Association between platelet counts and clinical outcomes in acute fatty liver of pregnancy: A retrospective cohort study.

OBJECTIVES: To investigate whether platelet counts are associated with clinical outcomes in patients with acute fatty liver of pregnancy (AFLP). METHODS: We retrospectively analyzed 140 patients with AFLP admitted to the Third Affiliated Hospital of Guangzhou Medical University between January 2010 and August 2022. In this cohort study, we used smooth curve fitting, Kaplan-Meier analysis, and multivariable logistic regression analysis to examine the independent relationship between platelet counts and 42-day postpartum mortality in AFLP. RESULTS: There were 140 patients with AFLP, of which 15 died and 53 (37.86%) had thrombocytopenia. The overall 42-day postpartum maternal mortality was 10.7%. We observed a U-shaped relationship between the platelet counts and 42-day postpartum mortality. Two different slopes were observed below and above the inflection point at approximately 220 × 109 /L. After adjusting for some confounders, patients with thrombocytopenia (<100 × 109 /L) were found to have increased 42-day postpartum mortality compared with middle-tertile and highest-tertile patients. Patients with thrombocytopenia had a higher 42-day postpartum mortality, and higher proportions of intensive care unit admissions, postpartum hemorrhage, and multiple organ failure (P < 0.05). CONCLUSIONS: A U-shaped association between platelet counts and 42-day postpartum mortality was observed in patients with AFLP. Thrombocytopenia is associated with poorer adverse clinical outcomes in women with AFLP.

Vascular endothelial growth factor induces the migration of human airway smooth muscle cells by activating the RhoA/ROCK pathway.

BACKGROUND: Airway remodeling due to increased airway smooth muscle cell (ASMC) mass, likely due to enhanced proliferation, hypertrophy, and migration, has been proven to be highly correlated with decreased lung function in asthma patients. Vascular endothelial growth factor (VEGF) mediates vascular and extravascular remodeling and inflammation and has been proven to be involved in the progression of asthma. Previous studies have focused on the effects of VEGF on ASMC proliferation, but few researchers have focused on the effects of VEGF on human ASMC migration. The purpose of this study was to explore the effect of VEGF on the migration of ASMCs and its related signaling pathway mechanism to provide evidence for the treatment of airway remodeling. METHODS: We examined the effects of VEGF induction on ASMC migration and explored the mechanisms involved in ASMC migration. RESULTS: We found by wound healing and Transwell assays that VEGF promoted ASMC migration. Through the Cell Counting Kit-8 (CCK-8) experiment, we found that VEGF had no significant effect on the proliferation of ASMCs, which excluded the involvement of cell proliferation in the process of wound healing. Moreover, a cellular immunofluorescence assay showed that VEGF promoted F-actin reorganization, and Western blotting showed that VEGF improved RhoA activation and myosin phosphatase targeting subunit-1 (MYPT1) and myosin light chain (MLC) phosphorylation in ASMCs. Treatment with the ROCK inhibitor Y27632 significantly attenuated the effects of VEGF on MYPT1/MLC activation and cell migration. CONCLUSION: In conclusion, the results suggest that the promigratory function of VEGF activates the RhoA/ROCK pathway, induces F-actin reorganization, improves the migration of ASMCs, and provides a better rationale for targeting the RhoA/ROCK pathway for therapeutic approaches in airway remodeling.

Maternal and fetal/neonatal outcomes of pregnancies complicated by pulmonary hypertension: a retrospective study of 154 patients.

OBJECTIVES: To determine the main clinical and demographic outcomes related to Pulmonary Hypertension (PH) and adverse obstetric and fetal/neonatal outcomes. METHODS: This study retrospectively analyzed the medical record data of 154 patients with PH who were admitted to the Third Affiliated Hospital of Guangzhou Medical University between January 2011 and December 2020. RESULTS: According to the severity of elevated Pulmonary Artery Systolic Pressure (PASP), 82 women (53.2%) were included in the mild PH group, 34 (22.1%) were included in the moderate PH group, and 38 (24.7%) were included in the severe PH group. There were significant differences in the incidence of heart failure, premature delivery, Very-Low-Birth-Weight (VLBW) infants, and Small-for-Gestational-Age (SGA) infants among the three PH groups (p < 0.05). Five (3.2%) women died within 7-days after delivery, 7 (4.5%) fetuses died in utero, and 3 (1.9%) neonates died. The authors found that PASP was an independent risk factor for maternal mortality. After adjustment for age, gestational weeks, systolic blood pressure, Body Mass Index (BMI), mode of delivery, and anesthesia, the risk of maternal mortality in the severe PH group was 20.21 times higher than that in the mild-moderate PH group (OR = 21.21 [95% CI 1.7∼264.17]), p < 0.05. All 131 (85.1%) patients were followed up for 12 months postpartum. CONCLUSIONS: The authors found that the risk of maternal mortality in the severe PH group was significantly higher than that in the mild-moderate group, highlighting the importance of pulmonary artery pressure screening before pregnancy, early advice on contraception, and multidisciplinary care.

Pregnancy outcomes in women with pulmonary hypertension: a retrospective study in China.

