[Association between the inter-aural latency difference of brainstem auditory evoked potential wave V and neonatal hyperbilirubinemia].

OBJECTIVE: To study brainstem auditory evoked potential (BAEP) in neonates with hyperbilirubinemia using short auditory stimuli (60 dBnHL), and to investigate the differences in the inter-aural latency difference (ILD) of wave V between neonates with different total serum bilirubin (TSB) levels. METHODS: A prospective study was conducted in neonates with hyperbilirubinemia who were admitted to the Department of Neonatology, Yuhuan People's Hospital of Zhejiang Province, from May 2019 to October 2020. The neonates were divided into a severe group (n=50) and a mild group (n=50) according to their TSB levels. The mild group was divided into two subgroups: 7-10 days (n=20) and 11-14 days (n=20) according to their age. ILD was compared between the neonates with different TSB levels, and its diagnostic value was analyzed. RESULTS: Compared with the mild group, the severe group had significantly higher proportions of neonates with abnormal hearing threshold and abnormal ILD (P < 0.05) and a significantly larger ILD of wave V (P < 0.05). The latency of wave V (left ear) in the 7-10 days subgroup was significantly longer than that in the 11-14 days subgroup (P < 0.05), but there was no significant difference in the ILD of wave V between the two groups (P > 0.05). The receiver operating characteristic (ROC) analysis showed that ILD had predictive value for hearing impairment caused by neonatal hyperbilirubinemia (P < 0.05), with an area under the ROC curve of 0.727 as well as a sensitivity of 52.4% and a specificity of 90.9% at the optimal cut-off value of 0.365 ms. CONCLUSIONS: Serum bilirubin in neonates affects the ILD of BAEP wave V, especially in those with severe hyperbilirubinemia. ILD at the optimal cut-off value of ≥0.4 ms shows potential value in the diagnosis of hearing impairment caused by neonatal hyperbilirubinemia.

[Clinical effect of multi-oil fat emulsion for parenteral nutrition support in extremely low birth weight infants].

OBJECTIVE: To study the clinical effect of multi-oil fat emulsion for parenteral nutrition support in extremely low birth weight (ELBW) infants. METHODS: A retrospective analysis was performed for 49 ELBW infants who were admitted from January 1, 2018 to July 30, 2020, with an age of ≤14 days on admission and a duration of parenteral nutrition of > 14 days. According to the type of lipid emulsion received, the ELBW infants were divided into two groups: soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) (n=26) and medium-chain triglycerides/long-chain triglycerides (MCT/LCT) (n=23). The two groups were compared in terms of clinical features, complications, nutrition support therapy, and outcome. RESULTS: The 49 ELBW infants had a mean birth weight of (892±83) g and a mean gestational age of (28.2±2.3) weeks. There was no significant difference between the two groups in the incidence rates of hemodynamically significant patent ductus arteriosus, intraventricular hemorrhage, neonatal necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia (BPD), grade Ⅲ BPD, sepsis, and pneumonia (P > 0.05). There was also no significant difference in the duration of parenteral nutrition, the age of total enteral nutrition, and head circumference/body length/body weight at discharge between the two groups (P > 0.05). Of all the infants, 22 (45%) had parenteral nutrition-associated cholestasis (PNAC), with 13 (50%) in the SMOF group and 9 (39%) in the MCT/LCT group but there was no significant difference in the incidence of PNAC between the two groups (P > 0.05); however, the infants with PNAC in the SMOF group had significantly lower peak values of direct bilirubin and alanine aminotransferase than those in the MCT/LCT group (P < 0.05). CONCLUSIONS: The application of multi-oil fat emulsion in ELBW infants does not reduce the incidence rate of complications, but compared with MCT/LCT emulsion, SMOF can reduce the severity of PNAC in ELBW infants.

[Possibility of mother-to-child vertical transmission of coronavirus infection from the perspectives of severe acute respiratory syndrome, Middle East respiratory syndrome, and coronavirus disease 2019].

