Bronchopulmonary dysplasia (BPD) is a major complication in preterm infants, particularly those born before 33 weeks of gestation. Inhaled nitric oxide (iNO) is widely used to manage pulmonary hypertension (PH) and improve oxygenation, but its role in reducing BPD incidence in preterm infants with PH during the early postnatal period remains unclear. This study aimed to evaluate the impact of early iNO administration, both alone and in combination with pulmonary surfactant (PS), on the incidence of BPD in preterm infants diagnosed with PH within the first three days of life. A retrospective cohort study was conducted on 56 preterm infants (< 33 weeks gestation) with confirmed PH and hypoxemia (PaO₂ < 50 mmHg at FiO₂ ≥ 30%). Clinical outcomes, including BPD incidence, were compared between infants receiving iNO and/or PS and those who did not. Multivariate logistic regression was used to identify independent predictors of BPD. The incidence of BPD was significantly lower in the iNO group (15%) compared to the non-iNO group (63.9%) (P = 0.012). Infants receiving both iNO and PS demonstrated the best outcomes, with a marked reduction in BPD risk. Male gender and lack of PS therapy were associated with increased BPD risk. Multivariate analysis confirmed iNO (OR = 0.097, 95% CI: 0.014-0.682; P = 0.019) and PS (OR = 0.125, 95% CI: 0.021-0.728; P = 0.021) as independent protective factors against BPD. Early administration of iNO, particularly in combination with PS, significantly reduces the incidence of BPD in preterm infants with PH. These findings highlight the potential benefits of iNO and PS as preventive therapies in this high-risk population. Further prospective studies are needed to validate these results and guide clinical practice.

Objectives The aim of this study was to evaluate the impact of an antibiotic stewardship program on the resistance profiles of Klebsiella pneumoniae (K. pneumoniae) in the neonatal intensive care unit (NICU). This was achieved by examining changes in the antimicrobial resistance patterns of K. pneumoniae isolates collected from preterm infants in a level 3 NICU between 2013 and 2022. Methods We examined antibiotic resistance patterns in all isolated K. pneumoniae strains cultured from preterm infants (gestational age < 37 weeks, postnatal age > 3 days) admitted to our NICU between 2013 and 2022. To assess temporal trends, we divided the study period into three phases (2013-2015, 2016-2018, and 2019-2022) to correlate antibiotic usage trends with resistance dynamics. Multivariable logistic regression was performed to identify risk factors associated with prevalence of multidrug-resistant (MDR) K. pneumoniae colonization or infection in the NICU. Results Antimicrobial use, measured in defined daily doses(DDDs) per 100 patient-days, dropped sharply from 30.8 during 2013-2015 to 12.9 in 2016-2018, then fell further to 6.9 in 2019-2022. The rates of MDR K. pneumoniae isolation among all isolated K. pneumoniae strains decreased significantly from 57.7% in 2013-2015 to 31.8% in 2019-2022 (p = 0.001). The resistance rate to aztreonam declined from 60.8% during 2013-2015 to 41.0% in 2016-2018, then further decreased to 25.0% in 2019-2022. The resistance rate to cefepime decreased from 70.1% to 33.3% and finally to 10.2% across the same periods. The resistance rate to piperacillin-tazobactam declined significantly from 53.6% (2013-2015) to 15.2% (2016-2018) and further to 6.8% (2019-2022). The resistance rate to imipenem also declined from 51.5% (2013-2015) to 4.2% (2016-2018) and ultimately to 1.1% (2019-2022). Multivariable logistic regression analysis reveales that exposure to third-generation or higher cephalosporins (aOR = 2.460, 95%CI: 1.386 to 4.365, p = 0.002) or glycopeptide antibiotics (aOR = 1.887, 95%CI: 1.100 to 3.237, p = 0.021) prior to specimen collection increases the risk of isolating MDR K. pneumonia strains. Conclusions This study demonstrates that reducing broad-spectrum antibiotic use in NICUs may lower the prevalence of MDR K. pneumoniae colonization and infection in premature infants.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) can result from various factors, including sepsis, one of the high-risk causes of ALI/ARDS. Recent research emphasizes the role of Glutamate metabolism in ALI/ARDS. Our study found a strong correlation between the difference in serological Glutamate levels of arterial vs venous blood and the progression of lung injury. High arterial - venous (A-V) Glutamate discrepancies were significantly associated with severity in ALI/ARDS patients. Additionally, the subunit of Glutamate transporter system XC- was notably elevated in mouse lungs affected by sepsis and LPS-induced macrophages. Pharmacological inhibition of system XC- or knocking down xCT worsened sepsis-related lung injury in mice. We also showed that xCT in macrophages is essential for activating system XC- for Glutamate transport, offering protection against sepsis-related ALI. Our findings highlight the therapeutic potential of Glutamate transport in mitigating lung injury and provide a promising approach for predicting ALI/ARDS prognosis.

