Development and validation of a nomogram for predicting the prognosis in children with spinal cord injuries.

AIMS: This research aims to construct and verify an accurate nomogram for forecasting the 3-, 5-, and 7-year outcomes in pediatric patients afflicted with spinal cord injury (SCI). METHODS: Pediatric patients with SCI from multiple hospitals in China, diagnosed between Jan 2005 and Jan 2020, were incorporated into this research. Half of these patients were arbitrarily chosen for training sets, and the other half were designated for external validation sets. The Cox hazard model was employed to pinpoint potential prognosis determinants related to the American Spinal Injury Association (ASIA) and Functional Independence Assessment (FIM) index. These determinants were then employed to formulate the prognostic nomogram. Subsequently, the bootstrap technique was applied to validate the derived model internally. RESULTS: In total, 224 children with SCI were considered for the final evaluation, having a median monitoring duration of 68.0 months. The predictive nomogram showcased superior differentiation capabilities, yielding a refined C-index of 0.924 (95% CI: 0.883-0.965) for the training cohort and a C-index of 0.863 (95% CI: 0.735-0.933) for the external verification group. Additionally, when applying the aforementioned model to prognostic predictions as classified by the FIM, it demonstrated a high predictive value with a C-index of 0.908 (95% CI: 0.863-0.953). Moreover, the calibration diagrams indicated a consistent match between the projected and genuine ASIA outcomes across both sets. CONCLUSION: The crafted and verified prognostic nomogram emerges as a dependable instrument to foresee the 3-, 5-, and 7-year ASIA and FIM outcomes for children suffering from SCI.

Analysis of the association between the acetabular morphology and femoral head in children aged 0-3 years with developmental hip dysplasia.

Background: Magnetic resonance imaging (MRI) has been advocated as a routine examination for preoperative and postoperative assessment of Developmental Dysplasia of the Hip (DDH). However, there is limited research regarding the correlation between acetabulum and femoral head morphology using preoperative MRI measurements. Objective: To explore the correlation between acetabulum and femoral head morphology in children with DDH aged 0-3 years, using MRI measurements as indicators. Methods: A Retrospective Analysis of MRI Data from 172 Children Diagnosed with Developmental Dysplasia of the Hip (DDH) at Nanjing Medical University Affiliated Children's Hospital, spanning from January 2017 to January 2022. Measurements were taken to assess various parameters reflecting hip socket morphology as well as the development status of the femoral head and ossifying nucleus. The correlation between these factors was explored using Pearson correlation analysis and multiple-factor linear regression. Statistical analysis was conducted using SPSS 18.0 software. Results: Pearson correlation analysis revealed statistically significant associations between the length of the ossifying nucleus ratio and age(mo.), BAI, BCAD, CTAD, and CTAD. The height of the ossifying nucleus ratio displayed statistically significant correlations with age(mo.) and BTAD. The length of the femoral head ratio exhibited statistically significant correlations with CAI, BCEA, and BCAD. Furthermore, the height of the femoral head ratio demonstrated a statistically significant correlation with BCEA. After adjusting for age(mo.), BMI, BCEA, and CCEA, BPoAcet and CPoAcet was found to be correlated with the length of the ossifying nucleus ratio. Preoperatively, the CAI, BAxAcet, BPoAcet, CPoAcet, and BTAD were correlated with the height of ossifying nucleus ratio after correcting for age, BMI, BCEA, and CCEA. Conclusion: The measurement parameters of hip socket morphology on MRI are associated with femoral head development, making them potential predictive indicators for femoral head development in DDH patients. These findings offer valuable insights for clinical decisions regarding the timing and approach of surgery in patients with developmental hip dislocation.

Neonatal hypertrophic cardiomyopathy with dyspnoea as the first symptom: a case report.

