The current clinical landscape of neonatal respiratory failure in Jiangsu Province of China: patient demographics, NICU treatment interventions, and patient outcomes.

INTRODUCTION: Neonatal respiratory failure (NRF) is a serious condition that often has high mortality and morbidity, effective interventions can be delivered in the future by identifying the risk factors associated with morbidity and mortality. However, recent advances in respiratory support have improved neonatal intensive care units (NICUs) care in China. We aimed to provide an updated review of the clinical profile and outcomes of NRF in the Jiangsu province. METHODS: Infants treated for NRF in the NICUs of 28 hospitals between March 2019 and March 2022 were retrospectively reviewed. Data collected included baseline perinatal and neonatal parameters, NICU admission- and treatment-related data, and patient outcomes in terms of mortality, major morbidity, and survival without major morbidities. RESULTS: A total of 5548 infants with NRF were included in the study. The most common primary respiratory disorder was respiratory distress syndrome (78.5%). NRF was managed with non-invasive and invasive respiratory support in 59.8% and 14.5% of patients, respectively. The application rate of surfactant therapy was 38.5%, while that of neonatal extracorporeal membrane oxygenation therapy was 0.2%. Mortality and major morbidity rates of 8.5% and 23.2% were observed, respectively. Congenital anomalies, hypoxic-ischemic encephalopathy, invasive respiratory support only and inhaled nitric oxide therapy were found to be significantly associated with the risk of death. Among surviving infants born at < 32 weeks of gestation or with a birth weight < 1500 g, caffeine therapy and repeat mechanical ventilation were demonstrated to significantly associate with increased major morbidity risk. CONCLUSION: Our study demonstrates the current clinical landscape of infants with NRF treated in the NICU, and, by proxy, highlights the ongoing advancements in the field of perinatal and neonatal intensive care in China.

Limosilactobacillus reuteri in immunomodulation: molecular mechanisms and potential applications.

Frequent use of hormones and drugs may be associated with side-effects. Recent studies have shown that probiotics have effects on the prevention and treatment of immune-related diseases. Limosilactobacillus reuteri (L. reuteri) had regulatory effects on intestinal microbiota, host epithelial cells, immune cells, cytokines, antibodies (Ab), toll-like receptors (TLRs), tryptophan (Try) metabolism, antioxidant enzymes, and expression of related genes, and exhibits antibacterial and anti-inflammatory effects, leading to alleviation of disease symptoms. Although the specific composition of the cell-free supernatant (CFS) of L. reuteri has not been clarified, its efficacy in animal models has drawn increased attention to its potential use. This review summarizes the effects of L. reuteri on intestinal flora and immune regulation, and discusses the feasibility of its application in atopic dermatitis (AD), asthma, necrotizing enterocolitis (NEC), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS), and provides insights for the prevention and treatment of immune-related diseases.

Impact of hypertensive disorders of pregnancy on neonatal outcomes among infants born at 24+0-31+6 weeks' gestation in China: A multicenter cohort study.

Objective: To describe the rate of hypertensive disorder of pregnancy (HDP) among mothers of very preterm infants (VPIs) admitted to Chinese neonatal intensive care units (NICUs), and to investigate the relationship between HDP and the outcomes of VPIs. Study design: Cohort study of all VPIs born at a gestational age of 24+0-31+6 weeks and admitted to 57 tertiary NICUs of the Chinese Neonatal Network (CHNN) in 2019. Infants with severe congenital anomalies or missing maternal HDP information were excluded. Two multivariate logistic regression models were generated to assess the relationship between HDP and neonatal outcomes. Results: Among 9,262 infants enrolled, 1,744 (18.8%) infants were born to mothers with HDP, with an increasing incidence with increasing gestational age. VPIs born to mothers with HDP had higher gestational age but lower birth weight and were more likely to be small for gestational age. Mothers with HDP were more likely to receive antenatal steroids, MgSO4 and cesarean section. Infants in the HDP group showed higher observed rates of mortality or any morbidity than infants in the non-HDP group (50.2% vs. 47.2%, crude odds ratio (OR) 1.13, 95% CI 1.02-1.26). However, the associations between HDP and adverse outcomes were not significant after adjustment. In the HDP group, mothers of 1,324/1,688 (78.4%) infants were diagnosed with preeclampsia/eclampsia. Infants born to mothers with preeclampsia/eclampsia had significantly lower odds of early death and severe retinopathy of prematurity. Conclusions: Nearly one-fifth of VPIs were born to mothers with HDP in Chinese NICUs. No significant association was identified between HDP and adverse neonatal short-term outcomes of VPIs, while long-term follow-up of these infants is needed.