This article evaluates the potential influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnant women on the development of coronavirus disease 2019 in neonates and discusses the possibility of mother-to-child vertical transmission of SARS-CoV-2. With reference to related articles published up to now and the information on official websites, a retrospective review was performed for the clinical manifestations and laboratory examination results of the neonates born to the mothers with infection during pregnancy during the epidemics of severe acute respiratory syndrome and Middle East respiratory syndrome and after the outbreak of SARS-CoV-2 infection since December 2019. Based on the limited data, there is no conclusive evidence for mother-to-child vertical transmission of coronavirus disease 2019, and more cases need to be collected for further evaluation.

[Application of vacuum stretcher combined with feeding in cranial magnetic resonance imaging examination for neonates: a prospective randomized controlled study].

OBJECTIVE: To study the effect and safety of vacuum stretcher combined with feeding in cranial magnetic resonance imaging (MRI) examination for neonates. METHODS: A prospective study was performed for the neonates with hyperbilirubinemia, with a gestational age of >34 weeks and stable vital signs, who needed cranial MRI examination and did not need oxygen inhalation hospitalized in the Department of Neonatology, Children's Hospital of Zhejiang University School of Medicine, from September to November, 2019. The neonates were randomly divided into a vacuum stretcher combined with feeding group and a conventional sedation group. Vital signs were monitored before, during, and after MRI examination. The success rate of MRI procedure was recorded. RESULTS: A total of 80 neonates were enrolled in the study, with 40 neonates in the vacuum stretcher combined with feeding group and 40 in the conventional sedation group. The vacuum stretcher combined with feeding group had a significantly higher success rate of MRI procedure than the conventional sedation group (P<0.05). As for the neonates who underwent successful MRI examination, the fastest heart rate after examination in the vacuum stretcher combined with feeding group was significantly lower than that in the conventional sedation group (P<0.05), while there were no significant differences between the two groups in transcutaneous oxygen saturation, respiratory rate, and body temperature before and after MRI examination (P>0.05). No complications, such as apnea, acute allergic reactions, and malignant fever, were observed. CONCLUSIONS: Vacuum stretcher combined with feeding can improve the success rate of MRI procedure and reduce the use of sedatives, and meanwhile, it does not increase related risks.

[Clinical features of neonatal enterovirus infection].

OBJECTIVE: To study the clinical features of neonatal enterovirus infection, especially severe enterovirus infection. METHODS: A retrospective analysis was performed for the clinical data of 244 neonates with enterovirus infection. According to the severity of infection, they were divided into a common infection group with 231 neonates and a severe infection group with 13 neonates. Clinical features were compared between the two groups. RESULTS: Of the 244 neonates, 207 (84.8%) developed the disease in May to October, with the highest number of patients in June to July. Compared with the common infection group, the severe infection group had a significantly lower gestational age at birth and a significantly higher proportion of preterm infants (P<0.05). Compared with the common infection group, the severe infection group had a significantly earlier onset time (P<0.05) and significantly higher incidence rates of skin petechiae and ecchymosis, respiratory symptoms, sepsis-like manifestations (poor appetite, crying less, and less movement), concomitant diseases (such as pneumonia, myocarditis, necrotic hepatitis, and coagulation disorder), thrombocytopenia, prolonged prothrombin time, elevated creatine kinase-MB, and elevated alanine aminotransferase (P<0.05). The severe infection group had a significantly higher mortality rate than the common infection group (P<0.05). CONCLUSIONS: There are significant differences in onset time, common clinical manifestations, and concomitant diseases between the neonates with common and severe enterovirus infection. In the enterovirus epidemic season, if the neonates have rashes and/or sepsis-like manifestations such as poor appetite and less movement, especially if the laboratory tests suggest liver damage and coagulation dysfunction, it is necessary to pay particular attention to the possibility of severe enterovirus infection.

[Emergency plan for inter-hospital transfer of newborns with SARS-CoV-2 infection].

Since December 2019, the outbreak of coronavirus disease (COVID-19) has become the most serious public health issue. As the special population with immature immune function, newborns with COVID-19 have been reported. Newborns with suspected or confirmed COVID-19 should be transferred to designated hospitals for isolation treatment. An emergency transfer response plan for newborns with COVID-19 has been worked out. This plan puts forward the indications for neonatal COVID-19 transfer, organization management, protection strategies for medical staff, work procedures, and disinfection methods for transfer equipment, in order to provide guidance and suggestions for the inter-hospital transfer of suspected or confirmed neonatal COVID-19.

