[Research progress on the relationship between anemia and neonatal necrotizing enterocolitis]. / è´«è¡€ä¸Žæ–°ç”Ÿå„¿åæ­»æ€§å°è‚ ç»“è‚ ç‚Žå‘ç— å ³ç³»çš„ç ”ç©¶è¿›å±•.

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

Self-assembled miR-134-5p inhibitor nanoparticles ameliorate experimental bronchopulmonary dysplasia (BPD) via suppressing ferroptosis.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants with increased levels of reactive oxygen species (ROS) and ferroptosis. Herein, we designed a peptide-based nanoparticle to deliver therapeutic molecules to pulmonary, thereby ameliorating BPD. The BPD-induced damages of lung tissues were detected by H&E and immunohistochemistry staining. Inflammatory cytokines, Fe2+, and ROS levels were quantified by the indicated kits, respectively. The targeting relationship was verified by luciferase reporter assay and pull-down assay. Subsequently, self-assembled miR-134-5p inhibitor nanoparticles with pulmonary epithelial cell-targeting were synthesized. The characteristics were detected by transmission electron microscopy, luminescence imaging, and dynamic light scattering. A significant ferroptosis was observed in the BPD mice. The protein level of GPX4 was decreased significantly compared to the control group. Constantly, miR-134-5p showed positive regulation on ferroptosis by targeting GPX4. The designed nanoparticles were mainly accumulated in the lung region. Besides, it ameliorated experimental bronchopulmonary dysplasia via suppressing ferroptosis, in vivo and in vitro. Our findings provided a miR-134-5p/GPX4 axis in regulating ferroptosis of BPD and prompted the potential of applying the peptide-based nanoparticle to BPD treatment.

Gentamicin promoted the production of CD4+CD25+ Tregs via the STAT5 signaling pathway in mice sepsis.

BACKGROUND: Increasing studies have reported that gentamicin (GNT) plays an essential role in sepsis; however, its underlying mechanism is still unclear. In this study, we investigated the mechanism of GNT in sepsis. RESULTS: We observed that GNT enhanced survival and alleviated inflammatory injuries of the lungs, liver, kidneys, and intestines in mice with sepsis. Furthermore, regulatory T cells (Tregs) showed enhanced inhibitory function, and pro-inflammatory cytokines IL-1ß, TNF-α, and IL-2 and anti-inflammatory cytokine IL-10 showed decreased and increased peritoneal fluid levels, respectively, after treatment with GNT. GNT showed enhanced phosphorylation of signal transducer and activator of transcription 5 (p-STAT5) in Tregs in vivo and in vitro. The STAT5 inhibitor restrained the increased functional changes of Tregs and reduced inflammatory responses induced by GNT in vitro. Moreover, the STAT5 inhibitor reversed GNT-mediated impacts on survival and inflammation, and the percentage, apoptosis, and phenotypic and functional changes of Tregs in neonatal sepsis. CONCLUSIONS: Our study revealed that GNT regulates the function of Tregs via the STAT5 signaling pathway, alleviating inflammatory injuries, and provides novel evidence in the treatment of neonatal sepsis.

Predicting therapeutic drugs for hepatocellular carcinoma based on tissue-specific pathways.

Hepatocellular carcinoma (HCC) is a significant health problem worldwide with poor prognosis. Drug repositioning represents a profitable strategy to accelerate drug discovery in the treatment of HCC. In this study, we developed a new approach for predicting therapeutic drugs for HCC based on tissue-specific pathways and identified three newly predicted drugs that are likely to be therapeutic drugs for the treatment of HCC. We validated these predicted drugs by analyzing their overlapping drug indications reported in PubMed literature. By using the cancer cell line data in the database, we constructed a Connectivity Map (CMap) profile similarity analysis and KEGG enrichment analysis on their related genes. By experimental validation, we found securinine and ajmaline significantly inhibited cell viability of HCC cells and induced apoptosis. Among them, securinine has lower toxicity to normal liver cell line, which is worthy of further research. Our results suggested that the proposed approach was effective and accurate for discovering novel therapeutic options for HCC. This method also could be used to indicate unmarked drug-disease associations in the Comparative Toxicogenomics Database. Meanwhile, our method could also be applied to predict the potential drugs for other types of tumors by changing the database.

