Transcriptome sequencing reveals novel biomarkers and immune cell infiltration in esophageal tumorigenesis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide, and its development comprises a multistep process from intraepithelial neoplasia (IN) to carcinoma (CA). However, the critical regulators and underlying molecular mechanisms remain largely unknown. AIM: To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention. METHODS: A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide (4NQO) to C57BL/6 mice. Moreover, we established a control group without 4NQO treatment of mice. Then, transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses, including low-grade IN (LGIN), high-grade IN (HGIN), and CA, and controlled normal tissue (NOR) samples. Differentially expressed genes (DEGs) were identified in the LGIN, HGIN, and CA groups, and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The CIBERSORT algorithm was used to detect the pattern of immune cell infiltration. Immunohistochemistry (IHC) was also conducted to validate our results. Finally, the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice. RESULTS: Compared with those in the NOR group, a total of 681541, and 840 DEGs were obtained in the LGIN, HGIN, and CA groups, respectively. Using the intersection of the three sets of DEGs, we identified 86 genes as key genes involved in the development of ESCC. Enrichment analysis revealed that these genes were enriched mainly in the keratinization, epidermal cell differentiation, and interleukin (IL)-17 signaling pathways. CIBERSORT analysis revealed that, compared with those in the NOR group, M0 and M1 macrophages in the 4NQO group showed stronger infiltration, which was validated by IHC. Serum cytokine analysis revealed that, compared with those in the NOR group, IL-1ß and IL-6 were upregulated, while IL-10 was downregulated in the LGIN, HGIN, and CA groups. Moreover, the expression of the representative key genes, such as S100a8 and Krt6b, was verified in external human samples, and the results of immunohistochemical staining were consistent with the findings in mice. CONCLUSION: We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions. In addition, we found that macrophage infiltration and abnormal alterations in the levels of inflammation-associated cytokines, such as IL-1ß, IL-6, and IL-10, in the peripheral blood may be closely associated with the development of ESCC.

Hyperglycemia in pregnancy did not worsen the short-term outcomes of very preterm infants: a propensity score matching study.

Background: Hyperglycemia in pregnancy (HGP) has generally been considered a risk factor associated with adverse outcomes in offspring, but its impact on the short-term outcomes of very preterm infants remains unclear. Methods: A secondary analysis was performed based on clinical data collected prospectively from 28 hospitals in seven regions of China from September 2019 to December 2020. According to maternal HGP, all infants were divided into the HGP group or the non-HGP group. A propensity score matching analysis was used to adjust for confounding factors, including gestational age, twin or multiple births, sex, antenatal steroid administration, delivery mode and hypertensive disorders of pregnancy. The main complications and the short-term growth status during hospitalization were evaluated in the HGP and non-HGP groups. Results: A total of 2,514 infants were eligible for analysis. After matching, there were 437 infants in the HGP group and 874 infants in the non-HGP group. There was no significant difference between the two groups in main complications including respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus, culture positive sepsis, intraventricular hemorrhage, periventricular leukomalacia, anemia, feeding intolerance, metabolic bone disease of prematurity, or parenteral nutrition-associated cholestasis. The incidences of extrauterine growth retardation and increased growth retardation for weight and head circumference in the non-HGP group were all higher than those in the HGP group after matching (P < 0.05). Conclusions: HGP did not worsen the short-term outcomes of the surviving very preterm infants, as it did not lead to a higher risk of the main neonatal complications, and the infants' growth improved during hospitalization.

The role of nutrition in analysis of risk factors and short-term outcomes for late-onset necrotizing enterocolitis among very preterm infants: a nationwide, multicenter study in China.

