Introduction:Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by irreversible damage to the airways, alveoli, and pulmonary microvasculature. As the third leading cause of death worldwide, COPD remains without effective therapies to halt or reverse structural lung damage. Regenerative approaches utilizing lung-resident stem/progenitor cells present a promising therapeutic strategy; however, the underlying molecular mechanisms remain incompletely understood. This study aimed to investigate whether the reparative effects of airway basal stem cells (BCs) in COPD are mediated, at least in part, through paracrine mechanisms involving BC-derived extracellular vesicles (BC-EVs). Methods:Lineage-tracing analysis was performed to determine the involvement of endogenous BCs in epithelial repair following COPD-related lung injury. Airway BCs were isolated, expanded ex vivo, and transplanted into elastase-induced COPD mouse models, followed by histological evaluation and RNA-seq-based transcriptomic analysis to assess regenerative efficacy. For mechanistic studies, BC-EVs were collected from cultured BCs and characterized using transmission electron microscopy, Nano-Flow Cytometry, and Western blotting. Their biological activity was assessed by CCK-8 and tube formation assays. BC-EVs were delivered to COPD mice via nebulization, with in vivo imaging tracking distribution. Therapeutic efficacy was evaluated by histology and arterial blood gas analysis. Proteomic profiling was conducted to elucidate the molecular mechanisms underlying BC-EV-mediated repair. Results:Lineage tracing revealed active participation of endogenous BCs in epithelial repair. Transplantation of ex vivo-expanded BCs significantly restored alveolar architecture and alleviated pathological manifestations in COPD mice. Nebulized BC-EVs reproduced these benefits, promoting angiogenesis, enhancing epithelial repair, and improving lung function. Proteomic analyses revealed that BC-EVs were enriched in lung development-associated proteins and activated the PI3K-Akt signaling pathway, suggesting a mechanistic basis for their regenerative capacity. Conclusions:Airway basal stem cells are essential for lung epithelial regeneration, and together with their extracellular vesicles, provide a promising therapeutic strategy for COPD. The reparative effects of BCs are partially mediated by BC-EVs, which promote alveolar structure remodeling. This study delineates how BCs ameliorate COPD-induced lung injury and highlights BC-EVs as a viable cell-free therapeutic candidate with strong translational potential.

Compound dry-hot extremes (CDHEs) and ambient air pollution are growing public health threats under global climate change, yet their joint impacts on cardiovascular disease (CVD) risk remain poorly understood. We conducted a nationwide longitudinal cohort study using data from the China Family Panel Studies (CFPS), including 9,265 Chinese adults aged ≥ 18 years with 69,297 repeated observations between 2010 and 2018. We evaluated the independent, joint and heterogeneous effects of multi-dimensional CDHE metrics (accumulated days, frequency and average severity) and key air pollutants (e.g., PM2.5) on incident CVD. Mixed-effects Cox models, interaction analyses and stratified analyses were performed to examine the study objectives. Per interquartile range (IQR) increment in CDHE cumulative days and PM2.5 concentration were associated with 30

Objective: To evaluate the effects of long-term low molecular weight heparin (LMWH) use during pregnancy on labor process and pregnancy outcomes under different labor onset methods, aiming to inform clinical application strategies. Methods: This retrospective cohort study included parturients from November 2020 to November 2024. Subjects were grouped based on LMWH exposure and matched using propensity score matching (PSM, 1:2 ratio) for six baseline variables. Subgroup analyses were conducted by labor onset mode (induced vs. spontaneous). Clinical data, pregnancy complications, medications, delivery interventions, and pregnancy outcomes were compared. Multivariate regression analyses were used to assess LMWH’s effects. Results: LMWH use was associated with increased postpartum hemorrhage (PPH) risk (aOR = 2.497, P = 0.032) but reduced CS rates (aOR = 0.617, P = 0.027). In vaginal deliveries, LMWH users showed higher risks of forceps-assisted delivery (aOR = 3.512, P = 0.022) and episiotomy (aOR = 3.059, P = 0.007). In spontaneous labor, LMWH was linked to greater intrapartum blood loss and PPH risk. No significant impact was found on labor duration or neonatal outcomes. Conclusions: Long-term antenatal LMWH use increases PPH and operative vaginal delivery risk, particularly under spontaneous labor. Findings support individualized labor management in LMWH-treated pregnancies.

