[Clinical Confusion Concerning Increased D-Dimer Value during Pregnancy].

Plasma D-dimer, a special cross-linked fibrin derivative, is produced when fibrin is degraded by plasminase. During pregnancy, D-dimer increases along with the increase of gestational age, and the reference value of plasma D-dimer (≤0.5 mg/L) traditionally used for the screening of venous thrombosis in the normal population is not applicable to the pregnant population. Due to the lack of uniform D-dimer detection methods or measurement units, there is currently no unified D-dimer reference values for pregnancy or puerperium. Each region or laboratory should establish its own pregnancy D-dimer reference value for different gestational weeks through blood coagulation function testing of large numbers of samples of different gestational periods. More and more studies have been conducted to investigate the association between D-dimer and venous thromboembolism (VTE) during pregnancy, gestational hypertensive disorders (GHD) and pregnancy outcome. We reviewed, herein, the generation and measurement of D-dimer, the reference values of D-dimer during normal pregnancy, and the association between D-dimer and some pathological pregnancies, intending to help clinicians develop a more thorough understanding of D-dimer during pregnancy.

[Preeclampsia: An Obstetrician's Perspective].

Preeclampsia-eclampsia is a common obstetric critical disease and obstetricians have studied it assiduously for hundreds of years. We have attempted to explore the etiology, pathology, prevention, intervention, and treatment of preeclampsia-eclampsia, but we still have not arrived at a thorough understanding of its causes, and it is difficult to find effective prevention and treatment methods. Although the research process has been fraught with difficulties and frustrations, we are nonetheless gradually gaining a better understanding of the disease. Perhaps, in the near future, we will be able to acquire a full understanding of the disease and find better ways to ensure the health and safety of mothers and fetuses.

[Latest Research Findings on Prediction of Preeclampsia in Pregnant Women Based on Analysis of Cell-Free RNA in Peripheral Blood].

Preeclampsia gravely threatens the health of mothers and infants. At present, treatment based on the relevant mechanisms of pathogenesis is still not available, and there is no independent reliable clinical index for early prediction of preeclampsia. According to recent studies, analysis of the cell-free RNA in the peripheral blood of pregnant women has shown that testing certain cell-free RNA levels can help predict in advance the occurrence of preeclampsia before clinical symptoms appear. In this paper, we described the status of research and progress in using maternal cell-free RNA analysis in predicting preeclampsia. In addition, we stated that cell-free RNA in peripheral blood may become a promising, real-time and non-invasive monitoring method that can be used to explore the mechanisms of pathogenesis and pathophysiology of preeclampsia and to identify different subtypes of preeclampsia.

Deficiency of DICER reduces the invasion ability of trophoblasts and impairs the pro-angiogenic effect of trophoblast-derived microvesicles.

DICER is a key rate-limiting enzyme in the canonical miRNAs biogenesis pathway, and DICER and DICER-dependent miRNAs have been proved to play essential roles in many physiological and pathological processes. However, whether DICER is involved in placentation has not been studied. Successful spiral artery remodelling is one of the key milestones during placentation, which depends mostly on the invasion of trophoblasts and the crosstalk between trophoblasts and endothelial cells. In the present study, we show that DICER knockdown impairs the invasion ability of both primary extravillous trophoblasts (EVT) and HTR8/SVneo (HTR8) cell lines. The decreased invasion of HTR8 cells upon DICER knockdown (sh-Dicer) was partly due to the up-regulation of miR-16-2-3p, which led to a reduced expression level of the collagen type 1 alpha 2 chain (COL1A2) protein. Moreover, microvesicles (MVs) can be secreted by HTR8 cells and promote the tube formation ability of human umbilical cord vein endothelial cells (HUVECs). However, conditioned medium and MVs derived from sh-Dicer HTR8 cells have an anti-angiogenic effect, due to reduced angiogenic factors and increased anti-angiogenic miRNAs (including let-7d, miR-1-6-2 and miR-15b), respectively. In addition, reduced protein expression of DICER is found in PE placenta by immunoblotting and immunohistochemistry. In summary, our study uncovered a novel DICER-miR-16-2-COL1A2 mediated pathway involved in the invasion ability of EVT, and DICER-containing MVs mediate the pro-angiogenic effect of trophoblast-derived conditioned medium on angiogenesis, implying the involvement of DICER in the pathogenesis of PE.

