Hyperoxia exposure promotes endothelial-mesenchymal transition and inhibits regulatory T cell function in human pulmonary microvascular endothelial cells.

Objective: This study aims to investigate the effects of hyperoxia exposure on TGF-ß1-induced endothelial-mesenchymal transition (EndoMT) and regulatory T cell (Treg)-mediated immunomodulation in human pulmonary microvascular endothelial cells (HPMECs), which could provide a theoretical basis for further studies of the pathogenesis of bronchopulmonary dysplasia (BPD). Methods: A BPD cell model was established by exposing HPMECs to hyperoxia. Flow cytometry was used to isolate CD4 + CD3 + CD25 + CD127- Tregs from the peripheral blood samples of preterm infants. HPMECs were divided into four groups based on whether they were exposed to hyperoxia and/or co-cultured with Tregs. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to test the expression levels of TGF-ß1, α-SMA, Foxp3, IL-10, and reactive oxygen species (ROS). Results: The results showed that the expression levels of TGF-ß1 and α-SMA in HPMECs increased at 24 h, 48 h, and 72 h of hyperoxia exposure. In the co-culture group of HPMECs and Tregs, Foxp3 and IL-10 expressions decreased at 48 h and 72 h of hyperoxia exposure. ROS expression increased in the hyperoxia group of HPMECs at 24 h, 48 h, and 72 h of hyperoxia exposure, which were higher than those in the hyperoxia group of HPMECs and Tregs. Conclusion: These findings suggest that hyperoxia exposure promotes EndoMT in HMPECs and inhibits the immunosuppressive effect of Tregs. Despite this, Tregs still seem could protect HPMECs from oxidative stress injury.

[Role and mechanism of epithelial-mesenchymal transition in a rat model of bronchopulmonary dysplasia induced by hyperoxia exposure]. / 上皮-间å è´¨è½¬åŒ–åœ¨é«˜æ°§è¯±å¯¼å¤§é¼ æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯æ¨¡åž‹ä¸­çš„ä½œç”¨åŠæœºåˆ¶ç ”ç©¶.

OBJECTIVES: To investigate the role and mechanism of epithelial-mesenchymal transition (EMT) in a rat model of bronchopulmonary dysplasia (BPD). METHODS: The experiment consisted of two parts. (1) Forty-eight preterm rats were randomly divided into a normoxia group and a hyperoxia group, with 24 rats in each group. The hyperoxia group was exposed to 85% oxygen to establish a BPD model, while the normoxia group was kept in room air at normal pressure. Lung tissue samples were collected on days 1, 4, 7, and 14 of the experiment. (2) Rat type II alveolar epithelial cells (RLE-6TN) were randomly divided into a normoxia group (cultured in air) and a hyperoxia group (cultured in 95% oxygen), and cell samples were collected 12, 24, and 48 hours after hyperoxia exposure. Hematoxylin-eosin staining was used to observe alveolarization in preterm rat lungs, and immunofluorescence was used to detect the co-localization of surfactant protein C (SPC) and α-smooth muscle actin (α-SMA) in preterm rat lung tissue and RLE-6TN cells. Quantitative real-time polymerase chain reaction and protein immunoblotting were used to detect the expression levels of EMT-related mRNA and proteins in preterm rat lung tissue and RLE-6TN cells. RESULTS: (1) Compared with the normoxia group, the hyperoxia group showed blocked alveolarization and simplified alveolar structure after 7 days of hyperoxia exposure. Co-localization of SPC and α-SMA was observed in lung tissue, with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 7 and 14 days of hyperoxia exposure compared to the normoxia group. In the hyperoxia group, the mRNA and protein levels of TGF-ß1, α-SMA, and N-cadherin were increased, while the mRNA and protein levels of SPC and E-cadherin were decreased at 7 and 14 days of hyperoxia exposure compared to the normoxia group (P<0.05). (2) SPC and α-SMA was observed in RLE-6TN cells, with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 24 and 48 hours of hyperoxia exposure compared to the normoxia group. Compared to the normoxia group, the mRNA and protein levels of SPC and E-cadherin in the hyperoxia group were decreased, while the mRNA and protein levels of TGF-ß1, α-SMA, and E-cadherin in the hyperoxia group increased at 48 hours of hyperoxia exposure (P<0.05). CONCLUSIONS: EMT disrupts the tight connections between alveolar epithelial cells in a preterm rat model of BPD, leading to simplified alveolar structure and abnormal development, and is involved in the development of BPD. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 765-773.