AIM:Preeclampsia poses a high-risk factor for placental abruption. The precise understanding of the accompanying symptoms and disease phenotype of preeclampsia, in order to promptly identify the occurrence of placental abruption in preeclamptic women, remains unclear. METHODS:The obstetric data of preeclamptic women were retrospectively analyzed between January 2016 and June 2023 in our hospital. Based on the presence or absence of placental abruption, they were categorized into two groups: placental abruption group and non-placental abruption group. Logistic regression analysis was employed to identify risk factors for placental abruption in preeclamptic women. RESULTS:A total of 709 preeclamptic women were enrolled, of whom 39 cases experienced placental abruption. Compared to the non-placental abruption group, the placental abruption group exhibited a younger age, lower BMI at delivery, and higher incidence of HELLP syndrome (p < 0.05). The risk factors for placental abruption in preeclamptic women included systolic blood pressure/10 (aOR 1.293, 95% CI 1.031-1.613), blurred vision (aOR 3.847, 95% CI 1.175-12.600), positive urine protein (aOR 3.081, 95% CI 1.157-8.208), platelet count/10 (aOR 0.923, 95% CI 0.860-0.991), and maternal age (aOR 0.899, 95% CI 0.836-0.966). The placental abruption group had shorter gestational age at delivery and higher rates of cesarean section delivery, fetal growth restriction, and neonatal asphyxia (p < 0.05). CONCLUSIONS:The occurrence of placental abruption in preeclampsia significantly impacts neonatal well-being. Close monitoring of blood pressure, particularly systolic blood pressure, urine protein, platelet counts, and visual acuity is crucial for preeclamptic women to early identify the occurrence of placental abruption.

BACKGROUND:This study compared labor characteristics and maternal-neonatal outcomes between pregnant women with diet-controlled (A1) gestational diabetes mellitus (GDM) and normoglycemic women, within a cohort of women undergoing induction of labor (IOL) at term. Furthermore, we aimed to identify risk factors associated with cesarean section (CS) in this specific population. MATERIAL AND METHODS:A total of 686 pregnant women were enrolled and divided into an A1 GDM group (n=256) and a non-GDM control group (n=430). Propensity score matching (PSM) was used to adjust for maternal age, BMI, gravidity, parity, and Bishop score, resulting in 254 matched pairs. Labor induction characteristics, clinical interventions, and maternal and neonatal outcomes were compared. Risk factors for CS were analyzed using univariate and multivariate logistic regression. RESULTS:The A1 GDM group had higher rates of episiotomy and postpartum blood loss, and greater fetal weight (P<0.05), but no significant difference in CS rates (9.8% vs. 11.4%) or most neonatal outcomes. Multivariate analysis showed that advanced maternal age (OR 1.177, 95% CI 1.089-1.272), nulliparity (OR 0.110, 95% CI 0.053-0.231), and lower Bishop score (OR 0.605, 95% CI 0.442-0.828) were independent risk factors for CS, while A1 GDM was not. CONCLUSIONS:In this cohort of women undergoing IOL at term, pregnancy outcomes for those with well-managed A1 GDM were comparable to non-GDM controls. After adjustment for confounders, A1 GDM was not observed to be an independent risk factor for CS, instead, maternal age, parity, and cervical readiness were the primary determinants of delivery mode.

The unprecedented demographic shifts toward an aging population pose significant challenges to global healthcare systems. Understanding the heterogeneity in disease prevalence among the elderly is crucial for effective public health strategies. Using prevalence data of 85 types of age-related diseases, we calculated the global heterogeneity of disease distribution by the Shannon Diversity Index (SHDI). We observed significant geographic variations in disease heterogeneity, with higher SHDI values in high-income Western countries such as the United States of America and Sweden and lower in South Asia and Oceania (p < 0.05). In 2021, SHDI values in elderly populations (age ≥60 years) for Europe and North America countries were an average of 1.12 times higher than in Oceania. While SHDI increases toward higher ages (for instance, in 2021, SHDI for adults above 95 years is 1.06 times higher than for ages between 60 and 64 years), the global SHDI tends to decrease nonlinearly over time. From 1990 to 2021, global age-standardized SHDI (age ≥60 years) averagely decreased by 1.2% for both men and women. Our analysis further revealed that socio-economic factors (e.g., socio-demographic indices, governance) strongly impacted global SHDI changes, while climatic and environmental factors (e.g., extreme climate and air pollution) showed significant differences across genders. Our study highlights the need for implementing comprehensive healthcare strategies, focusing on reducing health disparities and addressing environmental and socio-economic determinants to address inequalities in age-related diseases effectively.