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease, primarily affects preterm newborns and occurs after 7 days of life (late-onset NEC, LO-NEC). Unfortunately, over the past several decades, not much progress has been made in its treatment or prevention. This study aimed to analyze the risk factors for LO-NEC, and the impact of LO-NEC on short-term outcomes in very preterm infants (VPIs) with a focus on nutrition and different onset times. METHOD: Clinical data of VPIs were retrospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. A total of 2509 enrolled VPIs were divided into 2 groups: the LO-NEC group and non-LO-NEC group. The LO-NEC group was divided into 2 subgroups based on the onset time: LO-NEC occurring between 8 ~ 14d group and LO-NEC occurring after 14d group. Clinical characteristics, nutritional status, and the short-term clinical outcomes were analyzed and compared among these groups. RESULTS: Compared with the non-LO-NEC group, the LO-NEC group had a higher proportion of anemia, blood transfusion, and invasive mechanical ventilation (IMV) treatments before NEC; the LO-NEC group infants had a longer fasting time, required longer duration to achieve the target total caloric intake (110 kcal/kg) and regain birthweight, and showed slower weight growth velocity; the cumulative dose of the medium-chain and long-chain triglyceride (MCT/LCT) emulsion intake in the first week after birth was higher and breastfeeding rate was lower. Additionally, similar results including a higher proportion of IMV, lower breastfeeding rate, more MCT/LCT emulsion intake, slower growth velocity were also found in the LO-NEC group occurring between 8 ~ 14d when compared to the LO-NEC group occurring after 14 d (all (P < 0.05). After adjustment for the confounding factors, high proportion of breastfeeding were identified as protective factors and long fasting time before NEC were identified as risk factors for LO-NEC; early feeding were identified as protective factors and low gestational age, grade III ~ IV neonatal respiratory distress syndrome (NRDS), high accumulation of the MCT/LCT emulsion in the first week were identified as risk factors for LO-NEC occurring between 8 ~ 14d. Logistic regression analysis showed that LO-NEC was a risk factor for late-onset sepsis, parenteral nutrition-associated cholestasis, metabolic bone disease of prematurity, and extrauterine growth retardation. CONCLUSION: Actively preventing premature birth, standardizing the treatment of grade III ~ IV NRDS, and optimizing enteral and parenteral nutrition strategies may help reduce the risk of LO-NEC, especially those occurring between 8 ~ 14d, which may further ameliorate the short-term clinical outcome of VPIs. TRIAL REGISTRATION: ChiCTR1900023418 (26/05/2019).

Coordination-Driven Heterochiral Self-Assembly: Construction of Cd(II) Coordination Polymers with Sorption Behaviors for Iodine and Dyes.

A racemic bispyridyl ligand (L) was synthesized via a Schiff base condensation reaction. Four Cd(II) complexes, {[CdL2Cl2]·2DMF}n (1), [CdLI2]n (2), {[CdL2Br2]·4H2O}n (3), and {[CdL2(H2O)2](NO3)2·2CH3OH·8H2O}n (4), were synthesized and further characterized based on this ligand. Single-crystal structures show that the coordination-driven assembly of the bispyridyl ligand with Cd(II) salts bearing different counteranions can lead to multidimensional coordination polymers via a heterochiral self-discrimination process. Complex 1 exists as a one-dimensional (1D) looped chain polymer, and complex 2 exists as a 1D zigzag chain polymer. Complex 3 is a 2D grid coordination polymer, and complex 4 exists as a 3D framework polymer. Furthermore, the iodine sorption capacities of the four complexes were investigated in the solution of n-hexane and water as well as in the iodine steam. The dye sorption behaviors were investigated in water, which showed that complex 2 exhibited good adsorption for crystal violet (CV), while complex 4 had good adsorption capability toward direct yellow 4 (DY).

Predictive value of serum ß2-microglobulin in cardiac valve calcification in maintenance hemodialysis patients.

Background: Cardiac valve calcification (CVC) is associated with adverse cardiovascular events. We studied the risk factors of CVC in maintenance hemodialysis (MHD) patients and the value of serum ß2-microglobulin (ß2-MG) levels in predicting the incidence of CVC. ß2-MG is a middle molecular weight toxin. In recent years, researchers found that elevated blood ß2-MG was associated with coronary, thoracic, and abdominal aortic calcifications with significant correlations. ß2-MG has been emerging as a strong biomarker for cardiovascular mortality in uremic patients but its role in CVC is not well studied. This study looked specifically at CVC occurrence in relation to ß2-MG for MHD patients. Methods: Patients who underwent MHD for more than 3 months in the First People's Hospital of Nantong City from November 2012 to November 2019 with complete available data were included in the study. The patients were divided into the CVC group and the non-CVC group. The general information and clinical laboratory indicators of the patients were collected in a retrospective manner. We analyzed the risk factors for developing CVC in MHD patients using binary logistic regression method. Receiver operating characteristic (ROC) curves were used to calculate the cut-off value of ß2-MG for predicting CVC. The decision tree (DT) method was used to classify and explore the probability of CVC in patients with MHD. Results: The ß2-MG in the CVC group was significantly higher than that in the non-CVC group (t=6.750, P<0.001). Multivariate binary logistic regression analysis showed that gender, age, serum ß2-MG, and hemodialysis (HD) adequacy (Kt/V urea) were independent risk factors for CVC in MHD patients. ROC analysis showed that a ß2-MG value of 25 µg/L was the best cut-off point for predicting CVC in MHD patients. According to binary logistic regression analysis, the ß2-MG ≥25 µg/L group was 3.39 times more likely to develop CVC than the ß2-MG <25 µg/L group [odds ratio (OR), 3.39; 95% confidence interval (CI), 1.63-7.06; P=0.001]. The DT model determined that serum ß2-MG ≥25 µg/L and age >69 years were important determinants for predicting CVC in MHD patients. Conclusions: Serum ß2-MG in MHD patients has a positive correlation with the severity and occurrence of CVC.

