Effects of Maternal Pre-Pregnancy BMI and Gestational Weight Gain on the Development of Preeclampsia and Its Phenotypes: A Prospective Cohort Study in China.

Preeclampsia (PE) is a common and serious pregnancy-specific disorder, which is closely linked with adverse maternal and neonatal outcomes. This study aimed to evaluate whether maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) was associated with preeclampsia and its phenotypes. In this prospective study, 32,531 women with singleton pregnancies were finally included. Compared with women with normal pre-pregnancy BMI, women with overweight and obesity were at increased risk of PE (RR = 1.62, 95%CI: 1.57−1.66; RR = 2.04, 95%CI: 1.97−2.11, respectively), while those who were underweight had a lower risk of PE (RR = 0.84, 95%CI: 0.81−0.88). When compared with women who gained adequate GWG, pregnant women with inadequate GWG and excessive GWG had an increased risk of PE (RR = 1.15, 95%CI: 1.12−1.19; RR = 1.56, 95%CI: 1.52−1.60, respectively). The observed increased risk was generally similar for mild-, severe-, early- and late-onset PE, and the reduced risk was similar for severe- and late-onset PE. No significant interactions between GWG and pre-pregnancy BMI on the risk of PE were identified (p-interaction > 0.05). In conclusion, pre-pregnancy overweight or obesity and excessive GWG have established risk factors for PE, and that the potential risk may vary according to PE phenotypes. Moreover, the synergistic effect that may exist between pre-pregnancy BMI and GWG.

10 % fluorescein sodium vs 1 % isosulfan blue in breast sentinel lymph node biopsy.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is well accepted to be a standard procedure in breast cancer surgery with clinically negative lymph nodes. Isosulfan blue is the first dye approved by the USA Food and Drug Administration for the localization of the lymphatic system. Few alternative tracers have been investigated. In this study, we aimed to compare the differences between 10 % fluorescein sodium and 1 % isosulfan blue in breast sentinel lymph node biopsy and to investigate the feasibility of using 10 % fluorescein sodium as a new dye for breast sentinel lymph node biopsy. METHODS: A total of 30 New Zealand rabbits were randomly divided into the fluorescein sodium group and the isosulfan blue group (15 rabbits per group). Fluorescein sodium or isosulfan blue was injected subcutaneously into the second pair of mammary areolas. RESULTS: The average fading time of the second lymph nodes in the isosulfan blue group was significantly shorter than that in the fluorescein sodium group. Moreover, the detection rates of SLNs were higher in the fluorescein sodium group than in the isosulfan blue group. No significant differences between the fluorescein sodium group and isosulfan blue group were observed regarding the distances between the detected sentinel lymph nodes and second pair of mammary areolas, the distances between the second lymph nodes and second pair of mammary areolas, the number of detected sentinel lymph nodes and second lymph nodes, the average dyeing time of the sentinel and the second lymph nodes, and the average fading time of the second lymph nodes. CONCLUSIONS: In summary, we first reported that fluorescein sodium is a potential new tracer for breast sentinel lymph node biopsy.

Doxorubicin hydrochloric increases tumour coagulation and end-point survival in percutaneous microwave ablation of tumours in a VX2 rabbit tumour model.

PURPOSE: The aim of this study was to explore whether doxorubicin hydrochloric (DOX) combined with microwave ablation (MWA) is more effective at increasing tumour coagulation and prolonging end-point survival in a VX2 rabbit breast cancer model than each intervention individually. METHODS: New Zealand white rabbits with VX2 tumours were placed into treatment groups as follows: MWA (20 W for 5 min and 40 W for 5 min), intravenous injection of 4 mg/kg DOX, and combined therapy. Tumours were analysed at 4 h and 24 h after treatment to determine the temporal quantities of cleaved caspase-3 and Hsp70 using immunohistochemical staining and Western blots. Tumour coagulation areas were compared at 24 h after treatment. RESULTS: No significant difference in tumour coagulation was found between DOX-MWA and 40W-MWA (mean 4.52 cm(2) ± 0.48 (SD), 4.08 cm(2) ± 0.36, respectively; P > 0.05). A significant difference between tumour coagulation was found for DOX-MWA and 20W-MWA (mean 4.52 cm(2) ± 0.48 (SD), 1.69 cm(2) ± 0.34 cm(2), respectively; p < 0.01). Cleaved caspase-3 and Hsp70 demonstrated low level expression at 4 h and 24 h in the DOX group. Cleaved caspase-3 showed low expression at the coagulation margin in the 20W-MWA group, was highly expressed in DOX-MWA group, and continued to increase with time. Hsp70 in the 20W-MWA group increased significantly at the coagulation margin but demonstrated low expression in the DOX-MWA group at 4 h and 24 h. The animals in the combined treatment group had a longer survival time (mean 78.33 days ± 8.07 SD) than the 20W-MWA group (mean 57.17 days ± 8.77, p < 0.01) or the DOX group (mean 35.17 days ± 7.63, p < 0.01). CONCLUSION: A combination of DOX and MWA could increase tumour coagulation and end-point survival better than single therapy, which had some connection with the elevated expression of cleaved caspase-3 and low Hsp70 expression at the coagulation margin.

Targeted delivery of doxorubicin to breast cancer cells by aptamer functionalized DOTAP/DOPE liposomes.

Doxorubicin is used to treat numerous types of tumors including breast cancer, yet dose-associated toxicities limit its clinical application. Here, we demonstrated a novel strategy by which to deliver doxorubicin to breast cancer cells by conjugating cancer cell-specific single-strand DNA aptamers with doxorubicin-encapsulated DOTAP:DOPE nanoparticles (NPs). We utilizing a whole-cell-SELEX strategy, and 4T1 cells with high invasive and metastatic potential were used as target cells, while non-invasive and non-metastatic 67NR cells were used as subtractive cells. Ten potential aptamers were generated after multi-pool selection. Studies on the selected aptamers revealed that SRZ1 had the highest and specific binding affinity to 4T1 cells. Then we developed SRZ1 aptamer-carried DOTAP:DOPE-DOX NPs. In vitro uptake results which were conducted by FACS indicated that the aptamer significantly promoted the uptake efficiency of DOTAP:DOPE-DOX NPs by 4T1 cells. ATPlite assay was performed to test 4T1, 67NR and NMuMG cell viability after treatment with free doxorubicin, DOTAP:DOPE-DOX particles and aptamer­loaded DOTAP:DOPE-DOX particles. As expected, the aptamers effectively enhanced accumulation of doxorubicin in the 4T1 tumor tissues as determined by in vivo mouse body images and biodistribution analysis. Consistent with the in vitro findings, aptamer-conjugated doxorubicin-loaded DOTAP:DOPE particles markedly suppressed tumor growth and significantly increased the survival rate of 4T1 tumor-bearing mice. These studies demonstrated that aptamer SRZ1 could be a promising molecule for chemotherapeutic drug targeting deliver.