The relationship of immune cells with autism spectrum disorder: a bidirectional Mendelian randomization study.

BACKGROUND: Observational studies have indicated a correlation between immunological inflammation and the risk of autism spectrum disorder (ASD). However, the causal relationship between immunological inflammation and ASD remains uncertain. METHODS: Immunity-wide data sources were retrieved from the GWAS catalog. Genetic summary data on ASD were retrieved from two independent GWAS. We performed two independent bi-directional, two-sample Mendelian randomization (MR) analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between ASD and immune cell signatures. RESULTS: We have discovered 26 potential correlations between genetic predisposition in the immunophenotypes and ASD. The meta-analysis of the two inverse variance weighted (IVW)-produced estimates provided further evidence supporting the potential causal relationship between immunophenotypes and ASD. Based on the findings of the reverse MR analysis, it was determined that there are two potential negative causal relationships between ASD and immunophenotypes. However, the meta-analysis of the two IVW-derived MR estimates indicated that immunophenotypes were not significantly influenced by ASD (OR = 0.87, 95% CI = 0.73 -1.03, P = 0.09; OR = 0.91, 95% CI = 0.81-1.01, P = 0.08). CONCLUSIONS: This study expanded immune cell subtypes that were potentially causally associated with ASD risk as well as identified ASD-specific immune cell subtypes. The discovery has the potential to lead to earlier detection and more effective treatment techniques.

Elevated PGT promotes proliferation and inhibits cell apoptosis in preeclampsia by Erk signaling pathway.

Prostaglandins participate in maternal recognition of pregnancy, implantation and maintenance of gestation. Prostaglandin transporter (PGT), as a candidate molecule of prostaglandin carriers, might be involved in the pathogenesis of preeclampsia. In preeclampsia (PE) patients' placental tissue, we identified PGT by RNA sequencing, measured its expression pattern by quantitative real-time PCR and Western blot. PGT was found to be upregulated in preeclamptic placental tissue. The expression pattern of PGT in PE was double confirmed by eight Gene Expression Omnibus (GEO) databases. In abortion tissues at 6-8 weeks, we then observed the cellular location of PGT by Immunofluorescence technique (IF) and found PGT located in trophoblast cell of the placenta of early pregnancy. In vitro studies revealed that forced expression of PGT in HTR8/Sveno cell inhibited its apoptosis, but promoted its proliferation by activating Erk signaling. In vivo study, we used reduced uterine perfusion pressure (RUPP) rat model and L-NAME-induced preeclampsia-like rats to study the possible role of PGT in preeclampsia. And PGT was found to be upregulated in both preeclampsia rat models by Immunohistochemical (IHC) staining. Newly identified PGT plays an important role in trophoblast proliferation via Erk signaling, providing new insights for understanding the pathogenesis of PE.

The Enzyme 15-Hydroxyprostaglandin Dehydrogenase Inhibits a Shift to the Mesenchymal Pattern of Trophoblasts and Decidual Stromal Cells Accompanied by Prostaglandin Transporter in Preeclampsia.

Preeclampsia (PE) is a pregnancy complication beginning after 20 weeks of pregnancy that involves high blood pressure (systolic > 140 mmHg or diastolic > 90 mmHg), with or without proteinuria. Insufficient trophoblast invasion and abnormal decidualization are involved in PE development. However, whether unhealthy placenta and decidua have the same biological activities is unclear. The enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH; encoded by HPGD) degrades prostaglandin, and prostaglandin transporter (PGT), as a candidate molecule of prostaglandin carriers, helps transport prostaglandin into cells. Whether 15-PGDH and PGT are involved in PE has not been researched. In this study, we investigated the shared pathogenesis of foetal placenta and maternal decidua from the perspective of epithelial-mesenchymal transition (EMT)/mesenchymal-epithelial transition (MET) and explored the combined effects of 15-PGDH and PGT on the EMT/MET of trophoblasts and decidual stromal cells (DSCs). Here, we demonstrated that placental development and decidualization both involved EMT/MET. In PE, both trophoblasts and DSCs show more epithelial patterns. Moreover, 15-PGDH expression was downregulated in the placentas but upregulated in the deciduas of PE patients. Inhibiting 15-PGDH promotes a shift to a mesenchymal pattern of trophoblasts and DSCs depending on the PGT-mediated transport of prostaglandin E2 (PGE2). In conclusion, our results showed that inhibiting 15-PGDH promotes a shift to the mesenchymal pattern of trophoblasts and DSCs and may provide a new and alternative therapy for the treatment of PE.

