Novel biomarkers for prediction of atonic postpartum hemorrhage among 'low-risk' women in labor.

Background: Postpartum hemorrhage (PPH) is the primary cause of maternal mortality globally, with uterine atony being the predominant contributing factor. However, accurate prediction of PPH in the general population remains challenging due to a lack of reliable biomarkers. Methods: Using retrospective cohort data, we quantified 48 cytokines in plasma samples from 40 women diagnosed with PPH caused by uterine atony. We also analyzed previously reported hemogram and coagulation parameters related to inflammatory response. The least absolute shrinkage and selection operator (LASSO) and logistic regression were applied to develop predictive models. Established models were further evaluated and temporally validated in a prospective cohort. Results: Fourteen factors showed significant differences between the two groups, among which IL2Rα, IL9, MIP1ß, TNFß, CTACK, prenatal Hb, Lymph%, PLR, and LnSII were selected by LASSO to construct predictive model A. Further, by logistic regression, model B was constructed using prenatal Hb, PLR, IL2Rα, and IL9. The area under the curve (AUC) values of model A in the training set, internal validation set, and temporal validation set were 0.846 (0.757-0.934), 0.846 (0.749-0.930), and 0.875 (0.789-0.961), respectively. And the corresponding AUC values for model B were 0.805 (0.709-0.901), 0.805 (0.701-0.894), and 0.901 (0.824-0.979). Decision curve analysis results showed that both nomograms had a high net benefit for predicting atonic PPH. Conclusion: We identified novel biomarkers and developed predictive models for atonic PPH in women undergoing "low-risk" vaginal delivery, providing immunological insights for further exploration of the mechanism underlying atonic PPH.

Differences between Chronically Hepatitis B Virus-Infected Pregnant Women with and without Intrafamilial Infection: From Viral Gene Sequences to Clinical Manifestations.

INTRODUCTION: This study aimed to investigate the differences between pregnant women with chronic hepatitis B virus (HBV) infection and intrafamilial infection and those without intrafamilial infection. METHODS: HBV-DNA was extracted from the sera of 16 pregnant women with chronic hepatitis B (CHB) and their family members for gene sequencing and phylogenetic analyses. A total of 74 pregnant women with CHB were followed up from the second trimester to 3 months postpartum. Viral markers and other laboratory indicators were compared between pregnant women with CHB with and without intrafamilial infection. RESULTS: The phylogenetic tree showed that HBV lines in the mother-spread pedigree shared a node, whereas there was an unrelated genetic background for HBV lines in individuals without intrafamilial infection. From delivery to 3 months postpartum, compared with those without intrafamilial infection, pregnant women with intrafamilial infection were related negatively to HBV-DNA (ß = -0.43, 95% confidence interval [CI]: -0.76 to -0.12, p = 0.009), HBeAg (ß = -195.15, 95% CI: -366.35 to -23.96, p = 0.027), and hemoglobin changes (ß = -8.09, 95% CI: -15.54 to -0.64, p = 0.035) and positively to changes in the levels of alanine aminotransferase (ß = 73.9, 95% CI: 38.92-108.95, p < 0.001) and albumin (ß = 2.73, 95% CI: 0.23-5.23, p = 0.033). CONCLUSION: The mother-spread pedigree spread model differs from that of non-intrafamilial infections. Pregnant women with intrafamilial HBV infection have less hepatitis flares and liver damage, but their HBV-DNA and HBeAg levels rebound faster after delivery, than those without intrafamilial infection by the virus.

A comprehensive study on the risk factors and pathogen analysis of postoperative wound infections following caesarean section procedures.