Neonatal hypertrophic cardiomyopathy (HCM) is an idiopathic disease characterised by myocardial hypertrophy with normal or small ventricular chambers, a systolic hyperdynamic state and diastolic dysfunction. The etiology, pathogenesis and clinical manifestations of HCM are diverse, and it is likely to progress to sudden cardiac death. The highly heterogeneous nature of this disease determines the difficulty of its diagnosis, and it is especially rare to report that can be diagnosed conclusively in the neonatal period. However, when it does occur, the younger the age of onset is, the higher the mortality rate and the worse the prognosis. The genetic variants and diagnostic timing can affect the life course of the patient. This case report describes a neonate with a family history of HCM who was diagnosed with hypertrophic non-obstructive cardiomyopathy by echocardiography shortly after birth. At 4 years of age, the patient presented with slow weight gain, feeding difficulties, tachypnoea and diaphoresis, and cardiac ultrasound findings suggesting progression to severe hypertrophic obstructive cardiomyopathy, with a high likelihood of arrhythmias, heart failure, pulmonary hypertension, syncope and even sudden death. Neonatal congenital hypertrophic cardiomyopathy is extremely rare and difficult to diagnose before the onset of symptoms. Echocardiography has a definite diagnostic value in hypertrophic cardiomyopathy and helps in early detection and treatment. At the time of clinical diagnosis, children with hypertrophic cardiomyopathy should be asked about their family history and, if necessary, a survey of family members should be conducted for the early detection of mildly ill patients and gene carriers to enable timely intervention and treatment, which remains the focus of our research and efforts.

Enhanced copper anticorrosion from Janus-doped bilayer graphene.

The atomic-thick anticorrosion coating for copper (Cu) electrodes is essential for the miniaturisation in the semiconductor industry. Graphene has long been expected to be the ultimate anticorrosion material, however, its real anticorrosion performance is still under great controversy. Specifically, strong electronic couplings can limit the interfacial diffusion of corrosive molecules, whereas they can also promote the surficial galvanic corrosion. Here, we report the enhanced anticorrosion for Cu simply via a bilayer graphene coating, which provides protection for more than 5 years at room temperature and 1000 h at 200 °C. Such excellent anticorrosion is attributed to a nontrivial Janus-doping effect in bilayer graphene, where the heavily doped bottom layer forms a strong interaction with Cu to limit the interfacial diffusion, while the nearly charge neutral top layer behaves inertly to alleviate the galvanic corrosion. Our study will likely expand the application scenarios of Cu under various extreme operating conditions.

The combined effects of overweight/obesity and dietary antioxidant quality score on hypertension in children and adolescents.

BACKGROUND: This study was to evaluate the combined effects of overweight/obesity and DAQS on the risk of hypertension in children and adolescents. METHODS: In this cross-sectional study, the data of 14,316 subjects were extracted from the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression analysis was used to explore the associations of obesity and DAQS with the risk of hypertension. The combined effect of overweight/obesity and DAQS on the risk of hypertension was evaluated. RESULTS: Body mass index (BMI)-for-age < 85th percentile was associated with reduced risk of hypertension in children and adolescents [odds ratio (OR) = 0.48, 95% confidence interval (CI): 0.41-0.62]. No significant association between DAQS ≥ 3 and the risk of hypertension before and after the adjustment of confounders (P > 0.05). Subjects with BMI-for-age of < 85th percentile and DAQS < 3 was associated with decreased risk of hypertension (OR = 0.53, 95%CI: 0.35-0.79). People with BMI-for-age of < 85th percentile and DAQS ≥ 3 was correlated with decreased risk of hypertension (OR = 0.52, 95%CI: 0.36-0.74). Subgroup analysis revealed that in subjects aged ≥ 12 years, decreased risk of hypertension was observed in BMI-for-age < 85th percentile and DAQS < 3 group (OR = 0.48, 95%CI: 0.31-0.73) as well as BMI-for-age < 85th percentile and DAQS ≥ 3 group (OR = 0.47, 95%CI: 0.32-0.67). In boys, BMI-for-age < 85th percentile and DAQS < 3 group (OR = 0.45, 95%CI: 0.25-0.81) as well as BMI-for-age < 85th percentile and DAQS ≥ 3 group (OR = 0.40, 95%CI: 0.25-0.65) were correlated with decreased risk of hypertension. CONCLUSION: Overweight/obesity and DAQS had combined effects on the risk of hypertension in children and adolescents, which implied that for children and adolescents with normal weight, to keep normal weight combined with high quality of diet might be recommended.

Association between Cerebrospinal Fluid and Serum Biomarker Levels and Diagnosis, Injury Severity, and Short-Term Outcomes in Patients with Acute Traumatic Spinal Cord Injury.

