The role of myeloid differentiation of hematopoietic stem cells in pregnancy immunological tolerance: a systematic review.

The present research aimed to conduct a comprehensive critical analysis of existing literature, focusing on the differentiation of myeloid cells from hematopoietic stem cells within the context of immunological tolerance during pregnancy. A comprehensive systematic review was conducted by searching databases including PubMed, Scopus Biomedicine, EBSCOhost, ScienceDirect, Embase, Cochrane Library, and Web of Science. The focus was on the role of myeloid differentiation from hematopoietic stem cells in modulating immune tolerance, particularly during pregnancy and in certain disease states where they act to suppress the immune response. The quality of the evidence gathered was assessed using the GRADE rating system. Our analysis maintains objectivity and independence from the outcomes presented. The current systematic review offers a synthesis of existing research on the transformation of hematopoietic stem cells into fibroblasts across different tissue types. A thorough search of databases such as PubMed, EBSCOhost, Embase, ScienceDirect, Cochrane Library, and Web of Science was performed in conjunction with a specialist in medical information to identify original research on the derivation of fibroblasts following hematopoietic stem cell transplantation. This search yielded a total of 159 studies, of which 10 met the criteria for inclusion in this review. Reflecting on the constraints of this preliminary review, further in-depth and scientific investigations are warranted to comprehensively assess the impact of varied treatments, with a recommendation for clinicians to proceed with increased circumspection. The myeloid differentiation pathway of hematopoietic stem cells is pivotal in modulating the immune environment during pregnancy, supporting the sustenance of a healthy gestational period. Future research in this domain is expected to advance our understanding of the immunological processes occurring at the maternal-fetal boundary.

sFlt-1/PIGF ratio positive associated with non-dipper type change in ambulatory blood pressure monitoring(ABPM) for preeclampsia development.

In order to explore relationship of ambulatory blood pressure monitoring (ABPM) and soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) in suspected preeclampsia(PE), suspected PE participants in 28 + 0 to 33 + 6 weeks underwent ABPM and sFlt-1/PlGF from July 2020 to July 2022 were included(N = 476) in study. ABPM parameters were compared between sFlt-1/PlGF ≥38 and <38 groups. Correlation analysis was performed between ABPM and sFlt-1/PlGF, and logistic regression was used to explore prediction value for PE in 2 weeks. One hundred eighteen cases developed PE in 2 weeks with 114 from sFlt-1/PlGF ≥38 group. Daytime and nighttime BP were all increased,with increased non-dipper (58.4% vs. 30.3%), riser (22.1% vs. 13.1%) and and decreased Dipper (15.4% vs. 45.9%) type of ABPM in sFlt-1/PlGF ≥38 groups (P < 0.05).The riser group had the highest sFlt-1 and lowest PlGF. sFlt-1/PlGF and sFlt-1 were all positively correlated with systolic (SBP) & diastolic blood pressure(DBP)(P < 0.01), in which correlation coefficients of daytime and nighttime BP with sFlt-1 were ß = 150.05 & 157.67 for SBP, ß = 234 and 199.01 for DBP, respectively. However, PlGF was only negatively associated with nighttime SBP and DBP(P < 0.05), with no correlation with daytime BP (P > 0.05).Combining sFlt-1/PlGF and ABPM model, showed sFlt-1/PlGF (aOR = 2.01 (1.69-2.36)), Nighttime DBP (aOR = 1.14 (1.02-1.28)) contributed to preeclampsia prediction, and had improved predictive value compared to ABPM or sFlt-1/PlGF models alone(P < 0.05). sFlt-1/PlGF ratio was positively correlated with BP parameters, whereas PIGF was only negatively correlated with nocturnal BP and increased non-dipper type change in ABPM, which had a synergistic effect with sFlt-1/PlGF on PE prediction.

[Factors and neonatal outcomes associated with histologic chorioamnionitis after premature rupture of membranes in the preterms].