Lactobacillus for the treatment and prevention of atopic dermatitis: Clinical and experimental evidence.

Atopic dermatitis (AD) is a chronic inflammatory skin disease, accompanied by itching and swelling. The main pathological mechanism of AD is related to the imbalance between Type 2 helper cells (Th2 cells) and Type 1 helper cells (Th1 cells). Currently, no safe and effective means to treat and prevent AD are available; moreover, some treatments have side effects. Probiotics, such as some strains of Lactobacillus, can address these concerns via various pathways: i) facilitating high patient compliance; ii) regulating Th1/Th2 balance, increasing IL-10 secretion, and reducing inflammatory cytokines; iii) accelerating the maturation of the immune system, maintaining intestinal homeostasis, and improving gut microbiota; and iv) improving the symptoms of AD. This review describes the treatment and prevention of AD using 13 species of Lactobacillus. AD is commonly observed in children. Therefore, the review includes a higher proportion of studies on AD in children and fewer in adolescents and adults. However, there are also some strains that do not improve the symptoms of AD and even worsen allergies in children. In addition, a subset of the genus Lactobacillus that can prevent and relieve AD has been identified in vitro. Therefore, future studies should include more in vivo studies and randomized controlled clinical trials. Given the advantages and disadvantages mentioned above, further research in this area is urgently required.

[Antibiotic use in very low birth weight/extremely low birth weight infants in 15 hospitals in Jiangsu Province of China: a multicenter survey]. / 江苏省15家医院极低/è¶ ä½Žå‡ºç”Ÿä½“é‡å„¿æŠ—ç”Ÿç´ ä½¿ç”¨çŽ°çŠ¶è°ƒæŸ¥.

OBJECTIVES: To investigate the current status of antibiotic use in very low birth weight/extremely low birth weight infants in Jiangsu Province of China, and to provide a clinical basis for the quality and improvement of antibiotic management in the neonatal intensive care unit (NICU). METHODS: A retrospective analysis was performed on the data on general conditions and antibiotic use in the very low birth weight/extremely low birth weight infants who were admitted to 15 hospitals of Jiangsu Province from January 1, 2019 to December 31, 2020. A questionnaire containing 10 measures to reduce antibiotic use was designed to investigate the implementation of these intervention measures. RESULTS: A total of 1 920 very low birth weight/extremely low birth weight infants were enrolled, among whom 1 846 (96.15%) were treated with antibiotic, and the median antibiotic use rate (AUR) was 50/100 patient-days. The AUR ranged from 24/100 to 100/100 patient-days in the 15 hospitals. After adjustment for the confounding factors including gestational age, birth weight, and neonatal critical score, the Poisson regression analysis showed that there was a significant difference in the adjusted AUR (aAUR) among the hospitals (P<0.01). The investigation results showed that among the 10 measures to reduce antibiotic use, 8 measures were implemented in less than 50% of these hospitals, and the number of intervention measures implemented was negatively correlated with aAUR (rs=-0.564, P=0.029). CONCLUSIONS: There is a high AUR among the very low birth weight/extremely low birth weight infants in the 15 hospitals of Jiangsu Province, with a significant difference among hospitals. The hospitals implementing a relatively few measures to reduce antibiotic use tend to have a high AUR. It is expected to reduce AUR in very low birth weight/extremely low birth weight infants by promoting the quality improvement of antibiotic use management in the NICU.

Effects of Antioxidants in Human Milk on Bronchopulmonary Dysplasia Prevention and Treatment: A Review.