Acute traumatic spinal cord injury (SCI) is recognized as a global problem that can lead to a range of acute and secondary complications impacting morbidity and mortality. There is still a lack of reliable diagnostic and prognostic biomarkers in patients with SCI that could help guide clinical care and identify novel therapeutic targets for future drug discovery. The aim of this prospective controlled study was to determine the cerebral spinal fluid (CSF) and serum profiles of 10 biomarkers as indicators of SCI diagnosis, severity, and prognosis to aid in assessing appropriate treatment modalities. CSF and serum samples of 15 SCI and ten healthy participants were included in the study. The neurological assessments were scored on admission and at discharge from the hospital using the American Spinal Injury Association Impairment Score (AIS) grades. The CSF and serum concentrations of SBDP150, S100B, GFAP, NF-L, UCHL-1, Tau, and IL-6 were significantly higher in SCI patients when compared with the control group. The CSF GBDP 38/44K, UCHL-L1, S100B, GFAP, and Tau levels were significantly higher in the AIS A patients. This study demonstrated a strong correlation between biomarker levels in the diagnosis and injury severity of SCI but no association with short-term outcomes. Future prospective controlled studies need to be done to support the results of this study.

Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis.

BACKGROUND: Hypoxia-inducible factor prolyl hydroxylase inhibitors such as vadadustat may provide an oral alternative to injectable erythropoiesis-stimulating agents for treating anemia in patients receiving peritoneal dialysis. In two randomized (1:1), global, phase 3, open-label, sponsor-blind, parallel-group, active-controlled noninferiority trials in patients with dialysis-dependent chronic kidney disease (INNO2VATE), vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and hematological efficacy. Vadadustat's effects in patients receiving only peritoneal dialysis is unclear. METHODS: We conducted a post hoc analysis of patients in the INNO2VATE trials receiving peritoneal dialysis at baseline. The prespecified primary safety endpoint was time to first major cardiovascular event (MACE; defined as all-cause mortality or nonfatal myocardial infarction or stroke). The primary efficacy endpoint was mean change in hemoglobin from baseline to the primary evaluation period (Weeks 24-36). RESULTS: Of the 3923 patients randomized in the two INNO2VATE trials, 309 were receiving peritoneal dialysis (vadadustat, n = 152; darbepoetin alfa, n = 157) at baseline. Time to first MACE was similar in the vadadustat and darbepoetin alfa groups [hazard ratio 1.10; 95% confidence interval (CI) 0.62, 1.93]. In patients receiving peritoneal dialysis, the difference in mean change in hemoglobin concentrations was -0.10 g/dL (95% CI -0.33, 0.12) in the primary evaluation period. The incidence of treatment-emergent adverse events (TEAEs) was 88.2% versus 95.5%, and serious TEAEs was 52.6% versus 73.2% in the vadadustat and darbepoetin alfa groups, respectively. CONCLUSIONS: In the subgroup of patients receiving peritoneal dialysis in the phase 3 INNO2VATE trials, safety and efficacy of vadadustat were similar to darbepoetin alfa.

Cardiopulmonary Ultrasound-Guided Treatment of Premature Infants with Respiratory Failure and Patent Ductus Arteriosus: A Randomized, Controlled Trial.

OBJECTIVES: To evaluate the role of cardiopulmonary ultrasonography in the treatment of preterm infants with respiratory failure combined with patent ductus arteriosus (PDA). METHODS: A single-center, prospective, randomized, controlled trial of premature infants born in the authors' hospital with a birth weight ≤ 1500 g and respiratory failure combined with PDA was conducted from January 2020 to December 2021. The included infants were randomly assigned to the cardiopulmonary ultrasound-guided therapy group or the traditional therapy group. The primary outcome of this study was data on respiratory support and PDA. RESULTS: A total of 76 premature infants were included in the study. There were 39 patients in the cardiopulmonary ultrasound-guided therapy group and 37 patients in the traditional therapy group. There was no difference in the baseline data, and the cardiopulmonary ultrasound-guided therapy group had a higher initial positive end-expiratory pressure [difference in median = -1.5 cm H2O, 95% confidence interval (CI): -2.0 to -1.0, p < 0.0001], earlier use of ibuprofen to close the PDA (difference in median = 2.5 d, 95% CI: 1.0-4.0, p = 0.004), fewer patients requiring invasive respiratory support [risk ratio (RR) = 0.63, 95% CI: 0.41-0.99, p = 0.04], and a lower incidence of moderate to severe bronchopulmonary dysplasia (RR = 0.44, 95% CI: 0.44-0.96, p = 0.04). There was no difference in the incidence of adverse events. CONCLUSIONS: For premature infants with respiratory failure combined with PDA, cardiopulmonary ultrasonography can better guide respiratory support. The timely administration of drugs helps treat PDA, thereby decreasing the risk of intubation and BPD. TRIAL REGISTRATION: https://www.trialos.com/index/ , TRN: 20220420024607012, date of registration: 2022/03/28, retrospectively registered.