Postoperative wound infections (PWIs), a subtype of surgical site infections, are a significant concern for patients undergoing caesarean sections (C-sections). Understanding risk factors and pathogen profiles can greatly assist in early diagnosis and effective treatment. This study aimed to identify risk factors and analyse the pathogenic landscape contributing to PWIs in C-sections. A nested case-control study was carried out, utilising stringent criteria for case selection and control matching. Diagnostic criteria for surgical site infections included both clinical and microbiological parameters. Risk variables examined included patient age, Body Mass Index, duration of surgery and several other clinical indicators. Microbiological analysis was performed using the BD Phoenix-100 Automated Bacterial Identification System. Statistical analyses were conducted using SPSS version 26.0, and risk factors were evaluated through both univariate and multivariate analyses. A total of 50 patients, aged between 20 and 45 years (mean age 26.3 ± 5.6), developed PWIs following C-sections. The study revealed a temporal distribution and various clinical indicators of PWIs, including elevated white blood cell count and C-reactive protein levels. Gram-negative bacteria were found to be more prevalent at 57.4%. Notable pathogens included Pseudomonas aeruginosa and Acinetobacter baumannii. Antimicrobial resistance patterns were also identified, highlighting the need for a targeted antibiotic approach. Increased infection risks were linked to lack of prophylactic antibiotics, absence of preoperative povidone-iodine antisepsis, operations over an hour, anaemia, amniotic fluid contamination, diabetes, GTI, premature rupture of membranes and white blood cells counts above 10 × 109 /L. The study provides critical insights into the risk factors and microbial agents contributing to PWIs following C-sections. Our findings emphasise the importance of early diagnosis through clinical and laboratory parameters, as well as the need for constant surveillance and reassessment of antibiotic stewardship programs.

Pathophysiological interpretation of fetal heart rate tracings in clinical practice.

The onset of regular, strong, and progressive uterine contractions may result in both mechanical (compression of the fetal head and/or umbilical cord) and hypoxic (repetitive and sustained compression of the umbilical cord or reduction in uteroplacental oxygenation) stresses to a human fetus. Most fetuses are able to mount effective compensatory responses to avoid hypoxic-ischemic encephalopathy and perinatal death secondary to the onset of anaerobic metabolism within the myocardium, culminating in myocardial lactic acidosis. In addition, the presence of fetal hemoglobin, which has a higher affinity for oxygen even at low partial pressures of oxygen than the adult hemoglobin, especially increased amounts of fetal hemoglobin (ie, 180-220 g/L in fetuses vs 110-140 g/L in adults), helps the fetus to withstand hypoxic stresses during labor. Different national and international guidelines are currently being used for intrapartum fetal heart rate interpretation. These traditional classification systems for fetal heart rate interpretation during labor are based on grouping certain features of fetal heart rate (ie, baseline fetal heart rate, baseline variability, accelerations, and decelerations) into different categories (eg, category I, II, and III tracings, "normal, suspicious, and pathologic" or "normal, intermediary, and abnormal"). These guidelines differ from each other because of the features included within different categories and because of their arbitrary time limits stipulated for each feature to warrant an obstetrical intervention. This approach fails to individualize care because the "ranges of normality" for stipulated parameters apply to the population of human fetuses and not to the individual fetus in question. Moreover, different fetuses have different reserves and compensatory responses and different intrauterine environments (presence of meconium staining of amniotic fluid, intrauterine inflammation, and the nature of uterine activity). Pathophysiological interpretation of fetal heart rate tracing is based on the application of the knowledge of fetal responses to intrapartum mechanical and/or hypoxic stress in clinical practice. Both experimental animal studies and observational human studies suggest that, just like adults undertaking a treadmill exercise, human fetuses show predictable compensatory responses to a progressively evolving intrapartum hypoxic stress. These responses include the onset of decelerations to reduce myocardial workload and preserve aerobic metabolism, loss of accelerations to abolish nonessential somatic body movements, and catecholamine-mediated increases in the baseline fetal heart rate and effective redistribution and centralization to protect the fetal central organs (ie, the heart, brain, and adrenal glands), which are essential for intrauterine survival. Moreover, it is essential to incorporate the clinical context (progress of labor, fetal size and reserves, presence of meconium staining of amniotic fluid and intrauterine inflammation, and fetal anemia) and understand the features suggestive of fetal compromise in nonhypoxic pathways (eg, chorioamnionitis and fetomaternal hemorrhage). It is important to appreciate that the timely recognition of the speed of onset of intrapartum hypoxia (ie, acute, subacute, and gradually evolving) and preexisting uteroplacental insufficiency (ie, chronic hypoxia) on fetal heart rate tracing is crucial to improve perinatal outcomes.