Real-world evidence regarding the growth of very premature infants with small for gestational age after birth: a multicenter survey in China.

BACKGROUND: To analyze the real-world growth pattern of very premature infants (VPI) with small for gestational age (SGA) after birth by using the ΔZ value of weight at discharge. METHODS: The clinical data were collected from 28 hospitals in China from September 2019 to December 2020. They were divided into the EUGR(Extrauterine Growth Restriction) and the non-EUGR group according to the criterion of ΔZ value of weight at discharge < -1.28. RESULTS: This study included 133 eligible VPI with SGA. Following the criterion of ΔZ value, the incidence of EUGR was 36.84% (49/133). The birth weight, the 5-min Apgar score, and the proportion of male infants in the EUGR group were lower (P < 0.05). The average invasive ventilation time, cumulative duration of the administration of antibiotics, blood transfusion time, blood transfusion ratio, and total days of hospitalization were significantly higher in the EUGR group (P < 0.05). In the EUGR group, several factors exhibited higher values (P < 0.05), including the initiation of enteral feeding, the volume of milk supplemented with human milk fortifier (HMF), the duration to achieve complete fortification, the cumulative duration of fasting, the duration to achieve full enteral feeding, the length of parenteral nutrition (PN), the number of days required to attain the desired total calorie intake and oral calorie intake, as well as the age at which birth weight was regained. The average weight growth velocity (GV) was significantly lower in the EUGR group (P < 0.001). The incidences of patent ductus arteriosus with hemodynamic changes (hsPDA), neonatal necrotizing enterocolitis (NEC) stage≥ 2, late-onset sepsis (LOS), and feeding intolerance (FI) in the EUGR group were higher (P < 0.05). Multivariate logistic regression analysis showed that birth weight, male, and GV were the protective factors, while a long time to achieve full-dose fortification, slow recovery of birth weight, and NEC stage ≥2 were the independent risk factors. CONCLUSION: SGA in VPI can reflect the occurrence of EUGR more accurately by using the ΔZ value of weight at discharge. Enhancing enteral nutrition support, achieving prompt and complete fortification of breast milk, promoting greater GV, reducing the duration of birth weight recovery, and minimizing the risk of NEC can contribute to a decreased occurrence of EUGR. TRIAL REGISTRATION: CHICTR, ChiCTR1900023418. Registered 26/05/2019, http://www.chictr.org.cn .

Five Porous Complexes Constructed from a Racemic Ligand: Synthesis, Chiral Self-Assembly, Iodine Adsorption, and Desorption Properties.

Herein, a chiral bispyridyl ligand (L) was designed and synthesized using a Schiff base condensation reaction, followed by a 1,3-H shift. Five complexes, [Zn2L2(OAc)4] (1), {[CdLCl2(DMF)]·4H2O}n (2), [Cd2L2I4]·4H2O (3), {[CdL2(H2O)2](NO3)2·2CH3OH}n (4), and [Hg2L2Cl4]·2DMF (5), were synthesized and characterized upon its reaction with Zn(II), Cd(II), or Hg(II) ions, respectively. X-ray crystallography shows that the organic compound exists as a racemic ligand with equal amounts of its R- and S-isomers, and all of the synthesized complexes exhibit heterochiral self-assembly via a chiral self-discrimination process. Complexes 1, 3, and 5 exist as centrosymmetric binuclear metallamacrocycles, while complexes 2 and 4 exist as 1D looped-chain coordination polymers. Inspired by the assembled structures of the five complexes, I2 adsorption/desorption measurements for the complexes were carried out. The results show that complexes 1 and 5 exhibit good adsorption capacities toward I2 in n-hexane and in water, respectively.

One-Pot Synthesis of Diverse 1,4-[60]Fullerephenols via Three-Component Umpolung Cascade Coupling of Phenols, C60 , and Nucleophiles.

