points. After 1 year of treatment, the bone density of the lumbar spine L1-4 were (0.89±0.07) and (0.85±0.08) g·cm-3 for the treatment and control groups, respectively; the femoral trochanter bone density were (0.78±0.08) and (0.73±0.09) g·cm-3; the femoral neck bone density was (0.69±0.07) and (0.66±0.06) g·cm-3; the bone density in the Ward triangle area were (0.79±0.08) and (0.73±0.10) g·cm-3; the serum levels of type Ⅰ procollagen amino propeptide were (25.60±6.82) and (30.79±6.90) pg·mL-1; the levels of bone-specific alkaline phosphatase (BALP) were (15.87±4.03) and (17.91±3.71) ng·mL-1; the levels of Klotho protein were (885.20±32.60) and (810.76±33.15) pg·mL-1; the levels of 25-hydroxyvitamin D [25-(OH)D] were (35.70±6.72) and (32.29±6.34) ng·mL-1 for the treatment and control groups, respectively. The above indicators of the treatment group were statistically significantly different from those of the control group (all P<0.05). The main adverse drug reactions in the control group were mainly gastrointestinal discomfort and fatigue, while in the treatment group were mainly fever, muscle and bone pain, gastrointestinal discomfort and fatigue. The overall incidence of adverse drug reactions were 18.42% (7 cases/38 cases) in the control group and 21.43% (9 cases /42 cases) in the treatment group, with no statistically significant difference (P>0.05).

    Conclusion

    The combined treatment of zoledronic acid concentrate injection and alendronate sodium tablets in elderly postmenopausal T2DM patients with OP is obviously effective, capable of effectively alleviating pain, increasing bone density, raising serum Klotho and 25-(OH)D levels, and reducing BALP levels, with adverse drug reactions being controllable.

  • Xin WANG, Min LI, Qian DENG, Juan-juan WANG
    Chinese Journal of Clinical Pharmacology. 2025, 41(11): 1511-1516.
    Objective

    To observe the efficacy of low-dose triptorelin acetate injection combined with vitamin D drop in the treatment of central precocious puberty (CPP) in girls.

    Methods

    CPP children were divided into treatment group and control group using a cohort method. The treatment group received a low-dose of triptorelin acetate injection at 50 μg·kg-1 via intramuscular injection every 4 weeks, along with oral vitamin D drop at 400 units. The control group received standard dose treatment, starting with an initial dose of 100 μg·kg-1 via intramuscular injection, followed by a maintenance dose of 80 μg·kg-1 every 4 weeks. Both groups were treated continuously for 12 months. The clinical efficacy, physical development, hormone levels, secretion levels of peptides and hormones related to the hypothalamic-pituitary-gonadal axis were compared between the two groups, along with safety evaluation.

    Results

    During the trial, 42 cases were included in the treatment group and 37 cases in the control group. After treatment, the overall effective rates for the treatment and control groups were 90.48% (38 cases/42 cases) and 78.38% (29 cases/37 cases), respectively, with no statistically significant difference (P>0.05). After treatment, the predicted adult height for the treatment and control groups was (164.59±4.35) and (162.38±5.21) cm, respectively; the differences in bone age were (1.07±0.28) and (1.24±0.29) years; the growth rates were (5.35±1.17) and (5.93±1.24) cm·year-1; estradiol levels were (13.11±5.67) and (16.08±4.73) pg·mL-1; luteinizing hormone levels were (1.49±0.20) and (2.15±0.18) U·L-1; follicle-stimulating hormone levels were (4.95±0.74) and (6.14±0.87) pg·mL-1; neuropeptide kisspeptin levels were (1.02±0.19) and (1.20±0.40) μg·L-1; neurokinin B levels were (0.35±0.08) and (0.41±0.08) μg·L-1; anti-Müllerian hormone levels were (3.88±0.36) and (4.15±0.40) ng·L-1; insulin-like growth factor-1 levels were (216.91±25.43) and (231.64±30.87) ng·mL-1; 25-hydroxyvitamin D levels were (28.42±4.52) and (26.15±3.73) μg·L-1, with statistically significant difference (all P<0.05). The main adverse drug reactions in the treatment group included nausea and vomiting, as well as pain and swelling at the injection site. In the control group, the main adverse drug reactions included slight vaginal bleeding, nausea and vomiting, pain and swelling at the injection site and rashes near the injection site. The overall incidence of adverse drug reactions in the treatment group and control group were 7.14% (3 cases/42 cases) and 16.22% (6 cases/37 cases), without statistically significant difference (P>0.05).