BackgroundPreeclampsia, a hypertensive disorder during pregnancy affecting 2-8% of pregnancies globally, remains a leading cause of maternal and fetal morbidity. Current diagnostic reliance on late-onset clinical features and suboptimal biomarkers underscores the need for early molecular predictors. Ribosome biogenesis, critical for cellular homeostasis, is hypothesized to drive placental dysfunction in PE, though its role remains underexplored.MethodsWe integrated placental transcriptomic data from two datasets (GSE75010, GSE10588) to systematically investigate ribosome biogenesis dysregulation in preeclampsia. Functional enrichment analyses delineated the dysregulation of pathways, while weighted gene co-expression network analysis identified hub genes within ribosome biogenesis-associated modules. A multi-algorithm machine learning framework was employed to optimize predictive performance, with model interpretability achieved through SHapley Additive exPlanations and diagnostic accuracy validated by receiver operating characteristic curves. Immune microenvironment profiling and regulatory network analyses elucidated mechanistic links. Finally, qRT-PCR confirmed the differential expression of key genes in clinical samples.ResultsWe identified 25 ribosome biogenesis-related differentially expressed genes, which were significantly enriched in RNA degradation and rRNA processing. Weighted gene co-expression network analysis prioritized seven hub genes. A random forest model incorporating six key feature genes (GLUL, DDX28, NCL, RIOK1, SUV39H1, RRS1) demonstrated robust diagnostic performance, achieving an AUC of 0.972 in the training dataset and 0.917 in the validation dataset. SHapley Additive exPlanations interpretability analysis revealed SUV39H1 as the dominant risk contributor, while GLUL exhibited a protective effect. Regulatory network reconstruction identified 32 transcription factors, 24 RNA-binding proteins, and 62 miRNAs as putative upstream regulators of key genes. Immune Microenvironment Profiling linked key genes to altered placental immune cell populations. qRT-PCR confirmed that GLUL and NCL expression decreased and DDX28 and RIOK1 expression increased in clinical placental samples of preeclampsia group.ConclusionThis study identifies ribosome biogenesis as one of the pivotal molecular mechanisms to PE pathogenesis, leveraging SHAP-interpretable machine learning to pinpoint six biomarkers. Future research is requisite for the validation of CRISPR and the integration of multi-omics to translate the findings into clinical diagnosis and targeted therapy.

Cervical cancer remains the one of the most frequent malignant tumors in women around the world. Cisplatin-based chemotherapy is a prevalent treatment for advanced cervical cancer, but it has significant side effects that necessitate drug-free periods during treatment cycles. Unfortunately, tumors often relapse during these intervals, highlighting the need for strategies to prevent recurrence. In the present study, the biological changes in cervical cancer cells following the withdrawal of cisplatin chemotherapy were investigated. Afterwards, the application of selenium nanoparticles (SeNPs) modified with lentinan (LNT) to address tumor recurrence during these drug-free periods was explored. Specifically, in vitro experiments demonstrated that SeNPs@LNT effectively inhibited tumor recurrence by promoting DNA damage, inducing apoptosis, and disrupting mitochondrial membrane potential. Additionally, in vivo experiments showed that SeNPs@LNT had a strong antitumor effect on cervical cancer during the drug-free period. It also remarkable that SeNPs@LNT might prevent the development of drug resistance by suppressing the expression of the ABC transporter and VEGF. Our findings suggest that SeNPs@LNT is a promising candidate for maintaining chemotherapy efficacy during the drug-free intervals of cisplatin treatment.

Increasing occurrence of intrauterine adhesion (IUA) is a serious threat to the reproductive health of women in recent years. However, treatment options remain limited. Mesenchymal stem cell (MSC)-based therapies have shown a promising regenerative capacity of injured endometrium but have limited effectiveness by the low survival duration of transplanted cells. Herein, we present a bioactive hydrogel scaffold loaded with adipose tissue-derived MSC (AT-MSC) by using a three-dimensional (3D) bioprinting technology, which combines the characteristics of the synthetic thermos-responsive material PF-127 and the natural-derived, photo-polymerizable material GelMA. The composite hydrogel scaffold shows enhanced mechanical as well as biocompatibility. In addition, the porous structure endows the 3D-printed scaffold with a favorable growing environment for MSC and increase the retention rate of cells. Finally, the dual repair effects of the MSC-laden gel scaffold on endometrial damage and regeneration are validated in a rat IUA model. This study demonstrates that the composite system could improve neovascularization, increase number of glands, and ameliorate fibrotic formation of endometrium. Thus, it is believed that such bioactive MSC-loaded scaffold is a promising candidate for prevention of IUA with reliable endometrial regeneration properties.