The trend in delayed childbearing and its potential consequences on pregnancy outcomes: a single center 9-years retrospective cohort study in Hubei, China.

BACKGROUND: Due to the advancement of modern societies, the proportion of women who delay childbearing until or beyond 30 years has dramatically increased in the last three decades and has been linked with adverse maternal-neonatal outcomes. OBJECTIVE: To determine the trend in delayed childbearing and its negative impact on pregnancy outcomes. MATERIAL AND METHODS: A tertiary hospital-based retrospective study was conducted in Wuhan University Renmin Hospital, Hubei Province, China, during the years 2011-2019. The joinpoint regression analysis was used to find a trend in the delayed childbearing and the multiple binary logistic regression model was used to estimate the association between maternal age and pregnancy outcomes. RESULTS: Between 2011 and 2019, the trend in advanced maternal age (AMA ≥35 years) increased by 75% [AAPC 7.5% (95% CI: - 10.3, 28.9)]. Based on maternal education and occupation, trend in AMA increased by 130% [AAPC 11.8% (95% CI: 1.1, 23.7)] in women of higher education level, and 112.5% [AAPC 10.1% (95% CI: 9.4, 10.9)] in women of professional services. After adjusting for confounding factors, AMA was significantly associated with increased risk of gestational hypertension (aOR 1.5; 95% CI: 1.2, 2.1), preeclampsia (aOR 1.6; 95% CI: 1.4, 1.9), sever preeclampsia (aOR 1.7; 95% CI: 1.1, 2.6), placenta previa (aOR 1.8; 95% CI: 1.5, 2.2), gestational diabetes mellitus (aOR 2.5; 95% CI: 2.3, 2.9), preterm births (aOR 1.6; 95% CI: 1.4, 1.7), perinatal mortality (aOR 1.8; 95% CI: 1.3, 2.3), and low birth weight (aOR 1.3; 95% CI: 1.2, 1.4) compared with women aged < 30 years. CONCLUSION: Our findings show a marked increase in delayed childbearing and its negative association with pregnancy outcomes.

MALAT1 recruited the E3 ubiquitin ligase FBXW7 to induce CRY2 ubiquitin-mediated degradation and participated in trophoblast migration and invasion.

This study aimed to investigate the mechanism by which MALAT1 regulates CRY2 expression and participates in trophoblast migration and invasion. Three patients with unexplained recurrent spontaneous abortion, four patients with missed abortion, and four women who underwent artificial miscarriages were enrolled in this study. Quantitative reverse-transcription polymerase chain reaction and western blot analysis were used to detect RNA and protein expression, respectively. Trophoblast migration and invasion were detected by wound-healing and transwell invasion assays. RNA pull-down and Co-IP assays were used to indicate the interaction between MALAT1 and FBXW7 or the interaction between FBXW7 and CRY2. The results showed significantly decreased MALAT1 expression in the villous specimens from the RSA patients relative to that in the villous specimens from the missed abortion patients and the normal villous specimens. MALAT1 promoted trophoblast cell migration and invasion by negatively regulating CRY2 protein expression. MALAT1 recruited FBXW7 to impair CRY2 protein stability. In conclusion, MALAT1 downregulation in trophoblasts might be related to miscarriage. MALAT1 may recruit the E3 ubiquitin ligase FBXW7 to induce CRY2 ubiquitin-mediated degradation and participate in trophoblast migration and invasion.

Perinatal Transmission of 2019 Coronavirus Disease-Associated Severe Acute Respiratory Syndrome Coronavirus 2: Should We Worry?

We present 2 cases of coronavirus disease 2019 (COVID-19)-associated severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the third trimester of pregnancy. Both mothers and newborns had excellent outcomes. We failed to identify SARS-CoV-2 in all of the products of conception and the newborns. This report provided evidence of low risk of intrauterine infection by vertical transmission of SARS-CoV-2.

Case series of 20 pregnant women with 2019 novel coronavirus disease in Wuhan, China.