Rationale: Pulmonary fibrosis is a chronic progressive lung disease with limited therapeutic options. We previously revealed that there is iron deposition in alveolar epithelial type II cell (AECII) in pulmonary fibrosis, which can be prevented by the iron chelator deferoxamine. However, iron in the cytoplasm and the mitochondria has two relatively independent roles and regulatory systems. In this study, we aimed to investigate the role of mitochondrial iron deposition in AECII injury and pulmonary fibrosis, and to find potential therapeutic strategies. Methods: BLM-treated mice, MLE-12 cells, and primary AECII were employed to establish the mouse pulmonary fibrosis model and epithelial cells injury model, respectively. Mitochondrial transplantation, siRNA and plasmid transfection, western blotting (WB), quantitative real-time polymerase chain reaction (RT-qPCR), polymerase chain reaction (PCR), immunofluorescence, immunoprecipitation (IP), MitoSOX staining, JC-1 staining, oxygen consumption rate (OCR) measurement, and Cell Counting Kit -8 (CCK8) assay were utilized to elucidate the role of mitochondrial iron deposition in cell and lung fibrosis and determine its mechanism. Results: This study showed that prominent mitochondrial iron deposition occurs within AECII in bleomycin (BLM)-induced pulmonary fibrosis mouse model and in BLM-treated MLE-12 epithelial cells. Further, the study revealed that healthy mitochondria rescue BLM-damaged AECII mitochondrial iron deposition and cell damage loss. Mitoferrin-2 (MFRN2) is the main transporter that regulates mitochondrial iron metabolism by transferring cytosolic iron into mitochondria, which is upregulated in BLM-treated MLE-12 epithelial cells. Direct overexpression of MFRN2 causes mitochondrial iron deposition and cell damage. In this study, decreased ubiquitination of the ubiquitin ligase F-box/LRR-repeat protein 5 (FBXL5) degraded iron -reactive element -binding protein 2 (IREB2) and promoted MFRN2 expression as well as mitochondrial iron deposition in damaged AECII. Activation of the prostaglandin E2 receptor EP4 subtype (EP4) receptor signaling pathway counteracted mitochondrial iron deposition by downregulating IREB2-MFRN2 signaling through upregulation of FBXL5. This intervention not only reduced mitochondrial iron content but also preserved mitochondrial function and protected against AECII damage after BLM treatment. Conclusion: Our findings highlight the unexplored roles, mechanisms, and regulatory approaches of abnormal mitochondrial iron metabolism of AECII in pulmonary fibrosis. Therefore, this study deepens the understanding of the mechanisms underlying pulmonary fibrosis and offers a promising strategy for developing effective therapeutic interventions using the EP4 receptor activator.

Background To investigate the association between sex and neonatal respiratory distress syndrome (NRDS). Methods Neonates born at our hospital and transferred to the neonatal department within 1 h were retrospectively analyzed. Depending on whether they developed NRDS during their hospital stay, the neonates was divided into NRDS and non-NRDS groups. There were 142 neonates in the NRDS group (95 males and 47 females) and 310 neonates in the non-NRDS group (180 males and 140 females). The neonates’ data on gestational age (GA), sex, birth weight, white blood cell count (WBC), platelet count (PLT), C-reactive protein (CRP), total immunoglobulin M (total IgM), gestational diabetes mellitus(GDM), antenatal steroids use, meconium-stained amniotic fluid, and preterm premature rupture of membranes(PPROM) were gathered. Results 452 neonates (265 males and 187 females) were involved for the purpose of collecting basic characteristic. Multivariate analysis, males had a 1.87 times higher risk of NRDS than females ( P < 0.05) after controlling for the confounding effects of GA, birth weight, WBC, PLT, CRP, total IgM, GDM, antenatal steroids use, meconium-stained amniotic fluid, and PPROM. Conclusions Sex was associated with NRDS; males had a considerably higher risk of NRDS than females.

