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Objective@#To investigate the molecular mechanism of high phosphorylation levels of cofilin-1 (p-CFL-1) associated with paclitaxel resistance in epithelial ovarian cancer (EOC) cells.@*Methods@#Cells displaying varying levels of p-CFL-1 and CFL-1 were created by plasmid transfection and shRNA interference. Cell inhibition rate indicating paclitaxel efficacy was assessed by Cell Counting Kit-8 (CCK-8) assay. Apoptosis was assessed by flow cytometry and protein levels were detected by western blotting. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression levels of phosphokinases and phosphatases of CFL-1. Survival analysis evaluated the correlation between the prognosis of EOC patients and the levels of p-CFL-1 and slingshot-1 (SSH-1).@*Results@#High levels of p-CFL-1 were observed in EOC cells that survived treatment with high doses of paclitaxel. SKOV3 cell mutants with upregulated p-CFL-1 showed impaired paclitaxel efficacy, as well as decreased apoptosis rates and pro-survival patterns of apoptosis-specific protein expression. Cytoplasmic accumulation of p-CFL-1 inhibited paclitaxel-induced mitochondrial apoptosis. SSH-1 silencing mediated CFL-1 phosphorylation in paclitaxel-resistant SKOV3 cells. Clinically, the high level of p-CFL-1 and the low level of SSH-1 in EOC tissues were closely related to chemotherapy resistance and poor prognosis in EOC patients.@*Conclusion@#The SSH-1/p-CFL-1 signaling pathway mediates paclitaxel resistance by apoptosis inhibition in EOC and is expected to be a potential prognostic predictor.
Subject(s)
Female , Humans , Antineoplastic Agents, Phytogenic/therapeutic use , Apoptosis , Carcinoma, Ovarian Epithelial/metabolism , Cell Line, Tumor , Cofilin 1/metabolism , Drug Resistance, Neoplasm , Ovarian Neoplasms/metabolism , Paclitaxel/therapeutic use , Phosphoprotein Phosphatases/metabolism , PhosphorylationABSTRACT
Objective:To retrospectively characterize the perinatal birth defects in the latest 5 years in Minhang District of Shanghai， and provide the evidence to improve the preventive strategies. Methods:The data of perinatal birth defects was retrieved from “Shanghai information reporting system for children with birth defects and disabilities” ，which was recorded by five sentinel hospitals in Minhang District from January 2014 to December 2018. Average proportion of perinatal birth defects in the recent 5 years， annual variation， comparison with municipal data in the same period， difference between registered population and migrant population， difference between male and female， and common birth defects were determined. Results:The average proportion of perinatal birth defects in the recent 5 years was determined to be 6.24‰， which increased from 5.32‰ in 2014 to 7.90‰ in 2018. It was lower than the municipal proportion in Shanghai with an average of 11.02 ‰ （from 9.7 ‰ in 2014 to 14.00 ‰ in 2018）. The proportion was higher in resident population （9.15‰） than that in migrant population （5.57‰）. In addition， the proportion was higher in male infants （6.81‰） than that in female infants （5.59‰）. The first two common defects were congenital heart disease and polydactyly， while cleft lip and cleft lip with palate showed a decreasing trend. Conclusion:In the recent 5 years， the proportion of birth defect increases， which is consistent with the whole city. There remain challenges in the maternal and children healthcare.
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Objective To evaluate the effects of intervention based on internet platform for feeding disorders of infants with low birth weight (LBW), and to provide evidence for spreading and conducting intervention in communities. Methods A total of 994 infants aged 1 month born between January 2016 and February 2017 with LBW consulted in Department of Child Health Care of Minhang Maternal and Children Health Hospital were selected in this study.The participants were randomly divided into intervention group (499 cases) and control group (495 cases).The intervention group received health education in the assistance of a communication platform founded on internet, and the control group received health education by common pattern.After 12 months of intervention, a self-developed and normalized Chinese Infant Feeding Scale was used to assess the infants feeding disorder and feeding behaviors of caregivers were also investigated by filling out a specially designed questionnaire, to understand the occurrence of feeding disorders in the intervention group and the control group and the changes of feeding behavior of the parents. Results The score of feeding behavior questionnaire based on internet platform intervention was significantly higher than that of the control group (P < 0.05), and the parental feeding behavior was significantly improved in five aspects:food preparation, nutrition knowledge, feeding methods, feeding concept and feeding environment (P < 0.01).The incidence of feeding disorders in the intervention group was lower than that in the control group, and the difference was statistically significant (P < 0.05). Conclusion Interventions based on the internet platform for feeding disorders in LBW infants can reduce the incidence of feeding disorders and improve parental feeding behavior.
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Objective To evaluate the effects of intervention based on internet platform for feeding disorders of infants with low birth weight (LBW), and to provide evidence for spreading and conducting intervention in communities. Methods A total of 994 infants aged 1 month born between January 2016 and February 2017 with LBW consulted in Department of Child Health Care of Minhang Maternal and Children Health Hospital were selected in this study.The participants were randomly divided into intervention group (499 cases) and control group (495 cases).The intervention group received health education in the assistance of a communication platform founded on internet, and the control group received health education by common pattern.After 12 months of intervention, a self-developed and normalized Chinese Infant Feeding Scale was used to assess the infants feeding disorder and feeding behaviors of caregivers were also investigated by filling out a specially designed questionnaire, to understand the occurrence of feeding disorders in the intervention group and the control group and the changes of feeding behavior of the parents. Results The score of feeding behavior questionnaire based on internet platform intervention was significantly higher than that of the control group (P < 0.05), and the parental feeding behavior was significantly improved in five aspects:food preparation, nutrition knowledge, feeding methods, feeding concept and feeding environment (P < 0.01).The incidence of feeding disorders in the intervention group was lower than that in the control group, and the difference was statistically significant (P < 0.05). Conclusion Interventions based on the internet platform for feeding disorders in LBW infants can reduce the incidence of feeding disorders and improve parental feeding behavior.
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OBJECTIVE: Follicle stimulating hormone has been taken as an essential component in the management of infertility. Herein we reviewed the development history of FSH preparations to provide experience and lessons for the research of new FSH preparations, and give an example for the development of other gene medicine. METHODS: The manufacturing techniques and quality control methods of routine FSH preparations were summarized, and the key problems for the preparations were discussed. RESULTS AND CONCLUSION: The history of developing safe and effective FSH preparations was full of challenges of efficacy, safety and the pa-tients' compliance, etc. A series of problems of FSH preparations, such as low efficacy and immunogenicity of animal-sourced FSH preparations, safety of human cadaver FSH, and low purity of urinary FSH, have constantly facilitated both the reformation of manufacturing techniques and improvement of quality control methods of FSH preparations. With the introduction of recombinant DNA technology, recombinant FSH preparations of high purity and consistency are now available, which are safe and effective, and long-acting FSH preparations have improved the compliance of patients.