Prenatal diagnosis and treatment for fetal angiotensin converting enzyme deficiency.

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.

Omentin-1 induces mechanically activated fibroblasts lipogenic differentiation through pkm2/yap/pparγ pathway to promote lung fibrosis resolution.

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.

Factors influencing C-reactive protein status on admission in neonates after birth.

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.

The association between sex and neonatal respiratory distress syndrome.

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.

[Effect of improvement in antibiotic use strategy on the short-term clinical outcome of preterm infants with a gestational age of <35 weeks]. / æŠ—ç”Ÿç´ ä½¿ç”¨ç­–ç•¥æ”¹è¿›å¯¹èƒŽé¾„<35周早产儿近期临床结局的影响.

OBJECTIVES: To study the effect of improvement in antibiotic use strategy on the short-term clinical outcome of preterm infants with a gestational age of <35 weeks. METHODS: The medical data were retrospectively collected from 865 preterm infants with a gestational age of <35 weeks who were admitted to the Neonatal Intensive Care Unit of Xiangya Hospital of Central South University from January 1, 2014 to December 31, 2016. The improved antibiotic use strategy was implemented since January 1, 2015. According to the time of implementation, the infants were divided into three groups: pre-adjustment (January 1, 2014 to December 31, 2014; n=303), post-adjustment Ⅰ (January 1, 2015 to December 31, 2015; n=293), and post-adjustment Ⅱ (January 1, 2016 to December 31, 2016; n=269). The medical data of the three groups were compared. RESULTS: There were no significant differences among the three groups in gestational age, proportion of small-for-gestational-age infants, sex, and method of birth (P>0.05). Compared with the pre-adjustment group, the post-adjustment I and post-adjustment Ⅱ groups had a significant reduction in the rate of use of antibiotics and the duration of antibiotic use in the early postnatal period and during hospitalization (P<0.05), with a significant increase in the proportion of infants with a duration of antibiotic use of ≤3 days or 4-7 days and a significant reduction in the proportion of infants with a duration of antibiotic use of >7 days in the early postnatal period (P<0.05). Compared with the post-adjustment Ⅰ group, the post-adjustment Ⅱ group had a significant reduction in the duration of antibiotic use in the early postnatal period and during hospitalization (P<0.05), with a significant increase in the proportion of infants with a duration of antibiotic use of ≤3 days and a significant reduction in the proportion of infants with a duration of antibiotic use of 4-7 days or >7 days (P<0.05). Compared with the pre-adjustment group, the post-adjustment I and post-adjustment Ⅱ groups had significantly shorter duration of parenteral nutrition and length of hospital stay (P<0.05). There were gradual reductions in the incidence rates of grade ≥Ⅲ intraventricular hemorrhage (IVH) and late-onset sepsis (LOS) after the adjustment of antibiotic use strategy. The multivariate logistic regression analysis showed that the adjustment of antibiotic use strategy had no effect on short-term adverse clinical outcomes, and antibiotic use for >7 days significantly increased the risk of adverse clinical outcomes (P<0.05). CONCLUSIONS: It is feasible to reduce unnecessary antibiotic use by the improvement in antibiotic use strategy in preterm infants with a gestational age of <35 weeks, which can also shorten the duration of parenteral nutrition and the length of hospital stay and reduce the incidence rates of grade ≥Ⅲ IVH and LOS.

D-bifunctional protein deficiency caused by HSD17B4 gene mutation in a neonate. / HSD17B4åŸºå› çªå˜è‡´D-双功能蛋白缺乏症.

A 15-day-old boy was admitted to the hospital due to repeated convulsions for 14 days. The main clinical manifestations were uncontrolled seizures, hypoergia, feeding difficulties, limb hypotonia, and bilateral hearing impairment. Clinical neurophysiology showed reduced brainstem auditory evoked potential on both sides and burst-suppression pattern on electroencephalogram. Measurement of very-long-chain fatty acids in serum showed that C26:0 was significantly increased. Genetic testing showed a pathogenic compound heterozygous mutation, c.101C>T(p.Ala34Val) and c.1448_1460del(p.Ala483Aspfs*37), in the HSD17B4 gene. This article reports a case of D-bifunctional protein deficiency caused by HSD17B4 gene mutation and summarizes the epidemiological and clinical features, diagnosis, and treatment of this disease, with a focus on the differential diagnosis of this disease from Ohtahara syndrome.

Utilization pattern of kangaroo mother care after introduction in eight selected neonatal intensive care units in China.

