Termination of a second-trimester pregnancy with placenta accreta spectrum disorder.

Background: The termination of pregnancy in patients with placenta accreta spectrum disorder (PASD) during the second trimester remains uncertain. In addition, interventional radiology techniques, such as arterial embolization and balloon placement, are potential options. We evaluated the outcomes of pregnancy termination in patients with PASD during the second trimester and the effectiveness of preoperative interventional radiology techniques.Methods: This retrospective study analyzed 48 PASD patients who underwent pregnancy termination during the second trimester between January 2016 and May 2021.Results: Of the 48 patients, 20 (41.67%) underwent transvaginal termination, whereas 28 (58.33%) underwent cesarean section. Notably, no significant differences were observed in success rates between the transvaginal termination and cesarean section groups (80.00% vs. 92.86%, P = 0.38). Furthermore, no statistically significant differences were observed in the success rates (94.12% vs 90.32%, P = 1.00) and blood loss (512.35 ± 727.00 ml vs 804.00 ± 838.98 ml, P = 0.23) between the artery embolization and non-embolization groups. In the vaginal termination group, statistically significant differences were observed in gestational weeks (16.70 ± 3.12 vs 22.67 ± 3.63, P < 0.01) and blood loss (165.00 ± 274.43 ml vs 483.64 ± 333.53 ml, P = 0.04) between the (artery embolization and non-embolization) subgroups. Conversely, in the cesarean section group, no significant differences were observed in gestational weeks (23.59 ± 3.14 vs 23.20 ± 4.37, P = 0.79) and blood loss (811.11 ± 879.55 ml vs 989.47 ± 986.52 ml, P = 0.76) between the subgroups.Conclusions: Further studies are needed to evaluate the efficacy of vaginal termination in PASD patients during the second trimester. Regarding cesarean termination, arterial embolization did not demonstrate increased effectiveness.

Noninvasive prenatal testing, ultrasonographic findings and poor prenatal diagnosis rates for twin pregnancies: a retrospective study.

BACKGROUND: Noninvasive prenatal testing (NIPT) is increasingly used in the clinical prenatal screening of twin pregnancies, and its screening performance for chromosomal abnormalities requires further evaluation. For twin pregnancies with indications for prenatal diagnosis, there is a lack of clinical data to assess the prenatal diagnosis rate (PDR). The aim of this study was to evaluate the screening performance of NIPT for foetal chromosomal abnormalities in twin pregnancies and the PDR in the second and third trimesters. METHODS: Ultrasound scans were carried out for all twin pregnancies between 11 and 13+ 6 gestational weeks. For twin pregnancies with nuchal translucency thickness˂3.0 mm and no foetal structural malformations, NIPT was performed after blood sampling, followed by routine ultrasound monitoring. Women with twin pregnancies who underwent NIPT at the prenatal diagnostic centre of Xiangya Hospital from January 2018 to May 2022 were included in the study. Genetic counselling was offered to each pregnant woman when the NIPT result indicated a high risk of abnormalities or abnormal ultrasonographic (USG) findings were detected. We followed up twin pregnancies for NIPT results, USG findings, prenatal diagnosis results and pregnancy outcomes. RESULTS: In 1754 twin pregnancies, the sensitivity, specificity and positive predictive value of NIPT for trisomy 21 were 100%, 99.9% and 75%, and the corresponding values for sex chromosome aneuploidy (SCA) were 100%, 99.9% and 50%, respectively. For the 14 twin pregnancies for which the NIPT results indicated a high risk of abnormalities, the PDR was 78.6% (11/14). For the 492 twin pregnancies for which the NIPT results indicated a low risk of abnormalities, the rate of USG findings in the second and third trimesters was 39.4% (194/492); of these pregnancies, prenatal diagnosis was recommended for 16.7% (82/492), but it was actually performed in only 8.3% (41/492), and the PDR was 50% (41/82). There was no significant difference in the PDR between the NIPT high-risk and low-risk groups. CONCLUSIONS: The screening performance of NIPT for SCA in twin pregnancies needs to be further evaluated. When abnormal NIPT results or USG findings are used as the main prenatal diagnostic indicator in the second and third trimesters, the PDR is poor.

Comparison of risk assessments for venous thromboembolism during the puerperium.

