Objective The present study was designed to explore the inhibitory effects of the ADC drug Disitamab Vedotin(RC-48)on breast cancer cells with different HER-2 expression levels by utilizing a tumor organoid culture system.Methods Within the framework of the tumor organoid culture system,the breast cancer cell lines MCF-7(characterized by low HER-2 expression,Luminal A subtype)and BT-474(exhibiting high HER-2 expression,HER-2 positive subtype)were cultured independently and in various mixed ratios.The histological characteristics,as well as the expression levels and distribution of HER-2 in MCF-7 and BT-474 organoids,were analyzed via immunohistochemistry and immunofluorescence techniques.MCF-7 and BT-474 organoids were separately treated with Vedotin(RC-48),Disitamab,and Monomethyl auristatin E(MMAE).Additionally,a drug sensitivity test of Disitamab Vedotin(RC-48)was carried out on mixed MCF-7 and BT-474 cell ratios and on patient-derived breast cancer organoids,with the assessment conducted using the 3D-Glo method.Results In the tumor organoid culture system,immunohistochemistry and immunofluorescence analyses demonstrated that HER-2 was predominantly localized in the cell membrane.Specifically,BT-474 organoids exhibited robust HER-2 expression,while MCF-7 organoids displayed relatively low expression levels.When compared with MCF-7 organoids,RC48-ADC exerted a more pronounced inhibitory effect on BT-474 organoids,with IC50 values of 109.7 μg/mL and 2.792 μg/mL,respectively.The co-culture model further confirmed the bystander effect of RC-48,revealing that the ratio of HER-2-positive to HER-2-negative cells significantly influenced drug efficacy.Additionally,treatment with RC-48 led to a reduction in HER-2 expression in breast cancer organoids with diverse HER-2 expression levels.Conclusions The tumor organoid model can accurately mirror drug sensitivity and bystander effects.Within this model,RC-48 effectively inhibited HER-2 highly-expressing breast cancer cells,augmented the killing effect through the bystander mechanism,and downregulated HER-2 expression,thereby suggesting its potential for targeting HER2-associated breast cancer.

Objective The present study was designed to explore the inhibitory effects of the ADC drug Disitamab Vedotin(RC-48)on breast cancer cells with different HER-2 expression levels by utilizing a tumor organoid culture system.Methods Within the framework of the tumor organoid culture system,the breast cancer cell lines MCF-7(characterized by low HER-2 expression,Luminal A subtype)and BT-474(exhibiting high HER-2 expression,HER-2 positive subtype)were cultured independently and in various mixed ratios.The histological characteristics,as well as the expression levels and distribution of HER-2 in MCF-7 and BT-474 organoids,were analyzed via immunohistochemistry and immunofluorescence techniques.MCF-7 and BT-474 organoids were separately treated with Vedotin(RC-48),Disitamab,and Monomethyl auristatin E(MMAE).Additionally,a drug sensitivity test of Disitamab Vedotin(RC-48)was carried out on mixed MCF-7 and BT-474 cell ratios and on patient-derived breast cancer organoids,with the assessment conducted using the 3D-Glo method.Results In the tumor organoid culture system,immunohistochemistry and immunofluorescence analyses demonstrated that HER-2 was predominantly localized in the cell membrane.Specifically,BT-474 organoids exhibited robust HER-2 expression,while MCF-7 organoids displayed relatively low expression levels.When compared with MCF-7 organoids,RC48-ADC exerted a more pronounced inhibitory effect on BT-474 organoids,with IC50 values of 109.7 μg/mL and 2.792 μg/mL,respectively.The co-culture model further confirmed the bystander effect of RC-48,revealing that the ratio of HER-2-positive to HER-2-negative cells significantly influenced drug efficacy.Additionally,treatment with RC-48 led to a reduction in HER-2 expression in breast cancer organoids with diverse HER-2 expression levels.Conclusions The tumor organoid model can accurately mirror drug sensitivity and bystander effects.Within this model,RC-48 effectively inhibited HER-2 highly-expressing breast cancer cells,augmented the killing effect through the bystander mechanism,and downregulated HER-2 expression,thereby suggesting its potential for targeting HER2-associated breast cancer.

