Objective:To analyze the current status of red blood cell transfusion in very preterm infants (VPI) (gestational age at birth <32 weeks) from Chinese Neonatal Network (CHNN) in 2022.Methods:This cross-sectional study was based on the CHNN VPI cohort. It included 6 985 VPI admitted to CHNN 89 participating centers within 24 hours after birth in 2022. VPI with major congenital anomalies or those transferred to non-CHNN centers for treatment or discharged against medical advice were excluded. VPI were categorized based on whether they received red blood cell transfusions, their gestational age at birth, the type of respiratory support received during transfusion, and whether the pre-transfusion hemoglobin levels exceeded the thresholds. General characteristics, red blood cell transfusion rates, number of transfusions, timing of the first transfusion, and pre-transfusion hemoglobin levels were compared among different groups. The incidence of adverse outcomes between the group of VPI who received transfusions above the threshold and those who received transfusions below the threshold were compared. Comparison among different groups was conducted using χ2 tests, Kruskal-Wallis H tests, Mann-Whitney U test, and so on. Trends by gestational age at birth were evaluated by Cochran-Armitage tests and Jonckheere-Terpstra tests for trend. Results:Among the 6 985 VPI, 3 865 cases(55.3%) were male, with a gestational age at birth of 30.0 (28.6, 31.0) weeks and a birth weight of (1 302±321) g. Overall, 3 617 cases (51.8%) received red blood cell transfusion, while 3 368 cases (48.2%) did not. The red blood cell transfusion rate was 51.8% (3 617/6 985), with rates of 77.7% (893/1 150) for those born before 28 weeks gestational age and 46.7% (2 724/5 835) for those born between 28 and 31 weeks gestational age. A total of 9 616 times red blood cell transfusions were administered to 3 617 VPI, with 632 times missing pre-transfusion hemoglobin data, and 8 984 times included in the analysis. Of the red blood cell transfusions, 25.6% (2 459/9 616) were administered when invasive respiratory support was required, 51.3% (4 934/9 616) were receiving non-invasive respiratory support, while 23.1% (2 223/9, 616) were given when no respiratory support was needed. Compared to the non-transfusion group, the red blood cell transfusion group had a higher rate of pregnancy-induced hypertension in mothers, lower rates of born via cesarean section and mother′s antenatal steroid administration, smaller gestational age, lower birth weight, a higher proportion of small-for-gestational-age, multiple births, and proportions of Apgar score at the 5 th minute after birth ≤3 (all P<0.05). They were also less likely to be female, born in hospital or undergo delayed cord clamping (all P<0.01). Additionally, higher transport risk index of physiologic stability score at admission were observed in the red blood cell transfusion group ( P<0.001). The number of red blood cell transfusion was 2 (1, 3) times, with the first transfusion occurring at an age of 18 (8, 29) days, and a pre-transfusion hemoglobin level of 97 (86, 109) g/L. For VPI ≤7 days of age, the pre-transfusion hemoglobin levels for invasive respiratory support, non-invasive respiratory support, or no respiratory support, respectively, with no statistically significant differences between groups ( H=5.59, P=0.061). For VPI aged 8 to 21 days and≥22 days, the levels with statistically differences between groups (both P<0.01). Red blood cell transfusions above recommended thresholds were observed in all respiratory support categories at different stages of life, with the highest prevalence in infants aged 8 to 21 days and≥22 days who did not require respiratory support, at 90.1% (264/273) and 91.1%(1 578/1 732), respectively. The rate of necrotizing enterocolitis was higher in the above-threshold group ( χ2=10.59, P=0.001), and the duration of hospital stay was longer in the above-threshold group ( Z=4.67, P<0.001) compared to the below-threshold group. Conclusions:In 2022, the red blood cell transfusion rate was relatively high among VPI from CHNN. Pre-transfusion hemoglobin levels frequently exceeded recommended transfusion thresholds.