BACKGROUND: Kangaroo mother care (KMC) is an evidence-based and cost-effective intervention that could prevent severe complications for preterm babies, however it has not been widely adopted in China. In this study, we aim to investigate the feasibility and parental experience of adopting KMC in a Chinese context by studying the implementation of a KMC program in eight self-selected neonatal intensive care units (NICUs). METHODS: A cross-sectional study of 135 preterm infants discharged from eight NICUs in April 2018. For infants information was collected on postnatal day and corrected gestational age (GA) at KMC initiation, frequency and duration of KMC provision and whether the infant was receiving respiratory support. A nurse-administered questionnaire on parents' knowledge and experience of KMC provision was administered to parents providing KMC. RESULTS: One hundred thirty-five preterm infants received KMC, 21.2% of all preterm infants discharged. 65.2% of those who received KMC were below 32 weeks GA, 60.7% had a birth weight below 1500 g, and 20.7% needed respiratory support at KMC initiation. Average KMC exposure was greater in infants born at GA < 28 weeks that babies born at greater GA. 94.8% of parents that participated in the parental survey indicated that KMC was positively accepted by their family members; 60.4% of the parents claimed that KMC could relieve anxiety, 57.3% claimed it prompted more interactions with medical staff and 69.8% suggested it increased parental confidence in care for their infants. CONCLUSIONS: After advocacy, training and promotion, intermittent KMC was initiated on more immature and high-risk infants, and well-accepted by parents. We suggest continuing to promote KMC education to parents and enhancing preterm infant health.

[The metabolic networks of ferroptosis and links to lung diseases].

Ferroptosis is a newly discovered non-apoptotic form of regulated cell death driven by iron-dependent lipid peroxidation. The present studies have shown that many metabolic processes and homeostasis are affected by ferroptosis. It is related to many lung diseases, including acute lung injury, chronic obstructive pulmonary disease and pulmonary fibrosis, etc. Currently, the research on ferroptosis is still in its infancy. Previous studies have confirmed that ferroptosis is regulated by a variety of genes, and the mechanism is complex, mainly involving iron homeostasis and lipid peroxidation metabolism. This review summarizes some regulation networks of metabolic processes associated with ferroptosis and discusses the roles of ferroptosis in the pathophysiological progression of many lung diseases. We expected to provide new ideas and references for the treatment of these diseases.

[Fetal pleural effusion in the uterus and dyspnea after birth].

Neonatal chylothorax is a common cause of neonatal congenital pleural effusion and is often caused by the accumulation of chylous fluid in the thoracic cavity due to the rupture of the thoracic duct and its branched lymphatic vessels for a variety of reasons. Neonatal chylothorax caused by malignant tumors is extremely rare, and this is the first case of neonatal mediastinal neuroblastoma with chylothorax in China. The boy was found to have pleural effusion in the left thoracic cavity in the uterus, and experienced apnea at birth, as well as dyspnea and cyanosis as the main manifestations after birth. He was diagnosed with left chylothorax based on conventional biochemical analysis of pleural effusion. After the treatment including persistent chest drainage and symptomatic and supportive treatment, the drainage of the left thoracic cavity reached a volume of 90-180 mL per day. Neonatal refractory chylothorax was considered. Chest radiograph on day 13 after birth showed lesions in the upper left lung field, and contrast-enhanced plain CT scan of the chest suggested the possibility of posterior mediastinal neuroblastoma. The autopsy confirmed giant posterior mediastinal neuroblastoma (poorly differentiated), which involved the C7-T6 spinal canal and the nearby erector spinae, with a small amount of tumor tissue in the liver and both adrenal glands. Mediastinal tumor is considered the underlying cause of chylothorax in this case.

[Comparison of the efficacy of domestic and imported caffeine citrate in the treatment of apnea in preterm infants: a prospective randomized double-blind controlled trial].

OBJECTIVE: To compare the efficacy of domestic and imported caffeine citrate in the treatment of apnea in preterm infants. METHODS: A total of 98 preterm infants with a gestational age of 28 - <34 weeks between April 2018 and December 2019 were enrolled. They were randomly administered with domestic (n=48) or imported caffeine citrate (n=50) within 6 hours after birth. The therapeutic effects, complications, adverse effects and clinical outcomes were compared between the two groups. RESULTS: There were no significant differences in the incidence of apnea within 7 days after birth, daily frequency of apnea, the time of apnea disappearance, the failure rate of intubation-surfactant-extubation strategy, the time of non-invasive assisted ventilation, the duration of oxygen therapy, the duration of caffeine citrate therapy, the length of hospital stay, blood gas analysis results, liver and kidney function testing results between the two groups (P>0.05). There were no significant differences in the incidence of complications and the mortality rate between the two groups (P>0.05). There was no significant difference in the incidence of adverse effects between the two groups (P>0.05). CONCLUSIONS: The efficacy and safety of domestic caffeine citrate in the treatment of apnea are similar to those of imported caffeine citrate in preterm infants.

