Sepsis-associated acute lung injury (SALI) significantly jeopardizes the health and survival prospects of neonates. Although breast milk has been identified to decrease the incidence and mortality rates associated with sepsis, the specific protective components remain unclear. In our research, milk-derived antimicrobial peptide-1 (MAMP-1) is found to be significantly expressed and possessing favorable physicochemical properties within the breast milk for premature infants. In the experiment of MAMP-1 acting on lipopolysaccharide (LPS)-induced SALI in neonatal mice, MAMP-1 pretreatment significantly increased survival rates, attenuated lung tissue damage, and reduced pro-inflammatory cytokine levels in serum and lung tissue in LPS-challenged mice. Transcriptome analysis further revealed that MAMP-1 pretreatment inhibits the regulation of toll-like receptor 4 (TLR4) signaling pathway, upregulates lipid metabolism related genes, especially apolipoprotein A-IV (APOA4). This results in a reduced expression of key pro-inflammatory factors and cholesterol levels, while simultaneously increasing high-density lipoprotein cholesterol levels, thereby suppressing the dysregulated inflammatory response. These findings identify MAMP-1 as a promising breast milk-derived peptide for the prevention of neonatal SALI.

To investigate the impact of different feeding methods on the manifestation of novel coronavirus infection symptoms in newborns following maternal infection with the novel coronavirus. Among the 257 mother-infant pairs, participants were categorized into three groups according to feeding method: the direct breastfeeding group (n = 125), the bottle-feeding with expressed breast milk group (n = 87), and the artificial feeding group (n = 45). No statistically significant differences were observed in the maternal clinical manifestations of COVID-19 across the three groups (p > 0.05). Importantly, none of the newborns in any of the three groups exhibited symptoms of SARS-CoV-2 infection either during hospitalization or during the one-week follow-up after discharge.

MAMP-1 is a polypeptide derived from breast milk. It has a protective effect on the intestines of mice with necrotizing enterocolitis through the TLR4/PI3K/AKT/NFκB signaling pathway and positively regulates the gut microbiota.

This review explores the association between the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasomes and necrotizing enterocolitis (NEC) in neonates. It underscores the role of NLRP3 inflammasome overactivation in NEC pathogenesis and proposes that inhibiting NLRP3 inflammasome activation may improve therapeutic benefits. This review examines various strategies to inhibit NLRP3 inflammasome activation, detailing their pharmacological mechanisms. IMPACT: The aim of this review is to discuss the role of NLRP3 inflammasome in the progression of NEC. Abnormal NLRP3 inflammasome activation in patients with NEC and experimental models. Molecules and proteins have been identified as regulators of NLRP3 inflammasome activity, offering avenues for NEC treatment. The NLRP3 inflammasome is a key contributor to NEC. Novel NLRP3 inflammasome inhibitors are the focus of the development of NEC therapeutics.

Recent studies have demonstrated that the human antimicrobial peptide LL37 plays a critical role in immune regulation under both normal physiological conditions and during disease progression, as evidenced by its elevated levels observed in various chronic inflammatory diseases. A deeper understanding of its mechanism is essential for elucidating associated physiological and pathological processes, as well as for designing effective immune adjuvants and clinical therapeutics. In this study, we report that LL37 facilitates the assembly of unmethylated CpG dinucleotides (CpG ODNs), a clinically relevant immune adjuvant, into non-crystalline nanoparticles (NPs) with controlled size and zeta potential in a charge ratio-dependent manner. These assembled NPs enter cells via receptor-mediated macropinocytosis, coupled with LL37-mediated membrane penetration, thereby significantly enhancing cellular uptake of CpG compared to CpG alone, which enters cells through clathrin-mediated endocytosis. Consequently, the enhanced internalization of LL37-CpG NPs markedly boosts TNF-α production (>3.5-fold) in macrophages through interactions with lysosomal TLR9. This immunostimulatory mechanism offers an alternative perspective on how LL37 modulates nucleic acid assembly and activates immune cells, providing guidance for the application of peptide-CpG ODN complexes in vaccine adjuvants and immune modulation for disease treatment.