AIM: To evaluate perinatal outcomes regarding clinical presentation in pregnancy and the vertical transmission potential of COVID-19. METHODS: Clinical records, laboratory findings, and chest computed tomography (CT) scans were retrospectively reviewed from 20 pregnant patients with laboratory-confirmed COVID-19 who were admitted to Renmin Hospital of Wuhan University and The Third Hospital of Wuhan, from Jan 20 to Mar 16, 2020, including three in the first-trimester, two in the second-trimester, and 15 in the third-trimester. Evidence of vertical transmission was assessed by testing for neonatal throat swab samples. The pathological changes of COVID-19 on the placenta is evaluated by hematoxylin-eosin staining. RESULTS: The most common symptoms of the pregnant women with SARS-CoV-2 infection were fever and cough, which is comparable to the nonpregnant adults with COVID-19 infection. Nobody was transferred to intensive care unit (ICU) for treatment and there were no maternal and neonatal deaths. However, there was one case with induced abortions on first-trimester (due to pregnant woman's concerns about COVID-19), one diagnosed with ectopic pregnancy, no intrauterine fetal deaths during the study period. Delivery occurred in 15 patients in the third trimester. Their incidence of preterm birth was 20%. Three of the four preterm births were spontaneous. The average length of stay was 20.77 days. No neonatal SARS-CoV-2 infection was detected. There were two placentas found with acute chorioamnionitis, one showed normal placenta morphology. CONCLUSION: In this case series study, COVID-19 had no short-term adverse effect on pregnant women except premature birth. The vertical transmission of SARS-CoV-2 did not occur in our study.

Effect of preeclampsia and premature rupture of membrane on neonatal birth weight and length by gestational age: A retrospective study in China.

BACKGROUND: Preeclampsia (PE) and premature rupture of membrane (PROM) are considered significant risk factors for lower neonatal birth weight and birth length. However, very limited studies have reported the impact of PE and PROM on neonatal birth weight and birth length by gestational week. Therefore, we aimed to determine the effect of PE and PROM on neonatal birth weight and length by gestational age. MATERIALS AND METHODS: A total of 9707 singleton neonates were selected for this study. All the data were collected and documented in the obstetric register by the trained nurses in the Gynecology and Obstetrics Department. RESULTS: The neonatal mean birth weights and birth lengths were statistically significantly (P < 0.05) lowered among preeclamptic mothers compared to mothers without PE throughout the gestational age. Statistically significantly (P < 0.05) lowered mean birth weights and birth lengths were found among neonates born to mothers with PROM than among neonates born to mothers without PROM by all gestational weeks except for 32 weeks and 36 weeks. Moreover, in a multiple linear regression model, PE and PROM were significantly negatively associated with neonatal birth weights and birth lengths by almost all gestational weeks (ß <0, P < 0.05). CONCLUSION: We concluded that after adjustment for covariates and confounding factors, PE and PROM had a significantly negative association with neonatal birth weights and birth lengths by all gestational weeks.

Coronavirus disease 2019 in pregnant women: a report based on 116 cases.

BACKGROUND: The coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2, is a global public health emergency. Data on the effect of coronavirus disease 2019 in pregnancy are limited to small case series. OBJECTIVE: To evaluate the clinical characteristics and outcomes in pregnancy and the vertical transmission potential of severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: Clinical records were retrospectively reviewed for 116 pregnant women with coronavirus disease 2019 pneumonia from 25 hospitals in China between January 20, 2020, and March 24, 2020. Evidence of vertical transmission was assessed by testing for severe acute respiratory syndrome coronavirus 2 in amniotic fluid, cord blood, and neonatal pharyngeal swab samples. RESULTS: The median gestational age on admission was 38+0 (interquartile range, 36+0-39+1) weeks. The most common symptoms were fever (50.9%, 59/116) and cough (28.4%, 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal radiologic findings were found in 96.3% (104/108) of cases. Of the 116 cases, there were 8 cases (6.9%) of severe pneumonia but no maternal deaths. One of 8 patients who presented in the first trimester and early second trimester had a missed spontaneous abortion. Of 99 patients, 21 (21.2%) who delivered had preterm birth, including 6 with preterm premature rupture of membranes. The rate of spontaneous preterm birth before 37 weeks' gestation was 6.1% (6/99). One case of severe neonatal asphyxia resulted in neonatal death. Furthermore, 86 of the 100 neonates tested for severe acute respiratory syndrome coronavirus 2 had negative results; of these, paired amniotic fluid and cord blood samples from 10 neonates used to test for severe acute respiratory syndrome coronavirus 2 had negative results. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There is no evidence of vertical transmission of severe acute respiratory syndrome coronavirus 2 infection when the infection manifests during the third trimester of pregnancy.