Testis-enriched circular RNA circ-Bbs9 plays an important role in Leydig cell proliferation by regulating a CyclinD2-dependent pathway.

Circular RNAs belong to a new category of non-coding RNAs, characterised by a circular structure, conservation, stability and high expression in eukaryotes. They often show tissue- or cell-specific expression. Here, we identified a testis-enriched circular RNA (circRNA), circular Bbs9 (circ-Bbs9) that is highly expressed in mouse testis. An RNase R treatment experiment confirmed that circ-Bbs9 is indeed a circRNA. In situ hybridisation experiments showed that circ-Bbs9 is expressed in Leydig cells along seminiferous tubules and in the cytoplasm of the TM3 Leydig cell line. Knocking down the circ-Bbs9 in TM3 cells by lentivirus vectors arrested cell proliferation, whereas overexpression of circ-Bbs9 induced cell proliferation significantly. Knocking down circ-Bbs9 inhibited the protein level of cyclin D2 (Ccnd2) and RNA immunoprecipitation results showed that circ-Bbs9 interacts with Ccnd2. Our results show that use of the Hedgehog pathway Smoothened Agonist (SAG) HCl and antagonists cyclopamine and gant6 affects the expression levels of Glioma-Associated Oncogene Homolog 1 (Gli1), Ccnd2 and other genes in this pathway. Our research reveals that a Leydig cell-specific circRNA, circ-Bbs9, plays a critical role in Leydig cell proliferation through regulating the levels of cell cycle-related Ccnd2. Thus, our results emphasise the important role of circRNA in the male reproductive system.

Prevalence of anemia and iron deficiency anemia in Chinese pregnant women (IRON WOMEN): a national cross-sectional survey.

BACKGROUND: The current evidence about anemia and iron deficiency anemia (IDA) during pregnancy remains elusive in China. The purpose of this study is to investigate the prevalence of anemia and IDA and their risk factors in Chinese pregnant women. METHODS: A nationwide cross-sectional survey of pregnant women was conducted during their antenatal visits. Using a multi-stage sampling method, 24 hospitals from 16 provinces across China were selected. Structured questionnaires were administered to collect information from participants and to extract clinical data from electronic medical records. Mixed-effects logistic regression models were performed to determine the risk factors associated with anemia and IDA. RESULTS: In total, 12,403 pregnant women were enrolled, including 1018 (8.2%) at the first trimester, 3487 (28.1%) at the second, and 7898 (63.7%) at the third. Overall, 19.8% of women were diagnosed with anemia and 13.9% were diagnosed with IDA. The prevalence of anemia and IDA varied among regions and increased by gestational month, peaking at the eighth gestational month (24.0% for anemia and 17.8% for IDA). Pregnant women at advanced stage of gestation, non-local residents, multiple gestations, multiparity, pre-pregnancy underweight, and those experiencing severe nausea or vomiting during pregnancy, were associated with higher risks of anemia and IDA. CONCLUSIONS: The prevalence of anemia and IDA during pregnancy are similar to those from developed countries and vary across regions in China.

Inhibition of Frizzled-2 by small interfering RNA protects rat hepatic BRL-3A cells against cytotoxicity and apoptosis induced by Hypoxia/Reoxygenation.