A three-component umpolung cascade coupling reaction of phenols, C60 , and different nucleophiles which includes H2 O, alcohols, triphenylamines and carbazoles was developed. Furthermore, one-pot 1,4-bisphenol coupling on C60 has been realized by this method. This practical protocol features high chemo- and regioselectivity, wide substrate range, easy operation and low cost, thus providing a robust method for the one-pot synthesis of various unsymmetrical 1,4-[60]fullerephenols.

COLEC10 Induces Endoplasmic Reticulum Stress by Occupying GRP78 and Inhibits Hepatocellular Carcinoma.

Collectin subfamily member 10 (COLEC10), a C-type lectin mainly expressed in the liver, is involved in the development of hepatocellular carcinoma (HCC). However, its underlying molecular mechanism in HCC progression remains unknown. In this study, reduced COLEC10 expression in tumor tissues was validated using various HCC cohorts and was associated with poor patient prognosis. COLEC10 overexpression attenuated HCC cell growth and migration abilities in vitro and in vivo. We identified that COLEC10 was a novel interactor of 78-kDa glucose-regulated protein (GRP78), a master modulator of the unfolded protein response in the endoplasmic reticulum (ER). COLEC10 overexpression potentiated ER stress in HCC cells, as demonstrated by elevated expression levels of phosphorylated protein kinase RNA-like ER kinase, phosphorylated inositol-requiring protein 1α, activating transcription factor 4, DNA damage-inducible transcript 3, and X-box-binding protein 1s. The ER in COLEC10-overexpressing cells also showed a dilated and fragmented pattern. Mechanistically, COLEC10 overexpression increases GRP78 occupancy through direct binding by the C-terminal carbohydrate recognition domain in the ER, which released and activated the ER stress transducers protein kinase RNA-like ER kinase and phosphorylated inositol-requiring protein 1α, triggering the unfolded protein response activity. COLEC10-overexpressing HCC cells generated a relatively high reactive oxygen species level and switched to apoptotic cell death under sorafenib-treated conditions. Our study provides the first novel view that COLEC10 inhibits HCC progression by regulating GRP78-mediated ER stress signaling and may serve as a promising therapeutic and prognostic biomarker.

Altered resting-state network connectivity patterns for predicting attentional function in deaf individuals: An EEG study.

Multiple aspects of brain development are influenced by early sensory loss such as deafness. Despite growing evidence of changes in attentional functions for prelingual profoundly deaf, the brain mechanisms underlying these attentional changes remain unclear. This study investigated the relationships between differential attention and the resting-state brain network difference in deaf individuals from the perspective of brain network connectivity. We recruited 36 deaf individuals and 34 healthy controls (HC). We recorded each participant's resting-state electroencephalogram (EEG) and the event-related potential (ERP) data from the Attention Network Test (ANT). The coherence (COH) method and graph theory were used to build brain networks and analyze network connectivity. First, the ERPs of analysis in task states were investigated. Then, we correlated the topological properties of the network functional connectivity with the ERPs. The results revealed a significant correlation between frontal-occipital connection in the resting state and the amplitude of alert N1 amplitude in the alpha band. Specifically, clustering coefficients and global and local efficiency correlate negatively with alert N1 amplitude, whereas the characteristic path length positively correlates with alert N1 amplitude. In addition, deaf individuals exhibited weaker frontal-occipital connections compared to the HC group. In executive control, the deaf group had longer reaction times and larger P3 amplitudes. However, the orienting function did not significantly differ from the HC group. Finally, the alert N1 amplitude in the ANT task for deaf individuals was predicted using a multiple linear regression model based on resting-state EEG network properties. Our results suggest that deafness affects the performance of alerting and executive control while orienting functions develop similarly to hearing individuals. Furthermore, weakened frontal-occipital connections in the deaf brain are a fundamental cause of altered alerting functions in the deaf. These results reveal important effects of brain networks on attentional function from the perspective of brain connections and provide potential physiological biomarkers to predicting attention.

Effect of early initiation of enteral nutrition on short-term clinical outcomes of very premature infants: A national multicenter cohort study in China.