Trends in the antimicrobial susceptibility among Chinese neonates from 2012 to 2021: a multicenter study.

BACKGROUND: Antibiotic resistance is a serious global public health issue. However, there are few reports on trends in antimicrobial susceptibility in Chinese neonates, and most of the existing evidence has been derived from adult studies. We aimed to assess the trends in antimicrobial susceptibility of common pathogens in full-term neonates with invasive bacterial infections (IBIs) in China. METHODS: This cross-sectional survey study analyzed the antimicrobial susceptibility in Chinese neonates with IBIs from 17 hospitals, spanning from January 2012 to December 2021. Joinpoint regression model was applied to illustrate the trends and calculate the average annual percentage change (AAPC). Using Mantel-Haenszel linear-by-linear association chi-square test, we further compared the antibiotic minimum inhibitory concentrations (MICs) by pathogens between 2019 and 2021 to provide precise estimates of changes. RESULTS: The proportion of Escherichia coli with extended-spectrum-beta-lactamase-negative strains increased from 0.0 to 88.5% (AAPC = 62.4%, 95% confidence interval (CI): 44.3%, 82.9%), with two breakpoints in 2014 and 2018 (p-trend < 0.001). The susceptibility of group B Streptococcus (GBS) to erythromycin and clindamycin increased by 66.7% and 42.8%, respectively (AAPC = 55.2%, 95% CI: 23.2%, 95.5%, p-trend = 0.002; AAPC = 54.8%, 95% CI: 9.6%, 118.6%, p-trend < 0.001), as did Staphylococcus aureus to penicillin (AAPC = 56.2%; 95% CI: 34.8%, 81.0%, p-trend < 0.001). However, the susceptibility of Enterococcus spp. to ampicillin declined from 100.0 to 25.0% (AAPC = - 11.7%, 95% CI: - 15.2%, - 8.1%, p-trend < 0.001), and no significant improvement was observed in the antibiotic susceptibility of Escherichia coli to ampicillin, gentamicin, and cephalosporin. Additionally, the proportion of GBS/Staphylococcus aureus with relatively low MIC values for relevant antibiotics also increased in 2021 compared to 2019. CONCLUSIONS: Antimicrobial susceptibility of the most prevalent pathogens in full-term neonates seemed to have improved or remained stable over the last decade in China, implying the effectiveness of policies and practice of antibiotic stewardship had gradually emerged.

Mortality and extrauterine growth restriction of necrotizing enterocolitis in very preterm infants with heart disease: a multi-center cohort study.

