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Abstract Background The occurrence of severe intraventricular hemorrhage (sIVH) was high in the very preterm infants (VPIs) in China. The management strategies significantly contributed to the occurrence of sIVH in VPIs. However, the status of the perinatal strategies associated with sIVH for VPIs was rarely described across the multiple neonatal intensive care units (NICUs) in China. We aim to investigate the characteristics of the perinatal strategies associated with sIVH for VPIs across the multiple NICUs in China. Methods This was a retrospective analysis of data from a prospective cohort of Chinese Neonatal Network (CHNN) dataset, enrolling infants born at 24+0—31+6 from 2019 to 2021. Eleven perinatal practices performed within the first 3 days of life were investigated including antenatal corticosteroids use, antenatal magnesium sulphate therapy, intubation at birth, placental transfusion, need for advanced resuscitation, initial inhaled gas of 100% FiO2 in delivery room, initial invasive respiratory support, surfactant and caffeine administration, early enteral feeding, and inotropes use. The performances of these practices across the multiple NICUs were investigated using the standard deviations of differences between expected probabilities and observations. The occurrence of sIVH were compared among the NICUs. Results A total of 24,226 infants from 55 NICUs with a mean (SD) gestational age of 29.5 (1.76) and mean (SD) birthweight of 1.31(0.32) were included. sIVH was detected in 5.1% of VPIs. The rate of the antenatal corticosteroids, MgSO4 therapy, and caffeine was 80.0%, 56.4%, and 31.5%, respectively. We observed significant relationships between sIVH and intubation at birth (AOR 1.52, 95% CI 1.13 to 1.75) and initial invasive respiratory support (AOR 2.47, 95% CI 2.15 to 2.83). The lower occurrence of sIVH (4.8%) was observed corresponding with the highest utility of standard antenatal care, the lowest utility of invasive practices, and early enteral feeding administration. Conclusions The current evidence-based practices were not performed in each VPI as expected among the studied Chinese NICUs. The higher utility of the invasive practices could be related to the occurrence of sIVH.

This review aims to explore the current application of Cranial Ultrasound Screening (CUS) in the diagnosis and treatment of brain diseases in extremely preterm infants. It also discusses the potential role of emerging ultrasound-derived technologies such as Super Microvascular Structure Imaging (SMI), Shear Wave Elastography (SWE), Ultrafast Doppler Ultrasound (UfD), and 3D ventricular volume assessment and automated segmentation techniques in clinical practice. A systematic search of medical databases was conducted using the keywords ''(preterm OR extremely preterm OR extremely low birth weight) AND (ultrasound OR ultrasound imaging) AND (neurodevelopment OR brain development OR brain diseases OR brain injury OR neuro*)'' to identify relevant literature. The titles, abstracts, and full texts of the identified articles were carefully reviewed to determine their relevance to the research topic. CUS offers unique advantages in early screening and monitoring of brain diseases in extremely preterm infants, as it can be performed at the bedside without the need for anesthesia or special monitoring. This technique facilitates early detection and intervention of conditions such as intraventricular hemorrhage, white matter injury, hydrocephalus, and hypoxic-ischemic injury in critically ill preterm infants. Continuous refinement of the screening and follow-up processes provides reliable clinical decision-making support for healthcare professionals and parents. Emerging ultrasound technologies, such as SWE, SMI, and UfD, are being explored to provide more accurate and in-depth understanding of brain diseases in extremely preterm infants. SWE has demonstrated its effectiveness in assessing the elasticity of neonatal brain tissue, aiding in the localization and quantification of potential brain injuries. SMI can successfully identify microvascular structures in the brain, offering a new perspective on neurologic diseases. UfD provides a high-sensitivity and quantitative imaging method for the prevention and treatment of neonatal brain diseases by detecting subtle changes in red blood cell movement and accurately assessing the status and progression of brain diseases. CUS and its emerging technologies have significant applications in the diagnosis and treatment of brain diseases in extremely preterm infants. Future research aims to address current technical challenges, optimize and enhance the clinical decision-making capabilities related to brain development, and improve the prevention and treatment outcomes of brain diseases in extremely preterm infants.

