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Multiple theories have been proposed to explain the pathogenesis of early-onset preeclampsia (EOPE), and angiogenic dysfunction is an important part of this pathogenesis. Carnitine palmitoyltransferase (CPT1A) is a key rate-limiting enzyme in the metabolic process of fatty acid oxidation (FAO). FAO regulates endothelial cell (EC) proliferation during vascular germination and is also essential for ab initio deoxyribonucleotide synthesis, but its role in EOPE needs to be further elucidated. In the present study, we investigated its functional role in EOPE by targeting the circHIPK3/miR-124-3p/CPT1A axis. In our study, reduced expression of circHIPK3 and CPT1A and increased expression of miR-124-3p in placental tissues from patients with EOPE were associated with EC dysfunction. Here, we confirmed that CPT1A regulates fatty acid oxidative activity, cell proliferation, and tube formation in ECs by regulating FAO. Functionally, knockdown of circHIPK3 suppressed EC angiogenesis by inhibiting CPT1A-mediated fatty acid oxidative activity, which was ameliorated by CPT1A overexpression. In addition, circHIPK3 regulates CPT1A expression by sponging miR-124-3p. Hence, circHIPK3 knockdown reduced fatty acid oxidation in ECs by sponging miR-124-3p in a CPT1A-dependent manner and inhibited EC proliferation and tube formation, which may have led to aberrant angiogenesis in EOPE. Thus, strategies targeting CPT1A-driven FAO may be promising approaches for the treatment of EOPE. KEY MESSAGES: Decreased Carnitine palmitoyltransferase (CPT1A) expression in preeclampsia(PE). CPT1A overexpression promotes FAO activity and tube formation in ECs. CircHIPK3 can affect CPT1A expression and impaire angiogenesis of EOPE. CircHIPK3 regulates CPT1A expression by acting as a ceRNA of miR-124-3p in HUVECs. Confirming the effect of circHIPK3/miR-124-3p/CPT1A axis on EOPE.
Subject(s)
Carnitine O-Palmitoyltransferase , Fatty Acids , MicroRNAs , Oxidation-Reduction , Pre-Eclampsia , MicroRNAs/genetics , MicroRNAs/metabolism , Carnitine O-Palmitoyltransferase/metabolism , Carnitine O-Palmitoyltransferase/genetics , Humans , Pre-Eclampsia/metabolism , Pre-Eclampsia/genetics , Female , Pregnancy , Fatty Acids/metabolism , Cell Proliferation , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/genetics , RNA, Circular/genetics , RNA, Circular/metabolism , Placenta/metabolism , Adult , Human Umbilical Vein Endothelial Cells/metabolism , AngiogenesisABSTRACT
Introduction: We evaluated the quality of the published clinical practice guidelines on placenta accreta spectrum (PAS) disorders to provide reference for the development of high-quality PAS guidelines. Methods: China National Knowledge Infrastructure (CNKI), Wan Fang, PubMed, Embase, Web of Science, and Cochrane Library were systematically searched. Quality assessments were conducted using the appraisal of guidelines for research and evaluation (AGREE) II framework and Reporting Items for practice Guidelines in Healthcare (RIGHT) checklist. Intraclass correlation coefficients (ICCs) were used to measure the agreement among reviewers. Results: In total, 13 guidelines from different countries, published between 2015 and 2021 were included. There included 9 official guidelines, 3 consensuses, and 1 standard reference and covered subjects including epidemiology, diagnosis and treatment. The mean standardized scores across 6 domains (scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence) were 53.63%, 27.35%, 33.57%, 72.01%, 19.39% and 41.02%, respectively. Of the 13 guidelines, 11 were classified as grade B, whereas 2 as grade C. According to the RIGHT checklist, the overall reporting rate of the 13 guidelines ranged from 28.57% to 54.29%. Conclusion: The current guidelines for PAS demonstrate commendable methodological and reporting qualities. However, the methodological and reporting quality of PAS CPGs still need to be further improved, particularly in stakeholder involvement, the rigor of development, applicability, and editorial independence domains.
