This review article discusses the most common umbilical cord vessel anomalies and umbilical cord emergencies, as well as their implications on anesthetic management. Umbilical cord anomalies and emergencies pose significant risks to both the fetus and the mother. Fetal complications can include fetal heart tone issues, hypoxia, preterm delivery, unexpected neonatal ICU admissions, exsanguination, and fetal demise. Maternal complications can include emergency cesarean delivery and postpartum hemorrhage. Recognition of these anomalies and their potential complications is essential to the proper management of these patients. Anesthesia providers must be familiar with and available for patients with various umbilical cord pathologies to provide safe and effective care for the best maternal and neonatal outcomes if umbilical cord emergencies arise. Coordinated efforts should be in place for multidisciplinary emergency response systems.

The 2025 recommendations from the International Liaison Committee on Resuscitation are updated from the 2020 version. The algorithm is unchanged from 2015. Ten topics are addressed in the 2025 recommendations: Anticipation and preparation, Umbilical cord management, Initial steps, Assessment of heart rate at birth, Ventilation and oxygenation, Circulatory support, Drug and fluid administration, Post-resuscitation care, Prognostication during cardio-pulmonary resuscitation and Family presence. Among changes since 2020 are an update of umbilical cord handling. Assessment of heart rate is now including auscultation as well as pulse-oximetry. We identified 51 recommendations given for topics published between the 2020 and the 2025 versions. Of these, 19 were weak and only three were strong recommendations, 6 were conditional and 15 recommendations are classified as good practice. Seven had insufficient evidence to draw any conclusion, and one was not graded. The certainty of evidence was low or very low for 25 recommendations and moderate for four only. Conclusion: The present recommendations for newborn resuscitation are improved; however, they are still based on weak evidence with mostly low or very-low certainty. This indicates extensive research to establish truly evidence-based recommendations for newborn resuscitation is still needed.

Mesenchymal stem cell‑derived extracellular vesicles (MSC‑EVs) have garnered research attention due to their unique biological functionalities and therapeutic potential. Compared with the parent MSCs from which they originate, MSC‑EVs are typically free from systemic allergic reactions, hemolysis, pyrogenic reactions, abnormal hematological changes, and vascular and muscle irritation problems, and thus, exhibit therapeutic potential. The present review provides a comprehensive analysis of numerous isolation methodologies for MSC‑EVs, with each method being evaluated based on key parameters, including principles, advantages, limitations and applications. Notably, the therapeutic potential of MSC‑EVs in the treatment of tuberculosis (TB) has been emphasized. MSC‑EVs have demonstrated unique capacities to modulate the T helper cell (Th)1/Th2/T regulatory cell balance, promote M2 macrophage polarization, alleviate inflammation through microRNA‑mediated mechanisms and enhance host defense through antimicrobial peptide responses. The integration of MSC‑EVs with anti‑TB therapy can improve lung, kidney and bladder health by reducing TNF‑α levels and increasing IL‑10/TGF‑β ratios. Notably, functional discrepancies between EVs derived from distinct MSC sources, such as umbilical cord vs. bone marrow cells, underscore the need for targeted optimization strategies. Adequate risk assessment is important before clinical trials, particularly concerning immunogenicity, potential pro‑inflammatory effects and promotion of TB latency. The present review explores the potential clinical applications of MSC‑EVs in TB and other infectious diseases, offering key insights into their therapeutic potential, with the aim of guiding future research.

Early-life exposure to F-53B remodels the pulmonary immune microenvironment and enhances susceptibility to neutrophil-predominant asthma via dysregulation of arachidonic acid metabolism.

Ultrasound-guided HUC-MSCs transplantation alleviates neuropathic pain in CCI rats: a mechanistic study based on microglia/macrophage polarization and the NLRP3 inflammasome.

Thermoreversible cell-derived extracellular matrix only hydrogel (CEOgel): Development, characterization, and applications.

Experimental and data modeling approaches of umbilical cord blood allogenic response identify cytokine profiles as potential biomarkers associated with the initial stages of alloreactivity and immunomodulation.

Para-uterine imaging protocol: Stabilizing living mouse embryos within the maternal abdomen for in vivo imaging and visually guided physiology.