Congenital heart disease (CHD) and patent ductus arteriosus (PDA) are risk factors of necrotizing enterocolitis (NEC) in infants. However, it is unclear whether the prognosis of NEC is different between very preterm infants (VPIs) with and without heart diseases. This was an observational cohort study that enrolled VPIs (born between 24+0 and 31+6 weeks) admitted to 79 tertiary neonatal intensive care units (NICU) in the Chinese Neonatal Network (CHNN) between 2019 and 2021. The exposure was CHD or isolated PDA, and VPIs with NEC were divided into three groups: complicated with CHD, with isolated PDA, and without heart diseases. The primary outcomes were NEC-related adverse outcomes (death or extrauterine growth restriction (EUGR)). Logistic regression models were used to adjust potential confounders and calculate the odds ratios (ORs) and 95% confidential intervals (CIs) for each outcome. A total of 1335 VPIs with NEC were enrolled in this study, including 65 VPIs with CHD and 406 VPIs with isolated PDA. The VPIs with heart diseases had smaller gestational ages and lower body weights at birth, more antenatal steroids use, and requiring inotrope prior to the onset of NEC. While suffering from NEC, there was no significant increased risks in NEC-related death in VPIs with either CHD (adjusted OR [aOR]: 1.10; 95% CI: 0.41-2.50) or isolated PDA (aOR: 1.25; 95% CI 0.82-1.87), and increased risks in EUGR were identified in either survival VPIs with CHD (aOR: 2.35; 95% CI: 1.31-4.20) or isolated PDA (aOR: 1.53; 95% CI: 1.16-2.01) in survivors. The composite outcome (death or EUGR) was also more often observed in VPIs with either CHD (aOR: 2.07; 95% confidence interval [CI]: 1.20-3.60) or isolated PDA (aOR: 1.51; 95% CI: 1.17-1.94) than that without heart diseases. VPIs with either CHD or isolated PDA were associated with significantly prolonged duration of fasting, extended time to achieve full enteral feeding, and longer ventilation duration and hospitalization duration. Similar characteristics were also seen in VPIs with isolated PDA, with the exception that VPIs with CHD are more likely to undergo surgical intervention and maintain a prolonged fast after NEC.     Conclusion: In VPIs with NEC, CHD and isolated PDA are associated with an increased risk in worse outcomes. We recommend that VPIs with cardiac NEC be managed with aggressive treatment and nutrition strategies to prevent EUGR. What is Known: • CHD and PDA are risk factors for NEC in infants, which can lead to adverse outcomes such as death and EUGR. • NEC in infants with heart disease differs clinically from that in infants without heart disease and should be recognized as a separate disease process. What is New: • CHD and isolated PDA are associated with increased risks of EUGR in VPIs with NEC. • Risk factors associated with VPIs with cardiac NEC suggested these patients should be managed with aggressive treatment and nutrition strategies to adverse outcomes.

Early enteral nutrition with exclusive donor milk instead of formula milk affects the time of full enteral feeding for very low birth weight infants.

This study investigated the effects of exclusive donor milk or formula in the first 7 days after birth, on the time to full enteral feeding, growth, and morbidity of adverse events related to premature infants. This was a retrospective study carried out from July 2014 to December 2019 at the Department of Neonatology of Shanghai Children's Hospital. All infants with a birth weight < 1,500 g and a gestational age ≤ 32 who received exclusive donor milk or formula in the first 7 days after birth were included in this study. The time to full enteral feeding (defined as 150 mL/kg) in the donor milk group was significantly shorter than in the formula group (18 vs. 22 days, p = 0.01). Donated breast milk was also associated with a lower incidence of NEC (4.4 vs. 7%, p < 0.01), ROP (3.8 vs. 13.2%, p < 0.01), and culture-confirmed sepsis (11 vs. 22.6%, p < 0.01). Using donated breast milk instead of current formula milk for early enteral nutrition can shorten the time to full enteral feeding and reduce the incidence of NEC, ROP, and sepsis.

Two Debaryomyces hansenii strains as starter cultures for improving the nutritional and sensory quality of dry-cured pork belly.

Dry-cured meat products are gaining attention owing to their distinctive sensory characteristics and health benefits. In this study, two Debaryomyces hansenii strains were investigated for their potential as starter cultures for dry-cured pork belly products. After preliminary screening, these D. hansenii strains, namely, S20 and S26, both exhibiting with excellent aroma-producing capacity in a dry-cured meat model, were selected as single-strain starter cultures. For comparison, a non-inoculated control was also evaluated. In S20- and S26-inoculated pork belly, yeast dominated the microbiota and improved microbiological safety by suppressing Enterobacteriaceae growth. Compared with the non-inoculated control, the inoculated pork belly yielded higher hardness and redness (a*) values. Starter culture inoculation accelerated proteolysis in pork belly, improving the content of total free amino acids (TFFAs) and several essential free amino acids (Thr, Val, Met, Ile, Leu, and Phe) at the end of processing. Moreover, the inoculated samples exhibited higher levels of fat oxidation-derived aldehydes as well as esters, acids, alcohols and other compounds than the non-inoculated control at the end of the 95-day ripening period. Overall, these findings provide new insights into the application of D. hansenii isolated from dry-cured ham to dry-cured pork belly.