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BACKGROUND: Osteoarthritis is a common degenerative joint disease that is highly prevalent in the elderly population. Along with the occurrence of sports injuries, osteoarthritis is gradually showing a younger trend. Osteoarthritis has many causative factors, and its pathogenesis is currently unknown. Cellular senescence is a stable form of cell cycle arrest exhibited by cells in response to external stimuli and plays a role in a variety of diseases. And it is only in the last decade or so that cellular senescence has gradually become cross-linked with osteoarthritis. However, there is no comprehensive bibliometric analysis in this field. The aim of this study is to present the current status and research hotspots of cellular senescence in the field of osteoarthritis, and to predict the future trends of cellular senescence in osteoarthritis research from a bibliometric perspective. METHODS: This study included 298 records of cellular senescence associated with osteoarthritis from 2009 to 2023, with data from the Web of Science Core Collection database. CiteSpace, Scimago Graphica software, VOSviewer, and the R package "bibliometrix" software were used to analyze regions, institutions, journals, authors, and keywords to predict recent trends in cellular senescence related to osteoarthritis research. RESULTS: The number of publications related to cellular senescence associated with osteoarthritis is increasing year by year. China and the United States contribute more than 70% of the publications and are the mainstay of research in this field. Central South University is the most active institution with the largest number of publications. International Journal of Molecular Sciences is the most popular journal in the field with the largest number of publications, while Osteoarthritis and Cartilage is the most cited journal. Loeser, Richard F. is not only the most prolific author, but also the most frequently cited author, contributing greatly to the field. CONCLUSION: In the last decade or so, this is the first bibliometric study that systematically describes the current status and development trend of research on cellular senescence associated with osteoarthritis. The study comprehensively and systematically summarizes and concludes the research hotspots and development trends, providing valuable references for researchers in this field.
Subject(s)
Bibliometrics , Cellular Senescence , Osteoarthritis , Osteoarthritis/pathology , Cellular Senescence/physiology , HumansABSTRACT
BACKGROUND: Acute fatty liver of pregnancy (AFLP) is an uncommon but potentially life-threatening complication. Lacking of prognostic factors and models renders prediction of outcomes difficult. This study aims to explore factors and develop a prognostic model to predict three-month mortality of AFLP. METHODS: This retrospective study included 78 consecutive patients fulfilling both clinical and laboratory criteria and Swansea criteria for diagnosis of AFLP. Univariate and multivariate cox regression analyses were used to identify predictive factors of mortality. Predictive efficacy of prognostic index for AFLP (PI-AFLP) was compared with the other four liver disease models using receiver operating characteristic (ROC) curve. RESULTS: AFLP-related three-month mortality of two medical centers was 14.10% (11/78). International normalised ratio (INR, hazard ratio [HR] = 3.446; 95% confidence interval [CI], 1.324-8.970), total bilirubin (TBIL, HR = 1.005; 95% CI, 1.000-1.010), creatine (Scr, HR = 1.007; 95% CI, 1.001-1.013), low platelet (PLT, HR = 0.964; 95% CI, 0.931-0.997) at 72 h postpartum were confirmed as significant predictors of mortality. Artificial liver support (ALS, HR = 0.123; 95% CI, 0.012-1.254) was confirmed as an effective measure to improve severe patients' prognosis. Predictive accuracy of PI-AFLP was 0.874. Area under the receiver operating characteristic curves (AUCs) of liver disease models for end-stage liver disease (MELD), MELD-Na, integrated MELD (iMELD) and pregnancy-specific liver disease (PSLD) were 0.781, 0.774, 0.744 and 0.643, respectively. CONCLUSION: TBIL, INR, Scr and PLT at 72 h postpartum are significant predictors of three-month mortality in AFLP patients. ALS is an effective measure to improve severe patients' prognosis. PI-AFLP calculated by TBIL, INR, Scr, PLT and ALS was a sensitive and specific model to predict mortality of AFLP.