N-methyl-d-aspartate (NMDA) receptor (NMDAR) activation mediates glutamate (Glu) toxicity and involves bleomycin (BLM)-induced acute lung injury (ALI). We have reported that bone marrow-derived mesenchymal stem cells (BM-MSCs) are NMDAR-regulated target cells, and NMDAR activation inhibits the protective effect of BM-MSCs on BLM-induced pulmonary fibrosis, but its effect on ALI remains unknown. Here, we found that Glu release was significantly elevated in plasma of mice at d 7 after intratracheally injected with BLM. BM-MSCs were pretreated with NMDA (the selective agonist of NMDAR) and transplanted into the recipient mice after the BLM challenge. BM-MSCs administration significantly alleviated the pathological changes, inflammatory response, myeloperoxidase activity, and malondialdehyde content in the damaged lungs, but NMDA-pretreated BM-MSCs did not ameliorate BLM-induced lung injury in vivo. Moreover, NMDA down-regulated prostaglandin E2 (PGE2) secretion and cyclooxygenase (COX)-2 expression instead of COX-1 expression in BM-MSCs in vitro. We also found that NMDAR1 expression was increased and COX-2 expression was decreased, but COX-1 expression was not changed in primary BM-MSCs of BLM-induced ALI mice. Further, the cultured supernatants of lipopolysaccharide (LPS)-pretreated RAW264.7 macrophages were collected to detect inflammatory factors after co-culture with NMDA-pretreated BM-MSCs. The co-culture experiments showed that NMDA precondition inhibited the anti-inflammatory effect of BM-MSCs on LPS-induced macrophage inflammation, and PGE2 could partially alleviate this inhibition. Our findings suggest that NMDAR activation attenuated the protective effect of BM-MSCs on BLM-induced ALI in vivo. NMDAR activation inhibited COX-2 expression and PGE2 secretion in BM-MSCs and weakened the anti-inflammatory effect of BM-MSCs on LPS-induced macrophage inflammation in vitro. In conclusion, NMDAR activation attenuates the protective effect of BM-MSCs on BLM-induced ALI via the COX-2/PGE2 pathway. Keywords: Acute Lung Injury, BM-MSCs, NMDA receptor, COX-1/2, PGE2.

BACKGROUND:This research will explore non-linear relationship between vitamin D status on admission and bronchopulmonary dysplasia (BPD) in preterm infants. METHODS:Data were retrospectively collected on preterm infants ≤32 weeks gestation and ≥28 weeks gestation hospitalized in our hospital between Jan. 2019 and Jul. 2022, which were classified into BPD and non-BPD groups according to BPD diagnostic criteria. Independent influences between the two groups were staged using comparison of differences between groups, univariate analysis, multivariate analysis, smoothed curve fitting, and threshold effect staging. RESULTS:255 preterm infants were enrolled in this research, including 135 males and 120 females, with a mean gestational age of 30.59 ± 0.86 weeks. Vitamin D status on admission was an independent protective factor for BPD in preterm infants, with a 6% reduction in the probability of BPD for every 1 ng/ml increase in vitamin D status on admission (p = 0.036). There was also a non-linear relationship, with each 1 ng/ml increase in vitamin D status on admission being associated with an 87% reduction in the incidence of BPD when vitamin D status was <12.82 ng/ml (p = 0.010). CONCLUSION:Vitamin D status on admission and BPD are non-linearly in preterm infants at 28-32 weeks gestation. IMPACT STATEMENT:Analyzing the relationship between vitamin D status on admission and BPD. A nonlinear relationship and turning point between vitamin D status on admission and BPD was derived by curve fitting and threshold effect. We provide a new reference point for vitamin D supplementation for the prevention of neonatal BPD and to avoid ineffective overmedication.