[A multicenter survey of antibiotic use in very and extremely low birth weight infants in Hunan Province].

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (rs=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (rs=0.196, P<0.01). CONCLUSIONS: Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.

Excessive activation of NMDA receptor inhibits the protective effect of endogenous bone marrow mesenchymal stem cells on promoting alveolarization in bronchopulmonary dysplasia.

We studied the role of bone marrow mesenchymal stem cells (MSCs) in our established model of bronchopulmonary dysplasia (BPD) induced by intrauterine hypoxia in the rat. First, we found that intrauterine hypoxia can reduce the number of MSCs in lungs and bone marrow of rat neonates, whereas the administration of granulocyte colony-stimulating factor or busulfan to either motivate or inhibit bone marrow MSCs to lungs altered lung development. Next, in vivo experiments, we confirmed that intrauterine hypoxia also impaired bone marrow MSC proliferation and decreased cell cycling activity. In vitro, by using the cultured bone marrow MSCs, the proliferation and the cell cycling activity of MSCs were also reduced when N-methyl-d-aspartic acid (NMDA) was used as an NMDA receptor (NMDAR) agonist. When MK-801 or memantine as NMDAR antagonists in vitro or in vivo was used, the reduction of cell cycling activity and proliferation were partially reversed. Furthermore, we found that intrauterine hypoxia could enhance the concentration of glutamate, an amino acid that can activate NMDAR, in the bone marrow of neonates. Finally, we confirmed that the increased concentration of TNF-ɑ in the bone marrow of neonatal rats after intrauterine hypoxia induced the release of glutamate and reduced the cell cycling activity of MSCs, and the latter could be partially reversed by MK-801. In summary, intrauterine hypoxia could decrease the number of bone marrow MSCs that could affect lung development and lung function through excessive activation of NMDAR that is partially caused by TNF-ɑ.

NMDA receptor activation inhibits the antifibrotic effect of BM-MSCs on bleomycin-induced pulmonary fibrosis.

Endogenous glutamate (Glu) release and N-methyl-d-aspartate (NMDA) receptor (NMDAR) activation are associated with lung injury in different animal models. However, the underlying mechanism is unclear. Bone marrow-derived mesenchymal stem cells (BM-MSCs), which show potential use for immunomodulation and tissue protection, play a protective role in pulmonary fibrosis (PF) process. Here, we found the increased Glu release from the BM cells of bleomycin (BLM)-induced PF mice in vivo. BLM stimulation also increased the extracellular Glu in BM-MSCs via the antiporter system xc- in vitro. The gene expression of each subunit of NMDAR was detected in BM-MSCs. NMDAR activation inhibited the proliferation, migration, and paracrine function of BM-MSCs in vitro. BM-MSCs were derived from male C57BL/6 mice, transfected with lentiviral vectors carrying the enhanced green fluorescence protein gene, pretreated with NMDA, and transplanted into the female recipient mice that were intratracheally injected with BLM to induce PF. Transplantation of NMDA-pretreated BM-MSCs significantly aggravated PF as compared with that in the normal BM-MSCs transplantation group. The sex determination gene Y chromosome and green fluorescence protein genes of BM-MSCs were detected to observe BM-MSCs homing in the fibrotic lungs. Moreover, NMDAR activation inhibited BM-MSC migration by downregulating the stromal cell-derived factor-1/C-X-C chemokine receptor type 4 signaling axis. NMDAR activation aggravated the transforming growth factor-ß1-induced extracellular matrix production in alveolar epithelial cells and fibroblasts through the paracrine effects of BM-MSCs. In summary, these findings suggested that NMDAR activation-mediated Glu excitotoxicity induced by BLM in BM-MSCs abolished the therapeutic effects of normal BM-MSCs transplantation on BLM-induced PF.

Excessive Activation of NMDA Receptors Induced Neurodevelopmental Brain Damage and Cognitive Deficits in Rats Exposed to Intrauterine Hypoxia.