Bronchopulmonary dysplasia (BPD) is a severe chronic lung illness that affects neonates, particularly premature infants. It has far-reaching consequences for infant health and their families due to intractable short- and long-term repercussions. Premature infant survival and long-term quality of life are severely harmed by BPD, which is characterized by alveolarization arrest and hypoplasia of pulmonary microvascular cells. BPD can be caused by various factors, with oxidative stress (OS) being the most common. Premature infants frequently require breathing support, which results in a hyperoxic environment in the developing lung and obstructs lung growth. OS can damage the lungs of infants by inducing cell death, inhibiting alveolarization, inducing inflammation, and impairing pulmonary angiogenesis. Therefore, antioxidant therapy for BPD relieves OS and lung injury in preterm newborns. Many antioxidants have been found in human milk, including superoxide dismutase, glutathione peroxidase, glutathione, vitamins, melatonin, short-chain fatty acids, and phytochemicals. Human milk oligosaccharides, milk fat globule membrane, and lactoferrin, all unique to human milk, also have antioxidant properties. Hence, human milk may help prevent OS injury and improve BPD prognosis in premature infants. In this review, we explored the role of OS in the pathophysiology of BPD and related signaling pathways. Furthermore, we examined antioxidants in human milk and how they could play a role in BPD to understand whether human milk could prevent and treat BPD.

Variation of Neonatal Outcomes and Care Practices for Preterm Infants <34 Weeks' Gestation in Different Regions of China: A Cohort Study.

Background: To compare outcomes and care practices of preterm infants born at <34 weeks' gestation in the different regions of China from 2015 to 2018. Methods: This cohort study enrolled all infants born at <34 weeks and admitted to 25 tertiary neonatal intensive care units across China from May 1st, 2015, to April 30th, 2018. The participating hospitals were categorized into three groups according to their distinct geographic locations: eastern China, central China, and western China. Multilevel mixed-effects logistic regression models were used to assess the independent association between neonatal outcomes and regions. Results: A total of 27,532 infants at <34 weeks' gestation were enrolled in our study. Overall, 14,178 (51.5%) infants were from 12 hospitals in eastern China, 8,069 (29.3%) from 9 hospitals in central China, and 5,285 (19.2%) from 4 hospitals in western China. Infants in eastern China had the lowest rates of mortality or any morbidity (23.3%), overall mortality (7.6%), in-hospital mortality (3.7%), and discharge against medical advice (DAMA, 6.3%), compared with central (27.8, 11.3, 5.0, and 10.6%, respectively) and western China (37.4, 19.4, 7.7, and 19.4%, respectively). Multilevel mixed-effects logistic regression showed that infants in western China were exposed to the highest risks of mortality or any morbidity, overall mortality, in-hospital mortality, and DAMA. Significant variations of care practices existed in three regions. Infants in central China had the longest duration of the first course of invasive ventilation, the lowest rate of continuous positive airway pressure within 24 h after birth, the lowest rate of breast milk feeding, the latest initiation of feeds, and the longest duration of total parenteral nutrition among the three regions. Conclusions: We identified marked disparities in outcomes and clinical care practices of preterm infants born at <34 weeks' gestation in different regions of China. Targeted quality improvement efforts are needed to improve the outcomes of premature infants in different regions of China.

A multicenter retrospective study on survival rate and complications of very preterm infants. / æžæ—©äº§å„¿å­˜æ´»çŽ‡å’Œå¹¶å‘ç—‡çš„å¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To study the survival rate and the incidence of complications of very preterm infants and the factors influencing the survival rate and the incidence of complications. METHODS: The medical data of the very preterm infants with a gestational age of <32 weeks and who were admitted to the Department of Neonatology in 11 hospitals of Jiangsu Province in China from January 2018 to December 2019 were retrospectively reviewed. Their survival rate and the incidence of serious complications were analyzed. A multivariate logistic regression analysis was used to evaluate the risk factors for death and serious complications in very preterm infants. RESULTS: A total of 2 339 very preterm infants were enrolled, among whom 2 010 (85.93%) survived and 1 507 (64.43%) survived without serious complications. The groups with a gestational age of 22-25+6 weeks, 26-26+6 weeks, 27-27+6 weeks, 28-28+6 weeks, 29-29+6 weeks, 30-30+6 weeks, and 31-31+6 weeks had a survival rate of 32.5%, 60.6%, 68.0%, 82.9%, 90.1%, 92.3%, and 94.8% respectively. The survival rate tended to increase with the gestational age (P<0.05) and the survival rate without serious complications in each gestational age group was 7.5%, 18.1%, 34.5%, 52.2%, 66.7%, 75.7%, and 81.8% respectively, suggesting that the survival rate without serious complications increased with the gestational age (P<0.05). The multivariate logistic regression analysis showed that high gestational age, high birth weight, and prenatal use of glucocorticoids were protective factors against death in very preterm infants (P<0.05), and 1-minute Apgar score ≤3 was a risk factor for death in very preterm infants (P<0.05); high gestational age and high birth weight were protective factors against serious complications in very preterm infants who survived (P<0.05), while 5-minute Apgar score ≤3 and maternal chorioamnionitis were risk factors for serious complications in very preterm infants who survived (P<0.05). CONCLUSIONS: The survival rate is closely associated with gestational age in very preterm infants. A low 1-minute Apgar score (≤3) may increase the risk of death in very preterm infants, while high gestational age, high birth weight, and prenatal use of glucocorticoids are associated with the reduced risk of death. A low 5-minute Apgar score (≤3) and maternal chorioamnionitis may increase the risk of serious complications in these infants, while high gestational age and high birth weight may reduce the risk of serious complications.