Frizzled-2 plays an important role in maintaining normal hepatic cell functionality. This study aimed to investigate the role of inhibition of Frizzled-2 in protecting rat liver BRL-3A cells from Hypoxia/Reoxygenation (H/R). In vitro H/R hepatic cell model was established by culturing BRL-3A cells under H/R condition. Frizzled-2 siRNA was transfected into BRL-3A cells to inhibit Frizzled-2 signaling. Wnt5a and Frizzled-2 were significantly increased in BRL-3A cells upon H/R treatment. H/R treatment induced cell cytotoxicity, the early apoptosis rate and the intracellular Ca2+ level in BRL-3A cells while silencing frizzled-2 gene decreased the H/R induced cell cytotoxicity, apoptosis and intracellular Ca2+ level. In vivo mice study further showed the up-regulation of Frizzled-2/Wnt 5 pathway and cleaved Caspase-3 expression in liver tissues under ischemia and reperfusion injury (IRI). In summary, inhibition of Frizzled-2 by its siRNA may protects BRL-3A cells by attenuating the H/R induced cell cytotoxicity and apoptosis.

[Development of a Predictive Model for Adverse Outcomes of Preeclampsia].

OBJECTIVE: To determine factors associated with adverse outcomes of preeclampsia and develop a predictive model. METHODS: Clinical data of 2 532 patients with preeclampsia who were admitted to our hospital from 2005 to 2014 were extracted for the study. The patients were divided into two groups, including 990 (39.1%) with adverse outcomes and 1 542 (60.9%) without adverse outcomes. Factors associated with adverse outcomes were identified through univariate analyses. The predictive model was developed through multivariate logistic regression analyses using a randomly selected sample containing 80% of the cases. The remaining 20% of cases served for the purpose of validation and the establishment of the ROC curve. RESULTS: Primiparas, educational attainments, prenatal care, multiple births, edema, chest pain, dyspnea, dizziness, headache, blurred vision, intrahepatic cholestasis of pregnancy, gestational diabetes, cardiovascular disease, blood pressure, urine protein, liver and kidney functions were found to be associated with adverse outcomes of preeclampsia. Multiple births, edema, dyspnea, blurred vision, cardiovascular disease, liver and kidney functions entered into the logistic regression model (P<0.05). The Logit(P) model had a good fitness of data and 77.1% accuracy in predicting adverse outcomes. The area under the curve (AUC) of the ROC curve was 0.804 [P<0.01, 95% confidence interval CI): 0.758 to 0.849]. The highest sensitivity was achieved when the cut-off point set risk value at 0.300, [CM(155mm]with 58.6% patients having adverse outcomes representing 83.8% true positive rate and 46.8% false positive rate. CONCLUSION: Adverse outcomes of preeclampsia can be predicted through multiple births, edema, dyspnea, blurred vision, cardiovascular disease, liver and kidney functions. Risk value ≥0.300 is recommended.

Progress in the understanding of the etiology and predictability of fetal growth restriction.

Fetal growth restriction (FGR) is defined as the failure of fetus to reach its growth potential for various reasons, leading to multiple perinatal complications and adult diseases of fetal origins. Shallow extravillous trophoblast (EVT) invasion-induced placental insufficiency and placental dysfunction are considered the main reasons for idiopathic FGR. In this review, first we discuss the major characteristics of anti-angiogenic state and the pro-inflammatory bias in FGR. We then elaborate major abnormalities in placental insufficiency at molecular levels, including the interaction between decidual leukocytes and EVT, alteration of miRNA expression and imprinted gene expression pattern in FGR. Finally, we review current animal models used in FGR, an experimental intervention based on animal models and the progress of predictive biomarker studies in FGR.Free Chinese abstract: A Chinese translation of this abstract is freely available at http://www.reproduction-online.org/content/153/6/R215/suppl/DC1.

[Severe Adverse Pregnancy Outcomes in Placenta Previa and Prior Cesarean Delivery].