Abstract Background In China, ~1,072,100 small for gestational age (SGA) births occur annually. These SGA newborns are a high-risk population of developmental delay. Our study aimed to evaluate the genetic profile of SGA newborns in the newborn intensive care unit (NICU) and establish a prognosis prediction model by combining clinical and genetic factors. Methods A cohort of 723 SGA and 1317 appropriate for gestational age (AGA) newborns were recruited between June 2018 and June 2020. Clinical exome sequencing was performed for each newborn. The gene-based rare-variant collapsing analyses and the gene burden test were applied to identify the risk genes for SGA and SGA with poor prognosis. The Gradient Boosting Machine framework was used to generate two models to predict the prognosis of SGA. The performance of two models were validated with an independent cohort of 115 SGA newborns without genetic diagnosis from July 2020 to April 2022. All newborns in this study were recruited through the China Neonatal Genomes Project (CNGP) and were hospitalized in NICU, Children’s Hospital of Fudan University, Shanghai, China. Results Among the 723 SGA newborns, 88(12.2%) received genetic diagnosis, including 42(47.7%) with monogenic diseases and 46(52.3%) with chromosomal abnormalities. SGA with genetic diagnosis showed higher rates in severe SGA(54.5% vs. 41.9%, P=0.0025) than SGA without genetic diagnosis. SGA with chromosomal abnormalities showed higher incidences of physical and neurodevelopmental delay compared to those with monogenic diseases (45.7% vs. 19.0%, P=0.012). We filtered out 3 genes (ITGB4, TXNRD2, RRM2B) as potential causative genes for SGA and 1 gene (ADIPOQ) as potential causative gene for SGA with poor prognosis. The model integrating clinical and genetic factors demonstrated a higher area under the receiver operating characteristic curve (AUC) over the model based solely on clinical factors in both the SGA-model generation dataset (AUC=0.9[95% confidence interval 0.84–0.96] vs. AUC=0.74 [0.64–0.84]; P=0.00196) and the independent SGA-validation dataset (AUC=0.76 [0.6–0.93] vs. AUC=0.53[0.29–0.76]; P=0.0117). Conclusion SGA newborns in NICU presented with roughly equal proportions of monogenic and chromosomal abnormalities. Chromosomal disorders were associated with poorer prognosis. The rare-variant collapsing analyses studies have the ability to identify potential causative factors associated with growth and development. The SGA prognosis prediction model integrating genetic and clinical factors outperformed that relying solely on clinical factors. The application of genetic sequencing in hospitalized SGA newborns may improve early genetic diagnosis and prognosis prediction.

Abstract Background Though there has been an increase in the number of neonates with hypoxic-ischemic encephalopathy (HIE) treated by therapeutic hypothermia (TH) in recent years, the effect of therapeutic hypothermia on mild HIE neonates is still uncertain. Objectives This study aims to explore the safety and efficacy of therapeutic hypothermia in neonates with mild HIE. Methods Retrospectively collected between January 2010 to December 2022 at Children’s Hospital of Fudan University, neonates with mild HIE were divided into TH and non-TH groups. Clinical data of the mild HIE neonates and their mothers’ general information during pregnancy were collected. SPSS 23.0 was used to compare the general condition, the incidence of adverse events, and efficacy in the two groups. Results A total of 71 neonates with mild HIE were included, including 31 in the TH group and 40 in the non-TH group. Compared with the non-TH group, the TH group had significantly lower 5-minute Apgar scores [6 (5–7) points vs. 7 (5–8) points, p = 0.033 ], but a higher rate of tracheal intubation at birth (68%, 21/31 vs. 40%, 16/40, p = 0.02), a higher rate of chest compressions > 30 s (39%, 12/31 vs. 15%, 6/40, p = 0.023), the later initiation enteral feeding [4 (3–4) days vs. 1 (1–2) days, p

Abstract The shape and internal structure of an atomic nucleus can change significantly with increasing excitation energy, angular momentum, or isospin asymmetry. As an example of this structural evolution, linear-chain configurations in carbon or heavier isotopes have been predicted for decades. Recent studies have found non-stability of this structure in 12C while evidenced its appearance in 16C. It is then necessary to investigate the linear-chain molecular structures in 14C to clarify the exact location on the nuclear chart where this structure begins to emerge, and thus to benchmark theoretical models. Here we show a cluster-decay experiment for 14C with all final particles coincidentally detected, allowing a high Q-value resolution, and thus a clear decay-path selection. Unambiguous spin-parity analyses are conducted, strongly evidencing the emergence of the π-bond linear-chain molecular rotational band in 14C. The present results encourage further studies on even longer chain configurations in heavier neutron-rich nuclei.