ObjectiveThis study sought to analyze the value of point of care ultrasound (POCUS) in early diagnosis and monitoring of deep abscess in newborns.MethodsRetrospective analysis of the clinical data of two newborns admitted to the Neonatal Intensive Care Unit (NICU) of our hospital and diagnosed with deep abscess of the newborn. Combined with literature analysis, the value of POCUS in early diagnosis and monitoring of deep abscess of the newborn was evaluated.ResultsThe two newborns reported in this article were all admitted to NICU due to” “fever”. POCUS was used to assist in early diagnosis of “liver abscess” and “lung abscess”. Subsequently, POCUS was used to monitor lesion changes and adjust treatment plans. All patients were cured and discharged with a good prognosis.ConclusionsDeep abscesses in newborns are very rare and often life-threatening, but apart from fever, they often have no specific clinical manifestations and are easily misdiagnosed or missed. POCUS, as a bedside auxiliary examination tool, has high accuracy, radiation free, non-invasive, and convenient, and has high diagnostic and monitoring value in early diagnosis and monitoring of deep abscess in newborns.

Antibiotic resistance is a serious global public health issue. However, there are few reports on trends in antimicrobial susceptibility in Chinese neonates, and most of the existing evidence has been derived from adult studies. We aimed to assess the trends in antimicrobial susceptibility of common pathogens in full-term neonates with invasive bacterial infections (IBIs) in China. This cross-sectional survey study analyzed the antimicrobial susceptibility in Chinese neonates with IBIs from 17 hospitals, spanning from January 2012 to December 2021. Joinpoint regression model was applied to illustrate the trends and calculate the average annual percentage change (AAPC). Using Mantel-Haenszel linear-by-linear association chi-square test, we further compared the antibiotic minimum inhibitory concentrations (MICs) by pathogens between 2019 and 2021 to provide precise estimates of changes. The proportion of Escherichia coli with extended-spectrum-beta-lactamase-negative strains increased from 0.0 to 88.5

Neonatal necrotizing enterocolitis (NEC) is the most common inflammatory intestinal disease in preterm infants, with a high incidence and mortality rate. The etiology and mechanisms of NEC are not yet fully understood, and multiple factors contribute to its occurrence and development. Recent studies have found that anemia is a risk factor for NEC in neonates, but the specific pathogenic mechanism remains unclear. This article reviews recent research on the relationship between anemia and NEC, providing a reference for further understanding the impact of anemia on intestinal injury and its association with NEC.

BackgroundPoint-of-care ultrasound (POCUS) can guide umbilical vein catheter placement in real time and monitor catheter tip position, allowing avoidance of severe complications due to catheter malposition. This study aims to explore the effectiveness of POCUS in guiding venous catheter insertion and monitoring complications.MethodsSixty-eight neonates with ultrasound-guided venous catheter insertion at the Neonatal Department of Dongguan Children's Hospital between December 2020 and February 2022 were included. POCUS was applied to monitor catheter tip location daily until catheter removal. A displacement range exceeding the intersection of the inferior vena cava and right atrium by ±0.5 cm was considered misalignment.ResultsSixty-four neonates had a displaced catheter tip (94.1%, 64/68), with a median displacement distance of 0.4 cm (minimum −0.2 cm, maximum 1.2 cm). Ten neonates had a misalignment (14.7%, 10/68) caused by displacement. Displacement usually occurs within 2–4 days after placement, with displacement rates of 94.1% (64/68), 90.6% (58/64), and 98.3% (59/60) on days 2, 3, and 4, respectively, and could still occur on day 9 post-placement. In addition, misalignment mainly occurs on the second day after placement. During the monitoring process, 58 neonates had catheter tip displacement ≥2 times, resulting in 252 displacement and 22 misalignment incidents. Among them, the catheter tip migrated outward from the inferior vena cava seven times, all of which were removed in time. Ultrasound was used for positioning 486 times, and x-ray was indirectly avoided 486 times.ConclusionThe catheter tip is prone to displacement and misalignment after umbilical vein catheterization, which most commonly occurs on days 2–4. POCUS is recommended for daily monitoring of the tip location during umbilical vein catheterization until catheter removal.

BackgroundNecrotizing enterocolitis (NEC) is a severe inflammatory bowel disease that may lead to perforation, causing high morbidity and mortality in preterm infants. Abdominal ultrasound (AUS) has been shown to provide benefits in diagnosing and managing NEC in recent years.ObjectiveThis study focused on the utility of AUS in the diagnosis and evaluation of surgical NEC.Patients and methodsIn this retrospective study, available data of the patients diagnosed from January 2019 to June 2022 were reviewed. The sensitivity and specificity of AUS in diagnosing a perforation were analyzed. Typical cases for the application of AUS in monitoring and evaluating the progression, complications, and sequela of NEC were described.ResultsThere were 69 neonates diagnosed with NEC and examined by AUS, of whom eight patients developed a perforation. AUS was used for diagnosing a perforation in eight patients with key features of pneumoperitoneum and/or complex ascites, allowing us to find four locations of perforation, with a sensitivity and specificity of 100%.ConclusionAUS plays an important role in diagnosing and evaluating surgical NEC in newborn infants, with good sensitivity and specificity.