Subject(s)
Fatty Liver , Pregnancy Complications , Female , Humans , Pregnancy , Fatty Liver/diagnosis , Fatty Liver/mortality , Prognosis , Retrospective Studies , ROC Curve , Severity of Illness Index , Pregnancy Complications/diagnosis , Pregnancy Complications/mortality , Models, BiologicalABSTRACT
Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F2α and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is clinically used to treat postpartum hemorrhage (PPH). However, off-target activation of closely related receptors such as the prostaglandin E receptor subtype EP3 (EP3 receptor) by carboprost results in side effects and limits the clinical application. Meanwhile, the FP receptor selective agonist latanoprost is not suitable to treat PPH due to its poor solubility and fast clearance. Here, we present two cryo-EM structures of the FP receptor bound to carboprost and latanoprost-FA (the free acid form of latanoprost) at 2.7 Å and 3.2 Å resolution, respectively. The structures reveal the molecular mechanism of FP receptor selectivity for both endogenous prostaglandins and clinical drugs, as well as the molecular mechanism of G protein coupling preference by the prostaglandin receptors. The structural information may guide the development of better prostaglandin drugs.
Subject(s)
Carboprost , Dinoprost , Receptors, Prostaglandin , Female , Humans , Carboprost/pharmacology , Dinoprost/pharmacology , Latanoprost , Ligands , Receptors, Prostaglandin/agonists , Receptors, Prostaglandin/chemistry , Cryoelectron MicroscopyABSTRACT
Background: The termination of pregnancy in patients with placenta accreta spectrum disorder (PASD) during the second trimester remains uncertain. In addition, interventional radiology techniques, such as arterial embolization and balloon placement, are potential options. We evaluated the outcomes of pregnancy termination in patients with PASD during the second trimester and the effectiveness of preoperative interventional radiology techniques.Methods: This retrospective study analyzed 48 PASD patients who underwent pregnancy termination during the second trimester between January 2016 and May 2021.Results: Of the 48 patients, 20 (41.67%) underwent transvaginal termination, whereas 28 (58.33%) underwent cesarean section. Notably, no significant differences were observed in success rates between the transvaginal termination and cesarean section groups (80.00% vs. 92.86%, P = 0.38). Furthermore, no statistically significant differences were observed in the success rates (94.12% vs 90.32%, P = 1.00) and blood loss (512.35 ± 727.00 ml vs 804.00 ± 838.98 ml, P = 0.23) between the artery embolization and non-embolization groups. In the vaginal termination group, statistically significant differences were observed in gestational weeks (16.70 ± 3.12 vs 22.67 ± 3.63, P < 0.01) and blood loss (165.00 ± 274.43 ml vs 483.64 ± 333.53 ml, P = 0.04) between the (artery embolization and non-embolization) subgroups. Conversely, in the cesarean section group, no significant differences were observed in gestational weeks (23.59 ± 3.14 vs 23.20 ± 4.37, P = 0.79) and blood loss (811.11 ± 879.55 ml vs 989.47 ± 986.52 ml, P = 0.76) between the subgroups.Conclusions: Further studies are needed to evaluate the efficacy of vaginal termination in PASD patients during the second trimester. Regarding cesarean termination, arterial embolization did not demonstrate increased effectiveness.
Subject(s)
Abortion, Induced , Placenta Accreta , Pregnancy , Humans , Female , Pregnancy Trimester, Second , Cesarean Section , Placenta Accreta/diagnostic imaging , Placenta Accreta/therapy , Retrospective StudiesABSTRACT
Introduction: To evaluate the methodological quality of diagnosis and treatment guidelines/consensus related to ectopic pregnancy. Materials and methods: Use the "Appraisal of Guidelines and Research and Evaluation" (AGREE II) method to evaluate the differences among the guideline/consensus. Results: We appraised 9 clinical practice guidelines for ectopic pregnancy (9 clinical practice guidelines from 5 countries) including the United States, United Kingdom, Ireland, Canada, and China. The guidelines received the highest scores for clarity of presentation (82.72%) and lowest scores for editorial independence (30.56%). The comprehensive recommendations of the 7 guidelines were Grade B, the other 2 guidelines were Grade C. Conclusion: The overall quality of the ectopic pregnancy guidelines had room for improvement. It is recommended to supplement and improve the four fields of "independence", "rigor", "participants" and "application", especially the "independence" and "application" fields.
