Booster vaccinations are highly recommended in combating the SARS-CoV-2 Omicron variant and its subvariants. However, the optimal booster vaccination strategies and related immune mechanisms with different prior vaccinations are under-revealed. In this study, we systematically evaluated the immune responses in mice and hamsters with different prime-boost regimens before their protective efficacies against Omicron were detected. We found that boosting with Ad5-nCoV, S_WT-2P or S_Omicron-6P induced significantly higher levels of neutralization activities against Omicron variants than CoronaVac and ZF2001 by eliciting stronger germinal center (GC) responses. Specifically, S_Omicron-6P induced even stronger antibody responses against Omicron variants in CoronaVac and Ad5-nCoV-primed animals than non-Omicron-specific vaccines but with limited differences as compared to Ad5-nCoV and S_WT-2P. In addition, boosting with a specific vaccine has the potential to remodel the existing immune profiles. These findings indicated that adenovirus-vectored vaccines and mRNA vaccines would be more effective than other types of vaccines as booster shots in combating Omicron infections. Moreover, the protective efficacies of the vaccines in booster vaccinations are highly related to GC reactions in secondary lymphatic organs. In summary, these findings provide timely important information on prime-boost regimens and future vaccine design.

Obstructive sleep apnea(OSA)is a dis-order characterized by chronic intermittent hypoxia and sleep fragmentation,usually manifested by ob-struction of the upper respiratory tract,resulting in sleep fragmentation,intermittent hypoxia,and hy-percapnia.OSA and significant comorbidities are as-sociated with perioperative complications.Opioids,as the most commonly used pain relievers,may fur-ther affect perioperative pain management in OSA and comorbidities.Studies have shown that OSA patients are more susceptible to the respiratory de-pressant effects of opioids.OSA also increases the risk of opioid-induced respiratory depression.There-fore,understanding the effects and mechanisms of opioids on OSA has important clinical significance for optimizing drug use,improving prognosis,and reducing respiratory adverse events.This article aims to review the effects of opioids on OSA and their relationship.