    Conclusion

    In children with CPP, the application of low-dose triptorelin combined with vitamin D drop can improve clinical efficacy, physical development, growth-related factors, hormone levels and the secretion levels of peptides and hormones associated with the hypothalamic-pituitary-gonadal axis. It can also slow the development of secondary sexual characteristics and inhibit gonadal development, while demonstrating good safety.

  • Yong-qiang WANG, Bo-fei TAN, Yue ZHU
    Chinese Journal of Clinical Pharmacology. 2025, 41(11): 1517-1521.
    Objective

    To observe the clinical efficacy and safety of tislelizumab injection in the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and resistance to targeted therapy.

    Methods

    Patients with advanced NSCLC and EGFR mutations were assigned to control group and treatment group. The control group received 500 mg·m-2 pemetrexed disodium for injection by intravenous infusion on the first day + 7.5 mg·kg-1 bevacizumab injection by intravenous infusion every 3 weeks + 80 mg·m-2 nedaplatin by intravenous infusion on the first day. On the basis of control group, the treatment group received 200 mg tislelizumab injection by intravenous infusion every 3 weeks. Two groups were treated for 3 cycles with 3 weeks per cycle. The clinical efficacy, tumor markers, quality of life and safety were compared between two groups.

    Results

    Treatment group was enrolled 51 cases; control group was enrolled 51 cases. After treatment, the overall effective rates of treatment and control groups were 54.90% (28 cases / 51 cases) and 21.57% (11 cases / 51 cases), with statistically significant difference (P<0.01). After treatment, the levels of carcinoembryonic antigen (CEA) in treatment and control groups were (6.67±1.24) and (11.58±1.36) ng·mL-1; the levels of cytokeratin-19 fragments were (7.64±1.47) and (12.25±1.63) ng·mL-1; the levels of neuron-specific enolase were (22.65±2.81) and (25.05±2.94) ng·mL-1; the quality of life scores were (73.67±6.24) and (64.45±5.36) points; the median progression-free survival were 7.00 and 10.00 months; the median overall survival were 14.00 and 20.00 months, respectively. The differences of above indexes were statistically significant between two groups (all P<0.05). The adverse drug reactions of two groups were nausea and vomiting, liver function impairment and renal function impairment. The incidences of total adverse drug reactions in treatment and control groups were 27.45% (14 cases/51 cases) and 31.37% (16 cases/51 cases), without statistically significant difference (P>0.05).

    Conclusion

    Tislelizumab injection has a definitive clinical efficacy in the treatment of patients with advanced NSCLC harboring EGFR mutations and resistance to targeted therapy, which can reduce the tumor marker levels, improve the quality of life, with high safety.

  • Lu-mei WANG, Jing CHEN, Bin WANG
    Chinese Journal of Clinical Pharmacology. 2025, 41(11): 1522-1526.
    Objective

    To observe the clinical efficacy and safety of agomelatine combined with paroxetine tablets in patients with depression and insomnia, and its effects on neurotransmitter levels and sleep.

    Methods

    The patients with depression and insomnia were divided into control group and treatment group, according to random number table. Control group was treated with paroxetine tablets 20 mg, oral, treatment course was 8 weeks. Treatment group was treated with agomelatine 25 mg and paroxetine tablets 20 mg, once a day, treatment course was 8 weeks. The Hamilton depression rating scale (HAMD), Montreal cognitive assessment scale (MoCA), neurotransmitters [norepinephrine (NE), 5-hydroxytryptamine (5-HT), dopamine (DA)], Pittsburgh sleep quality index (PSQI) and incidence of adverse drug reactions between two groups were compared.

