1.Phase Ⅲ, multicenter, randomized comparative study of LY01005 and Zoladex ? for patients with premenopausal breast cancer
Xiying SHAO ; Qingyuan ZHANG ; Zhaofeng NIU ; Man LI ; Jingfen WANG ; Zhanhong CHEN ; Ruizhen LUO ; Guangdong QIAO ; Jianguo WANG ; Liyuan QIAN ; Ronghua YANG ; Zhendong CHEN ; Jian WANG ; Yumin YAO ; Jianghua OU ; Tao SUN ; Qiao CHENG ; Yongsheng WANG ; Jian HUANG ; Hongying ZHAO ; Wuyun SU ; Zhong OUYANG ; Yu DING ; Lilin CHEN ; Sumei YANG ; Mengsheng CUI ; Aimin ZANG ; Enxiang ZHOU ; Peizhi FAN ; Jing ZHANG ; Qiang LIU ; Yuee TENG ; Hui LI ; Jianyun NIE ; Jin YANG ; Xiaojia WANG ; Zefei JIANG
Chinese Journal of Oncology 2025;47(4):340-348
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.
2.Effect of losartan on high salt intake induced by angiotensin Ⅱ in the locus coeruleus of the brain
Junbao YAN ; Yixiang CHEN ; Xiaoyan NIU ; Zhaofeng LU
The Journal of Practical Medicine 2025;41(20):3155-3164
Objective By observing the effect of angiotensin Ⅱ in the locus coeruleus of the brain on high salt intake and the impact of losartan on this effect,this study explores effective implementation methods for salt restriction strategies.Methods Brain catheterization and microinjection were used to administer single microinjection of Ang Ⅱ into the locus coeruleus of rats,as well as combined microinjection of saline,Ang Ⅱ,and angiotensin Ⅱ type 1 receptor,AT1R antagonist losartan was used to observe the changes in the intake and water intake of hypertonic sodium chloride solution in rats with different sodium intake models;Single microinjection of Ang Ⅱ into the locus coeruleus of rats was performed to observe changes in water intake in water deprived rats,as well as changes in urine output,sodium excretion,horizontal and vertical activity in normal rats.Results Whether in rats treated with"water deprivation partial rehydration(WD-PR)"or in rats treated with"subcutaneous combined injection of furosemide(FURO)and Captopril(CAP)(FURO-CAP)",microinjection of 0.1 ng,1 ng,and 10 ng doses of Ang Ⅱ into the locus coeruleus caused a dose-dependent increase in 0.3 mol/L NaCl intake and water intake.However,pre injection of AT1R antagonist losartan at doses of 0.5 μ g,5 μ g,and 50 μ g significantly inhibited the injection of 10 ng Ang Ⅱ into the same site in a dose-dependent manner.The increase in intake of 0.3 mol/L NaCl and water caused by it.Compared with injection of saline into the locus coeruleus,injection of 10.0ng dose of Ang Ⅱ into the locus coeruleus significantly increased the horizontal and vertical activity of rats,but had no significant effect on renal excretion.Conclusion Losartan can inhibit the high salt intake induced by Ang Ⅱ in the locus coeruleus of the brain,and can be used as an effective drug in the salt limiting strategy for controlling hypertension.
3.Effect of losartan on high salt intake induced by angiotensin Ⅱ in the locus coeruleus of the brain
Junbao YAN ; Yixiang CHEN ; Xiaoyan NIU ; Zhaofeng LU
The Journal of Practical Medicine 2025;41(20):3155-3164
Objective By observing the effect of angiotensin Ⅱ in the locus coeruleus of the brain on high salt intake and the impact of losartan on this effect,this study explores effective implementation methods for salt restriction strategies.Methods Brain catheterization and microinjection were used to administer single microinjection of Ang Ⅱ into the locus coeruleus of rats,as well as combined microinjection of saline,Ang Ⅱ,and angiotensin Ⅱ type 1 receptor,AT1R antagonist losartan was used to observe the changes in the intake and water intake of hypertonic sodium chloride solution in rats with different sodium intake models;Single microinjection of Ang Ⅱ into the locus coeruleus of rats was performed to observe changes in water intake in water deprived rats,as well as changes in urine output,sodium excretion,horizontal and vertical activity in normal rats.Results Whether in rats treated with"water deprivation partial rehydration(WD-PR)"or in rats treated with"subcutaneous combined injection of furosemide(FURO)and Captopril(CAP)(FURO-CAP)",microinjection of 0.1 ng,1 ng,and 10 ng doses of Ang Ⅱ into the locus coeruleus caused a dose-dependent increase in 0.3 mol/L NaCl intake and water intake.However,pre injection of AT1R antagonist losartan at doses of 0.5 μ g,5 μ g,and 50 μ g significantly inhibited the injection of 10 ng Ang Ⅱ into the same site in a dose-dependent manner.The increase in intake of 0.3 mol/L NaCl and water caused by it.Compared with injection of saline into the locus coeruleus,injection of 10.0ng dose of Ang Ⅱ into the locus coeruleus significantly increased the horizontal and vertical activity of rats,but had no significant effect on renal excretion.Conclusion Losartan can inhibit the high salt intake induced by Ang Ⅱ in the locus coeruleus of the brain,and can be used as an effective drug in the salt limiting strategy for controlling hypertension.
