Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

OBJECTIVE：To study the effects a nd mechanism of X iaozheng decoction on the proliferation and migration of uterine leiomyoma cells in rat. METHODS ：Female SD rats were randomly divided into normal control group ，model group ， chemical medicine positive control group （Mifepristone tablets ，2.25 mg/kg），TCM positive control group （Guizhi fuling capsules ， 200 mg/kg），Xiaozheng decoction low-dose ，medium-dose and high-dose groups （1.4，2.8，5.6 g/kg），with 15 rats in each group. Except for normal control group ，other groups were given intramuscular injection of estrogen and progesterone to induce uterine leiomyomas model. On the second day after modeling ，rats in administration groups were given relevant medicine intragastrically ； normal control group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 4 months. After last administration ，the uterus was removed and its morphology was observed ；the uterine coefficient was calculated. Uterine leiomyoma cells or uterine smooth muscle cells were isolated and cultured. The proliferation rate and migration rate of cells were detected by MTT method and cell scratch test ；flow cytometry was used to detect the cell apoptosis rate ；mRNA expression of HMGB 1 were detected by RT-qPCR. The expression of phosphorylated protein kinase B （p-Akt），nuclear factor κB inhibitor α （IκBα）and phosphorylated transforming growth factor β-activated kinase 1（p-TAK1）were detected by ELISA ；the protein expression of HMGB 1，phospholipid 3 kinase（PI3K），p-Akt in cytoplasm and nuclear factor κB p65（NF-κB p65）in nucleus were detected by Western blot assay. RESULTS ：Compared with normal control g roup，the myometrium of the model group was significantly thickened ，the number of uterine smooth muscle cells were significantly increased and the sizes were 83777930。E-mail：jianghua_ouyang@126.com different，the arrangement of muscle fibers in so me areas was disordered，the uterine coefficient ，and the relative expression of HMGB 1 mRNA and protein were increased significantly （P＜ 0.01）. Compared with model group ，the thickening of uterine myometrium and other symptoms were improved to different extents in Xiaozheng decoction groups and positive control groups ；the uterine coefficient ，cell proliferation rate ，migration rate ，mRNA and protein expression of HMGB 1，the expression of p-Akt and IκBα，protein expression of PI 3K and p-Akt （except for Xiaozheng decoction low-dose group ）in cytoplasm were all decreased significantly （P＜0.05 or P＜0.01）；the cell apoptosis rate ，the expression of p-TAK 1，protein expression of NF-κB p65 in nucleus were all increased significantly （P＜0.05 or P＜0.01）. The effects of Xiaozheng decoction showed a dose-dependent trend. CONCLUSIONS ：Xiaozheng decoction can inhibit the proliferation and migration of uterine leiomyoma cells by down-regulating the expression of HMGB 1，PI3K and p-Akt ，up-regulating the expression of NF-κB p65，so as to promote cell apoptosis.