Abstract： ObjectiveThe study aims to explore the effects and regulatory roles of glucose transporter 1 （GLUT1） on the proliferation， migration， adhesion， and angiogenesis of human umbilical vein endothelial cells （HUVECs） under ischemia-hypoxic conditions. MethodsIn vitro experiments were conducted to subject HUVECs to an ischemia-hypoxic-mimicking environment （1% O₂， 5% CO₂， 94% N₂）. The biological characteristics of HUVECs under normoxic and ischemia-hypoxic conditions were compared by assessing cell viability， proliferation capacity， and examining the expression changes of GLUT1， HIF-1α， and VEGFA proteins under ischemia-hypoxia using Western blot technology. Further， GLUT1 was overexpressed using plasmid transfection and the proliferation， migration， adhesion， and angiogenic capabilities of HUVECs were evaluated through scratch assays， cell adhesion assays， and tube formation assays. Mitochondrial morphological changes were observed by transmission electron microscopy，and oxygen consumption rate （OCR） was detected by Seahorse metabolic analyzer to evaluate mitochondrial function. ResultsCompared with normoxic conditions， the ischemia-hypoxic environment significantly inhibited the proliferation， cell viability， migration， and adhesion capabilities of HUVECs and impaired their angiogenic potential. The expression levels of GLUT1， HIF-1α and VEGFA proteins were also markedly reduced. However， when GLUT1 expression was upregulated， the migration， adhesion， and angiogenic capabilities of HUVECs were significantly improved， and the protein expression levels of HIF-1α， VEGFA and VEGFR were increased. Transmission electron microscopy revealed that ischemic-hypoxia leads to mitochondrial swelling and matrix damage， while GLUT1 overexpression significantly alleviates mitochondrial morphology abnormalities. OCR results suggest that GLUT1 overexpression may enhance oxidative phosphorylation of endothelial cells in ischemic-hypoxic environments to improve energy metabolism. These results suggest that GLUT1 may influence the function and angiogenic potential of HUVECs by regulating glucose metabolism and energy supply. ConclusionsThis study reveals the significant regulatory role of GLUT1 in the function of HUVECs under ischemia-hypoxic conditions， potentially through modulating cellular energy metabolism and signal transduction pathways， thereby affecting cell proliferation， migration， adhesion， and angiogenesis. These findings provide a new perspective on the role of GLUT1 in cardiovascular diseases and may offer potential targets for the development of new therapeutic strategies.

Objective To predict the lymph node metastasis status of patients with invasive pulmonary adenocarcinoma by constructing machine learning models based on primary tumor radiomics, peritumoral radiomics, and habitat radiomics, and to evaluate the predictive performance and generalization ability of different imaging features. Methods A retrospective analysis was performed on the clinical data of 1 263 patients with invasive pulmonary adenocarcinoma who underwent surgery at the Department of Thoracic Surgery, Jiangsu Province Hospital, from 2016 to 2019. Habitat regions were delineated by applying K-means clustering (average cluster number of 2) to the grayscale values of CT images. The peritumoral region was defined as a uniformly expanded area of 3 mm around the primary tumor. The primary tumor region was automatically segmented using V-net combined with manual correction and annotation. Subsequently, radiomics features were extracted based on these regions, and stacked machine learning models were constructed. Model performance was evaluated on the training, testing, and internal validation sets using the area under the receiver operating characteristic curve (AUC), F1 score, recall, and precision. Results After excluding patients who did not meet the screening criteria, a total of 651 patients were included. The training set consisted of 468 patients (181 males, 287 females) with an average age of (58.39±11.23) years, ranging from 29 to 78 years, the testing set included 140 patients (56 males, 84 females) with an average age of (58.81±10.70) years, ranging from 34 to 82 years, and the internal validation set comprised 43 patients (14 males, 29 females) with an average age of (60.16±10.68) years, ranging from 29 to 78 years. Although the habitat radiomics model did not show the optimal performance in the training set, it exhibited superior performance in the internal validation set, with an AUC of 0.952 [95%CI (0.87, 1.00)], an F1 score of 84.62%, and a precision-recall AUC of 0.892, outperforming the models based on the primary tumor and peritumoral regions. Conclusion The model constructed based on habitat radiomics demonstrated superior performance in the internal validation set, suggesting its potential for better generalization ability and clinical application in predicting lymph node metastasis status in pulmonary adenocarcinoma.