Association between Neonatal Outcomes and Admission Hypothermia among Very Preterm Infants in Chinese Neonatal Intensive Care Units: A Multicenter Cohort Study.

OBJECTIVE: We aimed to investigate the relationship between admission hypothermia and outcomes among very preterm infants (VPIs) in neonatal intensive care units (NICUs) in China. We also investigated the frequency of hypothermia in VPIs in China and the variation in hypothermia across Chinese Neonatal Network (CHNN) sites. STUDY DESIGN: This retrospective cohort study enrolled infants with 240/7 to 316/7 weeks of gestation with an admission body temperature ≤37.5 °C who were admitted to CHNN-participating NICUs between January 1 and December 31, 2019. RESULTS: A total of 5,913 VPIs were included in this study, of which 4,075 (68.9%) had hypothermia (<36.5 °C) at admission. The incidence of admission hypothermia varied widely across CHNN sites (9-100%). Lower gestational age (GA), lower birth weight, antenatal steroid administration, multiple births, small for GA, Apgar scores <7 at the 5th minute, and intensive resuscitation were significantly associated with admission hypothermia. Compared with infants with normothermia (36.5-37.5 °C), the adjusted odds ratios (ORs) for composite outcome among infants with admission hypothermia <35.5 °C increased to 1.47 (95% confidence interval [CI], 1.15-1.88). The adjusted ORs for mortality among infants with admission hypothermia (36.0-36.4 and <35.5 °C) increased to 1.41 (95% CI, 1.09-1.83) and 1.93 (95% CI, 1.31-2.85), respectively. Admission hypothermia was associated with a higher likelihood of bronchopulmonary dysplasia, but was not associated with necrotizing enterocolitis ≥stage II, severe intraventricular hemorrhage, cystic periventricular leukomalacia, severe retinopathy of prematurity, or sepsis. CONCLUSION: Admission hypothermia remains a common problem for VPIs in a large cohort in China and is associated with adverse outcomes. Continuous quality improvement of admission hypothermia in the future may result in a substantial improvement in the outcomes of VPIs in China. KEY POINTS: · Admission hypothermia is common in VPIs.. · The incidence of admission hypothermia in VPIs remains high in China.. · Admission hypothermia is associated with adverse outcomes in VPIs..

TGF-α/EGFR signaling promotes lipopolysaccharide-induced abnormal elastin deposition and alveolar simplification.

Bronchopulmonary dysplasia (BPD) is characterized by shortened secondary septa and fewer, larger alveoli. Elastin deposition to the distal tips of the secondary septa is critical for elongation of the secondary septa. Alveolar myofibroblasts, which are thought to migrate to the septal tips during alveolarization, are mainly responsible for elastin production and deposition. Antenatal exposure to inflammation induces abnormal elastin deposition, thereby increasing the risk of developing BPD. Here, we found that lipopolysaccharide (LPS) significantly increased the expression of transforming growth factor-α (TGF-α) in an LPS-induced rat model of BPD and in LPS-treated human pulmonary epithelial cells (BEAS-2B). In addition, in vitro experiments suggested that LPS upregulated TGF-α expression via toll-like receptor 4 (TLR4)/tumor necrosis factor α-converting enzyme (TACE) signaling. Increased TGF-α levels via its receptor epidermal growth factor receptor (EGFR)-induced lysyl oxidase (LOX) overactivation and cell division cycle 42 (Cdc42) activity inhibition of myofibroblasts. Similarly, in vivo LOX overactivation and inhibition of Cdc42 activity were observed in the lungs of LPS-exposed pups. LOX overactivation led to abnormal elastin deposition, and inhibition of Cdc42 activity disturbed the directional migration of myofibroblasts and disrupted elastin localization. Most importantly, the EGFR inhibitor erlotinib partially rescued LOX overactivation and Cdc42 activity inhibition, and improved elastin deposition and alveolar development in antenatal LPS-treated rats. Taken together, our data suggest that TGF-α/EGFR signaling is critically involved in the regulation of elastin deposition and represents a novel therapeutic target.