Optimizing the management of acute, prolonged decelerations and fetal bradycardia based on the understanding of fetal pathophysiology.

Any acute and profound reduction in fetal oxygenation increases the risk of anaerobic metabolism in the fetal myocardium and, hence, the risk of lactic acidosis. On the contrary, in a gradually evolving hypoxic stress, there is sufficient time to mount a catecholamine-mediated increase in the fetal heart rate to increase the cardiac output and redistribute oxygenated blood to maintain an aerobic metabolism in the fetal central organs. When the hypoxic stress is sudden, profound, and sustained, it is not possible to continue to maintain central organ perfusion by peripheral vasoconstriction and centralization. In case of acute deprivation of oxygen, the immediate chemoreflex response via the vagus nerve helps reduce fetal myocardial workload by a sudden drop of the baseline fetal heart rate. If this drop in the fetal heart rate continues for >2 minutes (American College of Obstetricians and Gynecologists' guideline) or 3 minutes (National Institute for Health and Care Excellence or physiological guideline), it is termed a prolonged deceleration, which occurs because of myocardial hypoxia, after the initial chemoreflex. The revised International Federation of Gynecology and Obstetrics guideline (2015) considers the prolonged deceleration to be a "pathologic" feature after 5 minutes. Acute intrapartum accidents (placental abruption, umbilical cord prolapse, and uterine rupture) should be excluded immediately, and if they are present, an urgent birth should be accomplished. If a reversible cause is found (maternal hypotension, uterine hypertonus or hyperstimulation, and sustained umbilical cord compression), immediate conservative measures (also called intrauterine fetal resuscitation) should be undertaken to reverse the underlying cause. In reversible causes of acute hypoxia, if the fetal heart rate variability is normal before the onset of deceleration, and normal within the first 3 minutes of the prolonged deceleration, then there is an increased likelihood of recovery of the fetal heart rate to its antecedent baseline within 9 minutes with the reversal of the underlying cause of acute and profound reduction in fetal oxygenation. The continuation of the prolonged deceleration for >10 minutes is termed "terminal bradycardia," and this increases the risk of hypoxic-ischemic injury to the deep gray matter of the brain (the thalami and the basal ganglia), predisposing to dyskinetic cerebral palsy. Therefore, any acute fetal hypoxia, which manifests as a prolonged deceleration on the fetal heart rate tracing, should be considered an intrapartum emergency requiring an immediate intervention to optimize perinatal outcome. In uterine hypertonus or hyperstimulation, if the prolonged deceleration persists despite stopping the uterotonic agent, then acute tocolysis is recommended to rapidly restore fetal oxygenation. Regular clinical audit of the management of acute hypoxia, including the "the onset of bradycardia to delivery interval," may help identify organizational and system issues, which may contribute to poor perinatal outcomes.

Single-cell RNA sequencing reveals transcriptional profiles of monocytes in HBV-infected pregnant women during mid-pregnancy.

There is a growing body of evidence that innate immunity also plays an important role in the progression of hepatitis B virus (HBV) infection. However, there is less study on systematically elucidating the characteristics of innate immunity in HBV-infected pregnant women. We compared the features of peripheral blood mononuclear cells in three healthy pregnant women and three HBV-infected pregnant women by single-cell RNA sequencing. 10 DEGs were detected between groups and monocytes were the main expression source of most of the DEGs, which involved in the inflammatory response, apoptosis and immune regulation. Meanwhile, qPCR and ELISA were performed to verify above genes. Monocytes displayed immune response defect, reflecting poor ability of response to IFN. In addition, eight clusters were identified in monocytes. We identified molecular drivers in monocytes subpopulations.TNFSF10+ monocytes, MT1G+ monocytes and TUBB1+ monocytes were featured with different gene expression pattern and biological function.TNFSF10+ monocytes and MT1G+ monocytes were characterized by high levels of inflammation response.TNFSF10+ monocytes, MT1G+ monocytes and TUBB1+ monocytes showed decreased response to IFN. Our results dissects alterations in monocytes related to the immune response of HBV-infected pregnant women and provides a rich resource for fully understanding immunopathogenesis and developing effective preventing HBV intrauterine infection strategies.