The use of umbilical cord blood (UCB) as a stem cell source in haematopoietic stem cell transplant (HSCT) has greatly declined in recent years. It has largely been replaced by mismatched unrelated and family donors, facilitated by advances in transplant technologies, including post-transplant cyclophosphamide to prevent graft-versus-host disease (GVHD). UCB remains a distinctive source of haematopoietic stem cells (HSCs) with unique immunologic and practical advantages, including for those with malignant and non-malignant diseases. Compared to other cell sources, UCB transplantation (UCBT) offers comparable survival with reduced chronic GVHD (cGVHD) and with a potent graft-versus-leukaemia (GVL) effect. These outcomes likely reflect the biology of cord-derived lymphocytes-particularly naïve, adaptable CD8+ T-cells capable of rapid differentiation and tumour-directed cytotoxicity without sustained alloreactivity. UCB permits greater human leukocyte antigen (HLA) mismatch tolerance, especially when transplant is performed T-cell replete and can be accessed immediately, reducing time to transplant for high-risk leukaemia. In addition, recent advances in ex vivo expansion technologies have overcome historical limitations of low cell dose and delayed engraftment, expanding UCB's applicability to older paediatric and adult recipients. This review discusses the evidence of using UCB as a preferred stem cell source in patients with relapsed/refractory haematological malignancies and how we may interrogate the properties of UCB to improve outcomes in these high-risk cohorts.

Nebulized delivery of multi-modular stem cell-derived exosomes for the treatment of pulmonary fibrosis.

Dual-targeted engineered mesenchymal stem cell-derived extracellular vesicles delivering Nedd4 attenuate renal fibrosis in diabetic kidney disease.

JOURNAL/nrgr/04.03/01300535-202606000-00078/figure1/v/2026-02-11T151048Z/r/image-tiff Ischemic stroke remains a leading cause of disability and death, with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue. However, the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation. In this study, we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early (6 hours) or delayed (3 days) time point post-ischemia. Compared with delayed treatment, early administration of exosomes resulted in significantly superior efficacy, as evidenced by improved neurological function scores and reduced infarct volumes. Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes, including Ccl2 , Ccl5 , Cxcl10 , Il-1 β, Il-6 , Itgam , Itgax , and Tnf-α . Metabolomic profiling of these brain tissues further identified modulation of key metabolites, including trimethylamine N-oxide, glutathione, 1-stearoyl-rac-glycerol, and phosphatidylcholine, suggesting that alteration of metabolic pathways contributes to the therapeutic effect. Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid, lysine, propanoate, and tyrosine. These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes, particularly when administered early post-ischemia, exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain, highlighting their potential as a therapeutic intervention for ischemic stroke.

Extracellular vesicle-mediated transcellular mitophagy as a modulatory target for moderate hyperoxia-induced alveolar developmental arrest in bronchopulmonary dysplasia.

Cord-blood-PRP attenuates fibrogenic features of TGFβ-activated hepatic stellate cells in in vitro and animal models.

Spinal cord injury (SCI) is a debilitating neurological condition that leads to physical dependence, substantial financial burden, and psychological stress. Current for SCI, such as stem cell therapy, pharmacological interventions, and neural implants offer limited functional recovery. Among emerging strategies, exosome-based therapies in nerve damage can reduce neuroinflammation and promote neural repair by angiogenesis and neurogenesis. MicroRNAs (miRNAs) are key modulators of inflammatory and regenerative pathways in SCI. Specifically, miR-19a-3p, miR-19b-3p, and miR-27b have been implicated in regulating neuroinflammatory responses, neuronal survival, and tissue remodeling. Dysregulation of these miRNAs following SCI can exacerbate inflammation and hinder recovery. In this study, exosomes were extracted and characterized using flowcytometry for surface markers CD81 and CD9, scanning electron microscopy (SEM), dynamic light scattering (DLS), and Zeta potential analysis. Thirty-two female rats were randomly assigned into four groups: laminectomy only, contusion, contusion + PBS, and contusion + exosomes. SCI were induced using contusion model and thirty minutes after the injury, the exosome-treated group received an intravenous injection of 100 μl of exosomes via the tail vein for 7 days. Motor and behavioral functions were assessed through the open-field test, Basso, Beattie, and Bresnahan (BBB) scale and narrow beam test (NBT). Eight weeks after the SCI, real time PCR, Western blotting was utilized to assess changes in inflammatory cytokines, while histological changes were observed using hematoxylin and eosin (H&E) staining and stereology. In vivo experiments showed that the administration of exosomes significantly enhanced functional recovery and behavioral test outcomes following SCI. The treatment also resulted in a significant reduction in inflammatory cytokine levels and a marked decrease in the size of the cavity in the group treated with exosomes. Molecular analysis revealed that exosome therapy modulated the expression of miR-19a-3p, miR-19b-3p, and miR-27b, which are key regulators of neuroinflammation and neural repair. These findings suggest that exosomes hold strong therapeutic potential for treating SCI by modulating inflammation and promoting neural repair. Collectively, these findings indicate a potential mechanism through which exosomes exert their neuroprotective effects, particularly by regulating inflammatory and regenerative pathways.

