The effects of first-trimester subchorionic hematoma on pregnancy outcomes: a retrospective cohort study.

BACKGROUND: Although first-trimester subchorionic hematoma (SCH) always concerns expectant parents, its clinical significance remains controversial. This study aimed to examine the relationship between SCH and its association with subsequent miscarriage and other perinatal outcomes in singleton pregnancies. METHODS: We conducted a retrospective cohort study including 43,660 women who underwent routine prenatal care since the first trimester and then were followed up for maternal and neonatal outcomes. SCH was detected in the first-trimester ultrasound examinations. Robust Poisson regression was used to estimate adjusted risk associations of SCH with maternal and neonatal outcomes. RESULTS: A total of 815 (1.87%) SCH cases were detected in the first-trimester ultrasound examinations. The rate of miscarriage was statistically significantly higher in women with SCH than without [35.21% vs. 23.92%, P < 0.01; adjusted relative risk (RR):1.44, 95% confidence interval (CI): 1.31-1.58]. Subgroup analysis of women with SCH showed a clear trend that the earlier SCH occurred, the higher the risk of miscarriage was [adjusted RR (95% CI) for onset at the gestational weeks of 8-9, 6-7, and < 6 vs. ≥ 10: 1.30 (0.69-2.46), 2.33 (1.28-4.23), and 4.18 (2.30-7.58), respectively; Ptrend < 0.01]. In addition, women with SCH volume ≥ 1 ml showed higher risk than did those with SCH volume < 1 ml [adjusted RR (95% CI) for 1-4.9 ml, and ≥ 5 ml vs. < 1 ml: 1.36 (1.10-1.68) and 1.56 (1.18-2.07), respectively]. There was no statistically significant difference in the rates of other pregnancy outcomes between women with and without SCH. CONCLUSIONS: First-trimester SCH, particularly when characterized by early presence and large size, might significantly increase the risk of miscarriage. Data from this study suggest no associations between SCH and other maternal and neonatal outcomes.

The intervention effect of nicotine on cervical fibroblast-myofibroblast differentiation in lipopolysaccharide-induced preterm birth model through activating the TGF-ß1/Smad3 pathway.

Currently, the clinical treatment of preterm birth, mainly using uterine contraction inhibitors, does not fundamentally reduce the incidence of premature birth (PTB). Premature cervical ripening is an important factor in PTB. We previously found that nicotine-treated pregnant murine had significant cervical resistance to stretch and higher collagen cross-links compared to the control animals, and nicotine prolonged gestation and inhibited cervical ripening. However, the regulatory effects of nicotine on premature cervical ripening and its role in PTB remain unclear. To investigate the effects of nicotine on cervical TGF-ß1/Smad3 pathway and fibroblast-myofibroblast differentiation regulated by this pathway in PTB-like models. Intraperitoneal injection with 15 µg lipopolysaccharide (LPS) in 200 µl PBS into pregnant mice was used to induce the PTB-like model. Mice were randomly divided into four groups: control group, LPS-treated group, LPS + Nicotine co-treated group and LPS + Nicotine+α-BGT co-treated group. Pregnancy outcomes were monitored. The collagen content was assessed by Picrosirius red staining. Expressions of genes and proteins in the TGF-ß/Smad3 pathway were detected by double immunofluorescence staining and quantitative Real-time PCR (qRT-PCR). myofibroblast differentiation were investigated by double immunofluorescence staining and qRT-PCR. Ultrastructures were analyzed by conventional transmission electron microscopy. The rate of PTB and neonatal mortality at birth was significantly higher in the LPS-treated group than in the control group; collagen content also decreased remarkably; the expression of TGF-ß1 in macrophages and p-Smad3 in fibroblasts were reduced; the expression of α-smooth muscle actin (α-SMA, markers for activated fibroblasts) was down-regulated while the expression of calponin and smoothelin (markers for fibroblasts at rest) was up-regulated. Nicotine improved pregnancy outcomes and inhibited collagen degradation, activated the TGF-ß1/Smad3 pathway and promoted cervical fibroblast-myofibroblast differentiation in PTB-like mice; such effects could be reversed by α-bungarotoxin (α-BGT). Nicotine inhibited premature cervical ripening in PTB-like models in relation with up-regulating the TGF-ß/Smad3 pathway and promoting fibroblast to differentiate into myofibroblasts.

The lncRNA MALAT1 rs619586 G Variant Confers Decreased Susceptibility to Recurrent Miscarriage.

Cardiovascula disease and recurrent miscarriage have shared risk factors, and some cardiovascular disease-related candidate genes have been confirmed to be associated with recurrent miscarriage. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that is considered to be associated with susceptibility to cardiovascular disease. However, whether lncRNA MALAT1 polymorphisms are related to recurrent miscarriage susceptibility is unclear. We genotyped three lncRNA MALAT1 polymorphisms (rs591291, rs619586, and rs3200401) in 284 patients and 392 controls using TaqMan methods. Logistic regression was used to evaluate the odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age. Our results showed that the rs619586 G variant had protective effects against recurrent miscarriage (AG vs. AA: adjusted OR = 0.670, 95% CI = 0.457-0.982, p = 0.040; GG vs. AA: adjusted OR = 0.278, 95% CI = 0.079-0.975, p = 0.046; GG/AG vs. AA adjusted OR = 0.621, 95% CI = 0.429-0.900, p = 0.012). In a combined analyses of protective genotypes, with regard to the three single nucleotide polymorphisms (SNPs), we found that individuals with two or three protective genotypes exhibited a significantly lower risk of recurrent miscarriage than those with no or only one protective genotype (adjusted OR = 0.369, 95% CI = 0.199-0.684, p = 0.002). Moreover, the decrease in recurrent miscarriage risk with two or three protective genotypes was most pronounced in women less than 35 years of age (OR = 0.290, 95% CI = 0.142-0.589, p < 0.001) and in women with 2-3 miscarriages (adjusted OR = 0.270, 95% CI = 0.126-0.580, p < 0.001). In conclusion, our study suggests that the rs619586 G variant may have potential protective effects conferring a decreased risk of recurrent miscarriage in the southern Chinese population.

Targeted delivery of paclitaxel by functionalized selenium nanoparticles for anticancer therapy through ROS-mediated signaling pathways.

As a therapeutic anticancer agent, the clinical use of paclitaxel (PTX) is limited by its poor water solubility and serious adverse side effects. The targeted-specific intracellular delivery of an anticancer drug as a new therapeutic modality is promising for cancer treatment. The anticancer activity of selenium nanoparticles (SeNPs) with low toxicity and excellent activity has attracted increasing attention for use in biomedical intervention in recent years. In this study, ß-cyclodextrin (ß-CD)-folate (FA)-modified selenium nanoparticles (SeNPs) loaded with paclitaxel (PTX) (Se@ß-CD-FA@PTX) were successfully fabricated through a layer-by-layer method. The nanosystem is able to enter cancer cells through FA receptor-mediated endocytosis to achieve targeted-specific intracellular delivery. Se@ß-CD-FA@PTX was found to increase the selectivity between normal and cancer cells. The viability in MCF-7 cells was remarkably lower than in MCF 10A cells, which may promote the specific targeted delivery of Se@ß-CD-FA@PTX into MCF-7 cells. Moreover, Se@ß-CD-FA@PTX was found to enhance the cytotoxic effect on MCF-7 cells via the induction of apoptosis activation of ROS-mediated p53 and AKT signaling pathways. The results demonstrate that Se@ß-CD-FA@PTX nanoparticles provide a strategy for the design of cancer-targeted nanosystems for use in cancer therapy.