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.

Antibody-drug conjugates(ADCs)represent a major breakthrough in the treatment of human epidermal growth factor receptor-2(HER-2)-positive breast cancer as they are responsible for significantly improving clinical outcomes.However,their widespread use is accom-panied by severe adverse effects that not only impact the quality of life of patients and treatment adherence but also life-threatening,ulti-mately leading to treatment discontinuation.This article systematically reviews the underlying mechanisms and management strategies for ADC-related toxicities in HER-2-positive breast cancer.Additionally,it focuses on key adverse events,including thrombocytopenia,interstitial lung disease,and cardiotoxicity,that are induced by ADCs such as trastuzumab emtansine(T-DM1)and trastuzumab deruxtecan(T-DXd).Based on the clinical evidence,we proposed early monitoring and standardized intervention measures,emphasizing the importance of timely recognition and systematic management to mitigate risks.Furthermore,we explored future directions for optimizing ADC design to reduce their toxicity and provide valuable insights into their safe clinical application.

Antibody-drug conjugates(ADCs)represent a major breakthrough in the treatment of human epidermal growth factor receptor-2(HER-2)-positive breast cancer as they are responsible for significantly improving clinical outcomes.However,their widespread use is accom-panied by severe adverse effects that not only impact the quality of life of patients and treatment adherence but also life-threatening,ulti-mately leading to treatment discontinuation.This article systematically reviews the underlying mechanisms and management strategies for ADC-related toxicities in HER-2-positive breast cancer.Additionally,it focuses on key adverse events,including thrombocytopenia,interstitial lung disease,and cardiotoxicity,that are induced by ADCs such as trastuzumab emtansine(T-DM1)and trastuzumab deruxtecan(T-DXd).Based on the clinical evidence,we proposed early monitoring and standardized intervention measures,emphasizing the importance of timely recognition and systematic management to mitigate risks.Furthermore,we explored future directions for optimizing ADC design to reduce their toxicity and provide valuable insights into their safe clinical application.

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 investigate the correlation between D-dimer, serum potassium and thromboelastography parameters and progressive hemorrhagic injury (PHI) after brain injury. 【Methods】 The data of 209 patients with traumatic brain injury (TBI) in our hospital from January 2018 to May 2021 were collected and analyzed. The patients were divided into PHI group (161 cases) and non-PHI group (48 cases) according to CT scan whether the total bleeding lesions had increased by 25%. Univariate analysis and multivariate Logistic regression were used to analyze the risk factors of PHI, and receiver operating curve (ROC) was used to analyze the predictive value of D-dimer, serum potassium and thromboelastography (TEG) parameters used alone and in combination. 【Results】 PHI occurred in 48 (23.0 %) out of 209 TBI patients. In univariate analysis, there were statistically significant differences in GCS score, age, light emission, systolic blood pressure, serum potassium, blood calcium, blood glucose, R value, PT, APTT, INR, D-dimer, arachnoid hemorrhage, subdural hematoma, cerebral contusion and midline location between the two groups (P<0.05). Five independent risk factors were determined by multivariate Logistic analysis (P<0.05): D-dimer ≥3.52 μg/mL, serum potassium <3.70 mmol/L, R value ≥5.65 min, subdural hematoma and cerebral contusion. PHI model was constructed according to independent risk factors, and the maximum area under the curve (AUC) of D-dimer plus serum potassium plus R value plus subdural hematoma plus cerebral contusion was 0.889 9. 【Conclusion】 D-dimer ≥3.52 μg/mL, serum potassium <3.70 mmol/L, R value ≥5.65 min, subdural hematoma and cerebral contusion are significant influences for PHI occurrance in TBI patients.

Objective To screen out significant differential genes for predicting the effect of neoadjuvant chemotherapy (NAC) and select the most suitable breast cancer patients for NAC. Methods A total of 60 breast cancer patients' samples before and after NAC were collected for high-throughput RNA-Seq. We selected AHNAK, CIDEA, ADIPOQ and AKAP12 as the candidate genes that related to tumor chemotherapeutic resistance. We analyzed the correlation of AHNAK, CIDEA, ADIPOQ, AKAP12 expression levels with the effect of NAC by logistic regression analysis, constructed a prediction model and demonstrated the model by the nomogram. Results AHNAK, CIDEA, ADIPOQ and AKAP12 expression were up-regulated in the residual tumor tissues of non-pCR group after NAC(P < 0.05). Compared with pCR group, non-pCR group presented higher expression levels of AHNAK, CIDEA, ADIPOQ and AKAP12 (P < 0.05). The high expression levels of AHNAK, CIDEA, ADIPOQ and AKAP12 significantly reduced the pCR rate of NAC for breast cancer (P < 0.05). Our prediction model which AHNAK, CIDEA, ADIPOQ and AKAP12 were involved in showed a good fitting effect with H1 test (χ²=6.3967, P=0.4945) and the ROC curve (AUC 0.8249, 95%CI: 0.722-0.9271). Conclusion AHNAK, CIDEA, ADIPOQ and AKAP12 may be novel marker genes for NAC effect on breast cancer. The efficacy prediction model based on this result is expected to be a new method to select the optimal patients of breast cancer for neoadjuvant chemotherapy.

With the extensive use of sentinel lymph node biopsy (SLNB), some breast cancer patients could avoid axillary lymph node dissection (ALND) and its complications. Neoadjuvant chemotherapy plays an important role in the multimodality therapies of breast cancer. After neoadjuvant chemotherapy, some patients with breast cancer were down-staged from positive axillary lymph node (cN+ ) to clinically negative (cN0). For these patients, the feasibility and safety of sentinel lymph node biopsy remains controversial. However, with the application of new technologies, SLNB is expected to become the main treatment for breast cancer patients with stage cN0 after neoadjuvant chemotherapy.

With the extensive use of sentinel lymph node biopsy ( SLNB), some breast cancer patients could avoid axillary lymph node dissection (ALND) and its complications. Neoadjuvant chemotherapy plays an important role in the multimodality therapies of breast cancer. After neoadjuvant chemotherapy, some patients with breast cancer were down?staged from positive axillary lymph node (cN+) to clinically negative ( cN0). For these patients, the feasibility and safety of sentinel lymph node biopsy remains controversial. However, with the application of new technologies, SLNB is expected to become the main treatment for breast cancer patients with stage cN0 after neoadjuvant chemotherapy.

With the extensive use of sentinel lymph node biopsy ( SLNB), some breast cancer patients could avoid axillary lymph node dissection (ALND) and its complications. Neoadjuvant chemotherapy plays an important role in the multimodality therapies of breast cancer. After neoadjuvant chemotherapy, some patients with breast cancer were down?staged from positive axillary lymph node (cN+) to clinically negative ( cN0). For these patients, the feasibility and safety of sentinel lymph node biopsy remains controversial. However, with the application of new technologies, SLNB is expected to become the main treatment for breast cancer patients with stage cN0 after neoadjuvant chemotherapy.

As a kind of breast cancer surgery choice,the nipple-sparing mastectomy (NSM)saves the patients′nipple-areola complex (NAC)which has significant meaning for patients′cosmetic results and posto-peration reconstruction.However,the clinical application of NSMis still in controversial.Some hot topics about oncological safety of NSM have appeared in recent years,such as the screening criterion of the enrolled patients,the situation of NAC involvement and the complications after NSM and handing methods.