OBJECTIVES: The management of enteral nutrition in very preterm infants (VPIs) is still controversial, and there is no consensus on the optimal time point after birth at which enteral nutrition can be started. The aim of this study was to investigate the effect of early initiation of enteral nutrition on the short-term clinical outcomes of VPIs. METHODS: Data of infants (n = 2514) born before 32 wk of gestation were collected from 28 hospitals located in seven different regions of China. Based on whether enteral feeding was initiated within or after 24 h since birth, the infants were divided into an early initiation of enteral feeding (EIEF) group and a delayed initiation of enteral feeding (DIEF) group. RESULTS: Compared with the DIEF group, the EIEF group was more likely to tolerate enteral nutrition and had less need for parenteral nutrition (all P < 0.05). The EIEF group was associated with lower incidence rates of feeding intolerance, extrauterine growth restriction (EUGR), and late-onset sepsis (LOS) (all P < 0.05). There was no significant difference in the incidence of necrotizing enterocolitis (NEC) (Bell stage ≥2) between the two groups (P = 0.118). The multivariate logistic regression analysis revealed that EIEF was a protective factor against EUGR (odds ratio [OR], 0.621; 95% confidence interval [CI], 0.544-0.735; P < 0.001), feeding intolerance (OR, 0.658; 95% CI, 0.554-0.782; P < 0.001), and LOS (OR, 0.706; 95% CI, 0.550-0.906; P = 0.006). CONCLUSIONS: Early initiation of enteral feeding was associated with less frequency of feeding intolerance, EUGR, and LOS, and it may shorten the time to reach total enteral feeding without increasing the risk of NEC.

Changes in endemic patterns of respiratory syncytial virus infection in pediatric patients under the pressure of nonpharmaceutical interventions for COVID-19 in Beijing, China.

A series of nonpharmaceutical interventions (NPIs) was launched in Beijing, China, on January 24, 2020, to control coronavirus disease 2019. To reveal the roles of NPIs on the respiratory syncytial virus (RSV), respiratory specimens collected from children with acute respiratory tract infection between July 2017 and Dec 2021 in Beijing were screened by capillary electrophoresis-based multiplex PCR (CEMP) assay. Specimens positive for RSV were subjected to a polymerase chain reaction (PCR) and genotyped by G gene sequencing and phylogenetic analysis using iqtree v1.6.12. The parallel and fixed (paraFix) mutations were analyzed with the R package sitePath. Clinical data were compared using SPSS 22.0 software. Before NPIs launched, each RSV endemic season started from October/November to February/March of the next year in Beijing. After that, the RSV positive rate abruptly dropped from 31.93% in January to 4.39% in February 2020; then, a dormant state with RSV positive rates ≤1% from March to September, a nearly dormant state in October (2.85%) and November (2.98%) and a delayed endemic season in 2020, and abnormal RSV positive rates remaining at approximately 10% in summer until September 2021 were detected. Finally, an endemic RSV season returned in October 2021. There was a game between Subtypes A and B, and RSV-A replaced RSV-B in July 2021 to become the dominant subtype. Six RSV-A and eight RSV-B paraFix mutations were identified on G. The percentage of severe pneumonia patients decreased to 40.51% after NPIs launched. NPIs launched in Beijing seriously interfered with the endemic season of RSV.

Correlation between lactate dehydrogenase and QTc interval prolongation in maintenance hemodialysis patients: a cross-sectional study.

BACKGROUND: Corrected QT (QTc) interval prolongation is one of the common causes of sudden cardiac death in patients with maintenance hemodialysis (MHD) patients. However, there are few studies on QTc prolongation in MHD patients. The concentration of lactate dehydrogenase (LDH) in hemodialysis population increased, and LDH was associated with the mortality of MHD patients. This study aimed to investigate the relationship between QTc interval prolongation and LDH in MHD patients. METHODS: This is a cross-sectional observational study. Patients who underwent MHD for more than 3 months in the Second Affiliated Hospital of Nantong University from November 2012 to November 2019 with complete data were selected as the research subjects. The patients were divided into the normal QTc interval group and the QTc interval prolongation group. The general data of patients and clinical laboratory indicators were collected retrospectively from the electronic medical record system. Pearson correlation analysis and binary logistic regression were used to analyze the correlation between LDH and QTc interval prolongation; the cut-off value of LDH predicting QTc interval prolongation was calculated by receiver operating characteristic (ROC) curve. RESULTS: The LDH level in the prolonged QTc interval group was significantly higher than that in the normal group (301.96±110.91 vs. 215.39±67.65, t=-8.03, P<0.001). QTc interval and LDH (r=0.386) were positively correlated. Binary logistic regression analysis showed that LDH, serum potassium <4 mmol/L, serum phosphorus, and left ventricular end-diastolic diameter (LVDd) were independent related factors for QTc interval prolongation. The ROC curve results showed that LDH =220 U/L was the best cutoff point for predicting QTc interval prolongation in MHD patients, with a sensitivity of 81.45% and a specificity of 59.35%. Binary logistic regression analysis showed that the LDH >220 U/L group was 6.34 times more likely to have QTc interval prolongation than the LDH ≤220 U/L group (OR 6.34, 95% CI: 3.47-11.58, P<0.001). CONCLUSIONS: LDH in MHD patients is closely related to QTc interval prolongation. Serum LDH, ionic calcium, serum phosphorus and potassium may predict QTc interval prolongation. Monitoring related indicators can remind clinicians to intervene as soon as possible to reduce the potential risk of arrhythmia and sudden cardiac death (SCD).