Evaluation of nutrition status of very preterm infants in neonatal intensive care units using different growth indicators.

BACKGROUND:  Nutrition status of very preterm infants in the neonatal intensive care unit (NICU) is strongly associated with postnatal growth. This study aimed to develop indicators of nutrition status using growth data of very preterm infants during hospitalization. METHODS: The data of 596 newborns from eight NICUs were retrospectively analyzed. Inclusion criteria were birth at <32 weeks' gestation, NICU admission ≤24 h after delivery, and length of hospital stay ≥28 days. Three indicators were evaluated: (indicator I) prevalence of extrauterine growth restriction (EUGR); (indicator II) z-score for change in weight from birth to discharge, adjusted for birth weight z-score and gestational age; and (indicator III) change in weight z-score from birth to discharge, adjusted for birth weight z-score, gestational age, and time to regain birth weight. Using data from NICU 1 as the reference for the latter two indicators, we established linear regression models of the adjusted change in weight z-score from birth to discharge. The difference between the observed value and the baseline value (calculated by the two models) served as the nutrition indices. RESULTS: The prevalence of EUGR differed significantly between the eight NICUs (P = .009). Statistically significant differences were found between the mean indices calculated by the other two models (all P < .05). CONCLUSIONS: Indicator III, change in weight z-score from birth to discharge (adjusted for birth weight z-score, gestational age, and time to regain birth weight), appears to be the most accurate for evaluating the quality of nutrition in the NICU.

Branched-chain fatty acids in the vernix caseosa and meconium of infants born at different gestational ages.

The functional lipid components found in breast milk, vernix caseosa, and meconium are Branched-chain Fatty Acids (BCFA). The goal of this study was to establish the existence of BCFA in vernix and meconium in infants born at different gestational ages. TLC plates and GC-MS were examined for the lipids in vernix caseosa and meconium. The results indicated that there were nine BCFA in vernix caseosa, including iso-12:0, anteiso-13:0, iso-14:0, iso-15:0, anteiso-15:0, iso-16:0, anteiso-17:0, iso-18:0, and iso-20:0. Five BCFA (iso-12:0, anteiso-13:0, iso-14:0, iso-15:0, and anteiso-15:0) were not contained in the meconium, suggesting that some of the BCFA may be digested and consumed by infants. In the vernix caseosa, the content of BCFA in triacylglycerol (TAG) and free fatty acid (FFA) was 15.59% and 11.82%, respectively. The vernix caseosa's wax ester fraction contained the highest content of BCFA, reaching up to 16.81%. The carbon chain length of fatty acids (FA) ranged from 12 to 24 in the vernix caseosa and 14 to 22 in meconium samples. The gestational age was likely to affect BCFA concentrations, with the vernix caseosa and meconium BCFA content being significantly higher in full-term infants than in preterm infants (p < .001). Further research is required into the relationship between BCFA and gut microbiotas.

[Clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation: a multicenter retrospective analysis].

