Metabolic regulation of cell growth and proliferation.

Cellular metabolism is at the foundation of all biological activities. The catabolic processes that support cellular bioenergetics and survival have been well studied. By contrast, how cells alter their metabolism to support anabolic biomass accumulation is less well understood. During the commitment to cell proliferation, extensive metabolic rewiring must occur in order for cells to acquire sufficient nutrients such as glucose, amino acids, lipids and nucleotides, which are necessary to support cell growth and to deal with the redox challenges that arise from the increased metabolic activity associated with anabolic processes. Defining the mechanisms of this metabolic adaptation for cell growth and proliferation is now a major focus of research. Understanding the principles that guide anabolic metabolism may ultimately enhance ways to treat diseases that involve deregulated cell growth and proliferation, such as cancer.

Identification of SARS-CoV-2 inhibitors using lung and colonic organoids.

There is an urgent need to create novel models using human disease-relevant cells to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) biology and to facilitate drug screening. Here, as SARS-CoV-2 primarily infects the respiratory tract, we developed a lung organoid model using human pluripotent stem cells (hPSC-LOs). The hPSC-LOs (particularly alveolar type-II-like cells) are permissive to SARS-CoV-2 infection, and showed robust induction of chemokines following SARS-CoV-2 infection, similar to what is seen in patients with COVID-19. Nearly 25% of these patients also have gastrointestinal manifestations, which are associated with worse COVID-19 outcomes1. We therefore also generated complementary hPSC-derived colonic organoids (hPSC-COs) to explore the response of colonic cells to SARS-CoV-2 infection. We found that multiple colonic cell types, especially enterocytes, express ACE2 and are permissive to SARS-CoV-2 infection. Using hPSC-LOs, we performed a high-throughput screen of drugs approved by the FDA (US Food and Drug Administration) and identified entry inhibitors of SARS-CoV-2, including imatinib, mycophenolic acid and quinacrine dihydrochloride. Treatment at physiologically relevant levels of these drugs significantly inhibited SARS-CoV-2 infection of both hPSC-LOs and hPSC-COs. Together, these data demonstrate that hPSC-LOs and hPSC-COs infected by SARS-CoV-2 can serve as disease models to study SARS-CoV-2 infection and provide a valuable resource for drug screening to identify candidate COVID-19 therapeutics.

Role of Mitochondria in Ferroptosis.

Ferroptosis is a regulated necrosis process driven by iron-dependent lipid peroxidation. Although ferroptosis and cellular metabolism interplay with one another, whether mitochondria are involved in ferroptosis is under debate. Here, we demonstrate that mitochondria play a crucial role in cysteine-deprivation-induced ferroptosis but not in that induced by inhibiting glutathione peroxidase-4 (GPX4), the most downstream component of the ferroptosis pathway. Mechanistically, cysteine deprivation leads to mitochondrial membrane potential hyperpolarization and lipid peroxide accumulation. Inhibition of mitochondrial TCA cycle or electron transfer chain (ETC) mitigated mitochondrial membrane potential hyperpolarization, lipid peroxide accumulation, and ferroptosis. Blockage of glutaminolysis had the same inhibitory effect, which was counteracted by supplying downstream TCA cycle intermediates. Importantly, loss of function of fumarate hydratase, a tumor suppressor and TCA cycle component, confers resistance to cysteine-deprivation-induced ferroptosis. Collectively, this work demonstrates the crucial role of mitochondria in cysteine-deprivation-induced ferroptosis and implicates ferroptosis in tumor suppression.

Proline biosynthesis is a vent for TGFß-induced mitochondrial redox stress.

The production and secretion of matrix proteins upon stimulation of fibroblasts by transforming growth factor-beta (TGFß) play a critical role in wound healing. How TGFß supports the bioenergetic cost of matrix protein synthesis is not fully understood. Here, we show that TGFß promotes protein translation at least in part by increasing the mitochondrial oxidation of glucose and glutamine carbons to support the bioenergetic demand of translation. Surprisingly, we found that in addition to stimulating the entry of glucose and glutamine carbon into the TCA cycle, TGFß induced the biosynthesis of proline from glutamine in a Smad4-dependent fashion. Metabolic manipulations that increased mitochondrial redox generation promoted proline biosynthesis, while reducing mitochondrial redox potential and/or ATP synthesis impaired proline biosynthesis. Thus, proline biosynthesis acts as a redox vent, preventing the TGFß-induced increase in mitochondrial glucose and glutamine catabolism from generating damaging reactive oxygen species (ROS) when TCA cycle activity exceeds the ability of oxidative phosphorylation to convert mitochondrial redox potential into ATP. In turn, the enhanced synthesis of proline supports TGFß-induced production of matrix proteins.