    Results

    Treatment group was enrolled 60 cases; control group was enrolled 60 cases. After 8 weeks of treatment, the HAMD in treatment group and control group were (17.33±1.54) and (21.19±1.87) scores; MoCA were (29.01±0.19) and (28.52±0.21) scores; NE levels were (65.56±4.63) and (53.74±4.52) ng·mL-1; 5-HT levels were (165.82±7.17) and (149.63±8.48) ng·mL-1; DA levels were (582.73±17.52) and (543.85±20.38) ng·mL-1, sleep latency were (1.09±0.12) and (1.53±0.15) scores; sleep efficiency were (1.12±0.17) and (1.58±0.20) scores; hypnotic drug were (1.01±0.13) and (1.42±0.15) scores; subjective sleep quality were (1.14±0.10) and (1.62±0.16) scorse; sleep persistence were (1.16±0.11) and (1.55±0.13) scores; the score for sleep disorders were (1.07±0.14) and (1.52±0.17) scores; daytime functional disorders were (0.99±0.16) and (1.51±0.18) scores, all with statistically significant difference (all P<0.05). The adverse drug reactions in treatment group and control group were 11.67% and 8.33%, with no statistically significant differences (P>0.05).

    Conclusion

    Administration of agomelatine and paroxetine tablets to patients with depression and insomnia can improve depressive symptoms, cognitive function, sleep conditions, regulate the expression of neurotransmitters such as NE and 5-HT, and has good safety.

  • Zhuo WU, Shuai-shuai FAN, Xiao-dong WEN
    Chinese Journal of Clinical Pharmacology. 2025, 41(11): 1527-1531.
    Objective

    To analyze the preventive effect of potassium citrate sustained-release tablets on stent mural calculi after ureteral lithotripsy for upper urinary tract calculi and influence on urinary calcium ion and urinary oxalic acid concentration.

    Methods

    The patients with upper urinary tract calculi who underwent ureteral lithotripsy were randomly divided into control group and treatment group. Both groups of patients received routine dietary guidance and health education after surgery. The control group received routine anti-infection, pain relief and stone removal treatment after surgery, while the treatment group received oral potassium citrate sustained-release tablets on the basis of the control group after surgery (1.08 g per time, 3 times a day) continuously until the ureteral stent tube was removed. The ureteral stent tube was removed at 4 or 8 weeks after surgery based on the patient’s recovery status, and the occurrence of stent mural calculi was observed, and 24-hour urine samples were collected from patients during follow-up at 4 weeks after surgery to detect urine pH, levels of uric acid, oxalic acid and citric acid and concentrations of calcium and phosphorus ions. The differences in occurrence of ureteral stent calculi and urine detection indicators were compared between the two groups.

    Results

    In treatment group, 42 cases were enrolled but 2 cases were lost to follow-up, and 40 cases were finally included for statistical analysis. In control group, 43 patients were included but 3 patients were lost to follow-up, thus 40 patients were enrolled for statistical analysis. Ureteral stents were removed at 4 weeks or 8 weeks after surgery in both groups. The treatment group had a total of 64 ureteral stent tubes retained, and the incidence rate of stent mural calculi was 1.56% (1 case/64 cases). The control group had a total of 62 ureteral stent tubes retained, and the incidence rate of stent mural calculi was 11.29% (7 cases/62 cases, P<0.05). At 4 weeks after surgery, the calcium ion concentrations in treatment group and control group were (2.63±0.66) and (3.45±1.02) mmol·L-1, oxalic acid levels were (0.41±0.04) and (0.52±0.07) mmol·L-1, phosphorus ion concentrations were (12.36±2.38) and (16.01±2.16) mmol·L-1, uric acid levels were (2.02±0.17) and (2.43±0.23) mmol·L-1, urine pH values were 6.85±0.34 and 6.24±0.34, urine citric acid levels were (1.61±0.22) and (1.39±0.17) mmol·L-1, respectively (all P<0.05). The adverse drug reactions in treatment group during medication included nausea and diarrhea, with a total incidence rate of 10.00% (4 cases/40 cases). No adverse drug reactions were observed in the control group.

    Conclusion

    Potassium citrate sustained-release tablets can reduce the incidence rate of stent mural calculi after ureteral lithotripsy for upper urinary tract calculi, and lower the concentrations of urinary calcium ion and oxalic acid.

  • Chen-yu HU, Jia-zhen TIAN, Han-yu YAN, Ting ZHANG, A-bu-li-zi AMIER, Xiang-quan MI
    Chinese Journal of Clinical Pharmacology. 2025, 41(11): 1532-1537.
    Objective

    To investigate the inhibition of NG108-15 cells proliferation by Xanthohumol (XN) and its effects on reactive oxygen species (ROS), extracellular signal-regulated kinase (ERK) pathway and cell cycle.