OBJECTIVE: To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation. METHODS: A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation (n=1 184), tracheal intubation (n=166), and extensive cardiopulmonary resuscitation (ECPR; n=116). The three groups were compared in terms of general information and clinical outcomes. RESULTS: Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid (P < 0.05). As the intensity of resuscitation increased, the Apgar scores at 1 minute and 5 minutes gradually decreased (P < 0.05), and the proportion of infants with Apgar scores of 0 to 3 at 1 minute and 5 minutes gradually increased (P < 0.05). Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly higher mortality rate and incidence rates of moderate-severe bronchopulmonary dysplasia and serious complications (P < 0.05). The incidence rates of grade Ⅲ-Ⅳ intracranial hemorrhage and retinopathy of prematurity (stage Ⅲ or above) in the tracheal intubation group were significantly higher than those in the non-tracheal intubation group (P < 0.05). CONCLUSIONS: For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.

Sodium Propionate Enhances Nrf2-Mediated Protective Defense Against Oxidative Stress and Inflammation in Lipopolysaccharide-Induced Neonatal Mice.

BACKGROUND: Alveolar arrest and the impaired angiogenesis caused by chronic inflammation and oxidative stress are two main factors in bronchopulmonary dysplasia (BPD). Short-chain fatty acids (SCFAs), especially propionate, possess anti-oxidant and anti-inflammatory effects. The present study was designed to examine the roles of sodium propionate (SP) on lipopolysaccharide (LPS)-challenged BPD and its potential mechanisms. METHODS: WT, Nrf2-/- mice and pulmonary microvascular endothelial cells (HPMECs) were used in this study. LPS was performed to mimic BPD model both in vivo and vitro. Lung histopathology, inflammation and oxidative stress-related mRNA expressions in lungs involved in BPD pathogenesis were investigated. In addition, cell viability and angiogenesis were also tested. RESULTS: The increased nuclear factor erythroid 2-related factor (Nrf2) and decreased Kelch-like ECH-associated protein-1 (Keap-1) expressions were observed after SP treatment in the LPS-induced neonatal mouse model of BPD. In LPS-induced wild-type but not Nrf2-/- neonatal mice, SP reduced pulmonary inflammation and oxidative stress and exhibited obvious pathological alterations of the alveoli. Moreover, in LPS-evoked HPMECs, SP accelerated Nrf2 nuclear translocation presented and exhibited cytoprotective and pro-angiogenesis effects. In addition, SP diminished the LPS-induced inflammatory response by blocking the activation of nuclear factor-kappa B pathway. Moreover, pretreatment with ML385, an Nrf2 specific inhibitor, offsets the beneficial effects of SP on inflammation, oxidative stress and angiogenesis in LPS-evoked HPMECs. CONCLUSION: SP protects against LPS-induced lung alveolar simplification and abnormal angiogenesis in neonatal mice and HPMECs in an Nrf2-dependent manner.

miR-296-5p Inhibits the Secretion of Pulmonary Surfactants in Pulmonary Epithelial Cells via the Downregulation of Wnt7b/ß-Catenin Signaling.

Neonatal respiratory distress syndrome (NRDS) is a common disease that occurs in premature infants. However, the mechanisms underlying the disease remain unclear. microRNAs (miRNAs) have been indicated to play a crucial role in the development of NRDS. In this study, we aimed to explore the regulatory mechanisms of miR-296-5p in NRDS. The expression levels of miR-296-5p in preterm infants with NRDS were determined using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). A549 cells were transfected with lentiviral vectors encoding miR-296-5p, and the transfection efficiency was determined using RT-qPCR. Flow cytometry and CCK8 assay were performed to measure apoptosis and proliferation of A549 cells, respectively. The protein levels of pulmonary surfactant SP-A (SFTPA1), SP-B, Wnt7b, and ß-catenin were measured using western blotting. We demonstrated an upregulation of miR-296-5p in NRDS. The miR-296-5p was successfully overexpressed in A549 cells via lentivirus transfection, and the upregulation of miR-296-5p inhibited cell proliferation and secretion of SP-A and SP-B and also induced downregulation of the Wnt7b/ß-catenin in vitro. Therefore, miR-296-5p inhibits cell proliferation and secretion of pulmonary surfactants in A549 cells via downregulation of Wnt7b/ß-catenin signaling.

Dose-dependent effect of human milk on Bronchopulmonary dysplasia in very low birth weight infants.