Dynamically Cross-Linked, Self-Healable, and Stretchable All-Hydrogel Supercapacitor with Extraordinary Energy Density and Real-Time Pressure Sensing.

Wearable electronics with flexible, integrated, and self-powered multi-functions are becoming increasingly attractive, but their basic energy storage units are challenged in simultaneously high energy density, self-healing, and real-time sensing capability. To achieve this, a fully flexible and omni-healable all-hydrogel, that is dynamically crosslinked PVA@PANI hydrogel, is rationally designed and constructed via aniline/DMSO-emulsion-templated in situ freezing-polymerization strategy. The PVA@PANI sheet, not only possesses a honeycombed porous conductive mesh configuration with superior flexibility that provides numerous channels for unimpeded ions/electron transport and maximizes the utilization efficiency of pseudocapacitive PANI, but also can conform to complicated body surface, enabling effective detection and discrimination of body movements. As a consequence, the fabricated flexible PVA@PANI sheet electrode demonstrates an unprecedented specific capacitance (936.8 F g-1 ) and the assembled symmetric flexible all-solid-state supercapacitor delivers an extraordinary energy density of 40.98 Wh kg-1 , outperforming the previously highest-reported values of stretchable PVA@PANI hydrogel-based supercapacitors. What is more, such a flexible supercapacitor electrode enables precisely monitoring the full-range human activities in real-time, and fulfilling a quick response and excellent self-recovery. These outstanding flexible sensing and energy storage performances render this emerging PVA@PANI hydrogel highly promising for the next-generation wearable self-powered sensing electronics.

SARS-CoV-2 Infection Induces Ferroptosis of Sinoatrial Node Pacemaker Cells.

BACKGROUND: Increasing evidence suggests that cardiac arrhythmias are frequent clinical features of coronavirus disease 2019 (COVID-19). Sinus node damage may lead to bradycardia. However, it is challenging to explore human sinoatrial node (SAN) pathophysiology due to difficulty in isolating and culturing human SAN cells. Embryonic stem cells (ESCs) can be a source to derive human SAN-like pacemaker cells for disease modeling. METHODS: We used both a hamster model and human ESC (hESC)-derived SAN-like pacemaker cells to explore the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the pacemaker cells of the heart. In the hamster model, quantitative real-time polymerase chain reaction and immunostaining were used to detect viral RNA and protein, respectively. We then created a dual knock-in SHOX2:GFP;MYH6:mCherry hESC reporter line to establish a highly efficient strategy to derive functional human SAN-like pacemaker cells, which was further characterized by single-cell RNA sequencing. Following exposure to SARS-CoV-2, quantitative real-time polymerase chain reaction, immunostaining, and RNA sequencing were used to confirm infection and determine the host response of hESC-SAN-like pacemaker cells. Finally, a high content chemical screen was performed to identify drugs that can inhibit SARS-CoV-2 infection, and block SARS-CoV-2-induced ferroptosis. RESULTS: Viral RNA and spike protein were detected in SAN cells in the hearts of infected hamsters. We established an efficient strategy to derive from hESCs functional human SAN-like pacemaker cells, which express pacemaker markers and display SAN-like action potentials. Furthermore, SARS-CoV-2 infection causes dysfunction of human SAN-like pacemaker cells and induces ferroptosis. Two drug candidates, deferoxamine and imatinib, were identified from the high content screen, able to block SARS-CoV-2 infection and infection-associated ferroptosis. CONCLUSIONS: Using a hamster model, we showed that primary pacemaker cells in the heart can be infected by SARS-CoV-2. Infection of hESC-derived functional SAN-like pacemaker cells demonstrates ferroptosis as a potential mechanism for causing cardiac arrhythmias in patients with COVID-19. Finally, we identified candidate drugs that can protect the SAN cells from SARS-CoV-2 infection.

