Explore the vast range of titles available.

Bromodomain-containing protein 4 (BRD4) is a member of the bromodomain and extra terminal (BET) protein family that has gained wide attention in the field of cancer due to its role in the formation of super enhancers (SEs) and the regulation of oncogene expression. However, there is increasing evidence that BRD4 also plays a pivotal role in a variety of cardiovascular diseases, suggesting that understanding the mechanisms of BRD4 in these diseases is important to advance studies and clinical treatment. In this article, we summarize the mechanisms of BRD4 in cardiovascular diseases, including pulmonary arterial hypertension, heart failure, atherosclerosis, and hypertension. In addition, we discuss small molecule inhibitors of BRD4 as novel therapeutic strategies for cardiovascular diseases.

Background Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants and hyperoxia exposure is a major cause. In hyperoxic lung injury animal model, alveolar simplification and pro-inflammatory cells infiltration are the main pathophysiologic changes. Caffeine is a drug used to treat apnea in premature infants. Early use of caffeine can decrease the rate and the severity of BPD while the mechanisms are still unclear. The purpose of this study was to evaluate the effects of caffeine on inflammation and lung development in neonatal mice with hyperoxic lung injury and to explore the possible mechanism. Methods Following 14 d of 75% oxygen exposure in newborn mouse, the BPD model was established. Caffeine at a dose of 1 g/L was added in drinking water to nursing mouse. We measured the concentration of caffeine in serum and oxidative stress in lung by commercially available kits. Adenosine 2A receptor (A 2A R) expression and lung inflammation were measured by Immunohistochemistry and western blotting. Apoptosis and surfactant protein-C (SFTPC) levels were measured by immunofluorescence. The inflammasome and NF-κB pathway proteins were assessed by western blotting. Results We found that the caffeine concentration in plasma at present dose significantly decreased the expression of A 2A R protein in mice lung. Caffeine treatment significantly reduced oxidative stress, improved weight gain, promoted alveolar development, attenuated inflammatory infiltration and lung injury in hyperoxia-induced lung injury mice. Moreover, caffeine decreased the cell apoptosis in lung tissues, especially the Type II alveolar epithelial cell. The expression of NLRP3 inflammasome protein and NF-κB pathway were significantly inhibited by caffeine treatment. Conclusion Caffeine treatment can protect hyperoxia-induced mice lung from oxidative injury by inhibiting NLRP3 inflammasome and NF-κB pathway.

Background The burden and characteristics of respiratory viral infections in children hospitalized for acute respiratory tract infections (ARTIs) during the post-COVID-19 pandemic era are unclear. We analyzed the epidemiological and clinical characteristics of pediatric patients hospitalized with common respiratory virus infections before and after relaxation of non-pharmaceutical interventions in Hangzhou, China and evaluated the diagnostic value of the six-panel respiratory pathogen detection system. Methods Six types of respiratory viruses were detected in respiratory samples from children with suspected ARTIs by multiplex real-time quantitative polymerase chain reaction (RT-qPCR). Changes in virus detection rates and epidemiological and clinical characteristics, obtained from electronic health records, were analyzed. Binary logistic regression was used to identify respiratory tract infections risk factors. Multiplex RT-qPCR and targeted next-generation sequencing results were compared in random samples. Results Among the 11,056 pediatric samples, 3228 tested positive for one or more of six common respiratory pathogens. RSV and PIV-3 detection rates differed significantly across age groups (both P  < 0.001), and were more common in younger children. PIV-1 was more common in infants, toddlers, and preschoolers than in school-age children ( P  < 0.001). FluB was predominantly detected in school-age children ( P  < 0.001). RSV-, ADV-, and PIV-1-positivity rates were higher in 2022 than in 2023. Seasonal viral patterns differed across years. RSV (OR 9.156. 95% CI 5.905–14.195) and PIV-3 (OR 1.683, 95% CI 1.133–2.501) were risk factors for lower respiratory tract infections. RSV-positivity was associated with severe pneumonia ( P  = 0.044). PIV-3 (OR 0.391, 95% CI 0.170–0.899), summer season (OR 1.982, 95% CI 1.117–3.519), and younger age (OR 0.938, 95% CI 0.893–0.986) influenced pneumonia severity. Multiplex RT-qPCR showed good diagnostic performance. Conclusion After changes in COVID-19 prevention and control strategies, six common respiratory viruses in children were prevalent in 2022–2023, with different seasonal epidemic characteristics and age proclivities. RSV and PIV-3 cause lower, and FluA, FluB, and ADV more typically cause upper respiratory tract infections. Infancy and summer season influence severe pneumonia risk. Multiplex RT-qPCR is valuable for accurate and timely detection of respiratory viruses in children, which facilitates management, treatment, and prevention of ARTIs.