Relationships of Cadmium, Lead, and Mercury Levels With Albuminuria in US Adults: Results From the National Health and Nutrition Examination Survey Database, 2009-2012.

In this cross-sectional study, we evaluated associations between cadmium, lead, and mercury levels and the presence of albuminuria in US adults who participated in the National Health and Nutrition Examination Survey during the period 2009-2012. A total of 2,926 adults aged ≥20 years were included, representing a population-based sample of 18,264,307 persons. Data on blood and urinary levels of cadmium, lead, and mercury and urinary albumin concentration (albuminuria, measured as albumin:creatinine ratio (ACR) ≥30 mg/g) were obtained. Multivariate linear regression was used to analyze associations between log-transformed cadmium, lead, and mercury levels and the presence of albuminuria. Urinary ACR was significantly higher among participants with a blood cadmium level of 0.349-0.692 µg/L (quartile 3) than in those with a blood cadmium level less than or equal to 0.243 µg/L (quartile 1) (crude ß = 0.15, 95% confidence interval (CI): 0.01, 0.28). Participants with a urinary cadmium level greater than or equal to 0.220 µg/L had a significantly higher ACR (0.220-0.403 µg/L (quartile 3): crude ß = 0.12 (95% CI: 0.03, 0.21); ≥0.404 µg/L (quartile 4): crude ß = 0.29 (95% CI: 0.18, 0.39)) than those with a urinary cadmium level less than or equal to 0.126 µg/L (quartile 1). In conclusion, only blood and urinary cadmium levels, not mercury or lead levels, were associated with albuminuria among adults in this population.

[Long-term prognosis of neonates with necrotizing enterocolitis].

OBJECTIVE: To investigate the long-term prognosis of neonates with necrotizing enterocolitis (NEC). METHODS: A total of 83 preterm infants with NEC who survived and were discharged between December 2014 and September 2016 were enrolled and divided into surgery group (n=57) and non-surgery group (n=26). There were 0, 33 and 24 cases of stage I, II and III NEC respectively in the surgery group and 7, 19 and 0 cases respectively in the non-surgery group. The physical development and neurodevelopmental outcomes of the infants were followed up after discharge. RESULTS: Of the 83 infants, the mean corrected age at the end of follow-up was 21±6 months. Of the 83 infants, 31 (37%) had subnormal body weight, and the surgery group had a higher rate of subnormal body weight than the non-surgery group (P<0.05). Twenty-two infants (27%) had subnormal body length and 14 children (17%) had subnormal head circumference among the 83 infants. Eighteen infants (22%) had motor developmental delay/developmental disorders, and the surgery group had a higher incidence rate of the disorders than the non-surgery group (28% vs 8%; P<0.05). Five infants (6%) were diagnosed with cerebral palsy, among whom 4 were in the surgery group and 1 was in the non-surgery group. CONCLUSIONS: Long-term physical development and neurodevelopmental outcomes may be adversely affected in neonates with NEC, in particular in those with severe conditions who need surgical treatment, suggesting that long-term follow-up should be performed for neonates with NEC.

[Clinical features and prognosis of bronchopulmonary dysplasia complicated by pulmonary hypertension in preterm infants].

OBJECTIVE: To study the clinical features and prognosis of bronchopulmonary dysplasia (BPD) complicated by pulmonary hypertension (PH) in preterm infants. METHODS: A retrospective analysis was performed on the clinical data of 191 preterm infants with BPD. RESULTS: In the 191 preterm infants with BPD, 37 (19.4%), all with moderate or severe BPD, developed PH beyond 36 weeks' corrected age. The incidence rates of PH in infants with moderate and severe BPD were 5.7% (5/87) and 47.8% (32/67) respectively. Gestational age and birth weight were lower in infants with PH than in those without PH (P<0.01). Infants with PH had higher incidence rates of small for gestational age (SGA), severe BPD, surgical ligation of patent ductus arteriosus (PDA), neonatal respiratory distress syndrome, hemodynamically significant PDA, and pneumonia than those without PH (P<0.01). Durations of oxygen therapy, intubation, and positive pressure ventilation were longer in infants with PH than in those without PH (P<0.01). Infants with PH had higher incidence rates of retinopathy of prematurity and extrauterine growth retardation, a higher mortality, and a longer length of hospital stay compared with those without PH (P<0.01). In the 37 infants with PH (6 with mild PH, 14 with moderate PH, and 17 with severe PH), those with mild or moderate PH all survived; 15(88%) out of 17 infants with severe PH died. CONCLUSIONS: The incidence of PH is high in preterm infants with moderate or severe BPD. Regular screening of pulmonary artery pressure is recommended for infants with BPD. Infants with low gestational age and birth weight, SGA, and severe BPD are more likely to develop PH. Infants with BPD complicated by PH have relatively high incidence rates of complications, high mortality, and poor prognosis.