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.

Objective: We aimed to investigate the clinical and genetic risk factors associated with neonatal severe unconjugated hyperbilirubinemia.Methods: This was a retrospective, 1:1 matched, case–control study. We included 614 neonates diagnosed with severe unconjugated hyperbilirubinemia (serum total bilirubin level ≥425 μmol/L or serum total bilirubin concentration that met exchange transfusion criteria) from the China Neonatal Genomes Project in Children’s Hospital of Fudan University. Clinical exome sequencing data were analyzed using a data analysis pipeline of Children’s Hospital of Fudan University. The factors associated with severe unconjugated hyperbilirubinemia were assessed using univariable and multivariable logistic regression analyses. Interaction analyses were examined between clinical and genetic risk factors.Results: ABO/Rh incompatibility hemolysis (odds ratio [OR] 3.36, 95% confidence interval [CI] 2.32–4.86), extravascular hemorrhage (OR 2.95, 95% CI 2.24–3.89), weight loss (OR 5.46, 95% CI 2.88–10.36), exclusive breastmilk feeding (OR 3.56, 95% CI 2.71–4.68), and the homozygous mutant of UGT1A1 211G>A (OR 2.35, 95% CI 1.54–3.59) were all identified as factors significantly associated with severe unconjugated hyperbilirubinemia. The presence of UGT1A1 211G>A mildly increased the risk of severe unconjugated hyperbilirubinemia caused by ABO/Rh incompatibility hemolysis (OR 3.98, 95% CI 2.19–7.23), although the effect is not statistically significant.Conclusion: ABO/Rh incompatibility hemolysis, extravascular hemorrhage, weight loss, exclusive breastmilk feeding, and the homozygous mutant of UGT1A1 211G>A were found to be risk factors for severe unconjugated hyperbilirubinemia. Clinical factors remain the most crucial and preventable determinants in managing severe unconjugated hyperbilirubinemia, with a minimal genetic contribution. The establishment of preconception care practices and the reinforcement of screening for the aforementioned risk factors are essential steps for preventing severe unconjugated hyperbilirubinemia.

Summary: Background: The optimal treatment strategy for patent ductus arteriosus (PDA) in extremely preterm infants is currently highly controversial. This study aimed to evaluate the association between PDA treatment and short-term outcomes among extremely preterm infants. Methods: This cohort study included all extremely preterm infants (≤27 and 6/7 weeks) who were admitted to hospitals participating in the Chinese Neonatal Network from January 2019 to December 2021, and were diagnosed to have PDA by echocardiogram. PDA treatment was defined as medical treatment and/or surgical ligation of PDA during hospitalization. Short-term outcomes included death, bronchopulmonary dysplasia (BPD), death/BPD, retinopathy of prematurity, necrotizing enterocolitis, and severe brain injury. Multivariate logistic regression was used to evaluate the association between PDA treatment and outcomes. Subgroup analysis were performed among infants with different respiratory support on 3 and 7 days of life. Findings: A total of 2494 extremely preterm infants with the diagnosis of PDA were enrolled, of which 1299 (52.1%) received PDA treatment. PDA treatment was significantly associated with lower risk of death (adjusted odds ratio, 0.48; 95% confidence interval, 0.38–0.60). The decreased risk of death was accompanied by increased risk of BPD and death/BPD. In subgroup analysis according to respiratory support, PDA treatment was associated with lower risk of death among infants who required invasive ventilation. However, the beneficial effect on death was not significant among infants who did not require invasive ventilation. Interpretation: PDA treatment was associated with reduced mortality in extremely preterm infants, but this beneficial effect was mainly present among infants who required invasive ventilation. Funding: This study was funded by the Shanghai Science and Technology Commission's Scientific and Technological Innovation Action Plan (21Y21900800) and the Canadian Institutes of Health Research (CTP87518).