Progesterone has been widely used to prevent preterm birth (PTB), and its specific therapeutic mechanism is still unclear. Myometrium aquaporins (AQPs) were associated with PTB. This study aimed to investigate the effect of progesterone on PTB and its underlying molecular mechanisms related to myometrium AQPs (AQP1, AQP5). We used lipopolysaccharide (LPS) to stimulate pregnant mice and human uterine smooth muscle cells (HUSMCs), thereby establishing a PTB model. Immunohistochemistry and immunocytochemistry revealed localizations of AQP1 and AQP5 in mice myometrium and HUSMCs, respectively. Western blots were used to detect AQP1, AQP5, iNOS, and COX2 expression in HUSMCs and mice myometrium. Enzyme-linked immunosorbent assay was used to measure the serum concentrations of progesterone in pregnant mice. Immunohistochemistry revealed localizations of AQP1, AQP5 mainly in mice myometrium. Progesterone significantly prevented PTB in pregnant mice induced by LPS, without affecting the number of embryos per litter or the rate of atrophic embryos, while also increasing the expression levels of AQPs. In HUSMCs, progesterone upregulated AQP1, AQP5 expression and activated the activity of β-Catenin. Inhibiting β-Catenin with XAV939 eliminated these alterations. Progesterone could prevent PTB in pregnant mice, possibly through upregulating myometrium AQP1, AQP5 expression via activating the activity of β-Catenin.

Fetal growth restriction (FGR) is characterized by the inability of the fetus to achieve its growth potential due to pathological factors, most commonly impaired placental trophoblast cell function. Currently, effective prevention and treatment methods of FGR are limited. We aimed to explore the pathogenesis of FGR and provide potential strategies for mitigating its occurrence. The case-control study compared AQP3 expression in placental trophoblast cells of pregnant women with FGR and those with normal pregnancies. Then mouse FGR models were induced via cadmium exposure, and placental trophoblast cells (JEG-3) were similarly treated. The study assessed the effects of Sodium tanshinone IIA sulfonate (STS) and the role of the PI3K/Akt pathway in improving AQP3 expression and trophoblast cell function. Placental trophoblast cells in FGR cases exhibited significantly reduced AQP3 expression. AQP3-knockdown cells displayed dysfunction. Cadmium exposure in mice and JEG-3 cells led to decreased AQP3 expression and trophoblast cell dysfunction, both of which were ameliorated by STS. Fetal mouse weight increased with STS treatment. STS upregulated AQP3 expression and improved trophoblast cell function in AQP3-knockdown cells. Inhibiting the PI3K/Akt pathway diminished STS's beneficial effects. ThereforeSTS may enhance AQP3 expression in placental trophoblast cells affected by FGR through the activation of the PI3K/Akt pathway, ultimately bolstering placental trophoblast cell function and alleviating FGR. As above, STS appears to be a potential therapeutic agent for alleviating FGR.

Background To investigate the labor characteristics and maternal-neonatal outcomes associated with induction of labour (IOL) in pregnant women with hypertensive disorders of pregnancy (HDP), as well as to identify the risk factors for the failed induction of labor. Material and methods This cohort study enrolled 425 pregnant women who underwent IOL, and they were divided into two groups: the HDP group and the normotensive pregnancies group. Labor induction characteristics, interventions and maternal and neonatal outcomes were compared. Univariate analysis and logistic regression analysis were conducted to identify the risk factors for the failed IOL. Results Compared to the control group, the HDP group exhibited a significantly higher rate of cesarean section (CS), and newborns in the HDP group were more likely to be transferred to the neonatal intensive care unit (P < 0.05). There was little difference in labor durations and intrapartum interventions between the two groups of women with successful IOL, except for a higher rate of mediolateral episiotomy in the HDP group. Parity (OR 0.201; 95 % CI 0.053 to 0.763), bishop score (OR 0.658; 95 % CI 0.512 to 0.845), birth weight (OR 1.001; 95 % CI 1.000 to 1.002), and hypertensive disorders of pregnancy (HDP) (OR 2.502; 95 % CI 1.374 to 4.559) were identified as factors associated with an increased risk of failed IOL. Conclusions Women with HDP exhibited an increased risk of CS rate and mediolateral episiotomy after IOL compared to those with normotensive pregnancies, while the characteristics of induced labor, most intrapartum interventions and maternal and neonatal outcomes were similar.