Objective To explore the factors influencing C-reactive protein (CRP) status in neonates on admission after birth. Methods 820 newborns born and hospitalized at Xiangya Hospital of Central South University from Jan. 2020 to Dec. 2020 were retrospectively analyzed. Maternal medical history and medication use during pregnancy, neonatal demographic information and status at birth were collected through the electronic medical record system. Statistical software was used to analyze the possible relationship between perinatal factors and CRP on admission after birth. Results A total of 820 neonates were analyzed, including 463 males and 357 females with a mean gestational age (GA) of 36.07 ± 3.30 weeks. (1) Multifactor Logistic regression analysis: larger GA (OR: 1.13, 95%CI: 1.00-1.28, P = 0.042), premature rupture of membranes (PROM) ≥ 18 h (OR: 2.39, 95%CI: 1.35–4.23, P = 0.003) and maternal autoimmune diseases (OR: 5.30, 95%CI: 2.15–13.07, P < 0.001) were independent risk factors for CRP ≥ 8 mg/L. Cesarean delivery (OR 0.40, 95%CI: 0.26–0.60, P < 0.001) was independent protective factor for CRP ≥ 8 mg/L. (2) Threshold effect analysis: A non-linear relationship was found between GA and CRP. When GA is less than 33.9 weeks, the risk of CRP ≥ 8 mg/L was reduced by 28% with one week increased ( P < 0.001), and when GA is more than 33.9 weeks, the risk of CRP ≥ 8 mg/L was increased by 61% with one week increased ( P < 0.001). Conclusions GA, PROM, maternal autoimmune diseases and cesarean delivery were all independent influences neonatal CRP ≥ 8 mg/L on admission, and there was a nonlinear relationship between GA and neonatal CRP ≥ 8 mg/L on admission.

Background Studies have shown that the release of endogenous glutamate (Glu) participates in lung injury by activating N-methyl-D-aspartate receptor (NMDAR), but the mechanism is still unclear. This study was to investigate the effects and related mechanisms of Glu on the lipid synthesis of pulmonary surfactant (PS) in isolated rat lung tissues. Methods The cultured lung tissues of adult SD rats were treated with Glu. The amount of [3H]-choline incorporation into phosphatidylcholine (PC) was detected. RT-PCR and Western blot were used to detect the changes of mRNA and protein expression of cytidine triphosphate: phosphocholine cytidylyltransferase alpha (CCTα), a key regulatory enzyme in PC biosynthesis. Western blot was used to detect the expression of NMDAR1, which is a functional subunit of NMDAR. Specific protein 1 (Sp1) expression plasmids were used. After transfected with Sp1 expression plasmids, the mRNA and protein levels of CCTα were detected by RT-PCR and Western blot in A549 cells. After treated with NMDA and MK-801, the mRNA and protein levels of Sp1 were detected by RT-PCR and Western blot in A549 cells. Results Glu decreased the incorporation of [3H]-choline into PC in a concentration- and time- dependent manner. Glu treatment significantly reduced the mRNA and protein levels of CCTα in lungs. Glu treatment up-regulated NMDAR1 protein expression, and the NMDAR blocker MK-801 could partially reverse the reduction of [3H]-choline incorporation induced by Glu (10−4 mol/L) in lungs. After transfected with Sp1 plasmid for 30 h, the mRNA and protein expression levels of CCTα were increased and the protein expression of Sp1 was also up-regulated. After A549 cells were treated with NMDA, the level of Sp1 mRNA did not change significantly, but the expression of nucleus protein in Sp1 was significantly decreased, while the expression of cytoplasmic protein was significantly increased. However, MK-801could reverse these changes. Conclusions Glu reduced the biosynthesis of the main lipid PC in PS and inhibited CCTα expression by activating NMDAR, which were mediated by the inhibition of the nuclear translocation of Sp1 and the promoter activity of CCTα. In conclusion, NMDAR-mediated Glu toxicity leading to impaired PS synthesis may be a potential pathogenesis of lung injury.