Utility of cytokines to predict neonatal sepsis.

BACKGROUND: Sepsis is an important cause of neonatal morbidity and mortality worldwide. Diagnosis and treatment of neonatal sepsis relies on clinical judgment and interpretation of nonspecific laboratory tests. In a prospective cohort, we measured inflammatory cytokines as a potential biomarker for neonatal sepsis. METHODS: Serum inflammatory cytokine levels were evaluated in the early stage of neonatal sepsis and after antimicrobial treatment. Receiver operating characteristic curves assessed the diagnostic value of cytokines. We performed multiple logistic regression analysis to characterize the role of each cytokine independently for infants with culture proven sepsis. RESULTS: C-reactive protein, interleukin (IL)-6, IL-10 and IL-6/IL-10 levels were significantly elevated in neonatal sepsis when compared with the control group and there were 1.4 (95% confidence interval (CI): 1.2-1.5), 4.9 (95% CI: 4.6-5.1), 5.1 (95% CI: 4.5-5.6), and 10.2 (95% CI: 9.2-11.1) fold greater odds, respectively, to predict neonatal sepsis when increased. After effective treatment, median IL-6 (pretreatment value: 263.0 pg/ml and post-treatment value: 7.4 pg/ml) and IL-6/IL-10 levels (pretreatment value: 16.6 and post-treatment value: 1.4) significantly decreased. The areas under the curve for IL-6, IL-10, IL-6/IL-10 and C-reactive protein for differential diagnosis were 0.98, 0.82, 0.90, and 0.88, respectively. CONCLUSION: IL-6 and IL-6/IL-10 outperformed C-reactive protein to diagnose neonatal sepsis. Of the cytokines studied, IL-6 was the most sensitive, whereas IL-6/IL-10 was the most specific predictor of neonatal sepsis.

Airway administration of corticosteroids for prevention of bronchopulmonary dysplasia in premature infants: a meta-analysis with trial sequential analysis.

BACKGROUND: Uncertainly prevails with regard to the use of inhalation or instillation steroids to prevent bronchopulmonary dysplasia in preterm infants. The meta-analysis with sequential analysis was designed to evaluate the efficacy and safety of airway administration (inhalation or instillation) of corticosteroids for preventing bronchopulmonary dysplasia (BPD) in premature infants. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL from their inceptions to February 2017. All published randomized controlled trials (RCTs) evaluating the effect of airway administration of corticosteroids (AACs) vs placebo or systemic corticosteroid in prematurity were included. All meta-analyses were performed using Review Manager 5.3. RESULTS: Twenty five RCTs retrieved (n = 3249) were eligible for further analysis. Meta-analysis and trial sequential analysis corrected the 95% confidence intervals estimated a lower risk of the primary outcome of BPD (relative risk 0.71, adjusted 95% confidence interval 0.57-0.87) and death or BPD (relative risk 0.81, adjusted 95% confidence interval 0.71-0.97) in AACs group than placebo and it is equivalent for preventing BPD than systemic corticosteroids. Moreover, AACs fail to increasing risk of death compared with placebo (relative risk 0.90, adjusted 95% confidence interval 0.40-2.03) or systemic corticosteroids (relative risk 0.81, 95% confidence interval 0.62-1.06). CONCLUSIONS: Our findings suggests that AACs (especially instillation of budesonide using surfactant as a vehicle) are an effective and safe option for preventing BPD in preterm infants. Furthermore, the appropriate dose and duration, inhalation or instillation with surfactant as a vehicle and the long-term safety of airway administration of corticosteroids needs to be assessed in large trials.