Primary carnitine deficiency (PCD) caused by pathogenic variants in the solute carrier family 22 member 5 (SLC22A5) gene is a rare autosomal recessive disease that results in defective fatty acid oxidation. PCD can be detected through tandem mass spectrometry (MS/MS), but transplacental transport of free carnitine from mothers may cause false negatives or positives during newborn screening (NBS). This study aimed to analyze the genetic characteristics of SLC22A5 and estimate the prevalence of PCD in the Chinese population, providing useful information for NBS and genetic counseling. We manually curated SLC22A5 pathogenic or likely pathogenic (P/LP) variants according to the American College of Medical Genetics and Genomics (ACMG) guidelines and identified 128 P/LP variants. Based on the China Neonatal Genomes Project (CNGP), the estimated PCD prevalence was 1:17,456, which was higher than that in other populations. The genotype–phenotype association analysis showed that patients carrying homozygous c.760C>T and c.844C>T were more likely to present cardiomyopathy, whereas those carrying homozygous c.1400C>G were more likely to be asymptomatic (all p-values < 0.05). We found that there was no significant difference in initial C0 concentrations between patients and carriers, but there was a significant difference in the second-tier screening of C0 concentration between them (p-value < 0.05). We established a cost-effective variant panel containing 10 high-frequency sites and developed a screening algorithm incorporating gene panels with MS/MS, which could rescue one more patient who was undetected from MS/MS. In conclusion, the prevalence of PCD in the Chinese population is relatively high. The combination of conventional NBS with genetic sequencing is suggested for early diagnosis of PCD.

Background: Acute respiratory distress syndrome (ARDS) could account for a considerable proportion of neonatal death, while the genetic etiology and pathophysiology of neonatal ARDS remain elusive. In this case-control study, 515 neonates were enrolled in the China Neonatal Genomes Project (CNGP, NCT03931707) from August 2016 to June 2021, including 196 ARDS and 319 non-ARDS matched by sex, gestational age, birth weight, perinatal asphyxia, pneumonia, sepsis, and necrotizing enterocolitis. Clinical exome sequencing was used to detect genetic variants. Collapsing analyses together with permutation tests were used to identify ARDS risk genes enriched for rare variants in ARDS samples. In silico functional interaction analysis and expression pattern studies at different stages of lung development were used to investigate the biological functions of the risk genes. Results: Collapsing analyses identified that rare variants were significantly abundant in the genes associated with the precursor of the lamellar body and there were eight predicted risk genes with strong confidence (P

This paper assessed the impacts of environmental smog early-warning signals on road traffic deaths. For an accurate assessment, we used the daily traffic death data from 2016 to 2020 in 295 Chinese cities and constructed a rigorous Regression Discontinuity Design (RDD) strategy to identify the causality and adopted the high-dimensional fixed-effect method to deal with the interference of meteorological factors. The results indicate that light smog and moderate smog early warnings decreased road fatalities by about 3.6% and 4.3%, respectively. Surprisingly, the heavy smog early-warning signal had no significant effect, possibly because of the self-consciousness mechanism instead of the early-warning signal mechanism. Further heterogeneity analysis showed that women drivers, highly-educated drivers, older drivers (over 60 years), two-wheeled vehicle drivers, and drivers on country roads and freeways are more sensitive to smog early-warning signals.