OBJECTIVE: To investigate the severe adverse pregnancy outcomes in pregnancies with placenta previa and prior cesarean delivery and its risk factors. METHODS: This retrospective casecontrol study reviewed all pregnancies with placenta previa and prior cesarean delivery delivered by repeat cesarean section in our institution between January 2005 and June 2015,and investigated the incidence of severe adverse pregnancy outcome. A composite of severe adverse pregnancy outcomes (including transfusion of 10 units or more red blood cells,maternal ICU admission,unanticipated injuries,repeat operation,hysterectomy,and maternal death) and other maternal and neonatal outcomes were described. Univariate and multivariable logistic regression analysis were used to quantify the effects of risk factors on severe adverse pregnancy outcomes. RESULTS: There were 478 women with placenta previa and prior cesarean delivery in our hospital over the last decade. The average age of them was 32.5±4.8 years old,most women were beyond 30 years old,the average gravidity and parity were 4 and 1,131 cases (27.4%) had severe adverse pregnancy outcomes. Transfusion of 10 units or more red blood cells happened in 75 cases (15.7%,75/478); 44 cases (9.2%,44/478) necessitated maternal ICU admission; unanticipated bladder injury occurred in 11 cases,but non ureter or bowel injury happened; All 4 repeat operations were due to delayed hemorrhage after conservative management during cesarean delivery,and an emergent hysterectomy was performed for all of the 4 cases. Hysterectomy (107 cases,22.4%) was the most common severe adverse pregnancy outcome. Among all 311 morbidly adherent placenta cases finally confirmed by pathological or surgical findings or both,only 172 (55.3%) were suspected before delivery. Multivariable logistic regression analysis showed that the risk of severe adverse pregnancy outcomes was significantly increased by pernicious placenta previa (i.e. anterior placenta overlying the prior cesarean scar),suspicion of morbidly adherent placenta before delivery and hemoglobin before delivery lower than 100 g/L,and the corresponding odds ratios and 95% confidence intervals were 2.4 (1.5-3.8),3.6 (2.3-5.6) and 2.5 (1.6-3.9),respectively. CONCLUSION: Pernicious placenta previa,suspicion of morbidly adherent placenta before delivery and hemoglobin before delivery lower than 100 g/L were associated with severe adverse pregnancy outcomes in women with placenta previa and prior cesarean delivery .

[Risk Factors for Blood Transfusion in Women with Postpartum Hemorrhage: a Case-control Study].

OBJECTIVE: To investigate the risk factors for increased red blood cells (RBCs) transfusion ratio in the women with postpartum hemorrhage (PPH). METHODS: This case-control study obtained the inpatient medical records of 112 441 pregnant women from 37 hospitals in 2011. There were 4 131 women diagnosed with PPH,record data of those patients were analyzed,including basic characteristics of patients,the level of hospital,pregnancy related complications,prenatal hemoglobin (Hb),mode of delivery,details of postpartum blood loss and blood transfusion,and maternal and neonatal outcomes. Multiple logistic regression analysis was used to identify risk factors for increased RBCs transfusion ratio. RESULTS: There were 61 339 (54.6%) out of 112 441 women received with Cesarean section and 637 (15.4%) out of 4 131 women with PPH had blood transfusion,one to four units of RBCs were sufficient for a majority of those patients. It demonstrated that level of hospital,multiple,placenta preiva,abruptio placenta,pre-eclampsia or eclampsia,pre-delivery hemoglobin,gestational age and labor method were independent risk factors for RBCs transfusion. CONCLUSION: Cesarean section and pregnant complications are important risk factors for blood transfusion in women with PPH .

Activity and distribution of plasma platelet-activating factor acetylhydrolase in women with gestational diabetes mellitus and their neonates.

BACKGROUND: Abnormal activity and distribution of plasma platelet-activating factor acetylhydrolase (PAF-AH) are associated with chronic inflammatory status. In this study, we investigate the activity and distribution of plasma PAF-AH and their association with metabolic components in mothers with gestational diabetes mellitus (GDM) and in their neonates. METHODS: Based on the International Association of Diabetes Pregnancy Study Group criteria, we performed a case-controlled study of 101 women with GDM, 98 women with uncomplicated pregnancies, 142 neonates of mothers with GDM and 121 neonates of mothers with uncomplicated pregnancies. Plasma PAF-AH, high-density lipoprotein (HDL)-associated PAF-AH (H-PAF-AH) and apolipoprotein (apo) B-containing lipoprotein-associated PAF-AH (apoB-PAF-AH) activities were measured using the trichloroacetic acid precipitation procedure with PAF C-16 as a substrate. RESULTS: The plasma PAF-AH and apoB-PAF-AH activities, triglyceride (TG) levels, atherogenic index and TG/HDL-C ratio were increased, and the H-PAF-AH proportions were decreased in the mothers with GDM compared with the control mothers (p < 0.05). Multivariate regression analyses demonstrated that the apoB and TG levels were significant predictors of plasma PAF-AH or apoB-PAF-AH activities, while the low-density lipoprotein-cholesterol levels, weight gain during pregnancy and age were associated with H-PAF-AH activities. The neonates of mothers with GDM had higher plasma insulin and glucose concentrations (p < 0.05) and tended to exhibit increased serum apoB levels (p = 0.062) compared with the neonates of mothers with uncomplicated pregnancies. CONCLUSIONS: The mothers with GDM presented with a state of chronic inflammation, and these mothers and their neonates also exhibited unfavourable metabolic profiles in terms of glucose and lipids. Copyright © 2016 John Wiley & Sons, Ltd.