Purpose The purpose of this study was to investigate the risk factors for umbilical artery thrombosis (UAT) and the relationship between umbilical artery thrombosis and perinatal outcomes. Methods This was a retrospective study that enrolled singleton pregnant women who were diagnosed with umbilical artery thrombosis. The control group recruited pregnant woman with three umbilical vessels or those with isolated single umbilical artery (iSUA) who were matched with umbilical artery thrombosis group. The risk factors and perinatal outcomes were compared between the groups. Results Preconception BMI (OR [95%CI]: 1.212 [1.038–1.416]), abnormal umbilical cord insertion (OR [95%CI]: 16.695 [1.333-209.177]) and thrombophilia (OR [95%CI]: 15.840 [1.112-223.699]) were statistically significant risk factors for umbilical artery thrombosis. An elongated prothrombin time (OR [95%CI]: 2.069[1.091–3.924]) was strongly associated with the occurrence of UAT. The risks of cesarean delivery, preterm birth, fetal growth restriction, neonatal asphyxia, and intraamniotic infection were higher in pregnancies with UAT than in pregnancies with three umbilical vessels or isolated single umbilical artery ( P <0.05). Additionally, the incidence of thrombophilia was higher in pregnant women with umbilical artery thrombosis than those with isolated single umbilical artery ( P = 0.032). Abnormal umbilical cord insertion was also found to be associated with an elevated risk of iSUA (OR [95%CI]: 15.043[1.750-129.334]). Conclusions Abnormal umbilical cord insertion was the risk factor for both umbilical artery thrombosis and isolated single umbilical artery. The pregnancies with umbilical artery thrombosis had a higher risk of the adverse perinatal outcomes.

This study aimed to investigate the relationship between phthalates exposure and estrogen and progesterone levels, as well as their role in late-onset preeclampsia. A total of 60 pregnant women who met the inclusion and exclusion criteria were recruited. Based on the diagnosis of preeclampsia, participants were divided into two groups: normotensive pregnant women (n = 30) and pregnant women with late-onset preeclampsia (n = 30). The major metabolites of phthalates (MMP, MEP, MiBP, MBP, MEHP, MEOHP, MEHHP) and sex steroid hormones (estrogen and progesterone) were quantified in urine samples of the participants. No significant differences were observed in the levels of MMP, MEP, MiBP, MBP, MEHP, MEOHP, and MEHHP between women with preeclampsia and normotensive pregnant women (P > 0.05). The urinary estrogen showed a negative correlation with systolic blood pressure (rs= -0.46, P < 0.001) and diastolic blood pressure (rs= -0.47, P < 0.001). Additionally, the urinary estrogen and progesterone levels were lower in women with preeclampsia compared to those in normotensive pregnant women (P < 0.05). After adjusting for confounding factors, we observed a significant association between reduced urinary estrogen levels and an increased risk of preeclampsia (aOR = 0.09, 95

The rates of twin pregnancies and cesarean section have increased in recent years, and both of them are at high risks of postpartum hemorrhage (PPH). However, few studies have concentrated on the risks of PPH in twin pregnancies and cesarean deliveries. In this study, we aimed to identify the risk factors for PPH among twin-pregnant women with cesarean section. This was a retrospective observational study including 1,649 women with twin pregnancies delivered by cesarean section from 2016 to 2022 in the Second Affiliated Hospital of Wenzhou Medical University, China. The eligible women were divided into PPH group (n = 116) and non-PPH group (n = 1,533) according to the blood loss after delivery within 24 h. The baseline maternal and perinatal characteristics were compared between the two groups. Logistic regression analysis was conducted to identify the potential risk factors for PPH. We found nulliparity, assisted reproductive technology (ART) usage, preeclampsia or HELLP syndrome, placenta previa, placenta accreta and general anesthesia were more common in PPH group than non-PPH group (P < 0.05). Women in PPH group had higher maternal body mass index at delivery and higher combined birthweight of the twins than non-PPH group, but had lower parity (P < 0.05). Seven independent risk factors for PPH were identified after logistic regression analysis: ART usage (OR 2.354 95% CI 1.357–4.083, P = 0.002), preeclampsia or HELLP syndrome (OR 2.605, 95% CI 1.471–4.616, P = 0.001), placenta previa (OR 7.325, 95% CI 3.651–14.697, P < 0.001), placenta accreta (OR 6.296, 95% CI 1.316–30.12, P = 0.021), thrombocytopenia (OR 1.636, 95% CI 1.056–2.535, P = 0.027), general anesthesia (OR 2.394, 95% CI 1.223–4.686, P = 0.011), and combined birthweight (OR 1.00032, 95% CI 1.00005–1.00059, P = 0.020). Collectively, in women with twin pregnancies delivered by cesarean section, the use of ART, preeclampsia or HELLP syndrome, placenta previa, placenta accreta, thrombocytopenia, general anesthesia and the combined birthweight were identified as independent risk factors for PPH. More attention should be paid to women with these risk factors.