Objective: To compare the predictive value of different risk assessment methods for puerperium venous thromboembolism (VTE). Methods: This study included 55 women with and 165 women without puerperal VTE. Using the cases, 11 assessment methods were compared. Results: The area under the curve (AUC) value of the 11 assessments was highest for the modified Caprini risk assessment model for pregnancy (a modified risk scoring method from Caprini, AUC = 0.805). Pairwise comparison of the AUC values of the 11 assessment methods indicated no significant difference among the five methods with AUC values > 0.7. Among them, the modified Caprini, the risk scoring method recommended by the Swedish Guidelines (Swedish method), and the risk scoring method recommended by the Shanghai consensus (Shanghai method) performed better than the other six methods with AUC values < 0.7 (P < 0.05). The sensitivities of the five methods for predicting a high risk of VTE were 69.09-94.55% and the specificities were 25.45-77.58%. The sensitivity of the modified Caprini was higher than those of the risk management method from the Chinese consensus (Chinese consensus method), Royal College of Obstetricians and Gynaecologists risk assessment scale (RCOG), and Swedish method (P < 0.05), but the specificity was only 25.45%. No significant difference in sensitivity was detected among the Swedish, Shanghai, RCOG, and Chinese consensus methods, whereas the specificity of the Swedish method was higher than that of the Shanghai, RCOG, and Chinese consensus methods. Conclusion: The predictive value of different risk assessment methods for puerperium VTE varies greatly. Considering the sensitivity and specificity, the Swedish method may have better clinical application value among the 11 methods.

Development of a nanozyme-based electrochemical sensor for detection of stringent response.

PpGpp (Guanosine 3',5'-bisdiphosphate) and NADPH (nicotinamide adenine dinucleotide phosphate) are important biological compounds in stringent response of organisms and play a crucial role in their growth and survival. At present, there is no report on the method for comprehensively detection of stringent response. In this study, a nanozyme-based electrochemical sensor was fabricated by self-assembly and was used for detecting stringent response with high sensitivity (Km of ppGpp is 1.498 × 10-12 mol/L and Km of NADPH is 7.489 × 10-13 mol/L) and selectivity. The sensor exhibited advantages of fast response times (∼50 s), high specificity, and simple operation. The sensor was successfully used to detect stringent response in Arabidopsis thaliana leaf extracts, Escherichia coli extracts and serum samples from SD rats. Notably, the method does not require complex sample pretreatment and has high application potential for comprehensively detecting overall nutritional status that is involved in the stringent responses of animals, plants, and microorganisms.

Pregnancy outcomes and factors affecting the clinical effects of emergency cerclage in twin pregnancies with cervical dilation and prolapsed membranes.

OBJECTIVE: To determine the effect of mid-trimester emergency cerclage in women with twin pregnancies with cervical dilation and prolapsed membranes, and to identify risk factors predicting spontaneous preterm birth (sPTB) before 28 weeks, after cerclage. METHODS: Retrospective analysis of twin gestations with cervical dilation and prolapsed membranes treated with emergency cerclage or expectant management (2015-2020). The primary outcomes were the rate of sPTB before 28 weeks and the gestational latency. Multiple logistic regression analysis was used to determine the factors associated with sPTB before 28 weeks, after cerclage. RESULTS: Ninety-seven women were included, cerclage (n = 58) or no cerclage (n = 39). Cerclage placement was associated with significantly lower incidence of sPTB before 28 weeks of pregnancy (34.5% vs 82.1%) and prolongation of the gestational latency (46.71 ± 27.52 vs 10.95 ± 11.71 days). Positive cervical culture (odds ratio [OR] 10.69, 95% confidence interval [CI] 1.82-62.95), pregnancy duration at diagnosis less than 22 weeks (OR 9.42; 95% CI 1.69-52.69) and cervical dilation at least 4 cm (OR 7.92; 95% CI 1.40-44.71) were found to be independent risk factors for sPTB before 28 weeks, after cerclage. CONCLUSION: Emergency cerclage in women with twin pregnancies with cervical dilation and prolapsed membranes was associated with an overall 40% decrease in sPTB before 28 weeks and a prolongation of latency by 5 weeks. The strongest predictor of sPTB before 28 weeks after cerclage was a positive cervical culture.

Placenta Accreta Spectrum Outcomes Using Tourniquet and Forceps for Vascular Control.

