Potential Application of Intestinal Organoids in Intestinal Diseases.

To accurately reveal the scenario and mecahnism of gastrointestinal diseases, the establishment of in vitro models of intestinal diseases and drug screening platforms have become the focus of attention. Over the past few decades, animal models and immortalized cell lines have provided valuable but limited insights into gastrointestinal research. In recent years, the development of intestinal organoid culture system has revolutionized in vitro studies of intestinal diseases. Intestinal organoids are derived from self-renewal and self-organization intestinal stem cells (ISCs), which can replicate the genetic characteristics, functions, and structures of the original tissues. Consequently, they provide new stragety for studying various intestinal diseases in vitro. In the review, we will discuss the culture techniques of intestinal organoids and describe the use of intestinal organoids as research tools for intestinal diseases. The role of intestinal epithelial cells (IECs) played in the pathogenesis of inflammatory bowel diseases (IBD) and the treatment of intestinal epithelial dysfunction will be highlighted. Besides, we review the current knowledge on using intestinal organoids as models to study the pathogenesis of IBD caused by epithelial dysfunction and to develop new therapeutic approaches. Finally, we shed light on the current challenges of using intestinal organoids as in vitro models.

Performance of noninvasive prenatal screening in twin pregnancies: a retrospective study of 5469 twin pregnancies.

OBJECTIVES: To evaluate the performance of noninvasive prenatal screening (NIPS) for the fetal common aneuploidy screening in twin pregnancies. METHODS: The data of 5469 women with twin pregnancies were collected in this retrospective observational study between January 2017 and December 2018. Patients underwent NIPS as first-line screening or after standard serum screening for fetal aneuploidy. The performance of NIPS was examined, and a regression analysis was performed to investigate testing failure in cases of low fetal fraction. RESULTS: In this study, 2231 (40.8%) patients opted for NIPS as the primary prenatal screening test, and 3238 (59.2%) opted for serum screening, including 440 patients who opted for NIPS after serum screening. Among the 2671 pregnancies with available NIPS outcomes, 11 cases of aneuploidy were identified, seven of trisomy 21 and four of sex chromosome aneuploidy (SCA). The sensitivity and specificity for trisomy 21 were 100% (95% CI, 56.1-100.0%) and 100% (95% CI, 99.8-100.0%), respectively. The positive predictive value (PPV) for SCA was 40.0% (95% CI, 13.7-72.6%). No false negatives were found, with a negative predictive value (NPV) of 100% (95% CI, 99.8-100.0%) in total. In 32 pregnancies who failed NIPS test without available NIPS outcomes due to low fetal fraction, the regression analysis demonstrated that increasing BMI and assisted reproductive technology treatment were significant independent predictors. CONCLUSIONS: NIPS is a high-performing routine primary prenatal screening test in twin pregnancies, with a high PPV and low false positive rate for detecting trisomy 21. It is also useful to identify common sex chromosome aneuploidies in twin pregnancies, with similar performance to that reported in singleton pregnancy.

Clinical application of noninvasive prenatal screening for sex chromosome aneuploidies in 50,301 pregnancies: initial experience in a Chinese hospital.

To evaluate the clinical performance of noninvasive prenatal screening (NIPS) for fetal sex chromosome aneuploidies (SCAs), pregnant women were recruited in this retrospective observational study. The NIPS test was undertaken using high-throughput gene sequencing. In total,50,301 pregnant women were analysed for demographic characteristics and medical history. Of them, 308 women (0.61%) had high risk for fetal SCAs, including 138 for 45,X, 111 for 47,XXY, 42 for 47,XXX, and 17 for 47,XYY. After the pre-test counselling, 182 participants chose to undergo invasive prenatal diagnosis, confirming 59 positive cases. The combined positive predictive value of NIPS was 32.42% (59/182), 18.39% (16/87), 44.4% (12/27), 39.29% (22/56), and 75% (9/12) for detecting SCAs, 45,X, 47,XXX, 47,XXY, and 47,XYY, respectively. NIPS can be a useful method to detect the fetal SCAs using high-throughput gene sequencing, though accuracy can still be improved, especially for 45,X. Although the value of NIPS compare favorably with those seen in traditional screening approaches for SCAs, it is important to highlight the limitations of NIPS while educating clinicians and patients.