[Short-term clinical outcomes of neonates of secundiparous mothers: a single-center cohort study].

OBJECTIVE: To investigate the short-term clinical outcomes of neonates of secundiparous mothers, and to provide a reference for the clinical practice after the change in birth policy. METHODS: A cohort study was performed for the parturients and their neonates born in Yongkang Maternal and Child Health Care Hospital in Zhejiang, China between June 2015 and April 2016. According to the parity of the mother, the neonates were divided into primiparous group and secundiparous group. The short-term clinical outcomes of neonates were compared between the two groups. RESULTS: A total of 4 091 neonates who met the inclusion criteria were enrolled, and there were 2 023 neonates in the primiparous group and 2 068 in the secundiparous group. In the secundiparous group, most mothers (57.16%) were aged 26-34 years, and 16.49% were aged above 35 years. Compared with the primiparous group, the secundiparous group had a significantly higher rate of births by cesarean section (42.55% vs 25.06%; P<0.05). The percentages of neonatal respiratory distress syndrome (NRDS; 8.6% vs 3.4%) and transient tachypnea of the newborn (TTN; 7.2% vs 2.6%; P<0.05) in hospitalized neonates from the secundiparous group were significantly higher than in those from the primiparous group. CONCLUSIONS: Elderly parturient women are not the major population of secundiparous parturients. The neonates of secundiparous mothers have a higher rate of births by cesarean section, which might be associated with increased percentages of NRDS and TTN in hospitalized neonates from the secundiparous mothers.

[Clinical epidemiological characteristics of neonatal respiratory failure: an analysis of 1,108 neonates].

OBJECTIVE: To investigate the clinical epidemiological characteristics of neonatal respiratory failure in 1,108 neonates, and to provide a reference for improvement in clinical treatment and multicenter clinical studies. METHODS: The clinical data of 1,108 neonates with respiratory failure were collected with questionnaires, and statistical analysis was performed for the epidemiological indices including primary diseases, clinical therapeutic methods, treatment outcome, and fatality. RESULTS: In all the neonates with respiratory failure, the median gestational age was 37 weeks+1 day, the median birth weight was 2,600 g, the median age in days on admission to neonatal intensive care unit was 0.71 days (17 hours), and the boy/girl ratio was 3.1:1. The major primary diseases were respiratory distress syndrome (30.51%), pulmonary infection/sepsis (23.55%), and wet lung (13.18%). Of all the neonates, 48.64% received nasal continuous positive airway pressure (nCPAP), 12.81% received high-frequency oscillatory ventilation, 13.45% received pulmonary surfactant, and 8.66% received nitric oxide inhalation therapy. The fatality was 24.19%. CONCLUSIONS: The major primary disease for neonatal respiratory failure is respiratory distress syndrome. Pulmonary surfactant, nCPAP, high-frequency oscillatory ventilation, and nitric oxide inhalation therapy are major therapeutic methods for neonatal respiratory failure, but neonatal respiratory failure still has a high fatality.

[Factors influencing the prognosis of patent ductus arteriosus in very low birth weight infants].

OBJECTIVE: To investigate the factors influencing the prognosis of patent ductus arteriosus (PDA) in very low birth weight (VLBW) infants. METHODS: A total of 194 VLBW infants who were admitted from January 2012 to December 2014 were enrolled as study subjects. According to cardiac ultrasound findings and treatment outcome, these infants were divided into non-PDA group, spontaneous closure group, pharmaceutical closure group, and surgical closure group. Their clinical and echocardiographic characteristics were analyzed. RESULTS: The spontaneous closure rate of PDA was 58.7%. The spontaneous closure group showed significantly higher gestational age, birth weight, and proportion of small-for-gestational-age infants than the pharmaceutical and surgical closure groups (P<0.05). The pharmaceutical and surgical closure groups had a significantly higher incidence rate of neonatal respiratory distress syndrome and a significantly higher proportion of infants who were given pulmonary surfactant (PS) than the spontaneous closure group (P<0.05). During different periods of time, the spontaneous closure group had a significantly smaller ductus arteriosus diameter than the pharmaceutical and surgical closure groups (P<0.05). The multivariate logistic regression analysis showed that gestational age, application of PS, and ductus arteriosus diameter at 48 hours were significantly associated with the prognosis of PDA. The major transductal flow pattern in the spontaneous closure group was closing pattern, while in the pharmaceutical and surgical closure groups, the main flow patterns were pulmonary hypertension and growing patterns within 48 hours and growing pattern on days 4 and 7. CONCLUSIONS: The VLBW infants have a high spontaneous closure rate of PDA. A decreased closure rate of PDA is associated with the lower gestational age and the application of PS. PDA with a large ductus arteriosus diameter and a growing or pulsatile flow pattern cannot easily achieve spontaneous closure.