Objective: To investigate the effect of hypertensive disorder complicating pregnancy (HDCP) on the mortality and early complications of premature infants. Methods: The general clinical data of preterm infants with gestational age 24-36^{+ 6} weeks were collected from the cooperative units in the task group from January 1, 2013 to December 31, 2014.According to the severity of HDCP, the infants were divided into 4 groups: HDCP group, preeclampsia group, eclampsia group and non HDCP group, the mortality and major complications of preterm infants were compared, and the influencing factors were analyzed. Results: The mortality rate of preterm in the HDCP group was significantly higher than that of non HDCP group, and there was statistical significance (χ²=9.970, P=0.019). Eclampsia had a highest fatality rate (4.8%) in the early stage, compared with non HDCP group (2.2%), and the difference was statistically significant.Comparison of HDCP group (1.8%) and eclampsia group (3.2%) suggested that there was no statistically significant difference.The incidence of respiratory distress syndrome (RDS) in preterm in HDCP group was significantly higher than that of non HDCP group, and there was statistical significance (χ²=13.241, P=0.004). Eclampsia group showed the highest incidence (35.4%), compared with non HDCP group (16.2%), the difference was statistically significant, but compared with HDCP group (19.9%), preeclampsia group (17.1%), there was no significant diffe-rence.The incidence of bronchopulmonary dysplasia (BPD) in preterm in HDCP group was significantly higher than that of non HDCP group (χ²=9.592, P=0.022), the highest incidence showed up in eclampsia group (9.7%), compared with non HDCP group (2.0%) and HDCP group (1.7%), the difference was statistically significant.But there was no statistically significant difference, compared with preeclampsia group.As the degree of HDCP aggravated, the incidence of BPD gradually rose.There was no significant impact on necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH) and sepsis of HDCP (χ²=7.054, 7.214, 0.358, 3.852; P=0.070, 0.065, 0.949, 0.278). Considering the overall outcome of the child, that was, whether the child died or survived, he had at least one complication, and HDCP had an effect on it (χ²=15.697, P=0.001), so the incidence increased while the degree of HDCP rose gradually.After adjusting gestational age, birth weight, sex, way of delivery, placental abruption and front placenta, prenatal hormonal, gestational diabetes, neonatal asphyxia and other factors, the results displayed that HDCP was the factor leading to the death of premature baby (OR=2.159, 95%CI: 1.093-4.266), and comparison between preeclampsia and eclampsia showed no statistical difference (P=0.714, 0.389); HDCP had no significant influence on RDS, BDP, ICH, NEC, ROP and sepsis. Conclusions HDCP leads to increased risk of premature death, but also leads to the increased incidence of RDS and BPD, but it had no obvious effect on NEC, ROP, IVH, sepsis and other complications.

Objective To explore the safety and efficacy of intrathecal administration of adipose stem cells de-rived from bioactive secretome (ASCBS)in treatment of whiter matter injury (WMI)in the preterm infants. Methods Sixty - three cases of WMI were recruited according to the uniform standards from multiple medical centers and they were divided into 3 gestational age (GA)subgroups,which were 21 cases in group A (GA 24 - 28 + 6 ),20 cases in group B (GA 29 - 32 + 6 ),and 22 cases in group C (GA 33 - 36 + 6 ). The patients were randomly divided into treatment groups and control groups by tossing coins. The treatment groups received lumbar puncture followed with ASCBS intra-thecal injection once daily for 3 consecutive days. Follow - up study included Neonatal Behavioral Neurological Assess-ment (NBNA)at term - equivalent age and neurodevelopment at corrected age of 6 - month. Neurodevelopment was assessed by using the Bayley Scales of Infant Development and Peabody Developmental Motor Scale. The survival rates, NBNA scores,mental development index (MDI),psychomotor develop index (PDI),total motor development quotient, gross motor development quotient and fine motor development among each subgroup were compared. Results Sixty -three cases were recruited,including 31 in the treatment group and 32 in the control group. Only 1 case in the treatment groups lost in the follow - up. No clinical side effects were found in the treatment groups. There was no significant diffe-rence in the survival rate and complication in the preterms in all subgroups of the treatment group and control group (all P > 0. 05). The gross and total motor development quotient in the treatment group A was higher than that in the control group A(gross motor development quotient:98. 330 ± 6. 282 in treatment group A,90. 330 ± 3. 777 in control group A, P = 0. 040;total motor development quotient:97. 330 ± 4. 803 in treatment group A,91. 000 ± 4. 472 in control group A,P = 0. 023). The rest findings showed no significant difference between groups. Conclusion The treatment of WMI in preterm infants with ASCBS is safe and can promote the motor development of preterm infants with GA in 24 - 28 weeks.