ObjectiveTo investigate the association between estimated glucose disposal rate （eGDR） and the severity of coronary heart disease. MethodsWe conducted a hospital-based cross-sectional study that included 1258 patients （mean age： 62（53-68） years） who underwent coronary angiography for suspected coronary artery disease （53.9% were male）. Insulin resistance level （IR） was calculated according to eGDR formula： eGDR = 21.158 - （0.09 × WC） - （3.407 × hypertension） - （0.551 × HbA1c） ［hypertension （yes = 1 / no = 0）， HbA1c = HbA1c （%）］. Subjects were grouped according to the eGDR quantile. CAD severity was determined by the number of narrowed vessels： no-obstructive CAD group （all coronary stenosis were<50%， n=704）， Single-vessel CAD group （only one involved major coronary artery stenosis≥50%， n=205）， Multi-vessel CAD group （two or more involved major coronary arteries stenosis≥50%， n=349）； Multivariate logistic regression model was used to analyze the association between eGDR and CAD severity. The linear relationship between eGDR and CAD in the whole range of eGDR was analyzed using restricted cubic spline. Subgroup analyses were used to assess the association between eGDR and CAD severity in different diabetic states. Receiver operating characteristic （ROC） curve analysis were used to evaluate the value of eGDR in improving CAD recognition. ResultsA decrease in the eGDR index was significantly associated with an increased risk of CAD severity （OR： 2.79； 95%CI： 1.72~4.55； P<0.001）. In multivariate logistic regression models， individuals with the lowest quantile of eGDR （T1） were 2.79 times more likely to develop multi-vessel CAD than those with the highest quantile of eGDR （T3） （OR： 2.79； 95%CI： 1.72~4.55； P<0.001）. Multivariate restricted cubic spline analysis showed that eGDR was negatively associated with CAD and multi-vessel CAD （P-nonlinear>0.05）. In non-diabetic patients， compared with the reference group （T3）， the T1 group had a significantly increased risk of CAD （OR： 1.42； 95% CI： 1.00~2.01； P<0.05） and multi-vessel CAD （OR： 1.86； 95%CI： 1.21~2.86； P<0.05）. No statistical association was found between eGDR and CAD in diabetic patients. In ROC curve analysis， when eGDR was added to traditional model for CAD， significant improvements were observed in the model's recognition of CAD and multi-vessel CAD. ConclusionOur study shows eGDR levels are inversely associated with CAD and CAD severity. eGDR， as a non-insulin measure to assess IR， could be a valuable indicator of CAD severity for population.

ObjectiveTo investigate the effects of Bushen Huoxue prescription on the cardiac function， inflammation， and quality of life of the patients with chronic heart failure resistant to diuretics. MethodA total of 78 patients who met the inclusion criteria were randomized into observation and control groups （39 cases）. Both groups received standardized treatment for diuretic resistance in accordance with the guidelines. In addition， the observation group received Bushen Huoxue prescription. The cardiac function indicators， total response rate regarding symptom alleviation， exercise endurance， urine volume， body mass， quality of life， and levels of inflammatory cytokines were compared between the two groups before and after treatment. ResultBefore treatment， the two groups of patients showed no significant differences in terms of 24 h urine volume， body mass， 6 minute walk test （6MWT）， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP） level， left ventricular ejection fraction （LVEF）， stroke volume （SV）， and serum levels of interleukin-6 （IL-6）， interleukin-4 （IL-4）， and tumor necrosis factor-alpha （TNF-α）. After treatment， the observation group outperformed the control group in terms of the response rates regarding traditional Chinese medicine symptom scores and New York Heart Association （NYHA） grading of cardiac function （P<0.05）. After treatment， the body mass， MLHFQ score， and IL-6， TNF-α， and NT-proBNP levels decreased in both groups （P<0.05， P<0.01）， and the observation group showed more significant decreases than the control group （P<0.05， P<0.01）. Both groups showed increases in 24-h urine volume， 6MWT， LVEF， SV， and IL-4 after treatment （P<0.05， P<0.01）， and the observation group showed more significant increases than the control group （P<0.05， P<0.01）. ConclusionThe combination of Bushen Huoxue prescription with standardized treatment is effective in ameliorating the clinical symptoms of the patients with chronic heart failure resistant to diuretics. Moreover， it alleviates diuretic resistance and improves the cardiac function without causing obvious adverse reactions.

Objective:To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks′ gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021.Methods:This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results:Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions:With the increasing number of extremely preterm infants at 22-25 weeks′ gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