BACKGROUND: In recent years, with the development of monitoring conditions and the application of pulmonary vascular-targeted drugs, pregnancy outcomes in women with pulmonary hypertension (PH) have improved, but the maternal mortality rate is still high. The purpose of this study was to describe the maternal-foetal outcomes in pregnant women with PH. METHODS: The clinical data of 154 pregnant women with PH who were admitted to the Third Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2020 were collected and descriptively analysed. RESULTS: Among the 154 pregnant women with PH, 6 (3.9%) had idiopathic pulmonary arterial hypertension (iPAH), 41 (26.6%) had pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH), 45 (29.2%) had PAH related to other diseases (oPAH), and 62 (40.3%) had PH related to left heart disease (LHD-PH). The systolic pulmonary artery pressure (sPAP) was 36-49 mmHg in 53.2% of the patients, 50-69 mmHg in 22.1% of the patients and ≥ 70 mmHg in 24.7% of the patients. Five (3.2%) pregnant women died within 1 week after delivery; iPAH patients had the highest mortality rate (3/6, 50%). Fifty-four patients (35.1%) were admitted to the intensive care unit (ICU), and the incidence of heart failure during pregnancy was 14.9%. A total of 70.1% of the patients underwent caesarean section; 42.9% had premature infants; 28.6% had low-birth-weight (LBW) infants; 13.0% had very-low-birth-weight (VLBW) infants; 3.2% had extremely-low-birth-weight (ELBW) infants; 61% had small for gestational age (SGA) infants; and 1.9% experienced neonatal mortality. CONCLUSION: There were significant differences in the maternal-foetal outcomes in the iPAH, CHD-PAH, oPAH and LHD-PH groups. Maternal mortality was highest in the iPAH group; therefore, iPAH patients should be advised to prevent pregnancy. Standardized and multidiscipline-assisted maternal management is the key to improving maternal-foetal outcomes.

Maternal and fetal/neonatal outcomes of pregnancies complicated by pulmonary hypertension: a retrospective study of 154 patients

Abstract Objectives: To determine the main clinical and demographic outcomes related to Pulmonary Hypertension (PH) and adverse obstetric and fetal/neonatal outcomes. Methods: This study retrospectively analyzed the medical record data of 154 patients with PH who were admitted to the Third Affiliated Hospital of Guangzhou Medical University between January 2011 and December 2020. Results: According to the severity of elevated Pulmonary Artery Systolic Pressure (PASP), 82 women (53.2%) were included in the mild PH group, 34 (22.1%) were included in the moderate PH group, and 38 (24.7%) were included in the severe PH group. There were significant differences in the incidence of heart failure, premature delivery, Very-Low-Birth-Weight (VLBW) infants, and Small-for-Gestational-Age (SGA) infants among the three PH groups (p < 0.05). Five (3.2%) women died within 7-days after delivery, 7 (4.5%) fetuses died in utero, and 3 (1.9%) neonates died. The authors found that PASP was an independent risk factor for maternal mortality. After adjustment for age, gestational weeks, systolic blood pressure, Body Mass Index (BMI), mode of delivery, and anesthesia, the risk of maternal mortality in the severe PH group was 20.21 times higher than that in the mildmoderate PH group (OR = 21.21 [95% CI 1.7~264.17]), p < 0.05. All 131 (85.1%) patients were followed up for 12 months postpartum. Conclusions: The authors found that the risk of maternal mortality in the severe PH group was significantly higher than that in the mild-moderate group, highlighting the importance of pulmonary artery pressure screening before pregnancy, early advice on contraception, and multidisciplinary care.

Effects of Different Intervention Factors on Vascular Endothelial Growth Factor-Induced Human Airway Smooth Muscle Cell Migration.

Background: Asthma airway remodeling is closely related to the abnormal migration of human airway smooth muscle cells (ASMCs), and vascular endothelial growth factor (VEGF) is involved in the pathophysiological process of asthma. This study aimed to investigate the effect of VEGF on ASMC migration through in vitro cell experiments and to intervene in ASMC migration with different asthma drugs and signaling pathway inhibitors to provide a basis for screening effective drugs for airway remodeling. Methods: The effect of VEGF on the proliferation of ASMCs was detected by the CCK-8 method, and the effect of VEGF on the migration of ASMCs was proven by scratch and transwell assays. Different asthma drugs and signaling pathway inhibitors were used to interfere with the migration of ASMCs. The number of migrating cells was compared between the intervention and nonintervention groups. Results: Our results showed that VEGF induction enhanced ASMC migration; pretreatment with the commonly used asthma drugs (salbutamol, budesonide, and ipratropium bromide) significantly attenuated VEGF-induced ASMC migration; and inhibitors SB203580, LY294002, and Y27632 blocked the VEGF-induced activation of p38 MAPK, PI3K, and ROCK signaling pathway targets in ASMCs and inhibited migration. Conclusion: This study shows that the current commonly used asthma drugs salbutamol, budesonide, and ipratropium have potential value in the treatment of airway remodeling, and the p38 MAPK, PI3K, and ROCK signaling pathway targets are involved in the VEGF-induced ASMC migration process. Signaling pathway inhibitor drugs may be a new way to treat asthma-induced airway remodeling in asthma patients in the future. However, the related mechanism and safety profile still need further research.