Objective·To screen a long non-coding RNA(lncRNA)signature and construct a competing endogenous RNA(ceRNA)network associated with the prognosis of pediatric sepsis based on the Gene Expression Omnibus(GEO)database,and explore their potential application value in the prognosis assessment of children with sepsis.Methods·Microarray data in GSE4607,GSE26440,GSE26378,and GSE9692 in the GEO database were used to compare the differences in lncRNA profiles between the survival and non-survival groups of children with septic shock.Then,multivariate linear regression,LASSO analysis,and receiver operating characteristic(ROC)curves were used to evaluate the capacity of the lncRNA signature for predicting the outcome of pediatric sepsis.The potential targeted microRNAs(miRNAs)and their downstream mRNAs,targeted by the screened lncRNAs,were used to construct a protein-protein interaction(PPI)network and perform pathway enrichment analysis.Results·Transcriptomic data from GSE4607,GSE26440,GSE26378 and GSE9692 revealed 55 differentially expressed lncRNAs associated with prognosis,and miR503 host gene(MIR503HG),TAPT1 antisense RNA 1(TAPT1-AS1),apoptosis-associated transcript in bladder cancer(AATBC),SBF2 antisense RNA 1(SBF2-AS1),MGC16275,and small nucleolar RNA host gene 15(SNHG15)were identified as a 6-lncRNA signature(lncSig6)associated with the prognosis of pediatric septic shock by LASSO regression analysis.The area under the ROC curve(AUC)of lncSig6 was 0.859(95％CI 0.722-0.996)and 0.854(95％CI 0.687-1.000)in internal and external validation,respectively.As lncRNA act as miRNA sponge,a lncRNA-miRNA-mRNA network based on 3 lncRNAs(MIR503HG,SNHG15,and SBF2-AS1)was constructed and involved in the regulation of signaling pathways,including forkhead box O(FoxO)signaling pathway,phosphatidylinositol 3 kinase-protein kinase B(PI3K-AKT)signaling pathway,cell senescence,insulin signaling pathway,hypoxia-inducible protein-1(HIF-1)signaling pathway and advanced glycation end products(AGEs)and receptor of AGEs(RAGE)signaling pathway.Conclusion·The lncSig6 can be used as an evaluation method to predict the prognosis of septic shock in children,and the constructed ceRNA molecular networks can provide an experimental basis for the study of signaling pathways.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective:To investigate the feasibility and clinical effects of ultra early enteral nutrition (≤24 h) in critically ill children supported by extracorporeal membrane oxygenation (ECMO).Methods:A retrospective cohort study was conducted. Clinical data of 43 critically ill children who received ECMO support in the pediatric intensive care unit (PICU) of Shanghai Children′s Hospital from January 2016 to December 2023 were collected, including general information, nutritional support modalities, and enteral nutrition tolerance. Based on the timing of enteral nutrition initiation, patients were divided into the within 24 h enteral nutrition group and the after 24 h enteral nutrition group. Nutritive indicators, nutritional intake, duration of ECMO support, duration of mechanical ventilation duration, and mortality rates were compared between the 2 groups using the two independent sample t test, Mann-Whitney U test, χ2 test and Fisher′s exact test. Results:Among the 43 children, 25 were male and 18 were female, with an age of 47 (18, 97) months. There were no statistically significant differences between the within 24 h enteral nutrition group (21 cases) and the after 24 h enteral nutrition group (22 cases) in terms of age, body mass index Z score, total protein, albumin, hemoglobin levels before ECMO support, duration of ECMO support, duration of mechanical ventilation, length of PICU stay, number of enteral nutrition intolerance events, number of enteral nutrition interruption, or mortality rate (all P>0.05). The protein intake adequacy rate during ECMO support was higher in the within 24 h enteral nutrition group than in the after 24 h enteral nutrition group (0 (0, 21%) vs. 0 (0, 0), U=175.00, P<0.05). Conclusions:Ultra early enteral nutrition is safe for children supported by ECMO. Initiating enteral nutrition within 24 h can increase the proportion of days with adequate protein intake in ECMO children without increasing the occurance of enteral nutrition intolerance or interruptions.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Obstructive sleep apnea(OSA)is a dis-order characterized by chronic intermittent hypoxia and sleep fragmentation,usually manifested by ob-struction of the upper respiratory tract,resulting in sleep fragmentation,intermittent hypoxia,and hy-percapnia.OSA and significant comorbidities are as-sociated with perioperative complications.Opioids,as the most commonly used pain relievers,may fur-ther affect perioperative pain management in OSA and comorbidities.Studies have shown that OSA patients are more susceptible to the respiratory de-pressant effects of opioids.OSA also increases the risk of opioid-induced respiratory depression.There-fore,understanding the effects and mechanisms of opioids on OSA has important clinical significance for optimizing drug use,improving prognosis,and reducing respiratory adverse events.This article aims to review the effects of opioids on OSA and their relationship.