Immunomodulatory hybrid micro-nanofiber scaffolds enhance vascular regeneration.

The inertness of synthetic polymer materials and the insufficient mechanical strength of reprocessed decellularized extracellular matrix (dECM) limited their promotive efforts on tissue regeneration. Here, we prepared a hybrid scaffold composed of PCL microfibers and human placental extracellular matrix (pECM) nanofibers by co-electrospinning, which was grafted with heparin and further absorbed with IL-4. The hybrid scaffold with improved hemocompatibility firstly switched macrophages to anti-inflammatory phenotype (increased by 18.1%) and then promoted migration, NO production, tube formation of endothelial cells (ECs), and migration and maturation of vascular smooth muscle cells (VSMCs), and ECM deposition in vitro and in vivo. ECs coverage rate increased by 8.6% and the thickness of the smooth muscle layer was 1.8 times more than PCL grafts at 12 wks. Our study realized the complementary advantages of synthetic polymer materials and dECM materials, and opened intriguing perspectives for the design and construction of small-diameter vascular grafts (SDVGs) and immune-regulated materials for other tissue regeneration.

Physiological CTG interpretation: the significance of baseline fetal heart rate changes after the onset of decelerations and associated perinatal outcomes.

OBJECTIVE: To determine the perinatal outcomes in fetuses with baseline fetal heart rate changes with preceding decelerations on the cardiotocography (CTG) trace, and to interpret CTG traces from the aspect of fetal physiology. MATERIALS AND METHODS: A retrospective analysis of 500 consecutive CTG traces was carried out. The presence of repetitive variable and late decelerations followed by the changes in the baseline including baseline tachycardia and abnormal baseline variability were determined. Perinatal outcomes including Apgar scores and umbilical arterial pH at birth, NNU admission, and meconium-stained amniotic fluid were analyzed. We interpreted the changes in CTG based on fetal physiology. RESULTS: When repetitive variable and late decelerations were present without tachycardia (n = 81), none of the fetuses had an Apgar score <7 at 5 minutes or an umbilical cord pH <7. After the onset of fetal tachycardia (n = 262), fetuses showed decreased Apgar scores and umbilical arterial pH(p < .01), however, there was no significant difference in the rate of abnormal 5 min Apgar score, abnormal PH and NNU admission, if the baseline variability remained normal. However, if the baseline variability was abnormal (n = 44), (either increased or reduced) after tachycardia, there was a statistically significant increase in poor perinatal outcomes. Fetuses with abnormal versus normal variability had lower Apgar scores ≤7 at 5 min (29.6 versus 0.9%, p = .000); umbilical cord arterial pH <7 at birth (29.5 versus 0%, p = .000); increased admission to the NNU (27.3 versus 3.7%, p = .000) and increased incidence of meconium-stained amniotic fluid (38.6 versus 22.5%, p = .024). These serial changes in CTG could be interpreted and predicted by the application of fetal physiology. CONCLUSIONS: There were significant differences in perinatal outcomes when fetuses were exposed to evolving intrapartum hypoxic stress culminating in an abnormal baseline fetal heart rate variability, which was preceded by repetitive decelerations, followed by an increase in the baseline heart rate. However, despite ongoing decelerations, if the baseline variability remained normal, none of the fetuses had a pH of <7. Therefore, the knowledge of fetal physiological response to evolving hypoxic stress can be reliably used to determine fetal compensation.

Plasma microRNA-16-5p, -17-5p and -20a-5p: Novel diagnostic biomarkers for gestational diabetes mellitus.