Coordination-Driven Self-Assembly of Complexes Constructed from Two Helical Ligands: Synthesis, Structures, and Selective Gas Adsorption Properties.

Two helical ligands (L1 and L2) were designed and synthesized by a Schiff base condensation reaction. Eight complexes, {[Zn(L1)I2]·H2O}n (1), [Cd2(L1)2I4(CH3OH)2] (2), [Hg2(L1)2I4] (3), [Ag(L1)NO3]n (4), [Ag2(L1)2(NO3)2DMSO]·H2O (5), {[Zn2(L2)2Cl4]·2CHCl3}n (6), {[Ag(L2)]·NO3}n (7), and {[Ag(L2)NO3]·CH3OH}n (8), were synthesized and characterized based on these two ligands. The crystal structures show that both Schiff base compounds exist as racemic ligands with equal amounts of P- and M-helicity, and the assembly of these racemic ligands with metal ions can lead to homochiral or heterochiral complexes via a chiral self-recognition or self-discrimination process. Complexes 2, 3, and 5 exist as heterochiral metallomacrocycles with a figure-eight conformation. Complexes 1, 6, and 8 exist as one-dimensional (1D) homochiral helical chain coordination polymers, while complexes 4 and 7 exist as 1D heterochiral helical chain coordination polymers. Furthermore, gas and vapor adsorption measurements show that all of the synthesized complexes exhibit good selective adsorption capacities toward methanol and ethanol vapor over N2, H2, and O2.

Factors influencing extrauterine growth retardation in singleton-non-small for gestational age infants in China: A prospective multicenter study.

BACKGROUND: The incidence of extrauterine growth retardation (EUGR) varies considerably in different countries due to the distinct definitions and inclusion criteria of individual studies. Most studies included small for gestational age (SGA) very preterm infants (VPIs), resulting in a higher incidence of EUGR. Experts have suggested the accurate definition of "EUGR" in SGA infants is not "true EUGR". The postnatal growth curve of multiple premature births also differs from that of singletons. As far as we know, there is no study about relationship between singleton-non-SGA preterm infants and EUGR. OBJECTIVES: To analyze the factors influencing EUGR among VPIs who were singleton-non-SGA in China. METHODS: A prospective-multicenter study was conducted in 28 hospitals distributed through China from September 2019 to December 2020. The clinical data on singleton-non-SGA among VPIs were divided into EUGR group (n = 692) and non-EUGR group (n = 912). RESULTS: Compared to non-EUGR group, the mean gestational age (GA), mean birth weight (BW) and percentage of BW in Fenton curve in EUGR group were lower (P < 0.001 for all). The incidence of EUGR among distinct GA groups (classifications of GA < 28weeks, 28-28+6 weeks, 29-29+6 weeks, 30-30+6 weeks and 31-31+6 weeks) and distinct BW groups (classifications of BW<1000 g, 1000-1249 g, 1250-1499 g, 1500-1999g and 2000-2500 g) were statistically significant (P = 0.004 and P <.001). Logistic regression analysis indicated that later addition of human milk fortifier (HMF), later attainment of HMF sufficient fortification, later return to BW, more accumulative days of fasting, longer duration of parenteral nutrition, total duration of oxygen support and moderate/severe bronchopulmonary dysplasia (BPD) were risk factors for the development of EUGR in singleton-non-SGA VPIs (P < 0.001, P = 0.002, P < 0.001, P = 0.002, P = 0.017, P = 0.003 and P = 0.002, respectively). The use of full-course antenatal steroids, greater BW as a percentile of the Fenton curve, breastfeeding initiation and faster average velocity of weight growth effectively protected against EUGR (P = 0.008, P < 0.001, P < 0.001 and P < 0.001, respectively). CONCLUSIONS: The overall incidence of EUGR was 43.1% among singleton-non-SGA VPIs in China. Raising the full-course antenatal steroids usage, reducing the incidence of moderate and severe BPD, attaching importance to the management of enteral nutrition in VPIs and increasing the weight growth velocity can reduce the incidence of EUGR.

