MircoRNA-25-3p in skin precursor cell-induced Schwann cell-derived extracellular vesicles promotes axon regeneration by targeting Tgif1.

Nerve injury often leads to severe dysfunction because of the lack of axon regeneration in adult mammal. Intriguingly a series of extracellular vesicles (EVs) have the obvious ability to accelerate the nerve repair. However, the detailed molecular mechanisms to describe that EVs switch neuron from a transmitter to a regenerative state have not been elucidated. This study elucidated the microRNA (miRNA) expression profiles of two types of EVs that promote nerve regeneration. The functions of these miRNAs were screened in vitro. Among the 12 overlapping miRNAs, miR-25-3p was selected for further analysis as it markedly promoted axon regeneration both in vivo and in vitro. Furthermore, knockdown experiments confirmed that PTEN and Klf4, which are the major inhibitors of axon regeneration, were the direct targets of miR-25-3p in dorsal root ganglion (DRG) neurons. The utilization of luciferase reporter assays and functional tests provided evidence that miR-25-3p enhances axon regeneration by targeting Tgif1. Additionally, miR-25-3p upregulated the phosphorylation of Erk. Furthermore, Rapamycin modulated the expression of miR-25-3p in DRG neurons. Finally, the pro-axon regeneration effects of EVs were confirmed by overexpressing miR-25-3p and Tgif1 knockdown in the optic nerve crush model. Thus, the enrichment of miR-25-3p in EVs suggests that it regulates axon regeneration, proving a potential cell-free treatment strategy for nerve injury.

Infant Alstrom syndrome diagnosed by a new gene mutation: a case report.

Alstrom syndrome is a rare autosomal recessive disorder resulting from an ALMS1 gene mutation. Here, we present the clinical data of a case of an infant diagnosed with Alstrom syndrome through whole-exome sequencing. A 2-month-old male infant was admitted to Sichuan Provincial Maternity and Child Health Care Hospital on 30 May 2019 after "coughing for half a day and dyspnea for 2 hours". He was diagnosed with severe pneumonia, acute congestive heart failure, Grade III cardiac function, acute respiratory failure, and myocarditis. After treatment, he was discharged with a prescription for oral medication. After a 4-month follow-up, the patient's left ventricle exhibited spherical enlargement and a decrease in left ventricular function. The infant's whole-exome sequencing results revealed compound heterozygous mutations in the ALMS1 gene: c.2179dup (p. Y727Lfs*12), a frameshift mutation, that was heterozygous and originated from the mother, while c.11140C>T (p. Q3714*) was a heterozygous nonsense mutation that originated from the father. Both mutations are classified as "category 1-pathogenic mutations" according to the American College of Medical Genetics and Genomics (ACMG) assessment. A novel ALMS1 mutation was identified in this case report, highlighting the importance of genetic testing for the early diagnosis of Alstrom syndrome.

Association of Maternal Glucose Concentrations During Pregnancy With Cardiovascular Alterations in Early Childhood: A Prospective Birth Cohort Study.

BACKGROUND: Maternal hyperglycemia has been associated with cardiovascular disease risks in offspring. Previous studies were mostly conducted to test this association in pregnancies with (pre)gestational diabetes mellitus. However, the association may not be limited to populations with diabetes only. OBJECTIVES: The aim of this study was to assess the association between gestational glucose concentrations in women without (pre)gestational diabetes mellitus and childhood cardiovascular alterations at the age of 4 y. METHODS: Our study was based on the Shanghai Birth Cohort. Briefly, among 1016 nondiabetic mothers (age: 30.8 ± 3.42 y; BMI: 21.3 ± 2.94) and their offsprings (age: 4.41 ± 0.22 y; BMI: 15.0 ± 1.56; 53.0% males), results of maternal 1-h oral OGTT between 24 and 28 gestational weeks were obtained. Childhood blood pressure (BP) measurement, echocardiography, and vascular ultrasound were performed at 4 y old. Linear regression and binary logistic regression were conducted to test the association between maternal glucose and childhood cardiovascular outcomes. RESULTS: Compared with children from mothers with glucose concentrations in the lowest quartile, children from mothers in the highest quartile had higher BP (systolic: 97.0 ± 7.41 compared with 98.9 ± 7.82 mmHg, P = 0.006; diastolic: 56.8 ± 5.83 compared with 57.9 ± 6.03 mmHg, P = 0.051) and lower left ventricular ejection fraction (92.5 ± 9.15 compared with 90.8 ± 9.16 %, P = 0.046). Also, higher maternal OGTT 1-h glucose concentrations across the full range were associated with higher childhood BP (systolic: ß: 0.56; 95% CI: 0.19, 0.93; diastolic: ß: 0.36; 95% CI: 0.05, 0.66). Logistic regression showed, compared with children from mothers in the lowest quartile, children from mothers in the highest quartile had a 58% (OR=1.58; 95% CI: 1.01, 2.47) higher odds of elevated systolic BP (≥90th percentile). CONCLUSIONS: In a population without (pre)gestational diabetes mellitus, higher maternal OGTT 1-h glucose were associated with childhood cardiovascular structure and function alterations. Further studies are needed to assess whether interventions to reduce gestational glucose will mitigate subsequent cardiometabolic risks in offspring.