Epigenetics of Notch1 regulation in pulmonary microvascular rarefaction following extrauterine growth restriction.

BACKGROUND: Extrauterine growth restriction (EUGR) plays an important role in the developmental origin of adult cardiovascular diseases. In an EUGR rat model, we reported an elevated pulmonary arterial pressure in adults and genome-wide epigenetic modifications in pulmonary vascular endothelial cells (PVECs). However, the underlying mechanism of the early nutritional insult that results in pulmonary vascular consequences later in life remains unclear. METHODS: A rat model was used to investigate the physiological and structural effect of EUGR on early pulmonary vasculature by evaluating right ventricular systolic pressure and pulmonary vascular density in male rats. Epigenetic modifications of the Notch1 gene in PVECs were evaluated. RESULTS: EUGR decreased pulmonary vascular density with no significant impact on right ventricular systolic pressure at 3 weeks. Decreased transcription of Notch1 was observed both at 3 and 9 weeks, in association with decreased downstream target gene, Hes-1. Chromatin immunoprecipitation and bisulfite sequencing were performed to analyze the epigenetic modifications of the Notch1 gene promoter in PVECs. EUGR caused a significantly increased H3K27me3 in the proximal Notch1 gene promoter, and increased methylation of single CpG sites in the distal Notch1 gene promoter, both at 3 and 9 weeks. CONCLUSIONS: We conclude that EUGR results in decreased pulmonary vascular growth in association with decreased Notch1 in PVECs. This may be mediated by increased CpG methylation and H3K27me3 in the Notch1 gene promoter region.

Hypercoagulation and elevation of blood triglycerides are characteristics of Kawasaki disease.

BACKGROUND: Cardiovascular damages poses risks to children with Kawasaki disease (KD). Although hypertriglyceridemia and hypercholesteremia are risk factors of cardiovascular damages, studies on the blood lipid metabolism in KD are still limited. This study aims to analyze the blood lipids and coagulation in KD. METHODS: Triglyceride (TG) and cholesterol levels in the plasma and serum from 20 children with KD were examined in comparison with 10 healthy children (HC) as well as 10 children with high fever from identified bacterial infections (BT). Using electrospray ionization mass spectrometry, we profiled the lipid species. Blood coagulation was analyzed. Statistics was analyzed by one-way ANOVA using SigmaStat. RESULTS: We found that in KD, plasma TG level was significantly increased, but not serum TG. A total of 19 molecular species of TG were identified, and they were all increased in KD and BT patients, and more pronounced in KD. On the other hand, major molecular species of plasma phosphotidylcholine and lyso-phosphotidylcholine were decreased in KD and BT. Pronounced hypercoagulation was found in KD blood. CONCLUSION: Our data indicate hyperlipidemia in KD, especially for TG, which contributes to the hypercoagulation and the potential risk of cardiovascular damages. Evaluation of blood lipid levels in severe KD patients could provide valuable information for treatment and prognosis, thus would be worthy of consideration.

[Malnutrition in early life and cardiovascular disease in adulthood].

Epidemiological and experimental studies have demonstrated that the risk of cardiovascular disease (CVD) in adulthood is influenced by the environment in early life. Intrauterine and early postnatal malnutrition and the following catch-up growth have a long-term effect on blood pressure and endothelial function in adulthood. Well-established prenatal or/and postnatal animal models are used to study the impact of different nutritional intervention on CVD in adulthood. This article reviews the early original cause of chronic CVD in adulthood with the hypothesis of DOHaD (the developmental origins of health and disease), and proposes possible preventions in early life on the basis of this theory.