Stretchable Electrochemical Sensor for Real-Time Monitoring of Cells and Tissues.

Stretchable electrochemical sensors are conceivably a powerful technique that provides important chemical information to unravel elastic and curvilinear living body. However, no breakthrough was made in stretchable electrochemical device for biological detection. Herein, we synthesized Au nanotubes (NTs) with large aspect ratio to construct an effective stretchable electrochemical sensor. Interlacing network of Au NTs endows the sensor with desirable stability against mechanical deformation, and Au nanostructure provides excellent electrochemical performance and biocompatibility. This allows for the first time, real-time electrochemical monitoring of mechanically sensitive cells on the sensor both in their stretching-free and stretching states as well as sensing of the inner lining of blood vessels. The results demonstrate the great potential of this sensor in electrochemical detection of living body, opening a new window for stretchable electrochemical sensor in biological exploration.

C-reactive protein plays a marginal role in cognitive decline: a systematic review and meta-analysis.

OBJECTIVE: The objective of the study was to investigate the association between peripheral levels of C-reactive protein (CRP) and cognitive decline that is defined by 2-5 years of cognitive change in general cognitive function or specific cognitive domain. METHODS: We searched PubMed and Google for prospective/longitudinal studies that report the association between peripheral levels of CRP and risk of cognitive decline in the nondementia population. RESULTS: Out of 479 related articles from PubMed and Google, four studies with a total of 5255 non-demented subjects that report odds ratio (OR)/relative risk/hazard ratio of CRP levels and decline in general cognition met our criteria for meta-analysis. The association between higher levels of CRP and risk of global cognitive decline was weak but significant (OR, 1.27 [95% CI, 1.02 to 1.58]). However, the systematic review from six other articles that were not suitable for meta-analysis revealed a marginal association between CRP and cognitive decline in certain domains. CONCLUSION: Our analysis demonstrated a weak association between peripheral CRP level and global cognitive decline. Because of the small number of included studies and varied methodologies that they applied, caution should be taken when generalizing our finding to the full range of cognitive changes in different cognitive domains observed in non-demented people.

The causal role of circulating immunity-inflammation in preeclampsia: A Mendelian randomization.

Patients with systemic autoimmune diseases, such as systemic lupus erythematosus, were at a higher risk for preeclampsia. The causal relationship between immunological inflammation and preeclampsia (PE) remains uncertain. We aimed to investigate the causal relationship between circulating immune inflammation and PE. Genetically predicted blood immune cells and circulating inflammatory proteins were identified using two genome-wide association studies (GWAS). We used a two-sample Mendelian randomization (MR) method to determine whether circulating immunological inflammation causes PE. Our findings indicated that ten immunophenotypes were identified to be significantly associated with PE risk: CD62L- Dendritic Cell Absolute Count, CD86+ myeloid Dendritic Cell %Dendritic Cell, CD62L- myeloid Dendritic Cell Absolute Count, CD86+ myeloid Dendritic Cell Absolute Count, CD62L- myeloid Dendritic Cell %Dendritic Cell, CD62L- CD86+ myeloid Dendritic Cell %Dendritic Cell, CD62L- CD86+ myeloid Dendritic Cell Absolute Count, CD16 on CD14+ CD16+ monocyte, HLA DR+ Natural Killer Absolute Count, and T cell Absolute Count. Ninety-one inflammation-related proteins had no statistically significant effect on PE following false discovery rate (FDR) correction. Certain proteins exhibited unadjusted low p-values that merited mention. These proteins include interleukin-10 (OR = 0.76, 95%CI = 0.63-0.93, p = .006), fibroblast growth factor 21 (OR = 1.23, 95%CI = 1.01-1.47, p = .035), and Caspase 8 (OR = 0.65, 95%CI = 0.50-0.85, p = .001). The ELISA analysis demonstrated elevated levels of FGF-21 and decreased levels of IL-10 and Caspase-8 in the plasma of patients with PE. These findings reveal that immunophenotypes and circulating inflammatory proteins may induce PE, confirming the importance of peripheral Immunity-Inflammation in PE. The discovery has the potential to lead to earlier detection and more effective treatment techniques.

Role of CircCHD2 in the pathogenesis of gestational diabetes mellitus by regulating autophagy via miR-33b-3p/ULK1 axis.