Background Pulmonary hypertension (PH) is a complex pulmonary vascular disease characterized by an imbalance in vasoconstrictor/vasodilator signaling within the pulmonary vasculature. Recent evidence suggests that exposure to hypoxia early in life can cause alterations in the pulmonary vasculature and lead to the development of PH. However, the long-term impact of postnatal hypoxia on lung development and pulmonary function remains unknown. N 6 -methyladenosine (m 6 A) regulates gene expression and governs many important biological processes. However, the function of m 6 A in the development of PH remains poorly characterized. Thus, the purpose of this investigation was to test the two-fold hypothesis that (1) postnatal exposure to hypoxia would alter lung development leading to PH in adult rats, and (2) m 6 A modification would change in rats exposed to hypoxia, suggesting it plays a role in the development of PH. Methods Twenty-four male Sprague–Dawley rats were exposed to a hypoxic environment (F i O 2 : 12%) within 24 h after birth for 2 weeks. PH was defined as an increased right ventricular pressure (RVP) and pathologic changes of pulmonary vasculature measured by α-SMA immunohistochemical staining. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was performed to analyze m 6 A modification changes in lung tissue in 2- and 9-week-old rats that were exposed to postnatal hypoxia. Results Mean pulmonary arterial pressure, lung/body weight ratio, and the Fulton index was significantly greater in rats exposed to hypoxia when compared to control and the difference persisted into adulthood. m 6 A methyltransferase and demethylase proteins were significantly downregulated in postnatal hypoxia-induced PH. Distinct m 6 A modification peak-related genes differed between the two groups, and these genes were associated with lung development. Conclusions Our results indicate postnatal hypoxia can cause PH, which can persist into adulthood. The development and persistence of PH may be because of the continuous low expression of methyltransferase like 3 affecting the m 6 A level of PH-related genes. Our findings provide new insights into the impact of postnatal hypoxia and the role of m 6 A in the development of pulmonary vascular pathophysiology.

ObjectivesTo examine bronchopulmonary dysplasia (BPD) epidemiological data in Chinese very preterm infants and compare agreement between four diagnostic definitions and their predictive accuracy for discharge outcomes.DesignObservational epidemiologic study of a multicentre cohort of the Chinese Neonatal Network (CHNN).SettingTertiary neonatal intensive care units participating in the CHNN.Participants42 664 preterm infants born at <32 weeks’ gestational age from 2019 to 2023.MeasuresBPD was diagnosed using four definitions: Shennan 1988, the National Institute of Child Health and Human Development (NICHD) 2001 and 2018, and the Neonatal Research Network (NRN) 2019 definitions. BPD prevalence and severity were examined. Agreement was assessed using kappa statistics. Predictive accuracy for discharge outcomes was evaluated using c-statistics from multivariable generalised estimating equation models.ResultsAmong 42 664 infants (mean gestational age, 29.0 weeks; 43.1% females), BPD prevalence varied significantly: Shennan 1988: 37.0%, NICHD 2001: 51.1%, NICHD 2018: 37.0%, NRN 2019: 37.0%. NICHD 2001 and 2018 definitions classified more infants as severe BPD (16.4% and 10.1%, respectively), while NRN 2019 classified more as grade 2 (moderate; 15.0%). Shennan 1988 showed good agreement with NICHD 2018 (κ=1.0) and Jensen 2019 (κ=1.0). Shennan 1988 (c-statistic range: 0.921–0.974), NICHD 2018 (0.948-0.978) and NRN 2019 (0.949-0.982) demonstrated higher discriminative accuracy for discharge outcomes than NICHD 2001 (0.854–0.925).ConclusionsThis study found a high prevalence of BPD among very preterm infants in China, varying by definitions. The Shennan 1988, NICHD 2018 and NRN 2019 definitions showed good agreement and better predictive accuracy for outcomes at discharge compared with NICHD 2001. These definitions could be prioritised for clinical use in our population.