[Research status of the pathogenesis of pre-eclampsia].

Pre-eclampsia is a serious obstetric complication, not only affect maternal health, but also affect the long-term prognosis of offspring generation. Even though various theories on the pathogenesis of pre-eclampsia have been proposed in recent decades, it remains unclear due to the disadvantages in these theories. Therefore, the pathogenesis of pre-eclampsia keeps attracting a lot of research efforts in the field of obstetrics. In order to find the new break through points in the study of pre-eclampsia pathogenesis (pre-eclampsia related to genetic, epigenetic and expression changes of some genes), it is necessary to illustrate and understand the research status in this field, with integrating the related resources, updating the new progress, ideas and extensive research means.

[The Ala379Val polymorphism of platelet-activating factor acetylhydrolase gene in Chinese patients with pre-eclampsia].

OBJECTIVE: To investigate the relationship between the Ala379Val polymorphism of the platelet-activating factor acetylhydrolase gene (PAF-AH) and pre-eclampsia (PE) in Chinese pregnant women. METHODS: A total of 592 subjects (210 patients with PE and 382 healthy pregnant women) in Chengdu area were included in this study. The Ala379Val polymorphism of the PAF-AH gene was determined by PCR amplification and restriction analysis. Plasma PAF-AH and high-density lipoprotein-associated PAF-AH (H-PAF-AH) activities were measured by the trichloroacetic acid precipitation method using PAF as substrate and (3 H-acetyl) PAF as tracer. Low-density lipoprotein-associated PAF-AH (L-PAF-AH) activity was obtained by subtracting H-PAF-AH activity from plasma PAF-AH activity. RESULTS: The frequencies of the A and V alleles at Ala379Val site were 0.890 and 0.110 in the patient group, and 0.865 and 0.135 in control group, respectively. No significant differences in the frequencies of the genotypes and alleles were observed between the two groups (P>0.05). However, the body mass index (BMI) and the ratio of L-PAF-AH to H-PAF-AH activities were significantly higher, and H-PAF-AH activity was significantly lower, in patients with V alleles (AV + VV genotypes) compared to patients with AA homozygotes (P<0.05). CONCLUSION: The Ala379Val polymorphism of the PAF-AH gene was not associated with PE, but the V allele variation at this site might be associated with the increased BMI and the abnormal distribution of plasma PAF-AH activities in lipoproteins in patients with PE.

[Interaction between GNB3 C825T and ACE I/D polymorphisms in pre-eclampsia].