This study aims to analyze the incidence and causes of stillbirth, identify associated risk factors, and explore effective interventions. A retrospective analysis was conducted on 324 stillbirth cases admitted to the Obstetrics Department of Chongqing Health Center for Women and Children from January 2017 to December 2023. A comparison was made with live births in the same period. The study investigated the origins of stillbirth, identified key risk factors, and proposed strategies for the prevention and management of stillbirth. The stillbirth rate was 3.2 ‰, with no significant variation over the 7years (p>0.05). A "U-shaped" relationship was observed between maternal age and stillbirth. The incidence of stillbirth among multiparous women was significantly higher than among primiparous women. The top three maternal factors associated with stillbirth were genital malformations, severe preeclampsia, and infections, with stillbirth rates of 20 , 13, and 13 ‰, respectively. The top three umbilical cord and placental factors associated with stillbirth were identified as umbilical cord shortness, umbilical cord true knot, and placental abruption, with incidence rates of 19 , 17, and 11 ‰, respectively. Twin pregnancies had a stillbirth rate of 17 ‰. Advanced maternal age, multiparity, and twin pregnancies were identified as high-risk groups for stillbirth. To reduce stillbirth incidence, essential measures include strengthening pre-conception healthcare and counseling, proactively addressing pregnancy-related complications, improving monitoring methods throughout gestation and delivery, and refining midwifery skills.

Intraoperative nausea and vomiting are common during cesarean delivery under neuraxial anesthesia, and peritoneal traction is a major trigger. Flurbiprofen, a non-steroidal anti-inflammatory drug used for multimodal analgesia, is typically administered toward the end of surgery; whether earlier intraoperative administration is associated with reduced intraoperative nausea and vomiting remains unclear. We conducted a retrospective cohort study at a single tertiary university hospital in Japan from October 1, 2021 to September 30, 2025. Parturients undergoing cesarean delivery under neuraxial anesthesia were classified as an early group (intravenous flurbiprofen administered after umbilical cord clamping and by the start of peritoneal closure) or a non-early group (administered after the start of peritoneal closure or not administered intraoperatively). The primary outcome was intraoperative antiemetic use, pre-specified as a surrogate for intraoperative nausea and vomiting. Adjusted odds ratios were estimated using multivariable logistic regression with pre-specified sensitivity analyses. A total of 1398 parturients were included (early, n = 1062; non-early, n = 336). Intraoperative antiemetic use occurred in 172/1,062 (16.2%) and 91/336 (27.1%), respectively, corresponding to an absolute risk difference of - 10.9 percentage points. Early flurbiprofen administration was associated with lower odds of intraoperative antiemetic use (adjusted odds ratio 0.54; 95% confidence interval 0.41 to 0.73; P < 0.001), with consistent findings across sensitivity analyses. Early intraoperative flurbiprofen administration after umbilical cord clamping was associated with lower intraoperative antiemetic use during cesarean delivery under neuraxial anesthesia, suggesting that the timing of routine non-steroidal anti-inflammatory drug administration may be relevant to intraoperative nausea and vomiting management.

Stem cell therapies have shown promise in cerebral palsy (CP). However, their effects on brain metabolites, measured by proton magnetic resonance spectroscopy (1HMRS), remain unexplored. In this randomized clinical trial, we evaluated 1HMRS measures (N-acetyl aspartate [NAA], choline [Cho], creatine [Cr], myo-inositol [mI], NAA/Cho, and NAA/Cr) within periventricular white matter (PVWM) in children with CP at baseline and 12 months after a single intrathecal injection of umbilical cord-mesenchymal stem cells (UC-MSCs:20 × 106) or umbilical cord blood-mononuclear cells (UCB-MNCs:5 × 106/kg). Generalized Estimating Equations (GEEs) were employed to assess treatment efficacy, the adjusted effects of sex, CP type, and gestational age (GA) on post-treatment findings, and the association between metabolites and gross motor function measure (GMFM-66). Seventy-three participants were included: UCB-MNC (n = 27), UC-MSC (n = 26), and sham (n = 20). Primary analyses indicated no significant time*treatment interaction effects for any of the metabolites. In exploratory analyses, a significant CP type*treatment interaction was found for the post-intervention NAA/Cho (UC-MSC vs. sham; P-value = 0.02). Significant GA status*treatment interactions were also observed for post-intervention Cho (UC-MSC vs. sham; P-value = 0.009) and post-intervention mI (UCB-MNC vs. sham; P-value = 0.03). Additionally, longitudinal increases in NAA/Cr and NAA/Cho were positively associated with GMFM-66 improvement during the follow-up in UCB-MNC and UC-MSC groups, respectively, whereas Cho*time interaction was linked to smaller functional gains in the UCB-MNC group over time. Neither UC-MSC nor UCB-MNC had a significant overall effect on measured metabolite concentrations/ratios within the PVWM at 12 months following a single injection. Exploratory findings should be interpreted cautiously.Trial registration: The trial was registered in both the Iranian Registry of Clinical Trials (IRCT201706176907N13; registered on 12/07/2017) and ClinicalTrials.gov (NCT03795974; registered on 08/01/2019).