Erratum to "Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway".

[This corrects the article DOI: 10.1515/med-2022-0584.].

Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway.

miR-21 has been confirmed to be overexpressed in neonatal rat lungs with hyperoxia-mediated bronchopulmonary dysplasia (BPD). The specific function of miR-21 in BPD is still unclear. We established the hyperoxia-induced BPD rat model in vivo and the hyperoxia-induced pulmonary microvascular endothelial cells (PMVECs) model in vitro. Transwell assay was utilized to detect the migratory capability of PMVECs. Tube formation assay was utilized to measure angiogenesis ability. ELISA was utilized to test nitric oxide (NO) production and the intracellular and extracellular Asymmetric Dimethylarginine (ADMA) concentration. Furthermore, the interaction between miR-21 and dimethylarginine dimethylaminohydrolase 1 (DDAH1) was evaluated using luciferase reporter assay. We found that miR-21 expression in PMVECs was increased by hyperoxia stimulation. Inhibition of miR-21 improved the migratory and angiogenic activities of PMVECs and overexpression of miR-21 exerted the opposite effects. Furthermore, knockdown of miR-21 increased NO production and decreased intracellular and extracellular ADMA concentration in hyperoxia-treated PMVECs. Next we proved that miR-21 could bind to DDAH1 and negatively regulate its expression. Rescues assays showed that DDAH1 knockdown reversed the effects of miR-21 depletion on hyperoxia-mediated PMVEC functions, NO production, and ADMA concentration. Importantly, miR-21 downregulation restored alveolarization and vascular density in BPD rats. This study demonstrates that inhibition of miR-21 improves pulmonary vascular responses in BPD by targeting the DDAH1/ADMA/NO pathway.

Neonatal hemorrhage stroke and severe coagulopathy in a late preterm infant after receiving umbilical cord milking: A case report.

BACKGROUND: Umbilical cord milking (UCM) is an alternative placental transfusion method for delayed umbilical cord clamping in routine obstetric practice, allowing prompt resuscitation of an infant. Thus, UCM has been adopted at some tertiary neonatal centers for preterm infants to enhance placental-to-fetal transfusion. It is not suggested for babies less than 28 wk of gestational age because it is associated with severe brain hemorrhage. For late preterm or term infants who do not require resuscitation, cord management is recommended to increase iron levels and prevent the development of iron deficiency anemia, which is associated with impaired motor development, behavioral problems, and cognitive delays. Concerns remain about whether UCM increases the incidence of intraventricular hemorrhage. However, there are very few reports of late preterm infants presenting with neonatal hemorrhage stroke (NHS) and severe coagulopathy after receiving UCM. Here, we report a case of a late preterm infant born at 34 wk of gestation. She abruptly deteriorated, exhibiting signs and symptoms of NHS and severe coagulopathy after receiving UCM on the first day of life. CASE SUMMARY: A female preterm infant born at 34 wk of gestation received UCM after birth. She was small for her gestational age and described as vigorous with Apgar scores of 9 and 10 at one minute and five minutes of life, respectively. After hospitalization in the neonatal intensive care unit, she showed hypoglycemia and metabolic acidosis. The baby was administered glucose and sodium bicarbonate infusions. Intramuscular vitamin K1 was also used to prevent vitamin K deficiency. The baby developed umbilical cord bleeding and gastric bleeding on day 1 of life; a physical examination showed bilateral conjunctival hemorrhage, and a blood test showed thrombocytopenia, prolonged prothrombin time, prolonged activated partial thromboplastin time, low fibrinogen, raised D-dimer levels and anemia. A subsequent cranial ultrasound and computed tomography scan showed a left parenchymal brain hemorrhage with extension into the ventricular and subarachnoid spaces. The patient was diagnosed with NHS in addition to disseminated intravascular coagulation (DIC). Fresh frozen plasma (FFP) and prothrombin complex concentrate were given for coagulopathy. Red blood cell and platelet transfusions were provided for thrombocytopenia and anemia. A bolus of midazolam, intravenous calcium and phenobarbital sodium were administered to control seizures. The baby's clinical condition improved on day 5 of life, and the baby was hospitalized for 46 d and recovered well without seizure recurrence. Our case report suggests that preterm infants who receive UCM should undergo careful clinical assessment for intracranial hemorrhage, NHS and severe coagulopathy that may develop under certain circumstances. Supportive management, such as intensive care, FFP and blood transfusion, is recommended when the development of massive NHS and associated DIC is suspected. CONCLUSION: Our case report suggests that for late preterm infants who are small for gestational age and who receive UCM for alternative placental transfusion, neonatal health care professionals should be cautious in assessing the development of NHS and severe coagulopathy. Neonatal health care professionals should also be more cautious in assessing the complications of late preterm infants after they receive UCM.