    Methods

    NG108-15 cells were divided into control group (conventional culture), experimental-L group, experimental-M group, experimental-H group (20, 40, and 60 μmol·L-1 XN), NAC combined with XN experimental group [10 μmol·L-1 N-acetylcysteine (NAC)+40 μmol·L-1 XN] and ERK inhabitor combined with XN experimental group (20 μmol·L-1 ERK inhibitor PD98059+40 μmol·L-1 XN). Cell proliferation capacity was detected by cell counting kit 8 (CCK-8) and trypan blue staining assay; ROS levels were detected by ROS kit; cell cycle and apoptosis levels were detected by flow cytometry; protein relative expression levels of ERK, p-ERK and Caspase 3 were detected by Western blot.

    Results

    The cell proliferation activities of the control group and the experimental-L group, experimental-M group and experimental-H group were (99.89±1.52)%, (87.57±6.23)%, (51.96±3.08)% and (37.11±1.57)%, respectively; the cell death rates were (4.65±1.57)%, (15.54±1.94)%, (41.06±2.77)% and (65.22±5.81)%, respectively; the average fluorescence intensities of ROS in the control group, the experimental-M group and the NAC combined with XN experimental group were 176.51±25.17, 716.48±95.15 and 543.80±48.91. The relative expression levels of p-ERK protein in the control group, the experimental-M group, and the ERK inhibitor combined with XN experimental group were 0.54±0.04, 1.13±0.18 and 0.31±0.33; the proportions of G2 phase cells were (15.56±1.43)%, (20.31±2.17)% and (16.14±0.81)%, respectively. Compared with the control group, the above indicators in the experimental-L, -M, -H groups showed statistically significant differences (all P<0.001). Compared with the experimental-M group, the control group and the NAC combined with XN experimental group showed statistically significant differences (P<0.05, P<0.01, P<0.001). Compared with the experimental-M group, the ERK inhibitor combined with XN experimental group showed statistically significant differences (P<0.05, P<0.01, P<0.001).

    Conclusion

    Xanthohumol demonstrates potent inhibition of NG108-15 cells proliferation, with its molecular mechanism likely involving G2/M phase cell cycle arrest through ROS upregulation and activation of the ERK signaling pathway.

  • Ming-yuan XING, Xue-wu CHEN, Ting WU, Xue-ying LIN, Ming-quan FU, Kai-yu WANG
    Chinese Journal of Clinical Pharmacology. 2025, 41(11): 1538-1543.
    Objective

    To investigate the effect of Jinfu’an decoction on the apoptosis of non-small cell lung cancer cells (A549) by regulating phosphatidylinositol 3-kinase/ protein kinase B/ mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway mediated autophagy.

    Methods

    A549 cells were randomly divided into blank group, control group, combined group and experimental -L, -M, -H groups. The blank group was treated with 10% blank serum. The control group was treated with 20 μmol·L-1 PI3K specific activator (740Y-P). The experimental-L, -M, -H groups were treated with 5%, 10% and 20% Jinfu ’an decoction containing serum, respectively. The combined group was treated with 20% Jinfu ’an decoction serum +20 μmol·L-1 740Y-P. Flow cytometry was used to detect the apoptosis rate. Western blot was used to detect the expression levels of microtubule-associated protein 1A/1B -light chain 3 (LC3), sequestosome-1 (p62), Akt and mTOR.

    Results

    The apoptosis rates of experimental -H group, combined group, control group and blank group were (31.48±1.35)%, (14.91±1.26)%, (3.30±0.45)% and (7.73±0.50)%, respectively; the relative expression levels of LC3 Ⅱ/Ⅰ protein were 1.13±0.10, 0.77±0.06, 0.31±0.04 and 0.50±0.04, respectively; the relative expression levels of p62 protein were 0.32±0.03, 0.56±0.05, 1.07±0.06 and 0.83±0.06, respectively; the relative expression levels of p-Akt/Akt protein were 0.33±0.04, 0.80±0.07, 0.98±0.09 and 0.52±0.03, respectively; the relative expression levels of p-mTOR/mTOR protein were 0.53±0.04, 0.84±0.06, 1.14±0.08 and 1.01±0.06, respectively. The above indexes of the experimental -H group were statistically different from those of the combination group and the blank group (all P<0.05).

    Conclusion

    Jinfu’an decoction can promote the apoptosis of A549 cells, and its mechanism may be related to the inhibition of PI3K/Akt/mTOR signaling pathway and the activation of cell autophagy.