Thermal shakedown in granular materials with irregular particle shapes.

Granular materials with irregular particle shapes undergo a myriad of temperature variations in natural and engineered systems. However, the impacts of cyclic temperature variations on the mechanics of granular materials remain poorly understood. Specifically, little is known about the response of granular materials to cyclic temperature variations as a function of the following central variables: particle shape, applied stress level, relative density, and temperature amplitude. This paper presents advanced laboratory experiments to explore the impacts of cyclic temperature variations on the mechanics of granular materials, with a focus on sands. The results show that cyclic temperature variations applied to sands induce thermal shakedown: the accumulation of irreversible bulk deformations due to microstructural rearrangements caused by thermal expansions and contractions of the constituting particles. The deformation of sands caused by thermal shakedown strongly depends on particle shape, stress level, relative density, and temperature amplitude. This deformation is limited for individual thermal cycles but accumulates and becomes significant for multiple thermal cycles, leading to substantial compaction in sands and other granular materials, which can affect various natural and engineered systems.

Immune landscape of hepatocellular carcinoma tumor microenvironment identifies a prognostic relevant model.

Background: Various studies highlighted that immune cell-mediated inflammatory processes play crucial roles in the progression and treatment of hepatocellular carcinoma (HCC). However, the immune microenvironment of HCC is still poorly characterized. Exploring the role of immune-related genes (IRGs) and describing the immune landscape in HCC would provide insights into tumor-immune co-evolution along HCC progression. Methods: We integrated the datasets with complete prognostic information from the Cancer Genome Atlas (TCGA) database and GEO DataSets (GSE14520, GSE76427, and GSE54236) to construct a novel immune landscape based on the Cibersort algorithm and reveal the prognostic signature in HCC patients. Results: To describe the tumor microenvironment (TME) in HCC, immune infiltration patterns were defined using the CIBERSORT method, and a prognostic signature contains 5 types of immune cells, including 3 high-risk immune cells (T.cells. CD4. memory. resting, Macrophages.M0, Macrophages.M2) and 2 low-risk immune cells (Plasma. cells, T.cells.CD8), were finally constructed. A novel prognostic index, based on prognostic immune risk score (pIRG), was developed using the univariate Cox regression analyses and LASSO Cox regression algorithm. Furthermore, the ROC curve and KM curve showed that the TME signatures had a stable value in predicting the prognosis of HCC patients in the internal training cohort, internal validation, and external validation cohort. Differential genes analysis and qPCR experiment showed that the expression levels of AKR1B10, LAPTM4B, MMP9, and SPP1 were significantly increased in high-risk patients, while the expression of CD5L was lower. Further analysis found that AKR1B10 and MMP9 were associated with higher M0 macrophage infiltration, while CD5L was associated with higher plasma cell infiltration. Conclusions: Taken together, we performed a comprehensive evaluation of the immune landscape of HCC and constructed a novel and robust prognostic prediction model. AKR1B10, LAPTM4B, MMP9, SPP1, and CD5L were involved in important processes in the HCC tumor microenvironment and were expected to become HCC prediction markers and potential targets of treatment.

Using a new human milk fortifier to optimize human milk feeding among very preterm and/or very low birth weight infants: a multicenter study in China.

BACKGROUND: Human milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China. METHODS: VPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups. RESULTS: Demographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P-values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (ß = 0.6, 95%CI:0.1, 1.0; P = 0.01). CONCLUSIONS: The new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04283799).

Gestational age-specific hematological features in preterm infants with necrotizing enterocolitis.