Gestational diabetes mellitus (GDM) is a common pregnancy complication with a high incidence in women; however, its pathophysiology remains unknown. Our previous study suggested that the circCHD2/miR-33b-3p/ULK1 axis may be involved in GDM pathogenesis. However, the mechanism through which circCHD2 regulates GDM development requires further investigation. We found that high-glucose (HG, 25 mmol/L) significantly induced the expression of circCHD2, increased autophagy and apoptosis, and decreased cell viability in human placental trophoblast HTR-8/SVneo cells. In contrast, the downregulation of circCHD2 significantly attenuated the effects of HG on HTR-8/SVneo cells. MiR-33b-3p downregulated in the placenta of GDM patients was reduced by HG and detected as a target of circCHD2 using bioinformatics analysis, a dual-luciferase reporter assay, and qRT-PCR assay. Further studies showed that the inhibition of miR-33b-3p significantly blocked the effects of circCHD2 downregulation on cell viability, apoptosis, and autophagy in HG-treated HTR-8/SVneo cells. ULK1 is a target of miR-33b-3p, based on bioinformatics analysis, a dual-luciferase reporter assay, qRT-PCR assay, and Western blot analysis. Compared to miR-33b-3p, ULK1 is upregulated in the placenta of GDM patients. ULK1 overexpression notably blocked the effects of miR-33b-3p mimics on cell viability, apoptosis, and autophagy in HG-treated HTR-8/SVneo cells. These findings suggested that circCHD2 acts as an autophagy promoter via the miR-33b-3p/ULK1 axis to induce apoptosis in HTR-8/SVneo cells, suggesting that circCHD2 is a potential diagnostic and therapeutic target for GDM.

Single-Cell RNA Sequencing and Microarray Analysis Reveal the Role of Lipid-Metabolism-Related Genes and Cellular Immune Infiltration in Pre-Eclampsia and Identify Novel Biomarkers for Pre-Eclampsia.

Pre-eclampsia (PE) is a gestational hypertensive disorder that is characterized by hypertension and proteinuria, typically occurring after 20 weeks of gestation. Despite its global impact on pregnant women, the precise pathogenic mechanisms of PE remain unclear. Dysregulated lipid metabolism and immune cell infiltration contribute to PE development. Our study aimed to identify lipid-metabolism-related genes (LMRG-PEs) and investigate their association with immune infiltration. We utilized the "Seurat" R package for data quality control, cell clustering, and marker gene identification. The "SingleR" package enabled the matching of marker genes to specific cell types. Pseudotemporal ordering analysis was conducted using the "Monocle" package. Weighted correlation network analysis (WGCNA), gene set variation analysis (GSVA), and gene set enrichment analysis (GSEA) approaches were employed to explore lipid-metabolism-related genes, while potential targeted drugs were predicted using the drug-gene interaction database (DGIdb). Hub gene expression was validated through RT-qPCR. By analyzing single-cell RNA sequencing data, we identified and classified 20 cell clusters into 5 distinct types. Differential gene expression analysis revealed 186 DEGs. WGCNA identified 9 critical modules and 265 genes significantly associated with PE diagnosis, emphasizing the importance of the core genes PLA2G7 and PTGS2. RT-qPCR confirmed the significantly decreased expression of PLA2G7 and PTGS2 in PE patient tissues. These findings offer valuable insights into the molecular mechanisms of PE, particularly those involving lipid metabolism and immune infiltration. The identified hub genes have potential as therapeutic targets and biomarkers for future research and clinical applications.

Interactions between ultrasonographic cervical length and placenta accreta spectrum on severe postpartum hemorrhage in women with placenta previa.

OBJECTIVE: To explore the interactions between cervical length (CL) and placenta accreta spectrum (PAS) on severe postpartum hemorrhage (SPPH) in patients with placenta previa. METHODS: A retrospective case-control study was conducted at four medical centers in China, and 588 patients with placenta previa were included. The logistic regression analysis and restricted cubic splines (RCS) were used to evaluate the association between CL and SPPH. Furthermore, the joint effect of CL and PAS on SPPH was assessed, and the additive and multiplicative interactions were calculated. RESULTS: After adjusting for potential confounders, the negative linear dose-response relationship was confirmed by RCS, and the change of odds ratio (OR) was more significant when CL was 2.5 cm or less. The risk of SPPH was significantly higher when CL of 2.5 cm or less co-existed with placenta increta/percreta than when CL of 2.5 cm less, or placenta increta/percreta existed alone (adjusted OR [aOR]CL ≤2.5cm&placenta accreta/non-PAS 3.40, 95% confidence interval [CI] 1.37-8.45; aORplacenta increta/percreta&CL >2.5cm 4.75, 95% CI 3.03-7.47; aORCL ≤2.5cm&placenta increta/percreta 14.51, 95% CI 6.08-34.64), and there might be additive interaction between CL and placenta increta/percreta on SPPH (attributable proportion due to interaction 50.7%, 95% CI 6.1%-95.3%). CONCLUSION: If CL was routinely performed during PAS evaluation, the increased OR of short CL and PAS could allow better patient preparation through counseling.