[Clinical features of severe meconium aspiration syndrome (MAS) and early predicting factors for severe MAS in neonates with meconium-stained amniotic fluid]. / èƒŽç²ªæ±¡æŸ“ç¾Šæ°´æ–°ç”Ÿå„¿å‘ç”Ÿé‡åº¦èƒŽç²ªå¸å ¥ç»¼åˆå¾çš„ä¸´åºŠç‰¹å¾åŠé¢„è­¦å› ç´ åˆ†æž.

OBJECTIVES: To study the clinical features of severe meconium aspiration syndrome (MAS) and early predicting factors for the development of severe MAS in neonates with meconium-stained amniotic fluid (MSAF). METHODS: A total of 295 neonates who were hospitalized due to Ⅲ° MSAF from January 2018 to December 2019 were enrolled as subjects. The neonates were classified to a non-MAS group (n=199), a mild/moderate MAS group (n=77), and a severe MAS group (n=19). A retrospective analysis was performed for general clinical data, blood gas parameters, infection indicators, and perinatal clinical data of the mother. The respiratory support regimens after birth were compared among the three groups. The receiver operating characteristic (ROC) curve and multivariate logistic regression analysis were used to investigate predicting factors for the development of severe MAS in neonates with MSAF. RESULTS: Among the 295 neonates with MSAF, 32.5% (96/295) experienced MAS, among whom 20% (19/96) had severe MAS. Compared with the mild/moderate MAS group and the non-MAS group, the severe MAS group had a significantly lower 5-minute Apgar score (P<0.05) and a significantly higher blood lactate level in the umbilical artery (P<0.05). Compared with the non-MAS group, the severe MAS group had a significantly higher level of interleukin-6 (IL-6) in peripheral blood at 1 hour after birth (P<0.017). In the severe MAS group, 79% (15/19) of the neonates were born inactive, among whom 13 underwent meconium suctioning, and 100% of the neonates started to receive mechanical ventilation within 24 hours. Peripheral blood IL-6 >39.02 pg/mL and white blood cell count (WBC) >30.345×109/L at 1 hour after birth were early predicting indicators for severe MAS in neonates with MSAF (P<0.05). CONCLUSIONS: Meconium suctioning cannot completely prevent the onset of severe MAS in neonates with MSAF. The neonates with severe MAS may develop severe respiratory distress and require mechanical ventilation early after birth. Close monitoring of blood lactate in the umbilical artery and peripheral blood IL-6 and WBC at 1 hour after birth may help with early prediction of the development and severity of MAS.

TMT-based quantitative proteomic analysis reveals defense mechanism of wheat against the crown rot pathogen Fusarium pseudograminearum.

BACKGROUND: Fusarium crown rot is major disease in wheat. However, the wheat defense mechanisms against this disease remain poorly understood. RESULTS: Using tandem mass tag (TMT) quantitative proteomics, we evaluated a disease-susceptible (UC1110) and a disease-tolerant (PI610750) wheat cultivar inoculated with Fusarium pseudograminearum WZ-8A. The morphological and physiological results showed that the average root diameter and malondialdehyde content in the roots of PI610750 decreased 3 days post-inoculation (dpi), while the average number of root tips increased. Root vigor was significantly increased in both cultivars, indicating that the morphological, physiological, and biochemical responses of the roots to disease differed between the two cultivars. TMT analysis showed that 366 differentially expressed proteins (DEPs) were identified by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment in the two comparison groups, UC1110_3dpi/UC1110_0dpi (163) and PI610750_3dpi/PI610750_0dpi (203). It may be concluded that phenylpropanoid biosynthesis (8), secondary metabolite biosynthesis (12), linolenic acid metabolites (5), glutathione metabolism (8), plant hormone signal transduction (3), MAPK signaling pathway-plant (4), and photosynthesis (12) contributed to the defense mechanisms in wheat. Protein-protein interaction network analysis showed that the DEPs interacted in both sugar metabolism and photosynthesis pathways. Sixteen genes were validated by real-time quantitative polymerase chain reaction and were found to be consistent with the proteomics data. CONCLUSION: The results provided insight into the molecular mechanisms of the interaction between wheat and F. pseudograminearum.