Neonatal bacterial meningitis remains a common and life-threatening disease in newborns, with high mortality and morbidity.Despite its declining incidence in recent years, the rate of severe sequelae shows slight changes.The clinical manifestation of neonatal bacterial meningitis is atypical, and thus its diagnosis requires cerebrospinal fluid examination.Early detection and effective antibiotic treatment are the key to improve the survival rate.In addition, neonatal bacterial meningitis is often complicated with brain edema and intracranial hypertension, which would result in cerebral ischemia and hypoxia, and further aggravate brain injury.Therefore, more attention should be paid to the prevention and treatment of brain edema and intracranial hypertension while adopting antibiotic therapy in the treatment of neonatal bacterial meningitis.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by myofibroblast proliferation and abnormal accumulation of extracellular matrix in the lungs. After lung injury, M2 macrophages mediate the pathogenesis of pulmonary fibrosis by secreting fibrotic cytokines that promote myofibroblast activation. The TWIK-related potassium channel (TREK-1, also known as KCNK2) is a K2P channel that is highly expressed in cardiac, lung, and other tissues; it worsens various tumors, such as ovarian cancer and prostate cancer, and mediates cardiac fibrosis. However, the role of TREK-1 in lung fibrosis remains unclear. This study aimed to examine the effects of TREK-1 on bleomycin (BLM)-induced lung fibrosis. The results show that TREK-1 knockdown, mediated by the adenovirus or pharmacological inhibition of TREK-1 with fluoxetine, resulted in diminished BLM-induced lung fibrosis. TREK-1 overexpression in macrophages remarkably increased the M2 phenotype, resulting in fibroblast activation. Furthermore, TREK-1 knockdown and fluoxetine administration directly reduced the differentiation of fibroblasts to myofibroblasts by inhibiting the focal adhesion kinase (FAK)/p38 mitogen-activated protein kinases (p38)/Yes-associated protein (YAP) signaling pathway. In conclusion, TREK-1 plays a central role in the pathogenesis of BLM-induced lung fibrosis, which serves as a theoretical basis for the inhibition of TREK-1 as a potential therapy protocol for lung fibrosis.

Intracranial hypertension (ICH) is a serious threat to the health of neonates. However, early and accurate diagnosis of neonatal intracranial hypertension remains a major challenge in clinical practice. In this study, a predictive model based on quantitative magnetic resonance imaging (MRI) data and clinical parameters was developed to identify neonates with a high risk of ICH. Newborns who were suspected of having intracranial lesions were included in our study. We utilized quantitative MRI to obtain the volumetric data of gray matter, white matter, and cerebrospinal fluid. After the MRI examination, a lumbar puncture was performed. The nomogram was constructed by incorporating the volumetric data and clinical features by multivariable logistic regression. The performance of the nomogram was evaluated by discrimination, calibration curve, and decision curve. Clinical parameters and volumetric quantitative MRI data, including postmenstrual age (p = 0.06), weight (p = 0.02), mode of delivery (p = 0.01), and gray matter volume (p = 0.003), were included in and significantly associated with neonatal intracranial hypertension risk. The nomogram showed satisfactory discrimination, with an area under the curve of 0.761. Our results demonstrated that decision curve analysis had promising clinical utility of the nomogram. The nomogram, incorporating clinical and quantitative MRI features, provided an individualized prediction of neonatal intracranial hypertension risk and facilitated decision making guidance for the early diagnosis and treatment for neonatal ICH. External validation from studies using a larger sample size before implementation in the clinical decision-making process is needed.