Maternal plasma perfluoroalkyl substances concentrations in early pregnancy and cardiovascular development in offspring: A prospective cohort study.

BACKGROUND: High maternal plasma perfluoroalkyl substances (PFAS) concentrations has been associated with adverse birth outcomes, but data on early childhood cardiovascular health is limited. This study aimed to assess the potential association between maternal plasma PFAS concentrations during early pregnancy and cardiovascular development in offspring. MATERIAL AND METHODS: Cardiovascular development was assessed through blood pressure measurement, echocardiography and carotid ultrasound examinations among 957 children from the Shanghai Birth Cohort aged at 4 years old. Maternal plasma concentrations of PFAS were measured at mean gestational age of 14.4 (SD:1.8) weeks. The joint associations between PFAS mixture concentrations and cardiovascular parameters were analyzed using a Bayesian kernel machine regression (BKMR). The potential association of individual PFAS chemicals concentrations was explored using multiple linear regression. RESULTS: In BKMR analyses, carotid intima media thickness (cIMT), interventricular septum thickness in diastole and systole, posterior wall thicknesses in diastole and systole, and relative wall thickness were significantly lower when all log10-transformed PFAS were fixed at 75th percentile in comparison to at their 50th percentile[Estimated overall Risk:-0.31 (95%CI: -0.42, -0.20), -0.09 (95%CI: -0.11, -0.07), -0.21 (95%CI: -0.26, -0.16), -0.09 (95%CI: -0.11, -0.07), -0.07 (95%CI: -0.10, -0.04) and -0.005 (95%CI: -0.006, -0.004)].Furthermore, maternal plasma concentrations of individual short-chain PFAS was associated with a decrease in left ventricular wall thickness, intraventricular septum thickness and enlarged chamber volume, and long-chain with a decrease in cIMT. CONCLUSIONS: Our findings suggest that maternal plasma PFAS concentrations during early pregnancy was adversely associated with cardiovascular development in offspring, including thinner cardiac wall thickness and cIMT.

Different Associations of Systolic Blood Pressure and Body Mass Index With Cardiac Structure and Function in Young Children.

BACKGROUND: Both elevated systolic blood pressure (SBP) and excess weight can lead to early cardiovascular organ damage in children. In this study, we investigated whether there is a difference in the associations of SBP and body mass index (BMI) with cardiovascular structure and function in 4-year-old children. METHODS: In 1474 children (52.3% males) from the Shanghai Birth Cohort, physical examination and echocardiography were performed. Standardized linear regression models were used to evaluate the associations of BMI Z score and SBP Z score with cardiovascular parameters and to compare the strengths of these associations. RESULTS: The incidence of SBP elevation significantly increased in overweight children. SBP was positively related to heart rate, left ventricular (LV) ejection fraction and fraction shortening (ß=1.824 [95% CI, 1.014-2.634], 0.579 [0.294-0.864], and 0.480 [0.257-0.704], respectively). BMI Z score was positively associated with LV mass index (ß=1.225 [0.863-1.587]) and the risk of LV hypertrophy (odds ratio=1.428 [1.157-1.761]) but negatively related to measures of systolic function, including LV ejection fraction, LV fraction short, and global longitudinal strain (ß=-0.417 [-0.735 to -0.099], -0.302 [-0.551 to -0.053], and -0.392 [-0.621 to -0.163], respectively). No noteworthy additive or multiplicative interactions between BMI and SBP were detected. CONCLUSIONS: Elevations in both BMI and SBP were related to cardiac structure and function in children as young as 4 years old. Elevated SBP was associated with increased heart rate and LV ejection at the early stage of BP elevation. BMI showed a closer relationship with left heart diameters and geometry than SBP.

Prenatal diagnosis and multidisciplinary management: a case report of congenital granular cell epulis and literature review.

Congenital granular cell epulis (CGCE) is a rare benign soft tissue lesion that usually originates from the neonatal gingiva and can lead to difficulty in breathing and feeding upon birth. This current case report describes a female newborn with a gingival mass that was identified by prenatal fetal ultrasonography. At birth, the oral mass was observed to protrude from the mouth, which adversely affected feeding. The lips could not be closed. The breathing was unaffected. Through a multidisciplinary team approach involving several healthcare professionals, the mass was successfully removed under general anaesthesia during an uncomplicated surgical procedure. Postoperative histopathological examination confirmed that the mass was a CGCE of the newborn. The infant recovered well after the operation.