Background The interplay between intrauterine and early postnatal environments has been associated with an increased risk of cardiovascular diseases in adulthood, including pulmonary arterial hypertension (PAH). While emerging evidence highlights the crucial role of mitochondrial pathology in PAH, the specific mechanisms driving fetal-originated PAH remain elusive. Methods and results To elucidate the role of mitochondrial dynamics in the pathogenesis of fetal-originated PAH, we established a rat model of postnatal catch-up growth following intrauterine growth restriction (IUGR) to induce pulmonary arterial hypertension (PAH). RNA-seq analysis of pulmonary artery samples from the rats revealed dysregulated mitochondrial metabolic genes and pathways associated with increased pulmonary arterial pressure and pulmonary arterial remodeling in the RC group (postnatal catch-up growth following IUGR). In vitro experiments using pulmonary arterial smooth muscle cells (PASMCs) from the RC group demonstrated elevated proliferation, migration, and impaired mitochondrial functions. Notably, reduced expression of Mitofusion 2 (Mfn2), a mitochondrial outer membrane protein involved in mitochondrial fusion, was observed in the RC group. Reconstitution of Mfn2 resulted in enhanced mitochondrial fusion and improved mitochondrial functions in PASMCs of RC group, effectively reversing the Warburg effect. Importantly, Mfn2 reconstitution alleviated the PAH phenotype in the RC group rats. Conclusions Imbalanced mitochondrial dynamics, characterized by reduced Mfn2 expression, plays a critical role in the development of fetal-originated PAH following postnatal catch-up growth after IUGR. Mfn2 emerges as a promising therapeutic strategy for managing IUGR-catch-up growth induced PAH.

Background Human respiratory syncytial virus (HRSV) is the leading pathogens causing acute respiratory infections (ARI) in children under five years old. We aimed to investigate the distribution of HRSV subtypes and explore the relationship between viral subtypes and clinical symptoms and disease severity. Methods From November 2016 to April 2017, 541 children hospitalized because of ARI were included in the study. Throat swabs were collected for analysis and all samples were tested by multiplex one-step qRT-PCR for quantitative analysis and typing of HRSV. Patients’ demographics, clinical symptoms as well as laboratory and imaging results were retrieved from medical records. Results HRSV was detected in 19.6% of children hospitalized due to ARI. HRSV-positive children were younger ( P  < 0.001), had a higher frequency of wheezing and pulmonary rales ( P  < 0.001; P  = 0.003), and were more likely to develop bronchopneumonia ( P  < 0.001). Interleukin (IL) 10、CD4/CD8 (below normal range) and C-reactive protein levels between subtypes A and B groups were significantly different ( P  = 0.037; P  = 0.029; P  = 0.007), and gender differences were evident. By age-stratified analysis between subtypes A and B, we found significant differences in fever frequency and lymphocyte ratio ( P  = 0.008; P  = 0.03) in the 6–12 months age group, while the 12. 1–36 months age group showed significant differences in fever days and count of leukocytes, platelets, levels aspartate aminotransferase, IL-6, lactate dehydrogenase and proportion CD4 positive T cells( P  = 0.013; P  = 0.018; P  = 0.016; P  = 0.037; P  = 0.049; P  = 0.025; P  = 0.04). We also found a positive correlation between viral load and wheezing days in subtype A ( P  < 0.05), and a negative correlation between age, monocyte percentage and LDH concentration in subtype B ( P  < 0.05). Conclusions HRSV is the main causative virus of bronchopneumonia in infants and children. The multiplex one-step qRT-PCR not only provides a rapid and effective diagnosis of HRSV infection, but also allows its typing. There were no significant differences in the severity of HRSV infection between subtypes A and B, except significant gender-specific and age-specific differences in some clinical characteristics and laboratory results. Knowing the viral load of HRSV infection can help understanding the clinical features of different subtypes of HRSV infection.

Hypertensive disorders of pregnancy (HDP) may affect fetal development and result in preterm delivery. Necrotizing enterocolitis (NEC) is a severe gastrointestinal emergency in very preterm infants (VPIs, gestational age less than 32 weeks). The relationship between maternal HDP and NEC is controversial. Objective To investigate the association between maternal HDP and NEC in VPIs.This was a multicenter retrospective cohort study based on the data from the Chinese Neonatal Network (CHNN) which were collected between January 1, 2019 and December 31, 2021. Preterm infants born between 24+0 and 31+6 weeks of gestation were divided into HDP and no-HDP groups according to the 2015 Chinese guidelines for HDP. The primary outcome was the incidence of Bell’s stage II or higher NEC. Secondary outcomes included mortality and spontaneous intestinal perforation (SIP). Of 27,660 women were included in the study analysis, 5405 (19.5%) were HDP and 22256 (80.5%) were no-HDP. NEC occurred in 5.2% (283/5,404) among HDP mothers and 5.3% (1,191/22,256) among no-HDP mothers. No significant association was observed between HDP and Bell’s stage II or higher NEC (aOR 0.87, 95% CI [0.72, 1.05]). However, even after adjustment, maternal HDP appeared to be protective for NEC requiring surgical intervention (aOR 0.60, 95% CI [0.43, 0.83]). There was no significant correlation between maternal HDP and neonatal mortality and SIP. Maternal HDP was not significantly associated with the incidence of Bell’s stage II or higher NEC. However, it was associated with the lower rate of NEC requiring surgical intervention.