Objective·To screen a long non-coding RNA(lncRNA)signature and construct a competing endogenous RNA(ceRNA)network associated with the prognosis of pediatric sepsis based on the Gene Expression Omnibus(GEO)database,and explore their potential application value in the prognosis assessment of children with sepsis.Methods·Microarray data in GSE4607,GSE26440,GSE26378,and GSE9692 in the GEO database were used to compare the differences in lncRNA profiles between the survival and non-survival groups of children with septic shock.Then,multivariate linear regression,LASSO analysis,and receiver operating characteristic(ROC)curves were used to evaluate the capacity of the lncRNA signature for predicting the outcome of pediatric sepsis.The potential targeted microRNAs(miRNAs)and their downstream mRNAs,targeted by the screened lncRNAs,were used to construct a protein-protein interaction(PPI)network and perform pathway enrichment analysis.Results·Transcriptomic data from GSE4607,GSE26440,GSE26378 and GSE9692 revealed 55 differentially expressed lncRNAs associated with prognosis,and miR503 host gene(MIR503HG),TAPT1 antisense RNA 1(TAPT1-AS1),apoptosis-associated transcript in bladder cancer(AATBC),SBF2 antisense RNA 1(SBF2-AS1),MGC16275,and small nucleolar RNA host gene 15(SNHG15)were identified as a 6-lncRNA signature(lncSig6)associated with the prognosis of pediatric septic shock by LASSO regression analysis.The area under the ROC curve(AUC)of lncSig6 was 0.859(95％CI 0.722-0.996)and 0.854(95％CI 0.687-1.000)in internal and external validation,respectively.As lncRNA act as miRNA sponge,a lncRNA-miRNA-mRNA network based on 3 lncRNAs(MIR503HG,SNHG15,and SBF2-AS1)was constructed and involved in the regulation of signaling pathways,including forkhead box O(FoxO)signaling pathway,phosphatidylinositol 3 kinase-protein kinase B(PI3K-AKT)signaling pathway,cell senescence,insulin signaling pathway,hypoxia-inducible protein-1(HIF-1)signaling pathway and advanced glycation end products(AGEs)and receptor of AGEs(RAGE)signaling pathway.Conclusion·The lncSig6 can be used as an evaluation method to predict the prognosis of septic shock in children,and the constructed ceRNA molecular networks can provide an experimental basis for the study of signaling pathways.

Objective:To investigate the feasibility and clinical effects of ultra early enteral nutrition (≤24 h) in critically ill children supported by extracorporeal membrane oxygenation (ECMO).Methods:A retrospective cohort study was conducted. Clinical data of 43 critically ill children who received ECMO support in the pediatric intensive care unit (PICU) of Shanghai Children′s Hospital from January 2016 to December 2023 were collected, including general information, nutritional support modalities, and enteral nutrition tolerance. Based on the timing of enteral nutrition initiation, patients were divided into the within 24 h enteral nutrition group and the after 24 h enteral nutrition group. Nutritive indicators, nutritional intake, duration of ECMO support, duration of mechanical ventilation duration, and mortality rates were compared between the 2 groups using the two independent sample t test, Mann-Whitney U test, χ2 test and Fisher′s exact test. Results:Among the 43 children, 25 were male and 18 were female, with an age of 47 (18, 97) months. There were no statistically significant differences between the within 24 h enteral nutrition group (21 cases) and the after 24 h enteral nutrition group (22 cases) in terms of age, body mass index Z score, total protein, albumin, hemoglobin levels before ECMO support, duration of ECMO support, duration of mechanical ventilation, length of PICU stay, number of enteral nutrition intolerance events, number of enteral nutrition interruption, or mortality rate (all P>0.05). The protein intake adequacy rate during ECMO support was higher in the within 24 h enteral nutrition group than in the after 24 h enteral nutrition group (0 (0, 21%) vs. 0 (0, 0), U=175.00, P<0.05). Conclusions:Ultra early enteral nutrition is safe for children supported by ECMO. Initiating enteral nutrition within 24 h can increase the proportion of days with adequate protein intake in ECMO children without increasing the occurance of enteral nutrition intolerance or interruptions.

Sepsis cardiomyopathy (SIC) is sepsis complicated with heart dysfunction，and its definition，pathogenesis，diagnostic criteria and therapeutic measures have not been well established.The reported prevalence of SIC varied from 10% to 70% and the diagnosis based on the measures of heart function and biological markers.The most important indicator is reduced left heart ejection fraction.Currently，it is believed that SIC should avoid rapid high-dose liquid treatment on the basis of infection treatment.The use of inotropic drugs needs to consider the improvement of myocardial contractility and avoid inducing arrhythmia and adverse effects on vascular resistance.The appropriate timing of extracorporeal membrane oxygenation support is still be challenged.The review focusesd on the fluid management and progress，vasoactive drug therapy and mechanical assistance，and the development of novel targeted drugs in SIC.