Performance of Tönnis triple osteotomy in older children with developmental dysplasia of the hip (DDH) assisted by a 3D printing navigation template.

BACKGROUND: The objective of this study is to investigate the preparation of a navigation template via a computer-aided design (CAD) and 3D printing (3DP) in order to improve the effectiveness of Tönnis triple osteotomy in older children with developmental dysplasia of the hip (DDH). METHOD: Thirty-eight older children who received Tönnis triple osteotomy were included in this study. Among them, 20 were categorized as the 3DP navigation template group (3DP group), and the remaining 18 were categorized as the conventional surgery group (CS group). Data, including preoperative and postoperative pelvic sharp angle (SA), lateral center-edge angle (LCEA), acetabular roof angle (ARA), acetabular head index (AHI), crossover sign (COS), ischial spine sign (ISS), operation time (OT), intraoperative blood loss (IBL), and number of radiation exposures (NORE) were recorded for both groups. In addition, the therapeutic effect was evaluated at the last follow-up, according to the McKay criteria and Severin's criteria. RESULTS: In the 3DP and CS groups, the mean OT was 126.6 ± 17.6 min and 156.0 ± 18.6 min, respectively; the mean IBL was 115.0 ± 16.9 ml and 135.7 ± 26.5 ml, respectively; the NORE were 3.3 ± 0.8 times and 8.6 ± 1.3 times, respectively. There were significant differences in the OT, IBL, and NORE between the two groups (P = 0.03, 0.05, < 0.001, respectively). At the last follow-up, the 3DP and CS groups displayed SA of 41.8 ± 2.3° and 42.6 ± 3.1°, respectively; LCEA of 35.6 ± 4.2° and 37.1 ± 2.8°, respectively; ARA of 6.9 ± 1.8° and 9.8 ± 2.6°, respectively; and AHI of 86.6 ± 4.1% and 84.3 ± 2.8%, respectively; COS(+) of 5 hips and 4 hips, respectively; ISS(+) of 6 hips and 7 hips. We observed no statistical differences in the SA, LCEA, ARA, AHI, COS and ISS between the two groups (P = 0.918, 0.846, 0.643, 0.891, 0.841, 0.564, respectively). According to the McKay criteria, the 3DP group had 10 excellent, 6 good, and 4 general hips, whereas, the CS group had 12 excellent, 4 good, and 2 general hip. There was no statistical difference between the two groups (P = 0.698). In 3DP group the postoperative Severin's grading included 13 hips in grade I, 4 in grade II, 3 in grade III. Alternately, in the CS group, the postoperative Severin's grading included 11 hips in grade I, 5 in grade II, 2 in grade III. The Severin 's criteria also showed no statistical difference between the two groups (P = 0.945). CONCLUSIONS: Base on our analysis, our CAD-3DP-fabricated navigation template assisted Tönnis triple osteotomy in older DDH children, it reduced operation time and number of radiation exposures. However, no significant differences in radiological assessment and functional outcomes were observed when an experienced surgeon performs the surgery. Therefore, Surgeons who have less experience in triple osteotomy profit more from the application of this technology.

Visualizing the Anomalous Catalysis in Two-Dimensional Confined Space.

Confined nanospaces provide a new platform to promote catalytic reactions. However, the mechanism of catalytic enhancement in the nanospace still requires insightful exploration due to the lack of direct visualization. Here, we report operando investigations on the etching and growth of graphene in a two-dimensional (2D) confined space between graphene and a Cu substrate. We observed that the graphene layer between the Cu and top graphene layer was surprisingly very active in etching (more than 10 times faster than the etching of the top graphene layer). More strikingly, at a relatively low temperature (∼530 °C), the etched carbon radicals dissociated from the bottom layer, in turn feeding the growth of the top graphene layer with a very high efficiency. Our findings reveal the in situ dynamics of the anomalous confined catalytic processes in 2D confined spaces and thus pave the way for the design of high-efficiency catalysts.