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Objective: To compare the predictive value of different risk assessment methods for puerperium venous thromboembolism (VTE). Methods: This study included 55 women with and 165 women without puerperal VTE. Using the cases, 11 assessment methods were compared. Results: The area under the curve (AUC) value of the 11 assessments was highest for the modified Caprini risk assessment model for pregnancy (a modified risk scoring method from Caprini, AUC = 0.805). Pairwise comparison of the AUC values of the 11 assessment methods indicated no significant difference among the five methods with AUC values > 0.7. Among them, the modified Caprini, the risk scoring method recommended by the Swedish Guidelines (Swedish method), and the risk scoring method recommended by the Shanghai consensus (Shanghai method) performed better than the other six methods with AUC values < 0.7 (P < 0.05). The sensitivities of the five methods for predicting a high risk of VTE were 69.09-94.55% and the specificities were 25.45-77.58%. The sensitivity of the modified Caprini was higher than those of the risk management method from the Chinese consensus (Chinese consensus method), Royal College of Obstetricians and Gynaecologists risk assessment scale (RCOG), and Swedish method (P < 0.05), but the specificity was only 25.45%. No significant difference in sensitivity was detected among the Swedish, Shanghai, RCOG, and Chinese consensus methods, whereas the specificity of the Swedish method was higher than that of the Shanghai, RCOG, and Chinese consensus methods. Conclusion: The predictive value of different risk assessment methods for puerperium VTE varies greatly. Considering the sensitivity and specificity, the Swedish method may have better clinical application value among the 11 methods.
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This paper proposes an encryption scheme for floating probabilistic shaping orthogonal frequency division multiplexing passive optical networks (FPS-OFDM-PON). Four chaotic sequences are generated by the 4D hyperchaotic model for floating probabilistic shaping (FPS) and bubble sort encryption scheme. An experiment is conducted to demonstrate the transmission of a 70Gb/s (7×10Gb/s) FPS-OFDM-PON signal across a 2km weakly coupled 7-core fiber. The keyspace of the 4D hyperchaotic model reaches 10120. The results show that a 1.82 dB gain in receiver sensitivity compared with the conventional uniform 16QAM-OFDM due to the introduction of FPS. When the system is assaulted by an unlawful receiver, the bit error rate (BER) can still remain at 0.49, successfully assuring the system's security. Due to its good transmission and security performance, the scheme has important application prospects in the future optical access network.
ABSTRACT
Thermally oxidized MWCNTs (OMWCNTs) are fabricated by a thermal treatment of MWCNTs at 500 °C for 3 h in an oxygen-containing atmosphere. The oxygen content of OMWCNTs increases from 1.9 wt% for MWCNTs to 8.3 wt%. And the BET specific surface area of OMWCNTs enhances from 254.2 m2g-1for MWCNTs to 496.1 m2g-1. The Fe2O3/OMWCNTs nanocomposite is prepared by a hydrothermal method. Electrochemical measurements show that Fe2O3/OMWCNTs still keeps a highly reversible specific capacity of 653.6 mA h g-1after 200 cycles at 0.5 A g-1, which shows an obviously higher capacity than the sum of that of single Fe2O3and OMWCNTs. The OMWCNTs not only buffer the volume changes of Fe2O3nanoparticles but also provide high-speed electronic transmission channels in the charge-discharge process. The thermal oxidation method of OMWCNTs avoids using strong corrosive acids such as nitric acid and sulfuric acid, which has the advantages of safety, environmental protection, macroscopic preparation, etc.
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OBJECTIVES: Placentae from patients with preeclampsia have increased susceptibility to necroptosis and phosphoglycerate mutase 5 (PGAM5) plays a role in many necrosis pathways. We determined whether PGAM5 promotes necroptosis of trophoblast cells and the underlying mechanisms in this study. METHODS: The injury model was established by treating JEG3 cells with hypoxia for 24 h. The functional measurements were assessed by the cell counting kit-8, propidium iodide (PI)/Annexin V staining, JC-1 staining and firefly luciferase ATP assay. The expression of proteins in human placentae and JEG3 cells was measured Western blot. PGAM5 was knocked down to study its role in hypoxia-induced necroptosis. RESULTS: The placentae from patients with preeclampsia showed up-regulation of PGAM5 and decreased levels of p-Drp1-S637, accompanied by increased necroptosis-relevant proteins expression. The expression of PGAM5 in JEG3 cells was up-regulated under hypoxia, which promoted dephosphorylation of Drp1 at Serine 637 residue, mitochondrial dysfunction (elevated ROS level and reduced mitochondrial membrane potential and ATP content) and cellular necroptosis (increased PI+ /Annexin V+ cells and decreased cell viability), accompanied by increased expression of necroptosis-relevant proteins; knockdown of PGAM5 attenuated these phenomena. CONCLUSIONS: Our results indicate that PGAM5 can promote necroptosis in trophoblast cells through, at least in part, activation of Drp1. It may be used as a new therapeutic target to prevent trophoblast dysfunction in preeclampsia.