4.Phase Ⅲ, multicenter, randomized comparative study of LY01005 and Zoladex ? for patients with premenopausal breast cancer
Xiying SHAO ; Qingyuan ZHANG ; Zhaofeng NIU ; Man LI ; Jingfen WANG ; Zhanhong CHEN ; Ruizhen LUO ; Guangdong QIAO ; Jianguo WANG ; Liyuan QIAN ; Ronghua YANG ; Zhendong CHEN ; Jian WANG ; Yumin YAO ; Jianghua OU ; Tao SUN ; Qiao CHENG ; Yongsheng WANG ; Jian HUANG ; Hongying ZHAO ; Wuyun SU ; Zhong OUYANG ; Yu DING ; Lilin CHEN ; Sumei YANG ; Mengsheng CUI ; Aimin ZANG ; Enxiang ZHOU ; Peizhi FAN ; Jing ZHANG ; Qiang LIU ; Yuee TENG ; Hui LI ; Jianyun NIE ; Jin YANG ; Xiaojia WANG ; Zefei JIANG
Chinese Journal of Oncology 2025;47(4):340-348
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.
5.Efficacy and safety of camrelizumab combined with apatinib in the treatment of triple-negative breast cancer:a Meta-analysis and systematic review
Zhaofeng NIU ; Yanghai ZHAI ; Rui GENG
Chinese Journal of Pharmacoepidemiology 2024;33(10):1137-1146
Objective To systematically review the efficacy and safety of camrelizumab and apatinib in the treatment of triple-negative breast cancer.Methods PubMed,Web of Science,Embase,Cochrane Library,CNKI,and WanFang Data databases were electronically searched to collect clinical studies of carelizumab combined with apatinib(combination group)or it vs.carelizumab alone(single group)in the treatment of triple-negative breast cancer from inception to June 14,2024.Two reviewers independently screened the literature,extracted data,and assessed the risk of bias in the included studies.Meta-analysis was performed by using RevMan 5.4.1 and STATA 15 softwares.Results A total of 6 studies were included,1 randomized controlled trial,2 cohort studies,and 3 single-arm trials,involving 366 patients.The results of the Meta-analysis indicated that the objective response rate(ORR)(OR=2.77,95%CI 1.60 to 4.81,P<0.001),and disease control rate(DCR)(OR=2.27,95%CI 1.34 to 3.85,P=0.002)in the combination group were significantly higher than those of the single group.The results of the single-arm trial showed that after the treatment of camrelizumab combined with apatinib,the ORR and DCR of the patients were 28%(95%CI 0.04 to 0.52)and 65%(95%CI 0.37 to 0.92),respectively.The overall progression-free survival of the patients after the combined treatment was 5.66 months(95%CI 3.78 to 8.48).The incidences of leukopenia(OR=1.45,95%CI 0.50 to 4.17,P=0.49),rash(OR=1.11,95%CI 0.35 to 3.49,P=0.86),nausea and vomiting(OR=1.28,95%CI 0.36 to 4.61,P=0.70)were not statistically significantly between the combination group and the single group.Conclusion Current evidence shows that carilizumab combined with apatinib has synergistic efficacy in treating triple-negative breast cancer,improves cellular immune function,and has a controllable safety profile.Due to the limitations of the number and quality of studies included,the above conclusion still needs to be verified by more high-quality studies.