OBJECTIVE: To investigate factors and neonatal outcomes associated with histologic chorioamnionitis (HCA) in preterm premature rupture of membranes (PPROM). METHODS: From Jan. 2008 to Jun. 2011, 230 women with PPROM at 28 - 33(+6) weeks of gestation undergoing deliveries in the Second Affiliated Hospital of Wenzhou Medical College were studied retrospectively. According to placental histopathologic findings, those patients were categorized into two groups, including 138 cases in histologic chorioamnionitis (HCA group) and 65 cases in non-chorioamnionitis (control) group. Age, parity, gestational age of PPROM and delivery, latency period, oligohydramnios, white blood cell (WBC) count and serum C-reactive protein (CRP) level at admission and before delivery, the incidence of neonatal respiratory distress syndrome (NRDS), neonatal pneumonia, bronchopulmonary dysplasia, necrotizing enterocolitis, early-onset neonatal sepsis, abnormal brain sonography findings and mortality were compared between two groups. RESULTS: (1) The incidence of HCA was 68.0% (138/203) in all 203 cases with PPROM. (2) The occurring ruptured membrane gestation in HCA group was (31.1 ± 1.5) weeks, which were significantly earlier than (32.0 ± 1.3) weeks in control group (P < 0.05). The level of CRP of (8.2 ± 14.9) mg/L before delivery in HCA group was significantly higher than (5.5 ± 7.2) mg/L in control group (P < 0.05). The rate of oligohydramnios and cesearean sections were 55.1% (76/138) and 45.7% (63/138) in HCA group, which were significantly higher than 30.8% (20/65) and 29.2% (19/65) in control group (P < 0.05). There were no significant difference in patient's age, parity, WBC count and CRP at admission between two groups (P > 0.05). The latency period did not show significant difference between (140 ± 116) hours in HCA group and (129 ± 125) hours in control group (P > 0.05). (3) Using multivariable logistic regression models, oligohydramnios (OR = 2.937), gestational age of PPROM < 32 weeks (OR = 2.352), serum CRP level > 8 mg/L before delivery (OR = 4.923) and latency period > 48 - 168 hours (OR = 4.439) were significantly associated with HCA (P < 0.05). (4) The gestational age of delivery and birth weight of HCA group were significantly lower than those of control group [(32.0 ± 1.5) weeks vs. (32.7 ± 1.5) weeks, (1680 ± 379) g vs. (2017 ± 333) g, respectively, P < 0.05]. The incidence of Apgar < 7, abnormal brain sonograhy findings, neonatal pneumonia, bronchopulmonary dysplasia, early-onset neonatal sepsis and mortality in HCA group were significantly higher than those in control group [20.3% (28/138) vs. 7.7% (5/65), 14.5% (20/138) vs. 4.6% (3/65), 12.3% (17/138) vs. 3.1% (2/65), 5.8% (8/138) vs. 0, 6.5% (9/138) vs. 0, 12.3% (17/138) vs. 3.1% (2/65), respectively, P < 0.05]. The incidence of necrotizing enterocolitis (1.5%, 2/138) in HCA group was higher than that of control group (0) and the incidence of NRDS (18.8%, 26/138) in HCA group did not show statistical difference with 21.4% (14/65) in control group (P > 0.05). CONCLUSIONS: It was found that HCA was significantly correlated with lower gestational age of PPROM, higher serum CRP level before delivery, prolonged latency period and oligohydramnios in PPROM. HCA could increase the neonatal morbidity and mortality.

Maternal-fetal fluid balance and aquaporins: from molecule to physiology.

Maternal-fetal fluid balance is critical during pregnancy, and amniotic fluid is essential for fetal growth and development. The placenta plays a key role in a successful pregnancy as the interface between the mother and her fetus. Aquaporins (AQPs) form specific water channels that allow the rapid transcellular movement of water in response to osmotic/hydrostatic pressure gradients. AQPs expression in the placenta and fetal membranes may play important roles in the maternal-fetal fluid balance.

[Clinical outcomes and characteristics of concurrent eclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome].