Diagnostic status and epidemiological characteristics of community-acquired bacterial meningitis in children from 2019 to 2020: a multicenter retrospective study.

Community-acquired bacterial meningitis (CABM) is the main cause of morbidity and mortality in children. The epidemiology of CABM is regional and highly dynamic. To clarify the diagnostic status and epidemiological characteristics of children with CABM in this region, and pay attention to the disease burden, so as to provide evidence for the prevention and treatment of CABM. By retrospective case analysis, the clinical data of 918 CABM cases in children aged 0-14 years in Zhejiang Province from January, 2019 to December, 2020 were collected. The etiological diagnosis rate of CABM in children was 23.1%, the annual incidence rate 4.42-6.15/100,000, the annual mortality rate 0.06-0.09/100,000,the cure and improvement rate 94.4%, and the case fatality rate 1.4%. The total incidence of neuroimaging abnormalities was 20.6%. The median length of stay for CABM children was 20(16) days, with an average cost of 21,531(24,835) yuan. In addition, the incidence rate was decreased with age. Escherichia coli(E.coli) and group B Streptococcus agalactiae(GBS) were the principal pathogens in CABM infant<3 months(43.3%, 34.1%), and Streptococcus pneumoniae(S. pneumoniae) was the most common pathogen in children ≥ 3 months(33.9%). In conclusion, the annual incidence and mortality of CABM in children aged 0-14 years in Zhejiang Province are at intermediate and low level. The distribution of CABM incidence and pathogen spectrum are different in age; the incidence of abnormal neuroimaging is high; and the economic burden is heavy.

Analysis of Clinical Outcome and Prognosis of C-reactive Protein Combined with Albumin in Patients with Acute Myocardial Infarction.

Objective: This study aims to assess the combined predictive value of C-reactive protein (CRP) and albumin (ALB) for major adverse cardiovascular events (MACE) post-percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Methods: We analyzed data from continuously enrolled AMI patients who underwent emergency PCI at the First Affiliated Hospital of Xinjiang Medical University over six years, employing logistic regression to derive a predictive equation for in-hospital mortality and out-of-hospital MACE events. Primary endpoints: In-hospital death and out-of-hospital major adverse cardiovascular events. The patients were followed up for 1, 3, 6, and 12 months after discharge. The average follow-up time was 41 months. Results: Among the 601 patients studied, we observed 16 in-hospital deaths and 131 out-of-hospital MACE events. Multivariate logistic regression analysis showed that the independent predictors of out-of-hospital MACE events were age (OR=1.067, 95% CI 1.013-1.124, P = .028), C-reactive protein (OR=1.012, 95% CI 1.000-1.025, P = .045) and albumin (OR=0.874, 95% CI 0.785-0.973, P = .014). Our multivariate logistic regression analysis identified age, CRP, and albumin as independent predictors, with the combined equation yielding an ROC curve area of 0.85, effectively stratifying patients into high-risk and low-risk groups. Subsequent follow-up results validated this risk stratification approach. Conclusion: The study underscores the efficacy of combining CRP and albumin levels as a predictive measure for in-hospital death and out-of-hospital MACE events in AMI patients post-PCI.

MLL1 is essential for the senescence-associated secretory phenotype.

Oncogene-induced senescence (OIS) and therapy-induced senescence (TIS), while tumor-suppressive, also promote procarcinogenic effects by activating the DNA damage response (DDR), which in turn induces inflammation. This inflammatory response prominently includes an array of cytokines known as the senescence-associated secretory phenotype (SASP). Previous observations link the transcription-associated methyltransferase and oncoprotein MLL1 to the DDR, leading us to investigate the role of MLL1 in SASP expression. Our findings reveal direct MLL1 epigenetic control over proproliferative cell cycle genes: MLL1 inhibition represses expression of proproliferative cell cycle regulators required for DNA replication and DDR activation, thus disabling SASP expression. Strikingly, however, these effects of MLL1 inhibition on SASP gene expression do not impair OIS and, furthermore, abolish the ability of the SASP to enhance cancer cell proliferation. More broadly, MLL1 inhibition also reduces "SASP-like" inflammatory gene expression from cancer cells in vitro and in vivo independently of senescence. Taken together, these data demonstrate that MLL1 inhibition may be a powerful and effective strategy for inducing cancerous growth arrest through the direct epigenetic regulation of proliferation-promoting genes and the avoidance of deleterious OIS- or TIS-related tumor secretomes, which can promote both drug resistance and tumor progression.