BACKGROUND AND AIM: Human milk has potential protective effects against bronchopulmonary dysplasia (BPD). However, studies on the association between the dose of human milk and BPD in China are limited. This study aimed to evaluate the dose-dependent effects of human milk on BPD and other neonatal morbidities in very low birth weight (VLBW) infants. METHODS: This retrospective cohort study of preterm infants was conducted on preterm infants of gestational age ≤ 34 weeks and birth weight < 1500 g admitted to the multicenter clinical research database for breastfeeding quality improvement in Jiangsu province. The multivariate analysis was performed to compare the effect outcomes of daily graded doses [1-24 mL/(kg · day), 25-49 mL/(kg · day), and ≥ 50 mL/(kg · day) of body weight] of human milk on neonatal outcomes throughout the first 4 weeks of life versus a reference group receiving no human milk. The models were adjusted for potential confounding variables. RESULTS: Of 964 included infants, 279 (28.9%) received exclusive preterm formula, 128 (13.3%) received 1-24 ml/(kg · day), 139 (14.4%) received 25-49 ml/(kg · day), and 418 (43.4%) received ≥50 ml/(kg · day) human milk for the first 4 weeks of life. Compared with infants receiving exclusive formula, those receiving the highest volume of human milk daily [≥50 mL/(kg · day)] had lower incidences of BPD [27.5% in ≥50 mL/(kg · day) vs 40.1% in 0 mL/(kg · day) human milk, P = 0.001)], moderate and severe BPD [8.9% in ≥50 mL/(kg · day) vs 16.1% in 0 mL/(kg · day), P = 0.004], necrotizing enterocolitis [NEC; 3.8% in ≥50 mL/(kg · day) vs 10.8% in 0 mL/(kg · day), P = 0.001], late-onset sepsis [LOS; 9.3% in ≥50 mL/(kg · day) vs 19.7% in 0 mL/(kg · day), P <0.01], and extrauterine growth retardation [EUGR; 38.5% in ≥50 mL/(kg · day) vs 57.6% in 0 mL/(kg · day), P <0.01)]. The logistic regression indicated that those receiving ≥50 ml/kg · day human milk had lower odds of BPD [adjusted odds ratio (AOR) 0.453; 95% confidence interval (CI): 0.309, 0.666], moderate and severe BPD (AOR 0.430; 95% CI: 0.249, 0.742), NEC (AOR 0.314; 95% CI: 0.162, 0. 607), LOS (AOR 0.420; 95% CI: 0.263, 0.673), and EUGR (AOR 0.685; 95% CI: 0.479, 0.979). CONCLUSIONS: A daily threshold amount of ≥50 ml/(kg · day) human milk in the first 4 weeks of life was associated with lower incidence of BPD as well as NEC, LOS, and EUGR in VLBW infants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03453502 . Registration date: March 5, 2018. This study was retrospectively registered.

Small RNA Sequencing Reveals Differentially Expressed miRNAs in Necrotizing Enterocolitis in Rats.

Necrotizing enterocolitis (NEC) is the leading cause of death due to gastrointestinal disease in preterm infants. The role of miRNAs in NEC is still unknown. The objective of this study was to identify differentially expressed (DE) miRNAs in rats with NEC and analyze their possible roles. In this study, a NEC rat model was established using Sprague-Dawley rat pups. Small RNA sequencing was used to analyze the miRNA expression profiles in the NEC and control rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out to identify target mRNAs for the DE miRNAs and to explore their potential roles. The DE miRNAs were verified by real-time quantitative PCR (RT-qPCR). The status of intestinal injury and the elevated levels of inflammatory cytokines in the NEC group confirmed that the NEC model was successfully established. The 16 miRNAs were found to be differentially expressed between the NEC group and the control group of rats. Bioinformatics analysis indicated that the parental genes of the DE miRNAs were predominantly implicated in the phosphorylation, cell migration, and protein phosphorylation processes. Moreover, the DE miRNAs were mainly found to be involved in the pathways of axon guidance, endocytosis, and focal adhesion, as well as in the Wnt signaling pathway, which is related to colitis. The expression patterns of the candidate miRNAs (rno-miR-27a-5p and rno-miR-187-3p), as assessed by RT-qPCR, were in accordance with the expression patterns obtained by miRNA-sequencing. The miRNA/mRNA/pathway network revealed that rno-miR-27a-5p and rno-miR-187-3p might be involved in NEC via the Wnt signaling pathway. We found an altered miRNA expression pattern in rats with NEC. We hypothesize that rno-miR-27a-5p and rno-miR-187-3p might mediate the NEC pathophysiological processes via the Wnt signaling pathway.