BackgroundGalloway–Mowat syndrome type 3 (GAMOS3) is an extremely rare and severe autosomal-recessive disease characterized by early-onset nephrotic syndrome (NS), microcephaly and neurological impairment. Reported GAMOS cases have gradually increased since pathogenic OSGEP variants were identified as the aetiology in 2017.MethodsUsing whole-exome sequencing and a data analysis process established by Children's Hospital of Fudan University, the clinical and molecular features of 3 infants with OSGEP mutations were summarized. Literature regarding the clinical features of GAMOS3 caused by OSGEP variants was reviewed.ResultsThirty-seven individuals (3 from this study) from 34 families were included. Twenty-two different OSGEP variants were identified. The c.740G>A (p.Arg247Gln) variant in OSGEP was detected in 15 families (44%), all from Asia. Most affected individuals (including patients I and II in this study) showed a typical phenotype, including microcephaly (92%) with brain anomalies (97%), developmental delay (81%), congenital NS (54%), and craniofacial (94%) and skeletal dysmorphism (84%). Renal manifestations varied from proteinuria (94%, median onset = 1.5 months) to NS (83%) and end-stage renal disease (48%, 11 months) during follow-up. Patients with congenital NS had a lower survival probability (median survival time = 3 months) than those without congenital NS (78 months) (P < 0.01, log-rank test).ConclusionGAMOS3 is a progressive renal-neurological syndrome with a poor prognosis, especially with congenital NS. Microcephaly with dysmorphic features are vital clues to further evaluate renal impairment and brain anomalies. Timely molecular diagnosis is crucial for clinical decision-making, appropriate treatment and genetic counselling.

Abstract Background The number of cumulative confirmed cases of COVID-19 in the United States has risen sharply since March 2020. A county health ranking and roadmaps program has been established to identify factors associated with disparity in mobility and mortality of COVID-19 in all counties in the United States. The risk factors associated with county-level mortality of COVID-19 with various levels of prevalence are not well understood. Methods Using the data obtained from the County Health Rankings and Roadmaps program, this study applied a negative binomial design to the county-level mortality counts of COVID-19 as of August 27, 2020 in the United States. In this design, the infected counties were categorized into three levels of infections using clustering analysis based on time-varying cumulative confirmed cases from March 1 to August 27, 2020. COVID-19 patients were not analyzed individually but were aggregated at the county-level, where the county-level deaths of COVID-19 confirmed by the local health agencies. Clustering analysis and Kruskal–Wallis tests were used in our statistical analysis. Results A total of 3125 infected counties were assigned into three classes corresponding to low, median, and high prevalence levels of infection. Several risk factors were significantly associated with the mortality counts of COVID-19, where higher level of air pollution (0.153, P

Abstract Background Loss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) is one of the causes of STAT3 hyperimmunoglobulin E (IgE) syndrome (STAT3-HIES), while gain-of-function (GOF) mutations in STAT3 lead to immune dysregulation diseases. We retrospectively analyzed the age, common clinical symptoms, immunologic and molecular manifestations in 11 patients with LOF STAT3 mutations and 1 patient with a GOF STAT3 mutation. Methods Twelve patients were enrolled in our study. Serum immunoglobulin measurements, lymphocyte subset detection and whole-exome sequencing were performed. Results The median age at diagnosis of STAT3-HIES patients was 4.74 years. Eczema, recurrent respiratory infections, fevers, abscesses and Staphylococcus aureus infections were the classic manifestations. Elevated serum IgE levels are not always observed in conjunction with high eosinophil counts. A moderate viral DNA load was also measured in peripheral blood mononuclear cells. We noticed that c. 1144C>T was the most common mutation site, followed by c.1311C>A. Additionally, c.1311C>A and c. 1826G>C are two novel mutations. Eight patients achieved notable improvement after receiving intravenous immunoglobulin. Conclusion We updated the current knowledge of this topic. We found an earlier median age at diagnosis, a higher survival rate, and a general lack of nonimmunological abnormalities; we also described the treatment details and novel mutations involve in STAT3-HIES and compared STAT3 LOF and GOF mutations.

We calculate the centrality dependence for coherent photoproduction of very low-pTJ/ψ at Relativistic Heavy Ion Collider (RHIC) and Large Hadron Collider (LHC) energies within the impact parameter-dependent saturated color dipole model. By using the large equivalent photon fluxes, we present the differential cross-section of very low-pTJ/ψ produced by coherent photonuclear in peripheral heavy ion collisions. The numerical results demonstrate that our calculation agrees with J/ψ data in peripheral heavy ion collisions at Relativistic Heavy Ion Collider (RHIC) energies.