[Impact of mild hypothermia therapy on hemodynamics during the induction stage in neonates with moderate to severe hypoxic-ischemic encephalopathy].

OBJECTIVE: To study the changes in hemodynamics during the induction stage of systemic mild hypothermia therapy in neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE). METHODS: A total of 21 neonates with HIE who underwent systemic mild hypothermia therapy in the Department of Neonatology, Dongguan Children's Hospital Affiliated to Guangdong Medical University, from July 2017 to April 2020 were enrolled. The rectal temperature of the neonates was lowered to 34℃ after 1-2 hours of induction and maintained at this level for 72 hours using a hypothermia blanket. The impedance method was used for noninvasive hemodynamic monitoring, and the changes in heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), cardiac output (CO), cardiac index (CI), and total peripheral resistance (TPR) from the start of hypothermia induction to the achievement of target rectal temperature (34℃). Blood lactic acid (LAC) and resistance index (RI) of the middle cerebral artery were recorded simultaneously. RESULTS: The 21 neonates with HIE had a mean gestational age of (39.6±1.1) weeks, a mean birth weight of (3 439±517) g, and a mean 5-minute Apgar score of 6.8±2.0. From the start of hypothermia induction to the achievement of target rectal temperature (34℃), there were significant reductions in HR, CO, and CI (P < 0.05), while there was no significant change in SV and MAP (P > 0.05). There was a significant increase in TPR (P < 0.05) and a significant reduction in LAC (P < 0.05), while there was no significant change in RI (P > 0.05). CONCLUSIONS: The systemic mild hypothermia therapy may have a significant impact on hemodynamics in neonates with moderate to severe HIE, and continuous hemodynamic monitoring is required during the treatment.

Clinical features and prognosis of severe meconium aspiration syndrome with acute respiratory distress syndrome. / é‡åº¦èƒŽç²ªå¸å ¥ç»¼åˆå¾å¹¶å‘æ€¥æ€§å‘¼å¸çª˜è¿«ç»¼åˆå¾ä¸´åºŠç‰¹å¾åŠè½¬å½’åˆ†æž.

OBJECTIVES: To study the clinical features and prognosis of neonates with severe meconium aspiration syndrome (MAS) and acute respiratory distress syndrome (ARDS). METHODS: A retrospective analysis was performed on the medical data of 60 neonates with severe MAS who were admitted from January 2017 to December 2019. According to the presence or absence of ARDS, they were divided into two groups: ARDS (n=45) and non-ARDS (n=15). Clinical features and prognosis were compared between the two groups. RESULTS: Among the 60 neonates with severe MAS, 45 (75%) developed ARDS. Arterial blood gas analysis showed that the ARDS group had a significantly higher median oxygenation index within 1 hour after birth than the non-ARDS group (4.7 vs 2.1, P<0.05), while there was no significant difference between the two groups in white blood cell count, C-reactive protein (CRP), and interleukin-6 (IL-6) on admission and the peak values of procalcitonin, CRP, and IL-6 during hospitalization (P>0.05). The ARDS group had a significantly higher incidence rate of shock than the non-ARDS group (84% vs 47%, P<0.05). There was no significant difference between the two groups in the incidence rates of persistent pulmonary hypertension, pneumothorax, pulmonary hemorrhage, hypoxic-ischemic encephalopathy, intracranial hemorrhage, and disseminated intravascular coagulation (P>0.05). The ARDS group required a longer median duration of mechanical ventilation than the non-ARDS group (53 hours vs 3 hours, P<0.05). In the ARDS group, 43 neonates (96%) were cured and 2 neonates (4%) died. In the non-ARDS group, all 15 neonates (100%) were cured. CONCLUSIONS: Neonates with severe MAS and ARDS tend to develop respiratory distress earlier, require a longer duration of mechanical ventilation, and have a higher incidence rate of shock. During the management of children with severe MAS, it is recommended to closely monitor oxygenation index, give timely diagnosis and treatment of ARDS, evaluate tissue perfusion, and actively prevent and treat shock. Citation.