Objective:To investigate the impact of age,various hormonal levels,and biochemical markers on penile cavernous body vascular function in patients with erectile dysfunction(ED).Me-thods:A retrospective analysis of clinical data from male patients with ED who underwent color duplex Doppler ultrasonography(CDDU)and intracavernosal injection test(ICI)at the Reproductive Medicine Center of Peking University Third Hospital from January 2020 to August 2023.Data were managed and processed using SPSS 29.0,and a multivariable Logistic regression analysis was conducted.Results:A total of 700 ED patients were included,with 380 showing negative ICI results and 320 positive.In the study,84 patients had a peak systolic velocity(PSV)＜25 cm/s,while 616 had PSV ≥ 25 cm/s;202 patients had end-diastolic velocity(EDV)＞5 cm/s,and 498 had EDV ≤5 cm/s.264 patients had ab-normal PSV and/or EDV results,and 436 had normal results for both.Patients with vascular ED had sig-nificantly lower estrogen levels(t=-3.546,P＜0.001),lower testosterone levels(t=-2.089,P=0.037),and a higher rate of hyperglycemia(x2=12.772,P=0.002)compared with those with non-vascular ED.The patients with arterial ED were older(t=3.953,P＜0.001),had a higher rate of hyperglycemia(x2=9.518,P=0.009),and a higher estrogen/testosterone ratio(t=2.330,P=0.020)compared with those with non-arterial ED.The patients with mixed arteriovenous ED had higher age(t=3.567,P＜0.001),lower testosterone levels(t=-2.288,P=0.022),a higher rate of hyperglycemia(x2=12.877,P=0.002),and a larger estrogen/testosterone ratio(t=2.096,P=0.037)compared with those with normal findings.Multifactorial Logistic regression analysis indicated that higher levels of estrogen were a protective factor for vascular ED(OR=1.009,95％CI:1.004-1.014),and glucose 7.0 mmol/L was a risk factor(OR=0.381,95％CI:0.219-0.661).Older age was a risk factor for arte-rial ED(OR=0.960,95％CI:0.938-0.982).Additionally,older age(OR=0.976,95％CI:0.958-0.993)and glucose levels of 5.6-6.9 mmol/L(OR=0.591,95％CI:0.399-0.876)were also risk fac-tors for mixed arterio-venous ED.Conclusion:Hyperglycemia and aging may impair penile cavernous body vascular function,while higher levels of estrogen may have a protective effect on it.

Innate and adaptive immune responses initiated by infection depend on recognition and control of pathogens by macrophages,dendritic cells,T cells and so on.Notch signaling pathway is a highly conserved pathway,which is activated by interac-tion of receptors and ligands,thus coordinating important life processes of cells.At present,it has been confirmed that Notch signaling pathway is involved in development,differentiation,maturation and activation of many kinds of immune cells,and plays an important role in infectious diseases.In this review,we mainly focus on the role of Notch signaling pathway in immune regulation during different pathogens infection and its interaction with other signaling pathways.Additionally,therapeutic methods and challenges of developing Notch signaling as a target in infectious diseases are also discussed.

BACKGROUND: Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV). METHODS: We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development. RESULTS: We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron. CONCLUSION Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Child ; Humans ; Neurodevelopmental Disorders/epidemiology* ; Genetic Testing ; Phenotype ; Brain/pathology* ; Genetic Background ; SOX Transcription Factors/genetics*

Objective:To explore the clinical value of cardiac MR (CMR) compression sensing (CS) ultrafast cine sequence in evaluating left and right ventricular systolic function by comparing with traditional segmented acquisition cine sequence (Seg).Methods:Twenty-seven patients with various heart disease were prospectively included. Seg, breath holding CS (bhCS) and free breathing CS (fbCS) covering the left and right ventricles using multi slices in short axis were performed in random order. Friedman test was used to evaluate the overall image quality (grade 1-5 score), blood pool myocardial signal ratio (BMC) and edge sharpness under different methods. Biventricular end diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV), ejection fraction (EF) and left ventricular myocardial mass (Mass) were measured for all three methods. The agreements of the functional measurements between bhCS and Seg (gold standard), and between fbCS and Seg were analyzed by Bland-Altman, and the correlation test was performed.Results:Twenty-four patients with diagnostic images(overall image quality score≥2) for all three methods were included in further analysis. The total imaging time of Seg, bhCS and fbCS decreased successively[375.0 (332.0, 405.6) vs. 50.0 (47.8, 53.7) vs. 20.0 (17.8, 23.7) s, χ 2=48.00, P<0.001]. The overall image quality of fbCS was slightly lower than that of Seg ( Z=-2.67, P=0.023), and there was no difference between Seg and bhCS ( Z=-1.44, P=0.447), bhCS and fbCS ( Z=1.23, P=0.660). There were no differences in edge sharpness (χ 2=1.08, P=0.582) and BMC (χ 2=0.58, P=0.747) for three methods. Bland-Altman polts showed good agreement for biventricular functional measurements between bhCS and Seg, and between fbCS and Seg. All functional measurements of bhCS and fbCS were highly correlated with that of seg ( r>0.96, P<0.001). Conclusions:Compared with traditional sequences, CS ultrafast cine sequences can save scanning time and provide similar image quality. No matter whether breath holding or not, the cardiac functional results of CS sequence and traditional cine sequence have good agreement and high correlation.