AIM: To explore whether plasma microRNA-16-5p, -17-5p and -20a-5p can be used as diagnostic biomarkers in gestational diabetes mellitus (GDM) and to investigate the relationship between those microRNAs and the risk factors of GDM (body mass index [BMI], insulin resistance [IR] and tumor necrosis factor-α (TNF-α)). METHODS: A total of 85 pregnant women with GDM and 72 pregnant women without GDM were enrolled in this study. The plasma concentration of microRNAs (microRNA-16-5p, -17-5p, -19a-3p, -19b-3p, -20a-5p) was measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Spearman's correlation analysis was used to evaluate the correlation between those microRNAs and the risk factors of GDM, and receiver operating characteristic curve analysis was used to evaluate diagnostic sensitivity and specificity. RESULTS: Compared with non-GDM women, the relative and absolute expression of plasma microRNA-16-5p, -17-5p, -20a-5p from GDM women were significantly upregulated, when those women were diagnosed as GDM. During pregnancy, the expression of those microRNAs from GDM women also were significantly upregulated. The expression of those microRNAs was also positively correlated with IR, a risk factor of GDM. Plasma microRNA-16-5p, -17-5p, -20a-5p reflected an obvious separation between GDM women and non-GDM women, with areas under the curve of 0.92 (95%CI: 0.871-0.984), 0.88 (95%CI: 0.798-0.962), and 0.74 (95%CI: 0.618-0.870), respectively, cut-offs >2554, 1820, 3886 copies/µL, respectively; sensitivity 41.6%, 21.4% and 17.8%, respectively; and specificity 95.8%, 95.4% and 95.4%, respectively. CONCLUSION: Plasma microRNA-16-5p, -17-5p and -20a-5p are potential diagnostic biomarkers in GDM.

Therapeutic effects of uterine artery embolisation (UAE) and methotrexate (MTX) conservative therapy used in treatment of cesarean scar pregnancy.

PURPOSES: Cesarean scar pregnancy (CSP) is a rare and severe complication after cesarean section. The incidence of CSP has been increased significantly in recent years. In this retrospective case study of 131 CSP patients, the therapeutic effects and prognosis were compared between the two treatment groups: uterine artery embolization and systemic methotrexate injection conservative therapy. In addition, the necessary of subsequent dilation and curettage as a further treatment was also evaluated. METHODS: The 131 CSP patients were assigned into two groups receiving uterine artery embolization (UAE) or MTX conservative therapy. Based on patients' myometrial thickness and reducing degree of ß-hCG level, each of the two treatment group was further divided into two subgroups according to whether the patient received subsequent dilation and curettage as further treatment. The therapeutic effect of two treatment groups was compared. RESULTS: The results indicated that both UAE and MTX conservative treatment achieved the expected therapeutic effect, and the recovery time in dilation and curettage subgroup was significantly shorter than that of the non-curettage subgroup. One hundred and thirty patients resumed normal menstrual cycles within 3-10 months after the treatment. CONCLUSIONS: The individualized therapeutic regimen is an important factor to achieve the desired therapeutic effect based on the specific indications. Dilation and curettage could shorten the recovery time significantly.

Synthesis and Biological Evaluation of Novel Olean-28,13ß-lactams as Potential Antiprostate Cancer Agents.

γ-Lactam is an important structural motif in a large number of biologically active natural products and synthetic small pharmaceutical molecules. However, there is currently no effective approach to construct γ-lactam ring directly from natural rigid polycyclic amides. Herein, we report a facile methodology for synthesis of a new group of olean-28,13ß-lactams (10a-j) from their corresponding amides, promoted by an easily available reagent 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), through an intramolecular dehydrogenative C-N coupling reaction via a radical ion mechanism. Biological evaluation indicated that the most active lactam 10h displayed potent antiproliferative activity against human cancer cells but 13.84- to 16.92-fold less inhibitory activity on noncancer cells in vitro. In addition, 10h significantly inhibited the growth of implanted prostate cancer in vivo. Furthermore, 10h induced cell cycle arrest and apoptosis and down-regulated the AKT/mTOR signaling in DU-145 cells. Finally, 10h was more stable in rat plasma and human liver microsomes than CDDO-Me and had little hERG channel inhibitory activity. Collectively, 10h may be a potential antiprostate cancer agent for further investigation.