The global increase in the aging population presents critical challenges for healthcare systems, social security, and economic stability worldwide. Although the studies of the global rate of aging have increased more than four times in the past two decades, few studies have integrated the potential combined effects of socio-economic, climatic, and environmental factors. We calculated the geographic heterogeneity of aging population growth rates from 218 countries between 1960 and 2022. Public databases were then integrated to assess the impacts of seven global stressors: socio-economic vulnerability, temperature, drought, seasonality, climate extremes, air pollution, and greening vulnerability on growth rates of aging population (a totally 156 countries). Linear regression models were primarily used to test the statistically significant effects of these stressors on the rate of aging, and multiple model inference was then used to test whether the number of stressors exceeding specific thresholds (e.g., > 25, 50, and 75

Abstract Background Self-management plays an important role in the disease management of glaucoma patients. Evidence suggests that tailoring self-management support to patients' individual needs may enhance program effectiveness. However, most research on self-management support has focused solely on the performance of self-management tasks or the efficacy of support programs, neglecting the crucial aspect of addressing patients' unique needs for self-management. Therefore, in this study, we conducted an in-depth investigation into the self-management challenges and support needs of patients with primary glaucoma, providing a basis for nursing staff to implement self-management support. Method The phenomenological method and semistructured interviews were used in this study. A total of 20 patients with primary glaucoma were recruited between June and December 2022. Colaizzi’s analysis method was used to analyse the interview data. Results Challenges for patients include becoming an expert in glaucoma, managing negative emotions, adapting to daily life changes and resuming social activities. To address these challenges, four themes of patient self-management support needs were identified:(1)health information support,༈2༉social support,༈3༉psychological support, and༈4༉daily living support. Conclusion Patients with primary glaucoma experience varying degrees of challenge in dealing with medical, emotional, and social aspects. Comprehending the support needs of patients, healthcare professionals should deliver targeted, personalized and comprehensive self-management interventions to enhance their capacity of patients to perform self-management and improve their quality of life.

Background: Intertwin delivery interval (ITDI) is defined as the interval time between the delivery of the first and the second twin and may be controlled by obstetricians during cesarean deliveries. Several studies have demonstrated the relationship between ITDI and the adverse neonatal outcomes during vaginal births. However, few studies have explored the relationship between ITDI and maternal outcomes in cesarean deliveries. We hypothesized that ITDI may influence the occurrence and the development of postpartum hemorrhage by affecting uterine contraction. The purpose of this study was to investigate the relationship between ITDI and postpartum hemorrhage, and between ITDI and the maternal adverse outcomes that related to the blood loss in women with twin pregnancies delivered by cesarean section. Methods: A retrospective cohort of 1649 pregnant women with diamniotic twins was recruited from 2016 to 2022. They were categorized into the short ITDI group (0 min < ITDI ≤ 3 min), the medium ITDI group (3 min < ITDI ≤ 6 min) and the long ITDI group (6 min < ITDI ≤ 9 min) according to the range of ITDI of the eligible individuals (0-9 min). The primary outcome including PPH and the secondary outcomes including uterotonic administration, emergency operation, severe maternal morbidity and total blood loss ≥ 1500 ml were compared among the groups, and the relationship between ITDI and these outcomes was explored. Results: Little differences were found in the rates of postpartum hemorrhage, emergency operation, severe maternal morbidity and total blood loss ≥1500 ml among the three groups ( P > 0.05). No relationship was found between ITDI and postpartum hemorrhage ( P > 0.05). Women with long ITDI were at a decreased risk of uterotonic administration (adjusted OR = 0.369, 95% CI = 0.228-0.597, P < 0.001). Conclusions: Although the long ITDI did not reduce the incidence of postpartum hemorrhage during the cesarean delivery, the uterotonic administration was decreased though appropriately prolonged ITDI.