Intrauterine hypoxia is one of the most common stressors in fetuses, which can lead to abnormal brain development and permanent neurological deficits in adulthood. Neurological disorder excitotoxicity induced by hypoxia or ischemia may involve N-methyl-D-aspartate receptors (NMDARs), which are known to participate in the maturation and plasticity of developmental neurons. Inhibition of NMDARs has been reported to improve neurological outcomes in traumatic brain injuries and Alzheimer's disease. Here, we investigated if antenatal blockade of NMDARs induced by memantine could alleviate neurodevelopmental brain damage and long-term cognitive deficits in intrauterine hypoxia rats. Pregnant rats were assigned to four groups: air control, air + memantine, hypoxia, and hypoxia + memantine. The rats were exposed to hypoxic conditions (FiO2 = 0.095-0.115) for 8 h/day (hypoxia group) or given a daily memantine injection (5 mg/kg, i.p.) before hypoxia exposure from pregnant day 19 (G19) to G20 (hypoxia + memantine group).The influence of NMDARs antenatal blockade by memantine on intrauterine hypoxia-induced brain developmental damage and cognitive function was then studied. Intrauterine hypoxia resulted in decreased fetal body weight, brain weight, cognitive function, hippocampal neuron numbers, and Ki-67 proliferation index in the hippocampus. Memantine preventive treatment in pregnant rats before hypoxia exposure alleviated the aforementioned damage in vivo. Excessive activation of NMDARs contributes to fetal brain developmental damage and cognitive ability impairment induced by intrauterine hypoxia, which could be alleviated by antenatal memantine preventative treatment.

Antenatal blockade of N-methyl-D-aspartate receptors by Memantine reduces the susceptibility to diabetes induced by a high-fat diet in rats with intrauterine growth restriction.

Intrauterine growth retardation (IUGR) is closely related to the later development of type 2 diabetes in adulthood. Excessive activation of N-methly-D-aspartate receptors (NMDARs) causes excitatory neurotoxicity, resulting in neuronal injury or death. Inhibition of NMDARs enhances the glucose-stimulated insulin secretion and survival of islet cells in type 2 diabetic mouse and human islets. Here, we examined whether antenatal blockade of NMDARs by Memantine could decrease the risk of diabetes induced by a high-fat (HF) diet at adulthood in IUGR rats. Pregnant SD rats were assigned to four groups: control, IUGR, Memantine, and Memantine + IUGR. The pregnant rats were exposed to hypoxic conditions (FiO2 = 0.105) for 8 h/day (IUGR group) or given a daily Memantine injection (5 mg/kg, i.p.) before hypoxia exposure from embryonic day (E) 14.5 to E 20.5 (Memantine + IUGR). The offspring were fed an HF diet with 60% of the calories from age 4 to 12 weeks. We found that NMDAR mRNAs were expressed in the fetal rat pancreas. An HF diet resulted in a high rate of diabetes at adulthood in the IUGR group. Antenatal Memantine treatment decreased the risk of diabetes at adulthood of rats with IUGR, which was associated with rescued glucose tolerance, increased insulin release, improved the insulin sensitivity, and increased expression of genes related to beta-cell function in the pancreas. Together, our results suggest that antenatal blockade of NMDARs by Memantine in pregnant rats improves fetal development and reduces the susceptibility to diabetes at adulthood in offspring.

[Methods for establishing animal model of bronchopulmonary dysplasia and their evaluation].

With the development of treatment, the survival rate of premature infants has significantly increased, especially extremely premature infants and very low birth weight infants. This has led to an increase in incidence of bronchopulmonary dysplasia (BPD) year by year. BPD has been one of the most common respiratory system diseases in premature infants, especially the small premature infants. Arrested alveolar development is an important cause of BPD. Therefore, the mechanism of arrested alveolar development and the intervention measures for promoting alveolar development are the focuses of research on BPD. Selecting the appropriate animal model of BPD is the key to obtaining meaningful results in the basic research on BPD. Based on above, several common methods for establishing an animal model of BPD and the corresponding changes in pathophysiology are summarized and evaluated in order to provide a reference for selecting the appropriate animal model in studies on the pathogenesis, pathophysiology, and prevention and control strategies of BPD.

N-methyl-D-aspartate receptor activation mediates lung fibroblast proliferation and differentiation in hyperoxia-induced chronic lung disease in newborn rats.

