Incidence and Risk Factors of Obstetric Anal Sphincter Injuries after Various Modes of Vaginal Deliveries in Chinese Women

Background: Obstetric anal sphincter injuries (OASIS) can cause an adverse impact on women′s physical and mental health. There was lack of published data in Chinese population particularly on studying the risk of OASIS for nonrotational outlet forceps. This study was to determine the incidence and risk factors of OASIS. Methods: This is a retrospective cohort study carried out in a tertiary referral hospital in Hong Kong. The control group was selected randomly. Univariate and multivariate logistic regression analysis was performed to evaluate the influence of potential risk factors on OASIS. This study reviewed the obstetric records of OASIS women and random control from January 2011 to June 2014. Univariate and multivariate logistic regression analysis was performed to evaluate the influence of potential risk factors on OASIS. Results: Of 15,446 women delivered, 49 had OASIS. The percentage of OASIS increased from 0.3% (2011) to 0.38% (2014). There was an increasing trend of OASIS in attempted spontaneous vaginal delivery without episiotomy (P < 0.01), but it did not increase the OASIS risk (P = 0.46). Univariate analysis of 49 cases and 438 control subjects showed that forceps delivery (odds ratio [OR] =8.73, P < 0.01), prolong second stage of labor (OR = 1.43, P < 0.01) increased the risk for OASIS. In multivariate regression models, only forceps delivery (OR = 6.28, P < 0.01) proved to be independent risk factor. Conclusions: The incidence of OASIS in Chinese women was increased after 2012, but still lower than the reported figures in the literature. Outlet forceps delivery could be a possible associated risk factor

Pro-inflammatory cytokines stimulate CFTR-dependent anion secretion in pancreatic ductal epithelium

Abstract Background Loss of CFTR-dependent anion and fluid secretion in the ducts of the exocrine pancreas is thought to contribute to the development of pancreatitis, but little is known about the impact of inflammation on ductal CFTR function. Here we used adult stem cell-derived cell cultures (organoids) obtained from porcine pancreas to evaluate the effects of pro-inflammatory cytokines on CFTR function. Methods Organoids were cultured from porcine pancreas and used to prepare ductal epithelial monolayers. Monolayers were characterized by immunocytochemistry. Epithelial bicarbonate and chloride secretion, and the effect of IL-1β, IL-6, IFN-γ, and TNF-α on CFTR function was assessed by electrophysiology. Results Immunolocalization of ductal markers, including CFTR, keratin 7, and zonula occludens 1, demonstrated that organoid-derived cells formed a highly polarized epithelium. Stimulation by secretin or VIP triggered CFTR-dependent anion secretion across epithelial monolayers, whereas purinergic receptor stimulation by UTP, elicited CFTR-independent anion secretion. Most of the anion secretory response was attributable to bicarbonate transport. The combination of IL-1β, IL-6, IFN-γ, and TNF-α markedly enhanced CFTR expression and anion secretion across ductal epithelial monolayers, whereas these cytokines had little effect when tested separately. Although TNF-α triggered apoptotic signaling, epithelial barrier function was not significantly affected by cytokine exposure. Conclusions Pro-inflammatory cytokines enhance CFTR-dependent anion secretion across pancreatic ductal epithelium. We propose that up-regulation of CFTR in the early stages of the inflammatory response, may serve to promote the removal of pathogenic stimuli from the ductal tree, and limit tissue injury

Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma

Despite advancements in cancer immunotherapy, solid tumors remain formidable challenges. In glioma, profound inter- and intra-tumoral heterogeneity of antigen landscape hampers therapeutic development. Therefore, it is critical to consider alternative sources to expand the repertoire of targetable (neo-)antigens and improve therapeutic outcomes. Accumulating evidence suggests that tumor-specific alternative splicing (AS) could be an untapped reservoir of antigens. In this study, we investigated tumor-specific AS events in glioma, focusing on those predicted to generate major histocompatibility complex (MHC)-presentation-independent, cell-surface antigens that could be targeted by antibodies and chimeric antigen receptor-T cells. We systematically analyzed bulk RNA-sequencing datasets comparing 429 tumor samples (from The Cancer Genome Atlas) and 9166 normal tissue samples (from the Genotype-Tissue Expression project), and identified 13 AS events in 7 genes predicted to be expressed in more than 10% of the patients, including PTPRZ1 and BCAN, which were corroborated by an external RNA-sequencing dataset. Subsequently, we validated our predictions and elucidated the complexity of the isoforms using full-length transcript amplicon sequencing on patient-derived glioblastoma cells. However, analyses of the RNA-sequencing datasets of spatially mapped and longitudinally collected clinical tumor samples unveiled remarkable spatiotemporal heterogeneity of the candidate AS events. Furthermore, proteomics analysis did not reveal any peptide spectra matching the putative antigens. Our investigation illustrated the diverse characteristics of the tumor-specific AS events and the challenges of antigen exploration due to their notable spatiotemporal heterogeneity and elusive nature at the protein levels. Redirecting future efforts toward intracellular, MHC-presented antigens could offer a more viable avenue