Objective: To evaluate the use of tourniquet and forceps to reduce bleeding during surgical treatment of severe placenta accreta spectrum (placenta increta and placenta percreta). Methods: A tourniquet was used in the lower part of the uterus during surgical treatment of severe placenta accreta spectrum. Severe placenta accreta spectrum was classified into two types according to the relative position of the placenta and tourniquet during surgery: upper-tourniquet type, in which the entire placenta was above the tourniquet, and lower-tourniquet type, in which part or all of the placenta was below the tourniquet. The surgical effects of the two types were retrospectively compared. We then added forceps to the lower-tourniquet group to achieve further bleeding reduction. Finally, the surgical effects of the two types were prospectively compared. Results: During the retrospective phase, patients in the lower-tourniquet group experienced more severe symptoms than did patients in the upper-tourniquet group, based on mean intraoperative blood loss (upper-tourniquet group 787.5 ml, lower-tourniquet group 1434.4 ml) intensive care unit admission rate (upper-tourniquet group 1.0%, lower-tourniquet group 33.3%), and length of hospital stay (upper-tourniquet group 10.2d, lower-tourniquet group 12.1d). During the prospective phase, after introduction of the revised surgical method involving forceps (in the lower-tourniquet group), the lower-tourniquet group exhibited improvements in the above indicators (intraoperative average blood loss 722.9 ml, intensive care unit admission rate 4.3%, hospital stays 9.0d). No increase in the rate of complications was observed. Conclusion: The relative positions of the placenta and tourniquet may influence the perioperative risk of severe placenta accreta spectrum. The method using a tourniquet (and forceps if necessary) can improve the surgical effect in cases of severe placenta accreta spectrum.

Expression of SARS-CoV-2 entry genes ACE2 and TMPRSS2 at single cell resolution in the peripartum decidua.

Angiotensin-converting enzyme 2 (ACE2) is the key receptor for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). However, the susceptibility of the decidua to infection during the peripartum period has not been explored, even though this may affect vertical transmission. The objective of this study was to investigate the expression of ACE2 and related genes in the decidua during delivery. Here, single-cell RNA sequencing was used to characterize the transcriptomes of decidual cells before and after the onset of labor. During the peripartum period, ACE2 expression was highly heterogeneous. ACE2 was expressed principally in decidual stromal cells, uterine smooth muscle cells, and extravillous trophoblasts. Comparison of the transcriptomes of ACE2-positive and ACE2-negative cells indicated that ACE2-positive cells exhibited integrin clusters on the cell surface interactions. ACE2-positive cells were compared before and after labor onset. After delivery, the number of ACE2-positive cells was slightly higher than before delivery. Before labor onset, ACE2-positive decidual stromal cells were in the regulation of membrane protein ectodomain proteolysis cluster. After labor onset, the upregulated genes changed to include cell junction assembly genes. The susceptibility of decidual cells to SARS-CoV-2 infection is thus heterogeneous during the peripartum period.

A Biallelic Frameshift Mutation in Nephronectin Causes Bilateral Renal Agenesis in Humans.

BACKGROUND: Bilateral renal agenesis (BRA) is a lethal con genital anomaly caused by the failure of normal development of both kidneys early in embryonic development. Oligohydramnios on fetal ultrasonography reveals BRA. Although the exact causes are not clear, BRA is associated with mutations in many renal development genes. However, molecular diagnostics do not pick up many clinical patients. Nephronectin (NPNT) may be a candidate protein for widening diagnosis. It is essential in kidney development, and knockout of Npnt in mice frequently leads to kidney agenesis or hypoplasia. METHODS: A consanguineous Han family experienced three cases of induced abortion in the second trimester of pregnancy, due to suspected BRA. Whole-exome sequencing (WES)-based homozygosity mapping detected underlying genetic factors, and a knock-in mouse model confirmed the renal agenesis phenotype. RESULTS: WES and evaluation of homozygous regions in II:3 and II:4 revealed a pathologic homozygous frameshift variant in NPNT (NM_001184690:exon8:c.777dup/p.Lys260*), which leads to a premature stop in the next codon. The truncated NPNT protein exhibited decreased expression, as confirmed in vivo by the overexpression of WT and mutated NPNT. A knock-in mouse model homozygous for the detected Npnt mutation replicated the BRA phenotype. CONCLUSIONS: A biallelic loss-of-function NPNT mutation causing an autosomal recessive form of BRA in humans was confirmed by the corresponding phenotype of knock-in mice. Our results identify a novel genetic cause of BRA, revealing a new target for genetic diagnosis, prenatal diagnosis, and preimplantation diagnosis for families with BRA.