OBJECTIVE: the purpose was to describe the outcomes and characteristics of the obstetric patients with concurrent eclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP) syndrome. METHODS: we retrospectively collected the materials between December 1999 and December 2008 in Obstetric Critical Care Center of Guangzhou. There were 76 patients in rolled then they were divided into two groups according to with or without HELLP syndrome. All the patients were injected Magnesium Sulfate to control seizure and to prevent the recurring of seizure. We analyzed the characteristics (such as age, gestational weeks, blood pressure after seizure), complications, biochemistry markers, the rate for intensive care unit (ICU) admittion, the need for mechanical ventilation, the Glasgow coma score (GCS) when admitted into ICU, computed tomography scan (CT) or magnetic resonance imaging (MRI), death rate of maternal and others, then compared between the two groups. RESULTS: (1) general data: There were 17 patients admitted with both eclampsia and HELLP syndrome, and 59 patients admitted eclampsia without HELLP syndrome. The incidence of eclampsia with HELLP syndrome was 22% (17/76). In eclampsia with HELLP syndrome group, the systolic blood pressure was higher and the rate of preterm also was higher [(182 ± 20) mm Hg (1 mm Hg = 0.133 kPa) vs. (159 ± 21) mm Hg, P < 0.05]. But in regard to the age, gestational weeks, the rate of regular prenatal care and diastolic blood pressure, there were no differences between the two groups. (2) Biochemistry markers: the aspartate transaminase (AST), lanine transaminase (ALT), blood urea nitrogen and creatinine were significantly increased in eclampsia with HELLP syndrome group than eclampsia without HELLP syndrome group [(879 ± 337) U/L vs. (90 ± 27) U/L, (344 ± 83) U/L vs. (43 ± 11)U/L, (2245 ± 294) U/L vs. (485 ± 61) U/L, (14 ± 9) mmol/L vs. (7 ± 3) mmol/L, (140 ± 92) µmol/L vs. (83 ± 28) µmol/L, P < 0.01, P < 0.05], and the platelet was lower in eclampsia with HELLP syndrome group [(38 ± 13) × 10(9)/L vs (172 ± 46) × 10(9)/L, P < 0.01]. (3) Clinical outcomes: The maternal death rate was 35% (6/17) in eclampsia with HELLP syndrome patients, and significantly higher than the rate in eclampsia without HELLP syndrome group (3%, 2/59) (P < 0.05). There were more patients admitted to ICU and more patients who need mechanical ventilation in eclampsia with HELLP syndrome (13/17 vs. 34%, 9/17 vs. 24/, P < 0.05), also more patients with GCS ≤ 8 in eclampsia with HELLP syndrome when admitted to ICU (8/17 vs. 7/59, P < 0.05), compared to the eclampsia without HELLP syndrome group. There were more patients complicated with cerebral venous thrombosis and cerebral hemorrhage in eclampsia with HELLP syndrome group than other group (8/17 vs. 7%, P < 0.05). Five of six patients died of cerebral hemorrhage in eclampsia with HELLP syndrome group, while other two missing cases in eclampsia without HELLP syndrome group all died of cerebral hemorrhage. The all missing cases were performed CT or MRI and seven (7/8) of them showed cerebral hemorrhage. CONCLUSION: the incidence of concurrent eclampsia and HELLP syndrome was not rare, it happened seriously and with more mortalities, such as cerebral hemorrhage, and also the maternal mortality rate was significantly higher. It should be warning that the obstetrician should take great attention for these women, and consider life support treatment for them.

Cyclosporin A ameliorates eclampsia seizure through reducing systemic inflammation in an eclampsia-like rat model.