Antibiotics are essential for treating neonatal sepsis, but abuse or inappropriate use of antibiotics have harmful adverse effects. The inappropriate use of antibiotics has led to the significant increase in bacterial antimicrobial resistance in the neonatal intensive care unit (NICU). The aim of this study was to retrospectively analyze the changes in antibiotic usages in a NICU after the implementation of an antibiotic stewardship program and to determine the impact of this implementation on the short-term clinical outcomes of very low birth weight (VLBW) infants. The antibiotic stewardship program was initiated in the NICU in early 2015. For analysis, all eligible VLBW infants born from 1 January 2014 to 31 December 2016 were enrolled, and we classified the year 2014 as pre-stewardship, 2015 as during stewardship, and 2016 as post-stewardship. A total of 249 VLBW infants, including 96 cases in the 2014 group, 77 cases in the 2015 group, and 76 cases in the 2016 group, were included for final analysis. Empirical antibiotics were used in over 90% of VLBW infants in all three groups during their NICU stay. Over the 3-year period, the duration of an initial antibiotic course was significantly reduced. The proportion of patients receiving an initial antibiotic course for ≤3 days gradually increased (2.1% vs. 9.1% vs. 38.2%, p < 0.001), while the proportion of babies treated with an initial antibiotic course >7 days significantly decreased (95.8% vs. 79.2% vs. 39.5%, p < 0.001). The total days of antibiotic usage during the entire NICU stay also showed a significant reduction (27.0 vs. 21.0 vs. 10.0, p < 0.001). After adjusting for confounders, the reduction in antibiotic usage was associated with decreased odds of having an adverse composite short-term outcome (aOR = 5.148, 95% CI: 1.598 to 16.583, p = 0.006). To assess the continuity of antibiotic stewardship in the NICU, data from 2021 were also analyzed and compared to 2016. The median duration of an initial antibiotic course further decreased from 5.0 days in 2016 to 4.0 days in 2021 (p < 0.001). The proportion of an initial antibiotic course in which antibiotics were used for ≤3 days increased (38.2% vs. 56.7%, p = 0.022). Total antibiotic usage days during the entire NICU stay also decreased from 10.0 days in 2016 to 7.0 days in 2021 (p = 0.010). The finding of this study strongly suggests that restricting antibiotic use in VLBW infants is beneficial and can be achieved safely and effectively in China.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease characterized by extensive extracellular matrix (ECM) deposition by activated myofibroblasts, which are specialized hyper-contractile cells that promote ECM remodeling and matrix stiffening. New insights on therapeutic strategies aimed at reversing fibrosis by targeting myofibroblast fate are showing promise in promoting fibrosis resolution. Previously, we showed that a novel adipocytokine, omentin-1, attenuated bleomycin (BLM)-induced lung fibrosis by reducing the number of myofibroblasts. Apoptosis, deactivation, and reprogramming of myofibroblasts are important processes in the resolution of fibrosis. Here we report that omentin-1 reverses established lung fibrosis by promoting mechanically activated myofibroblasts dedifferentiation into lipofibroblasts. Omentin-1 promotes myofibroblasts lipogenic differentiation by inhibiting dimerization and nuclear translocation of glycolytic enzymes pyruvate kinase isoform M2 (PKM2) and activation of the downstream Yes-associated protein (YAP) by increasing the cofactor fructose-1,6-bisphosphate (F1, 6BP, FBP). Moreover, omentin-1 activates proliferator-activated receptor gamma (PPARγ) signaling, the master regulator of lipogenesis, and promotes the upregulation of the lipogenic differentiation-related protein perilipin 2 (PLIN2) by suppressing the PKM2-YAP pathway. Ultimately, omentin-1 facilitates myofibroblasts transformation into the lipofibroblast phenotype, with reduced collagen synthesis and enhanced degradation properties, which are crucial mechanisms to clear the ECM deposition in fibrotic tissue, leading to fibrosis resolution. Our results indicate that omentin-1 targets mechanical signal accelerates fibrosis resolution and reverses established lung fibrosis by promoting myofibroblasts lipogenic differentiation, which is closely associated with ECM clearance in fibrotic tissue. These findings suggest that targeting mechanical force to promote myofibroblast lipogenic differentiation is a promising therapeutic strategy against persistent lung fibrosis.