Single-cell RNA sequencing reveals heterogeneity and differential expression of decidual tissues during the peripartum period.

OBJECTIVES: The decidua is a tissue that contacts both maternal and foetal components and is pivotal to labour onset due to its location. Due to the heterogeneity of decidual tissue, it is challenging to study its role in the peripartum period. Herein, we analysed the transcriptomes of peripartum decidua at single-cell resolution. MATERIALS AND METHODS: Single-cell RNA sequencing was performed for 29 231 decidual cells before and after delivery to characterize the transcriptomes. RESULTS: Eight major cell types (including endothelial cells, fibroblasts) and subtypes of decidual stromal cells, extravillous trophoblasts and T cells were identified and found to have various functions. Compared with before delivery, the activation of decidual stromal cell, extravillous trophoblast and T-cell subtypes to different degrees was observed after delivery. Furthermore, the activation involved multiple functions, such as cell proliferation, and several pathways, such as the activator protein 1 pathway. The results of pseudotemporal ordering showed differentiation of decidual stromal cell and extravillous trophoblast subtypes, suggesting inhomogeneity of these subgroups in decidualization (decidual stromal cell) and invasion (extravillous trophoblast). CONCLUSIONS: The peripartum decidual tissue is heterogeneous. This study revealed changes in the decidua and its components at single-cell resolution; these findings provide a new perspective for the study of peripartum decidua.

LncRNA MALAT-1 promotes growth and metastasis of epithelial ovarian cancer via sponging microrna-22.

LncRNAs and miRNAs are emerging players in epithelial ovarian cancer (EOC). LncRNA MALAT-1 and miR-22 play vital roles in the onset and development of multiple cancers. Both of them are abnormally expressed in ovarian cancer, but the molecular basis for their involvement in EOC is unclear. In this study, we found MALAT-1 was up-regulated but miR-22 was down-regulated in EOC tissues and cell lines when compared to normal ovarian epithelial cell line IOSE80. Both of MALAT-1shRNA and miR-22 mimics inhibited ovarian cell proliferation, migration, and invasion, while simultaneously overexpressing MALAT-1 and miR-22 largely canceled out this inhibitory effect. Consistently, MALAT-1 silencing and miR-22 overexpression restrained tumor growth and metastasis to lungs in nude mice, which could be largely counteracted by co-overexpressing MALAT-1 and miR-22. Mechanistically, MALAT-1 targeted and sponged miR-22, counteracting its inhibitory effect on c-myc and c-myc-mediated epithelial-mesenchymal transition. Our findings for the first time demonstrated that MALAT-1 supports EOC progression through sponging miR-22, providing a novel insight into the role of MALAT-1 in ovarian cancer.

Single-cell transcriptomics analysis showing functional heterogeneity in decidual stromal cells during labor.

To investigate the heterogeneity of decidual stromal cells (DSCs) and their functional alterations during delivery, we conducted single-cell RNA sequencing analysis to characterize the transcriptomic profiles of DSCs before and after labor onset. According to their transcriptomic profiles, DSCs (6382 cells) were clustered into five subgroups with different functions. Similar to stromal cells, cells in cluster 1 were involved in cell substrate adhesion. On the other hand, cells in clusters 2 and 3 were enriched in signal transduction-related genes. Labor onset led to significant alterations in many pathways, including the activator protein 1 pathway (all clusters), as well as in the response to lipopolysaccharide (clusters 1-3). The downregulated genes were involved in coagulation, ATP synthesis, and oxygen homeostasis, possibly reflecting the oxygen and energy balance during delivery. Our findings highlight that peripartum DSCs are heterogeneous and play multiple roles in labor.

Mahanimbine Exerts Anticancer Effects on Human Pancreatic Cancer Cells by Triggering Cell Cycle Arrest, Apoptosis, and Modulation of AKT/Mammalian Target of Rapamycin (mTOR) and Signal Transducer and Activator of Transcription 3 (STAT3) Signalling Pathways.