Whole-exome sequencing analysis identifies distinct mutational profile and novel prognostic biomarkers in primary gastrointestinal diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma, and about 10% of DLBCL cases primarily occur in the gastrointestinal tract. Previous reports have revealed that primary gastrointestinal-DLBCL (pGI-DLBCL) harbors different genetic mutations from other nodal or extranodal DLBCL. However, the exonic mutation profile of pGI-DLBCL has not been fully addressed. METHODS: We performed whole-exome sequencing of matched tumor tissues and blood samples from 53 pGI-DLBCL patients. The exonic mutation profiles were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed. RESULTS: A total of 6,588 protein-altering events were found and the five most frequent mutated genes in our pGI-DLBCL cohort were IGLL5 (47%), TP53 (42%), BTG2 (28%), P2RY8 (26%) and PCLO (23%). Compared to the common DLBCL, significantly less or absence of MYD88 (0%), EZH2 (0%), BCL2 (2%) or CD79B (8%) mutations were identified in pGI-DLBCL. The recurrent potential driver genes were mainly enriched in pathways related to signal transduction, infectious disease and immune regulation. In addition, HBV infection had an impact on the mutational signature in pGI-DLBCL, as positive HBsAg was significantly associated with the TP53 and LRP1B mutations, two established tumor suppressor genes in many human cancers. Moreover, IGLL5 and LRP1B mutations were significantly correlated with patient overall survival and could serve as two novel prognostic biomarkers in pGI-DLBCL. CONCLUSIONS: Our study provides a comprehensive view of the exonic mutation profile of the largest pGI-DLBCL cohort to date. The results could facilitate the clinical development of novel therapeutic and prognostic biomarkers for pGI-DLBCL.

Analysis of "true extrauterine growth retardation" and related factors in very preterm infants-A multicenter prospective study in China.

Objective: To investigate the incidence and related factors of extrauterine growth retardation (EUGR) and "true EUGR" in very preterm infants (VPI) from different regions of China. Materials and methods: Clinical data of VPI were prospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. The infants were divided into a small for gestational age (SGA) group or non-SGA group at birth, with non-SGA infants at 36 weeks of gestation or at discharge being further divided into a EUGR group or a non-EUGR group. Infants in the EUGR and non-SGA group were defined as "true EUGR." The general information of VPI, such as maternal complications during pregnancy, use of enteral nutrition and parenteral nutrition, and complications during hospitalization were compared between the groups. Results: Among the 2,514 VPI included in this study, 47.3, 41.5, and 33.3% of VPI were below the 10th percentile, and 22.6, 22.4, and 16.0% of VPI were below the 3rd percentile for weight, height, and head circumference at 36 weeks of gestation or at discharge, respectively, by the percentile on the 2013 Fenton curve. The incidences of EUGR and "true EUGR" evaluated by weight were 47.3 and 44.5%, respectively. Univariate analysis showed that there were statistically significant differences in the aspects of perinatal and nutritional characteristics, treatment, and complications between the groups. Multivariate analysis showed that in non-SGA infants, the cumulative caloric intake during the first week was a protective factor for "true EUGR," while days to reach total enteral nutrition, late initiation of human milk fortifier, and moderate to severe bronchopulmonary dysplasia were independent risk factors for "true EUGR." Conclusion: More attention should be paid to the nutritional management of VPI to prevent "true EUGR." Cumulative caloric intake should be ensured and increased during the first week, total enteral nutrition should be achieved as early as possible, human milk fortifier should be added early, and moderate to severe bronchopulmonary dysplasia should be prevented. These strategies are very important for reducing the incidence of "true EUGR" in VPI.

ED50 value of remifentanil in inhibiting coughing during extubation in children with snoring.

Objective: This study aimed to determine the effective dose 50% (ED50) value of remifentanil in inhibiting coughing during extubation in children with snoring. Methods: The subjects were children who scored a grade I in the American Society of Anesthesiology (ASA) metric and who were undergoing tonsillectomy (with or without adenoidectomy) under general anesthesia. Using Dixon's up-and-down sequential method, the initial infusion rate of remifentanil was 0.06 µg/kg/min, and the difference between the infusion rates of the two adjacent groups was 0.01 µg/kg/min. If a child had no cough response during extubation, the infusion rate for the next child was reduced by 0.01 µg/kg/min. If that child had cough response, the infusion rate for the next child was increased by 0.01 µg/kg/min, and the test was terminated when seven pairs of children with positive-negative alternating results were obtained. The ED50 value and its 95% confidence interval (CI) were calculated by probit regression. The times for extubation, awakening, agitation, and respiratory complications after extubation were compared between the two groups. Results: 1) The ED50 value of a continuous infusion of remifentanil required to inhibit the cough response of children during extubation was 0.042 µg/kg/min, and the 95% confidence interval was 0.025-0.062 µg/kg/min. 2) The total dosage and infusion rate of remifentanil in the cough suppression group were higher than those in the cough group (p < 0.05), but the differences in the times for extubating and awakening between the two groups were not statistically significant (p > 0.05). 3) There was no correlation between the infusion rate of remifentanil and the time for extubating and awakening in the cough suppression group; the r values were 0.13 and 0.12, respectively, and p > 0.05. 4) The differences in postoperative respiratory complications between the two groups were not statistically significant (p > 0.05). Conclusion: The ED50 value of a continuous infusion of remifentanil required to inhibit the cough response of children during extubation after tonsillectomy (with or without adenoidectomy) was 0.042 µg/kg/min, and a low-dose infusion of remifentanil does not affect the times for awakening and extubating in children.