Growth patterns in early childhood and cardiovascular structure and function at 4 years old: A prospective cohort study.

BACKGROUND AND AIMS: Childhood overweight and obesity are lifetime risk factors for cardiovascular disease but the relationship between dynamic body mass index (BMI) change and cardiovascular structure and function in early childhood remains unclear. METHODS AND RESULTS: This cohort study consisted 525 participants with 6 distinct representative growth patterns to examine the associations between BMI growth patterns and subsequent cardiovascular structure and function at age 4. BMIs were obtained at birth, 2 and 4 years old. Cardiovascular assessments were performed, including blood pressure (BP), cardiac geometric parameters, left ventricular (LV) function, speckle-tracking, integrated backscatter analysis and carotid intima-media thickness. Compared to the stable normal BMI pattern, children with the stable overweight (OW) pattern had significantly greater LV anatomic parameters in fully adjusted models. Children with the catch-up (CU) pattern revealed a uniform trend and had poorer strain. LV diameters and integrated backscatter signals were larger for those with BMI gain and lose pattern. Children with BMI lose pattern showed improved tendency involving LV mass index and BP. Both OW and CU patterns were associated with high systolic BP [odds ratio (95% CI): OW: 3.67 (1.08, 12.47); CU: 4.24 (1.75, 10.28)]. Compared to static BMI measurements at birth, 2 and 4 years old, dynamic BMI growth patterns were more predictive of cardiovascular structure and function at 4. CONCLUSIONS: Children with overweight-related BMI growth patterns in early childhood experienced undesirable cardiovascular functional or structural changes as early as 4 years old, indicating that early intervention is needed and potentially beneficial.

Association of Maternal Gestational Weight Gain With Left Ventricle Geometry and Function in Offspring at 4 Years of Age: A Prospective Birth Cohort Study.

Background: Maternal gestational weight gain (GWG) may be associated with cardiovascular diseases in the offspring from childhood to adulthood. We aimed to investigate the association between maternal GWG and the left ventricle (LV) geometry and function in the offspring, and explore the influence of the intrauterine environment on early childhood cardiac change. Methods: Data of 981 mother-offspring pairs from the Shanghai Birth Cohort was used. Maternal pre-pregnancy weight and height, weight in the first trimester (≤ 12 weeks), and before delivery were measured. The echocardiography, blood pressure, and anthropometry assessment were evaluated in the offspring at 4 years of age. Results: Interventricular septal thickness during diastole had a significantly positive correlation with total GWG [ß = 0.009, (0.001, 0.017)]. In the second and third trimesters, LV mass index [ß = 0.149, (0.015,0.282)], interventricular septal thickness in systole [ß = 0.027, (0.011,0.043)], and in diastole [ß = 0.014, (0.005,0.023)] were positively associated with GWG. The risks of eccentric [OR = 1.115, (1.232, 1.010)] and concentric hypertrophy [OR = 1.133, (1.259,1.018)] increased with the elevation of maternal GWG. Conclusions: This study suggested that the excessive maternal GWG was associated with the thickening of the interventricular septum in the offspring, especially during the second and third trimesters. Excessive GWG in the second and third trimesters was a risk factor for LV eccentric and concentric hypertrophy in the offspring.

Is echocardiography necessary for all single umbilical artery fetuses? A retrospective study in a selected Chinese population.

AIM: Previous evidence on the relationship between single umbilical artery (SUA) and congenital heart disease (CHD) is controversial. We thus conducted a retrospective study to explore the potential risk factors associated with CHD in SUA fetuses, and verify if all these SUA fetuses should be referred for detail fetal echocardiography. METHODS: We reviewed medical records of SUA fetuses referred to Xinhua Hospital for fetal echocardiography between September 2009 and February 2014. All the pregnancies were divided into two groups of CHD and non-CHD according to the results of fetal echocardiography. The maternal and fetal characteristics were compared via χ2 test and Fishers' test. Furthermore, Poisson regression was used to analyze the risk factors associated with CHD in SUA pregnancies. RESULTS: Nineteen CHD cases (12.5%) were detected among 152 SUA fetuses, all with abnormal cardiac views during obstetric screening ultrasound (P < 0.001). χ2 test showed that abnormal cardiac screening findings, extracardiac abnormality and infection or threatened abortion during first trimester were significantly associated with prenatal detection of CHD (P < 0.001). Multivariable Poisson regression after adjustment found that SUA fetuses with extracardiac abnormality had 4.74 (95% confidence interval: 1.89, 11.90) times higher risk of CHD. CONCLUSION: Incidence of CHD was higher in SUA cases, and CHD fetuses could be screened efficiently by abnormal cardiac screening during obstetric screening ultrasound. SUA fetuses with extracardiac abnormality and maternal risk factors have higher risk of CHD, and should be strongly recommended for fetal echocardiography. In contrast, SUA fetuses without above situations might only need routine obstetric follow-up.