Many studies have confirmed the association of aquaporins (AQPs) with abnormal amniotic fluid volume (AFV). In our previous experiments, we found that Tanshinone IIA was able to regulate the expression of AQP1 and AQP3. However, the exact mechanism by which Tanshinone IIA regulates AQPs protein expression and its effect on AFV remains unclear. The purpose of this study was to investigate the effects of Tanshinone IIA on AFV and the possible molecular mechanism of regulation of AQP1 and AQP3.The expression of AQPs protein in the amniotic membranes was compared between pregnant women with normal pregnancy and those with isolated oligohydramnios. The AQP1 knockout (AQP1-KO) mice and wild-type (WT) mice were treated with saline or Tanshinone IIA (10 mg/kg) at 13.5GD and 16.5GD. Human amniotic epithelium cells (hAECs) from pregnant women with normal AFV and isolated oligohydramnios were incubated with 35 μmmol/L Tanshinone IIA or 25 mmol/L LiCl [inhibitor of glycogen synthetic kinase 3β (GSK-3β)]. The protein expressions of AQPs, GSK-3β, phospho-GSK-3β (Ser9) in fetal membranes of mice and human amniotic epithelium cells were detected by western blotting.The expression of AQP1 protein in the amniotic membrane of isolated oligohydramnios was increased compared with normal pregnancy. The AFV in AQP1-KO mice is higher than that in WT mice. In wild-type mice, AFV in Tanshinone IIA group was significantly higher than that in control group, and AQP1 protein expression was significantly lower than that in control group, but in AQP1 knockout mice, Tanshinone IIA reduced amniotic fluid volume and AQP3 protein expression at 16.5GD. Tanshinone IIA reduced AQP1, AQP3 and p-GSK-3β (Ser9) protein expression in normal hAECs, and this effect was inhibited by LiCl. In hAECs with oligohydramnios, the down-regulation of AQP1 and up-regulation of AQP3 by Tanshinone IIA was independent of GSK-3β signaling pathway.Tanshinone IIA may increase AFV in normal pregnancy by downregulating AQP1 protein expression in the fetal membranes, which may be associated with p-GSK-3β signaling pathway. But a larger AFV in AQP1-KO mice was significantly attenuated by Tanshinone IIA, which may be related to AQP3. Tanshinone IIA is a promising drug for the treatment of amniotic fluid abnormality.

Background Although in vitro fertilization (IVF) can increase the incidence of hypertensive disorders of pregnancy (HDP), the pregnancy outcomes and disease phenotype of HDP in singleton pregnancies conceived via IVF remain unclear. Methods This retrospective cohort study enrolled 1130 singleton pregnancies with HDP from 2016 to 2020. According to the mode of conception, they were allocated into IVF (n = 102) and natural conception (NC) groups (n = 1028). All IVF pregnancies were subdivided into frozen embryo transfer (FET) group (n = 42) and fresh embryo transfer (ET) group (n = 60). Demographic data, pregnancy outcomes and disease phenotypes of HDP among the groups were compared. The risk factors for severe preeclampsia (PE) and early-onset PE were analyzed. Results The incidences of early-onset PE ( P< 0.001), severe PE ( P = 0.016), cesarean section ( P< 0.001) and preterm births ( P = 0.003) in the IVF-HDP group were significantly higher than those in the NC-HDP group, and gestational age at diagnosis of HDP (P = 0.027) and gestational age at delivery (P = 0.004) were earlier and birthweight of the neonates (P = 0.033) were lower in the IVF group. In singleton pregnancies with HDP, IVF was associated with increased risks for both severe PE and early-onset PE (aOR 1.945, 95% CI 1.256, 3.014; and aOR 2.373, 95% CI 1.537, 3.663, respectively), as well as FET, family history of preeclampsia, intrahepatic cholestasis of pregnancy, gestational hypothyroidism and multiparity were associated with increased risks of severe PE and early-onset PE. Conclusions In singleton pregnancies with HDP, IVF was associated with an increased incidence of the disease phenotype (severe or early-onset PE), as well as an increased incidence of pregnancy outcomes related to severe PE and early-onset PE.