Intrauterine growth restriction neonates present with increased angiogenesis through the Notch1 signaling pathway.

Intrauterine growth restriction (IUGR) is associated with increased perinatal mortality and morbidity, and plays an important role in the development of adult cardiovascular diseases. This study brings forward a hypothesis that Human umbilical vein endothelial cells (HUVECs) from IUGR newborns present dysfunctions and varying changes of signaling pathways as compared to the Control group. Similar pathways may also be present in pulmonary or systemic vasculatures. HUVECs were derived from newborns. There were three groups according to the different fetal origins: normal newborns (Control), IUGR from poor maternal nutrition (IUGR1), and pregnancy-induced hypertension (IUGR2). We found that IUGR-derived HUVECs showed a proliferative phenotype compared to those from normal subjects. Interestingly, two types IUGR could cause varying degrees of cellular dysfunction. Meanwhile, the Notch1 signaling pathway showed enhanced activation in the two IUGR-induced HUVECs, with subsequent activation of Akt or extracellular signal regulated protein kinases1/2 (ERK1/2). Pharmacological inhibition or gene silencing of Notch1 impeded the proliferative phenotype of IUGR-induced HUVECs and reduced the activation of ERK1/2 and AKT. In summary, elevated Notch1 levels might play a crucial role in IUGR-induced HUVECs disorders through the activation of ERK1/2 and AKT. These pathways could be potential therapeutic targets for prevention of the progression of IUGR associated diseases later in life.

Probing the carbon emissions in 30 regions of China based on symbolic regression and Tapio decoupling.

Against the background of energy shortages and severe air pollution, countries around the world are aware of the importance of energy conservation and emission reduction; China is actively achieving emission reduction targets. In this study, we use a symbolic regression to classify China's regions according to the degree of influencing factors and calculate and analyze the inherent decoupling relationship between carbon emissions and economic growth in each region. Based on our results, we divided the 30 regions of the country into six categories according to the main influencing factors: GDP (13 regions), energy intensity (EI; 7 regions), industrial structure (IS; 3 regions), urbanization rate (UR; 3 regions), car ownership (CO; 2 regions), and household consumption level (HCL; 2 regions). Then, according to the order of the average carbon emissions in each region from high to low, these regions were further categorized as Type-EI, Type-UR, Type-GDP, Type-IS, Type-CO, or Type-HCL regions. The decoupling coefficient of the Type-UR region was the smallest with an expansive coupling and weak decoupling, whereas the other regions showed expansive negative decoupling, expansive coupling, and weak decoupling. Among them, the reduction rate of the decoupling coefficient in the Type-EI region was the largest at 6.65%. EI and GDP regions were the most notable contributors to emissions, based on which we provide policy recommendations.

MicroRNA-214 promotes alveolarization in neonatal rat models of bronchopulmonary dysplasia via the PlGF-dependent STAT3 pathway.

BACKGROUND: Recently, the role of several microRNAs (miRNAs or miRs) in pulmonary diseases has been described. The molecular mechanisms by which miR-214 is possibly implicated in bronchopulmonary dysplasia (BPD) have not yet been addressed. Hence, this study aimed to investigate a putative role of miR-214 in alveolarization among preterm neonates with BPD. METHODS: Microarray-based gene expression profiling data from BPD was employed to identify differentially expressed genes. A BPD neonatal rat model was induced by hyperoxia. Pulmonary epithelial cells were isolated from rats and exposed to hyperoxia to establish cell injury models. Gain- and loss-of-function experiments were performed in BPD neonatal rats and hyperoxic pulmonary epithelial cells. MiR-214 and PlGF expression in BPD neonatal rats, and eNOS, Bcl-2, c-myc, Survivin, α-SMA and E-cadherin expression in hyperoxic pulmonary epithelial cells were measured using RT-qPCR and Western blot analysis. The interaction between PlGF and miR-214 was identified using dual luciferase reporter gene and RIP assays. IL-1ß, TNF-a, IL-6, ICAM-1 and Flt-1 expression in the rat models was measured using ELISA. RESULTS: The lung tissues of neonatal rats with BPD showed decreased miR-214 expression with elevated PlGF expression. PlGF was found to be a target of miR-214, whereby miR-214 downregulated PlGF to inactivate the STAT3 pathway. miR-214 overexpression or PlGF silencing decreased the apoptosis of hyperoxic pulmonary epithelial cells in vitro and restored alveolarization in BPD neonatal rats. CONCLUSION: Overall, the results demonstrated that miR-214 could facilitate alveolarization in preterm neonates with BPD by suppressing the PlGF-dependent STAT3 pathway.