目的:探讨肺表面活性物质(PS)治疗新生儿呼吸窘迫综合征(NRDS)前给予经鼻持续气道正压通气(nCPAP)呼吸支持的最佳时间窗.方法:选择2017年1月至2019年12月期间我院收治的NRDS患儿100例.根据随机数字表法分为A组(给予PS前预先进行小于2h的nCPAP,n=33)、B组(给予PS前预先进行2-4h的nCPAP,n=33)和C组(立即给予PS,n=34).对比三组患儿的血气分析指标、肺功能指标、临床指标和并发症发生率.结果:A组、B组给予PS后4h、给予PS后24 h动脉血氧分压(PaO2)、pH值高于C组,且B组高于A组(P＜0.05),而动脉二氧化碳分压(PaCO2)低于C组,且B组低于A 组(P＜0.05).A组、B组给予PS后4 h、给予PS后24h潮气量(VT)、肺动态顺应性(CD)高于C组,且B组高于A组(P＜0.05),而吸气阻力(Raw)低于C组,且B组低于A组(P＜0.05).B组用药后3天内需气管插管行机械通气例数少于A组和C组,住院时间短于A组和C组(P＜0.05),A组、C组的用药后3天内需气管插管行机械通气例数、住院时间对比无明显差异(P＞0.05).三组患儿并发症发生率未见统计学差异(P＞0.05).结论:给予PS前预先进行2-4h的nCPAP,可较好地改善患儿血气分析指标和肺功能,有助于改善患儿预后.

OBJECTIVE:To elucidate an etiology in a case with persistent oligohydramnios by prenatal diagnosis and actively treat the case to achieve good prognosis. METHODS:We performed whole exome sequencing (WES) of DNA from the fetus and parents. Serial amnioinfusions were conducted until birth. Pressors were required to maintain normal blood pressure. The infant angiotensin-converting enzyme (ACE) activity, angiotensin II (Ang II, a downstream product of ACE), and compensatory enzymes (CEs) activities were measured. Compensatory enzyme activities in plasma from age-matched healthy controls were also detected. RESULTS:We identified a fetus with a severe ACE mutation prenatally. The infant was born prematurely without pulmonary dysplasia. Hypotension and anuria resolved spontaneously. He had almost no ACE activity, but his Ang II level and CE activity exceeded the upper limit of the normal range and the upper limit of the 95% confidence interval of controls, respectively. His renal function also largely recovered. CONCLUSION:Fetuses with ACE mutations can be diagnosed prenatally through WES. Serial amnioinfusion permits the continuation of pregnancy in fetal ACE deficiency. Compensatory enzymes for defective ACE appeared postnatally. Renal function may be spared by preterm delivery; furthermore, for postnatal vasopressor therapy to begin, improving renal perfusion pressure before nephrogenesis has been completed.

背景 临床已将脑电监测广泛用于早产儿脑发育评估及脑损伤患儿脑功能评估,无临床症状的足月高危新生儿(简称高危儿)生后早期脑电变化的临床报道较少.目的 探讨高危儿生后早期行脑电筛查的必要性.设计 回顾性队列研究.方法 回顾性采集高危儿生后 72h内行脑电生理监测病例的基本信息、孕母信息、产时信息、振幅整合脑电图(aEEG)及视频脑电图(vEEG)信息,以vEEG为脑电监测的金标准,aEEG为筛查手段,基于《发育调查问卷(3)》的语言、大动作、精细动作、解决问题和个人-社会的 5 个能区,选取《贝利婴儿发展量表》12 月龄时的共同类似问题自制神经行为发育筛查问卷,以 12 月龄时神经行为预后为结局.主要结局指标 生后早期脑电监测对 12 月龄时神经行为预后的筛查效果.结果 符合本文纳入和排除标准的 398 例高危儿进入本文分析.男 205 例(51.5％),女 193 例,胎龄 37+0～41+2(38.9±1.1)周,生命体征均平稳,无缺氧表现及神经系统临床表现.均在生后 72h内进行了aEEG和vEEG检查,aEEG真阳性 46 例,真阴性 325 例,假阳性 0 例,假阴性 27 例,aEEG 的敏感度 63.0％(95％CI:51.7％～74.4％),特异度 100％(95％CI:100％～100％).vEEG 脑电异常组(真阳性 46 例,假阴性 27 例)和 vEEG 脑电正常组(真阴性 325 例,假阳性 0 例)高危儿出生体重、小于胎龄儿、住院天数、阴道分娩、产钳助产、宫内窘迫、胎心＜100 次/分、脐动脉血气pH值、BE值、乳酸差异有统计学意义.386 例(97.0％)完成了 12 月龄时神经行为发育筛查问卷电话随访,vEEG脑电正常组较vEEG脑电异常组(4.1％vs 40.3％)神经行为发育筛查问卷五大能区总分、语言、大动作、精细动作、解决问题和个人-社会能区得分 10 分比例差异均有统计学意义.结论 以vEEG为金标准,aEEG的敏感度为 63.0％,特异度为 100％,脑电正常和异常的高危儿分别有 4.1％和 40.3％于 12 月龄随访神经行为发育异常,因此生后早期行aEEG脑电筛查是必要的.