Background Aberrations in the preterm microbiome following antibiotic therapy have been reported in previous studies. The objective of this study was to probe potential underlying mechanisms between this observation and susceptibility to adverse prematurity-related outcomes. Results Metagenomic shotgun sequencing was performed on 133 stool and 253 skin samples collected at 1 and 3 weeks of age from 68 infants born at <36 weeks postmenstrual age and birth weight <2000 g. After accounting for gestational age and maternal antibiotics, the distribution of organisms in all samples and the corresponding metabolic pathway abundance were compared between infants exposed to postnatal antibiotics and antibiotics-naïve infants. In antibiotic-naïve infants, gestational and postnatal age imparted similar trajectories on maturation of the microbial community and associated metabolic functional capacity, with postnatal age exerting greater contribution. Antibiotic exposure was associated with reversal in maturation trajectory from the first week to the third week of age ( p < 0.001). Butyrate-producing genera, including Clostridium and Blautia , were significantly more abundant in antibiotic-naïve neonates at 3 weeks postnatal age. Correspondingly, metabolic pathways required for short-chain fatty acid synthesis were significantly increased in antibiotic-naïve infants, but not in antibiotic-exposed neonates, at 3 weeks after birth. Conclusions Early brief antibiotic exposure markedly disrupts developmental trajectory of the neonatal microbiome and its corresponding functional capacity. Our findings may provide a mechanistic explanation for the known associations between antibiotic use and adverse outcomes in preterm infants. 459naA43GFKEq_9gJQNK48 Video Abstract

Background Bronchopulmonary dysplasia (BPD) is a major complication affecting the survival rate and long-term outcomes of preterm infants. A large, prospective, multicenter cohort study was conducted to evaluate early nutritional support during the first week of life for preterm infants with a gestational age < 32 weeks and to verify nutritional risk factors related to BPD development. Methods A prospective multicenter cohort study of very preterm infants was conducted in 40 tertiary neonatal intensive care units across mainland China between January 1, 2020, and December 31, 2021. Preterm infants who were born at a gestational age < 32 weeks, < 72 h after birth and had a respiratory score > 4 were enrolled. Antenatal and postnatal information focusing on nutritional parameters was collected through medical systems. Statistical analyses were also performed to identify BPD risk factors. Results The primary outcomes were BPD and severity at 36 weeks postmenstrual age. A total of 1410 preterm infants were enrolled in this study. After applying the exclusion criteria, the remaining 1286 infants were included in this analysis; 614 (47.7%) infants were in the BPD group, and 672 (52.3%) were in the non-BPD group. In multivariate logistic regression model, the following six factors were identified of BPD: birth weight (OR 0.99, 95% CI 0.99–0.99; p  = 0.039), day of full enteral nutrition (OR 1.03, 95% CI 1.02–1.04; p  < 0.001), parenteral protein > 3.5 g/kg/d during the first week (OR 1.65, 95% CI 1.25–2.17; p  < 0.001), feeding type (formula: OR 3.48, 95% CI 2.21–5.49; p  < 0.001, mixed feed: OR 1.92, 95% CI 1.36–2.70; p  < 0.001; breast milk as reference), hsPDA (OR 1.98, 95% CI 1.44–2.73; p  < 0.001), and EUGR ats 36 weeks (OR 1.40, 95% CI 1.02–1.91; p  = 0.035). Conclusions A longer duration to achieve full enteral nutrition in very preterm infants was associated with increased BPD development. Breastfeeding was demonstrated to have a protective effect against BPD. Early and rapidly progressive enteral nutrition and breastfeeding should be promoted in very preterm infants. Trial registration The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2000030125 on 24/02/2020) and in www.ncrcch.org (No. ISRCTN84167642 on 25/02/2020).