OBJECTIVE: To verify the hypothesis if interaction between the G protein beta3 subunit (GNB3) C825T polymorphism and angiotensin-I converting enzyme (ACE) insertion/deletion (I/D) could lead to the increased risk of pre-eclampsia. METHODS: Analyses of ACE and GNB3 genotypes were performed in 188 preeclamptic patients and 273 normal pregnant controls by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism in Chinese population, respectively. RESULTS: The distributions of alleles and genotypes for the GNB3 C825T and ACE I/D polymorphisms were not found to be significantly associathed with pre-eclamptic status. No significant interaction of the influence of GNB3 T allele and ACE genotypes on the risk of pre-eclampsia was observed (OR 0.439-1.203, all P>0.05). However, we found that in homozygous 825T genotype carriers with the ACE II genotype in controls diastolic blood pressure (DBP) levels showed highest [(77.61 +/- 1.26) mmHg (1 mmHg=0.133 kPa)] among other three genotype combinations [TT/ID, (70.94 +/- 1.64) mmHg; CT/ID, (73.15 +/- 0.89) mmHg; CT/DD, (72.57 +/- 2.14) mmHg] (all P<0.05). No significant effect on systolic blood pressure (SBP) or DBP levels in the patients were observed. CONCLUSION: Our data suggest no significant interaction of the GNB3 825T allele carriers with the ACE I/D polymorphism in pre-eclampsia in Chinese population in Chengdu area. However there is the interaction of the two genes on DBP levels in pregnancy women without pre-eclampsia in the population.

Peripartum hysterectomy in 38 hospitals in China: a population-based study.

OBJECTIVE: To investigate the incidence, indications, risk factors and transfusions of peripartum hysterectomy in China. METHODS: A population-based study was conducted using inpatient records of 38 hospitals between 1 January 2011 and 31 December 2011; multivariate logistic regression analysis was used to identify independent risk factors for peripartum hysterectomy. RESULTS: During the study period, there were 43 peripartum hysterectomy cases out of 114,420 deliveries (0.38‰). Abnormal placentation was major indication for peripartum hysterectomy. Several factors significantly increased the risk of peripartum hysterectomy in this population: placenta previa/accreta [adjusted odds ratio (aOR) 49.7, 95 % CI 25.0-98.9], maternal age ≥35 years (aOR 8.1, 95% CI 4.0-16.0), preeclampsia/eclampsia (aOR 7.5, 95% CI 2.6-21.7), cesarean delivery (aOR 3, 95% CI 1.1-8.0), and multiparity (aOR 2.7, 95% CI 1.2-5.4). In contrast, multiple gestations did not. CONCLUSIONS: Placenta previa/accreta, maternal age ≥35 years, preeclampsia/eclampsia, cesarean delivery and multiparity were risk factors of peripartum hysterectomy.

[Expression of NKG2A and NKG2C receptors and their ligand HLA-E in decidua of preeclampsia patients].

OBJECTIVE: To investigatethe expressions of NKG2A, NKG2C receptors and their ligand HLA-E in decidua of preeclampsia patients. METHODS: Decidua tissues were collected from 30 patients with mild preeclampsia, 42 patients with severe preeclampsia and 46 normal pregnancy as contrast. The expressions of NKG2A, NKG2C protein were detected by immunohistochemitry and mRNAs of NKG2A, NKG2C and HLA-E genes were detected by RT-PCR. RESULTS: The expression of HLA-E mRNA was significantly decreased in preeclampsia, especially in severe preeclampsia patients (P < 0.05); The mRNA and protein expression of NKG2A, NKG2C in severe preeclampsia group were significantly higher than that in normal pregnancy group (P < 0.05); In the severe preeclampsia group, the ratio of expression level of NKG2A and NKG2C was significantly lower than that of normal group and the mRNA and protein expression of NKG2C receptor were both significantly higher than that of NKG2A (P < 0.05); The mRNA expression level of HLA-E, NKG2A and NKG2C were closely related with clinical and biochemical indexes,such as blood pressure of late pregnancy and 24-hour proteinuria. CONCLUSION: The decreased expression of HLA-E and the unevenly increase of NKG2A and NKG2C may involve in the pathogenesis of preeclampsia.

Association of blood parameters in early pregnancy with anemia during late pregnancy: a multicenter cohort study in China.