Suppressing Excess Lead Iodide Aggregation and Reducing N-Type Doping at Perovskite/HTL Interface for Efficient Perovskite Solar Cells.

Excess lead iodide (PbI2 ) aggregation at the charge carrier transport interface leads to energy loss and acts as unstable origins in perovskite solar cells (PSCs). Here, a strategy is reported to modulate the interfacial excess PbI2 by introducing π-conjugated small-molecule semiconductors 4,4'-cyclohexylbis[N,N-bis(4-methylphenyl)aniline] (TAPC) into perovskite films through an antisolvent addition method. The coordination of TAPC to PbI units through the electron-donating triphenylamine groups and π-Pb2+ interactions allows for a compact perovskite film with reduced excess PbI2 aggregates. Besides, preferred energy level alignment is achieved due to the suppressed n-type doping effect at the hole transport layer (HTL) interfaces. As a result, the TAPC-modified PSC based on Cs0.05 (FA0.85 MA0.15 )0.95 Pb(I0.85 Br0.15 )3 triple-cation perovskite achieved an improved PCE from 18.37% to 20.68% and retained ≈90% of the initial efficiency after 30 days of aging under ambient conditions. Moreover, the TAPC-modified device based on FA0.95 MA0.05 PbI2.85 Br0.15 perovskite produced an improved efficiency of 23.15% compared to the control (21.19%). These results provide an effective strategy for improving the performance of PbI2 -rich PSCs.

An Immuno-Cardiac Model for Macrophage-Mediated Inflammation in COVID-19 Hearts.

[Figure: see text].

Coexistence of ferroelectricity and ferromagnetism in hex-GeS nanowires.

The existence of one-dimensional (1D) ferroelectricity and ferromagnetism provides an opportunity to expand the field of research in low-dimensional magnetoelectric and multiferroics and explore the future development of high-performance nanometer devices. Here, we predict a novel 1D ferroelectric hex-GeS nanowire with coexisting ferromagnetism. The electric polarization comes from the atomic displacements between Ge and S atoms, and it exhibits a far-higher than room temperature ferroelectric Curie temperature TEc = 830 K. The ferromagnetism, stemming from the Stoner instability, can be tuned by hole doping and maintained over a wide range of hole concentrations. Additionally, an indirect-direct-indirect band gap transition can be achieved via strain engineering and the bonding nature of the near-band-edge electronic orbitals revealed this transition mechanism. These results offer a platform to investigate 1D ferroelectric and ferromagnetic systems, and the presented hex-GeS nanowire demonstrates the potential for high-performance electronic and spintronic applications.

Cytoplasmic chromatin triggers inflammation in senescence and cancer.

Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders.

A predictive model for preterm infants with bronchopulmonary dysplasia based on ferroptosis-related lncRNAs.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most challenging chronic lung disease for prematurity, with difficulties in early identification. Given lncRNA emerging as a novel biomarker and the regulator of ferroptosis, this study aims to develop a BPD predictive model based on ferroptosis-related lncRNAs (FRLs). METHODS: Using a rat model, we firstly explored mRNA levels of ferroptosis-related genes and ferrous iron accumulation in BPD rat lungs. Subsequently, a microarray dataset of umbilical cord tissue from 20 preterm infants with BPD and 34 preterm infants without BPD were downloaded from the Gene Expression Omnibus databases. Random forest and LASSO regression were conducted to identify diagnostic FRLs. Nomogram was used to construct a predictive BPD model based on the FRLs. Finally, umbilical cord blood lymphocytes of preterm infants born before 32 weeks gestational age and term infants were collected and determined the expression level of diagnostic FRLs by RT-qPCR. RESULTS: Increased iron accumulation and several dysregulated ferroptosis-associated genes were found in BPD rat lung tissues, indicating that ferroptosis was participating in the development of BPD. By exploring the microarray dataset of preterm infants with BPD, 6 FRLs, namely LINC00348, POT1-AS1, LINC01103, TTTY8, PACRG-AS1, LINC00691, were determined as diagnostic FRLs for modeling. The area under the receiver operator characteristic curve of the model was 0.932, showing good discrimination of BPD. In accordance with our analysis of microarray dataset, the mRNA levels of FRLs were significantly upregulated in umbilical cord blood lymphocytes from preterm infants who had high risk of BPD. CONCLUSION: The incorporation of FRLs into a predictive model offers a non-invasive approach to show promise in improving early detection and management of this challenging chronic lung disease in premature infant, enabling timely intervention and personalized treatment strategies.