Our previous studies have shown that the maternal hyperinflammatory response in pre-eclampsia lowered the eclampsia-like seizure threshold. Cyclosporin A (CsA), which is an effective immunosuppressant, could attenuate the inflammatory responses in LPS-induced pre-eclampsia rats. Here, we hypothesized that CsA may ameliorate seizure severity through reducing systemic inflammation in pre-eclampsia/eclampsia. In the current study, the effects of CsA on pre-eclampsia manifestation, eclampsia-like seizure activities and systemic inflammation were examined in a pre-eclampsia model. Pregnant rats were given an intraperitoneal injection of the epileptogenic drug pentylenetetrazol (PTZ) following a tail vein injection of lipopolysaccharide to establish the eclampsia-like seizure model. CsA (5 mg/kg) was administered intravenously through the tail after LPS infusion. Mean systolic blood pressure and proteinuria in pre-eclampsia were detected. After PTZ injection, seizure activity was assessed, inflammatory responses were determined and pregnancy outcomes were analyzed. The results showed that CsA treatment significantly decreased blood pressure and proteinuria and increased the fetal and placental weight (P < 0.01). Meanwhile, CsA treatment significantly reduced serum IL-1ß, TNF-α, and IL-17 levels (P < 0.01), decreased the seizure scores and prolonged the latency to seizure (P < 0.01). CsA effectively attenuated pre-eclampsia manifestation and eclampsia-like seizure severity. In addition, CsA treatment significantly reduced the inflammatory cytokine levels and improved pregnancy outcomes following eclampsia-like seizures. The decreased inflammatory cytokines in pre-eclampsia are coincident with attenuated pre-eclampsia manifestation after CsA treatment, suggesting that CsA treatment might decrease the eclampsia-like seizure severity through decreasing systemic inflammation in pre-eclasmpsia/eclampsia.

Evaluation of cervical maturity by cervical collagen measurement using light-induced fluorescence (LIF) during pregnancy.

OBJECTIVE: The study aimed to evaluate cervical ripening by measuring cervical collagen levels in non-pregnant women, women with a normal pregnancy, and postpartum women by light-induced fluorescence (LIF). METHODS: Cervical collagen content in normal pregnant women (n = 165) at various times of gestation was measured by LIF with a collascope, which is specifically designed to measure fluorescence of collagen. Cervical LIF in non-pregnant women (n = 12) and postpartum women (n = 14) was also detected. The demographic characteristics of women at various times were recorded. The Bishop score at 40 to 41 gestational weeks (n = 37) before the onset of labor was analyzed. RESULTS: Cervical LIF values progressively declined from the non-pregnant state to late gestation (R = -0.836) and reached their lowest levels during parturition and then increased at postpartum. LIF values and the Bishop score were significantly negatively correlated (R = -0.83). In patients with a Bishop score ≥6, the first stage of labor was shortened with a decrease in LIF values (R = 0.718). CONCLUSIONS: Cervical collagen levels as measured by LIF could be a useful method for evaluating cervical maturity.

Neuroimaging findings in women who develop neurologic symptoms in severe preeclampsia with or without eclampsia.

Eclampsia is a leading cause of maternal and fetal morbidity and mortality worldwide, and its pathogenesis remains elusive. Our objective was to investigate neuroimaging findings in women who developed neurologic symptoms in severe preeclampsia with or without eclampsia to further understand the relationship between neuroimaging findings and the pathogenesis of eclamptic seizures. This retrospective study included 79 women with severe preeclampsia/eclampsia who underwent brain MRI/CT examination between 2005 and 2017. We analyzed imaging findings, clinical data, and laboratory data in order to compare patients with severe preeclampsia to those with eclampsia and patients with abnormal imaging findings to those with normal CT or MRI. A total of 41 of 79 women were diagnosed with eclampsia, 36 (88.80%) of which had abnormal neuroimaging findings, including cerebral edema (19 cases), infarction (5 cases), cerebral venous thrombosis (5 cases), and cerebral hemorrhage (7 cases). Five patients died of cerebral hemorrhage. Of the 38 cases of severe preeclampsia, 21 (55.26%) cases had abnormal imaging findings, including cerebral edema (20 cases), and 1 case had cerebral hemorrhage. Serum uric acid was significantly higher in patients with abnormal imaging findings than in patients without them (P = 0.004). The imaging findings in women with neurologic symptoms were similar between the severe preeclampsia and eclampsia groups. Our results suggest that eclampsia may not be a diagnosis with a unique pathogenesis; rather, it may be best considered a severe symptom of the intracranial pathophysiology of preeclampsia. We suggest that cranial imaging should be performed early in the management of patients with severe preeclampsia who develop new neurologic symptoms.