[Effect of different antibiotic use strategies on infection in neonates with premature rupture of membranes and high-risk factors for neonatal infection].

OBJECTIVE: To study the effect of different antibiotic use strategies on infection in neonates with premature rupture of membranes and the high-risk factors for neonatal infection. METHODS: A retrospective analysis was performed for the clinical data of 223 neonates with premature rupture of membranes. According to the antibiotic use strategies, they were classified into two groups: study group (n=95) and control group (n=128). The neonates in the study group were given antibiotics based on risk assessment and infection screening, and those in the control group were given antibiotics based on risk assessment alone after admission. General status and prognosis were compared between the two groups. According to the presence or absence of infection, the neonates were classified into two groups: infection group (n=32) and non-infection group (n=191). The clinical data were compared between the two groups. A logistic regression model was used to investigate the high-risk factors for infection in neonates with premature rupture of membranes. RESULTS: Compared with the control group, the study group had a significantly longer time of premature rupture of membranes, a significantly higher rate of cesarean section, and a significantly lower antibiotic use rate at admission and a significantly lower total antibiotic use rate (P<0.05). The study group also had a significantly higher incidence rate of infection and a significantly lower incidence rate of sepsis (P<0.05). There were no significant differences in the incidence rates of other complications between the two groups (P>0.05). Compared with the non-infection group, the infection group had a significantly lower gestational age, a significantly longer time of premature rupture of membranes, a significantly higher rate of cesarean section, and significantly higher levels of C-reactive protein (CRP) and procalcitonin on admission and during reexamination (P<0.05), with fever as the most common symptom. The logistic regression analysis showed that preterm birth and cesarean section were high-risk factors for infection in neonates with premature rupture of membranes (P<0.05). CONCLUSIONS: Strict adherence to the indications for antibiotic use in neonates with premature rupture of membranes does not increase the incidence rate of complications. Neonates with premature rupture of membranes, especially preterm infants and infants delivered by cesarean section, should be closely observed for the change in disease conditions, and infection indices including CRP should be reexamined in case of fever and antibiotics should be used to prevent serious infection.

[Mortality rate and cause of death in hospitalized neonates: an analysis of 480 cases].