Objective:To study the safety and feasibility of early enteral feeding during therapeutic hypothermia guided by intestinal ultrasound in neonates with hypoxic-ischemic encephalopathy (HIE).Methods:From January 2019 to December 2021, neonates with HIE who received therapeutic hypothermia in the neonatology department of our hospital were retrospectively selected. They were assigned into the ultrasound-guided observation group (admitted from May 2020 to December 2021) and the control group (admitted from January 2019 to April 2020). In the ultrasound-guided observation group, intestinal ultrasound was performed during therapeutic hypothermia. Based on clinical manifestations and ultrasound results, a small amount of enteral feeding [20 ml/(kg·d)] was initiated and gradually increased to total enteral feeding after rewarming. In the control group, 5 ml (once every 3 h) of glucose and sodium chloride solution was given during 72 h of therapeutic hypothermia. After rewarming, enteral feeding was started and gradually increased to total enteral feeding without intestinal ultrasound. The time to start enteral feeding, the time to achieve total enteral feeding, the incidences of feeding intolerance, necrotizing enterocolitis (NEC) and late-onset sepsis were compared between the two groups.Results:A total of 17 cases were in the ultrasound-guided observation group and 18 cases in the control group. The median time to start enteral feeding and to achieve total enteral feeding in the ultrasound-guided observation group were earlier than the control group [36.0 (33.5, 39.0) h vs. 77.0 (74.0, 79.3) h, 6.0 (5.5, 6.5) d vs. 8.0 (7.0, 9.0) d, P<0.001]. No significant difference existed in the incidence of feeding intolerance between the two groups. Neither groups had NEC or late-onset sepsis. Conclusions:Early enteral feeding during therapeutic hypothermia in neonates with HIE is safe and feasible. Intestinal ultrasound helps implementing feeding plan and achieving early total enteral feeding.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants with increased levels of reactive oxygen species (ROS) and ferroptosis. Herein, we designed a peptide-based nanoparticle to deliver therapeutic molecules to pulmonary, thereby ameliorating BPD. The BPD-induced damages of lung tissues were detected by H&E and immunohistochemistry staining. Inflammatory cytokines, Fe 2+ , and ROS levels were quantified by the indicated kits, respectively. The targeting relationship was verified by luciferase reporter assay and pull-down assay. Subsequently, self-assembled miR-134-5p inhibitor nanoparticles with pulmonary epithelial cell-targeting were synthesized. The characteristics were detected by transmission electron microscopy, luminescence imaging, and dynamic light scattering. A significant ferroptosis was observed in the BPD mice. The protein level of GPX4 was decreased significantly compared to the control group. Constantly, miR-134-5p showed positive regulation on ferroptosis by targeting GPX4. The designed nanoparticles were mainly accumulated in the lung region. Besides, it ameliorated experimental bronchopulmonary dysplasia via suppressing ferroptosis, in vivo and in vitro. Our findings provided a miR-134-5p/GPX4 axis in regulating ferroptosis of BPD and prompted the potential of applying the peptide-based nanoparticle to BPD treatment.

INTRODUCTION:Very preterm (VPT) infants may experience varying degrees of neurodevelopmental challenges. Lack of early markers for neurodevelopmental disorders may delay referral to early interventions. The detailed General Movements Assessment (GMA) could help us to identify early markers for VPT infants at risk of atypical neurodevelopmental clinical phenotype in the very early stage of life as soon as possible. Preterm infants with high risk of atypical neurodevelopmental outcomes will have the best possible start to life if early precise intervention in critical developmental windows is allowed.METHODS AND ANALYSIS:This is a nationwide, multicentric prospective cohort study that will recruit 577 infants born <32 weeks of age. This study will determine the diagnostic value of the developmental trajectory of general movements (GMs) at writhing and fidgety age with qualitative assessment for different atypical developmental outcomes at 2 years evaluated by the Griffiths Development Scales-Chinese. The difference in the General Movement Optimality Score (GMOS) will be used to distinguish normal (N), poor repertoire (PR) and cramped sychronised (CS) GMs. We plan to build the percentile rank of GMOS (median, 10th, 25th, 75th and 90th percentile rank) in N, PR and CS of each global GM category and analyse the relationship between GMOS in writhing movements and Motor Optimality Score (MOS) in fidgety movements based on the detailed GMA. We explore the subcategories of the GMOS list, and MOS list that may identify specific early markers that help us to identify and predict different clinical phenotypes and functional outcomes in VPT infants.ETHICS AND DISSEMINATION:The central ethical approval has been confirmed from the Research Ethical Board of Children's Hospital of Fudan University (ref approval no. 2022(029)) and the local ethical approval has been also obtained by the corresponding ethics committees of the recruitment sites. Critical analysis of the study results will contribute to providing a basis for hierarchical management and precise intervention for preterm infants in very early life.TRIAL REGISTRATION NUMBER:ChiCTR2200064521.

Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that occurs in preterm infants and lacks effective treatment. We aim to reveal the relationship between amniotic fluid (AF) peptides and lung development by analyzing the differences in the composition of AF peptides at different gestational periods, thus providing a new means of prevention and treatment for BPD. Methods: Based on the stages of lung development, we collected AF by amniocentesis in two different gestational periods, using the 25th week of pregnancy as the cut-off. We conducted a peptide omics analysis of these AF samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Additionally, we verified the regulatory effects of hyperoxia and the peptide COL5A2 on BPD-related cells [(mouse lung epithelial (MLE-12) cells] by 5-Ethynyl-2'-deoxyuridine (EdU) staining, JC-1 staining, flow cytometry, and reactive oxygen species (ROS) assay. Results: There were 131 differentially expressed peptides, including 85 up-regulated and 46 down-regulated [fold change (FC) ≥1.2 or ≤1/1.2, P<0.05], in the ≥25 weeks’ gestation group compared to the <25 weeks’ gestation group. Further bioinformatics analysis revealed that the precursor proteins of the differentially expressed peptides between these two groups were involved in the regulation of the developmental process, anatomical structure development, and other biological processes, suggesting that these differential peptides may play a key role in lung development. We found peptide COL5A2 with the sequence GPPGEPGPPG and verified the regulatory effects of COL5A2 on the proliferation, apoptosis, cell viability, and ROS levels of MLE-12 cells by cell assays. Conclusions: In this study, peptidomic studies using AF from different gestational periods revealed that peptides in AF may be involved in lung development. They could be used in the future to assist in the postnatal development of preterm infants and provide new therapeutic prospects for BPD.

目的 探讨0～1个月婴儿不同病原学社区获得性肺炎(CAP)的肺脏超声特点.方法 将因CAP在我院住院的154例0～1个月婴儿设为肺炎组,另选同期160例因黄疸住院、无肺部疾病的婴儿作为对照组.两组均进行肺脏超声检查.比较两组的肺脏超声征象.结果 肺炎组肺脏超声征象为胸膜线异常、A线减少或消失、B线增多、肺间质综合征、肺实变及肺搏动;对照组肺脏超声征象正常,胸膜线及A线清晰存在,存在肺滑,无或仅有少量B线,无肺实变及肺搏动.154例CAP患儿中,86例呼吸道病原学阳性,68例呼吸道病原学阴性.病原学阳性患儿中,95.3％可见胸膜线异常,93.0％可见B线增多,62.8％可见不同程度的肺实变,12.8％可见肺搏动.病原学阳性患儿的胸膜线异常、B线增多、A线减少或消失、肺间质综合征、肺实变及肺搏动占比均高于病原学阴性患儿.结论 0～1个月CAP婴儿的肺脏超声特点为胸膜线异常、肺间质综合征、不同程度的肺实变,以呼吸道合胞病毒肺炎、沙眼衣原体肺炎、百日咳肺炎患儿居多.肺实变多位于双肺背侧,以右上肺背侧多见.

Lung ultrasound (LUS) can be used to diagnose various neonatal lung diseases. It more sensitively diagnoses pulmonary edema, pneumothorax, pulmonary consolidation, and atelectasis than traditional X-ray and quickly determines the cause of dyspnea. As a component of severe ultrasound, LUS enables rapid bedside visualization of lung diseases and plays a major role in guiding the differential diagnosis of disease, ventilator treatment, and lung recruitment. This study introduced the application of LUS in the diagnosis and treatment of critically ill neonates with lung diseases.