BACKGROUND: This study aimed to investigate gestational age-specific hematological features in preterm infants with necrotizing enterocolitis (NEC) and identify predictive hematological biomarkers for surgical NEC. METHODS: We conducted a retrospective study comparing gestational age (GA)-specific clinical data between medical NEC (m-NEC) and surgical NEC (s-NEC) subgroups, stratified by GA as <28 weeks, 28 ≤ GA < 32 weeks, and 32 ≤ GA < 37 weeks. Multivariate logistic analysis and receiver operating characteristic curve were used to identify the independent predictors of s-NEC. RESULTS: In comparison to m-NEC at NEC onset, s-NEC infants exhibited the following findings: In GA < 28 weeks, s-NEC infants had lower platelet counts. In 28 ≤ GA < 32 weeks, lower absolute lymphocyte counts, and significant percent drop in platelets, lymphocytes, and monocytes were observed. In 32 ≤ GA < 37 weeks, lower absolute lymphocyte counts and significant percent drop in lymphocytes were found. Independent predictors were able to distinguish s-NEC from m-NEC. The area under the curve (AUC) for platelet counts in GA < 28 weeks was 0.880, while C-reactive protein in 28 ≤ GA < 32 weeks had an AUC of 0.889. The AUC for lymphocyte counts in 32 ≤ GA < 37 weeks was 0.892. CONCLUSION: This study identified hematological abnormalities in the development of NEC based on gestational age. Independent predictors may help clinicians distinguish surgical NEC from medical NEC. IMPACT: Necrotizing enterocolitis (NEC) patients with different gestational ages (GA) exhibit different hematological features and independent predictors of surgical NEC differ among different GAs. Our research made the current studies about peripheral hematological features with NEC more complete by analyzing peripheral data collected within 24 h of birth, at day 5-7, day 3-4, day 1-2 before NEC onset, at the time of NEC onset, day 1, day 2, day 3, day 4-5, day 6-7 after NEC onset. Our study is helpful to clinicians in developing a more detailed diagnostic strategy based on GA for the early identification of surgical NEC.

Pseudohypoaldosteronism type 1b in fraternal twins of a Chinese family: report of two cases and literature review

SUMMARY Here, we report the clinical observations of two Chinese fraternal twins who presented with severe dehydration, poor feeding, and absence of stimuli responses within a few days of birth. Trio clinical exome sequencing of the family identified compound heterozygous intronic variants (c.1439+1G>C and c.875+1G>A) in SCNN1A gene in these two patients. Sanger sequencing results showed that the c.1439+1G>C variant was inherited from the mother, and c.875+1G>A from the father, rarely reported in pseudohypoaldosteronism type 1 with sodium epithelial channel destruction (PHA1b) patients. Case 2 received timely symptomatic treatment and management after obtaining these results, which improved the clinical crisis. Our results suggest that the compound heterozygous splicing variants in SCNN1A were responsible for PHA1b in these Chinese fraternal twins. This finding extends the knowledge of the variant spectrum in PHA1b patients and highlights the application of exome sequencing in critically ill newborns. Finally, we discuss supportive case management, particularly in maintaining blood potassium concentration.

Reduction of absolute monocyte counts is associated with the severity of preterm necrotizing enterocolitis

Abstract Objective: Necrotizing enterocolitis (NEC) is characterized by a rich infiltration of macrophages in the intestines, which is derived from monocytes in the blood. The authors aimed to explore the changing trend of absolute monocyte counts (AMC) over time in NEC infants and to verify whether the reduction of AMC correlates with the severity of NEC and whether it can be used to identify infants who need surgery. Method: The authors collected the clinical data of 66 control and 222 NEC infants. The NEC infants were divided into medical NEC (M-NEC) and surgical NEC (S-NEC). The counting of mono-cyte and their percentage change were compared at the time of birth, before NEC (baseline), the onset of NEC and after NEC (recovery). In addition, the same comparison was made among stages 1, 2 and 3 of Bell's staging, respectively. Results: The authors found that the AMC in NEC infants decreased sharply at the onset. Further comparison was made between 172 cases of M-NEC and 50 cases of S-NEC. It was discovered that the AMC reduced more in S-NEC infants at onset, but it increased more at recovery. In addition, the authors found that among stage 1,2 and 3, stage 3 had the lowest AMC and the largest percentage decrease at the onset. Conclusion: The AMC decreases sharply in NEC infants at onset, and the degree of decline is associated with the severity of NEC. AMC is expected to be a marker of NEC and provide a reference for clinicians in the diagnosis and treatment of NEC.