Factors associated with afebrile presentation and delayed defervescence of bacterial meningitis in children under 3 years of age: a multi-centre retrospective analysis.

BACKGROUND: This multi-center study aimed to identify factors affecting fever and delayed defervescence in bacterial meningitis (BM) patients under 3 years of age because of the variability of fever in this patient population. METHODS: Only BM patients under 3 years treated at 49 centers in China from November 2018 to end-April 2021 were included in the study. Univariate and multivariate logistic regression analyses were performed to determine factors associated with afebrile presentation and fever of delayed defervescence. RESULTS: A total of 863 BM patients under 3 years were included in the study. Coagulase negative staphylococcus was associated with afebrile presentation (OR = 1.176), while septicaemia and ear-nose-throat infections were associated with fever (P < 0.05). The patients with fever were assigned into early and delayed defervescence groups based on defervescence time (less than and more than or equal to one week). Furthermore, Streptococcus agalactiae meningitis (OR = 1.124), concomitant gastrointestinal infection (OR = 1.276), encephalomalacia (or = 1.339), and subdural effusion (OR = 1.454) were independently associated with delayed defervescence (all P < 0.05). CONCLUSIONS: The findings can aid in the efficient utilization of fever in auxiliary diagnosis and evaluating the condition of the disease.

Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis.

Ferroptosis, a form of regulated necrosis driven by iron-dependent peroxidation of phospholipids, is regulated by cellular metabolism, redox homeostasis, and various signaling pathways related to cancer. In this study, we found that activating mutation of phosphatidylinositol 3-kinase (PI3K) or loss of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) function, highly frequent events in human cancer, confers ferroptosis resistance in cancer cells, and that inhibition of the PI3K-AKT-mTOR signaling axis sensitizes cancer cells to ferroptosis induction. Mechanistically, this resistance requires sustained activation of mTORC1 and the mechanistic target of rapamycin (mTOR)C1-dependent induction of sterol regulatory element-binding protein 1 (SREBP1), a central transcription factor regulating lipid metabolism. Furthermore, stearoyl-CoA desaturase-1 (SCD1), a transcriptional target of SREBP1, mediates the ferroptosis-suppressing activity of SREBP1 by producing monounsaturated fatty acids. Genetic or pharmacologic ablation of SREBP1 or SCD1 sensitized ferroptosis in cancer cells with PI3K-AKT-mTOR pathway mutation. Conversely, ectopic expression of SREPB1 or SCD1 restored ferroptosis resistance in these cells, even when mTORC1 was inhibited. In xenograft mouse models for PI3K-mutated breast cancer and PTEN-defective prostate cancer, the combination of mTORC1 inhibition with ferroptosis induction resulted in near-complete tumor regression. In conclusion, hyperactive mutation of PI3K-AKT-mTOR signaling protects cancer cells from oxidative stress and ferroptotic death through SREBP1/SCD1-mediated lipogenesis, and combination of mTORC1 inhibition with ferroptosis induction shows therapeutic promise in preclinical models.

Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients.