Relationship of maternal factors and obstetric complications with term singleton vs term twin neonatal outcomes: A retrospective study in China.

Background: Neonatal birth weight and length are important indicators of neonatal survival and morbidity during later life and are influenced by maternal factors and obstetrical complications. Therefore, we aimed to determine the relationship of maternal factors and obstetric complications with term singleton vs term twin neonatal outcomes in Wuhan University Renmin Hospital, Hubei, China. Methods: A total of 10517 neonatal births were recorded in a tertiary-hospital-based retrospective study and term singleton (n=7787) and term twins (n=169) were included for data analysis. Birth weight and birth length were measured immediately after birth. Correlation, independent student t-test, and backward multiple linear regression were used for statistical analysis. Results: Women with singleton gestation have an increased rate of obstetric complications compared to women with twin gestation. However, a higher frequency of cesarean section and breech were found in twin gestation compared to singleton gestation. Weight before pregnancy, gestational weight gain, and gestational diabetes mellitus were significantly positive (p<0.05) associated with singleton neonatal birth length and weight. In contrast, preeclampsia, placenta previa, oligohydramnios, premature rupture of membrane, breech, and multiparity had a significantly negative (p<0.05) association with singleton neonatal birth length and weight. Maternal age was significantly positive (p<0.05) associated with only singleton neonatal birth weight. Moreover, the nuchal cord was significantly positive (p<0.05) associated with singleton neonatal birth length. On the other hand, maternal age and multiparity were significantly positive (p<0.05) associated with twins' neonatal birth length and weight. Furthermore, gestational weight gain was significantly positive (p<0.05) associated with only twins' neonatal birth weight. Conclusion: In term gestation, obstetric complications were significantly associated with singleton birth size rather than twin birth size.

Three categories of similarities between the placenta and cancer that can aid cancer treatment: Cells, the microenvironment, and metabolites.

Cancer is one of the most harmful diseases, while pregnancy is a common condition of females. Placenta is the most important organ for fetal growth, which has not been fully understand. It's well known that placenta and solid tumor have some similar biological behaviors. What's more, decidua, the microenvironment of placenta, and metabolism all undergo adaptive shift for healthy pregnancy. Interestingly, decidua and the tumor microenvironment (TME); metabolism changes during pregnancy and cancer cachexia all have underlying links. However, whether the close link between pregnancy and cancer can bring some new ideas to treat cancer is still unclear. So, in this review we note that pregnancy may offer clues to treat cancer related to three categories: from cell perspective, through the shared development process of the placenta and cancer; from microenvironment perspective, though the shared features of the decidua and TME; and from metabolism perspective, through shared metabolites changes during pregnancy and cancer cachexia. Firstly, comparing gene mutations of both placenta and cancer, which is the underlying mechanism of many similar biological behaviors, helps us understand the origin of cancer and find the key factors to restore tumorigenesis. Secondly, exploring how decidua affect placenta development and similarities of decidua and TME is helpful to reshape TME, then to inhibit cancer. Thirdly, we also illustrate the possibility that the altered metabolites during pregnancy may reverse cancer cachexia. So, some key molecules changed in circulation of pregnancy may help relieve cachexia and make survival with cancer realized.

Changes in adverse pregnancy outcomes in women with advanced maternal age (AMA) after the enactment of China's universal two-child policy.