[Safety and efficacy of caffeine use started at different time in preterm infants: a multicenter study in Jiangsu Province, China].

OBJECTIVE: To study the efficacy and safety of caffeine used in the early (≤72 hours after birth) and late (>72 hours after birth) stage in preterm infants with a gestational age of ≤31 weeks. METHODS: A retrospective analysis was performed for 640 preterm infants (with a gestational age of ≤31 weeks) who were admitted to the neonatal intensive care unit of eight hospitals in Jiangsu Province, China. Of the 640 preterm infants, 510 were given caffeine in the early stage (≤72 hours after birth; early use group) and 130 were given caffeine in the late stage (>72 hours after birth; late use group). The clinical data were compared between the two groups. RESULTS: There were no significant differences in birth weight, Apgar score, sex, gestational age, and age on admission between the two groups (P>0.05). Compared with the late use group, the early use group had a significantly younger age at the beginning and withdrawal of caffeine treatment (P<0.05) and a significantly shorter duration of caffeine treatment (P<0.05). There was no significant difference in respiratory support on admission between the two groups (P>0.05). Compared with the late use group, the early use group had significantly lower incidence rate of apnea (P<0.05) and significantly shorter oxygen supply time and length of hospital stay (P<0.05). There were no significant differences between the two groups in the incidence rates of neonatal intracranial hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity, and patent ductus arteriosus at discharge and NBNA score at the corrected gestational age of 40 weeks (P>0.05). However, significant differences were found in the incidence of bronchopulmonary dysplasia and the rate of home oxygen therapy, but there was no significant difference in the mortality rate between the two groups (P>0.05). CONCLUSIONS: Early use of caffeine can shorten the duration of caffeine treatment, oxygen supply time, and length of hospital stay, with little adverse effect, in preterm infants with a gestational age of ≤31 weeks.

Combination of 16S rRNA and procalcitonin in diagnosis of neonatal clinically suspected sepsis.

OBJECTIVE: To investigate the application of 16S rRNA in diagnosing patients with neonatal sepsis. METHODS: We studied 60 consecutive neonatal patients with clinically suspected sepsis and 20 non-infective cases as controls. All patients were diagnosed with sepsis by clinical and experimental criteria. Clinical characteristics were recorded and 16S rRNA sequencing was conducted for all patients. The sensitivity, specificity, and accuracy of the detection methods were analyzed. RESULTS: The detection limit of 16S rRNA sequencing was 1 × 102 CFU/mL. For suspected sepsis, the positive rate of 16S rRNA detection was 93.3%, which was similar to that of procalcitonin detection (85%), and was significantly higher than that of bacterial culture (51.7%). The specificity of procalcitonin detection (74.1%) was significantly lower than that of 16S rRNA detection (100%). Moreover, the combination of 16S rRNA and procalcitonin detection showed a sensitivity of 100%, specificity of 74.1%, and accuracy of 92.0%. For proven sepsis, the sensitivity and specificity of 16S rRNA detection were both 100.0%, and those for procalcitonin were 87.1% and 87.0%, respectively. CONCLUSION: Detection of 16S rRNA has high sensitivity and specificity in diagnosing sepsis. The combination of 16S rRNA and procalcitonin has even better sensitivity with acceptable specificity.

Inhibition of HMGB1 improves necrotizing enterocolitis by inhibiting NLRP3 via TLR4 and NF-κB signaling pathways.

