To understand the prevalence of functional constipation in pregnant women and to analyze the impact of its risk factors. We searched hospital databases for women who were 37–41 weeks pregnant (1698 cases) from July 2012 to January 2014 in four hospitals in Shanghai. We reviewed factors including general data, living and eating habits, psychological history, past history of defecation in the 6 months before pregnancy and defecation after pregnancy. Data were analyzed using SPSS software. Pregnant women who were more than 35 years old, with a pre-pregnancy body mass index >24, who were highly educated and employed in a sedentary occupation, showed a higher prevalence of functional constipation. Multivariate logistic regression analysis indicated that the prevalence of functional constipation among pregnant women was related to age, pre-pregnancy body mass index, diet, exercise, occupation, psychological factors, threatened abortion in early pregnancy and constipation history. The prevalence rate of functional constipation in pregnant women was significantly higher than in the general population.

Efficient delivery of small interfering RNAs (siRNAs) to the targeted cells has remained a significant challenge in clinical applications. In the present study, we developed a novel aptamer–siRNA chimera delivery system mediated by cationic Au-Fe ₃ O ₄ nanoparticles (NPs). The chimera constructed by VEGF RNA aptamer and Notch3 siRNA was bonded with heterogeneous Au-Fe ₃ O ₄ nanoparticles by electrostatic interaction. The obtained complex exhibited much higher silencing efficiency against Notch3 gene compared with chimera alone and lipofectamine-siRNA complex, and improved the antitumor effects of the loaded chimera. Moreover, the efficient delivery of the chimera by Au-Fe ₃ O ₄ NPs could reverse multi-drug resistance (MDR) of ovarian cancer cells against the chemotherapeutic drug cisplatin, indicating its potential capability for future targeted cancer therapy while overcoming MDR.

Aim: The aim of this study was to observe the effect of attenuated Salmonella typhi as a tumor‐targeting delivery vector for multidrug‐resistance gene (MDR1) small interfering RNA (siRNA).Material and Methods: The cisplatin (DDP)‐resistant ovarian cancer cell line SKOV‐3/DDP was established by treatment with gradually increasing concentrations of cisplatin. MDR1 siRNA expression plasmid containing short hairpin RNA (shRNA) of MDR1 gene was constructed and transformed into attenuated Salmonella typhi strain SL7207. SKOV‐3/DDP cells were incubated with recombinant Salmonella and then subjected to analysis of MDR1 expression by real‐time polymerase chain reaction and Western blot. SKOV‐3/DDP tumor‐bearing mice were established by subcutaneously injecting BALB/c nude mice with SKOV‐3/DDP cells, and were orally inoculated with Salmonella carrying MDR1 siRNA plasmid and simultaneously injected intraperitoneally with cisplatin. Tumor growth and mouse survival were observed.Results: Compared with parental cell line, the DDP‐resistant SKOV‐3/DDP cells expressed a much higher level of MDR1. The expression of MDR1 in SKOV‐3/DDP cells infected with the Salmonella strain bearing MDR1 siRNA plasmid in vitro was detected to be downregulated and DDP tolerance of these cells was reversed. Tumor‐bearing nude mice that were orally receiving recombinant Salmonella experienced a slow tumor growth and became more sensitive to DDP.Conclusion: Attenuated Salmonella typhi may represent a promising vector for in vivo administration of RNA interference therapy against malignant tumors.

Background: The endometrial thickness is a key factor for successful implantation. Thin endometrium is associated with lower implantation rate and pregnancy rate. Lacking of a better understanding for the cellular and molecular mechanisms of thin endometrium, managing patients with thin endometrium still represents a major challenge for clinicians.Methods: In this study, we combined four single-cell RNA sequencing (scRNA-seq) and one bulk sequencing (bulk-seq) data for thin endometrium to perform an integrated analysis for endometrial cells in proliferating phase. Cell proportion and differentially expressed genes (DEGs) were analyzed to determine the disease-specific cell type and signaling pathways. The cell-cell communication among cell types were inferred by “CellChat” to illustrate the differential intercellular communication under normal and thin endometrium conditions. GSEA and GSVA were applied to identify dysfunctional signals and metabolic pathways before and after thin endometrium.Results: Integration of scRNA-seq identified eight cell types. The proportion of stromal cells showed a significant difference between normal and thin endometrial tissue. The DEGs in diverse cell types revealed enriched pathways in a cell-specific manner. Aberrant cell-cell signaling transduction was found in almost all cell types, especially in immune cells and epithelial cells. Furthermore, dysfunctional metabolic signaling pathways were induced in a cell-type dependent way. The down-regulation of carbohydrate metabolism and nucleotide metabolism was observed and the energy metabolism switch was indicated.Conclusion: Conclusively, we discover dysfunctional signals and metabolic pathways in thin endometrium, providing insight into mechanisms and therapeutic strategies for the atrophic endometrium.

Numerous clinical therapeutic agents have been identified as DNA damaging. The present study revealed that isoproterenol (Iso) resulted in DNA damage in vascular smooth muscle cells (VSMCs) and increased the levels of intracellular oxygen free radicals. Administration of chlorogenic acid (CGA) inhibited this effect. Pretreatment with CGA abrogated the increase in protein expression levels of γ‑H2A histone family member X, phosphorylated ataxia telangiectasia mutated, phosphorylated Rad3‑related protein, breast cancer 1 and C‑terminal Src homologous kinase induced by Iso. In addition, the increase in levels of intracellular reactive oxygen species (ROS) induced by Iso was inhibited by CGA pretreatment in a dose‑dependent manner. The results of the present study suggest that CGA may inhibit Iso‑induced VSMC damage via the suppression of ROS generation. Therefore, CGA may be a novel agent for the treatment of vascular diseases.

Malignant bowel obstruction (MBO) is a serious complication which causes high death rate and low quality of life (QOL) for patients diagnosed at an advanced stage of ovarian cancer. RNA interference (RNAi) could be a promising method for the treatment of ovarian cancer and could decrease the morbidity of MBO. Gab2 gene is overexpressed in ovarian cancer compared with normal ovarian tissue, and regulates the migratory behaviors and E-cadherin expression via activation of the PI3K pathway in ovarian cancer cells. Here, chitosan–polyethyleneimine (PEI, M_w 1800) copolymer nanoparticles were synthesized as nanocarriers to deliver Gab2 siRNA into SKOV3 cells. The silencing effects against the Gab2 gene and the antitumor effects by the chitosan–PEI–Gab2 siRNA nanoparticles (chitosan–PEI–Gab2 NPs) were studied. Results showed that highly efficient silencing effects against Gab2 expression and its downstream effector, AKT protein, at more than 90% deregulation were obtained by chitosan–PEI NP mediated Gab2 siRNA delivery, so as to exhibit obvious antitumor effects against SKOV3 cells with low cytotoxicity, and induce cell apoptosis in early and late stages. The study will provide novel strategies to overcome MBO in ovarian cancer by the efficient knockdown of Gab2 expression.