The universal two-child policy (TCP; 2016) in China has affected many aspects of maternal-neonatal health. A tertiary hospital-based retrospective study (2011-2019) was used to find the association of these policy changes with maternal age and pregnancy outcomes in women with AMA (≥ 35 years) in the Hubei Province, China. The proportion of neonatal births to women with AMA increased by 68.8% from 12.5% in the one-child policy (OCP) period to 21.1% in the universal TCP period [aOR 1.76 (95% CI: 1.60, 1.93)]. In the univariate analysis, the proportion of preterm births (29.4% to 24.1%), low birth weight (LBW) (20.9% to 15.9%), and hypertensive disorders of pregnancy (HDP) (11.5% to 9.2%) significantly (p < 0.05) decreased in women with AMA from the OCP period to universal TCP period. However, the proportion of intrauterine growth restriction (IUGR) (0.2% to 0.7%) and gestational diabetes mellitus (GDM) (1.7% to 15.6%) was significantly (p < 0.05) increased over the policy changes. After adjusting for confounding factors, only the risk of GDM increased [aOR 10.91 (95% CI: 6.05, 19.67)] in women with AMA from the OCP period to the universal TCP period. In conclusion, the risk of GDM increased in women with AMA from the OCP period to the universal TCP period.

Systematic external evaluation of four preoperative risk prediction models for severe postpartum hemorrhage in patients with placenta previa: A multicenter retrospective study.

AIM: To compare and evaluate the validity of the existing risk prediction models for severe postpartum hemorrhage (SPPH) in patients with placenta previa. METHODS: We conducted a systematic literature review to collect the existing risk prediction models for SPPH in patients with placenta previa, and recruited patients with placenta previa who underwent cesarean section in Tongji Hospital (Wuhan, China) and 4 cooperative hospitals from January 2018 to June 2021. We defined SPPH as total blood loss ≥1500 mL or transfusion packed red blood cell ≥4 U. The risk of SPPH of each patient was predicted by the collected models, respectively. Then we calculated the sensitivity, specificity, coincidence rate (CCR), positive predictive value (PPV), negative predictive value (NPV) and drawn the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) curve of each model. RESULTS: This external cohort contained 1172 patients of whom 284 patients (24.23%) experienced SPPH, and 4 risk prediction models were collected in this study. After evaluated by this external cohort, the area under the ROC curve (AUC), sensitivity, specificity, CCR, PPV and NPV of the four models ranged from 0.644 to 0.755, 38.38% to 86.31%, 42.75% to 86.49%, 56.23% to 74.83%, 38.68% to 47.60%, 81.15% to 87.45%, respectively. The model established by Kim JW et al. had the highest sensitivity, NPV, AUC and net benefit, the model established by Lee JY et al. had the highest specificity, CCR and PPV. CONCLUSIONS: The four prediction models showed moderate predictive performance, the discrimination indicators and benefit indicators of each model were not simultaneously ideal in this population. The prediction models should be further optimized to improve the discrimination ability and benefit, and prospective external validation studies should also be carried out before they are applied to clinical practice.

Long noncoding RNA expression profiling identifies MIR210HG as a novel molecule in severe preeclampsia.

OBJECTIVE: Preeclampsia (PE) is a potentially fatal pregnancy-specific complication. Nevertheless, the pathogenesis of PE remains indistinct. Recently, increasing studies emphasized that long noncoding RNAs (lncRNAs) functions as imperative regulators in PE. The aim of this study was to compare the lncRNAs transcript profile of placentae in early onset severe preeclampsia (EOSP) with lncRNAs in normal pregnancy (NP) and to evaluate the role of lncRNA MIR210HG (microRNA 210 host gene) in the PE pathogenesis. METHODS: Using RNA sequencing, we compared transcriptome profiles of placentae in EOSP (n = 3) and NP (n = 3). Bioinformatic tools were used to predict the function of differentially expressed genes while qRT-PCR was used to verify RNA sequencing data. The role of MIR210HG in HTR8/SVneo migration and invasion were analyzed by in vitro MIR210HG gene overexpression. RESULTS: Our results showed that 527 lncRNAs and 600 mRNAs were differentially expressed in placental samples of EOSP, and the analysis identified 63 key EOSP related genes. As indicated by bioinformatics analyses, lncRNA MIR210HG was a potential pathogenic marker of PE. LncRNA-MIR210HG expression was upregulated in placental samples of PE and enriched in the canonical Wnt signalling pathway. MiR210HG overexpression inhibited HTR8/SVneo cell migration and invasion in vitro. Additionally, miR210HG upregulated dickkopf-1 expression via the sponging of microRNA-520a-3p (miR-520a-3p), thus repressing trophoblast migration and invasion. CONCLUSION: Our study showed that MiR210HG is a novel upregulated lncRNA in the placentas of PE and MiR210HG regulates the migration and invasive potential of HTR-8/SVneo cell by targeting the miR-520a-3p/Dickkopf-1 axis.