OBJECTIVE: To investigate the mortality rate and the cause of death of hospitalized neonates. METHODS: The clinical data of 480 neonates who died between January 2008 and December 2014 were collected. The mortality rates of neonates with different gestational ages, birth weights, sexes, and ages in days were analyzed. The abnormal perinatal factors, cause of death, and death grade were summarized. RESULTS: Among the 41 910 hospitalized neonates, 480 (1.1%) died, and the mortality rates of preterm infants and full-term infants were 1.7% and 0.7%, respectively. The mortality rate of hospitalized neonates decreased from 1.4% in 2008 to 1.1% in 2014, and the decrease was more apparent in the preterm infants with a gestational age of <32 weeks and the neonates with a birth weight of <1 000 g. Among preterm infants and full-term infants, those with a lower gestational age tended to have a higher mortality rate, but post-term infants had an increased mortality rate. The infants with a lower birth weight tended to have a higher mortality rate. Male neonates had a significantly higher mortality rate than female neonates (1.31% vs 0.92%; P<0.05). Among the neonates who died, 61.3% had definite abnormal perinatal factors, including abnormal amniotic fluid (29.4%), premature rupture of membranes (16.9%), placental abnormality (16.9%), fetal intrauterine distress (14.0%), and abnormal umbilical cord (12.3%). Among the 480 neonates who died, 57 (11.9%) died within 24 hours after birth, 181 (37.7%) died within 2-7 days, and 242 (50.4%) died within 8-28 days. The three most common causes of death were infection, birth defect, and respiratory distress syndrome. The most common cause of death was respiratory distress syndrome in 2008-2011 and infection in 2012-2014. Respiratory distress syndrome was the most common cause of death in preterm infants with a gestational age of <32 weeks, neonates with a birth weight of <1 500 g, and neonates who died with 24 hours; infection was the most common cause of death in neonates with a gestational age of 32-42 weeks, neonates with a birth weight of 1 500-4 000 g, and neonates who died within 8-28 days. Neonatal asphyxia was the major cause of death in post-term infants. Inevitable deaths (grade 1) accounted for 54.4%, deaths that could be avoided under certain conditions (grade 2) accounted for 23.3%, and deaths caused by concerns about prognosis or economic reasons (grade 3) accounted for 22.3%. CONCLUSIONS: In recent years, the treatment of neonates has gradually improved, and the mortality rate of neonates is gradually decreasing, especially in neonates with low gestational age and birth weight. Important measures for reducing the mortality rate in neonates include enhancing perinatal management, reducing abnormal perinatal factors, preventing infection, and increasing parents' confidence in treatment.

Edaravone attenuates hippocampal damage in an infant mouse model of pneumococcal meningitis by reducing HMGB1 and iNOS expression via the Nrf2/HO-1 pathway.

AIM: Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a free radical scavenger that has shown potent antioxidant, anti-inflammatory and neuroprotective effects in variety of disease models. In this study, we investigated whether edaravone produced neuroprotective actions in an infant mouse model of pneumococcal meningitis. METHODS: C57BL/6 mice were infected on postnatal d 11 by intracisternal injection of a certain inoculum of Streptococcus pneumoniae. The mice received intracisternal injection of 10 µL of saline containing edaravone (3 mg/kg) once a day for 7 d. The severity of pneumococcal meningitis was assessed with a clinical score. In mice with severe meningitis, the survival rate from the time of infection to d 8 after infection was analyzed using Kaplan-Meier curves. In mice with mild meningitis, the CSF inflammation and cytokine levels in the hippocampus were analyzed d 7 after infection, and the clinical neurological deficit score was evaluated using a neurological scoring system d 14 after infection. The nuclear factor (erythroid-derived 2)-like 2 knockout (Nrf2 KO) mice and heme oxygenase-1 knockout (HO-1 KO) mice were used to confirm the involvement of Nrf2/HO-1 pathway in the neuroprotective actions of edaravone. RESULTS: In mice with severe meningitis, edaravone treatment significantly increased the survival rate (76.4%) compared with the meningitis model group (32.2%). In mice with mild meningitis, edaravone treatment significantly decreased the number of leukocytes and TNF- levels in CSF, as well as the neuronal apoptosis and protein levels of HMGB1 and iNOS in the hippocampus, but did not affect the high levels of IL-10 and IL-6 in the hippocampus. Moreover, edaravone treatment significantly improved the neurological function of mice with mild meningitis. In Nrf2 KO or HO-1 KO mice with the meningitis, edaravone treatment was no longer effective in improving the survival rate of the mice with severe meningitis (20.2% and 53.6%, respectively), nor it affected the protein levels of HMGB1 and iNOS in the hippocampus of the mice with mild meningitis. CONCLUSION: Edaravone produces neuroprotective actions in a mouse model of pneumococcal meningitis by reducing neuronal apoptosis and HMGB1 and iNOS expression in the hippocampus via the Nrf2/HO-1 pathway. Thus, edaravone may be a promising agent for the treatment of bacterial meningitis.