Objective: The aim of this single-center retrospective study was to analyze the clinical characteristics, treatment options, and course of neonatal-onset congenital portosystemic shunts (CPSS).Methods: We included all patients with CPSS who presented with clinical symptoms within the neonatal period in our institution between 2015 and 2020.Results: Sixteen patients were identified, including 13 patients with intrahepatic portosystemic shunts (IPSS) and three patients with extrahepatic portosystemic shunts (EPSS). The median age of diagnosis was 16 days (range prenatal 24 weeks−12 months). Hyperammonemia (60%), neonatal cholestasis (44%), elevated liver enzyme (40%), hypoglycemia (40%), thrombocytopenia (38%), and coagulation abnormalities (23%) appeared in neonatal CPSS. Twelve patients (75%) presented with congenital anomalies, of which congenital heart disease (CHD) (44%) was the most common. Thirteen patients with IPSS initially underwent conservative treatment, but two of them were recommended for the catheter interventional therapy and liver transplantation, respectively, due to progressive deterioration of liver function. Spontaneous closure occurred in nine patients with IPSS. The shunt was closed using transcatheter embolization in one patient with EPSS type II. Another patient with EPSS type II underwent surgical treatment of CHD firstly. The remaining patient with EPSS type Ib received medical therapy and refused liver transplantation.Conclusion: Hyperammonemia, neonatal cholestasis, elevated liver enzyme, hypoglycemia, and thrombocytopenia are the main complications of neonatal CPSS. Moreover, CPSS is associated with multiple congenital abnormalities, especially CHD. Intrahepatic portosystemic shunts may close spontaneously, and conservative treatment can be taken first. Extrahepatic portosystemic shunts should be closed to prevent complications.

ObjectivesCentral nervous system (CNS) infection has a high incidence and mortality in neonates, but conventional tests are time-consuming and have a low sensitivity. Some rare genetic diseases may have some similar clinical manifestations as CNS infection. Therefore, we aimed to evaluate the performance of metagenomic next-generation sequencing (mNGS) in diagnosing neonatal CNS infection and to explore the etiology of neonatal suspected CNS infection by combining mNGS with whole exome sequencing (WES).MethodsWe prospectively enrolled neonates with a suspected CNS infection who were admitted to the neonatal intensive care unit(NICU) from September 1, 2019, to May 31, 2020. Cerebrospinal fluid (CSF) samples collected from all patients were tested by using conventional methods and mNGS. For patients with a confirmed CNS infection and patients with an unclear clinical diagnosis, WES was performed on blood samples.ResultsEighty-eight neonatal patients were enrolled, and 101 CSF samples were collected. Fourty-three blood samples were collected for WES. mNGS showed a sample diagnostic yield of 19.8% (20/101) compared to 4.95% (5/101) for the conventional methods. In the empirical treatment group, the detection rate of mNGS was significantly higher than that of conventional methods [27% vs. 6.3%, p=0.002]. Among the 88 patients, 15 patients were etiologically diagnosed by mNGS alone, five patients were etiologically identified by WES alone, and one patient was diagnosed by both mNGS and WES. Twelve of 13 diagnoses based solely on mNGS had a likely clinical effect. Six patients diagnosed by WES also experienced clinical effect.ConclusionsFor patients with a suspected CNS infections, mNGS combined with WES might significantly improve the diagnostic rate of the etiology and effectively guide clinical strategies.

Abstract Background Persistent pulmonary hypertension of the newborn (PPHN) is a severe clinical problem among neonatal intensive care unit (NICU) patients. The genetic pathogenesis of PPHN is unclear. Only a few genetic polymorphisms have been identified in infants with PPHN. Our study aimed to investigate the potential genetic etiology of PPHN. Methods This study recruited PPHN patients admitted to the NICU of the Children’s Hospital of Fudan University from Jan 2016 to Dec 2017. Exome sequencing was performed for all patients. Variants in reported PPHN/pulmonary arterial hypertension (PAH)-related genes were assessed. Single nucleotide polymorphism (SNP) association and gene-level analyses were carried out in 74 PPHN cases and 115 non-PPHN controls with matched baseline characteristics. Results Among the patient cohort, 74 (64.3%) patients were late preterm and term infants (≥ 34 weeks gestation) and 41 (35.7%) were preterm infants (