BACKGROUND: Low-hemoglobin concentration and anemia are important risk factors for the health and development of women and children. The aim of this study was to investigate the correlation between blood indicators in early pregnancy among non-anemia women and anemia in the third trimester among pregnant women in China with uncomplicated pregnancies >36 weeks. METHODS: This was a multicenter, prospective cohort study. Pregnant women registered at the survey hospitals from May 2019 to December 2020 were included and followed up until delivery and discharge. The predictive value of serum ferritin (SF) and routine blood indexes (platelet count, red blood cell count, hemoglobin level, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) were analyzed using a receiver operating characteristic (ROC) curve for the occurrence of anemia in the third trimester. RESULTS: The area under the ROC curve of the first trimester hemoglobin for predicting anemia during late pregnancy (cutoff value 128 g/L, sensitivity 82.3%, specificity 49.6%) and iron deficiency anemia (cutoff value 124 g/L, sensitivity 66.3%, specificity 66.4%) in the third trimester was larger than those of other blood variables. CONCLUSIONS: Hemoglobin levels in the first trimester were significantly better predictors of anemia during the third trimester than the other indices. Our study contributes to the clinical practice of early intervention for anemia, thus taking effective measures to improve maternal and infant outcomes.

Causal effects of hypertensive disorders of pregnancy on future gynecologic tumors: A two-sample Mendelian randomization study.

BACKGROUND: Numerous observational studies have investigated the potential link between hypertensive disorders of pregnancy (HDPs) and the subsequent risks of gynecologic tumors, yet the findings have been inconsistent. In this study, we utilized Mendelian randomization (MR) approach to assess the influence of HDPs on the future risks of ovarian, cervical, endometrial, and breast cancer and uterine fibroids, controlling for confounding factors. METHODS: The genome-wide association studies (GWAS) summary data relevant to HDPs was obtained from the FinnGen databases (10,736 cases and 136,325 controls). Gynecologic tumor outcomes were extracted from the IEU Open GWAS project and UK Biobank (47,690 cases and 1, 092,073 controls). The inverse variance weighted (IVW) approach was selected as the principal method for MR analysis, supplemented by MR-Egger, weighted median, weighted model, simple model methods, MR pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out method. Multivariate MR (MVMR) analysis was conducted after adjusting systolic blood pressure (SBP), body mass index (BMI) and type 2 diabetes mellitus (T2DM). RESULTS: Our univariate MR analysis (UVMR) results revealed no significant relationship between HDPs and the risks of ovarian cancer (odds ratio [OR] = 0.924, p = 0.360), cervical cancer (OR = 1.230, p = 0.738), endometrial cancer (OR = 1.006, p = 0.949), uterine fibroids (OR = 1.155, p = 0.158), and breast cancer (OR = 0.792, p = 0.241) by IVW test. Similar results were observed in gestational hypertension and preeclampsia/eclampsia. Additionally, our study detected neither heterogeneity nor pleiotropy. MVMR analysis also provided no evidence of a causal association between HDPs and common gynecologic tumors after adjusting SBP, BMI, and T2DM. CONCLUSION: We discovered no causal relationship between HDPs and ovarian, cervical, endometrial, breast cancer, and uterine fibroids in European populations. However, present analysis did not explore the effect of HDPs on the subtypes of gynecologic tumors across varied ethnic populations, which may require additional research.

Stem Cell-Based Strategies: The Future Direction of Bioartificial Liver Development.

Acute liver failure (ALF) results from severe liver damage or end-stage liver disease. It is extremely fatal and causes serious health and economic burdens worldwide. Once ALF occurs, liver transplantation (LT) is the only definitive and recommended treatment; however, LT is limited by the scarcity of liver grafts. Consequently, the clinical use of bioartificial liver (BAL) has been proposed as a treatment strategy for ALF. Human primary hepatocytes are an ideal cell source for these methods. However, their high demand and superior viability prevent their widespread use. Hence, finding alternatives that meet the seed cell quality and quantity requirements is imperative. Stem cells with self-renewing, immunogenic, and differentiative capacities are potential cell sources. MSCs and its secretomes encompass a spectrum of beneficial properties, such as anti-inflammatory, immunomodulatory, anti-ROS (reactive oxygen species), anti-apoptotic, pro-metabolomic, anti-fibrogenesis, and pro-regenerative attributes. This review focused on the recent status and future directions of stem cell-based strategies in BAL for ALF. Additionally, we discussed the opportunities and challenges associated with promoting such strategies for clinical applications.