Neonatal mortality and morbidity among infants between 24 to 31 complete weeks: a multicenter survey in China from 2013 to 2014.

BACKGROUND: The outcome of preterm infants has been varied in different hospitals and regions in developing countries. Regular clinical monitor are needed to know the effects of health care. This study aimed to describe the survival and morbidity rates of extreme to very preterm infants in 15 neonatal-intensive care hospitals in China. METHODS: Data were collected from January 1, 2013 to December 31, 2014 for preterm neonates with gestational age (GA) between 24 and 31 complete weeks born in hospitals from our collaborative study group. The primary outcomes were survival and major morbidities prior to hospital discharge. Major morbidities included bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA) and sepsis. Mutivariate logistic regression was used to analyze the risk factor influencing on the outcomes. RESULTS: The preterm birth rate was 9.9 % (13 701/138 240). The proportion of extreme to very preterm infants was 1.1 % and 11.8 % respectively. The survival rate prior to discharge was increased with increasing GA (0, 24 weeks; 28 %, 25 weeks; 84.8 %, 26 weeks; 83.5 %, 27 weeks; 87.4 %, 28 weeks; 90.7 %, 29 weeks; 93.9 %, 30 weeks; 96 %, 31 weeks). Rate of survival and without severe morbidity according to GA were 0 at 24 weeks, 8 % at 25 weeks, 60.6 % at 26 weeks; 53.2 % at 27 weeks; 62.3 % at 28 weeks; 67.9 % at 29 weeks; 79.1 % at 30 weeks, 85.8 % at 31 weeks respectively. Rate of antenatal steroid use was 56 %. The antenatal steroid use was lower in GA < 28 weeks infants than that in GA between 28 and 32 weeks (28-44.3 % vs 49.7-60.1 %, P < 0.05). Infants at the lowest GAs had a highest incidence of morbidities. Overall, 58.5 % had respiratory distress syndrome, 12.5 % bronchopulmonary dysplasia, 3.9 % necrotizing enterocolitis, 15.4 % intraventricular hemorrhage, 5.4 % retinopathy of prematurity, 28.4 % patent ductus arteriosus, and 9.7 % sepsis. Mortality and morbidity were influenced by gestational age (OR = 0.891, 95 % CI: 0.796-0.999, p = 0.0047 and OR = 0.666, 95 % CI: 0.645-0.688, p = 0.000 respectively), birth weight (OR = 0.520, 95 % CI: 0.420-0.643, p = 0.000 and OR = 0.921, 95 % CI: 0.851-0.997, p = 0.041 respectively), SGA (OR = 1.861, 95 % CI: 1.148-3.017, p = 0.012 and OR = 1.511, 95 % CI: 1.300-1.755, p = 0.000 respectively), Apgar score <7 at 5 min (OR = 1.947, 95 % CI: 1.269-2.987, p = 0.002 and OR = 2.262, 95 % CI: 1.950-2.624, p = 0.000 respectively). The survival rate was increased with more prenatal steroid use (OR = 1.615, 95 % CI: 1.233-1.901, p = 0.033). CONCLUSION: Although most of the preterm infants with GAs ≥26 weeks survived, a high complication in survivors still can be observed. Rate of survival of GAs less than 26 weeks was still low, and quality improvement methods should be used to look into increasing the use of antenatal steroids in the very preterm births.

Point-of-care ultrasound in early diagnosis and monitoring of deep abscess in newborns: a case report of two cases.

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

An endogenous amniotic fluid-derived 10-amino acid peptide improves lung development and hyperoxia injury.

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

Application of abdominal ultrasonography in surgical necrotizing enterocolitis: a retrospective study.

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

Point-of-care ultrasound for monitoring catheter tip location during umbilical vein catheterization in neonates: a prospective study.

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

Early markers of neurodevelopmental disorders based on general movements for very preterm infants: study protocol for a multicentre prospective cohort study in a clinical setting in China.