Background: Experimental research suggests that fine particulate matter (PM2.5) exposure might affect embryonic development. However, only few population-based studies have investigated the impact of maternal exposure to PM2.5 on the early pregnancy loss. Objectives: To estimate associations between clinically recognized early pregnancy loss (CREPL) and exposure to ambient PM2.5 at individual residences during peri-conception periods, with the aim to identify susceptible exposure time windows. Methods: CREPL cases and normal early pregnancy controls (of similar age and gravidity presenting within one week, a total of 364 pairs) were recruited between July 2017 and July 2018 among women residing in Tianjin, China. Average ambient PM2.5 concentrations of ten exposure windows (4 weeks, 2 weeks and 1 week before conception; the first, second, third and fourth single week, the first and second 2-week periods, and the entire 4-week period after conception) at the women's residential addresses were estimated using temporally-adjusted land use regression models. Associations between PM2.5 exposures at specific peri-conception time windows and CREPL were examined using conditional logistic regression models, adjusted for covariates. Results: Based on adjusted models, CREPL was significantly associated with a 10 μg/m3 increase in PM2.5 exposure during the second week after conception (OR = 1.15; 95% CI: 1.04, 1.27; p = 0.005), independent of effects at other time windows. There was also an association of CREPL with PM2.5 during the entire 4-week period after conception (OR = 1.22; 95% CI: 1.02, 1.46; p = 0.027). There was little evidence for associations with exposure during pre-conception exposure windows. Conclusions: Maternal exposures to ambient PM2.5 during a critical time window following conception are associated with CREPL, with the second week after conception possibly being the exposure window of most vulnerability. Future studies should focus on replicating these findings and on pathogenic mechanisms. Keywords: Adverse pregnancy outcomes, Air pollution, Land use regression models, Miscarriage, Particulate matter

Mutations in SCN1A and SCN2A are associated with a wide spectrum of epilepsy related disorders in human. This dataset presented variants and clinical features of SCN1A and SCN2A genes. A total of 48 cases were presented, including 33 SCN1A mutations and 14 SCN2A mutations. While 22 mutations were novel in SCN1A and 11 were novel in SCN2A. The clinical features were included of gender, birth history, family history, seizure onset age, seizure types, frequency of seizures, initial and follow-up EEGs, brain MRI findings, antiepileptic drugs, prognosis and developmental data. The data can provide insights on novel mutations and different phenotypes of SCN1A and SCN2A.

Background: Serious games are potential alternatives for supplementing traditional simulation-based education for neonatal resuscitation training. However, evidence regarding the benefits of using serious games to improve long-term knowledge retention of neonatal resuscitation in undergraduate medical students is lacking.Objective: We designed a serious computer game “NEOGAMES” to train undergraduate medical students in neonatal resuscitation in a cost-friendly and accessible way and to examine whether serious game-based training improves long-term knowledge retention in medical students.Methods: “NEOGAMES” consists of a screen with images of an incubator, a baby, visual objects, anatomy, action cards, monitors, real-time feedback, and emotional components. Undergraduate medical students from Shanghai Medical College of Fudan University were invited to participate and were allocated to a game group or a control group. Participants in the game group played the game before the training. All the participants completed three written tests, pre- and post-training knowledge tests and a follow-up test after 6 months.Results: Eighty-one medical students participated in the study. The student demographic characteristics of the groups were comparable, including sex, age, and grade point average (GPA). Significant short-term knowledge improvement was noticed only for male students in the game group based on their 5.2-point higher test scores than those of the controls (p = 0.006). However, long-term knowledge improvement at 6 months was identified for both male and female students in the game group, with test scores 21.8 and 20 points higher, respectively, than those of the controls (P < 0.001). The long-term knowledge retention in the game group was almost 3 times higher than that in the control group.Conclusions: Long-term knowledge retention was nearly 3 times higher for the game group than for the control group. The improvement in knowledge supports the use of serious games for undergraduate medical education.