[Relationship between expression of endothelial nitric oxide synthase and NADPH oxidase in lungs of mice exposed to chronic hypoxia].

OBJECTIVE: To explore the relationship between the expression of endothelial nitric oxide synthase (eNOS) and NADPH oxidase (NOX) in the lungs of mice treated by chronic hypoxic exposure. METHODS: Thirty male wild-type (WT) C57Bl/6 mice and thirty male eNOS-knockout (KO) C57BL/6 mice were randomly divided into normoxic groups (exposed to normoxia for 7 days or 21 days), hypoxic groups (exposed to 10% oxygen for 7 days or 21 days), and treatment groups (exposed to 10% oxygen and orally administrated 10 mmol/L 4-hydroxy TEMPO in drinking water for 7 days or 21 days) (n=6 in each group). The remodeling of the small pulmonary arteries was evaluated by the percentage of media wall thickness (MT%). The weight ratio of right ventricle to left ventricle plus septum (RV/[LV+S]) was calculated to evaluate the hypertrophy of right ventricle. Real-time PCR was used to measure the mRNA expression of NOX2, NOX4, and eNOS in mouse lungs. ELISA was used to determine the concentration of reactive oxygen species (ROS) in mouse lungs. RESULTS: In WT mice and KO mice, the hypoxic groups had significantly increased pulmonary vascular remodeling and RV/[LV+S] compared with the normoxic and treatment groups (P<0.05), but there were no significant differences between the normoxic and treatment groups (P>0.05). In WT mice, the hypoxic and treatment groups had significantly lower ROS concentrations than the normoxic group (P<0.05), but there were no significant differences between the hypoxic and treatment groups (P>0.05). In WT mice, the mRNA expression of eNOS, NOX2, and NOX4 was significantly higher in the hypoxic group than in the normoxic group (P<0.05), and 4-hydroxy TEMPO reversed their over-expression. In the normoxic group, the KO mice had significantly higher NOX2 and NOX4 mRNA expression than the WT mice (P<0.05); in KO mice, the hypoxic group showed no significant changes in NOX4 mRNA expression (P>0.05), but had significantly reduced NOX2 mRNA expression (P<0.05), as compared with the normoxic group; the treatment group had reduced expression of NOX2 mRNA expression and increased NOX4 mRNA expression (P<0.05), as compared with the hypoxic group. CONCLUSIONS: eNOS plays a key role in the regulation of expression of NOX2 and NOX4 in the lungs exposed to hypoxia. It suggests that NOX and eNOS may physically interact with one another in pulmonary vascular remodeling induced by chronic hypoxia.

[Clinical efficacy of preferred use of high-frequency oscillatory ventilation in treatment of neonatal pulmonary hemorrhage].

OBJECTIVE: To investigate the clinical efficacy and safety of preferred use of high-frequency oscillatory ventilation (HFOV) in the treatment of neonatal pulmonary hemorrhage. METHODS: The clinical efficacy of preferred use of HFOV (preferred use group) and rescue use of HFOV after conventional mechanical ventilation proved ineffective (rescue use group) in the treatment of 26 cases of neonatal pulmonary hemorrhage was retrospectively analyzed. The oxygenation index (OI), pulmonary hemorrhage time, hospitalization time, ventilation time, oxygen therapy time, complications, and outcome of the two groups were compared. RESULTS: Compared with the rescue use group, the preferred use group had significantly lower IO values at 1, 6, 12, 24, 48, and 72 hours after treatment (P<0.05). Compared with the rescue use group, the preferred use group had a significantly lower incidence of ventilator associated pneumonia (VAP) (P<0.05) and a significantly higher cure rate (P<0.05). There were no statistically significant differences in the incidences of pneumothorax, intracranial hemorrhage, and digestive tract hemorrhage between the two groups (P>0.05). Compared with those in the rescue use group, children who survived in the preferred use group had significantly shorter pulmonary hemorrhage time, hospitalization time, ventilation time, and oxygen therapy time (P<0.05). CONCLUSIONS: Compared with the rescue use of HFOV, preferred use of HFOV can better improve oxygenation function, reduce the incidence of VAP, shorten the course of disease, and increase cure rate while not increasing the incidence of adverse effects.