Magnesium Sulfate Provides Neuroprotection in Eclampsia-Like Seizure Model by Ameliorating Neuroinflammation and Brain Edema.

Eclampsia is a hypertensive disorder of pregnancy that is defined by the new onset of grand mal seizures on the basis of preeclampsia and a leading cause of maternal and fetal mortality worldwide. Presently, magnesium sulfate (MgSO4) is the most effective treatment, but the mechanism by which MgSO4 prevents eclampsia has yet to be fully elucidated. We previously showed that systemic inflammation decreases the seizure threshold in a rat eclampsia-like model, and MgSO4 treatment can decrease systemic inflammation. Here, we hypothesized that MgSO4 plays a neuroprotective role in eclampsia by reducing neuroinflammation and brain edema. Pregnant Sprague-Dawley rats were given an intraperitoneal injection of pentylenetetrazol following a tail vein injection of lipopolysaccharide to establish the eclampsia-like seizure model. Seizure activity was assessed by behavioral testing. Neuronal loss in the hippocampal CA1 region (CA1) was detected by Nissl staining. Cerebrospinal fluid levels of S100-B and ferritin, indicators of neuroinflammation, were detected by enzyme-linked immunosorbent assay, and ionized calcium binder adapter molecule 1 (Iba-1, a marker for microglia) and glial fibrillary acid protein (GFAP, a marker for astrocytes) expression in the CA1 area was determined by immunofluorescence staining. Brain edema was measured. Our results revealed that MgSO4 effectively attenuated seizure severity and CA1 neuronal loss. In addition, MgSO4 significantly reduced cerebrospinal fluid levels of S100-B and ferritin, Iba-1 and GFAP activation in the CA1 area, and brain edema. Our results indicate that MgSO4 plays a neuroprotective role against eclampsia-like seizure by reducing neuroinflammation and brain edema.

Decreased seizure threshold in an eclampsia-like model induced in pregnant rats with lipopolysaccharide and pentylenetetrazol treatments.

OBJECTIVE: Eclampsia is a poorly understood but potentially fatal complication of pregnancy. Research to date on this disorder has been hampered by the lack of a suitable animal model. To correct this deficiency, this report describes the generation of a rat eclampsia-like model using pentylenetetrazol (PTZ) in a previously established rat preeclampsia model. METHOD: Rats were administered lipopolysaccharide (1.0 µg/kg) by tail vein injection on gestational day 14 to establish preeclampsia (PE). PE and control rats (non-pregnant, NP; normal-pregnant, P) were injected intraperitoneally (i.p.) with PTZ (40 mg/kg) to induce seizures. In separate experiments, MgSO4 (270 mg/kg IP) was injected in advance of PTZ into PE rats to observe its effect on PTZ-induced seizures. RESULTS: PE conditions were verified in rats after LPS administration by significantly higher blood pressure (P<0.01) and urinary albumin excretion (P<0.05), elevated sFlt-1 (P<0.05) and decreased PlGF serum levels (P<0.05), and evidence of hepatic dysfunction compared to control groups. PTZ successfully induced seizure activity in all groups studied. Latency to seizure was significantly (P<0.01) less in the PE-PTZ group (73.2 ± 6.6 sec.) than in PTZ-treated controls (107.0 ± 7.4 sec.). Pretreatment with MgSO4 prolonged (P<0.05) latency to seizure, shortened seizure duration and decreased seizure rates. Significant increased (P<0.05) in the serum levels of the inflammatory cytokines TNF-α and IL-1ß in PE and PE-PTZ groups, and decreased (P<0.05) in their levels following MgSO4 administration. CONCLUSION: This PTZ-induced eclampsia-like rat model is comparable to the human condition of eclampsia and may serve as a useful research tool for future studies of this disease. The increased inflammatory cytokines in preeclampsia are coincident with a decreased threshold for PTZ-induced seizures, suggesting that an inflammatory mechanism may contribute to the susceptibility to seizure activity and inflammation might have an important role in eclampsia.