Subject(s)
Necroptosis , Pre-Eclampsia , Adenosine Triphosphate , Annexin A5 , Cell Line, Tumor , Dynamins/metabolism , Female , Humans , Hypoxia , Phosphoglycerate Mutase/genetics , Phosphoglycerate Mutase/metabolism , Phosphoprotein Phosphatases/metabolism , Pregnancy , Trophoblasts/metabolismABSTRACT
BACKGROUND: Intrauterine adhesion and cesarean scar diverticulum are the main complications of poor healing after uterine injury. Human umbilical cord MSCs transplantation has been regarded as the most potential treatment in the clinic, the safety and efficacy of which in the clinic, however, remains unclear. METHODS: In this study, ten patients were enrolled: six with intrauterine adhesion and four with cesarean scar diverticulum. All the patients were injected with human umbilical cord MSCs twice into the uterus. Beside the chest X-ray, ECG and abdominal ultrasound, many laboratory tests including blood routine, liver and renal function, ovarian function, tumor biomarkers, and immune function were used to estimate the safe after stem cell transplanted. In addition, the efficacy of stem cell transplanted was shown by the endometrial thickness, the volume of the uterus, and cesarean scar diverticulum based on 3D ultrasound imaging. RESULTS: We found that all results of these laboratory tests were normal in these enrolled patients before and after cell injection. Meanwhile, the results of the chest X-ray and ECG were also normal in the treatment process. The abdominal ultrasound showed that the size of the left and right kidneys was inconsistent in one patient after cell therapy, while those of other patients were normal. In addition, endometrial thickness, the volume of the uterus, and cesarean scar diverticulum showed an improving tendency, but no significant difference was noted. CONCLUSION: In summary, intrauterine injection of clinically graded human umbilical cord MSCs was safe for poor healing after uterus injury. Trial registration NCT03386708. Registered 27 December 2017, https://clinicaltrials.gov/ct2/show/NCT03386708?cond=CSD&cntry=CN&draw=2&rank=2.
Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Cicatrix/diagnostic imaging , Cicatrix/pathology , Cicatrix/therapy , Female , Humans , Mesenchymal Stem Cell Transplantation/adverse effects , Mesenchymal Stem Cell Transplantation/methods , Pregnancy , Umbilical Cord , Uterus/diagnostic imaging , Uterus/pathologyABSTRACT
This study aimed to reveal the key targets and molecular mechanisms of aspirin in preventing preeclampsia. We used bioinformatics databases to collect the candidate targets for aspirin and preeclampsia. The biological functions and signaling pathways of the intersecting targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, the hub targets were identified by cytoscape plugin cytoHubba from the protein-protein interaction network. We collected 90 targets for aspirin in preventing preeclampsia. The biological processes of the intersecting targets are mainly involved in xenobiotic metabolic process, inflammatory response, negative regulation of apoptotic process, and protein phosphorylation. The highly enriched pathways were FoxO signaling pathway, circadian rhythm, insulin resistance, arachidonic acid metabolism, and drug metabolism-cytochrome P450. The hub targets for aspirin in preventing preeclampsia were tumor protein p53 (TP53), C-X-C motif chemokine ligand 8 (CXCL8), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 14 (MAPK14), epidermal growth factor receptor (EGFR), estrogen receptor (ESR1), and prostaglandin-endoperoxide synthase 2 (PTGS2). Molecular docking results showed good bindings between the proteins and aspirin. In conclusion, these findings highlight the key targets and molecular mechanisms of aspirin in preventing preeclampsia.