Exploring prediction model and survival strategies for pulmonary hemorrhage in premature infants: a single-center, retrospective study.

BACKGROUND: Pulmonary hemorrhage is a potentially fatal event especially for preterm infants, which can lead to serious complications and even death. Many risk factors have been associated with the development of massive pulmonary hemorrhage. However, there is still no effective strategy to prevent massive pulmonary hemorrhage. The purpose of this study is to explore prediction model and survival strategies for massive pulmonary hemorrhage in premature infants. METHODS: In this retrospective study, we included all premature infants with birth weight <1,500 g who were hospitalized in our neonatal intensive care unit (NICU) between January 01 2010 and December 31 2019. RESULTS: Of 599 preterm infants, 51 developed massive pulmonary hemorrhage. The logistic regression analysis showed that patent ductus arteriosus [odds ratio (OR) =11.4, 95% confidence interval (CI): 4.79-27.0, P<0.0001], coagulopathy (OR =6.56, 95% CI: 2.83-15.2, P<0.0001), and 10-minute Apgar Score (OR =0.52, 95% CI: 0.37-0.73, P=0.0001) were risk factors for massive pulmonary hemorrhage. Whether or not surfactant is used, the positive predictive value of combined patent ductus arteriosus and coagulopathy for predicting massive pulmonary hemorrhage was 68.9% and 70.4%, respectively. Of the 51 preterm infants with massive pulmonary hemorrhage, 25 died and 26 survived. The survivors group had higher positive end-expiratory pressure compared with the deceased group after the onset of massive pulmonary hemorrhage. After adjusting for potential risk factors, the multiple logistic regression analysis showed that higher positive end-expiratory pressure levels are closely related to survival. CONCLUSIONS: Patent ductus arteriosus combined with coagulopathy has a high predictive value for massive pulmonary hemorrhage. Higher positive end-expiratory pressure levels may reduce mortality in massive pulmonary hemorrhage.

Food protein-induced enterocolitis syndrome presenting after necrotizing enterocolitis in a preterm neonate: a case report.

When bloody stools occur in a very-low-birth-weight infant in the neonatal intensive care unit (NICU), necrotizing enterocolitis (NEC) is a prime consideration, though food protein-induced enterocolitis syndrome (FPIES) can be causative and is difficult to distinguish from NEC. Food allergy is an adverse reaction following exposure to food due to an abnormal immunologic response to food, and cow's milk allergy (CMA) is the most likely form of food allergy in infants. The clinical features and proper management of patients with FPIES are important to differentiate FPIES from NEC. However, there are very few study reports of preterm infants presenting with food allergy-induced enterocolitis after NEC. Here, we report a case of a very-low-birth-weight infant born at 28 weeks of gestational age who developed recurrent episodes of bloody stools when he was fed cow's milk or given breast milk fortified with milk after NEC recovery on day of life (DOL) 29, 46, and 54. A male preterm infant born at 28 weeks of gestational age presented with bloody stools on DOL 7. He was diagnosed with early-onset NEC with abdominal tenderness, sluggish bowel sounds, increased C-reactive protein (CRP) level and pneumatosis intestinalis (PI). After recovery from NEC on DOL 20, the infant developed three recurrent episodes of bloody stools after being fed cow's milk or breast milk fortified with dairy milk. He was suspected of having recurrent episodes of NEC, but the infant was fairly healthy and did not present abdominal tenderness or abnormal bowel sounds on physical examination. Consecutive blood tests revealed normal CRP levels and increasing eosinophil levels. Abdominal radiograph revealed mild thickening of the small bowel, with no evidence of PI. The infant was finally diagnosed with FPIES in addition to NEC. After the infant received hydrolyzed formula, the bloody stool symptoms were finally resolved. Our case suggests that infants with recurrent episodes of bloody stools with increasing systemic eosinophils count should be considered for the diagnosis of FPIES with cow's milk formula. Rapid improvement and non-progression of systemic symptoms and signs after removing exposure to milk protein may differentiate FPIES from NEC.