Autophagy is a crucial cellular degradation pathway that maintains homeostasis during stress. Preterm infants are exposed to significant oxidative and metabolic stress during the perinatal transition. This study aimed to evaluate the levels of autophagy markers (Beclin-1, LC3B-I and LC3B-II) in the umbilical cord blood of preterm infants and investigate their association with neonatal morbidities and mortality. This prospective multicentre cohort study included 60 preterm infants. Umbilical cord blood samples were analysed for Beclin-1, LC3B-I and LC3B-II levels using Western blot. The LC3B-I/LC3B-II ratio was calculated as an indicator of autophagic flux. The relationship between these markers and major neonatal outcomes (respiratory distress syndrome (RDS), intraventricular haemorrhage (IVH), haemodynamically significant patent ductus arteriosus (hsPDA), early neonatal sepsis (ENS) and mortality) was evaluated using Mann-Whitney U tests and multivariable logistic regression adjusted for gestational age. A significant positive correlation was observed between gestational age and Beclin-1 levels (r=0.406, p=0.005). In subgroup analyses, non-survivors exhibited significantly lower median Beclin-1 levels (0.45 vs 0.92, p=0.047) and a depressed LC3B-I/LC3B-II ratio (0.48 vs 1.90, p=0.018) compared with survivors. Similarly, infants with IVH had significantly lower LC3B-I levels (0.07 vs 0.65, p=0.011). However, in multivariable logistic regression analyses adjusted for gestational age, the independent statistical significance of these markers was attenuated, suggesting that the observed autophagic impairment is closely linked to gestational immaturity. No significant associations were found for RDS, hsPDA or ENS. This study identifies lower cord blood Beclin-1 levels and an altered LC3B ratio as potential markers of vulnerability in preterm infants, particularly for mortality and IVH. The findings suggest that autophagic capacity at birth is developmentally regulated, with more immature infants displaying compromised autophagy initiation.

Neonatal uterine bleeding (NUB) has been hypothesized as a relatively common early-life event potentially linked to the later development of endometriosis through retrograde menstruation. However, its true prevalence and biological nature remain uncertain. This study aimed to determine the prevalence, biological features, and maternal-neonatal correlates of reddish diaper staining in newborns, and to evaluate its purported association with endometriosis. A prospective cross-sectional study was conducted between September 2023 and March 2024 at a tertiary obstetric center with postpartum outpatient follow-up. A total of 638 pregnant women with singleton pregnancies (530 female and 108 male fetuses) were enrolled. Participants completed prenatal questionnaires, and neonatal outcomes, including diaper staining, were assessed during follow-up. Diapers with reddish staining were collected and analyzed using light microscopy and biochemical assays to identify the presence and origin of blood. Umbilical cord blood samples from female newborns were analyzed for steroid hormone concentrations. Reddish diaper staining was observed in 22% of female and 13% of male neonates. Only two female samples (2.5%) tested positive for menstrual blood. Most of the reddish diapers contained urate crystals rather than blood. Maternal characteristics, exposure to endocrine-disrupting factors, and cord blood steroid hormone levels did not differ significantly between female neonates with and without reddish diaper staining. These findings indicate that reddish diaper staining in neonates is predominantly due to urate crystal excretion rather than true NUB.By identifying a major and previously unrecognized confounder, this study calls into question a long-standing biological assumption and reshapes current understanding of NUB and its supposed link to endometriosis. Our results provide a substantial paradigm shift in the interpretation of this phenomenon, redefining its clinical and biological significance and opening new perspectives for research in early-life determinants of reproductive health.