Subject(s)
Computational Biology , Pre-Eclampsia , Aspirin/pharmacology , Aspirin/therapeutic use , Computational Biology/methods , Female , Gene Regulatory Networks , Humans , Molecular Docking Simulation , Network Pharmacology , Pre-Eclampsia/genetics , Pre-Eclampsia/prevention & control , PregnancyABSTRACT
OBJECTIVE: To evaluate the clinical characteristics and prognosis of TBI patients from 2016 to 2019 admitted to Port Moresby General Hospital (PMGH) of Papua New Guinea (PNG) and compare the results with previous researches to analyze current clinical characteristics and prognosis. METHODS: A retrospective study was performed on 389 TBI patients in Port Moresby General Hospital (PMGH) over a 48-month period (from January 2016 to December 2019). The clinical and radiographic data were collected. Patients were followed up for at least 3 months, and outcomes were assessed using the Glasgow Outcome Scale (GOS). Univariate and multivariate logistic regressions were performed to analyze the prognosis and intracranial infection of patients, as well as the effect of surgery on the prognosis of TBI patients. RESULTS: The average age of the 389 TBI patients was 24.9 years old, and the most common age was 18-40 years old, accounting for 55.5%. The proportion of male patients was 79.4%, and the proportion of juvenile patients (≤18 years) was 30.8%. The most primary cause of injury was fighting and brawling (38.0%). At admission, patients had an average GCS score of 9.1, and patients with severe TBI accounted for 46.8%. Overall, 32.1% of the patients had a good prognosis, with a mortality rate of 13.9% (54 cases). Analyzing the relationship between surgical treatment and prognosis in 303 patients with moderate or severe TBI, there was no statistical significance. Univariate and logistic regression analyses for poor prognosis included gender, GCS, multiple injuries, Rotterdam CT scores, and intracranial infection. Univariate and logistic regression analyses for intracranial infection included GCS, open brain trauma, and postoperative drainage time. CONCLUSION: Despite there has been a secular trend towards reduced incidence of TBI, the prognosis of moderate or severe TBI patients who received surgery showed no significant improvement, indicating that PNG, as a backward developing country, faced a huge problem in TBI prevention and control.
Subject(s)
Brain Injuries, Traumatic/diagnosis , Adolescent , Adult , Aged , Brain Injuries, Traumatic/mortality , Brain Injuries, Traumatic/surgery , Child , Child, Preschool , Computational Biology , Female , Glasgow Coma Scale , Glasgow Outcome Scale , Humans , Infant , Logistic Models , Male , Middle Aged , Papua New Guinea/epidemiology , Prognosis , Retrospective Studies , Surgical Wound Infection/etiology , Young AdultABSTRACT
Intercellular communication in the decidua plays important roles in relaying information between the maternal and fetal systems in the maintenance of pregnancy and the transition to labor. To date, several studies have explored cell-cell communications in the decidua during different periods of pregnancy, but studies systematically decoding the intercellular communication network, its internal cascades, and their involvement in labor are still lacking. In this study, we reconstructed a decidual cell-cell communication network based on scRNA-seq of peripartum decidua via the CellCall method. The results showed that endometrial cells (EECs) and extravillous trophoblasts relayed most of the common intercellular signals in the decidua both before delivery (DBD) and after delivery (DAD). Endothelial cells and EECs controlled many WNT-signaling-related intercellular communication factors that differed between DBD and DAD, some of which could be candidate biomarkers for the diagnosis of labor. Analysis of intercellular communications related to T cells identified abundant maternal-fetal immune-tolerance-related communication, such as TNFSF14-TNFRSF14/LTBR and FASLG-FAS signalings. We further explored the characteristics of the B cell receptor (BCR) and T cell receptor (TCR) repertoires by single-cell BCR/TCR sequencing. The results showed no significant differences in clonal expansion of B/T cells between DAD and DBD, indicating there was no significant change to adaptive immunity at the maternal-fetal interface during delivery. In summary, the findings provide a comprehensive view of the intercellular communication landscape in the peripartum decidua and identified some key intercellular communications involved in labor and maternal-fetal immune tolerance. We believe that our study provides valuable clues for understanding the mechanisms of pregnancy and provides possible diagnostic strategies for the onset of labor.