The study of the origin of asymmetries in mirror β decay is extremely important to understand the fundamental nuclear force and the nuclear structure. The experiment was performed at the National Laboratory of Heavy Ion Research Facility in Lanzhou (HIRFL) to measure the β-delayed γ rays of 26P by silicon array and Clover-type high-purity Germanium (HPGe) detectors. Combining with results from the β decay of 26P and its mirror nucleus 26Na, the mirror asymmetry parameter δ ( ≡ft+/ft−− 1) was determined to be 46(13)% for the transition feeding the first excited state in the daughter nucleus. Our independent results support the conclusion that the large mirror asymmetry is close to the proton halo structure in 26P.

Enterococcus faecalis is becoming an increasingly important opportunistic pathogen worldwide, especially because it can cause life-threatening nosocomial infections. Treating E. faecalis infections has become increasingly difficult because of the prevalence of multidrug-resistant E. faecalis strains. Because bacteriophages show specificity for their bacterial hosts, there has been a growth in interest in using phage therapies to combat the rising incidence of multidrug-resistant bacterial infections. In this study, we isolated a new lytic phage, EF-P29, which showed high efficiency and a broad host range against E. faecalis strains, including vancomycin-resistant strains. The EF-P29 genome contains 58,984 bp (39.97% G+C), including 101 open reading frames, and lacks known putative virulence factors, integration-related proteins or antibiotic resistance determinants. In murine experiments, the administration of a single intraperitoneal injection of EF-P29 (4 × 105 PFU) at 1 h after challenge was sufficient to protect all mice against bacteremia caused by infection with a vancomycin-resistant E. faecalis strain (2 × 109 CFU/mouse). E. faecalis colony counts were more quickly eliminated in the blood of EF-P29-protected mice than in unprotected mice. We also found that exogenous E. faecalis challenge resulted in enrichment of members of the genus Enterococcus (family Enterococcaceae) in the guts of the mice, suggesting that it can enter the gut and colonize there. The phage EF-P29 reduced the number of colonies of genus Enterococcus and alleviated the gut microbiota imbalance that was caused by E. faecalis challenge. These data indicate that the phage EF-P29 shows great potential as a therapeutic treatment for systemic VREF infection. Thus, phage therapies that are aimed at treating opportunistic pathogens are also feasible. The dose of phage should be controlled and used at the appropriate level to avoid causing imbalance in the gut microbiota.

Introduction: Stroke is characterized by high incidence, recurrence rate, and mortality. Patients with acute ischemic stroke (AIS) who are ineligible for acute revascularization therapy require more effective medication treatments. A previous clinical study showed that Ruyi Zhenbao tablets and Baimai ointments might be effective against AIS; however, high-quality clinical evidence supporting their application in AIS is lacking. To explore the efficacy of the two classic Tibetan medicines in the treatment of AIS, a randomized clinical trial will be conducted in patients with AIS who are not eligible for thrombolytic treatment. Methods: A prospective, randomized, multiple-center, double-blinded, placebo-controlled, and parallel-group trial will be conducted. We shall randomize 480 eligible participants to either the intervention or the control group. The distribution ratio of each group will be 1:1:1:1, including 120 patients each in the dual-medication group, the Baimai ointment group, the Ruyi Zhenbao tablet group, and the placebo group. Participants will be treated with medication for 8 weeks, and they will receive three follow-up visits: at 4 weeks (D29), 8 weeks (D56), and 90 days (D90) after commencing treatment. The primary outcome will be D90 change in the simplified Fugl-Meyer score from baseline to posttreatment. The secondary outcomes are as follows: D29 change of simplified Fugl-Meyer score from baseline to posttreatment; proportion of participants whose D29 NIHSS scores decreased by four or more points from baseline D90 proportion of subjects with mRS score of 0–2 (inclusive); D90 proportion of subjects with Barthel index score ≥95; D90 incidence of cardiovascular and cerebrovascular events. Safety endpoint includes mortality within 90 days; proportion of subjects with adverse events/serious adverse events within 90 days. Conclusion: This research protocol lays a solid groundwork for its practical execution. This study is poised to serve as a reference for other Tibetan medicine researchers, contributing to the reduction of stroke-related expenditures globally and, in turn, benefiting a broader population of stroke patients.