BACKGROUND: Previous studies have suggested that endogenous glutamate and its N-methyl-D-aspartate receptors (NMDARs) play important roles in hyperoxia-induced acute lung injury in newborn rats. We hypothesized that NMDAR activation also participates in the development of chronic lung injury after withdrawal of hyperoxic conditions. METHODS: In order to rule out the anti-inflammatory effects of NMDAR inhibitor on acute lung injury, the efficacy of MK-801 was evaluated in vivo using newborn Sprague-Dawley rats treated starting 4 days after cessation of hyperoxia exposure (on postnatal day 8). The role of NMDAR activation in hyperoxia-induced lung fibroblast proliferation and differentiation was examined in vitro using primary cells derived from the lungs of 8-day-old Sprague-Dawley rats exposed to hyperoxic conditions. RESULTS: Hyperoxia for 3 days induced acute lung injury in newborn rats. The acute injury almost completely disappeared 4 days after cessation of hyperoxia exposure. However, pulmonary fibrosis, impaired alveolarization, and decreased pulmonary compliance were observed on postnatal days 15 and 22. MK-801 treatment during the recovery period was found to alleviate the chronic damage induced by hyperoxia. Four NMDAR 2 s were found to be upregulated in the lung fibroblasts of newborn rats exposed to hyperoxia. In addition, the proliferation and upregulation of alpha-smooth muscle actin and (pro) collagen I in lung fibroblasts were detected in hyperoxia-exposed rats. MK-801 inhibited these changes. CONCLUSIONS: NMDAR activation mediated lung fibroblast proliferation and differentiation and played a role in the development of hyperoxia-induced chronic lung damage in newborn rats.

[Protective effect of NMDA receptor antagonist memantine on acute lung injury in mice].

OBJECTIVE: To investigate the protective effect of a non-specific NMDA receptor antagonist memantine on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. METHODS: Healthy male mice were divided into 4 groups: a normal group, a memantine group, an ALI group and a memantine+ALI group. The ALI group was induced by intraperitoneal injection of LPS (10 mg/kg). Memantine (10 mg/kg) was injected intraperitoneally before the injection of LPS to determine the effect of blockade of NMDA receptor in the memantine+ALI group. The lung wet/dry ratio was detected. HE staining was preformed to show the morphological changes in the lung tissue. Myeloperoxidase enzyme (MPO) activity and malondialdehyde (MDA) content in the lung tissue were detected. ELISA was used to detect the tumor necrosis factor-α (TNF-α) content and lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage fluid (BALF). RESULTS: Memantine pretreatment improved the LPS-induced ALI lung tissue morphological changes, reduced their lung wet/dry ratio, the levels of TNF-α and LDH activity in BALF, and also reduced the MPO and MDA content in the lung tissue. CONCLUSION: Blockade of NMDA receptors can ameliorate LPS-induced mice ALI.

[Effects of extensively hydrolyzed protein formula on feeding and growth in preterm infants: a multicenter controlled clinical study].

OBJECTIVE: To study the effects of extensively hydrolyzed protein formula (eHF) on the feeding and growth in preterm infants through a multicenter controlled clinical study. METHODS: Preterm infants admitted to eight upper first-class hospitals in China between February 2012 and December 2013 were randomly selected. They were divided into two observation groups and two control groups. The first observation group consisted of preterm infants with a gestational age of <32 weeks, who were fed with eHF for 10-14 days after birth and then with standard preterm formula (SPF) until discharge. The second observation group consisted of preterm infants with a gestational age of 32-34 weeks, who were fed with SPF after birth, but were switched to eHF (7-14 days) if suffering feeding intolerance at 6-8 days after birth. The two control groups with corresponding gestational ages kept to be fed with SPF after birth. Clinical data were recorded to compare feeding condition, physical growth, blood biochemical indices, and major complications between different groups. RESULTS: A total of 328 preterm infants were enrolled. Preterm infants with a gestational age of <32 weeks in the observation group had a significantly shorter meconium evacuation time than in the corresponding control group (P<0.05). They also had significantly lower levels of serum total bilirubin at weeks 1 and 2 after birth compared with the control group (P<0.05). The observation group needed more time in reaching enteral nutrition (EN) basic energy uptake of 50 kcal/(kg·d), partial parenteral nutrition (PPN), hospitalization, and corrected gestational age at discharge compared with the controlled infants (P<0.05). There was no difference in the incidence of extrauterine growth retardation (EUGR) at discharge between the two groups (P>0.05). Preterm infants with a gestational age of 32-34 weeks in the observation group had significantly lower serum total bilirubin levels at 2 weeks after birth compared with the corresponding control group (P<0.05). They required more time in achieving EN basic energy and PPN than in the control group (P<0.05). There was no difference in the incidence of EUGR at discharge between the two groups (P>0.05). CONCLUSIONS: For preterm infants, eHF can improve gastrointestinal motility, accelerate bilirubin metabolism and excretion and does not increase the incidence of EUGR.