6.Clinical efficacy of ultrasound-guided vacuum-assisted excision in the treatment of breast benign phyllode tumor and the risk factors of local recurrence after operation
Junqiang MA ; Xiaoke HOU ; Qiang GUO ; Zhaofeng NIU
International Journal of Surgery 2023;50(2):93-97
Objective:To investigate the clinical efficacy of ultrasound-guided vacuum-assisted excision (VAE) in the treatment of breast benign phyllode tumor and the risk factors of local recurrence after operation.Methods:A total of 256 cases of patients with breast benign phyllode tumor admitted to Yuncheng Central Hospital from January 2012 to January 2020 were included in the retrospective study, they were all female, of which 160 cases received ultrasound-guided VAE surgical treatment and 96 cases received open surgical treatment. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between groups. The Chi-square test or Fisher exact probability method was used to compare the data groups. Univariate analysis was performed on the factors related to the local recurrence of benign phyllode tumor after surgery, and then the factors with statistically significant differences in the univariate analysis were further incorporated into multivariate Logistic regression analysis. Results:Univariate analysis results showed that the maximum diameter of tumor ≥25 mm and the history of ipsilateral breast fibroadenoma were associated with postoperative local recurrence of breast benign phyllodes tumor ( P<0.05). Multivariate Logistic regression analysis results showed that tumor diameter ≥25 mm was an independent risk factor for postoperative local recurrence of breast benign phyllodes tumor ( P<0.05). Conclusion:Ultrasound-guided VAE in the treatment of breast benign phyllodes tumor patients with maximum diameter less than 25 mm can reduce the postoperative local recurrence rate, and patients with tumor maximum diameter greater than 25 mm should have the higher local recurrence risk.
7.Tendency of elderly patients with breast cancer to choose comprehensive treatment mode and its influencing factors
Rui GENG ; Junqiang MA ; Qiang GUO ; Zhaofeng NIU
Journal of International Oncology 2023;50(11):650-654
Objective:To analyze the tendency of elderly patients with breast cancer in the choice of treatment methods and related influencing factors.Methods:The data of 312 elderly patients with unilateral breast cancer treated in Yuncheng Central Hospital from January 2013 to December 2017 were collected for retrospective analysis. All patients' treatment options were analyzed, and the age of patients who chose different treatment options was compared. Univariate and logistic regression were used to analyze the chemotherapy choice tendency of elderly breast cancer patients, and Cox proportional risk model was used to analyze the influencing factors of 5-year survival of elderly breast cancer patients.Results:In the whole patient population, the selection rates of surgery, chemotherapy, radiotherapy, endocrine therapy and targeted therapy were respectively 97.44% (304/312), 81.41% (254/312), 7.05% (22/312), 68.27% (213/312), 3.85% (32/312). The mean age of all patients was (67.94±6.55) years. There were no statistically significant differences in the age of patients with different treatment methods (all P>0.05). The results of univariate analysis showed that, there were statistically significant differences in the depth of invasive cancer ( t=3.11, P=0.002), number of axillary lymph node metastasis ( t=6.54, P<0.001), comorbidities ( t=-4.85, P<0.001) and Eastern Cooperative Oncology Group (ECOG) score ( t=-4.56, P<0.001) between chemotherapy and non-chemotherapy patients, and there were no statistically significant differences in age ( t=-0.52, P=0.604), pathological type ( χ2=4.96, P=0.084), surgical type ( χ2=0.21, P=0.899), tumor differentiation degree ( χ2=3.28, P=0.194), estrogen receptor ( χ2=0.99, P=0.321), progesterone receptor ( χ2=0.89, P=0.346), and human epidermal growth factor receptor-2 ( χ2=0.58, P=0.445). The results of multifactor analysis showed that types of comorbidities ( OR=0.91, 95% CI: 0.85-0.99, P=0.024) and ECOG score ( OR=0.95, 95% CI: 0.92-0.99, P=0.007) were independent influencing factors for the use of chemotherapy after surgery in elderly breast cancer patients. A total of 74 patients died within 5 years after surgery, and the 5-year overall survival rate was 76.28%. More axillary lymph node metastasis ( RR=1.26, 95% CI: 1.09-1.46, P=0.001) and more complications ( RR=1.07, 95% CI: 1.02-1.13, P=0.007) were risk factors for prognosis. Conclusion:Surgery and chemotherapy are the main treatment methods for elderly patients with breast cancer. ECOG score and number of complications can directly affect the results of chemotherapy selection for such patients, the number of axillary lymph node metastasis and complications had significant influence on the long-term survival of the patients.

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