Background:The chronic lung condition known as bronchopulmonary dysplasia (BPD), which primarily affects newborns, especially preterm neonates, is brought on by prolonged oxygen consumption and mechanical ventilation. This case-control study sought to investigate the pathogenesis of BPD in preterm neonates by RNA sequencing (RNA-seq).Methods:First, RNA-seq samples were collected from 3 BPD and 3 healthy preterm neonates. Based on the sequencing data and microarray data sets, MERGE.57185.1, the key long non-coding RNA (lncRNA), was identified from the differentially expressed lncRNAs and the key module by a weighted gene co-expression network analysis (WGCNA), a Venn diagram, and an expression analysis. Next, the differentially expressed messenger RNAs (mRNAs) and microRNAs (miRNAs) that were strongly correlated to MERGE.57185.1 were identified in the protein-protein interaction networks and underwent a functional enrichment analysis and Spearman correlation analysis. Finally, the mRNA [i.e., eukaryotic translation initiation factor 5A (EIF5A)] and miRNA (i.e., hsa-miR-6833-5p) with the strongest correlations to MERGE.57185.1 were identified as the downstream targets.Results:Among the 32 genes in the dark-red module and the 158 differentially expressed lncRNAs, 21 overlapping genes were identified. In the gene expression analysis, MERGE.57185.1 (an oncogene) was identified as the key lncRNA in BPD. The results of the multiple bioinformatics analysis showed that the mRNA and the miRNA with the strongest correlations to MERGE.57185.1 were hsa-miR-6833-5p (a suppressor gene) and EIF5A (an oncogene), respectively. Hsa-miR-6833-5p was lowly expressed in the BPD group, while EIF5A was highly expressed in the BPD group.Conclusions:This study identified 1 key upregulated lncRNA (i.e., MERGE.57185.1) in preterm neonatal BPD, and revealed the MERGE.57185.1/hsa-miR-6833-5p/EIF5A mechanism in preterm neonatal BPD from the lncRNA-miRNA-mRNA network. This key lncRNA gene could serve as a promising diagnostic biomarker for prenatal examinations.

Objective:This study aimed to investigate the ability of serum cholic acid (CA) and lithocholic acid (LCA) in the diagnosis and perinatal prognosis assessment of intrahepatic cholestasis of pregnancy (ICP), and the relationship between both indicators and hypoxia-inducible factor-1α (HIF-1α).Methods:Between March 2020 and March 2021, pregnant women with high levels of total bile acid (TBA) in the late pregnancy with TBA ≥10 μmol/L and TBA <10 μmol/L (control group) were included for the retrospective study. Those with TBA ≥10 μmol/L were divided into the ICP group and the asymptomatic hypercholanaemia of pregnancy (AHP) group based on ICP symptoms. The comparison of the bile acid profiles, the receiver operating characteristic (ROC) curve analysis, and Pearson correlation analysis were conducted successively.Results:Nine types of bile acids were significantly higher in ICP and AHP than in the control group, while CA and LCA serum levels in the AHP group were significantly lower than those in the ICP group (P < 0.05). The ROC curve analysis showed that LCA, CA, and LCA+CA were all diagnostic indicators for ICP, and LCA+CA displayed the greatest diagnostic value (area under the curve (AUC), 0.923). Subgroup analysis using the LCA+CA cut-off point (3.28 μmol/L) as the subgroup indicator proved that the incidence of adverse perinatal outcomes and the placental HIF-1α positivity were significantly higher in the high LCA+CA group than in the low LCA+CA group (P < 0.05). Pearson correlation analysis revealed significant positive correlations of HIF-1α expression levels to LCA, CA and LCA+CA (r = 0.473, 0.537, 0.619, respectively. P < 0.05 in all).Conclusion:This study confirmed that CA and LCA have a predictive diagnostic value for ICP in pregnant women, and the combined evaluation is associated with adverse perinatal outcomes, and LCA+CA positively correlates to placental HIF-1α expression levels.

目的 探讨不同血清白蛋白水平与不同胎龄脓毒性休克新生儿平均动脉压的关系.方法 收集2017年1月至2019年12月广东医科大学附属东莞儿童医院NICU收治的140例诊断为脓毒性休克的新生儿临床资料,按胎龄分为足月组(n=89)和早产组(n=51).根据患儿血清白蛋白水平分为足月正常白蛋白组(≥35g/L,n=32)、足月低白蛋白组(＜35g/L,n=57)、早产正常白蛋白组(≥35g/L,n=6)和早产低白蛋白组(＜35g/L,n=45).分析血清白蛋白水平与不同胎龄脓毒性休克新生儿平均动脉压的关系.结果 低白蛋白血症在新生儿脓毒性休克中的总发生率为72.9％(102/140),其中早产组发生率为88.2％(45/51),明显高于足月组;脓毒性休克新生儿中,低白蛋白组平均动脉压明显低于正常白蛋白组,差异有统计学意义.Pearson相关分析显示,白蛋白与平均动脉压呈正相关.结论 脓毒性休克新生儿的血清白蛋白水平与其平均动脉压呈正相关,罹患脓毒性休克患儿,需要密切监测血清白蛋白水平,谨防低血压.