Intrauterine hypoxia is a common complication during pregnancy and could increase the risk of cardiovascular disease in offspring. However, the underlying mechanism is controversial. Memantine, an NMDA receptor antagonist, is reported to be a potential cardio-protective agent. We hypothesized that antenatal memantine treatment could prevent heart injury in neonatal offspring exposed to intrauterine hypoxia. Pregnant rats were exposed to gestational hypoxia or antenatal memantine treatment during late pregnancy. Newborns were then sacrificed to assess multiple parameters. The results revealed that Intrauterine hypoxia resulted in declining birth weight, heart weight, and an abnormally high heart weight/birth weight ratio. Furthermore, intrauterine hypoxia caused mitochondrial structural, functional abnormalities and decreased expression of DRP1, and upregulation of NMDAR1 in vivo. Antenatal memantine treatment,an NMDARs antagonist, improved these changes. In vitro, hypoxia increased the glutamate concentration and expression of NMDAR1. NMDAR activation may lead to similar changes in mitochondrial function, structure, and downregulation of DRP1 in vitro. Pharmacological blockade of NMDARs by the non-competitive NMDA antagonist MK-801 or knockdown of the glutamate receptor NR1 significantly attenuated the increased mitochondrial reactive oxygen species and calcium overload-induced by hypoxia exposure. These facts suggest that memantine could provide a novel and promising treatment for clinical use in intrauterine hypoxia during pregnancy to protect the cardiac mitochondrial function in the offspring. To our best knowledge, our research is the first study that shows intrauterine hypoxia can excessively activate cardiac NMDARs and thus cause mitochondrial dysfunction.

Background:A large number of our previous studies showed that endogenous glutamate and N-methyl-D-aspartate receptor (NMDAR) activation may be involved in various types of acute lung injury, airway inflammation, asthma, and pulmonary fibrosis. In animal models, the transplantation of exogenous bone marrow mesenchymal stem cells (BM-MSCs) is the most promising treatment for idiopathic pulmonary fibrosis. However, there are limited reports on the status of endogenous BM-MSCs in the process of bleomycin-induced pulmonary fibrosis in animals.Methods:We constructed a mouse model of bleomycin-induced pulmonary fibrosis. In vitro, the senescence model of BM-MSCs was constructed with hydrogen peroxide and high concentration of N-methyl-D-aspartate (NDMA). The changes in aging-related indexes were detected by senescence associated beta-galactosidase (SA-β-gal) staining, western blot, flow cytometry and real time-PCR. The epithelial-mesenchymal transformation (EMT) changes of mouse lung epithelial cells (MLE-12) co-cultured with senescent BM-MSCs were detected by immunofluorescence and western blotting.Results:We observed that endogenous BM-MSCs senescence occurs during bleomycin-induced pulmonary fibrosis in mice, and the model group had a higher expression level of the NMDAR subunit than the control group. We observed a significant increase in NMDAR subunit expression in a hydrogen peroxide-induced senescent cell model in vitro. BM-MSCs showed senescence-related phenotype and cell cycle arrest after high concentration of NMDA treatment. At the same time, the expression levels of the classic Wingless and int-1 (Wnt) pathway protein β-cantenin and downstream cyclin D1 also changed. In the co-culture of aged BM-MSCs and MLE-12 cells, EMT can be promoted in MLE-12 cells, and MK-801 can partially antagonize the occurrence of EMT. The NMDAR antagonist can partially prevent the above phenomenon.Conclusions:High concentrations of NMDA can promote senescence of BM-MSCs. NMDAR blockers may inhibit endogenous BM-MSCs aging through the WNT signaling pathway, thereby reducing the effect of bleomycin-induced pulmonary fibrosis.