BACKGROUND: COVID-19 is an infectious disease characterized by multiple respiratory and extrapulmonary manifestations, including gastrointestinal symptoms. Although recent studies have linked gut microbiota to infectious diseases such as influenza, little is known about the role of the gut microbiota in COVID-19 pathophysiology. METHODS: To better understand the host-gut microbiota interactions in COVID-19, we characterized the gut microbial community and gut barrier function using metagenomic and metaproteomic approaches in 63 COVID-19 patients and 8 non-infected controls. Both immunohematological parameters and transcriptional profiles were measured to reflect the immune response in COVID-19 patients. RESULTS: Altered gut microbial composition was observed in COVID-19 patients, which was characterized by decreased commensal species and increased opportunistic pathogenic species. Severe illness was associated with higher abundance of four microbial species (i.e., Burkholderia contaminans, Bacteroides nordii, Bifidobacterium longum, and Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes. These severity-related microbial features were further associated with host immune response. For example, the abundance of Bu. contaminans was associated with higher levels of inflammation biomarkers and lower levels of immune cells. Furthermore, human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in COVID-19 patients. The circulating levels of lipopolysaccharide-binding protein increased in patients with severe illness and were associated with circulating inflammation biomarkers and immune cells. Besides, proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients. CONCLUSIONS: Our results suggest that the dysbiosis of the gut microbiome and the dysfunction of the gut barrier might play a role in the pathophysiology of COVID-19 by affecting host immune homeostasis.

An End-Tidal Carbon Monoxide Nomogram for Term and Late-Preterm Chinese Newborns.

OBJECTIVE: To establish a reference nomogram for end-tidal CO corrected for ambient CO (ETCOc) levels in term and late-preterm Chinese newborns and then assess its efficacy to identify hemolytic hyperbilirubinemia. STUDY DESIGN: We conducted a prospective study by measuring concurrent ETCOc and total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) levels collected postnatally at 12, 24, 48, 72, 96, and 120 hours of age. ETCOc at the 25th, 50th, 75th, and 95th percentiles at each epoch were used to construct the reference nomogram. We then explored the ability of predischarge ETCOc and TSB/TcB metrics to predict the development of hyperbilirubinemia requiring phototherapy in early postnatal period and jaundice readmission in late postnatal period. RESULTS: Our nomogram, based on 990 measurements from 455 infants who were not nonhemolytic, displayed a steady line within 3 postnatal days, followed by a subsequent decline. From a cohort of infants with a serial ETCOc measurements (n = 130) and those readmitted (n = 21), we found that ETCOc and TSB/TcB ≥75th percentile can identify most hemolytic hyperbilirubinemia between 12 and 72 hours after birth with an area under the curve (AUC) of 0.741. An ETCOc ≥1.7 ppm alone between 96 and 120 hours after birth can identify most hemolytic hyperbilirubinemia with an AUC of 0.816. In addition, 90.5% of readmitted infants had an ETCOc ≥75th percentile. CONCLUSIONS: An ETCOc reference nomogram during the first 5 postnatal days in nonhemolytic term and late-preterm newborns can be used to identify hemolytic hyperbilirubinemia requiring phototherapy in the early postnatal period and readmission in the late postnatal period.

Effects of less invasive surfactant administration versus intubation-surfactant-extubation on bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome: a single-center, retrospective study from China.

BACKGROUND: This study evaluated the effects of less invasive surfactant administration (LISA) and intubation-surfactant-extubation (InSurE) on bronchopulmonary dysplasia (BPD) in preterm infants with respiratory distress syndrome (RDS). METHODS: Neonates with respiratory distress syndrome requiring surfactant, with gestational age < 32 weeks and birth weight < 1500 g admitted to our neonatal intensive care unit from January 2018 to December 2019, were retrospectively analyzed. LISA and InSurE were used independently. The incidence of BPD at 36 weeks postmenstrual age, pre-discharge mortality, and need for mechanical ventilation (MV) within 72 h of birth were compared between LISA and InSurE group. Secondary outcomes including necrotizing enterocolitis requiring surgery, retinopathy of prematurity ≥ stage 3, patent ductus arteriosus requiring medical therapy or surgery, and length of hospitalization were analyzed. RESULTS: Among the 148 included neonates, there were 46 and 102 infants in LISA group and InSurE group, respectively. There were no significant differences in BPD incidence, the severity of BPD at 36 weeks postmenstrual age, and the rate of MV within the first 72 h after birth between the two groups (P > 0.05, respectively). The incidences of necrotizing enterocolitis requiring surgery, retinopathy of prematurity ≥ stage 3, patent ductus arteriosus requiring medical therapy or surgery, and length of hospitalization did not differ significantly between the two groups (P > 0.05, respectively). CONCLUSIONS: For surfactant administration among preterm infants with respiratory distress syndrome, LISA did not decrease bronchopulmonary dysplasia and severity of BPD at 36 weeks postmenstrual age. The benefits of LISA would require further evaluations.