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

Case Report: Lung Ultrasound in Critically Ill Neonates With Lung Diseases: Experience From Several Typical Cases.

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

Genome-wide association, RNA-seq and iTRAQ analyses identify candidate genes controlling radicle length of wheat.

The radicle, present in the embryo of a seed, is the first root to emerge at germination, and its rapid growth is essential for establishment and survival of the seedling. However, there are few studies on the critical mechanisms underlying radicle and then radicle length in wheat seedlings, despite its importance as a food crop throughout the world. In the present study, 196 wheat accessions from the Huanghuai Wheat Region were screened to measure radicle length under 4 hydroponic culture environments over 3 years. Different expression genes and proteins (DEGs/DEPs) between accessions with extremely long [Yunong 949 (WRL1), Zhongyu 9,302 (WRL2)] and short roots [Yunong 201 (WRS1), Beijing 841 (WRS2)] were identified in 12 sets of root tissue samples by RNA-seq and iTRAQ (Isobaric tags for relative and absolute quantification). Phenotypic results showed that the elongation zone was significantly longer in root accessions with long roots compared to the short-rooted accessions. A genome-wide association study (GWAS) identified four stable chromosomal regions significantly associated with radicle length, among which 1A, 4A, and 7A chromosomes regions explained 7.17% to12.93% of the phenotypic variation. The omics studies identified the expression patterns of 24 DEGs/DEPs changed at both the transcriptional and protein levels. These DEGs/DEPs were mainly involved in carbon fixation in photosynthetic organisms, photosynthesis and phenylpropanoid biosynthesis pathways. TraesCS1A02G104100 and TraesCS2B02G519100 were involved in the biosynthesis of tricin-lignins in cell walls and may affect the extension of cell walls in the radicle elongation zone. A combination of GWAS and RNA-seq analyses revealed 19 DEGs with expression changes in the four accessions, among which, TraesCS1A02G422700 (a cysteine-rich receptor-like protein kinase 6, CRK6) also showed upregulation in the comparison group by RNA-seq, iTRAQ, and qRT-PCR. BSMV-mediated gene silencing also showed that TaCRK6 improves root development in wheat. Our data suggest that TaCRK6 is a candidate gene regulating radicle length in wheat.

Alagille syndrome due to a de novo NOTCH2 mutation presenting as prenatal oligohydramnios and congenital bilateral renal hypodysplasia: A case report.

Introduction: Here, we report the case of an infant suffering from Alagille syndrome (ALGS), manifesting with the atypical clinical manifestations of prenatal oligohydramnios and renal lesions. To the best of our knowledge, this is the first case of ALGS presenting as prenatal oligohydramnios and renal lesions caused by a de novo variant of the NOTCH2 gene. Case presentation: A 3-month-old male infant was hospitalized for severe malnutrition. He presented with prenatal oligohydramnios from 28+4 weeks of gestation. After birth, he failed to thrive and suffered from impaired motor development, thermoregulation disorders, congenital bilateral renal hypodysplasia, which initially manifested as stage 5 before improving to stage 3 chronic renal impairment, slightly elevated levels of transaminases, cholestasis, and dysmorphic facial features. We used a diagnostic screening panel of 4,047 pathogenic genes and whole exome sequencing (WES) to analyze the proband and his parents (who had normal kidneys). We found that the proband carried a de novo heterozygous splicing variant (c.5930-2A > G) in intron 33 of the NOTCH2 gene. Transcriptome sequencing confirmed that the mutation of this gene site would affect the splicing of NOTCH2 mRNA and lead to exon 33 skipping. Conclusions: Our case expands the spectrum of pathogenic variants of the NOTCH2 gene that are known to be associated with ALGS and characterized by prenatal oligohydramnios and renal lesions. It also reminds us of the necessity to monitor the liver and kidney function of the infant if a mother has oligohydramnios during pregnancy and we recommend ALGS as an additional differential diagnosis in prenatal renal abnormalities.