Human bocavirus 1 is a genuine pathogen for acute respiratory tract infection in pediatric patients determined by nucleic acid, antigen, and serology tests.

Background: Human bocavirus 1 (HBoV1), first discovered in 2005, was positive in symptomatic and healthy children and co-detected with other respiratory viruses. It is a long journey to decisively demonstrate the unique viral pathogenic function of acute respiratory tract infection (ARTI) in pediatric patients. Methods: Respiratory specimens collected from pediatric patients with ARTI from January 2017 to December 2021 were screened by a capillary electrophoresis-based multiplex PCR (CEMP) assay, then genotyped by PCR and sequencing for HBoV1. For the antigen test, a part of HBoV1 DNA positive nasopharyngeal aspirates (NPAs) was used as an antigen, while a rabbit anti-HBoV1 DR2 specific to HBoV1 was used as an antibody in the indirect-immunofluorescence assay (IFA). Finally, the levels of IgG specific to HBoV1 in acute and convalescent sera selected retrospectively from only HBoV1 DNA-positive patients were evaluated by IFA. Results: Among 9,899 specimens, 681 were positive for HBoV1 DNA (6.88%, 681/9899), which included 336 positives only for HBoV1 (49.34%, 336/681) and 345 (50.66%, 345/681) positives also for other pathogens. In the antigen test, there were 37 among 47 NPAs determined as HBoV1 antigen-positive (78.72%, 37/47), including 18 (48.65%, 18/37) positives solely for HBoV1 DNA. Among 4 pediatric patients with both acute and convalescent sera, there was one positive for HBoV1 antigen (D8873) and 2 lack the antigen results (D1474 and D10792), which showed seroconversion with a ≥ 4-fold increase in IgG levels. Conclusions: The combination results of nucleic acid, antigen, and serology tests answered that HBoV1 is a genuine pathogen for ARTI in pediatric patients.

Aetiology and outcomes of prolonged neonatal jaundice in tertiary centres: data from the China Neonatal Genome Project.

OBJECTIVE: To investigate the distribution of aetiologies and outcomes in neonates with prolonged neonatal jaundice. DESIGN: An observational study. SETTING: Multiple tertiary centres from the China Neonatal Genome Project. PATIENTS: Term infants with jaundice lasting more than 14 days or preterm infants with jaundice lasting more than 21 days were recruited between 1 June 2016 and 30 June 2020. MAIN OUTCOME MEASURES: Aetiology and outcomes were recorded from neonates with prolonged unconjugated hyperbilirubinaemia (PUCHB) and prolonged conjugated hyperbilirubinaemia (PCHB). RESULTS: A total of 939 neonates were enrolled, and known aetiologies were identified in 84.1% of neonates (790 of 939). Among 411 neonates with PCHB, genetic disorders (27.2%, 112 of 411) were the leading aetiologies. There were 8 deceased neonates, 19 neonates with liver failure and 12 with neurodevelopmental delay. Among 528 neonates with PUCHB, a genetic aetiology was identified in 2 of 219 neonates (0.9%) who showed disappearance of jaundice within 4 weeks of age and in 32 of 309 neonates (10.4%) with persistent jaundice after 4 weeks of age. A total of 96 of 181 neonates (53.0%) who received genetic diagnoses had their clinical diagnosis modified as a result of the genetic diagnoses. CONCLUSION: Known aetiologies were identified in approximately 80% of neonates in our cohort, and their overall outcomes were favourable. Genetic aetiology should be considered a priority in neonates with PCHB or the persistence of jaundice after 4 weeks of age. Moreover, genetic data can modify the clinical diagnosis and guide disease management, potentially improving outcomes.