BACKGROUND Pancreatic cancer causes tremendous mortality across the globe mainly due to late diagnosis and unavailability of efficient chemotheruptic agents. In the current study the anticancer potential of a plant derived alkaloid, Mahanimbine, was examined against a panel of pancreatic cancer cells. MATERIAL AND METHODS The cell proliferation was determined by MTT assay. Annexin V/PI and DAPI staining were performed to detect apoptosis. Cell cycle distribution was investigated by flow cytometery. Cell migration was detected by wound healing assay and protein expression was checked by western blotting. RESULTS The results revealed that Mahanimbine could inhibit the proliferation of the all the pancreatic cancer cells with lower cytoxicity against the normal cells. The IC50 ranged from 3.5 to 64 µM against the pancreatic cancer cell lines. The lowest IC50 of 3.5 µM was observed tor the Capan-2 and SW119 pancreatic cancer cell lines. The anticancer activity of Mahanimbine against the Capan-2 and SW119 cells was found to be due to G0/G1 cell cycle arrest and induction of apoptosis. Mahanimbine prompted apoptosis was also associated with decline in Bcl-2 and enhancement of the Bax expression. Further, it was observed that Mahanimbine could inhibit the AKT/mTOR and STAT3 signalling pathways in the Capan-2 and SW119 pancreatic cancer cells. The effects of the Mahanimbine were also examined on the migration of the Capan-2 and SW119 pancreatic cancer cells. It was found that Mahanimbine could inhibit the motility and migration of both the pancreatic cancer cell lines. CONCLUSIONS We found that Mahanimbine inhibits the proliferation of pancreatic cancer cells and as such Mahanimbine may prove beneficial in the management of pancreatic cancer.

Critical Role for Interleukin-25 in Host Protective Th2 Memory Response against Heligmosomoides polygyrus bakeri.

Infection with parasitic nematodes, especially gastrointestinal geohelminths, affects hundreds of millions of people worldwide and thus poses a major risk to global health. The host mechanism of defense against enteric nematode infection remains to be fully understood, but it involves a polarized type 2 immunity leading to alterations in intestinal function that facilitate worm expulsion. We investigated the role of interleukin-25 (IL-25) in host protection against Heligmosomoides polygyrus bakeri infection in mice. Our results showed that Il25 and its receptor subunit, Il17rb, were upregulated during a primary infection and a secondary challenge infection with H. polygyrus bakeri Genetic deletion of IL-25 (IL-25-/-) led to an attenuated type 2 cytokine response and increased worm fecundity in mice with a primary H. polygyrus bakeri infection. In addition, the full spectrum of the host memory response against a secondary infection with H. polygyrus bakeri was severely impaired in IL-25-/- mice, including delayed type 2 cytokine responses, an attenuated functional response of the intestinal smooth muscle and epithelium, diminished intestinal smooth muscle hypertrophy/hyperplasia, and impaired worm expulsion. Furthermore, exogenous administration of IL-25 restored the host protective memory response against H. polygyrus bakeri infection in IL-25-/- mice. These data demonstrate that IL-25 is critical for host protective immunity against H. polygyrus bakeri infection, highlighting its potential application as a therapeutic agent against parasitic nematode infection worldwide.

Type 2 immunity-dependent reduction of segmented filamentous bacteria in mice infected with the helminthic parasite Nippostrongylus brasiliensis.

BACKGROUND: Dynamic interactions between the host and gastrointestinal microbiota play an important role for local and systemic immune homeostasis. Helminthic parasites modulate the host immune response, resulting in protection against autoimmune disease but also increased susceptibility to pathogen infection. The underlying mechanisms remain largely unknown. RESULTS: We showed that the type 2 immune response to enteric Nippostrongylus brasiliensis infection in mice was associated with altered intestinal mucin and AMP expression and shifts in microbiota composition. Most strikingly, infection reduced concentrations of intestinal segmented filamentous bacteria (SFB), known inducers of T helper 17 cells, and IL-17-associated gene expression. Infected mice deficient in IL-13 or STAT6 did not reduce SFB or IL-17, and exogenous IL-25 replicated the effects of parasite infection in wild type mice. CONCLUSIONS: Our data show that parasite infection acts through host type 2 immunity to reduce intestinal SFB and expression of IL-17, providing an example of a microbiota-dependent immune modulation by parasites.