Effects of erythromycin on γ-glutamyl cysteine synthetase and interleukin-1β in hyperoxia-exposed lung tissue of premature newborn rats / Efeitos da eritromicina sobre a γ-glutamil-cisteína-sintetase e a interleucina-1β no tecido pulmonar exposto à hiperóxia de ratos recém-nascidos prematuros

Objective: To explore the effect of erythromycin on hyperoxia-induced lung injury. Methods: One-day-old preterm offspring Sprague-Dawley (SD) rats were randomly divided into four groups: group 1, air + sodium chloride; group 2, air + erythromycin;group 3, hyperoxia + sodium chloride; and group 4, hyperoxia + erythromycin. At one, seven, and 14 days of exposure, glutathione (GSH) and interleukin-1 beta (IL-1 beta) were detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), and bicinchoninic acid (BCA) was used to detect GSH protein. γ-glutamine-cysteine synthetase (γ-GCS) mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results: Compared with group 1, expressions of GSH and γ-GCS mRNA in group 3 were significantly increased at one and seven days of exposure (p < 0.05), but expression of γ-GCS mRNA was significantly reduced at 14 days; expression of IL-1 beta in group 3 was significantly increased at seven days of exposure (p < 0.05), and was significantly reduced at 14 days. Compared with group 3, expressions of GSH and γ-GCS mRNA in group 4 were significantly increased at one, seven, and 14 days of exposure (p < 0.05), but expressions of GSH showed a downward trend at 14 days; expression of IL-1 beta in group 4 was significantly reduced at one and seven days of exposure (p < 0.05). Conclusions: Changes in oxidant-mediated IL-1 beta and GSH are involved in the development of hyperoxia-induced lung injury. Erythromycin may up-regulate the activity of γ-GCS, increasing the expression of GSH, inhibiting the levels of oxidant-mediated IL-1 beta and alleviating hyperoxia-induced lung injury via an antioxidant effect. .

Objetivo: Explorar o efeito da eritromicina sobre lesões pulmonares induzidas por hiperóxia. Métodos: Uma prole de ratos Sprague-Dawley (SD) prematuros com um dia de vida foi dividida aleatoriamente em quatro grupos: grupo 1 ar + cloreto de sódio, grupo 2 ar + eritromicina, grupo 3 hiperóxia + cloreto de sódio e grupo 4 hiperóxia + eritromicina. Com um, sete e 14 dias de exposição, foram detectadas Glutationa (GSH) e Interleucina-1 beta (IL-1 beta) pelo ensaio imunossorvente ligado à enzima (ELISA), e o ácido bicinconinico (BCA) foi utilizado para detectar a proteína GSH. O mRNA da γ-glutamil-cisteina-sintetase (γ-GCS) foi detectado por reação em cadeia da polimerase via transcriptase reversa (RT-PCR). Resultados: Comparadas ao grupo 1, as expressões do mRNA da GSH e da γ-GCS no grupo 3 aumentaram significativamente com um e sete dias de exposição (p < 0,05), porém a expressão de mRNA da γ-GCS diminuiu significativamente aos 14 dias; a expressão de IL-1 beta no grupo 3 aumentou significativamente aos 7 dias de exposição (p < 0,05) e diminuiu significativamente aos 14 dias. Comparadas ao grupo 3, as expressões do mRNA da GSH e da γ-GCS no grupo 4 aumentaram significativamente com um, sete e 14 dias de exposição (p < 0,05), porém as expressões de GSH mostraram uma tendência de queda aos 14 dias; a expressão de IL-1 beta no grupo 4 foi reduzida significativamente com um e sete dias de exposição (p < 0,05). Conclusões: As variações de IL-1 beta e GSH mediadas por oxidantes estão envolvidas no desenvolvimento de lesão pulmonar induzida por hiperóxia. A eritromicina poderá regular positivamente a atividade da γ-GCS, aumentando a expressão de GSH, inibindo os níveis de interleucina-1beta mediada por ...