OBJECTIVE: To explore the relationship between high-mobility group box 1 (HMGB1) and NLR pyrin domain containing 3 (NLRP3) in the development of necrotizing enterocolitis (NEC). METHODS: NEC rat models were constructed and treated with HMGB1 inhibitor glycyrrhizin (GL) with different concentration. An inflammatory condition of intestinal tissue in newborn NEC rats was observed by hematoxylin and eosin staining. The messenger RNA (mRNA) and protein expression of HMGB1, NLRP3, toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), and caspase 1 were determined by real-time polymerase chain reaction and western blot analysis, respectively. The content of interleukin (IL)-1ß and tumor necrosis factor-α (TNF-α) was determined by enzyme-linked immunosorbent assay. Human intestinal epithelial cell lines were induced to NEC by lipopolysaccharides (LPSs). LPS-induced cells were transfected with small interfering RNA-HMGB1 and NLRP3 plasmid vector. The mRNA and protein expression of HMGB1, NLRP3, TLR4, NF-κB, caspase 1, IL-1ß, and TNF-α were determined by real-time PCR and western blot analysis, respectively. RESULTS: The mRNA and protein expression of HMGB1 and NLRP3 in the NEC group was significantly higher than the control group. Inhibition of HMGB1 expression improved intestinal inflammation in newborn NEC rats. The expression of HMGB1, NLRP3, TLR4, NF-κB, and caspase 1 was upregulated in NEC and was weakened after treating with GL. LPS induction to intestinal epithelial cells markedly increased the expression of HMGB1, NLRP3, TLR4, NF-κB, caspase 1, IL-1ß, and TNF-α. The knockdown of HMGB1 abolished the increase of expression, whereas further transfection with NLRP3 plasmid vector recovered the increase. CONCLUSION: HMGB1 and NLRP3 were all upregulated in the development of NEC. Inhibition on HMGB1 could improve the intestinal inflammation in NEC by inhibiting NLRP3 via TLR4 and NF-κB signaling pathways.

Protective effects of γ-aminobutyric acid against H2O2-induced oxidative stress in RIN-m5F pancreatic cells.

BACKGROUND: γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system and reported to maintain the redox homeostasis and insulin secretion function of pancreatic ß cells. This study tested the hypothesis that GABA maintains cellular redox status, and modulates glycogen synthase kinase (GSK)-3ß and antioxidant-related nuclear factor erythroid 2-related factor 2 (NRF2) nuclear mass ratio in the H2O2-injured RINm5F cells. METHODS: RINm5F cells were treated with/without GABA (50, 100 and 200 µmol/L) for 48 h and then exposed to 100 µmol/L H2O2 for 30 min. Viable cells were harvested, and dichloro-dihydro-fluorescein diacetate (DCFH-DA) was used to detect reactive oxygen species (ROS) level; cellular redox status and insulin secretion were measured; cell viability was determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay; mitochondrial membrane potential (MMP) was detected by flow cytometry; relative genes levels were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR); western blotting was used to determine protein expression of GSK-3ß and p-GSK-3ß (Ser9), and nuclear and cytoplasmic NRF2. RESULTS: H2O2 increased ROS production, and induced adverse affects in relation to antioxidant defense systems and insulin secretion. These changes were restored by treatment with 100 and 200 µmol/L GABA. In addition, 100 or 200 µmol/L GABA induced membrane depolarization and increased cell viability. These effects were mediated by Caspase-3, Bcl-2 associated X protein (Bax) and B-cell lymphoma-2 (Bcl-2) expression. Western blotting indicated that GABA inhibited GSK-3ß by increasing p-GSK-3ß (Ser9) level, and directed the transcription factor NRF2 to the nucleus. CONCLUSION: In rat insulin-producing RINm5F cells, GABA exerts its protective effect by regulating GSK-3ß and NRF2, which governs redox homeostasis by inhibiting apoptosis and abnormal insulin secretion by exposure to H2O2.

[Association between serum 25(OH)D levels at birth and bronchopulmonary dysplasia in preterm infants].

OBJECTIVE: To assess the association between serum 25-hydroxyvitamin D [25(OH)D] levels at birth and bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: This study recruited preterm infants with gestational age of below 34 weeks who were born between January 2014 and December 2016. These preterm infants were classified into two groups: BPD and control. The association between serum 25(OH)D levels at birth and BPD was analyzed. RESULTS: Serum 25(OH)D levels in the BPD group was significantly lower than those in the control group [(37±17 nmol/L vs 47±20 nmol/L; P<0.05), and the rate of vitamin D deficiency was significantly higher than those in the control group (90.2% vs 74.0%; P<0.05). The level of serum 25(OH)D was negatively correlated with the incidence of BPD (r=-0.201, P=0.001). CONCLUSIONS: Vitamin D deficiency at birth may be associated with BPD in preterm infants, but need to be further studied by multivariate analysis.